Method for preparing an ocular surface for ophthalmic procedure

Abstract

The present disclosure relates to a method for preparing an ocular surface for ophthalmic procedure. The method comprises topically administering a gel anesthetic composition to the ocular surface of a subject and topically administering an antiseptic composition to the ocular surface of the subject after administering the gel anesthetic composition to the ocular surface of the subject.

Description

METHOD FOR PREPARING AN OCULAR SURFACE FOR OPHTHALMICPROCEDURECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims the benefit of US Provisional Application No. 63 / 625,789 titled “THE EFFECTS OF LOW VISCOSITY CHLOROPROCAINE OPHTHALMIC GEL 3% ON THE BACTERICIDAL ACTION OF POVIDONE-IODINE: A COMPARISON VS TETRACAINE 0.5% OPHTHALMIC SOLUTION”, filed on January 26, 2024, the entire contents of which are incorporated by reference herein.FIELD OF INVENTION

[0002] This invention relates to a method for preparing an ocular surface for ophthalmic procedure.BACKGROUND

[0003] Topical local anesthetics play a pivotal role in ophthalmology and are widely used throughout most ophthalmic procedures and surgeries. The first FDA approved topical ocular anesthetic products included solutions like oxybuprocaine, proparacaine, and tetracaine. Reports of off-labeled use of urologic lidocaine 2% jelly for ophthalmic procedures showed a favorable profile which led to the development of a branded lidocaine 3.5% gel in 2008 (Akten Gel®, Thea Pharma, Waltham MA) indicated for ocular surface anesthesia during ophthalmic procedures. Studies leading to the FDA approval of these anesthetics did not involve patients undergoing an ophthalmic surgical procedure.

[0004] While the viscosity of gel formulations increases residency time on the ocular surface of the local anesthetic, which results in increased drug exposure in the deeper tissues and reduces its systemic absorption; in recent years, there have been reports of increased endophthalmitis rates linked to the use of higher viscosity topical medications around the time of povidone-iodine (PVI) application in various ophthalmic procedures. It is theorized that the higher viscosity of these medications may act as a barrier to PVI, preventing free molecular iodine from reaching the bacterial cell membrane and working as a cytotoxic agent.

[0005] Two individual in-vitro studies evaluating lidocaine gel before the application of PVI resulted in a decreased effectiveness of antisepsis and increased microbial survivability. Theinvestigators proposed that the gel barrier prevented the PVI from coming in contact with the bacteria. One retrospective analysis of 154,198 anti-VEGF injections found that use of lidocaine jelly and tetracaine gel (Tetravisc, now discontinued) was an independent risk factor for endophthalmitis after injection (p<0.001). Another retrospective analysis analyzing 15,920 cataract surgeries also found that use of lidocaine 2% gel prior to PVI prep was a potential risk factor for endophthalmitis. These findings have led some clinicians to apply PVI prior to any viscous gel anesthetics. However, this often leads to patient dissatisfaction due to the burning / stinging associated with PVI on an unanesthetized eye.BRIEF SUMMARY

[0006] In various embodiments, a method for preparing an ocular surface for ophthalmic procedure may be performed by firstly applying a gel anesthetic composition topically to the ocular surface of a subject. Subsequently, an antiseptic composition may be applied topically to the ocular surface of the subject following the application of the gel anesthetic composition.

[0007] This method is designed to ensure that the ocular surface is adequately numbed and disinfected, which helps to reduce discomfort and minimize the risk of infection during the ophthalmic procedure. The use of both anesthetic and antiseptic compositions in sequence optimizes patient comfort and safety.

[0008] The present disclosure is directed to a method for preparing an ocular surface for ophthalmic procedure. The method comprises topically administering a gel anesthetic composition to the ocular surface of a subject and topically administering an antiseptic composition to the ocular surface of the subject after administering the gel anesthetic composition to the ocular surface of the subject.

[0009] In some embodiments, the gel anesthetic composition may comprise one or more ester- based or amide-based local anesthetics. The one or more ester-based local anesthetics may comprise procaine, tetracaine, chloroprocaine, and benzocaine, and pharmaceutically acceptable salts thereof. In some embodiments, the one or more ester-based local anesthetics may be chloroprocaine or a pharmaceutically acceptable salt thereof. The chloroprocaine may have a concentration of about 1% to about 5% by weight of the gel anesthetic in the gel anesthetic composition. In some embodiments, the one or more amide-based local anesthetics may be lidocaine, bupivacaine, mepivacaine, and prilocaine, and pharmaceutically acceptable salts thereof.

[0010] In some embodiments, the gel anesthetic composition may have a viscosity from about 1200 cP to about 2000 cP.

[0011] In some embodiments, the antiseptic composition may be povidone-iodine, chlorhexidine, or both.

[0012] In some embodiments, the time period between topically administering the gel anesthetic composition to the ocular surface of the subject and topically administering the antiseptic composition to the ocular surface of the subject may range from about 5 minutes to about 30 minutes.

[0013] In some embodiments, the effectiveness of the antiseptic composition may not be statistically significantly different from administering an anesthetic solution to the ocular surface of the subject prior to administering the antiseptic composition to the ocular surface of the subject.

[0014] In some embodiments, the method may result in a reduction of colony forming units (CFU) in the subject’s eye by 70% or more.

[0015] In some embodiments, the gel anesthetic composition may be free of antimicrobial preservatives.

[0016] In some embodiments, the gel anesthetic composition may comprise one or more gelling agents, one or more pH adjusters, one or more tonicity agents, one or more stabilizers, or combinations thereof. In some embodiments, the one or more gelling agent comprises hydroxyethyl cellulose. In some embodiments, the gel anesthetic composition may have a pH from about 2.0 to about 7.0.

[0017] In some embodiments, topically administering the gel anesthetic composition may entail administering from 1 to 5 drops of the gel anesthetic composition to the ocular surface of the subject.

[0018] In some embodiments, topically administering the gel anesthetic composition may entail administering 2 drops of the gel anesthetic composition to the ocular surface of the subject.

[0019] In some embodiments, topically administering the gel anesthetic composition may entail administering 3 drops of the gel anesthetic composition to the ocular surface of the subject.

[0020] In some embodiments, the antiseptic composition may be a solution.

[0021] In some embodiments, topically administering an antiseptic composition to the ocular surface of the subject may be accomplished using eye drops, ocular inserts, punctal plugs, eye patches, ocular film or matrix, or sustained-release drug delivery systems.

[0022] In some embodiments, the ocular surface may be anesthetized for a duration from about 5 minutes to about 120 minutes.

[0023] The present disclosure is further directed to a method for preparing an ocular surface for ophthalmic procedure. The method includes topically administering a gel anesthetic composition to a subject’s eye and topically administering an antiseptic composition to the subject’s eye after administering the gel anesthetic composition to the subject’s eye.

[0024] The present disclosure is further directed to a method for reducing the risk of endophthalmitis in a subject undergoing an ophthalmic procedure. The method includes topically administering a gel anesthetic composition to the ocular surface of a subject and topically administering an antiseptic composition to the ocular surface of the subject after administering the gel anesthetic composition to the ocular surface of the subject.BRIEF DESCRIPTION OF DRAWINGS

[0025] FIG. 1 is a schematic illustration of the description of the study protocol that patients underwent in accordance with some embodiments of the present disclosure. OD = right eye; OS = left eye; PVI = povidone iodine.TERMS AND DEFINITIONS

[0026] Unless specific definitions are provided, the nomenclatures utilized in connection with, and the laboratory procedures and techniques of analytical chemistry, synthetic organic and inorganic chemistry described herein, are those known in the art. Standard chemical symbols are used interchangeably with the full names represented by such symbols. Thus, for example, the terms “hydrogen” and “H” are understood to have identical meaning. Standard techniques may be used for chemical syntheses, chemical analyses, formulating compositions and testing them. The foregoing techniques and procedures can be generally performed according to conventional methods well known in the art.

[0027] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention claimed. As used herein, the use of the singular includes the plural unless specifically statedotherwise. The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0028] As used herein, “or” means “and / or” unless stated otherwise. Furthermore, use of the term “including” as well as other forms, such as “includes,” and “included,” is not limiting.

[0029] “About” as used herein means that a number referred to as “about” comprises the recited number plus or minus 1-10% of that recited number. For example, “about” 100 degrees can mean 95-105 degrees or as few as 99-101 degrees depending on the context.

[0030] As used herein, the term “pharmaceutical composition” refers to a chemical or biological compound or substance, or a mixture or combination of two or more such compounds or substances, intended for use in the medical diagnosis, cure, treatment, or prevention of disease or pathology.

[0031] As used herein, the term “anesthetic” refers to a substance that that causes loss of sensation and therefore induces insensitivity or low sensitivity to pain.

[0032] As used herein, “pharmaceutically acceptable” refers to a carrier, whether diluent or excipient, that is compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.

[0033] The terms “administration of a composition” or “administering a composition” are defined to include an act of providing a compound or pharmaceutical composition of the application to the subject in need of treatment.

[0034] The term “preservative” for the purposes of the present invention refers to a chemical substance that is added to a pharmaceutical composition to prevent the growth of microbes. Microbes include but are not limited to bacteria, fungus, and viruses.

[0035] As used herein, “gel” refers to a semi-solid, jelly-like substance with a viscosity from about 500 cP to about 5000 cP.

[0036] As used herein, “endophthalmitis” refers to a severe, potentially sight-threatening infection that occurs inside the eye, typically involving the vitreous or aqueous humor. It is often caused by bacteria, fungi, or other pathogens, and it can lead to rapid vision loss if not treated promptly.

[0037] As used herein, “ocular surface” refers to refers to the external part of the eye that is exposed to the environment, primarily consisting of the cornea, conjunctiva, and tear film.

[0038] As used herein, “subject” refers to a person in need of an ocular surgery or ocular procedure, which may include but is not limited to procedures such as intravitreal injections, cataract surgery, corneal transplantation, retinal surgery, glaucoma surgery, strabismus surgery, anti-VEGF therapy, or combinations thereof.DETAILED DESCRIPTION

[0039] The present disclosure is directed to a method for preparing an ocular surface for ophthalmic procedure. Prior to ophthalmic procedure, the ocular surface of a subject must be prepared by anesthetizing and sterilizing the eye to prevent infection and reduce pain in the subject. The method comprises topically administering a gel anesthetic composition to the ocular surface of a subject followed by topically administering an antiseptic composition to the ocular surface of the subject after administering the gel anesthetic composition to the ocular surface of the subject. In some embodiments, the method comprises topically administering a gel anesthetic composition to a subject’s eye and topically administering an antiseptic composition to the subject’s eye after administering the gel anesthetic composition to the subject’s eye.

[0040] The present disclosure is also directed to a method for reducing the risk of endophthalmitis in a subject undergoing an ophthalmic procedure. The method includes topically administering a gel anesthetic composition to the ocular surface of a subject and topically administering an antiseptic composition to the ocular surface of the subject after administering the gel anesthetic composition to the ocular surface of the subject.

[0041] Ophthalmic procedures may range from minor diagnostic tests to more invasive surgeries. Examples of ophthalmic procedures include but are not limited to cataract surgery, glaucoma surgery, laser eye surgery, intravitreal injections, corneal transplant, ocular trauma repair, pterygium surgery, strabismus surgery, blepharoplasty, dacryocystorhinostomy, oculoplastic surgeries, or diagnostic procedures.Method

[0042] The method comprises topically administering a gel anesthetic composition to the ocular surface of a subject. Topical administration of the gel anesthetic composition may be accomplished using eye drops, ocular inserts, punctal plugs, eye patches, ocular film or matrix, sustained-release drug delivery systems, or for ocular drug delivery. Topical administration viaeye drops may be accomplished using bottles with a dropper tip, often equipped with a controlled-release mechanism to dispense a single drop at a time. Example of ocular inserts include but are not limited to punctal plugs or ocular films. Ocular films may be small, biodegradable films or inserts that gradually dissolve or are removed after a specified time. Punctal plugs may be small silicone or collagen plugs, often placed by an ophthalmologist. Sustained-release drug delivery systems include small implants or drug-filled reservoirs that may release medication over weeks to months.

[0043] In some embodiments, topically administering the gel anesthetic composition comprises administering from 1 to 10 drops of the gel anesthetic composition to the ocular surface of the subject. For example, 2 to 9 drops, 3 to 8 drops, or 4 to 6 drops of the gel anesthetic composition may be administered. In some embodiments, topically administering the gel anesthetic composition comprises administering 2 drops of the gel anesthetic composition to the ocular surface of the subject. In some embodiments, topically administering the gel anesthetic composition comprises administering 3 drops of the gel anesthetic composition to the ocular surface of the subject. In some embodiments, topically administering the gel anesthetic composition comprises administering 4 drops of the gel anesthetic composition to the ocular surface of the subject. In some embodiments, topically administering the gel anesthetic composition comprises administering 5 drops, 6 drops, 7 drops, 8 drops, 9 drops, or 10 drops of the gel anesthetic composition to the ocular surface of the subject.

[0044] The ocular surface may be anesthetized for a duration of about 5 to about 120 minutes, such as from about 5 minutes to about 30 minutes, about 5 minutes to about 60 minutes, about 5 minutes to about 90 minutes, or about 5 minutes to about 120 minutes. For example, the duration may be about 1 minute, about 2 minutes, about 3 minutes, about 4 minutes, about 5 minutes, about 6 minutes, about 7 minutes, about 8 minutes, about 9 minutes, about 10 minutes, about 11 minutes, about 12 minutes, about 13 minutes, about 14 minutes, about 15 minutes, about 16 minutes, about 17 minutes, about 18 minutes, about 19 minutes, about 20 minutes, about 21 minutes, about 22 minutes, about 23 minutes, about 24 minutes, about 25 minutes, about 26 minutes, about 27 minutes, about 28 minutes, about 29 minutes, about 30 minutes, about 31 minute, about 32 minutes, about 33 minutes, about 34 minutes, about 35 minutes, about 36 minutes, about 37 minutes, about 38 minutes, about 39 minutes, about 40 minutes, about 41 minute, about 42 minutes, about 43 minutes, about 44 minutes, about 45 minutes, about 46 minutes, about 47 minutes, about 48 minutes, about 49 minutes, about 50 minutes,about 51 minute, about 52 minutes, about 53 minutes, about 54 minutes, about 55 minutes, about 56 minutes, about 57 minutes, about 58 minutes, about 59 minutes, about 60 minutes, about 61 minute, about 62 minutes, about 63 minutes, about 64 minutes, about 65 minutes, about 66 minutes, about 67 minutes, about 68 minutes, about 69 minutes, about 70 minutes, about 71 minute, about 72 minutes, about 73 minutes, about 74 minutes, about 75 minutes, about 76 minutes, about 77 minutes, about 78 minutes, about 79 minutes, about 80 minutes, about 81 minute, about 82 minutes, about 83 minutes, about 84 minutes, about 85 minutes, about 86 minutes, about 87 minutes, about 88 minutes, about 89 minutes, about 90 minutes, about 91 minute, about 92 minutes, about 93 minutes, about 94 minutes, about 95 minutes, about 96 minutes, about 97 minutes, about 98 minutes, about 99 minutes, about 100 minutes, about 101 minute, about 102 minutes, about 103 minutes, about 104 minutes, about 105 minutes, about 106 minutes, about 107 minutes, about 108 minutes, about 109 minutes, about 110 minutes, about 111 minute, about 112 minutes, about 113 minutes, about 114 minutes, about 115 minutes, about 116 minutes, about 117 minutes, about 1 18 minutes, about 119 minutes, or about 120 minutes.

[0045] The method further comprises topically administering an antiseptic composition to the ocular surface of the subject after administering the gel anesthetic composition to the ocular surface of the subject. Topical administration of the gel anesthetic composition and the antiseptic composition may be accomplished using eye drops, ocular inserts, punctal plugs, eye patches, ocular film or matrix, or sustained-release drug delivery systems.

[0046] The time period between topically administering the gel anesthetic composition to the ocular surface of the subject and topically administering the antiseptic composition to the ocular surface of the subject is from about 3 minutes to about 40 minutes, such as from about 3 minutes to about 10 minutes, about 3 minutes to about 20 minutes, about 3 minutes to about 30 minutes, or about 3 minutes to about 40 minutes. The time period may be about 3 minutes, about 4 minutes, about 5 minutes, about 6 minutes, about 7 minutes, about 8 minutes, about 9 minutes, about 10 minutes, about 11 minutes, about 12 minutes, about 13 minutes, about 14 minutes, about 15 minutes, about 16 minutes, about 17 minutes, about 18 minutes, about 19 minutes, about 20 minutes, about 21 minutes, about 22 minutes, about 23 minutes, about 24 minutes, about 25 minutes, about 26 minutes, about 27 minutes, about 28 minutes, about 29 minutes, about 30 minutes, about 31 minute, about 32 minutes, about 33 minutes, about 34minutes, about 35 minutes, about 36 minutes, about 37 minutes, about 38 minutes, about 39 minutes, or about 40 minutes.

[0047] The effectiveness of the antiseptic composition may not be statistically significantly different from administering an anesthetic solution to the ocular surface of the subject prior to administering the antiseptic composition to the ocular surface of the subject. As surprisingly found by the inventors, the low viscosity of the gel anesthetic composition may act as a conduit rather than a barrier as seen in high viscosity anesthetic solution.

[0048] In some embodiments, the method may result in a reduction of colony forming units (CFU) in the subject’s eye by 70% or more. CFUs may include all types of viable microorganisms capable of growing into a colony on a solid medium. Viable microorganisms may be aerobic cultures. CFUs are not limited to bacteria; they may also include other types of microorganisms, such as fungi, yeasts, protozoa, algae, or archaea. The reduction of CFU in the subject's eye may be 71% or more, 72% or more, 73% or more, 74% or more, 75% or more, 76% or more, 77% or more, 78% or more, 79% or more, 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, or 99% or more.Gel Anesthetic composition

[0049] The anesthetic may be a gel anesthetic composition. The gel anesthetic composition may be free of antimicrobial preservatives. The gel anesthetic composition comprises one or more anesthetic agents. The gel anesthetic composition may further include one or more gelling agents, one or more pH adjusters, one or more tonicity agents, one or more stabilizers, or combinations thereof.

[0050] The concentration of the one or more anesthetic agents in the gel anesthetic composition may range from about 0.5% to about 10% by weight. In some embodiments, the concentration of the one or more anesthetic agents may range from about 0.5% to about 1.5%, about 0.5% to about 2.5%, about 0.5% to about 3.5%, about 0.5% to about 4.5%, about 0.5% to about 5.5%, about 0.5% to about 6.5%, about 0.5% to about 7.5%, about 0.5% to about 8.5%, about 0.5% to about 9.5%, about 0.5% to about 10%, about 1.5% to about 2.5%, about 1.5% to about 3.5%, about 1.5% to about 4.5%, about 1.5% to about 5.5%, about 1.5% to about 6.5%, about 1.5% to about 7.5%, about 1.5% to about 8.5%, about 1.5% to about 9.5%, about 1.5% toabout 10%, about 2.5% to about 2.5%, about 2.5% to about 3.5%, about 2.5% to about 4.5%, about 2.5% to about 5.5%, about 2.5% to about 6.5%, about 2.5% to about 7.5%, about 2.5% to about 8.5%, about 2.5% to about 9.5%, about 2.5% to about 10%, about 3.5% to about 4.5%, about 3.5% to about 5.5%, about 3.5% to about 6.5%, about 3.5% to about 7.5%, about 3.5% to about 8.5%, about 3.5% to about 9.5%, about 3.5% to about 10%, about 4.5% to about 5.5%, about 4.5% to about 6.5%, about 4.5% to about 7.5%, about 4.5% to about 8.5%, about 4.5% to about 9.5%, about 4.5% to about 10%, about 5.5% to about 6.5%, about 5.5% to about 7.5%, about 5.5% to about 8.5%, about 5.5% to about 9.5%, about 5.5% to about 10%, about 6.5% to about 7.5%, about 6.5% to about 8.5%, about 6.5% to about 9.5%, about 6.5% to about 10%, about 7.5% to about 8.5%, about 7.5% to about 9.5%, about 7.5% to about 10%, about 8.5% to about 9.5%, about 8.5% to about 10%, or about 9.5% to about 10% by weight. In some embodiments, the concentration of the one or more anesthetic agents may range from about 0.5% to about 4.5%, about 1% to about 4%, or about 1% to about 5% by weight. In some embodiments, the concentration of the one or more anesthetic agents may be about 0.5%, about 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 3.5%, about 4%, about 4.5%, about 5%, about 5.5%, about 6%, about 6.5%, about 7%, about 7.5%, about 8%, about 8.5%, about 9%, about 9.5%, or about 10% by weight.

[0051] The gel anesthetic composition may include one or more ester-based or amide-based local anesthetics. Examples of ester-based anesthetics include but are not limited to procaine, tetracaine, chloroprocaine, and benzocaine, and pharmaceutically acceptable salts thereof. Examples of amide-based local anesthetics include but are not limited to lidocaine, bupivacaine, mepivacaine, and prilocaine, and pharmaceutically acceptable salts thereof.

[0052] In some embodiments, the gel anesthetic composition may include chloroprocaine or a pharmaceutically acceptable salt thereof. The chloroprocaine may have a concentration in the gel anesthetic composition from about 1% to about 5% by weight of the gel anesthetic composition. The chloroprocaine concentration may range from about 1.5% to about 2%, about 1.5% to about 2.5%, about 1.5% to about 3%, about 1.5% to about 3.5%, about 1.5% to about 4%, about 1.5% to about 4.5%, 1.5% to about 5%, about 2% to about 2.5%, about 2% to about 3%, about 2% to about 3.5%, about 2% to about 4%, about 2% to about 4.5%, about 2% to about 5%, about 2.5% to about 3%, about 2.5% to about 3.5%, about 2.5% to about 4%, about 2.5% to about 4.5%, about 2.5% to about 5%, about 3% to about 3.5%, about 3% to about 4%, about 3% to about 4.5%, about 3% to about 5%, about 3.5% to about 4%, about 3.5% to about4.5%, about 3.5% to about 5%, 4% to about 4.5%, or about 4% to about 5% by weight. For example, the chloroprocaine concentration may be about 1%, about 1.25%, about 1.50%, about 1.75%, about 2%, about 2.25%, about 2.50%, about 2.75%, about 3%, about 3.25%, about 3.50%, about 3.75%, about 4%, about 4.25%, about 4.50%, about 4.75%, or about 5.0% by weight.

[0053] The gel anesthetic composition may include one or more gelling agents. The gelling agent may include natural polymers, synthetic polymers, starches, proteins, gums and resins, polysorbate 20, sorbitan esters, sodium hyaluronate, methylcellulose, or polyethylene glycol (PEG). Examples of natural polymer synthetic agents include but are not limited to hydroxyethyl cellulose (HEC), xanthan gum, guar gum, agar-agar, or pectin. The concentration of gelling agents in the gel anesthetic composition may range from about 0.1% to about 5% by weight of the gel anesthetic composition. The gelling agent concentration may range from about 0.5% to about 5%, about 1% to about 5%, about 1.5% to about 5%, about 2% to about 5%, about 2.5% to about 5%, about 3% to about 5%, about 3.5% to about 5%, about 4% to about 5%, about 4.5% to about 5%, about 0.5% to about 4.5%, about 1% to about 4.5%, about 1.5% to about 4.5%, about 2% to about 4.5%, about 2.5% to about 4.5%, about 3% to about 4.5%, about 3.5% to about 4.5%, about 4% to about 4.5%, about 0.5% to about 4.0%, about 1% to about 4%, about 1.5% to about 4%, about 2% to about 4%, about 2.5% to about 4%, about 3% to about 4%, about 3.5% to about 4%, about 0.5% to about 3.5%, about 1% to about 3.5%, about 1.5% to about 3.5%, about 2% to about 3.5%, about 2.5% to about 3.5%, about 3% to about 3.5%, about 0.5% to about 3%, about 1% to about 3%, about 1.5% to about 3%, about 2% to about 3%, about 2.5% to about 3%, about 0.5% to about 2.5%, about 1% to about 2.5%, about 1.5% to about 2.5%, about 2% to about 2.5%, about 0.5% to about 2%, about 1% to about 2%, about 1.5% to about 2%, about 0.5% to about 1.5%, about 1% to about 1.5%, or about 0.5% to about 1% by weight. In some embodiments, the concentration of gelling agents in the gel anesthetic composition may range from about 0.75% to about 1.5% by weight. For example, the concentration may be about 0.8%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, or about 1.5%. In some embodiments, the gelling agent may be hydroxyethyl cellulose (HEC).

[0054] The gel anesthetic composition may include one or more tonicity agents. The tonicity agents may be isotonic, hypertonic, or hypotonic. Examples of tonicity agents may include but are not limited to sodium chloride, dextrose, mannitol, sorbitol, polyethylene glycol, calciumchloride, potassium chloride, sodium bicarbonate, or combinations thereof. The concentration of tonicity agents in the gel anesthetic composition may range from about 0.1% to about 5% by weight of the gel anesthetic composition. The tonicity agent concentration may range from about 0.5% to about 5%, about 1% to about 5%, about 1.5% to about 5%, about 2% to about 5%, about 2.5% to about 5%, about 3% to about 5%, about 3.5% to about 5%, about 4% to about 5%, about 4.5% to about 5%, about 0.5% to about 4.5%, about 1% to about 4.5%, about 1.5% to about 4.5%, about 2% to about 4.5%, about 2.5% to about 4.5%, about 3% to about 4.5%, about 3.5% to about 4.5%, about 4% to about 4.5%, about 0.5% to about 4.0%, about 1% to about 4%, about 1.5% to about 4%, about 2% to about 4%, about 2.5% to about 4%, about 3% to about 4%, about 3.5% to about 4%, about 0.5% to about 3.5%, about 1% to about 3.5%, about 1.5% to about 3.5%, about 2% to about 3.5%, about 2.5% to about 3.5%, about 3% to about 3.5%, about 0.5% to about 3%, about 1% to about 3%, about 1.5% to about 3%, about 2% to about 3%, about 2.5% to about 3%, about 0.5% to about 2.5%, about 1% to about 2.5%, about 1.5% to about 2.5%, about 2% to about 2.5%, about 0.5% to about 2%, about 1% to about 2%, about 1.5% to about 2%, about 0.5% to about 1.5%, about 1% to about 1.5%, or about 0.5% to about 1% by weight. In some embodiments, the concentration of tonicity agents in the gel anesthetic composition may range from about 0.1% to about 3% by weight.

[0055] The gel anesthetic composition may include one or more stabilizers. Examples of stabilizers may include but are not limited to antioxidants, chelating agents, or emulsifiers. Antioxidants include but are not limited to vitamin E or ascorbic acid. Chelating agents include but are not limited to EDTA. Emulsifiers include but are not limited to lecithin or polysorbates. The concentration of stabilizer in the gel anesthetic composition may range from about 0.1% to about 5% by weight of the gel anesthetic composition. The stabilizer concentration may range from about 0.5% to about 5%, about 1% to about 5%, about 1.5% to about 5%, about 2% to about 5%, about 2.5% to about 5%, about 3% to about 5%, about 3.5% to about 5%, about 4% to about 5%, about 4.5% to about 5%, about 0.5% to about 4.5%, about 1% to about 4.5%, about 1.5% to about 4.5%, about 2% to about 4.5%, about 2.5% to about 4.5%, about 3% to about 4.5%, about 3.5% to about 4.5%, about 4% to about 4.5%, about 0.5% to about 4.0%, about 1% to about 4%, about 1.5% to about 4%, about 2% to about 4%, about 2.5% to about 4%, about 3% to about 4%, about 3.5% to about 4%, about 0.5% to about 3.5%, about 1% to about 3.5%, about 1.5% to about 3.5%, about 2% to about 3.5%, about 2.5% to about 3.5%, about 3% to about 3.5%, about 0.5% to about 3%, about 1 % to about 3%, about1.5% to about 3%, about 2% to about 3%, about 2.5% to about 3%, about 0.5% to about 2.5%, about 1% to about 2.5%, about 1.5% to about 2.5%, about 2% to about 2.5%, about 0.5% to about 2%, about 1% to about 2%, about 1.5% to about 2%, about 0.5% to about 1.5%, about 1% to about 1.5%, or about 0.5% to about 1% by weight. In some embodiments, the concentration of stabilizer in the gel anesthetic composition may range from about 0.1% to about 3% by weight.

[0056] The gel anesthetic composition may be free of antimicrobial preservatives. Example of preservatives include but are not limited to benzalkonium chloride (BAK), phenoxyethanol, ethylhexylglycerin, caprylyl glycol, sodium benzoate, chlorhexidine digluconate, methylparaben and propylparaben, sorbic acid, polyquaternium-1, or combinations thereof. In some embodiments the gel anesthetic composition may be free of BAK.

[0057] The gel anesthetic composition may have one or more degradation products of chloroprocaine. Degradation products may include hydroxyprocaine, dihydrobenzoic acid (DHBA) 4-amino-2-chlorobenzoic acid (ACBA), or a combination thereof. The total amount of degradation products may be no more than about 3.5% by weight. For example, the total amount of degradation products may be no more than about 3.4% about, about 3.3%, about 3.2%, about 3.1%, about 3.0%, about 2.9%, about 2.8%, about 2.7%, about 2.6%, about 2.5%, about 2.4%, about 2.3%, about 2.2%, about 2.1%, about 2.0%, about 1.9%, about 1.8%, about1.7%, about 1.6%, about 1.5%, about 1.4%, about 1.3%, about 1.2%, about 1.1%, about 1.0%, about 0.9%, about 0.8%, about 0.7%, about 0.6%, about 0.5%, about 0.4%, about 0.3%, about0.2%, or about 0.1% by weight. In some embodiments, the total amount of degradation products may be less than about 1.5% by weight.

[0058] The viscosity of the anesthetic composition may range from about 300 cP to about 5000 cP, such as from about 300 cP to about 1000 cP, about 300 cP to about 2000 cP, about 300 cP to about 3000 cP, about 300 cP to about 4000 cP, or about 300 cP to about 5000 cP. For example, the viscosity may be from about 600 cP to about 4900 cP, about 700 cP to about 4800 cP, about 800 cP to about 4700 cP, about 900 cP to about 4600 cP, about 1000 cP to about 4500 cP, about 1100 cP to about 4400 cP, about 1200 cP to about 4300 cP, about 1300 cP to about 4200 cP, about 1400 cP to about 4100 cP, about 1500 cP to about 4000 cP, about 1600 cP to about 3900 cP, about 1700 cP to about 3800 cP, about 1800 cP to about 3700 cP, about 1900 cP to about 3600 cP, about 2000 cP to about 3500 cP, about 2100 cP to about 3400 cP, about 2200 cP to about 3300 cP, about 2300 cP to about 3200 cP, about 2400 cP to about 3100 cP, or about2500 cP to about 3000 cP. In some embodiments, the viscosity may be from about 300 cP to about 2000 cP. In some embodiments, the viscosity may be from about 1200 cP to about 2000 cP, about 1200 cP to about 1900 cP, about 1200 cP to about 1800 cP, about 1200 cP to about 1700 cP, about 1200 cP to about 1600 cP, or about 1200 cP to about 1400 cP, 1300 cP to about 2000 cP, about 1300 cP to about 1900 cP, about 1300 cP to about 1800 cP, about 1300 cP to about 1700 cP, about 1400 cP to about 2000 cP, about 1400 cP to about 1900 cP, about 1500 cP to about 1800 cP, about 1600 cP to about 2000 cP, about 1600 cP to about 1900 cP, about 1600 cP to about 1800 cP, or about 1700 cP to about 1900 cP . In some embodiments, the viscosity may be about 300 cP, about 400 cP, about 500 cP, about 600 cP, about 700 cP, about 800 cP, about 900 cP, about 1000 cP, about 1100 cP, about 1200 cP, about 1300 cP, about 1400 cP, about 1500 cP, about 1600 cP, about 1700 cP, about 1800 cP, about 1900 cP, about 2000 cP, about 2100 cP, about 2200 cP, about 2300 cP, about 2400 cP, about 2500 cP, about 2600 cP, about 2700 cP, about 2800 cP, about 2900 cP, about 3000 cP, about 3100 cP, about 3200 cP, about 3300 cP, about 3400 cP, about 3500 cP, about 3600 cP, about 3700 cP, about 3800 cP, about 3900 cP, about 4000 cP, about 4100 cP, about 4200 cP, about 4300 cP, about 4400 cP, about 4500 cP, about 4600 cP, about 4700 cP, about 4800 cP, about 4900 cP, or about 5000 cP.

[0059] The gel anesthetic composition may have a pH from about 2.0 to about 7.0. The pH of the gel anesthetic composition may be adjusted by adding pH adjusting agents. Examples of pH adjusting agents include but are not limited to hydrochloric acid or sodium hydroxide. For example, the pH may range from about 2.5 to about 7.0, about 2.5 to about 6.5, about 2.5 to about 6.0, about 2.5 to about 5.5, about 2.5 to about 5.0, about 2.5 to about 4.5, about 2.5 to about 4.0, about 2.5 to about 3.5, about 2.5 to about 3.0, 3.0 to about 7.0, about 3.0 to about6.5, about 3.0 to about 6.0, about 3.0 to about 5.5, about 3.0 to about 5.0, about 3.0 to about4.5, about 3.0 to about 4.0, about 3.0 to about 3.5, about 3.5 to about 7.0, about 3.5 to about6.5, about 3.5 to about 6.0, about 3.5 to about 5.5, about 3.5 to about 5.0, about 3.5 to about4.5, about 3.5 to about 4.0, 4.0 to about 7.0, about 4.0 to about 6.5, about 4.0 to about 6.0, about 4.0 to about 5.5, about 4.0 to about 5.0, about 4.0 to about 4.5, 4.5 to about 7.0, about 4.5 to about 6.5, about 4.5 to about 6.0, about 4.5 to about 5.5, about 4.5 to about 5.0, about 5.0 to about 7.0, about 5.0 to about 6.5, about 5.5 to about 6.0, about 6.0 to about 7.0, or about 6.0 to about 6.5. In some embodiments, the pH may range from about 3 to about 5. In some embodiments, the pH may be 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4,4.5, 4.6, 4.7, 4.8, 4.9, or 5.0.

[0060] The gel anesthetic composition may have an osmolality from about 145 mOsm / kg to about 175 mOsm / kg. For example, the osmolality may be from about 145 mOsm / kg to about 170 mOsm / kg, about 145 mOsm / kg to about 165 mOsm / kg, about 145 mOsm / kg to about 160 mOsm / kg, about 145 mOsm / kg to about 155 mOsm / kg, about 145 mOsm / kg to about 150 mOsm / kg, about 150 mOsm / kg to about 175 mOsm / kg, about 150 mOsm / kg to about 170 mOsm / kg, about 150 mOsm / kg to about 165 mOsm / kg, about 150 mOsm / kg to about 160 mOsm / kg, about 150 mOsm / kg to about 155 mOsm / kg, about 155 mOsm / kg to about 175 mOsm / kg, about 155 mOsm / kg to about 170 mOsm / kg, about 155 mOsm / kg to about 165 mOsm / kg, about 155 mOsm / kg to about 160 mOsm / kg, about 160 mOsm / kg to about 175 mOsm / kg, about 160 mOsm / kg to about 170 mOsm / kg, about 160 mOsm / kg to about 165 mOsm / kg, about 165 mOsm / kg to about 175 mOsm / kg, about 165 mOsm / kg to about 170 mOsm / kg, or about 170 mOsm / kg to about 175 mOsm / kg.Antiseptic composition

[0061] The antiseptic composition may include chlorhexidine, hydrogen peroxide, iodine tincture, benzalkonium chloride, silver sulfadiazine, octenidine dihydrochloride, povidone- iodine, or a pharmaceutically acceptable salt thereof, or any combination thereof. In some embodiments, the antiseptic composition may include povidone-iodine. Povidone-iodine is effective against a wide range of microorganisms, including bacteria, viruses, fungi, and protozoa.

[0062] The antiseptic composition may be a solution.EXAMPLES

[0063] A single site, prospective, randomized, patient-masked study evaluating the effects of chloroprocaine HC1 ophthalmic gel 3% compared to tetracaine ophthalmic solution 0.5% and their effects on the bactericidal action of povidone-iodine 5% (PVI).

[0064] The trial was conducted between June 2023 and October 2023 at one center in the United States after obtaining IRB approval and in accordance with the relevant guidelines of the Declaration of Helsinki and the International Conference on Harmonization guidelines on Good Clinical Practice (ICH E6). Signed informed consent was obtained from all patients and the study was registered on Clinicaltrials.gov identifier NCT05934253.

[0065] The primary objective of this study was to evaluate the mean percent change from baseline in colony forming units (CFU) before and after application of chloroprocaine or tetracaine, and PVI. After signing informed consent, patients were screened.

[0066] Inclusion criteria included patients at least 18 years of age with the ability to comprehend and sign a statement of informed consent. Exclusion criteria included: any ocular surgeries (intraocular, oculoplastic, corneal, or refractive) within the past three months or at any time that the investigator’s clinical judgement deemed it would interfere with outcome measures, clinically significant ocular trauma, diagnosis of lagophthalmos or other severe eyelid abnormalities, active ocular inflammation, active ocular infection, ocular infection within the last three months, moderate to severe (grade 2-4) allergic, vernal, or giant papillary conjunctivitis, patients under the age of 18, pregnant or breastfeeding, and monocular patients.

[0067] Patients that signed informed consent and met both inclusion and exclusion criteria immediately had their eyes randomized based on a predetermined randomization key. One eye was randomized to receive chloroprocaine ophthalmic gel 3% and the other to tetracaine ophthalmic solution 0.5%. Patients were masked from which eye received which intervention. All interventions were performed by a Fellowship trained Corneal specialist wearing a N95 surgical mask and surgical gloves to reduce risks of error and contamination.

[0068] The right eye (OD) was always the first treatment eye. The lower eyelid was carefully everted, and the conjunctival membrane and eyelid margin was then gently swabbed. The swab was then plated in a zig zag streaking pattern in blood agar culture plates that contained 5% sheep’s blood in a tryptic soy agar medium. Two drops of the randomized treatment were immediately applied to the eye after the swab. To simulate real world situations where there is often a gap of time between application of anesthetics, PVI and start of procedure, two minutes passed before application of PVI 5% was applied to the ocular surface. After an additional three minutes, one final drop of treatment was applied. The conjunctiva and lid margins were then swabbed again following the same procedure as the initial swab. FIG. 1 is a process flow diagram describing the study protocol that patients underwent. All steps were then repeated for the left eye (OS) with the other randomized anesthetic. Patients were exited from the study at the completion of these steps for their OS.

[0069] Cultures were sent to a regional independent pathology lab where they tested each plate for the presence of aerobic cultures. The pathogens were identified and the number of colony forming units (CFU) was identified. Results were analyzed by the investigator, who haddiscretion to void samples if they deemed the results to be contaminated or if the initial culture, prior to application of PVI, grew zero colonies.

[0070] Treatment related adverse events (TEAE) were not part of this study as they have been documented in each products package insert.Statistical analysis

[0071] Descriptive statistics (mean, standard deviation (SD), median, minimum, and maximum) of actual values and changes in CFUs from baseline to post PVI installation were recorded by treatment group. Baseline was defined as the culture obtained before any treatment installation. The distribution of the change from baseline in CFUs will be assessed for normality. The non-inferiority of the chloroprocaine treatment group compared to the tetracaine group was evaluated using two-sided 90% confidence intervals for the between-group difference in the mean change in CFUs.

[0072] The frequency and percentage of patients with no CFUs post PVI installation was also assessed by treatment group. Two-sided 90% confidence intervals will be calculated for the between-group difference in the percentage of patients with a CFU of 0. A Chi-square test will also be performed to compare the two treatments with respect to the proportion of patients with no CFUs post treatment. Confidence intervals were used to assess the similarity or noninferiority of chloroprocaine to tetracaine. All analyses were performed using Statistical Analysis System (SAS®) Software version 9.4.Results

[0073] A total of 100 patients were enrolled in the study, of which 18 were dropped as screening failure. The subsequent 82 patients were randomized based on a pre-set randomization key. 36 / 82 (44%) were randomized to chloroprocaine in the OD and tetracaine in the OS. 77% of subjects were female and the average age of participants was 37 years of age. 44% self-identified as Hispanic, 36.5% as Caucasian, 17% as Black / African American, and 2.5% as Asian / Pacificlslander. All 82 subjects who were randomized completed the study.

[0074] A total of six samples were deemed to be contaminated and excluded from analysis (three chloroprocaine group, three tetracaine group). No imputation method was applied during the analysis since no missing values were observed in the collected data. The primary endpoint for this study was the mean percent reduction in colony forming units (CFU) after PVI application from baseline.

[0075] In the chloroprocaine group, the average baseline CFU was 41.9. The average post PVI CFU was 8.7. This showed a 79.3% reduction in CFU from baseline post PVI application. In the tetracaine group, the average baseline CFU was 38.9. The average post PVI CFU was 10.8. This showed a 72.1% reduction in CFU from baseline post PVI application. The mean change from the baseline in CFU after PVI application was not statistically significant between chloroprocaine and tetracaine treated groups (change [A] = -7.2; 90% CI, -13.56 to 3.28).

[0076] The percentage of patients with no colonies (CFU=0) post PVI application was the same in both groups (32 [43.2%], 90% CI, -13.0% to 13.0%), which suggests non-inferiority of chloroprocaine compared to tetracaine in its effect on the bactericidal action of PVI. Not surprisingly, the vast majority of isolates were staphylococcus aureus (93.2%). The results are summarized in Table 1.Table 1. Summary of resultsDiscussion

[0077] The purpose of this in-vivo study was to compare the effects of chloroprocaine ophthalmic gel 3% with PVI compared to a low viscosity tetracaine ophthalmic solution while simulating real world practices. Previous studies have shown that high viscosity gel vehicles act as a barrier to PVI and may increase the risk of endophthalmitis following ophthalmic procedures. Tetracaine ophthalmic solution 0.5% was selected as the comparator because it is one of the most commonly used topical ophthalmic anesthetics and because of its viscosity being close to human tears, thus not causing a potential barrier effect to povidone-iodine. One concern when selecting tetracaine ophthalmic solution is that it contains benzalkonium chloride (BAK), a preservative used in approximately 70% of ophthalmic formulations, whilechloroprocaine ophthalmic gel 3% is preservative free. BAK has been shown in many studies to cause cytotoxic damage to conjunctival, corneal epithelial, and corneal endothelial cells. However, the proven antimicrobial activity of this preservative continues to make it a popular addition to new formulations. One study evaluated the antibacterial activity of BAK in ophthalmic tetracaine vs preservative free anesthetics and found that preservative free anesthetic solutions did not interfere with bacterial development in culture media while BAK containing solutions inhibited development of gram-positive bacteria S. aureus, but not P. aeruginosa.

[0078] Given the difference in viscosity and that chloroprocaine gel is preservative free while tetracaine solution contains (BAK), the researchers expected the results to be similar, with a skew towards tetracaine. However, despite these differences, chloroprocaine ophthalmic gel 3% showed a greater average percent reduction in CFU post PVI application compared to tetracaine ophthalmic solution 0.5%. The authors theorize that this lower viscosity gel could act as a conduit to PVI, rather than a barrier seen in higher viscosity gels, reducing its drainage from the eye, and thus allowing for more contact time with the surface of the eye.

[0079] One area of note is that only about 3 out of 4 eyes in both groups showed 10 or less CFU present post PVI application and only 34% of subjects showed zero CFU post PVI application in both groups. A similar study conducted by Ferguson, et al comparing PVI 5% to PVI 1% evaluated change in bacterial colonies before and one minute after application of PVI. This study found that PVI 5% decreased median CFU from 100 to 40 (60% decrease) while PVI 1% decreased median CFU from 120 to 100 (16.7% decrease).19 Further studies are needed to evaluate the time kill action of PVI in the ophthalmic setting to find the optimal time it should be utilized prior to start of the procedure as well as the associated risk of minor bacterial colonies.Conclusion

[0080] Data collected in this study demonstrates that preservative-free chloroprocaine ophthalmic gel 3% does not act as a barrier to the bactericidal actions of povidone-iodine 5% and that the reduction in CFU from PVI is non-inferior when compared to low viscosity tetracaine 0.5% ophthalmic solution with PVI.

[0081] Having described aspects of the invention in detail, it will be apparent that modifications and variations are possible without departing from the scope of aspects of the invention as definedin the appended claims. As various changes could be made in the above compositions, products, and methods without departing from the scope of aspects of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense.

[0082] While the foregoing description makes reference to particular illustrative embodiments, these examples should not be construed as limitations. The inventive system, methods, and products can be adapted for other uses or provided in other forms not explicitly listed above, and can be modified in numerous ways within the spirit of the present disclosure. Thus, the present invention is not limited to the disclosed embodiments but is to be accorded the widest scope consistent with the claims below.

[0083] Numerous examples are provided herein to enhance the understanding of the present disclosure. A specific set of embodiments are provided as follows.

[0084] Embodiment 1: A method for preparing an ocular surface for ophthalmic procedure comprising topically administering a gel anesthetic composition to the ocular surface of a subject; and topically administering an antiseptic composition to the ocular surface of the subject after administering the gel anesthetic composition to the ocular surface of the subject.

[0085] Embodiment 2: The method of embodiment 1, wherein the gel anesthetic composition comprises one or more ester-based or amide-based local anesthetics.

[0086] Embodiment 3: The method of embodiment 2, wherein the one or more ester-based local anesthetics comprise procaine, tetracaine, chloroprocaine, and benzocaine, and pharmaceutically acceptable salts thereof.

[0087] Embodiment 4: The method of embodiment 2 or embodiment 3, wherein the one or more ester-based local anesthetics is chloroprocaine or a pharmaceutically acceptable salt thereof.

[0088] Embodiment 5: The method of embodiment 4, wherein the chloroprocaine has a concentration in the gel anesthetic composition from about 1% to about 5% by weight of the gel anesthetic composition.

[0089] Embodiment 6: The method of embodiment 2, wherein the one or more amide-based local anesthetics comprises lidocaine, bupivacaine, mepivacaine, and prilocaine, and pharmaceutically acceptable salts thereof.

[0090] Embodiment 7: The method of any one of embodiments 1 to 6, wherein the gel anesthetic composition has a viscosity from about 1200 cP to about 2000 cP.

[0091] Embodiment 8: The method of any one of embodiments 1 to 7, wherein antiseptic composition comprises povidone-iodine, chlorhexidine, or both.

[0092] Embodiment 9: The method of any one of embodiments 1 to 8, wherein the time period between topically administering the gel anesthetic composition to the ocular surface of the subject and topically administering the antiseptic composition to the ocular surface of the subject ranges from about 5 minutes to about 30 minutes.

[0093] Embodiment 10: The method of any one of embodiments 1 to 9, wherein the effectiveness of the antiseptic composition is not statistically significantly different from administering an anesthetic solution to the ocular surface of the subject prior to administering the antiseptic composition to the ocular surface of the subject.

[0094] Embodiment 11 : The method of any one of embodiments 1 to 10, wherein the method results in a reduction of colony forming units (CFU) in the subject’s eye by 70% or more.

[0095] Embodiment 12: The method of any one of embodiments 1 to 11, wherein the gel anesthetic composition is free of antimicrobial preservatives.

[0096] Embodiment 13: The method of any one of embodiments 1 to 12, wherein the gel anesthetic composition comprises one or more gelling agents, one or more pH adjusters, one or more tonicity agents, one or more stabilizers, or combinations thereof.

[0097] Embodiment 14: The method of any one of embodiments 1 to 13, wherein the one or more gelling agent comprises hydroxy ethyl cellulose.

[0098] Embodiment 15: The method of any one of embodiments 1 to 14, wherein the gel anesthetic composition has a pH from about 2.0 to about 7.0.

[0099] Embodiment 16: The method of any one of embodiments 1 to 15, wherein topically administering the gel anesthetic composition comprises administering from 1 to 5 drops of the gel anesthetic composition to the ocular surface of the subject.

[0100] Embodiment 17: The method of embodiment 16, wherein topically administering the gel anesthetic composition comprises administering 2 drops of the gel anesthetic composition to the ocular surface of the subject.

[0101] Embodiment 18: The method of embodiment 16, wherein topically administering the gel anesthetic composition comprises administering 3 drops of the gel anesthetic composition to the ocular surface of the subject.

[0102] Embodiment 19: The method of any one of embodiments 1 to 18, wherein the antiseptic composition is a solution.

[0103] Embodiment 20: The method of any one of embodiments 1 to 19, wherein topically administering an antiseptic composition to the ocular surface of the subject is accomplished using eye drops, ocular inserts, punctal plugs, eye patches, ocular film or matrix, or sustained- release drug delivery systems.

[0104] Embodiment 21 : The method of any one of embodiments 1 to 20, wherein the ocular surface is anesthetized for a duration from about 5 minutes to about 120 minutes.

[0105] Embodiment 22: A method for preparing an ocular surface for ophthalmic procedure consisting of topically administering a gel anesthetic composition to a subject’s eye; and topically administering an antiseptic composition to the subject’s eye after administering the gel anesthetic composition to the subject’s eye.

[0106] Embodiment 23: A method for reducing the risk of endophthalmitis in a subject undergoing an ophthalmic procedure, the method comprising topically administering a gel anesthetic composition to the ocular surface of a subject; and topically administering an antiseptic composition to the ocular surface of the subject after administering the gel anesthetic composition to the ocular surface of the subject.

Claims

CLAIMSWhat is claimed is:

1. A method for preparing an ocular surface for ophthalmic procedure comprising: topically administering a gel anesthetic composition to the ocular surface of a subject; and topically administering an antiseptic composition to the ocular surface of the subject after administering the gel anesthetic composition to the ocular surface of the subject.

2. The method of claim 1, wherein the gel anesthetic composition comprises one or more ester- based or amide-based local anesthetics.

3. The method of claim 2, wherein the one or more ester-based local anesthetics comprise procaine, tetracaine, chloroprocaine, and benzocaine, and pharmaceutically acceptable salts thereof.

4. The method of claim 3, wherein the one or more ester-based local anesthetics is chloroprocaine or a pharmaceutically acceptable salt thereof.

5. The method of claim 4, wherein the chloroprocaine has a concentration in the gel anesthetic composition from about 1% to about 5% by weight of the gel anesthetic composition.

6. The method of claim 2, wherein the one or more amide-based local anesthetics comprises lidocaine, bupivacaine, mepivacaine, and prilocaine, and pharmaceutically acceptable salts thereof.

7. The method of claim 1, wherein the gel anesthetic composition has a viscosity from about 1200 cP to about 2000 cP.

8. The method of claim 1, wherein antiseptic composition comprises povidone-iodine, chlorhexidine, or both.

9. The method of claim 1, wherein the time period between topically administering the gel anesthetic composition to the ocular surface of the subject and topically administering the antiseptic composition to the ocular surface of the subject ranges from about 5 minutes to about 30 minutes.

10. The method of claim 1, wherein the effectiveness of the antiseptic composition is not statistically significantly different from administering an anesthetic solution to the ocular surface of the subject prior to administering the antiseptic composition to the ocular surface of the subject.

11. The method of claim 1, wherein the method results in a reduction of colony forming units (CFU) in the subject’s eye by 70% or more.

12. The method of claim 1, wherein the gel anesthetic composition is free of antimicrobial preservatives.

13. The method of claim 1, wherein the gel anesthetic composition comprises one or more gelling agents, one or more pH adjusters, one or more tonicity agents, one or more stabilizers, or combinations thereof.

14. The method of claim 1, wherein the one or more gelling agent comprises hydroxyethyl cellulose.

15. The method of claim 1, wherein the gel anesthetic composition has a pH from about 2.0 to about 7.0.

16. The method of claim 1 , wherein topically administering the gel anesthetic composition comprises administering from 1 to 5 drops of the gel anesthetic composition to the ocular surface of the subject.

17. The method of claim 16, wherein topically administering the gel anesthetic composition comprises administering 2 drops of the gel anesthetic composition to the ocular surface of the subject.

18. The method of claim 16, wherein topically administering the gel anesthetic composition comprises administering 3 drops of the gel anesthetic composition to the ocular surface of the subject.

19. The method of claim 1, wherein the antiseptic composition is a solution.

20. The method of claim 1, wherein topically administering an antiseptic composition to the ocular surface of the subject is accomplished using eye drops, ocular inserts, punctal plugs, eye patches, ocular film or matrix, or sustained-release drug delivery systems.

21. The method of claim 1, wherein the ocular surface is anesthetized for a duration from about 5 minutes to about 120 minutes.

22. A method for preparing an ocular surface for ophthalmic procedure consisting of: topically administering a gel anesthetic composition to a subject’s eye; and topically administering an antiseptic composition to the subject’s eye after administering the gel anesthetic composition to the subject’s eye.

23. A method for reducing the risk of endophthalmitis in a subject undergoing an ophthalmic procedure, the method comprising: topically administering a gel anesthetic composition to the ocular surface of a subject; and topically administering an antiseptic composition to the ocular surface of the subject after administering the gel anesthetic composition to the ocular surface of the subject.

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