Reduction or suppression of eye damage by administration of hyaluronidase

Abstract

The present invention provides a composition for reducing or eliminating vascular occlusion caused by hyaluronic acid soft tissue dermal fillers. [Solution] This disclosure provides for compositions comprising hyaluronidase, apparatus for housing such compositions, and methods and uses of such compositions and apparatus for reducing or eliminating hyaluronic acid-induced blockages in one or more blood vessels supplying an individual's eye; methods and uses of such compositions and apparatus for reducing or inhibiting vascular occlusion of an individual's eye; and methods and uses of such compositions and apparatus for reducing or inhibiting hyaluronic acid-induced vision loss in an individual.

Description

Technical Field

[0001] This application claims the benefit of priority of U.S. Patent Provisional Application No. 63 / 004,444, filed Apr. 2, 2020, the entire content of which is incorporated herein by reference, and has the right of its filing date in accordance with 35 U.S.C. § 119(e).

[0002] The present invention relates to the treatment of vision loss caused by the administration of hyaluronic acid soft tissue dermal fillers.

Background Art

[0003] The use of fillers to enhance the soft tissue of an individual's face has become one of the most common cosmetic procedures. For example, soft tissue filler injections are the second most common cosmetic procedure after botulinum toxin treatment. The most commercially prevalent soft tissue dermal fillers are those that use hyaluronic acid.

Summary of the Invention

Problems to be Solved by the Invention

[0004] Sadly, as the field of soft tissue enhancement has become more widespread, reports of adverse events have increased. Vision loss is one of the most tragic possible complications of soft tissue dermal filler injections. In particular, inadvertent intra-arterial injection of soft tissue dermal fillers can cause vascular occlusion, blocking blood flow to the eye and resulting in ischemia, necrosis, and vision loss. To date, over 100 documented cases of vision loss after the administration of soft tissue fillers have been reported. However, leading experts in soft tissue enhancement suspect that this documented number of cases is only a small part of the actual incidence of vision loss after soft tissue filler administration, due to inconsistent reporting by providers of these services.

[0005] Unfortunately, there is no proven effective treatment for vision loss following soft tissue filler injections. Therefore, if occlusive events occur in these blood vessels, the vision loss is permanent. Furthermore, even if vascular occlusion events are recognized early, visual impairment associated with soft tissue filler injections is almost irreversible unless blood flow is rapidly restored, which usually must be done within approximately 5 to 15 minutes after the occlusion occurs. Given the vulnerability of retinal tissue to vascular occlusion events caused by fillers, there is a need for methods to reduce or eliminate these blockages. [Means for solving the problem]

[0006] This disclosure provides solutions for soft tissue dermal fillers containing such hyaluronic acid. The compositions, apparatus, methods, and uses disclosed herein involve administering hyaluronidase into the suprachoroid space of the eye. Such administration delivers hyaluronidase to the blood vessels supplying the eye within approximately 5 minutes. This rapid delivery of hyaluronidase allows the enzyme to reduce or eliminate hyaluronic acid that causes vascular occlusion, thereby reducing or eliminating the risk of permanent damage to the eye.

[0007] Aspects of this specification disclose a method for reducing or eliminating, as needed, hyaluronic acid-induced blockages in one or more blood vessels supplying blood to an individual's eye. The disclosed method involves administering a composition comprising hyaluronidase to an individual in a manner that reduces or eliminates hyaluronic acid-induced blockages in one or more blood vessels supplying blood to the eye. In some aspects, the disclosed method administers the hyaluronidase-containing composition into the suprachoroidal space of the eye. In other aspects, the disclosed method administers the hyaluronidase-containing composition using a delivery system such as, for example, a needle and syringe, an ADG needle, or a microinjector. The disclosed method may administer the hyaluronidase-containing composition in single or multiple doses ranging from about 15 IU to about 10,000 IU of hyaluronidase.

[0008] Aspects of this specification disclose methods for reducing or suppressing vascular occlusion of an individual's eye as needed. The disclosed methods involve administering a composition comprising hyaluronidase to an individual in a manner that reduces or eliminates hyaluronic acid-induced blockages in one or more blood vessels supplying blood to the eye, thereby reducing or suppressing vascular occlusion of the eye. In some aspects, the disclosed methods involve administering the hyaluronidase-containing composition into the suprachoroidal space of the eye. In other aspects, the disclosed methods involve administering the hyaluronidase-containing composition using a delivery system such as, for example, a needle and syringe, an ADG needle, or a microinjector. The disclosed methods may administer the hyaluronidase-containing composition in single or multiple doses ranging from about 15 IU to about 10,000 IU of hyaluronidase.

[0009] Aspects of this specification disclose methods for reducing or suppressing, as needed, hyaluronic acid-induced vision loss in an individual. The disclosed methods include administering a composition containing hyaluronidase to an individual in a manner that reduces or eliminates hyaluronic acid-induced blockages in one or more blood vessels supplying blood to the eye, thereby reducing or suppressing hyaluronic acid-induced vision loss in the individual. In some aspects, the disclosed methods administer the hyaluronidase-containing composition into the suprachoroid space of the eye. In other aspects, the disclosed methods administer the hyaluronidase-containing composition using a delivery system such as, for example, a needle and syringe, an ADG needle, or a microinjector. The disclosed methods may administer the hyaluronidase-containing composition in single or multiple doses ranging from about 15 IU to about 10,000 IU of hyaluronidase.

[0010] Other embodiments of this specification disclose delivery systems, such as needles and syringes, ADG needles, or microinjectors, for containing compositions comprising hyaluronidase. In some embodiments, the disclosed delivery systems deliver the hyaluronidase-containing compositions into the suprachoroidal space of the eye. The disclosed delivery systems can administer the hyaluronidase-containing compositions in single or multiple doses ranging from about 15 IU to about 10,000 IU of hyaluronidase.

[0011] Other aspects of this specification disclose the use of compositions comprising hyaluronidase. In some aspects, the disclosed use comprises a composition comprising hyaluronidase contained in a delivery system such as a needle and syringe, an ADG needle, or a microinjector. In other aspects, the disclosed use comprises a composition comprising hyaluronidase contained in a choroidal microinjector. In other aspects, the disclosed use comprises a composition comprising hyaluronidase contained in an AGD needle. The disclosed use allows for the administration of a composition comprising hyaluronidase in single or multiple doses ranging from about 15 IU to about 10,000 IU of hyaluronidase.

[0012] Other aspects of this specification disclose the use of delivery systems, such as needles and syringes, ADG needles, or microinjectors, for containing compositions comprising hyaluronidase. In some aspects, the disclosed use comprises a choroidal microinjector containing a composition comprising hyaluronidase. In some aspects, the disclosed use comprises an ADG needle containing a composition comprising hyaluronidase. The disclosed use allows for the administration of a composition comprising hyaluronidase in single or multiple doses ranging from about 15 IU to about 10,000 IU of hyaluronidase.

[0013] Other aspects of this specification disclose the use of compositions containing hyaluronidase in the manufacture of pharmaceuticals. In some aspects, the disclosed pharmaceuticals include compositions containing hyaluronidase contained in a delivery system such as a needle and syringe, an ADG needle, or a microinjector. In other aspects, the disclosed pharmaceuticals include compositions containing hyaluronidase contained in a choroidal microinjector. In other aspects, the disclosed pharmaceuticals include compositions containing hyaluronidase contained in an ADG needle. The disclosed uses allow the administration of a hyaluronidase-containing composition in single or multiple doses ranging from about 50 IU to about 20,000 IU of hyaluronidase.

[0014] Other embodiments of this specification disclose compositions comprising hyaluronidase for use in inhibiting hyaluronic acid-induced blockages in one or more blood vessels supplying the eye. In some embodiments, the hyaluronidase-containing compositions are contained in a delivery system such as a needle and syringe, an ADG needle, or a microinjector. In other embodiments, the hyaluronidase-containing compositions are contained in a choroidal microinjector. In other embodiments, the hyaluronidase-containing compositions are contained in an ADG needle. The disclosed hyaluronidase-containing compositions may comprise single or multiple doses of hyaluronidase ranging from about 50 IU to about 20,000 IU.

[0015] Other embodiments of this specification disclose a delivery system, such as a needle and syringe, an ADG needle, or a microinjector, for containing a composition comprising hyaluronidase for use in preventing hyaluronic acid-induced blockages in one or more blood vessels supplying the eye. In some embodiments, the disclosed microinjector is a choroidal microinjector. The disclosed delivery system for containing a composition comprising hyaluronidase may contain single or multiple doses of hyaluronidase ranging from about 50 IU to about 20,000 IU.

[0016] The accompanying drawings incorporated herein and forming part thereof illustrate aspects of the subject matter disclosed in at least one of the exemplary embodiments thereof, which are further defined in the following description. Features, elements, and aspects of the disclosure are referenced numerically, and similar numerical terms in different drawings represent the same, equivalent, or similar features, elements, or aspects in one or more embodiments. The drawings are not necessarily to scale, and instead the emphasis is on illustrating the principles described and provided herein by exemplary embodiments of the invention. [Brief explanation of the drawing]

[0017] [Figure 1] This is a cross-sectional view showing the anatomical parts of the human eye. [Figure 2] This is a diagram showing blood vessels related to the human eye. [Figure 3] This is a photograph showing central retinal artery occlusion. [Figure 4] This is a photograph showing retinal artery branch occlusion. [Figure 5] This is a diagram showing a microinjector. [Figure 6] Figures 6A to 6D illustrate the administration of a hyaluronidase-containing composition into the suprachoroidal space of the eye using a microinjector, where Figure 6A shows the general location of the injection site, Figure 6B shows a cross-section of the eye at the injection site, Figure 6C shows the insertion of the microinjector at the suprachoroidal space level, and Figure 6D shows the administration of the composition disclosed herein into the suprachoroidal space. [Modes for carrying out the invention]

[0018] The eye is the organ of the visual system that detects light and converts it into electrochemical impulses for neurons. In humans, the eye is a complex optical system that collects light from the surrounding environment, adjusts its intensity with an aperture, focuses it through an assembly of adjustable lenses to form an image, converts this image into a series of electrical signals, and sends these signals to the brain through a complex neural pathway that connects the eye to the visual cortex and other areas of the brain via the optic nerve. The main anatomical structures of the human eye are shown in Figure 1.

[0019] Figure 2 shows the blood vessels that provide ocular circulation to the eye. The central retinal artery, the long and short posterior ciliary arteries, the anterior ciliary artery, and other arteries are all branches of the ophthalmic artery and provide arterial supply to the eye. The central retinal artery and the short posterior ciliary artery supply blood to the retina. The central retinal artery runs through or alongside the optic nerve, branches through the sclera, and supplies blood to the inner layers of the retina. The other branches of the ophthalmic artery supply nutrients to the eye and its muscles.

[0020] Unfortunately, when a soft tissue dermal filler, such as a hyaluronic acid filler, is administered to the face, the filler can enter the ocular circulation and lead to blockage of one or more blood vessels that supply the eye. Such blockages can impede or prevent blood flow, and as a result, oxygen and nutrients from the blocked blood vessels are lacking to the eye (Figures 3 and 4). If blood flow through the blocked blood vessels does not recover promptly, ocular ischemia, and / or damage to the retina with corresponding necrosis and loss of vision can occur. These adverse events occur rapidly, and permanent damage occurs within minutes after such ocular vascular occlusion.

[0021] Hyaluronidase is a type of enzyme that catalyzes the breakdown of hyaluronic acid. Thus, one possible solution to hyaluronic acid-caused blockage of one or more blood vessels that supply the eye is to administer hyaluronidase to the site of the blockage. However, there is no currently known method for effectively delivering hyaluronidase to the ocular circulation in a manner that reduces or eliminates hyaluronic acid-caused blockage of the ocular circulation.

[0022] The compositions, devices, and methods, and uses disclosed herein effectively deliver hyaluronidase to the ocular circulation in a manner that reduces or eliminates hyaluronic acid-caused blockage of one or more blood vessels that supply the eye. Such reduction or elimination of hyaluronic acid-caused vascular occlusion is related to the administration of hyaluronidase to the suprachoroidal space of the eye. Such administration ultimately delivers hyaluronidase to the blood vessels that supply the eye within about 90 minutes, preferably within 60 minutes, more preferably within 30 minutes, and most preferably within 5 - 15 minutes. This rapid delivery of hyaluronidase enables the enzyme to reduce or eliminate hyaluronic acid that causes vascular occlusion, thereby reducing or eliminating the risk of permanent damage to the eye.

[0023] Aspects of the present specification disclose pharmaceutical compositions. The pharmaceutical compositions disclosed herein refer to an active ingredient at a therapeutically effective concentration, such as hyaluronidase disclosed herein. Preferably, the pharmaceutical compositions disclosed herein do not produce adverse reactions, allergic reactions, or other undesirable or unwanted reactions when administered to an individual. The pharmaceutical compositions disclosed herein are useful for medical and veterinary applications. The pharmaceutical compositions disclosed herein can be formulated as liquid pharmaceutical compositions or as dry pharmaceutical compositions, such as, for example, lyophilized or freeze-dried formulations. The pharmaceutical compositions disclosed herein can be administered to an individual alone or in combination with an adjunctive active compound, agent, drug, or hormonal agent.

[0024] Aspects of the present specification disclose hyaluronidase. Hyaluronidase hydrolyzes hyaluronic acid. According to their enzymatic mechanism, hyaluronidases are hyaluronoglucosidases (EC 3.2.1.35), i.e., they cleave the (1->4)-bond between N-acetylglucosamine and glucuronate. The term "hyaluronidase" may also refer to hyaluronoglucuronidase (EC 3.2.1.36), which cleaves the (1->3)-bond. The pharmacokinetics of hyaluronidase have been evaluated in animal studies after intravitreal injection. The plasma half-life is 49 hours. The maximum concentration is achieved in the vitreous, retina, and sclera. The half-life in eye tissues is 60 - 112 hours. Hyaluronidase can be obtained commercially from animals and is usually extracted from sheep or bovine testes (Vitrase, Bausch Health Companies, Inc., Laval, Quebec, Canada), pigs, or bacteria. Hyaluronidase can also be obtained recombinantly, for example, by genetically engineering human recombinant DNA in Chinese hamster ovary cells (Hylenex, Halozyme Therapeutics, Inc., San Diego, CA).

[0025] This specification partially discloses therapeutically effective doses. A therapeutically effective dose of hyaluronidase is an amount sufficient to reduce or eliminate hyaluronic acid-induced blockages in one or more blood vessels of the eye. In aspects of this embodiment, a therapeutically effective dose of hyaluronidase is an amount sufficient to reduce one or more physiological conditions or symptoms associated with hyaluronic acid-induced blockages in one or more blood vessels of the eye, or an amount sufficient to protect an individual from one or more physiological conditions or symptoms associated with hyaluronic acid-induced blockages in one or more blood vessels of the eye. As used herein, the term “therapeutably effective dose” includes the terms “sufficient amount,” “therapeutably sufficient amount,” “effective amount,” “effective dose,” or “therapeutably effective dose,” and refers to the minimum amount of hyaluronidase required to achieve a desired therapeutic effect, and includes an amount sufficient to reduce or suppress one or more physiological conditions or symptoms associated with hyaluronic acid-induced blockages in one or more blood vessels of the eye.

[0026] In aspects of this embodiment, a therapeutically effective amount of hyaluronidase disclosed herein reduces or suppresses, for example, one or more physiological conditions or symptoms associated with hyaluronic acid-induced blockages in one or more blood vessels of the eye by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 100%. In other aspects of this embodiment, an effective amount of hyaluronidase disclosed herein reduces or suppresses, for example, one or more physiological conditions or symptoms associated with hyaluronic acid-induced blockages in one or more blood vessels of the eye by at most 10%, at most 20%, at most 30%, at most 40%, at most 50%, at most 60%, at most 70%, at most 80%, at most 90%, or at most 100%. In yet another embodiment of this embodiment, an effective amount of hyaluronidase disclosed herein is used to treat one or more physiological conditions or symptoms associated with hyaluronic acid-induced blockages in one or more blood vessels of the eye, for example, at concentrations of about 10% to about 100%, about 10% to about 90%, about 10% to about 80%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 10% to about 20%, about 20% to about 100%, about 20% to about 90%, about 20% to about 80%, about 20% to about 70%, about 20% to about 60%, about 20% to about 50%, about 20% to about 40%, about 20% to about 30%, about 30% to about 100%, and about 30% %~approx. 90%, approx. 30%~approx. 80%, approx. 30%~approx. 70%, approx. 30%~approx. 60%, approx. 30%~approx. 50%, approx. 30%~approx. 40%, approx. 40%~approx. 100%, approx. 40%~approx. 90%, approx. 40%~approx. 80%, approx. 40%~approx. 70%, approx. 40%~approx. 60%, approx. 40%~approx. 50%, approx. 50%~approx. 100%, approx. 50%~approx. 90%, approx. 5 Reduce or suppress by 0% to approximately 80%, approximately 50% to approximately 70%, approximately 50% to approximately 60%, approximately 60% to approximately 100%, approximately 60% to approximately 90%, approximately 60% to approximately 80%, approximately 60% to approximately 70%, approximately 70% to approximately 100%, approximately 70% to approximately 90%, approximately 70% to approximately 80%, approximately 80% to approximately 100%, approximately 80% to approximately 90%, or approximately 90% to approximately 100%.In yet another embodiment of this embodiment, an effective amount of hyaluronidase disclosed herein reduces or suppresses one or more physiological conditions or symptoms associated with hyaluronic acid-induced blockage in one or more blood vessels of the eye, for example, over a period of at least one week, at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least seven months, at least eight months, at least nine months, at least ten months, at least eleven months, or at least twelve months.

[0027] In aspects of this embodiment, a therapeutically effective amount of hyaluronidase disclosed herein restores or maintains one or more qualitative or quantitative aspects of vision by, for example, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 100%. In other aspects of this embodiment, an effective amount of hyaluronidase disclosed herein restores or maintains one or more qualitative or quantitative aspects of vision by, for example, at most 10%, at most 20%, at most 30%, at most 40%, at most 50%, at most 60%, at most 70%, at most 80%, at most 90%, or at most 100%. In yet another embodiment of this embodiment, an effective amount of hyaluronidase disclosed herein can be used to achieve one or more qualitative or quantitative aspects of vision, for example, about 10% to about 100%, about 10% to about 90%, about 10% to about 80%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 10% to about 20%, about 20% to about 100%, about 20% to about 90%, about 20% to about 80%, about 20% to about 70%, about 20% to about 60%, about 20% to about 50%, about 20% to about 40%, about 20% to about 30%, about 30% to about 100%, about 30% to about 90%, about 30% to about 80% %, approximately 30% to 70%, approximately 30% to 60%, approximately 30% to 50%, approximately 30% to 40%, approximately 40% to 100%, approximately 40% to 90%, approximately 40% to 80%, approximately 40% to 70%, approximately 40% to 60%, approximately 40% to 50%, approximately 50% to 100%, approximately 50% to 90%, approximately 50% to 80%, Recover or maintain approximately 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%.In yet another embodiment of this embodiment, an effective amount of hyaluronidase disclosed herein restores or maintains one or more qualitative or quantitative aspects of vision for, for example, over a period of at least one week, at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least seven months, at least eight months, at least nine months, at least ten months, at least eleven months, or at least twelve months.

[0028] The actual therapeutically effective dose of the hyaluronidase disclosed herein for use or administration to an individual may be determined by a person skilled in the art, taking into account, but not limited to, the type of hyaluronic acid blockage, specific physiological conditions or symptoms associated with the hyaluronic acid blockage, the cause of the hyaluronic acid blockage, the severity of the hyaluronic acid blockage, the desired degree of relief from the hyaluronic acid blockage, the desired duration of relief from the hyaluronic acid blockage, the specific soft tissue dermal filler used, the excretion rate of the specific hyaluronidase used, the pharmacodynamics of the specific hyaluronidase used, the properties of other compounds included in the treatment, the specific route of administration used, and factors including specific characteristics of the individual such as age, weight, and general health, medical history, and risk factors, or any combination thereof. It is known to a person skilled in the art that the effective dose of the hyaluronidase disclosed herein can be extrapolated from in vitro assays and in vivo administration studies using animal models prior to administration to humans. Dose level variations can be adjusted using standard empirical optimization routines well known to a person skilled in the art. The precise therapeutically effective dose level and pattern are preferably determined by the attending physician, taking the above factors into consideration.

[0029] Depending on the concentration of hyaluronidase in the compositions disclosed herein, the medication may be administered as a single dose or in multiple doses. Typically, when prescribed as a single dose, the concentration of hyaluronidase in the compositions disclosed herein is such that it effectively reduces or eliminates hyaluronic acid-induced blockages in one or more blood vessels of the eye. When the compositions disclosed herein are prescribed for multiple doses, the total amount of hyaluronidase administered cumulatively in multiple doses is such that it effectively reduces or eliminates hyaluronic acid-induced blockages in one or more blood vessels of the eye.

[0030] The compositions disclosed herein may contain hyaluronidase at concentrations ranging from about 15 IU / mL to about 20,000 IU / mL. In aspects of this embodiment, the compositions disclosed herein may contain, for example, at least 15 IU / mL, at least 25 IU / mL, at least 50 IU / mL, at least 100 IU / mL, at least 200 IU / mL, at least 300 IU / mL, at least 450 IU / mL, at least 600 IU / mL, at least 900 IU / mL, at least 1,000 IU / mL, at least 1,250 IU / mL, at least 1,500 IU / mL, at least 1,750 IU / mL, at least 2,000 IU / mL, at least 3,000 IU / mL, at least 4,000 IU / mL, and at least 5,000 IU / mL. The solution contains hyaluronidase at concentrations of 0 IU / mL, at least 6,000 IU / mL, at least 7,000 IU / mL, at least 8,000 IU / mL, at least 9,000 IU / mL, at least 10,000 IU / mL, at least 11,000 IU / mL, at least 12,000 IU / mL, at least 13,000 IU / mL, at least 14,000 IU / mL, at least 15,000 IU / mL, at least 16,000 IU / mL, at least 17,000 IU / mL, at least 18,000 IU / mL, at least 19,000 IU / mL, or at least 20,000 IU / mL.In other embodiments of this specification, the compositions disclosed herein include, for example, at most 15 IU / mL, at most 25 IU / mL, at most 50 IU / mL, at most 100 IU / mL, at most 200 IU / mL, at most 300 IU / mL, at most 450 IU / mL, at most 600 IU / mL, at most 900 IU / mL, at most 1,000 IU / mL, at most 1,250 IU / mL, at most 1,500 IU / mL, at most 1,750 IU / mL, at most 2,000 IU / mL, at most 3,000 IU / mL, at most 4,000 IU / mL, and at most 5,000 IU / mL. Contains hyaluronidase at concentrations of 0 IU / mL, at most 6,000 IU / mL, at most 7,000 IU / mL, at most 8,000 IU / mL, at most 9,000 IU / mL, at most 10,000 IU / mL, at most 11,000 IU / mL, at most 12,000 IU / mL, at most 13,000 IU / mL, at most 14,000 IU / mL, at most 15,000 IU / mL, at most 16,000 IU / mL, at most 17,000 IU / mL, at most 18,000 IU / mL, at most 19,000 IU / mL, or at most 20,000 IU / mL.

[0031] In yet another embodiment of this embodiment, the compositions disclosed herein include, for example, about 15 IU / mL to about 25 IU / mL, about 15 IU / mL to about 50 IU / mL, about 15 IU / mL to about 100 IU / mL, about 15 IU / mL to about 200 IU / mL, about 15 IU / mL to about 300 IU / mL, about 15 IU / mL to about 400 IU / mL, about 15 IU / mL to about 450 IU / mL, about 15 IU / mL to about 600 IU / mL, about 15 IU / mL to about 750 IU / mL, about 15 IU / mL to about 900 IU / mL, about 25 IU / mL to about 50 IU / mL, and about 25 IU / mL~about 100IU / mL, about 25IU / mL~about 200IU / mL, about 25IU / mL~about 300IU / mL, about 25IU / mL~about 400IU / mL, about 25IU / mL~about 450IU / mL, about 25IU / mL~about 600IU / mL, about 25IU / mL~about 7 50IU / mL, approximately 25IU / mL to approximately 900IU / mL, approximately 50IU / mL to approximately 100IU / mL, approximately 50IU / mL to approximately 200IU / mL, approximately 50IU / mL to approximately 300IU / mL, approximately 50IU / mL to approximately 400IU / mL, approximately 50IU / mL to approximately 450IU / mL, approximately 50IU / mL to about 600IU / mL, about 50IU / mL to about 750IU / mL, about 50IU / mL to about 900IU / mL, about 100IU / mL to about 200IU / mL, about 100IU / mL to about 300IU / mL, about 100IU / mL to about 400IU / mL, about 100IU / mL ~ about 450IU / mL, about 100IU / mL - about 600IU / mL, about 100IU / mL - about 750IU / mL, about 100IU / mL - about 900IU / mL, about 200IU / mL - about 300IU / mL, about 200IU / mL - about 400IU / mL, about 200IU / mL ~about 450IU / mL, about 200IU / mL to about 600IU / mL, about 200IU / mL to about 750IU / mL, about 200IU / mL to about 900IU / mL, about 300IU / mL to about 450IU / mL, about 300IU / mL to about 600IU / mL, about 300IU / mL to about 7 50IU / mL, about 300IU / mL to about 900IU / mL, about 450IU / mL to about 600IU / mL, about 450IU / mL to about 750IU / mL, about 450IU / mL to about 900IU / mL, about 450IU / mL to about 1,000IU / mL, about 450IU / mL to about 1,250 IU / mL, approximately 600 IU / mL to approximately 750 IU / mL, approximately 600 IU / mL to approximately 900 IU / mL, approximately 600 IU / mL to approximately 1,000 IU / mL, approximately 600 IU / mL to approximately 1,250 IU / mL, approximately 600 IU / mL to approximately 1,500 IU / mL, approximately 750 IU / mL to approximately 900 IU / mL, approximately 750 IU / mL to approximately 1,000 IU / mL, approximately 750 IU / mL to approximately 1,250 IU / mL, approximately 750 IU / mL to approximately 1,250 IU / mL, approximately 750 IU / mL to approximately 1,500 IU / mL, approximately 750 IU / mL to approximately 1,750 IU / mL, approximately 900 IU / mL to approximately 1,000 IU / mL, approximately 900 IU / mL ~ approx. 1,250 IU / mL, approx. 900 IU / mL ~ approx. 1,500 IU / mL, approx. 900 IU / mL ~ approx. 1,750 IU / mL, approx. 900 IU / mL ~ approx. 2,000 IU / mL, approx. 1,000 IU / mL ~ approx. 1,250 IU / mL, approx. 1,000 IU / mL ~ approx. 1,500 IU / mL, approx. 1,000 IU / mL ~ approx. 1,750 IU / mL, approx. 1,000 IU / mL ~ approx. 2,000 IU / mL, approx. 1,000 IU / mL ~ approx. 2,000 IU / mL, approx. 1,000 IU / mL ~ approx. 3,000 IU / mL, approx. 1,000 IU / mL ~ approx. 4,000 IU / mL, approx. 1,000 IU / mL ~ approx. 5,000 IU / mL L, approximately 1,000 IU / mL to approximately 6,000 IU / mL, approximately 1,000 IU / mL to approximately 7,000 IU / mL, approximately 1,000 IU / mL to approximately 8,000 IU / mL, approximately 1,000 IU / mL to approximately 9,000 IU / mL, approximately 1,000 IU / mL to approximately 10,000 IU / mL, approximately 2,000 IU / mL to approximately 3,000 IU / mL, approximately 2,000 IU / mL to approximately 4,000 IU / mL, approximately 2,000 IU / mL to approximately 5,000 IU / mL, approximately 2,000 IU / mL to approximately 6,000 IU / mL, approximately 2,000 IU / mL to approximately 7,000 IU / mL, approximately 2,000 IU / mL U / mL ~ approx. 8,000 IU / mL, approx. 2,000 IU / mL ~ approx. 9,000 IU / mL, approx. 2,000 IU / mL ~ approx. 10,000 IU / mL, approx. 2,500 IU / mL ~ approx. 3,000 IU / mL, approx. 2,500 IU / mL ~ approx. 4,000 IU / mL, approx. 2,500 IU / mL ~ approx. 5,000 IU / mL, approx. 2,500 IU / mL ~ approx. 6,000 IU / mL, approx. 2,500 IU / mL ~ approx. 7,000 IU / mL, approx. 2,500 IU / mL ~ approx. 8,000 IU / mL, approx. 2,500 IU / mL ~ approx. 9,000 IU / mL, approx. 2,500 IU / mL ~ approx. 10,000 IU / mL000IU / mL, approximately 3,000IU / mL to approximately 4,000IU / mL, approximately 3,000IU / mL to approximately 5,000IU / mL, approximately 3,000IU / mL to approximately 6,000IU / mL, approximately 3,000I U / mL ~ approx. 7,000IU / mL, approx. 3,000IU / mL ~ approx. 8,000IU / mL, approx. 3,000IU / mL ~ approx. 9,000IU / mL, approx. 3,000IU / mL ~ approx. 10,000IU / m L, about 4,000IU / mL to about 5,000IU / mL, about 4,000IU / mL to about 6,000IU / mL, about 4,000IU / mL to about 7,000IU / mL, about 4,000IU / mL to about 8 ,000IU / mL, approximately 4,000IU / mL to approximately 9,000IU / mL, approximately 4,000IU / mL to approximately 10,000IU / mL, approximately 5,000IU / mL to approximately 6,000IU / mL, approximately 5,00 0IU / mL ~ approx. 7,000IU / mL, approx. 5,000IU / mL ~ approx. 8,000IU / mL, approx. 5,000IU / mL ~ approx. 9,000IU / mL, approx. 5,000IU / mL ~ approx. 10,000IU / mL, approximately 6,000IU / mL ~ approximately 7,000IU / mL, approximately 6,000IU / mL ~ approximately 8,000IU / mL, approximately 6,000IU / mL ~ approximately 9,000IU / mL, approximately 6,000IU / mL ~ Contains hyaluronidase at concentrations of approximately 10,000 IU / mL, approximately 7,000 IU / mL to approximately 8,000 IU / mL, approximately 7,000 IU / mL to approximately 9,000 IU / mL, approximately 7,000 IU / mL to approximately 10,000 IU / mL, approximately 8,000 IU / mL to approximately 9,000 IU / mL, approximately 8,000 IU / mL to approximately 10,000 IU / mL, or approximately 9,000 IU / mL to approximately 10,000 IU / mL.

[0032] In yet another embodiment of this embodiment, the compositions disclosed herein include, for example, about 10,000 IU / mL to about 11,000 IU / mL, about 10,000 IU / mL to about 12,000 IU / mL, about 10,000 IU / mL to about 13,000 IU / mL, about 10,000 IU / mL to about 14,000 IU / mL, about 10,000 IU / mL to about 15,000 IU / mL, about 10,000 IU / mL to about 16,000 IU / mL, about 10,000 IU / mL to about 17,000 IU / mL, about 10,000 IU / mL to about 18,000 IU / mL, and about 10 ,000IU / mL~about 19,000IU / mL, about 10,000IU / mL~about 20,000IU / mL, about 11,000IU / mL~about 12,000IU / mL, about 11,000IU / mL~about 13,000IU / mL, about 11,000IU / mL~about 14,000IU / mL, about 11,000IU / mL to about 15,000IU / mL, about 11,000IU / mL to about 16,000IU / mL, about 11,000IU / mL to about 17,000IU / mL, about 11,000IU / mL to about 18,000IU / mL, about 11,000IU / mL to about 19 ,000IU / mL, about 11,000IU / mL to about 20,000IU / mL, about 12,000IU / mL to about 13,000IU / mL, about 12,000IU / mL to about 14,000IU / mL, about 12,000IU / mL to about 15,000IU / mL, about 12,000IU / mL ~ approx. 16,000IU / mL, approx. 12,000IU / mL ~ approx. 17,000IU / mL, approx. 12,000IU / mL ~ approx. 18,000IU / mL, approx. 12,000IU / mL ~ approx. 19,000IU / mL, approx. 12,000IU / mL ~ approx. 20,000IU / mL, approx. 13 ,000IU / mL~Approx. 14,000IU / mL, Approx. 13,000IU / mL~Approx. 15,000IU / mL, Approx. 13,000IU / mL~Approx. 16,000IU / mL, Approx. 13,000IU / mL~Approx. 17,000IU / mL, Approx. 13,000IU / mL~Approx. 18,000IU / mL, approximately 13,000IU / mL to approximately 19,000IU / mL, approximately 13,000IU / mL to approximately 20,000IU / mL, approximately 14,000IU / mL to approximately 15,000IU / mL, approximately 14,000IU / mL to approximately 16,000IU / mL, approximately 14,000IU / mL to approximately 17,000IU / mL, approximately 14,000IU / mL to approximately 18,000IU / mL, approximately 14,000IU / mL to approximately 19,000IU / mL, approximately 14,000IU / mL to approximately 20,000IU / mL, approximately 15,000IU / mL to approximately 16,000IU / mL, approximately 15,000IU / mL mL ~ approx. 17,000IU / mL, approx. 15,000IU / mL ~ approx. 18,000IU / mL, approx. 15,000IU / mL ~ approx. 19,000IU / mL, approx. 15,000IU / mL ~ approx. 20,000IU / mL, approx. 16,000IU / mL ~ approx. 17,000IU / mL, approx. 16, Contains hyaluronidase at concentrations of approximately 1,000 IU / mL to 18,000 IU / mL, approximately 16,000 IU / mL to 19,000 IU / mL, approximately 16,000 IU / mL to 20,000 IU / mL, approximately 17,000 IU / mL to 18,000 IU / mL, approximately 17,000 IU / mL to 19,000 IU / mL, approximately 17,000 IU / mL to 20,000 IU / mL, approximately 18,000 IU / mL to 19,000 IU / mL, approximately 18,000 IU / mL to 20,000 IU / mL, or approximately 19,000 IU / mL to 20,000 IU / mL.

[0033] A single dose of a composition containing hyaluronidase, used to effectively reduce or eliminate hyaluronic acid-induced blockages in one or more blood vessels of the eye, may contain approximately 15 IU to approximately 10,000 IU of hyaluronidase. In aspects of this embodiment, a single dose of a composition comprising hyaluronidase used to effectively reduce or eliminate hyaluronic acid-induced blockages in one or more blood vessels of the eye may contain, for example, an amount of hyaluronidase of at least 15 IU, at least 25 IU, at least 50 IU, at least 100 IU, at least 200 IU, at least 300 IU, at least 450 IU, at least 600 IU, at least 900 IU, at least 1,000 IU, at least 1,250 IU, at least 1,500 IU, at least 1,750 IU, at least 2,000 IU, at least 3,000 IU, at least 4,000 IU, at least 5,000 IU, at least 6,000 IU, at least 7,000 IU, at least 8,000 IU, at least 9,000 IU, or at least 10,000 IU. In other embodiments of this embodiment, a single dose of a composition comprising hyaluronidase used to effectively reduce or eliminate hyaluronic acid-induced blockages in one or more blood vessels of the eye is, for example, at most 15 IU, at most 25 IU, at most 50 IU, at most 100 IU, at most 200 IU, at most 300 IU, at most 450 IU, at most 600 IU, at most 900 IU, and many It may contain hyaluronidase in amounts of 1,000 IU, at most 1,250 IU, at most 1,500 IU, at most 1,750 IU, at most 2,000 IU, at most 3,000 IU, at most 4,000 IU, at most 5,000 IU, at most 6,000 IU, at most 7,000 IU, at most 8,000 IU, at most 9,000 IU, or at most 10,000 IU.

[0034] In yet another embodiment of this embodiment, a single dose of a composition comprising hyaluronidase used to effectively reduce or eliminate hyaluronic acid-induced blockages in one or more blood vessels of the eye is, for example, about 15 IU to about 25 IU, about 15 IU to about 50 IU, about 15 IU to about 100 IU, about 15 IU to about 200 IU, about 15 IU to about 300 IU, about 15 IU to about 400 IU, about 15 IU to about 450 IU, about 15 IU to about 600 IU, about 15 IU to about 750 IU, about 15 IU to about 900 IU, about 25 IU to about 50 IU, about 25 IU to about 100 IU, about 25 IU ~200IU, 25IU~300IU, 25IU~400IU, 25IU~450IU, 25IU~600IU, 2 5IU~Approx. 750IU, Approx. 25IU~Approx. 900IU, Approx. 50IU~Approx. 100IU, Approx. 50IU~Approx. 200IU, Approx. 50IU~Approx. 300IU , about 50IU to about 400IU, about 50IU to about 450IU, about 50IU to about 600IU, about 50IU to about 750IU, about 50IU to about 90 0IU, about 100IU to about 200IU, about 100IU to about 300IU, about 100IU to about 400IU, about 100IU to about 450IU, about 10 0IU ~ approx. 600IU, approx. 100IU ~ approx. 750IU, approx. 100IU ~ approx. 900IU, approx. 200IU ~ approx. 300IU, approx. 200IU ~ approx. 4 00IU, about 200IU to about 450IU, about 200IU to about 600IU, about 200IU to about 750IU, about 200IU to about 900IU, about 300IU ~ approx. 450IU, approx. 300IU ~ approx. 600IU, approx. 300IU ~ approx. 750IU, approx. 300IU ~ approx. 900IU, approx. 450IU ~ Approximately 600IU, approximately 450IU ~ approximately 750IU, approximately 450IU ~ approximately 900IU, approximately 450IU ~ approximately 1,000IU, approximately 450IU ~ approximately 1,25 0IU, about 600IU to about 750IU, about 600IU to about 900IU, about 600IU to about 1,000IU, about 600IU to about 1,250I U, about 600IU to about 1,500IU, about 750IU to about 900IU, about 750IU to about 1,000IU, about 750IU to about 1,250IU , about 750IU to about 1,500IU, about 750IU to about 1,750IU, about 900IU to about 1,000IU, about 900IU to about 1,250 IU, approximately 900IU ~ approximately 1,500IU, approximately 900IU ~ approximately 1,750IU, approximately 900IU ~ approximately 2,000IU, approximately 1,000IU ~ approximately 1,250IU, about 1,000IU to about 1,500IU, about 1,000IU to about 1,750IU, about 1,000IU to about 2,000IU, about 1 ,000IU ~ approx. 3,000IU, approx. 1,000IU ~ approx. 4,000IU, approx. 1,000IU ~ approx. 5,000IU, approx. 1,000IU ~ approx. 6,000IU, about 1,000IU to about 7,000IU, about 1,000IU to about 8,000IU, about 1,000IU to about 9,000IU, Approx. 1,000IU~Approx. 10,000IU, Approx. 2,000IU~Approx. 3,000IU, Approx. 2,000IU~Approx. 4,000IU, Approx. 2,000I U~about 5,000IU, about 2,000IU~about 6,000IU, about 2,000IU~about 7,000IU, about 2,000IU~about 8,000 IU, about 2,000IU to about 9,000IU, about 2,000IU to about 10,000IU, about 2,500IU to about 3,000IU, about 2.5 00IU ~ approx. 4,000IU, approx. 2,500IU ~ approx. 5,000IU, approx. 2,500IU ~ approx. 6,000IU, approx. 2,500IU ~ approx. 7, 000IU, about 2,500IU to about 8,000IU, about 2,500IU to about 9,000IU, about 2,500IU to about 10,000IU, about 3,000IU ~ approx. 4,000IU, approx. 3,000IU ~ approx. 5,000IU, approx. 3,000IU ~ approx. 6,000IU, approx. 3,000IU ~ Approx. 7,000IU, approx. 3,000IU ~ approx. 8,000IU, approx. 3,000IU ~ approx. 9,000IU, approx. 3,000IU ~ approx. 10,000I U, about 4,000IU to about 5,000IU, about 4,000IU to about 6,000IU, about 4,000IU to about 7,000IU, about 4,000 IU ~ approx. 8,000 IU, approx. 4,000 IU ~ approx. 9,000 IU, approx. 4,000 IU ~ approx. 10,000 IU, approx. 5,000 IU ~ approx. 6,0 00IU, about 5,000IU to about 7,000IU, about 5,000IU to about 8,000IU, about 5,000IU to about 9,000IU, about 5, 000IU ~ approx. 10,000IU, approx. 6,000IU ~ approx. 7,000IU, approx. 6,000IU ~ approx. 8,000IU, approx. 6,000IU ~ approx. 9,000 IU, approximately 6,000 IU to approximately 10,000 IU, approximately 7,000 IU to approximately 8,000 IU, approximately 7,000 IU to approximately 9,000 IU, approximately 7,000 IU to approximately 10,000 IU, approximately 8,000 IU to approximately 9,000 IU, approximately 8,000 IU to approximately 10,000 IU, or approximately 9,It can contain hyaluronidase in amounts ranging from 000 IU to approximately 10,000 IU.

[0035] With respect to multiple doses of the hyaluronidase-containing compositions disclosed herein, all doses of the administration should be carried out as quickly as possible to reduce or eliminate hyaluronic acid-induced blockages in one or more blood vessels of the eye. In aspects of this embodiment, all doses in multiple doses should be carried out within, for example, at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, or at least 90 minutes. In other embodiments of this model, all doses in a multiple-dose regimen are administered within, for example, no more than 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 11 minutes, 12 minutes, 13 minutes, 14 minutes, 15 minutes, 30 minutes, 45 minutes, 60 minutes, 75 minutes, or 90 minutes. In yet another embodiment of this embodiment, all doses in multiple administrations are, for example, approximately 2 to 3 minutes, approximately 2 to 4 minutes, approximately 2 to 5 minutes, approximately 2 to 6 minutes, approximately 3 to 4 minutes, approximately 3 to 5 minutes, approximately 3 to 6 minutes, approximately 4 to 5 minutes, approximately 4 to 6 minutes, approximately 5 to 6 minutes, approximately 5 to 7 minutes, approximately 5 to 8 minutes, approximately 5 to 9 minutes, approximately 5 to 10 minutes, approximately 5 to 11 minutes, approximately 6 to 7 minutes, approximately 6 to 8 minutes, approximately 6 to 9 minutes, approximately 6 to 10 minutes, approximately 6 to 11 minutes, approximately 7 to 8 minutes, approximately 7 to 9 minutes, approximately 7 It will be completed within 10 minutes to approximately 10 minutes, 7 minutes to approximately 11 minutes, 8 minutes to approximately 9 minutes, 8 minutes to approximately 10 minutes, 8 minutes to approximately 11 minutes, 9 minutes to approximately 10 minutes, 9 minutes to approximately 11 minutes, 10 minutes to approximately 11 minutes, 10 minutes to approximately 12 minutes, 10 minutes to approximately 13 minutes, 10 minutes to approximately 14 minutes, 10 minutes to approximately 15 minutes, 11 minutes to approximately 12 minutes, 11 minutes to approximately 13 minutes, 11 minutes to approximately 14 minutes, 11 minutes to approximately 15 minutes, 12 minutes to approximately 13 minutes, 12 minutes to approximately 14 minutes, 12 minutes to approximately 15 minutes, 13 minutes to approximately 14 minutes, 13 minutes to approximately 15 minutes, or within approximately 14 minutes to approximately 15 minutes.In yet another embodiment of this embodiment, all doses in multiple administrations are given within, for example, approximately 2 to 5 minutes, 2 to 10 minutes, 2 to 15 minutes, 5 to 10 minutes, 5 to 15 minutes, 5 to 30 minutes, 10 to 15 minutes, 10 to 30 minutes, 15 to 30 minutes, 15 to 45 minutes, 15 to 60 minutes, 15 to 75 minutes, or 15 to 90 minutes.

[0036] With respect to multiple doses of a composition comprising hyaluronidase disclosed herein, the number of doses is the number of times necessary to achieve an effective amount of hyaluronidase to reduce or eliminate blockage caused by hyaluronic acid in one or more blood vessels of the eye. In aspects of this embodiment, the number of doses in multiple doses is, for example, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, at least fourteen, or at least fifteen. In other aspects of this embodiment, the number of doses in multiple doses is, for example, at most two, at most three, at most four, at most five, at most six, at most seven, at most eight, at most nine, at most ten, at most eleven, at most twelve, at most thirteen, at most fourteen, or at most fifteen. In yet another embodiment of this embodiment, the number of doses in multiple administrations is, for example, about 2 to 3 times, about 2 to 4 times, about 2 to 5 times, about 2 to 6 times, about 3 to 4 times, about 3 to 5 times, about 3 to 6 times, about 4 to 5 times, about 4 to 6 times, about 5 to 6 times, about 5 to 7 times, about 5 to 8 times, about 5 to 9 times, about 5 to 10 times, about 5 to 11 times, about 6 to 7 times, about 6 to 8 times, about 6 to 9 times, about 6 to 10 times, about 6 to 11 times, about 7 to 8 times, about 7 to 9 times, 7 to approximately 10 times, approximately 7 to approximately 11 times, approximately 8 to approximately 9 times, approximately 8 to approximately 10 times, approximately 8 to approximately 11 times, approximately 9 to approximately 10 times, approximately 9 to approximately 11 times, approximately 10 to approximately 11 times, approximately 10 to approximately 12 times, approximately 10 to approximately 13 times, approximately 10 to approximately 14 times, approximately 10 to approximately 15 times, approximately 11 to approximately 12 times, approximately 11 to approximately 13 times, approximately 11 to approximately 14 times, approximately 11 to approximately 15 times, approximately 12 to approximately 13 times, approximately 12 to approximately 14 times, approximately 12 to approximately 15 times, approximately 13 to approximately 14 times, approximately 13 to approximately 15 times, or approximately 14 to approximately 15 times. In yet another embodiment of this embodiment, the number of doses in multiple administrations is, for example, about 2 to 5 times, about 2 to 10 times, about 2 to 15 times, about 5 to 10 times, about 5 to 15 times, or about 10 to 15 times.

[0037] Multiple doses of a composition containing hyaluronidase used to effectively reduce or eliminate hyaluronic acid-induced blockages in one or more blood vessels of the eye may contain a total amount of hyaluronidase ranging from about 15 IU to about 10,000 IU. In aspects of this embodiment, multiple doses of a composition containing hyaluronidase used to effectively reduce or eliminate hyaluronic acid-induced blockages in one or more blood vessels of the eye may contain a total amount of, for example, at least 15 IU, at least 25 IU, at least 50 IU, at least 100 IU, at least 200 IU, at least 300 IU, at least 450 IU, at least 600 IU, at least 900 IU, at least 1,000 IU, at least 1,250 IU, at least 1,500 IU, at least 1,750 IU, at least 2,000 IU, at least 3 It may contain hyaluronidase in amounts of 1,000 IU, at least 4,000 IU, at least 5,000 IU, at least 6,000 IU, at least 7,000 IU, at least 8,000 IU, at least 9,000 IU, at least 10,000 IU, at least 11,000 IU, at least 12,000 IU, at least 13,000 IU, at least 14,000 IU, at least 15,000 IU, at least 16,000 IU, at least 17,000 IU, at least 18,000 IU, at least 19,000 IU, or at least 20,000 IU. In other embodiments of this embodiment, multiple doses of a composition comprising hyaluronidase used to effectively reduce or eliminate hyaluronic acid-induced blockages in one or more blood vessels of the eye are, for example, at most 15 IU, at most 25 IU, at most 50 IU, at most 100 IU, at most 200 IU, at most 300 IU, at most 450 IU, at most 600 IU, at most 900 IU It may contain hyaluronidase in amounts of U, at most 1,000 IU, at most 1,250 IU, at most 1,500 IU, at most 1,750 IU, at most 2,000 IU, at most 3,000 IU, at most 4,000 IU, at most 5,000 IU, at most 6,000 IU, at most 7,000 IU, at most 8,000 IU, at most 9,000 IU, or at most 10,000 IU.

[0038] In yet another embodiment of this embodiment, multiple doses of a composition comprising hyaluronidase used to effectively reduce or eliminate hyaluronic acid-induced blockages in one or more blood vessels of the eye are, in total, for example, about 15 IU to about 25 IU, about 15 IU to about 50 IU, about 15 IU to about 100 IU, about 15 IU to about 200 IU, about 15 IU to about 300 IU, about 15 IU to about 400 IU, about 15 IU to about 450 IU, about 15 IU to about 600 IU, about 15 IU to about 750 IU, about 15 IU to about 900 IU, about 25 IU to about 50 IU, about 25 IU to about 100 IU , about 25IU to about 200IU, about 25IU to about 300IU, about 25IU to about 400IU, about 25IU to about 450IU, about 25IU to about 60 0IU, approximately 25IU ~ approximately 750IU, approximately 25IU ~ approximately 900IU, approximately 50IU ~ approximately 100IU, approximately 50IU ~ approximately 200IU, approximately 50IU ~ Approximately 300IU, approximately 50IU to approximately 400IU, approximately 50IU to approximately 450IU, approximately 50IU to approximately 600IU, approximately 50IU to approximately 750IU, approximately 50 IU ~ about 900IU, about 100IU - about 200IU, about 100IU - about 300IU, about 100IU - about 400IU, about 100IU - about 45 0IU, about 100IU to about 600IU, about 100IU to about 750IU, about 100IU to about 900IU, about 200IU to about 300IU, about 2 00IU~about 400IU, about 200IU~about 450IU, about 200IU~about 600IU, about 200IU~about 750IU, about 200IU~about 900IU, about 300IU to about 450IU, about 300IU to about 600IU, about 300IU to about 750IU, about 300IU to about 900IU, Approx. 450IU ~ Approx. 600IU, Approx. 450IU ~ Approx. 750IU, Approx. 450IU ~ Approx. 900IU, Approx. 450IU ~ Approx. 1,000IU, Approx. 450 IU ~ approx. 1,250 IU, approx. 600 IU ~ approx. 750 IU, approx. 600 IU ~ approx. 900 IU, approx. 600 IU ~ approx. 1,000 IU, approx. 600 IU ~1,250IU, 600IU~1,500IU, 750IU~900IU, 750IU~1,000IU, 750IU ~approx. 1,250IU, approx. 750IU ~ approx. 1,500IU, approx. 750IU ~ approx. 1,750IU, approx. 900IU ~ approx. 1,000IU, approx. 900 IU ~ approx. 1,250 IU, approx. 900 IU ~ approx. 1,500 IU, approx. 900 IU ~ approx. 1,750 IU, approx. 900 IU ~ approx. 2,000 IU, approx. 1,000IU ~ approx. 1,250IU, approx. 1,000IU ~ approx. 1,500IU, approx. 1,000IU ~ approx. 1,750IU, approx. 1,000IU ~ approx. 2 ,000IU, about 1,000IU to about 3,000IU, about 1,000IU to about 4,000IU, about 1,000IU to about 5,000IU, about 1 ,000IU ~ approx. 6,000IU, approx. 1,000IU ~ approx. 7,000IU, approx. 1,000IU ~ approx. 8,000IU, approx. 1,000IU ~ approx. 9,000IU, about 1,000IU to about 10,000IU, about 2,000IU to about 3,000IU, about 2,000IU to about 4,000IU, Approx. 2,000IU~Approx. 5,000IU, Approx. 2,000IU~Approx. 6,000IU, Approx. 2,000IU~Approx. 7,000IU, Approx. 2,000IU ~8,000IU, approx. 2,000IU ~ approx. 9,000IU, approx. 2,000IU ~ approx. 10,000IU, approx. 2,500IU ~ approx. 3,000I U, about 2,500IU to about 4,000IU, about 2,500IU to about 5,000IU, about 2,500IU to about 6,000IU, about 2,500 IU ~ approx. 7,000 IU, approx. 2,500 IU ~ approx. 8,000 IU, approx. 2,500 IU ~ approx. 9,000 IU, approx. 2,500 IU ~ approx. 10,00 0IU, about 3,000IU to about 4,000IU, about 3,000IU to about 5,000IU, about 3,000IU to about 6,000IU, about 3,0 00IU ~ approx. 7,000IU, approx. 3,000IU ~ approx. 8,000IU, approx. 3,000IU ~ approx. 9,000IU, approx. 3,000IU ~ approx. 10, 000IU, about 4,000IU to about 5,000IU, about 4,000IU to about 6,000IU, about 4,000IU to about 7,000IU, about 4 ,000IU ~ approx. 8,000IU, approx. 4,000IU ~ approx. 9,000IU, approx. 4,000IU ~ approx. 10,000IU, approx. 5,000IU ~ approx. 6,000IU, about 5,000IU to about 7,000IU, about 5,000IU to about 8,000IU, about 5,000IU to about 9,000IU, Approx. 5,000IU ~ Approx. 10,000IU, Approx. 6,000IU ~ Approx. 7,000IU, Approx. 6,000IU ~ Approx. 8,000IU, Approx. 6,000IU ~approximately 9,000 IU, approximately 6,000 IU~approximately 10,000 IU, approximately 7,000 IU~approximately 8,000 IU, approximately 7,000 IU~approximately 9,000 IU, approximately 7,000 IU~approximately 10,000 IU, approximately 8,000 IU~approximately 9,000 IU, approximately 8,000 IU~approximately 10,000 IU, or approximately 9,It can contain 000 IU to approximately 10,000 IU of hyaluronidase.

[0039] The hyaluronidase-containing compositions disclosed herein are formulated to rapidly cover a relatively large area of ​​the suprachoroidal space of the eye. Such rapid diffusion ensures that a sufficient amount of hyaluronidase is delivered to one or more blood vessels supplying the eye within approximately 90 minutes. In aspects of this embodiment, the hyaluronidase-containing compositions disclosed herein are formulated to rapidly cover a relatively large area of ​​the suprachoroidal space of the eye in, for example, at most 15 minutes, at most 30 minutes, at most 45 minutes, at most 60 minutes, at most 75 minutes, or at most 90 minutes. In other embodiments of this model, compositions comprising hyaluronidase disclosed herein are formulated to rapidly cover a relatively large area of ​​the suprachoroidal space of the eye in, for example, about 5 to 10 minutes, about 5 to 15 minutes, about 5 to 30 minutes, about 10 to 15 minutes, about 10 to 30 minutes, about 15 to 30 minutes, about 15 to 45 minutes, about 15 to 60 minutes, about 15 to 75 minutes, or about 15 to 90 minutes.

[0040] In some embodiments, rapid diffusion ensures that a sufficient amount of hyaluronidase is delivered to one or more blood vessels supplying the eye within about 5 to about 15 minutes. In aspects of this embodiment, the hyaluronidase-containing compositions disclosed herein are formulated to rapidly cover a relatively large area of ​​the suprachoroidal space of the eye in, for example, at most 1 minute, at most 2 minutes, at most 3 minutes, at most 4 minutes, at most 5 minutes, at most 10 minutes, or at most 15 minutes. In other embodiments of this model, compositions comprising hyaluronidase disclosed herein are formulated to rapidly cover a relatively large area of ​​the suprachoroidal space of the eye in, for example, about 1 to 3 minutes, about 1 to 5 minutes, about 1 to 7 minutes, about 1 to 10 minutes, about 1 to 15 minutes, about 3 to 5 minutes, about 3 to 7 minutes, about 3 to 10 minutes, about 3 to 15 minutes, about 5 to 7 minutes, about 5 to 10 minutes, about 5 to 15 minutes, or about 10 to 15 minutes.

[0041] The volume of the composition containing hyaluronidase delivered to the suprachoroidal space can be in the range of about 5 μL to about 500 μL. In this embodiment, the volume of the composition containing hyaluronidase delivered to the suprachoroidal space can be, for example, at least 5 μL, at least 10 μL, at least 20 μL, at least 30 μL, at least 40 μL, at least 50 μL, at least 75 μL, at least 100 μL, at least 200 μL, at least 300 μL, at least 400 μL, or at least 500 μL. In other embodiments of this embodiment, the volume of the composition containing hyaluronidase delivered to the choroidal space may be, for example, at most 5 μL, at most 10 μL, at most 20 μL, at most 30 μL, at most 40 μL, at most 50 μL, at most 75 μL, at most 100 μL, at most 200 μL, at most 300 μL, at most 400 μL, or at most 500 μL. In yet another embodiment of this embodiment, the volume of the composition containing hyaluronidase delivered to the choroidal space is, for example, about 5 μL to about 25 μL, about 5 μL to about 50 μL, about 5 μL to about 75 μL, about 5 μL to about 100 μL, about 10 μL to about 25 μL, about 10 μL to about 50 μL, about 10 μL to about 75 μL, about 10 μL to about 100 μL, about 25 μL to about 50 μL, about 25 μL to about 75 μL, about 25 μL to about 100 μL, about 25 μL to about 150 μL, about 50 μL to about 75 μL, about 50 μL to about 100 μL. The amount can be approximately 50 μL to 150 μL, approximately 50 μL to 200 μL, approximately 50 μL to 250 μL, approximately 100 μL to 150 μL, approximately 100 μL to 200 μL, approximately 100 μL to 250 μL, approximately 100 μL to 300 μL, approximately 100 μL to 400 μL, approximately 100 μL to 500 μL, approximately 200 μL to 300 μL, approximately 200 μL to 400 μL, approximately 200 μL to 500 μL, approximately 300 μL to 400 μL, approximately 300 μL to 500 μL, or approximately 400 μL to 500 μL.

[0042] Embodiments of this specification disclose delivery systems. Examples of delivery systems that are not limited include, for example, needles and syringes, ADG needles, ADG-like needles, or microinjectors. Examples of needle gauges useful for delivery systems such as needles and syringes, ADG needles, ADG-like needles, or microinjectors that are not limited include 21 gauge, 22 gauge, 23 gauge, 24 gauge, 25 gauge, 26 gauge, 27 gauge, 28 gauge, 29 gauge, 30 gauge, 31 gauge, 32 gauge, and 33 gauge.

[0043] Other aspects of this specification disclose microinjectors. Examples of microinjectors, not limited to them, include choroidal microinjectors. Compositions comprising hyaluronidase disclosed herein can be administered into the suprachoroidal space of the eye using a microinjector (Figure 5). Such microinjectors are commercially available and include, but are not limited to, the SCS® microinjector (Clearside Biomedical Inc., Alpharetta, GA).

[0044] Aspects of this specification disclose the suprachoroidal space, which is the space between the choroid and sclera extending around the posterior segment of the eye. The suprachoroidal space facilitates easy access to the choroid, retinal pigment epithelium, and retina.

[0045] Choroidal administration of hyaluronidase-containing compositions for the treatment of ocular vascular occlusion has several potential advantages, including high bioavailability and differentiated efficacy and safety. Choroidal administration allows access to the posterior tissues of the eye. As shown in Figures 6A–6D, the fluid injected into the choroid rapidly covers a relatively large area of ​​several square centimeters within seconds of administration. Furthermore, the distribution of hyaluronidase is mainly in the retina and choroid, with small amounts of the enzyme entering the anterior segment of the eye, resulting in a lower incidence of increased IOP (intraocular pressure) and cataract formation. Choroidal administration is also an attractive route for hyaluronidase delivery because it allows for scleral bypass without the risk of intraocular penetration. In addition to keeping systemic levels of hyaluronidase low, choroidal administration also facilitates the use of smaller amounts of hyaluronidase compared to intravitreous or other ocular delivery routes.

[0046] Aspects of this specification disclose methods for reducing or eliminating hyaluronic acid-induced blockages in one or more blood vessels supplying blood to the eye. The disclosed methods involve administering a composition comprising hyaluronidase to an individual in a manner that reduces or eliminates hyaluronic acid-induced blockages in one or more blood vessels supplying blood to the eye. In some aspects, the disclosed methods involve administering the hyaluronidase-containing composition into the suprachoroidal space of the eye. In other aspects, the disclosed methods involve administering the hyaluronidase-containing composition using a delivery system disclosed herein. The disclosed methods may administer the hyaluronidase-containing composition in single or multiple doses ranging from about 15 IU to about 10,000 IU of hyaluronidase.

[0047] In aspects of this embodiment, reducing or eliminating hyaluronic acid-induced blockages in one or more blood vessels supplying the eye reduces or suppresses one or more physiological conditions or symptoms associated with hyaluronic acid-induced blockages in one or more blood vessels of the eye by, for example, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% or more. In other aspects of this embodiment, reducing or eliminating hyaluronic acid-induced blockages in one or more blood vessels supplying the eye reduces or suppresses one or more physiological conditions or symptoms associated with hyaluronic acid-induced blockages in one or more blood vessels of the eye by, for example, at most 10%, at most 20%, at most 30%, at most 40%, at most 50%, at most 60%, at most 70%, at most 80%, at most 90%, or at most 100%.In yet another embodiment of this embodiment, reducing or eliminating hyaluronic acid-induced blockages in one or more blood vessels supplying blood to the eye reduces one or more physiological conditions or symptoms associated with hyaluronic acid-induced blockages in one or more blood vessels of the eye, for example, about 10% to about 100%, about 10% to about 90%, about 10% to about 80%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 10% to about 20%, about 20% to about 100%, about 20% to about 90%, about 20% to about 80%, about 20% to about 70%, about 20% to about 60%, about 20% to about 50%, about 20% to about 40%, about 20% to about 30%, about 3 0% to approximately 100%, approximately 30% to approximately 90%, approximately 30% to approximately 80%, approximately 30% to approximately 70%, approximately 30% to approximately 60%, approximately 30% to approximately 50%, approximately 30% to approximately 40%, approximately 40% to approximately 100%, approximately 40% to approximately 90%, approximately 40% to approximately 80%, approximately 40% to approximately 70%, approximately 40% to approximately 60%, approximately 40% to approximately 50%, approximately 50% to approximately 100%, approximately 50% to approximately Reduce or suppress by 90%, approximately 50% to approximately 80%, approximately 50% to approximately 70%, approximately 50% to approximately 60%, approximately 60% to approximately 100%, approximately 60% to approximately 90%, approximately 60% to approximately 80%, approximately 60% to approximately 70%, approximately 70% to approximately 100%, approximately 70% to approximately 90%, approximately 70% to approximately 80%, approximately 80% to approximately 100%, approximately 80% to approximately 90%, or approximately 90% to approximately 100%. In yet another embodiment of this embodiment, reducing or eliminating hyaluronic acid-induced blockages in one or more blood vessels supplying the eye reduces or suppresses one or more physiological conditions or symptoms associated with hyaluronic acid-induced blockages in one or more blood vessels of the eye, for example, over a period of at least one week, at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least seven months, at least eight months, at least nine months, at least ten months, at least eleven months, or at least twelve months.

[0048] Aspects of this specification disclose methods for reducing or suppressing vascular occlusion of an individual's eye as needed. Vascular occlusion is reduced or suppressed by reducing or eliminating blockages caused by hyaluronic acid in one or more blood vessels supplying the eye. The disclosed method involves administering a composition comprising hyaluronidase to an individual in a manner that reduces or eliminates blockages caused by hyaluronic acid in one or more blood vessels supplying the eye, thereby reducing or suppressing vascular occlusion of the eye. In some aspects, the disclosed method administers the composition comprising hyaluronidase into the suprachoroidal space of the eye. In other aspects, the disclosed method administers the composition comprising hyaluronidase using a microinjector. The disclosed method may administer the composition comprising hyaluronidase in single or multiple doses ranging from about 15 IU to about 10,000 IU of hyaluronidase.

[0049] In aspects of this embodiment, reducing or suppressing ocular vascular occlusion reduces or suppresses one or more physiological conditions or symptoms associated with hyaluronic acid-induced blockages in one or more blood vessels of the eye by, for example, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 100%. In other aspects of this embodiment, reducing or suppressing ocular vascular occlusion reduces or suppresses one or more physiological conditions or symptoms associated with hyaluronic acid-induced blockages in one or more blood vessels of the eye by, for example, at most 10%, at most 20%, at most 30%, at most 40%, at most 50%, at most 60%, at most 70%, at most 80%, at most 90%, or at most 100%. In yet another embodiment of this embodiment, reducing or suppressing ocular vascular occlusion is one or more physiological conditions or symptoms associated with hyaluronic acid-induced blockage in one or more blood vessels of the eye, for example, about 10% to about 100%, about 10% to about 90%, about 10% to about 80%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 10% to about 20%, about 20% to about 100%, about 20% to about 90%, about 20% to about 80%, about 20% to about 70%, about 20% to about 60%, about 20% to about 50%, about 20% to about 40%, about 20% to about 30%, about 30% to about 100%, about 30% to about 90%, approximately 30% to 80%, approximately 30% to 70%, approximately 30% to 60%, approximately 30% to 50%, approximately 30% to 40%, approximately 40% to 100%, approximately 40% to 90%, approximately 40% to 80%, approximately 40% to 70%, approximately 40% to 60%, approximately 40% to 50%, approximately 50% to 100%, approximately 50% to 90%, approximately 50% Reduce or suppress by approximately 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%.In yet another embodiment of this embodiment, reducing or suppressing ocular vascular occlusion reduces or suppresses one or more physiological conditions or symptoms associated with hyaluronic acid-induced blockage in one or more blood vessels of the eye, for example, over a period of at least one week, at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least seven months, at least eight months, at least nine months, at least ten months, at least eleven months, or at least twelve months.

[0050] Aspects of this specification disclose methods for reducing or suppressing, as needed, hyaluronic acid-induced vision loss in an individual. Hyaluronic acid-induced vision loss is reduced or suppressed by reducing or eliminating hyaluronic acid-induced blockages in one or more blood vessels supplying the eye. The disclosed method involves administering a composition comprising hyaluronidase to an individual in a manner that reduces or eliminates hyaluronic acid-induced blockages in one or more blood vessels supplying the eye, thereby reducing or suppressing the individual's hyaluronic acid-induced vision loss. In some aspects, the disclosed method administers the hyaluronidase-containing composition into the suprachoroid space of the eye. In other aspects, the disclosed method administers the hyaluronidase-containing composition using a delivery system disclosed herein. The disclosed method may administer the hyaluronidase-containing composition in single or multiple doses ranging from about 15 IU to about 10,000 IU of hyaluronidase.

[0051] In some embodiments, when the method disclosed herein involves multiple doses of hyaluronidase, such doses can be administered rapidly and consecutively. In aspects of these embodiments, 3 to 20 doses of the hyaluronidase-containing composition can be administered to the same eye within 5 to 15 minutes. In other embodiments, 5 to 15 doses of the hyaluronidase-containing composition can be administered to the same eye within 5 to 15 minutes. In yet another embodiment, 7 to 15 doses of the hyaluronidase-containing composition can be administered to the same eye within 5 to 15 minutes. In yet another embodiment, 8 to 12 doses of the hyaluronidase-containing composition can be administered to the same eye within 5 to 15 minutes. In yet another embodiment, 10 doses of the hyaluronidase-containing composition can be administered to the same eye within 5 to 15 minutes.

[0052] In aspects of this embodiment, reducing or eliminating hyaluronic acid-induced blockages in one or more blood vessels supplying the eye restores or maintains one or more qualitative or quantitative aspects of vision by, for example, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 100%. In other aspects of this embodiment, reducing or eliminating hyaluronic acid-induced blockages in one or more blood vessels supplying the eye restores or maintains one or more qualitative or quantitative aspects of vision by, for example, at most 10%, at most 20%, at most 30%, at most 40%, at most 50%, at most 60%, at most 70%, at most 80%, at most 90%, or at most 100%. In yet another embodiment of this embodiment, reducing or eliminating blockages caused by hyaluronic acid in one or more blood vessels supplying blood to the eye is one or more qualitative or quantitative aspects of vision, for example, about 10% to about 100%, about 10% to about 90%, about 10% to about 80%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 10% to about 20%, about 20% to about 100%, about 20% to about 90%, about 20% to about 80%, about 20% to about 70%, about 20% to about 60%, about 20% to about 50%, about 20% to about 40%, about 20% to about 30%, about 30% to about 100%, about 30% to about 90%, approximately 30% to 80%, approximately 30% to 70%, approximately 30% to 60%, approximately 30% to 50%, approximately 30% to 40%, approximately 40% to 100%, approximately 40% to 90%, approximately 40% to 80%, approximately 40% to 70%, approximately 40% to 60%, approximately 40% to 50%, approximately 50% to 100%, approximately 50% to 90%, approximately 50% Recover or maintain approximately 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%.In yet another embodiment of this embodiment, reducing or eliminating hyaluronic acid-induced blockages in one or more blood vessels supplying the eye restores or maintains one or more qualitative or quantitative aspects of vision for, for example, over a period of at least one week, at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least seven months, at least eight months, at least nine months, at least ten months, at least eleven months, or at least twelve months.

[0053] In one embodiment, as shown in Figures 6A–6D, a composition containing hyaluronidase can be administered into the suprachoroidal space. Referring to Figures 6A–6B, a delivery system, depicted as a microinjector, is positioned on a portion of the sclera, with the device perpendicular to the surface of the injection site. Referring now to Figure 6C, the device is then pressed against the scleral surface so that a “recess” is formed around the hub of the delivery system. As shown in Figure 6D, the needle of the delivery system is then inserted into the suprachoroidal space through the scleral layer, and the plunger of the device is gently pressed down, maintaining the recess on the surface of the eye for 3–5 seconds, to fully administer the hyaluronidase into the suprachoroidal space. Depending on the user's preference, administration can be performed with one or both hands.

[0054] The methods disclosed herein reduce or eliminate hyaluronic acid-induced blockages in one or more blood vessels supplying blood to the eye. In some embodiments, the methods disclosed herein reduce or eliminate hyaluronic acid-induced blockages in one or more blood vessels supplying blood to the eye within a timeframe that prevents, reduces, or stops vision loss or damage to other organs or tissues.

[0055] In some embodiments, the methods disclosed herein reduce or eliminate hyaluronic acid-induced blockages in one or more blood vessels supplying the eye within about 90 minutes. In aspects of this embodiment, hyaluronic acid-induced blockages in one or more blood vessels supplying the eye are reduced or eliminated in, for example, at most 15 minutes, at most 30 minutes, at most 45 minutes, at most 60 minutes, at most 75 minutes, or at most 90 minutes. In other embodiments of this embodiment, hyaluronic acid-induced blockages in one or more blood vessels supplying the eye are reduced or eliminated in, for example, about 5 to about 10 minutes, about 5 to about 15 minutes, about 5 to about 30 minutes, about 10 to about 15 minutes, about 10 to about 30 minutes, about 15 to about 30 minutes, about 15 to about 45 minutes, about 15 to about 60 minutes, about 15 to about 75 minutes, or about 15 to about 90 minutes.

[0056] In some embodiments, the methods disclosed herein reduce or eliminate hyaluronic acid-induced blockages in one or more blood vessels supplying the eye within about 5 to about 15 minutes. In aspects of these embodiments, the hyaluronic acid-induced blockages in one or more blood vessels supplying the eye are reduced or eliminated, for example, in at most 1 minute, at most 2 minutes, at most 3 minutes, at most 4 minutes, at most 5 minutes, at most 10 minutes, or at most 15 minutes. In other embodiments of this embodiment, blockages caused by hyaluronic acid in one or more blood vessels supplying blood to the eye are reduced or eliminated, for example, in about 1 to 3 minutes, 1 to 5 minutes, 1 to 7 minutes, 1 to 10 minutes, 1 to 15 minutes, 3 to 5 minutes, 3 to 7 minutes, 3 to 10 minutes, 3 to 15 minutes, 5 to 7 minutes, 5 to 10 minutes, 5 to 15 minutes, or 10 to 15 minutes.

[0057] Embodiments of this specification disclose kits. In one embodiment, the kit may include a container for containing a composition comprising the hyaluronidase disclosed herein. In another embodiment, the kit may include a plurality of containers, each of which may contain a composition comprising the hyaluronidase disclosed herein. For example, the kit may include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 or more containers, each of which may contain a composition comprising the hyaluronidase disclosed herein. Each of the disclosed containers may contain a single-dose composition comprising the hyaluronidase disclosed herein, a multi-dose composition comprising the hyaluronidase disclosed herein, or a combination thereof. Furthermore, each of the disclosed containers may contain the composition comprising the hyaluronidase disclosed herein in liquid or dry form.

[0058] In some embodiments, the container disclosed herein may be a vial or similar container for containing a composition comprising the hyaluronidase disclosed herein, and such a composition comprising the hyaluronidase disclosed herein needs to be transferred to a delivery system such as a needle and syringe, an ADG needle, or a microinjector. In some embodiments, the kit comprises one or more vials, e.g., 7 to 15 vials, or 8 to 12 vials, or 10 vials, each containing a composition comprising the hyaluronidase disclosed herein, and optionally, one or more delivery systems, e.g., 7 to 15 delivery systems, or 8 to 12 delivery systems, or 10 delivery systems, used to deliver the compositions disclosed as needed.

[0059] In some embodiments, the container disclosed herein may be a delivery system containing a composition comprising the hyaluronidase disclosed herein. In some embodiments, the kit comprises one or more delivery systems, e.g., 7 to 15 delivery systems, or 8 to 12 delivery systems, or 10 delivery systems, each of which may contain a composition comprising the hyaluronidase disclosed herein. In aspects of this embodiment, the kit comprises one or more microinjectors, e.g., 7 to 15 microinjectors, or 8 to 12 microinjectors, or 10 microinjectors, each of which may contain a composition comprising the hyaluronidase disclosed herein. In aspects of this embodiment, the kit comprises one or more ADG needles, e.g., 7 to 15 ADG needles, or 8 to 12 ADG needles, or 10 ADG needles, each of which may contain a composition comprising the hyaluronidase disclosed herein.

[0060] The kits disclosed herein may include other components. For example, the kits disclosed herein may further include a container for containing a solvent, such as water or a buffer, such as physiological saline. The solvents disclosed herein are useful for reconstituting the dried pharmaceutical compositions disclosed herein.

[0061] The kits disclosed herein may include a delivery system. The delivery system of the kit is useful for applying the compositions disclosed herein to a site of interest, for example, the suprachoroidal space disclosed herein. The delivery or application systems disclosed herein include, but are not limited to, one or more needles, syringes, ADG needles, and / or microinjectors. In one embodiment, the kit includes a single delivery system. In another embodiment, the kit includes multiple delivery systems. For example, each kit may include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 or more delivery systems. Within a kit, the delivery systems may be packaged individually or in sets of two or more. The delivery systems may be packaged so that they remain sterile until use. In certain embodiments, the delivery systems disclosed herein may be packaged in a plastic sheath. Furthermore, to prevent contamination, the delivery systems disclosed herein are preferably single-use, disposable delivery systems.

[0062] The kit may also include a set of instructions for use. These instructions may include information useful to the end user, such as, for example, how to use the delivery system to apply the compositions disclosed herein and / or how often to apply the compositions disclosed herein. Furthermore, such instructions may include information on how to mix the solvents disclosed herein to reconstitute the dried compositions disclosed herein. Such instructions may indicate that mixing should be performed at a specific time before application, for example, immediately before use. The instructions disclosed herein may also include information on how to apply the compositions disclosed herein directly to a site of interest, for example, the suprachoroidal space disclosed herein, and the order or timing to which the compositions disclosed herein should be applied to such a site of interest.

[0063] The contents of the kit, including the container, composition, delivery system, and instructions for use disclosed herein, are enclosed in an outer casing. The outer casing may be a box, a sealed bag, a foil pouch, etc. In certain embodiments, the delivery system, container, and instructions for use are enclosed in a box. In other embodiments of the kit, the container and instructions for use are housed in a first box, the delivery system in a second box, and the first and second boxes together in a third box.

[0064] Aspects of this specification can also be described by the following embodiments: 1. A method for reducing or eliminating, as necessary, a blockage caused by hyaluronic acid in one or more blood vessels supplying blood to an individual's eye, comprising administering to the individual a composition containing hyaluronidase in a manner that reduces or eliminates a blockage caused by hyaluronic acid in one or more blood vessels supplying blood to the eye. 2. A method for reducing or suppressing vascular occlusion of an individual's eye as needed, comprising administering to the individual a composition comprising hyaluronidase in such a manner as to reduce or eliminate blockages caused by hyaluronic acid in one or more blood vessels supplying blood to the eye, thereby reducing or suppressing vascular occlusion of the eye. 3. A method for reducing or suppressing, as necessary, hyaluronic acid-induced vision loss in an individual, comprising administering to the individual a composition containing hyaluronidase in such a manner that it reduces or eliminates blockages caused by hyaluronic acid in one or more blood vessels supplying blood to the eye, thereby reducing or suppressing hyaluronic acid-induced vision loss in the individual. 4. The method according to any one of Embodiments 1 to 3, wherein the composition is administered into the suprachoroidal space of the eye. 5. The method according to any one of Embodiments 1 to 4, wherein the composition is administered using a delivery system. 6. The composition contains at least 15 IU / mL, at least 25 IU / mL, at least 50 IU / mL, at least 100 IU / mL, at least 200 IU / mL, at least 300 IU / mL, at least 450 IU / mL, at least 600 IU / mL, at least 900 IU / mL, at least 1,000 IU / mL, at least 1,250 IU / mL, at least 1,500 IU / mL, at least 1,750 IU / mL, at least 2,000 IU / mL, at least 3,000 IU / mL, at least 4,000 IU / mL, and less than At least 5,000 IU / mL, at least 6,000 IU / mL, at least 7,000 IU / mL, at least 8,000 IU / mL, at least 9,000 IU / mL, at least 10,000 IU / mL, at least 11,000 IU / mL, at least 12,000 IU / mL, at least 13,000 IU / mL, at least 14,000 IU / mL, at least 15,000 IU / mL, at least 16,000 IU / mL, at least 17,000 IU / mL, at least 18,000 IU / mL, at least 19,000 IU / mL L, or a concentration of at least 20,000 IU / mL; and / or at most 15 IU / mL, at most 25 IU / mL, at most 50 IU / mL, at most 100 IU / mL, at most 200 IU / mL, at most 300 IU / mL, at most 450 IU / mL, at most 600 IU / mL, at most 900 IU / mL, at most 1,000 IU / mL, at most 1,250 IU / mL, at most 1,500 IU / mL, at most 1,750 IU / mL, at most 2,000 IU / mL, at most 3,000 IU / mL, at most 4,000 IU / mL, at most 5,000 IU / mL, at most 6,000 IU / mL, at most 7,000 IU / mL, at most 8,000 IU / mL, at most 9,000 IU / mL, at most 10,000 IU / mL, at most 11,000 IU / mL, at most 12,000 IU / mL, at most 13,000 IU / mL, at most 14,000 IU / mL, at most 15,000 IU / mL, at most 16,000 IU / mL, at most 17,000 IU / mL, at most 18,000 IU / mL, at most 19,000 IU / mL, or at most 20,Amounts of 000 IU / mL; or approximately 15 IU / mL to approximately 25 IU / mL, approximately 15 IU / mL to approximately 50 IU / mL, approximately 15 IU / mL to approximately 100 IU / mL, approximately 15 IU / mL to approximately 200 IU / mL, approximately 15 IU / mL to approximately 300 IU / mL, approximately 15 IU / mL to approximately 400 IU / mL, approximately 15 IU / mL to approximately 450 IU / mL, approximately 15 IU / mL to approximately 600 IU / mL, approximately 15 IU / mL to approximately 750 IU / mL, approximately 15 IU / mL to approximately 900 IU / mL, approximately 25 IU / mL to approximately 50 IU / mL, approximately 25 IU / mL to approximately 100 IU / mL, Approximately 25IU / mL to approximately 200IU / mL, approximately 25IU / mL to approximately 300IU / mL, approximately 25IU / mL to approximately 400IU / mL, approximately 25IU / mL to approximately 450IU / mL, approximately 25IU / mL to approximately 600IU / mL, approximately 25IU / mL to approximately 750IU / mL, approximately 25IU / mL mL ~ about 900IU / mL, about 50IU / mL - about 100IU / mL, about 50IU / mL - about 200IU / mL, about 50IU / mL - about 300IU / mL, about 50IU / mL - about 400IU / mL, about 50IU / mL - about 450IU / mL, about 50IU / mL - about 60 0IU / mL, about 50IU / mL to about 750IU / mL, about 50IU / mL to about 900IU / mL, about 100IU / mL to about 200IU / mL, about 100IU / mL to about 300IU / mL, about 100IU / mL to about 400IU / mL, about 100IU / mL to about 450I U / mL, about 100IU / mL to about 600IU / mL, about 100IU / mL to about 750IU / mL, about 100IU / mL to about 900IU / mL, about 200IU / mL to about 300IU / mL, about 200IU / mL to about 400IU / mL, about 200IU / mL to about 450I U / mL, about 200IU / mL to about 600IU / mL, about 200IU / mL to about 750IU / mL, about 200IU / mL to about 900IU / mL, about 300IU / mL to about 450IU / mL, about 300IU / mL to about 600IU / mL, about 300IU / mL to about 750I U / mL, about 300IU / mL to about 900IU / mL, about 450IU / mL to about 600IU / mL, about 450IU / mL to about 750IU / mL, about 450IU / mL to about 900IU / mL, about 450IU / mL to about 1,000IU / mL, about 450IU / mL to about 1,250 IU / mL, approximately 600 IU / mL to approximately 750 IU / mL, approximately 600 IU / mL to approximately 900 IU / mL, approximately 600 IU / mL to approximately 1,000 IU / mL, approximately 600 IU / mL to approximately 1,250 IU / mL, approximately 600 IU / mL to approximately 1,500 IU / mL, approximately 750 IU / mL to approximately 900 IU / mL, approximately 750 IU / mL to approximately 1,000 IU / mL, approximately 750 IU / mL to approximately 1,250 IU / mL, approximately 750 IU / mL to approximately 1,250 IU / mL, approximately 750 IU / mL to approximately 1,500 IU / mL, approximately 750 IU / mL to approximately 1,750 IU / mL, approximately 900 IU / mL to approximately 1,000 IU / mL, approximately 900 IU / mL ~ approx. 1,250 IU / mL, approx. 900 IU / mL ~ approx. 1,500 IU / mL, approx. 900 IU / mL ~ approx. 1,750 IU / mL, approx. 900 IU / mL ~ approx. 2,000 IU / mL, approx. 1,000 IU / mL ~ approx. 1,250 IU / mL, approx. 1,000 IU / mL ~ approx. 1,500 IU / mL, approx. 1,000 IU / mL ~ approx. 1,750 IU / mL, approx. 1,000 IU / mL ~ approx. 2,000 IU / mL, approx. 1,000 IU / mL ~ approx. 2,000 IU / mL, approx. 1,000 IU / mL ~ approx. 3,000 IU / mL, approx. 1,000 IU / mL ~ approx. 4,000 IU / mL, approx. 1,000 IU / mL ~ approx. 5,000 IU / mL L, approximately 1,000 IU / mL to approximately 6,000 IU / mL, approximately 1,000 IU / mL to approximately 7,000 IU / mL, approximately 1,000 IU / mL to approximately 8,000 IU / mL, approximately 1,000 IU / mL to approximately 9,000 IU / mL, approximately 1,000 IU / mL to approximately 10,000 IU / mL, approximately 2,000 IU / mL to approximately 3,000 IU / mL, approximately 2,000 IU / mL to approximately 4,000 IU / mL, approximately 2,000 IU / mL to approximately 5,000 IU / mL, approximately 2,000 IU / mL to approximately 6,000 IU / mL, approximately 2,000 IU / mL to approximately 7,000 IU / mL, approximately 2,000 IU / mL U / mL ~ approx. 8,000 IU / mL, approx. 2,000 IU / mL ~ approx. 9,000 IU / mL, approx. 2,000 IU / mL ~ approx. 10,000 IU / mL, approx. 2,500 IU / mL ~ approx. 3,000 IU / mL, approx. 2,500 IU / mL ~ approx. 4,000 IU / mL, approx. 2,500 IU / mL ~ approx. 5,000 IU / mL, approx. 2,500 IU / mL ~ approx. 6,000 IU / mL, approx. 2,500 IU / mL ~ approx. 7,000 IU / mL, approx. 2,500 IU / mL ~ approx. 8,000 IU / mL, approx. 2,500 IU / mL ~ approx. 9,000 IU / mL, approx. 2,500 IU / mL ~ approx. 10,000 IU / mL000 IU / mL, approximately 3,000 IU / mL to approximately 4,000 IU / mL, approximately 3,000 IU / mL to approximately 5,000 IU / mL, approximately 3,000 IU / mL to approximately 6,000 IU / mL, approximately 3,000 IU / mL to approximately 7,000 IU / mL, approximately 3,000 IU / mL to approximately 8,000 IU / mL, approximately 3,000 IU / mL to approximately 9,000 IU / mL, approximately 3,000 IU / mL to approximately 10,000 IU / mL, approximately 4,000 IU / mL to approximately 5,000 IU / mL, approximately 4,000 IU / mL to approximately 6,000 IU / mL, approximately 4,000 IU / mL to approximately 7,000 IU / mL mL, approximately 4,000 IU / mL to approximately 8,000 IU / mL, approximately 4,000 IU / mL to approximately 9,000 IU / mL, approximately 4,000 IU / mL to approximately 10,000 IU / mL, approximately 5,000 IU / mL to approximately 6,000 IU / mL, approximately 5,000 IU / mL to approximately 7,000 IU / mL, approximately 5,000 IU / mL to approximately 8,000 IU / mL, approximately 5,000 IU / mL to approximately 9,000 IU / mL, approximately 5,000 IU / mL to approximately 10,000 IU / mL, approximately 6,000 IU / mL to approximately 7,000 IU / mL, approximately 6,000 IU / mL to approximately 8,000 IU / mL, approximately 6, 000 IU / mL ~ approx. 9,000 IU / mL, approx. 6,000 IU / mL ~ approx. 10,000 IU / mL, approx. 7,000 IU / mL ~ approx. 8,000 IU / mL, approx. 7,000 IU / mL ~ approx. 9,000 IU / mL, approx. 7,000 IU / mL ~ approx. 10,000 IU / mL, approx. 8,000 IU / mL ~ approx. 9,000 IU / mL, approx. 8,000 IU / mL ~ approx. 10,000 IU / mL, approx. 10,000 IU / mL ~ approx. 11,000 IU / mL, approx. 10,000 IU / mL ~ approx. 12,000 IU / mL, approx. 10 Approximately 13,000 IU / mL, approximately 10,000 IU / mL to approximately 14,000 IU / mL, approximately 10,000 IU / mL to approximately 15,000 IU / mL, approximately 10,000 IU / mL to approximately 16,000 IU / mL, approximately 10,000 IU / mL to approximately 17,000 IU / mL, approximately 10,000 IU / mL to approximately 18,000 IU / mL, approximately 10,000 IU / mL to approximately 19,000 IU / mL, approximately 10,000 IU / mL to approximately 20,000 IU / mL, approximately 11,000 IU / mL to approximately 12,000 IU / mL, approximately 11,000 IU / mL to approximately 13,000 IU / mL, approximately 14,000 IU / mL, approximately 15,000 IU / mL, approximately 16,000 IU / mL, approximately 17,000 IU / mL, approximately 18,000 IU / mL, approximately 19,000 IU / mL, approximately 20,000 IU / mL, approximately 11,000 IU / mL to approximately 12,000 IU / mL, approximately 13,000 IU / mL000 IU / mL, approximately 11,000 IU / mL to approximately 14,000 IU / mL, approximately 11,000 IU / mL to approximately 15,000 IU / mL, approximately 11,000 IU / mL to approximately 16,000 IU / mL, approximately 11,000 IU / mL to approximately 17,000 IU / mL, approximately 11,000 IU / mL to approximately 18,000 IU / mL, approximately 11,000 IU / mL to approximately 19,000 IU / mL, approximately 11,000 IU / mL to approximately 20,000 IU / mL, approximately 12,000 IU / mL to approximately 13,000 IU / mL, approximately 12,000 IU / mL to approximately 14,000 IU / mL, approximately 12,000 IU / mL IU / mL ~ approx. 15,000 IU / mL, approx. 12,000 IU / mL ~ approx. 16,000 IU / mL, approx. 12,000 IU / mL ~ approx. 17,000 IU / mL, approx. 12,000 IU / mL ~ approx. 18,000 IU / mL, approx. 12,000 IU / mL ~ approx. 19,000 IU / mL, approx. 12,000 IU / mL ~ approx. 20,000 IU / mL, approx. 13,000 IU / mL ~ approx. 14,000 IU / mL, approx. 13,000 IU / mL ~ approx. 15,000 IU / mL, approx. 13,000 IU / mL ~ approx. 16,000 IU / mL, approx. 13,000 IU / mL ~ approx. 17,000 IU / mL Approximately 13,000 IU / mL to approximately 18,000 IU / mL, approximately 13,000 IU / mL to approximately 19,000 IU / mL, approximately 13,000 IU / mL to approximately 20,000 IU / mL, approximately 14,000 IU / mL to approximately 15,000 IU / mL, approximately 14,000 IU / mL to approximately 16,000 IU / mL, approximately 14,000 IU / mL to approximately 17,000 IU / mL, approximately 14,000 IU / mL to approximately 18,000 IU / mL, approximately 14,000 IU / mL to approximately 19,000 IU / mL, approximately 14,000 IU / mL to approximately 20,000 IU / mL, approximately 15,000 IU / mL Approximately 16,000 IU / mL, approximately 15,000 IU / mL to approximately 17,000 IU / mL, approximately 15,000 IU / mL to approximately 18,000 IU / mL, approximately 15,000 IU / mL to approximately 19,000 IU / mL, approximately 15,000 IU / mL to approximately 20,000 IU / mL, approximately 16,000 IU / mL to approximately 17,000 IU / mL, approximately 16,000 IU / mL to approximately 18,000 IU / mL, approximately 16,000 IU / mL to approximately 19,000 IU / mL, approximately 16,000 IU / mL to approximately 20,000 IU / mL, approximately 17,000 IU / mL to approximately 18,000 IU / mL, approximately 17,The method according to any one of Embodiments 1 to 5, comprising hyaluronidase in an amount of approximately 1,000 IU / mL to 19,000 IU / mL, approximately 17,000 IU / mL to 20,000 IU / mL, approximately 18,000 IU / mL to 19,000 IU / mL, approximately 18,000 IU / mL to 20,000 IU / mL, or approximately 19,000 IU / mL to 20,000 IU / mL. 7. The amount of hyaluronidase administered should be at least 15 IU, at least 25 IU, at least 50 IU, at least 100 IU, at least 200 IU, at least 300 IU, at least 450 IU, at least 600 IU, at least 900 IU, at least 1,000 IU, at least 1,250 IU, at least 1,500 IU, at least 1,750 IU, at least 2,000 IU, at least 3,000 IU, at least 4,000 IU, at least 5,000 IU, at least 6,000 IU, at least 7,000 IU, at least 8,000 IU, at least 9,0 00 IU, or at least 10,000 IU; and / or at most 15 IU, at most 25 IU, at most 50 IU, at most 100 IU, at most 200 IU, at most 300 IU, at most 450 IU, at most 600 IU, at most 900 IU, at most 1,000 IU, at most 1,250 IU, at most 1,500 IU, at most 1,750 IU, at most 2,000 IU, at most 3,000 IU, at most 4,000 IU, at most 5,000 IU, at most 6,000 IU, at most 7,000 IU, at most 8,000 IU, at most 9,000 IU, or at most 10,Amounts of 000 IU; or approximately 15 IU to 25 IU, approximately 15 IU to 50 IU, approximately 15 IU to 100 IU, approximately 15 IU to 200 IU, approximately 15 IU to 300 IU, approximately 15 IU to 400 IU, approximately 15 IU to 450 IU, approximately 15 IU to 600 IU, approximately 15 IU to 750 IU , about 15IU to about 900IU, about 25IU to about 50IU, about 25IU to about 100IU, about 25IU to about 200IU, about 25IU to about 300 IU, about 25IU to about 400IU, about 25IU to about 450IU, about 25IU to about 600IU, about 25IU to about 750IU, about 25IU to about 9 00IU, about 50IU to about 100IU, about 50IU to about 200IU, about 50IU to about 300IU, about 50IU to about 400IU, about 50IU ~450IU, 50IU~600IU, 50IU~750IU, 50IU~900IU, 100IU~200IU, approx. 100IU ~ approx. 300IU, approx. 100IU ~ approx. 400IU, approx. 100IU ~ approx. 450IU, approx. 100IU ~ approx. 600IU, approx. 100IU ~ Approximately 750IU, approximately 100IU to approximately 900IU, approximately 200IU to approximately 300IU, approximately 200IU to approximately 400IU, approximately 200IU to approximately 450IU, Approximately 200IU to approximately 600IU, approximately 200IU to approximately 750IU, approximately 200IU to approximately 900IU, approximately 300IU to approximately 450IU, approximately 300IU ~600IU, 300IU~750IU, 300IU~900IU, 450IU~600IU, 450IU~750I U, about 450IU to about 900IU, about 450IU to about 1,000IU, about 450IU to about 1,250IU, about 600IU to about 750IU, Approx. 600IU ~ Approx. 900IU, Approx. 600IU ~ Approx. 1,000IU, Approx. 600IU ~ Approx. 1,250IU, Approx. 600IU ~ Approx. 1,500IU, Approx. 750IU ~ approx. 900IU, approx. 750IU ~ approx. 1,000IU, approx. 750IU ~ approx. 1,250IU, approx. 750IU ~ approx. 1,500IU, approx. 750IU ~ approx. 1,750IU, approx. 900IU ~ approx. 1,000IU, approx. 900IU ~ approx. 1,250IU, approx. 900IU ~ approx. 1,500IU, Approx. 900IU ~ Approx. 1,750IU, Approx. 900IU ~ Approx. 2,000IU, Approx. 1,000IU ~ Approx. 1,250IU, Approx. 1,000IU ~ Approx. 1, 500IU, about 1,000IU to about 1,750IU, about 1,000IU to about 2,000IU, about 1,000IU to about 3,000IU, about 1,000IU ~ approx. 4,000IU, approx. 1,000IU ~ approx. 5,000IU, approx. 1,000IU ~ approx. 6,000IU, approx. 1,000IU ~7,000IU, approx. 1,000IU ~ approx. 8,000IU, approx. 1,000IU ~ approx. 9,000IU, approx. 1,000IU ~ approx. 10,0 00IU, about 2,000IU to about 3,000IU, about 2,000IU to about 4,000IU, about 2,000IU to about 5,000IU, Approx. 2,000IU ~ Approx. 6,000IU, Approx. 2,000IU ~ Approx. 7,000IU, Approx. 2,000IU ~ Approx. 8,000IU, Approx. 2,000 IU ~ approx. 9,000 IU, approx. 2,000 IU ~ approx. 10,000 IU, approx. 2,500 IU ~ approx. 3,000 IU, approx. 2,500 IU ~ approx. 4,000IU, about 2,500IU to about 5,000IU, about 2,500IU to about 6,000IU, about 2,500IU to about 7,000I U, about 2,500IU to about 8,000IU, about 2,500IU to about 9,000IU, about 2,500IU to about 10,000IU, about 3 ,000IU ~ approx. 4,000IU, approx. 3,000IU ~ approx. 5,000IU, approx. 3,000IU ~ approx. 6,000IU, approx. 3,000IU ~approx. 7,000IU, approx. 3,000IU ~ approx. 8,000IU, approx. 3,000IU ~ approx. 9,000IU, approx. 3,000IU ~ approx. 10, 000IU, about 4,000IU to about 5,000IU, about 4,000IU to about 6,000IU, about 4,000IU to about 7,000IU, Approx. 4,000IU ~ Approx. 8,000IU, Approx. 4,000IU ~ Approx. 9,000IU, Approx. 4,000IU ~ Approx. 10,000IU, Approx. 5,0 00IU ~ approx. 6,000IU, approx. 5,000IU ~ approx. 7,000IU, approx. 5,000IU ~ approx. 8,000IU, approx. 5,000IU ~ approx. The amount is 9,000 IU, approximately 5,000 IU to approximately 10,000 IU, approximately 6,000 IU to approximately 7,000 IU, approximately 6,000 IU to approximately 8,000 IU, approximately 6,000 IU to approximately 9,000 IU, approximately 6,000 IU to approximately 10,000 IU, approximately 7,000 IU to approximately 8,000 IU, approximately 7,000 IU to approximately 9,000 IU, approximately 7,000 IU to approximately 10,000 IU, approximately 8,000 IU to approximately 9,000 IU, approximately 8,000 IU to approximately 10,000 IU, or approximately 9,000 IU to approximately 10,000 IU, according to any one of embodiments 1 to 6. 8. The method according to any one of Embodiments 1 to 7, wherein the composition is administered as a single dose or in multiple doses. 9. The composition shall be in volumes of at least 5 μL, at least 10 μL, at least 20 μL, at least 30 μL, at least 40 μL, at least 50 μL, at least 75 μL, at least 100 μL, at least 200 μL, at least 300 μL, at least 400 μL, or at least 500 μL; and / or at most 5 μL, at most 10 μL, at most 20 μL L, at most 30 μL, at most 40 μL, at most 50 μL, at most 75 μL, at most 100 μL, at most 200 μL, at most 300 μL, at most 400 μL, or at most 500 μL; or approximately 5 μL to approximately 25 μL, approximately 5 μL to approximately 50 μL, approximately 5 μL to approximately 75 μL, approximately 5 μL to approximately 100 μL, approximately 10 μL to approximately 25 μL, approximately 10 μL to approximately 50 μL, approximately 10 μL ~ approx. 75 μL, approx. 10 μL ~ approx. 100 μL, approx. 25 μL ~ approx. 50 μL, approx. 25 μL ~ approx. 75 μL, approx. 25 μL ~ approx. 100 μL, approx. 25 μL ~ approx. Approximately 50μL to approximately 100μL, approximately 50μL to approximately 150μL, approximately 50μL to approximately 200μL, approximately 50μL to approximately 250μL, approximately 100μL to approximately 150μL, approximately 100μL to approximately 200μL, approximately 100 The method according to any one of Embodiments 1 to 8, administered in a volume of approximately μL to 250 μL, approximately 100 μL to 300 μL, approximately 100 μL to 400 μL, approximately 100 μL to 500 μL, approximately 200 μL to 300 μL, approximately 200 μL to 400 μL, approximately 200 μL to 500 μL, approximately 300 μL to 400 μL, approximately 300 μL to 500 μL, or approximately 400 μL to 500 μL. 10. The above methods are at most 1 minute, at most 2 minutes, at most 3 minutes, at most 4 minutes, at most 5 minutes, at most 10 minutes, at most 15 minutes, at most 30 minutes, at most 45 minutes, at most 60 minutes, at most 75 minutes, or at most 90 minutes; or about 1 minute to about 3 minutes, about 1 minute to about 5 minutes, about 1 minute to about 7 minutes, about 1 minute to about 10 minutes, about 1 minute to about 15 minutes, about 3 minutes to about 5 minutes, about 3 The method according to any one of Embodiments 1 to 9, wherein the fluid enters the suprachoroidal space in approximately 10 minutes to 7 minutes, approximately 3 minutes to 10 minutes, approximately 3 minutes to 15 minutes, approximately 5 minutes to 7 minutes, approximately 5 minutes to 10 minutes, approximately 5 minutes to 15 minutes, approximately 5 minutes to 30 minutes, approximately 10 minutes to 15 minutes, approximately 10 minutes to 30 minutes, approximately 15 minutes to 30 minutes, approximately 15 minutes to 45 minutes, approximately 15 minutes to 60 minutes, approximately 15 minutes to 75 minutes, and approximately 15 minutes to 90 minutes. 11. Blockages caused by hyaluronic acid in one or more blood vessels supplying the eye may occur in as little as 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10 minutes, or 15 minutes, 30 minutes, 45 minutes, 60 minutes, 75 minutes, or 90 minutes; or approximately 1 to 3 minutes, approximately 1 to 5 minutes, approximately 1 to 7 minutes, approximately 1 to 10 minutes, approximately 1 minute The method according to any one of Embodiments 1 to 10, wherein the noise is reduced or eliminated in approximately 15 minutes, approximately 3 to 5 minutes, approximately 3 to 7 minutes, approximately 3 to 10 minutes, approximately 3 to 15 minutes, approximately 5 to 7 minutes, approximately 5 to 10 minutes, approximately 5 to 15 minutes, approximately 5 to 30 minutes, approximately 10 to 15 minutes, approximately 10 to 30 minutes, approximately 15 to 30 minutes, approximately 15 to 45 minutes, approximately 15 to 60 minutes, approximately 15 to 75 minutes, and approximately 15 to 90 minutes. 12. A composition comprising hyaluronidase for use in reducing or eliminating hyaluronic acid-induced blockages in one or more blood vessels supplying blood to the eye. 13. Use of a composition comprising hyaluronidase to reduce or eliminate blockages caused by hyaluronic acid in one or more blood vessels supplying blood to the eye. 14. A composition comprising hyaluronidase for use in the manufacture of a drug for reducing or eliminating blockages caused by hyaluronic acid in one or more blood vessels supplying blood to the eye. 15. The use of the composition according to any one of embodiments 12 to 14, wherein the composition is administered using a delivery system. 16. A delivery system containing a composition comprising hyaluronidase for use in reducing or eliminating hyaluronic acid-induced blockages in one or more blood vessels supplying blood to the eye. 17. Use of a delivery system containing a composition comprising hyaluronidase to reduce or eliminate blockages caused by hyaluronic acid in one or more blood vessels supplying blood to the eye. 18. A composition comprising hyaluronidase for use in the manufacture of a drug for reducing or eliminating blockages caused by hyaluronic acid in one or more blood vessels supplying blood to the eye, the composition being contained in a delivery system. 19. The use of the composition according to any one of embodiments 12 to 18, wherein the composition is administered into the suprachoroidal space of the eye. 20. The composition contains at least 15 IU / mL, at least 25 IU / mL, at least 50 IU / mL, at least 100 IU / mL, at least 200 IU / mL, at least 300 IU / mL, at least 450 IU / mL, at least 600 IU / mL, at least 900 IU / mL, at least 1,000 IU / mL, at least 1,250 IU / mL, at least 1,500 IU / mL, at least 1,750 IU / mL, at least 2,000 IU / mL, at least 3,000 IU / mL, at least 4,000 IU / mL, and less At least 5,000 IU / mL, at least 6,000 IU / mL, at least 7,000 IU / mL, at least 8,000 IU / mL, at least 9,000 IU / mL, at least 10,000 IU / mL, at least 11,000 IU / mL, at least 12,000 IU / mL, at least 13,000 IU / mL, at least 14,000 IU / mL, at least 15,000 IU / mL, at least 16,000 IU / mL, at least 17,000 IU / mL, at least 18,000 IU / mL, at least 19,000 IU / mL L, or a concentration of at least 20,000 IU / mL; and / or at most 15 IU / mL, at most 25 IU / mL, at most 50 IU / mL, at most 100 IU / mL, at most 200 IU / mL, at most 300 IU / mL, at most 450 IU / mL, at most 600 IU / mL, at most 900 IU / mL, at most 1,000 IU / mL, at most 1,250 IU / mL, at most 1,500 IU / mL, at most 1,750 IU / mL, at most 2,000 IU / mL, at most 3,000 IU / mL, at most 4,000 IU / mL, at most 5,000 IU / mL, at most 6,000 IU / mL, at most 7,000 IU / mL, at most 8,000 IU / mL, at most 9,000 IU / mL, at most 10,000 IU / mL, at most 11,000 IU / mL, at most 12,000 IU / mL, at most 13,000 IU / mL, at most 14,000 IU / mL, at most 15,000 IU / mL, at most 16,000 IU / mL, at most 17,000 IU / mL, at most 18,000 IU / mL, at most 19,000 IU / mL, or at most 20,Amounts of 000 IU / mL; or approximately 15 IU / mL to approximately 25 IU / mL, approximately 15 IU / mL to approximately 50 IU / mL, approximately 15 IU / mL to approximately 100 IU / mL, approximately 15 IU / mL to approximately 200 IU / mL, approximately 15 IU / mL to approximately 300 IU / mL, approximately 15 IU / mL to approximately 400 IU / mL, approximately 15 IU / mL to approximately 450 IU / mL, approximately 15 IU / mL to approximately 600 IU / mL, approximately 15 IU / mL to approximately 750 IU / mL, approximately 15 IU / mL to approximately 900 IU / mL, approximately 25 IU / mL to approximately 50 IU / mL, approximately 25 IU / mL to approximately 100 IU / mL, Approximately 25IU / mL to approximately 200IU / mL, approximately 25IU / mL to approximately 300IU / mL, approximately 25IU / mL to approximately 400IU / mL, approximately 25IU / mL to approximately 450IU / mL, approximately 25IU / mL to approximately 600IU / mL, approximately 25IU / mL to approximately 750IU / mL, approximately 25IU / mL mL ~ about 900IU / mL, about 50IU / mL - about 100IU / mL, about 50IU / mL - about 200IU / mL, about 50IU / mL - about 300IU / mL, about 50IU / mL - about 400IU / mL, about 50IU / mL - about 450IU / mL, about 50IU / mL - about 60 0IU / mL, about 50IU / mL to about 750IU / mL, about 50IU / mL to about 900IU / mL, about 100IU / mL to about 200IU / mL, about 100IU / mL to about 300IU / mL, about 100IU / mL to about 400IU / mL, about 100IU / mL to about 450I U / mL, about 100IU / mL to about 600IU / mL, about 100IU / mL to about 750IU / mL, about 100IU / mL to about 900IU / mL, about 200IU / mL to about 300IU / mL, about 200IU / mL to about 400IU / mL, about 200IU / mL to about 450I U / mL, about 200IU / mL to about 600IU / mL, about 200IU / mL to about 750IU / mL, about 200IU / mL to about 900IU / mL, about 300IU / mL to about 450IU / mL, about 300IU / mL to about 600IU / mL, about 300IU / mL to about 750I U / mL, about 300IU / mL to about 900IU / mL, about 450IU / mL to about 600IU / mL, about 450IU / mL to about 750IU / mL, about 450IU / mL to about 900IU / mL, about 450IU / mL to about 1,000IU / mL, about 450IU / mL to about 1,250 IU / mL, approximately 600 IU / mL to approximately 750 IU / mL, approximately 600 IU / mL to approximately 900 IU / mL, approximately 600 IU / mL to approximately 1,000 IU / mL, approximately 600 IU / mL to approximately 1,250 IU / mL, approximately 600 IU / mL to approximately 1,500 IU / mL, approximately 750 IU / mL to approximately 900 IU / mL, approximately 750 IU / mL to approximately 1,000 IU / mL, approximately 750 IU / mL to approximately 1,250 IU / mL, approximately 750 IU / mL to approximately 1,250 IU / mL, approximately 750 IU / mL to approximately 1,500 IU / mL, approximately 750 IU / mL to approximately 1,750 IU / mL, approximately 900 IU / mL to approximately 1,000 IU / mL, approximately 900 IU / mL ~ approx. 1,250 IU / mL, approx. 900 IU / mL ~ approx. 1,500 IU / mL, approx. 900 IU / mL ~ approx. 1,750 IU / mL, approx. 900 IU / mL ~ approx. 2,000 IU / mL, approx. 1,000 IU / mL ~ approx. 1,250 IU / mL, approx. 1,000 IU / mL ~ approx. 1,500 IU / mL, approx. 1,000 IU / mL ~ approx. 1,750 IU / mL, approx. 1,000 IU / mL ~ approx. 2,000 IU / mL, approx. 1,000 IU / mL ~ approx. 2,000 IU / mL, approx. 1,000 IU / mL ~ approx. 3,000 IU / mL, approx. 1,000 IU / mL ~ approx. 4,000 IU / mL, approx. 1,000 IU / mL ~ approx. 5,000 IU / mL L, approximately 1,000 IU / mL to approximately 6,000 IU / mL, approximately 1,000 IU / mL to approximately 7,000 IU / mL, approximately 1,000 IU / mL to approximately 8,000 IU / mL, approximately 1,000 IU / mL to approximately 9,000 IU / mL, approximately 1,000 IU / mL to approximately 10,000 IU / mL, approximately 2,000 IU / mL to approximately 3,000 IU / mL, approximately 2,000 IU / mL to approximately 4,000 IU / mL, approximately 2,000 IU / mL to approximately 5,000 IU / mL, approximately 2,000 IU / mL to approximately 6,000 IU / mL, approximately 2,000 IU / mL to approximately 7,000 IU / mL, approximately 2,000 IU / mL U / mL ~ approx. 8,000 IU / mL, approx. 2,000 IU / mL ~ approx. 9,000 IU / mL, approx. 2,000 IU / mL ~ approx. 10,000 IU / mL, approx. 2,500 IU / mL ~ approx. 3,000 IU / mL, approx. 2,500 IU / mL ~ approx. 4,000 IU / mL, approx. 2,500 IU / mL ~ approx. 5,000 IU / mL, approx. 2,500 IU / mL ~ approx. 6,000 IU / mL, approx. 2,500 IU / mL ~ approx. 7,000 IU / mL, approx. 2,500 IU / mL ~ approx. 8,000 IU / mL, approx. 2,500 IU / mL ~ approx. 9,000 IU / mL, approx. 2,500 IU / mL ~ approx. 10,000 IU / mL000 IU / mL, approximately 3,000 IU / mL to approximately 4,000 IU / mL, approximately 3,000 IU / mL to approximately 5,000 IU / mL, approximately 3,000 IU / mL to approximately 6,000 IU / mL, approximately 3,000 IU / mL to approximately 7,000 IU / mL, approximately 3,000 IU / mL to approximately 8,000 IU / mL, approximately 3,000 IU / mL to approximately 9,000 IU / mL, approximately 3,000 IU / mL to approximately 10,000 IU / mL, approximately 4,000 IU / mL to approximately 5,000 IU / mL, approximately 4,000 IU / mL to approximately 6,000 IU / mL, approximately 4,000 IU / mL to approximately 7,000 IU / mL mL, approximately 4,000 IU / mL to approximately 8,000 IU / mL, approximately 4,000 IU / mL to approximately 9,000 IU / mL, approximately 4,000 IU / mL to approximately 10,000 IU / mL, approximately 5,000 IU / mL to approximately 6,000 IU / mL, approximately 5,000 IU / mL to approximately 7,000 IU / mL, approximately 5,000 IU / mL to approximately 8,000 IU / mL, approximately 5,000 IU / mL to approximately 9,000 IU / mL, approximately 5,000 IU / mL to approximately 10,000 IU / mL, approximately 6,000 IU / mL to approximately 7,000 IU / mL, approximately 6,000 IU / mL to approximately 8,000 IU / mL, approximately 6, 000 IU / mL ~ approx. 9,000 IU / mL, approx. 6,000 IU / mL ~ approx. 10,000 IU / mL, approx. 7,000 IU / mL ~ approx. 8,000 IU / mL, approx. 7,000 IU / mL ~ approx. 9,000 IU / mL, approx. 7,000 IU / mL ~ approx. 10,000 IU / mL, approx. 8,000 IU / mL ~ approx. 9,000 IU / mL, approx. 8,000 IU / mL ~ approx. 10,000 IU / mL, approx. 10,000 IU / mL ~ approx. 11,000 IU / mL, approx. 10,000 IU / mL ~ approx. 12,000 IU / mL, approx. 10 Approximately 13,000 IU / mL, approximately 10,000 IU / mL to approximately 14,000 IU / mL, approximately 10,000 IU / mL to approximately 15,000 IU / mL, approximately 10,000 IU / mL to approximately 16,000 IU / mL, approximately 10,000 IU / mL to approximately 17,000 IU / mL, approximately 10,000 IU / mL to approximately 18,000 IU / mL, approximately 10,000 IU / mL to approximately 19,000 IU / mL, approximately 10,000 IU / mL to approximately 20,000 IU / mL, approximately 11,000 IU / mL to approximately 12,000 IU / mL, approximately 11,000 IU / mL to approximately 13,000 IU / mL, approximately 14,000 IU / mL, approximately 15,000 IU / mL, approximately 16,000 IU / mL, approximately 17,000 IU / mL, approximately 18,000 IU / mL, approximately 19,000 IU / mL, approximately 20,000 IU / mL, approximately 11,000 IU / mL to approximately 12,000 IU / mL, approximately 13,000 IU / mL000 IU / mL, approximately 11,000 IU / mL to approximately 14,000 IU / mL, approximately 11,000 IU / mL to approximately 15,000 IU / mL, approximately 11,000 IU / mL to approximately 16,000 IU / mL, approximately 11,000 IU / mL to approximately 17,000 IU / mL, approximately 11,000 IU / mL to approximately 18,000 IU / mL, approximately 11,000 IU / mL to approximately 19,000 IU / mL, approximately 11,000 IU / mL to approximately 20,000 IU / mL, approximately 12,000 IU / mL to approximately 13,000 IU / mL, approximately 12,000 IU / mL to approximately 14,000 IU / mL, approximately 12,000 IU / mL IU / mL ~ approx. 15,000 IU / mL, approx. 12,000 IU / mL ~ approx. 16,000 IU / mL, approx. 12,000 IU / mL ~ approx. 17,000 IU / mL, approx. 12,000 IU / mL ~ approx. 18,000 IU / mL, approx. 12,000 IU / mL ~ approx. 19,000 IU / mL, approx. 12,000 IU / mL ~ approx. 20,000 IU / mL, approx. 13,000 IU / mL ~ approx. 14,000 IU / mL, approx. 13,000 IU / mL ~ approx. 15,000 IU / mL, approx. 13,000 IU / mL ~ approx. 16,000 IU / mL, approx. 13,000 IU / mL ~ approx. 17,000 IU / mL Approximately 13,000 IU / mL to approximately 18,000 IU / mL, approximately 13,000 IU / mL to approximately 19,000 IU / mL, approximately 13,000 IU / mL to approximately 20,000 IU / mL, approximately 14,000 IU / mL to approximately 15,000 IU / mL, approximately 14,000 IU / mL to approximately 16,000 IU / mL, approximately 14,000 IU / mL to approximately 17,000 IU / mL, approximately 14,000 IU / mL to approximately 18,000 IU / mL, approximately 14,000 IU / mL to approximately 19,000 IU / mL, approximately 14,000 IU / mL to approximately 20,000 IU / mL, approximately 15,000 IU / mL Approximately 16,000 IU / mL, approximately 15,000 IU / mL to approximately 17,000 IU / mL, approximately 15,000 IU / mL to approximately 18,000 IU / mL, approximately 15,000 IU / mL to approximately 19,000 IU / mL, approximately 15,000 IU / mL to approximately 20,000 IU / mL, approximately 16,000 IU / mL to approximately 17,000 IU / mL, approximately 16,000 IU / mL to approximately 18,000 IU / mL, approximately 16,000 IU / mL to approximately 19,000 IU / mL, approximately 16,000 IU / mL to approximately 20,000 IU / mL, approximately 17,000 IU / mL to approximately 18,000 IU / mL, approximately 17,The use described in any one of Embodiments 12 to 19, comprising hyaluronidase in amounts of approximately 000 IU / mL to 19,000 IU / mL, approximately 17,000 IU / mL to 20,000 IU / mL, approximately 18,000 IU / mL to 19,000 IU / mL, approximately 18,000 IU / mL to 20,000 IU / mL, or approximately 19,000 IU / mL to 20,000 IU / mL. 21. The amount of hyaluronidase administered should be at least 15 IU, at least 25 IU, at least 50 IU, at least 100 IU, at least 200 IU, at least 300 IU, at least 450 IU, at least 600 IU, at least 900 IU, at least 1,000 IU, at least 1,250 IU, at least 1,500 IU, at least 1,750 IU, at least 2,000 IU, at least 3,000 IU, at least 4,000 IU 0 IU, or at least 5,000 IU; and / or at most 15 IU, at most 25 IU, at most 50 IU, at most 100 IU, at most 200 IU, at most 300 IU, at most 450 IU, at most 600 IU, at most 900 IU, at most 1,000 IU, at most 1,250 IU, at most 1,500 IU, at most 1,750 IU, at most 2,000 IU, at most 3,000 IU, at most 4,000 IU, or at most 5,Amounts of 000 IU; or approximately 15 IU to 25 IU, approximately 15 IU to 50 IU, approximately 15 IU to 100 IU, approximately 15 IU to 200 IU, approximately 15 IU to 300 IU, approximately 15 IU to 400 IU, approximately 15 IU to 450 IU, approximately 15 IU to 600 IU, approximately 15 IU to 750 IU, Approximately 15IU to approximately 900IU, approximately 25IU to approximately 50IU, approximately 25IU to approximately 100IU, approximately 25IU to approximately 200IU, approximately 25IU to approximately 300I U, about 25IU to about 400IU, about 25IU to about 450IU, about 25IU to about 600IU, about 25IU to about 750IU, about 25IU to about 90 0IU, approximately 50IU ~ approximately 100IU, approximately 50IU ~ approximately 200IU, approximately 50IU ~ approximately 300IU, approximately 50IU ~ approximately 450IU, approximately 50IU ~ Approximately 600IU, approximately 50IU to approximately 750IU, approximately 50IU to approximately 900IU, approximately 100IU to approximately 200IU, approximately 100IU to approximately 300IU, approximately 1 00IU~about 450IU, about 100IU~about 600IU, about 100IU~about 750IU, about 100IU~about 900IU, about 200IU~about 300IU, about 200IU to about 450IU, about 200IU to about 600IU, about 200IU to about 750IU, about 200IU to about 900IU, about 300IU ~ approx. 450IU, approx. 300IU ~ approx. 600IU, approx. 300IU ~ approx. 750IU, approx. 300IU ~ approx. 900IU, approx. 450IU ~ Approximately 600IU, approximately 450IU ~ approximately 750IU, approximately 450IU ~ approximately 900IU, approximately 450IU ~ approximately 1,000IU, approximately 450IU ~ approximately 1,25 0IU, about 600IU to about 750IU, about 600IU to about 900IU, about 600IU to about 1,000IU, about 600IU to about 1,250I U, about 600IU to about 1,500IU, about 750IU to about 900IU, about 750IU to about 1,000IU, about 750IU to about 1,250IU , about 750IU to about 1,500IU, about 750IU to about 1,750IU, about 900IU to about 1,000IU, about 900IU to about 1,250 IU, approximately 900IU ~ approximately 1,500IU, approximately 900IU ~ approximately 1,750IU, approximately 900IU ~ approximately 2,000IU, approximately 1,000IU ~ approximately 1, 250IU, about 1,000IU to about 1,500IU, about 1,000IU to about 1,750IU, about 1,000IU to about 2,000IU, about 1, 000IU ~ approx. 3,000IU, approx. 1,000IU ~ approx. 4,000IU, approx. 1,000IU ~ approx. 5,000IU, approx. 2,000IU ~ approx. 3,The use described in any one of Embodiments 12 to 20, which is an amount of 000 IU, about 2,000 IU to about 4,000 IU, about 2,000 IU to about 5,000 IU, about 2,500 IU to about 3,000 IU, about 2,500 IU to about 4,000 IU, about 2,500 IU to about 5,000 IU, about 3,000 IU to about 4,000 IU, about 3,000 IU to about 5,000 IU, or about 4,000 IU to about 5,000 IU. 22. The use of the composition according to any one of Embodiments 12 to 21, wherein the composition is administered as a single dose or in multiple doses. 23. The composition or agent shall be in a volume of at least 5 μL, at least 10 μL, at least 20 μL, at least 30 μL, at least 40 μL, at least 50 μL, at least 75 μL, at least 100 μL, at least 200 μL, at least 300 μL, at least 400 μL, or at least 500 μL; and / or at most 5 μL, at most 10 μL, at most Also in volumes of 20 μL, at most 30 μL, at most 40 μL, at most 50 μL, at most 75 μL, at most 100 μL, at most 200 μL, at most 300 μL, at most 400 μL, or at most 500 μL; or in volumes of approximately 5 μL to approximately 25 μL, approximately 5 μL to approximately 50 μL, approximately 5 μL to approximately 75 μL, approximately 5 μL to approximately 100 μL, approximately 10 μL to approximately 25 μL, approximately 10 μL to approximately 50 μL, approximately 10μL to approximately 75μL, approximately 10μL to approximately 100μL, approximately 25μL to approximately 50μL, approximately 25μL to approximately 75μL, approximately 25μL to approximately 100μL, approximately 25μL to approximately 150μL, approximately 50μL to approximately 75μL , about 50 μL to about 100 μL, about 50 μL to about 150 μL, about 50 μL to about 200 μL, about 50 μL to about 250 μL, about 100 μL to about 150 μL, about 100 μL to about 200 μL, about 100 The use described in any one of Embodiments 12 to 22, administered in volumes of approximately μL to 250 μL, approximately 100 μL to 300 μL, approximately 100 μL to 400 μL, approximately 100 μL to 500 μL, approximately 200 μL to 300 μL, approximately 200 μL to 400 μL, approximately 200 μL to 500 μL, approximately 300 μL to 400 μL, approximately 300 μL to 500 μL, or approximately 400 μL to 500 μL. 24. The composition or agent may be dissolved in at most 1 minute, at most 2 minutes, at most 3 minutes, at most 4 minutes, at most 5 minutes, at most 10 minutes, at most 15 minutes, at most 30 minutes, at most 45 minutes, at most 60 minutes, at most 75 minutes, or at most 90 minutes; or approximately 1 minute to approximately 3 minutes, approximately 1 minute to approximately 5 minutes, approximately 1 minute to approximately 7 minutes, approximately 1 minute to approximately 10 minutes, approximately 1 minute to approximately 15 minutes, approximately 3 minutes to approximately 5 minutes, approximately The use described in any one of Embodiments 20 to 23, wherein the substance enters the suprachoroidal space in 3 to 7 minutes, 3 to 10 minutes, 3 to 15 minutes, 5 to 7 minutes, 5 to 10 minutes, 5 to 15 minutes, 5 to 30 minutes, 10 to 15 minutes, 10 to 30 minutes, 15 to 30 minutes, 15 to 45 minutes, 15 to 60 minutes, 15 to 75 minutes, or 15 to 90 minutes. 25. Blockages caused by hyaluronic acid in one or more blood vessels supplying the eye may occur in as little as 1 minute, as little as 2 minutes, as little as 3 minutes, as little as 4 minutes, as little as 5 minutes, as much as 10 minutes, as much as 15 minutes, as much as 30 minutes, as much as 45 minutes, as much as 60 minutes, as much as 75 minutes, or as much as 90 minutes; or approximately 1 minute to 3 minutes, approximately 1 minute to 5 minutes, approximately 1 minute to 7 minutes, approximately 1 minute to 10 minutes, approximately 1 minute to 1 The use according to any one of Embodiments 12 to 24, which is reduced or eliminated in 5 minutes, approximately 3 to 5 minutes, approximately 3 to 7 minutes, approximately 3 to 10 minutes, approximately 3 to 15 minutes, approximately 5 to 7 minutes, approximately 5 to 10 minutes, approximately 5 to 15 minutes, approximately 5 to 30 minutes, approximately 10 to 15 minutes, approximately 10 to 30 minutes, approximately 15 to 30 minutes, approximately 15 to 45 minutes, approximately 15 to 60 minutes, approximately 15 to 75 minutes, and approximately 15 to 90 minutes. 26. A kit comprising one or more containers, each containing a pharmaceutical composition comprising hyaluronidase. 27. The kit according to Embodiment 26, wherein the pharmaceutical composition is a liquid formulation. 28. The kit according to Embodiment 26, wherein the pharmaceutical composition is a dried formulation. 29. The kit according to any one of embodiments 26 to 28, wherein each of the one or more containers is a delivery system. 30. The kit according to any one of embodiments 26 to 28, further comprising a delivery system. 31. The kit according to any one of embodiments 26 to 30, further comprising another container containing a solvent. 32. A kit according to any one of embodiments 26 to 31, further including instructions for use.

[0065] Examples The following non-limiting examples are provided for illustrative purposes only to facilitate a more complete understanding of the representative embodiments currently conceivable. These examples should not be construed as limiting any of the embodiments described herein, including those relating to compounds, pharmaceutical compositions, or methods and uses disclosed herein.

[0066] Example 1 A rabbit model of vascular occlusion caused by fillers. In this embodiment, New Zealand white rabbits were used to simulate vascular occlusive vision loss associated with hyaluronic acid polymers. These animals were selected because the anatomical structure of their ocular blood vessels is similar to that of humans.

[0067] New Zealand white rabbits weighing 2.0–3.0 kg were acclimatized to the study environment for at least one week prior to the start of the study. After the acclimatization period, each individual was physically examined to determine their suitability for the study, including examinations of the skin and ears, eyes, abdomen, nervous system, behavior, and overall condition. Individuals deemed to be in good health were used in the study. The rabbits used were assigned to four groups of three, each uniquely identified by a cage card number.

[0068] On the day of the surgical procedure (day 0), all subjects were anesthetized and administered antibiotics. Then, each subject underwent a surgical procedure to expose the right carotid artery in their neck. Using a syringe with a needle of 25 gauge or less, 0.5 mL to 0.7 mL of hyaluronic acid dermal filler was injected into the right carotid artery from the cranial side for a minimum of 60 seconds. After the dermal filler administration was complete, the surgical incision site in the subject's neck was sutured closed. Approximately 5 minutes after dermal filler administration, an eyelid retractor was placed over the right eye of the subject undergoing one of the four treatment protocols. Subjects in Group 1 were the injection control group and received no further treatment. The compositions were administered to individuals in Group 2 and Group 3 via suprachorionic injection using a 30-gauge needle in the inferior nasal quadrant of the right eye. Individuals in Group 2 received 0.1 mL of phosphate-buffered saline (PBS) (control composition), while individuals in Group 3 received 0.1 mL of hyaluronidase (2,400 IU / mL). The individuals were allowed to recover normally from the anesthesia procedure. The left eye of all individuals remained untreated and was used as a control in these experiments.

[0069] To assess visual activity, both optical coherence tomography (OCT-A) and electroretinography (ERG) were performed. OCT-A is a non-contact retinal imaging system that uses infrared light to image retinal vascular structures and determine changes in vascular flow over time. In this study, OCT-A analysis was performed on each individual to assess 1) changes in vascular flow between day 0 pre-induction and day 0 post-induction, 2) changes in vascular flow between day 0 pre-induction and day 3 post-induction, and 3) changes in vascular flow between day 0 post-induction and day 3 post-induction. Full-field ERG was performed on both eyes of each individual on day 0 pre-induction to obtain baseline readings and on day 3 post-induction. Individuals were dark-adapted for at least one hour before ERG analysis. ERG was performed using a mini-ganzfeld light stimulator (Roland Instruments, Wiesbaden, Germany) with short flashes of 0.33 Hz delivered at maximum intensity. For each individual, 20 responses were amplified, filtered, and averaged (Retiport Electrophysiologic Diagnostic Systems, Roland Instruments, Wiesbaden, Germany). Standard ERG measurements as specified by the ISCEV standard were performed on the individuals, including scotopic (0.01 candela), scotopic (3 candela), and photopic (3 candela) measurements. Wave a and wave b ERG analysis was performed to determine the time course of wave a and wave b amplitude, and comparisons were made between day 0 (baseline) before induction and day 3 after induction under scotopic and photopic conditions.

[0070] On day 0 before induction, the right eye of individuals in Group 1 showed normal retinal blood flow based on OCT-A analysis (Table 1) and normal retinal neural activity based on ERG readings (Table 2). However, on day 3 after induction, all individuals showed a significant decrease in retinal blood flow, and ERG readings were flat or essentially flat in the right eye (Tables 1 and 2), indicating a significant loss of retinal blood flow and neural activity. As expected, the left eye of these individuals showed normal retinal blood flow and neural activity (Tables 1 and 2). Similarly, the right eye of individuals in Group 2 showed normal retinal blood flow based on OCT-A analysis (Table 1) and normal retinal neural activity based on ERG readings (Table 2). However, on day 3 after induction, all individuals showed a significant decrease in retinal blood flow, and ERG readings were flat or essentially flat in the right eye (Tables 1 and 2), indicating a significant loss of retinal blood flow and neural activity. As expected, the left eyes of these individuals showed normal retinal blood flow and nerve activity (Tables 1 and 2). Since both Group 1 and Group 2 individuals were control groups, these results demonstrate that hyaluronic acid polymers block blood flow to the retina, causing loss of retinal function, and that they may serve as an excellent model for hyaluronic acid polymer-associated vascular occlusive visual acuity loss. [Table 1] [Table 2]

[0071] Analysis of individuals in Group 3 demonstrated that hyaluronidase administration reversed vascular occlusion in the retina associated with hyaluronic acid polymers. On day 0 before induction, the right eye of individuals in Group 3 showed normal blood flow to the retina based on OCT-A analysis (Table 1) and normal neural activity in the retina based on ERG readings (Table 2). These baseline measurements indicate that individuals in Group 3 exhibited functional neural activity. Surprisingly, on day 3 after induction, all individuals also showed significant blood flow and neural activity in the retina (Tables 1 and 2). These levels could be distinguished from measurements obtained from the right eye on day 0 before induction and from measurements from the left eye control, but the measured activity still indicated a significant recovery from vascular occlusion caused by the presence of hyaluronic acid polymers. These results demonstrate that hyaluronic acid polymers block blood flow to the retina, causing loss of retinal function, and may serve as an excellent model for hyaluronic acid polymer-associated vascular occlusive visual acuity loss. Furthermore, remarkably, the administration of a small amount of hyaluronidase into the suprachoroidal space resolved hyaluronic acid dermal filler occlusion in the retinal circulation, enabling reperfusion of retinal tissue and re-establishment of neural activity.

[0072] Example 2 A rabbit model of vascular occlusion caused by fillers. New Zealand white rabbits are used to simulate hyaluronic acid-associated vascular occlusive vision loss. These individuals are selected because the anatomical structure of their ocular blood vessels is similar to that of humans. New Zealand white rabbits weighing 2.0–3.0 kg are divided into groups based on the dose and administration time of hyaluronidase.

[0073] Hyaluronic acid filler is administered into the internal carotid artery of subjects to induce central retinal artery occlusion. This arterial occlusion and subsequent ischemia are confirmed by both retinal fundus photography, OCT-A, and ERG analysis. Different doses of hyaluronidase are administered onto the choroid at several time points after occlusion to evaluate both the effect of the treatment dose and the effect of the timing. The control group is injected with hyaluronic acid filler in the same manner as the experimental group, but without hyaluronidase treatment. Fundus photography and electroretinography changes are recorded at 30, 60, 90, and 120 minutes after hyaluronidase administration. Electroretinography is performed at 60 and 120 minutes to check retinal reperfusion and electrophysiological function.

[0074] In a series of experiments, central retinal artery occlusion was induced in rabbits by injecting them with 0.5 mL to 0.9 mL of hyaluronic acid filler. The rabbits were divided into four experimental groups of two or three rabbits each. In group 1, 100 μL of hyaluronidase (400 IU / mL) was administered to the choroid 5 minutes after the hyaluronic acid filler injection. In group 2, 100 μL of hyaluronidase (400 IU / mL) was administered to the choroid 10 minutes after the hyaluronic acid filler injection. In group 3, 100 μL of hyaluronidase (600 IU / mL) was administered to the choroid 5 minutes after the hyaluronic acid filler injection. In group 4, 100 μL of hyaluronidase (650 IU / mL) was administered to the choroid 10 minutes after the hyaluronic acid filler injection.

[0075] In another series of experiments, central retinal artery occlusion was induced in rabbits by injecting them with 0.5 mL to 0.9 mL of hyaluronic acid filler. The rabbits were divided into four experimental groups of two or three rabbits each. In group 1, 100 μL of hyaluronidase (1,000 IU / mL) was administered to the choroid 5 minutes after the hyaluronic acid filler injection. In group 2, 100 μL of hyaluronidase (1,000 IU / mL) was administered to the choroid 10 minutes after the hyaluronic acid filler injection. In group 3, 100 μL of hyaluronidase (3,000 IU / mL) was administered to the choroid 5 minutes after the hyaluronic acid filler injection. In group 4, 100 μL of hyaluronidase (3,000 IU / mL) was administered to the choroid 10 minutes after the hyaluronic acid filler injection.

[0076] In another series of experiments, central retinal artery occlusion was induced in rabbits by injecting them with 0.5 mL to 0.9 mL of hyaluronic acid filler. The rabbits were divided into four experimental groups of 2 or 3 rabbits each. In group 1, 100 μL of hyaluronidase (10,000 IU / mL) was administered onto the choroid 5 minutes after the hyaluronic acid filler injection. In group 2, hyaluronic acid filler was administered to the rabbits. Ten minutes after the filler injection, 100 μL of hyaluronidase (10,000 IU / mL) was administered onto the choroid. For individuals in Group 3, 100 μL of hyaluronidase (15,000 IU / mL) was administered onto the choroid five minutes after the hyaluronic acid filler injection. For individuals in Group 4, 100 μL of hyaluronidase (15,000 IU / mL) was administered onto the choroid ten minutes after the hyaluronic acid filler injection.

[0077] In another series of experiments, central retinal artery occlusion was induced in rabbits by injecting them with 0.5 mL to 0.9 mL of hyaluronic acid filler. The rabbits were divided into four experimental groups of two or three rabbits each. In group 1, 100 μL of hyaluronidase (15,000 IU / mL) was administered onto the choroid 5 minutes after the hyaluronic acid filler injection. In group 2, hyaluronic acid filler was administered to the rabbits. Ten minutes after the filler injection, 100 μL of hyaluronidase (15,000 IU / mL) was administered onto the choroid. For individuals in Group 3, 100 μL of hyaluronidase (20,000 IU / mL) was administered onto the choroid five minutes after the hyaluronic acid filler injection. For individuals in Group 4, 100 μL of hyaluronidase (20,000 IU / mL) was administered onto the choroid ten minutes after the hyaluronic acid filler injection.

[0078] In another series of experiments, central retinal artery occlusion was induced in rabbits by injecting them with 0.5 mL to 0.9 mL of hyaluronic acid filler. The rabbits were divided into four experimental groups of two or three rabbits each. In group 1, 100 μL of hyaluronidase (400 IU / mL) was administered to the choroid 15 minutes after the hyaluronic acid filler injection. In group 2, 100 μL of hyaluronidase (400 IU / mL) was administered to the choroid 30 minutes after the hyaluronic acid filler injection. In group 3, 100 μL of hyaluronidase (650 IU / mL) was administered to the choroid 15 minutes after the hyaluronic acid filler injection. In group 4, 100 μL of hyaluronidase (650 IU / mL) was administered to the choroid 30 minutes after the hyaluronic acid filler injection.

[0079] In another series of experiments, central retinal artery occlusion was induced in rabbits by injecting them with 0.5 mL to 0.9 mL of hyaluronic acid filler. The rabbits were divided into four experimental groups of two or three rabbits each. In group 1, 100 μL of hyaluronidase (1,000 IU / mL) was administered to the choroid 15 minutes after the hyaluronic acid filler injection. In group 2, 100 μL of hyaluronidase (1,000 IU / mL) was administered to the choroid 30 minutes after the hyaluronic acid filler injection. In group 3, 100 μL of hyaluronidase (3,000 IU / mL) was administered to the choroid 15 minutes after the hyaluronic acid filler injection. In group 4, 100 μL of hyaluronidase (3,000 IU / mL) was administered to the choroid 30 minutes after the hyaluronic acid filler injection.

[0080] In another series of experiments, central retinal artery occlusion was induced in rabbits by injecting them with 0.5 mL to 0.9 mL of hyaluronic acid filler. The rabbits were divided into four experimental groups of 2 or 3 rabbits each. Individuals in Group 1 were administered 100 μL of hyaluronidase (10,000 IU / mL) onto the choroid 15 minutes after the hyaluronic acid filler injection, while individuals in Group 2 were administered hyaluronic acid filler... In group 3, 100 μL of hyaluronidase (10,000 IU / mL) was administered onto the choroid 30 minutes after the filler injection. In group 4, 100 μL of hyaluronidase (15,000 IU / mL) was administered onto the choroid 15 minutes after the hyaluronic acid filler injection. In group 4, 100 μL of hyaluronidase (15,000 IU / mL) was administered onto the choroid 30 minutes after the hyaluronic acid filler injection.

[0081] In another series of experiments, central retinal artery occlusion was induced in rabbits by injecting them with 0.5 mL to 0.9 mL of hyaluronic acid filler. The rabbits were divided into four experimental groups of two or three rabbits each. Individuals in Group 1 were administered 100 μL of hyaluronidase (15,000 IU / mL) onto the choroid 15 minutes after the hyaluronic acid filler injection, while individuals in Group 2 were administered hyaluronic acid filler... In group 3, 100 μL of hyaluronidase (15,000 IU / mL) was administered onto the choroid 30 minutes after the filler injection. In group 4, 100 μL of hyaluronidase (20,000 IU / mL) was administered onto the choroid 15 minutes after the hyaluronic acid filler injection. In group 4, 100 μL of hyaluronidase (20,000 IU / mL) was administered onto the choroid 30 minutes after the hyaluronic acid filler injection.

[0082] Analysis of the eyes of the experimental population using retinal fundus photography, OCT-A, and ERG analysis is expected to show no significant central retinal artery occlusion or visual impairment after hyaluronidase treatment. On the other hand, the control population is expected to show no improvement in visual impairment suggestive of central retinal artery occlusion or visual impairment caused by fillers.

[0083] In conclusion, the above description of embodiments of the present invention is presented for illustrative and explanatory purposes only. While aspects of the present invention are emphasized by reference to specific embodiments, it will be understood that those skilled in the art will immediately recognize that these described embodiments are merely illustrative of the principles constituting the present invention. Accordingly, the specific embodiments are not intended to be exhaustive or to limit the present invention to the exact forms disclosed. Therefore, it should be understood that embodiments of the subject matter disclosed are by no means limited to the specific elements, compounds, compositions, components, articles, apparatus, methodologies, uses, protocols, steps, and / or limitations described herein, unless expressly stated otherwise.

[0084] Furthermore, any grouping of alternative embodiments, elements, steps, and / or limitations of the present invention should not be construed as limitations. Each such grouping may be referenced and claimed individually or in any combination with other groupings disclosed herein. It is anticipated that one or more alternative embodiments, elements, steps, and / or limitations of a group may be included in or removed from a group for convenience and / or patentability reasons. When such inclusion or removal occurs, this specification shall be deemed to include groupings that satisfy the descriptions of all Markush groups used in the supplementary claims, as modified.

[0085] Furthermore, those skilled in the art will recognize that certain changes, modifications, substitutions, alternatives, additions, deletions, and partial combinations thereof can be made in accordance with the teachings herein without departing from the spirit of the invention. Furthermore, the following appendix claims and the claims introduced herein are intended to be construed as including all such changes, modifications, substitutions, alternatives, additions, deletions, and partial combinations that fall within their true spirit and scope. Therefore, the scope of the invention is not limited to those precisely shown and described herein.

[0086] Specific embodiments of the Invention, including the best mode known to the inventors for carrying out the Invention, are described herein. Of course, variations of these described embodiments will be obvious to those skilled in the art by reading the above description. The inventors anticipate that those skilled in the art will appropriately adopt such variations, and intend that the Invention may be carried out in ways other than those specifically described herein. Accordingly, the Invention includes all modifications and equivalents of the subject matter described in the accompanying claims, as permitted by applicable law. Furthermore, any combination of all possible variations of the above embodiments is incorporated into the Invention unless otherwise specified herein or unless it is clearly inconsistent with the context.

[0087] The words, phrases, and terms used herein are intended solely to describe specific embodiments, elements, steps, and / or limitations and are not intended to limit the scope of the invention as defined solely by the claims. Furthermore, such words, phrases, and terms are understood not only in their generally defined sense but also to include structures, materials, or functions beyond the scope of their generally defined sense by special definition herein. Thus, where an element, step, or limitation can be understood to encompass more than one meaning in the context of this specification, its use in a claim should be understood to be general to all possible meanings supported by this specification and the word itself.

[0088] Accordingly, the definitions and meanings of elements, steps, or limitations described in the claims below are defined herein to include not only combinations of elements, steps, or limitations as literally shown, but also all equivalent structures, materials, or actions to perform substantially the same function in substantially the same manner to obtain substantially the same results. In this sense, it is intended that equivalent substitutions of two or more elements, steps, or limitations may be made for any one of the elements, steps, or limitations of the claims below, or that a single element, step, or limitation may be replaced by two or more elements, steps, or limitations of such claims. While elements, steps, or limitations are described above as acting in a particular combination and may initially be claimed as such, it is clearly understood that one or more elements, steps, or limitations from a claimed combination may, in some cases, be removed from the combination, and that a claimed combination may cover a partial combination or a variation of a partial combination. Therefore, despite the fact that the elements, steps, and / or limitations of the claims are shown below in specific combinations, it should be clearly understood that the present invention includes other combinations of fewer, more, or different elements, steps, and / or limitations disclosed above, even if such combinations were not initially claimed. Furthermore, it is clearly considered that minor changes from the claimed subject matter, which are now publicly known or will be later devised, are equivalently within the scope of the claims. Thus, obvious substitutions, which are now publicly known or will later be publicly known to those skilled in the art, are defined as being within the scope of the defined elements. Accordingly, the claims are understood to include those specifically illustrated and described above, conceptually equivalents, obviously replaceables, and those essentially incorporating the essential idea of ​​the present invention.

[0089] Unless otherwise specified, all numbers used in this specification and in the claims to represent features, items, quantities, parameters, properties, terms, etc., are understood to be modified in all cases by the term “approximately.” As used herein, “approximately” means that the feature, item, quantity, parameter, property, or term thus modified includes a range of ±10 percent above and below the value of the described feature, item, quantity, parameter, property, or term. Therefore, unless otherwise stated, numerical parameters described herein and in the accompanying claims are variable approximations. For example, since mass spectrometers can vary slightly when determining the mass of a given analyte, the term “approximately” in relation to the mass of an ion or the mass / charge ratio of an ion refers to + / - 0.50 atomic mass units. At a minimum, and not as an attempt to limit the application of the doctrine of equivalents to the claims, each numerical representation should be interpreted by applying ordinary rounding techniques, at least in light of the reported number of significant figures.

[0090] Although the numerical ranges and values ​​representing the broad scope of the present invention are approximations, the numerical ranges and values ​​shown in specific embodiments are reported as accurately as possible. However, numerical ranges or values ​​inherently include certain errors that inevitably arise from the standard deviation found in each test measurement. The enumeration of numerical ranges of values ​​herein is merely intended to serve as a simple way to individually refer to the individual numerical values ​​that fall within those ranges. Unless otherwise specified herein, individual values ​​within numerical ranges are incorporated herein as if they were individually described herein.

[0091] The use of the terms “may” or “can” with respect to an embodiment or aspect of an embodiment also carries the alternative meaning of “cannot” or “cannot.” Therefore, where this specification discloses that an embodiment or aspect of an embodiment may or may be included as part of the subject matter of the invention, a negative limitation or exclusive condition is also explicitly intended, meaning that the embodiment or aspect of an embodiment may or may not be included as part of the subject matter of the invention. Similarly, the use of the term “optionally” with respect to an embodiment or aspect of an embodiment means that such an embodiment or aspect may or may not be included as part of the subject matter of the invention. Whether such a negative limitation or exclusive condition applies depends on whether the negative limitation or exclusive condition is stated in the claimed subject matter.

[0092] In the context describing the present invention (particularly in the context of the following claims), the terms “a,” “an,” “the,” and similar references are to be interpreted as encompassing both singular and plural forms unless otherwise specified herein or unless the context clearly contradicts this interpretation. Furthermore, order designations for identified elements, such as “first,” “second,” “third,” etc., are used to distinguish elements and, unless otherwise specified, do not indicate or imply a required or limited number of such elements, nor do they indicate a particular position or order of such elements. All methods described herein may be carried out in any suitable order unless otherwise specified herein or unless the context clearly contradicts this interpretation. The use of any and all examples or illustrative language provided herein (e.g., “etc.”) is merely intended to better illustrate the present invention and does not limit the scope of the invention to any other claimed invention. The language herein should not be interpreted as indicating any unclaimed elements essential to the carrying out of the present invention.

[0093] When used in the claims, whether at the time of filing or added by amendment, the open-ended transitional term “comprising,” its variations such as “comprise” and “comprises,” and its equivalent open-ended transitional phrases such as “contain,” “equip,” and “have,” encompass all explicitly enumerated elements, limitations, steps, integers, and / or features, either alone or in combination with unenumerated subject matter, where the specified elements, limitations, steps, integers, and / or features are essential, but other unspecified elements, limitations, steps, integers, and / or features may be added to still constitute the scope of the claims. Certain embodiments disclosed herein may be further limited in the claims by using the closed-ended transitional phrase “consisting of” or “consisting essentially of” (or its variations such as “consist of,” “consists of,” “consist essentially of,” and “consists essentially of,” instead of or as a modification of “comprising.” When used in the claims, whether at the time of filing or added by amendment, the closed-end transitional clause “consisting of” excludes any elements, limitations, steps, integers, or features not expressly described in the claims. The closed-end transitional clause “essentially consisting of” limits the scope of the claims to the explicitly enumerated elements, limitations, steps, integers, and / or features, and any other elements, limitations, steps, integers, and / or features that do not essentially affect the basic and novel features of the claimed subject matter. Thus, the meaning of the open-end transitional clause “including” is defined as encompassing all specifically enumerated elements, limitations, steps, and / or features, as well as any optional, additional, unspecified ones.The closed-end transitional clause “consisting of” is defined as including only the elements, limitations, steps, integers, and / or features specifically enumerated in the claims, whereas the closed-end transitional clause “essentially consisting of” is defined as including only the elements, limitations, steps, integers, and / or features specifically enumerated in the claims, and elements, limitations, steps, integers, and / or features that do not essentially affect the basic and novel features of the claimed subject matter. Thus, the open-end transitional clause “including” (and its equivalent open-end transitional clause) includes, in limited cases, the claimed subject matter specified by the closed-end transitional clause “consisting of” or “essentially consisting of” within the scope of its meaning. In this way, embodiments described herein or claimed in the word “including” explicitly and unambiguously provide explanation, activation, and support for the words “essentially consisting of” and “consisting of.”

[0094] Finally, all patents, patent publications, and other references cited and identified herein are incorporated herein individually and expressly by reference in their entirety, for example, to describe and disclose compositions and methodologies described in such publications that may be used in conjunction with the present invention. These publications are provided solely for their disclosures that precede the filing date of this application. In this regard, the inventors do not acknowledge, nor should be construed as acknowledging, that they do not have prior rights to such disclosures for the sake of prior art or for any other reason. All statements regarding dates or expressions regarding the contents of these documents are based on information available to the applicant and do not constitute an acknowledgment of the accuracy of the dates or contents of these documents.

Claims

1. A composition comprising hyaluronidase for use in reducing or eliminating blockages caused by hyaluronic acid in one or more blood vessels supplying blood to the eye of an individual in need thereof, wherein the concentration of the hyaluronidase is at least 3,000 IU / mL, and the composition is administered into the suprachoroidal space of the eye.

2. A composition comprising hyaluronidase for use in reducing or suppressing vascular occlusion of the eye of a person in need thereof, wherein the concentration of the hyaluronidase is at least 3,000 IU / mL, and the composition is administered into the suprachoroidal space of the eye.

3. A composition comprising hyaluronidase for use in reducing or suppressing hyaluronic acid-induced vision loss in an individual in need thereof, wherein the concentration of the hyaluronidase is at least 3,000 IU / mL, and the composition is administered into the suprachoroidal space of the eye.

4. The composition according to any one of claims 1 to 3, which is administered using a delivery system.

5. The composition according to claim 4, wherein the delivery system comprises a needle and a syringe, an ADG needle, or a microinjector.

6. The composition according to claim 5, wherein the microinjector is a choroidal microinjector.

7. The composition according to any one of claims 1 to 6, wherein the composition comprises hyaluronidase at a concentration of at least 10,000 IU / mL, at least 11,000 IU / mL, at least 12,000 IU / mL, at least 13,000 IU / mL, at least 14,000 IU / mL, at least 15,000 IU / mL, at least 16,000 IU / mL, at least 17,000 IU / mL, at least 18,000 IU / mL, at least 19,000 IU / mL, or at least 20,000 IU / mL.

8. The composition according to any one of claims 1 to 7, wherein the amount of hyaluronidase administered is at least 100 IU.

9. The composition described above is administered in a single dose or in multiple doses, as described in any one of claims 1 to 8.

10. The composition according to any one of claims 1 to 9, further comprising an auxiliary active compound, a drug, a local anesthetic, or a hormone.

11. A delivery system to the suprachoroidal space of the eye for reducing or eliminating hyaluronic acid-induced blockages in one or more blood vessels supplying blood to the eye of an individual who needs it, the delivery system comprising a composition containing at least 3,000 IU / mL of hyaluronidase.

12. A delivery system to the suprachoroidal space of the eye for reducing or suppressing vascular occlusion of the eye in individuals who require it, comprising a composition containing at least 3,000 IU / mL of hyaluronidase.

13. A delivery system to the suprachoroidal space of the eye for reducing or suppressing hyaluronic acid-induced vision loss in individuals who require it, the delivery system comprising a composition containing at least 3,000 IU / mL of hyaluronidase.

14. The delivery system according to any one of claims 11 to 13, wherein the delivery system includes a needle and a syringe, an ADG needle, or a microinjector.

15. The delivery system according to claim 14, wherein the microinjector is a choroidal microinjector.

16. The delivery system according to any one of claims 11 to 15, wherein the concentration of the hyaluronidase is at least 10,000 IU / mL, at least 11,000 IU / mL, at least 12,000 IU / mL, at least 13,000 IU / mL, at least 14,000 IU / mL, at least 15,000 IU / mL, at least 16,000 IU / mL, at least 17,000 IU / mL, at least 18,000 IU / mL, at least 19,000 IU / mL, or at least 20,000 IU / mL.

17. A kit comprising one or more containers, each containing a pharmaceutical composition comprising hyaluronidase, wherein the concentration of the hyaluronidase is at least 3,000 IU / mL.

18. The kit according to claim 17, wherein the pharmaceutical composition is a liquid formulation.

19. The kit according to claim 17, wherein the pharmaceutical composition is a dried formulation.

20. The kit according to any one of claims 17 to 19, wherein each of the one or more containers is a delivery system.

21. The kit according to any one of claims 17 to 19, further comprising a delivery system.

22. The delivery system comprises a needle and syringe, an ADG needle, or a microinjector, according to the kit of claim 20 or 21.

23. The kit according to claim 22, wherein the microinjector is a choroidal microinjector.

24. The kit according to any one of claims 17 to 23, further comprising an auxiliary active compound, drug, pharmacologic agent, local anesthetic, or hormone.

25. The kit according to any one of claims 17 to 24, further comprising another container for a solvent, instructions for use, or both.

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