Treatment of myopia

Abstract

The present invention provides a method of treating myopia, comprising administering to an eye of a subject in need thereof a composition comprising a copper-containing agent.

Description

[Technical field]

[0001] (Related Applications) This application claims the benefit of U.S. Provisional Patent Application No. 63 / 148,344, filed February 11, 2021, the disclosure of which is incorporated herein by reference in its entirety. [Background technology]

[0002] Myopia is a common cause of reduced vision. The defect that causes myopia is an overly steep cornea or slight elongation of the eyeball, which causes the eye's lens to focus light from distant objects in front of the retina. Uncorrected myopia is one of the leading causes of distance vision loss worldwide. In severe cases, the elongation of the eyeball stretches and thins parts of the interior of the eye, which increases the risk of retinal detachment, cataracts, glaucoma, and blindness. The prevalence of myopia is increasing and is predicted to affect approximately half of the world's population by 2050. Summary of the Invention

[0003] The present invention relates to a method of treating myopia, comprising administering to the eye of a subject in need thereof a composition comprising a copper-containing agent. [Brief description of the drawings]

[0004] [Figure 1A] 1 is a graph of peroxidase-linked fluorescent lox activity in normal corneal stromal cells showing dose response with copper perchlorate. [Figure 1B] 1 is a graph showing that copper perchlorate at a concentration as low as 100 nM induced greater LOX activity than copper sulfate in keratinizing human corneal stromal cells. [Diagram 2] FIG. 1 is a graph showing that copper perchlorate-treated sclera have higher lysinonorleucine (LNL) content than control untreated sclera (n=5 each); p=0.036 using paired t-test. [Diagram 3] 1 is a graph showing that sclera treated with copper perchlorate are less compliant (i.e., stiffer) than untreated sclera. [Figure 4] This graph shows that copper perchlorate treatment slowed the progression of myopia by 48% within 9 weeks of treatment (n=5). [Diagram 5] Graphs showing changes in vitreous chamber depth (VCD) (A,B) and axial length (AL) (C,D) in spontaneous myopic progression guinea pig pups (n=5). A,C show the mean changes, while B,D show the difference between copper perchlorate treated eyes (OD) and control eyes (OS). Copper perchlorate treatment showed a trend to slow the elongation of AL and VCD within 6 weeks of treatment. Error bars: SEM. [Figure 6] Topical administration of copper perchlorate (0.35 mg / ml) significantly delayed vitreous chamber depth elongation (A), axial elongation (B), and myopia progression (C) in spontaneously myopic guinea pig pups (n=5). *p<0.05. Error bars: SEM. [Figure 7] Mean refractive error measurements versus time for the right eye (treated eye) and left eye (control eye) in a genetic model of myopia in a guinea pig. [Figure 8] Peroxidase-linked fluorescent LOX activity in normal scleral cells showing a dose response to copper perchlorate. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0005] Myopia is a severely debilitating eye condition. The underlying defect in myopia is that an overly steep cornea or a slightly elongated eyeball causes the eye's lens to focus light from distant objects in front of the retina. That's why myopia is often called short-sightedness or near-sightedness. In severe cases, this elongation of the eyeball can stretch and thin parts of the interior of the eye, increasing the risk of retinal detachment, cataracts, glaucoma, and blindness. Myopia is much more serious than short-sightedness.

[0006] There are many causes of myopia that have been identified and studied, including genetic predisposition, prolonged book and screen use, and inadequate exposure to bright light. Regardless of the underlying cause of myopia (one or more of the above), the elongated eyeball associated with myopia weakens all affected eyes. Because the eye grows during childhood, myopia typically develops during childhood and adolescence and can persist throughout adulthood. Therefore, improved treatments for individuals, such as those in their early childhood and adolescence, can improve quality of life throughout their lifetime.

[0007] Accordingly, the present invention is a method of treating myopia, comprising administering a composition comprising a copper-containing agent to an eye of a subject in need thereof.

[0008] In certain embodiments, an ophthalmic composition or dosage form comprising a copper-containing agent is used in the methods of the invention. The ophthalmic composition or dosage form can include an amount of the copper-containing agent effective to treat myopia. The composition or dosage form can further include a pharma- ceutically acceptable carrier. In some embodiments, the dosage form can be an ophthalmic composition formulated as a topical eye drop. Such a composition can be carried in a container adapted to dispense the composition dropwise, for example, in a drop volume of about 5 μl to about 100 μl. In some embodiments, the ophthalmic composition can be a sustained release composition formulated to release the copper-containing agent over an extended period of time. The methods of the invention can include administering a therapeutically effective amount of a composition or dosage form described herein during a treatment period.

[0009] In certain embodiments, the copper-containing agent is a copper salt.In certain embodiments, the copper-containing agent is selected from copper sulfate, copper carbonate, copper acetate, copper chloride, copper gluconate, copper bromide, copper fluoride, copper nitrate, copper iodide, copper perchlorate, copper periodate, copper perbromate, copper permanganate, hemocyanin, copper molybdate, copper thiocyanate, copper tartrate, copper tetrafluoroborate, copper selenide, copper pyrophosphate, GHK-copper, copper tetraammine sulfate, copper histidine, and copper glycinate.In further embodiments, the copper-containing agent is selected from copper perchlorate, copper perbromate, copper periodate, and copper permanganate, their hydrates, or combinations thereof.In certain preferred embodiments, the copper-containing agent is copper perchlorate. In preparing the ophthalmic compositions described herein, the copper-containing agents used in the preparation may be anhydrous or hydrated (e.g., copper(II) perchlorate hexahydrate or copper(II) sulfate pentahydrate).

[0010] Ophthalmic compositions of copper-containing agents can be characterized based on the amount of copper in the composition, which can be conveyed as any suitable measure of concentration, such as molality, molarity, or weight percent of the copper-containing agent in the composition.

[0011] In some embodiments, the weight percentages provided herein are calculated based on the weight percentage of anhydrous copper(II) perchlorate in the ophthalmic composition, e.g., as a method of normalizing copper content independent of the weight of any associated counterions, complexes, or ligands.Therefore, if a different copper-containing agent is used, the weight percentages can be appropriately converted based on the molecular weight of the copper-containing agent.

[0012] For example, the copper-containing agent can be present in an amount of about 0.00001% by weight or from about 0.0001% by weight to about 5%, 10%, or 15% by weight. In some embodiments, the copper-containing agent can be present at about 0.0001% to about 5% by weight, about 0.0001% to about 4% by weight, about 0.0001% to about 3% by weight, about 0.0001% to about 2% by weight, about 0.0001% to about 1% by weight, about 0.0001% to about 0.75% by weight, about 0.0001% to about 0.5% by weight, about 0.0001% to about 0.25% by weight, about 0.0001% to about 0.1% by weight, about 0.0001% to about 0.075% by weight, about 0.0001% to about 0.05% by weight, about 0.0001% to about 0.025% by weight, or about 0.0001% to about 0.02% by weight.

[0013] Alternatively, in some embodiments, the copper-containing agent can be present at about 0.0005% to about 5% by weight, about 0.0005% to about 4% by weight, about 0.0005% to about 3% by weight, about 0.0005% to about 2% by weight, about 0.0005% to about 1% by weight, 0.0005% to about 0.75% by weight, about 0.0005% to about 0.5% by weight, about 0.0005% to about 0.25% by weight, about 0.0005% to about 0.1% by weight, about 0.0005% to about 0.075% by weight, about 0.0005% to about 0.05% by weight, about 0.0005% to about 0.025% by weight, or about 0.0005% to about 0.02% by weight.

[0014] Alternatively, in some embodiments, the copper-containing agent can be present at about 0.001% to about 5% by weight, about 0.001% to about 4% by weight, about 0.001% to about 3% by weight, about 0.001% to about 2% by weight, about 0.001% to about 1% by weight, about 0.001% to about 0.75% by weight, about 0.001% to about 0.5% by weight, about 0.001% to about 0.25% by weight, about 0.001% to about 0.1% by weight, about 0.001% to about 0.075% by weight, about 0.001% to about 0.05% by weight, about 0.001% to about 0.025% by weight, or about 0.001% to about 0.02% by weight.

[0015] Alternatively, in some embodiments, the copper-containing agent can be present at about 0.003 wt.% to about 5 wt.%, about 0.003 wt.% to about 4 wt.%, about 0.003 wt.% to about 3 wt.%, about 0.003 wt.% to about 2 wt.%, about 0.003 wt.% to about 1 wt.%, about 0.003 wt.% to about 0.75 wt.%, about 0.003 wt.% to about 0.5 wt.%, about 0.003 wt.% to about 0.25 wt.%, about 0.003 wt.% to about 0.1 wt.%, about 0.003 wt.% to about 0.075 wt.%, about 0.003 wt.% to about 0.05 wt.%, about 0.003 wt.% to about 0.025 wt.%, or about 0.003 wt.% to about 0.02 wt.%.

[0016] Alternatively, in some embodiments, the copper-containing agent can be present at about 0.005% to about 5% by weight, about 0.005% to about 4% by weight, about 0.005% to about 3% by weight, about 0.005% to about 2% by weight, about 0.005% to about 1% by weight, about 0.005% to about 0.75% by weight, about 0.005% to about 0.5% by weight, about 0.005% to about 0.25% by weight, about 0.005% to about 0.1% by weight, about 0.005% to about 0.075% by weight, about 0.005% to about 0.05% by weight, about 0.005% to about 0.025% by weight, or about 0.005% to about 0.02% by weight.

[0017] In further embodiments, the copper-containing agent can be present in an amount of about 0.05% to about 15% by weight, about 0.01% to about 10% by weight, or about 0.005% to about 5% by weight. In other embodiments, the copper-containing agent can be present in an amount of about 0.00001% to about 0.0001% by weight, about 0.0001% to about 0.0005% by weight, about 0.0001% to about 0.0002% by weight, about 0.0002% to about 0.0003% by weight, or about 0.0003% to about 0.0004% by weight. In still other embodiments, the copper-containing agent can be present in an amount of about 0.001% to about 0.01% by weight, or about 0.003% to about 0.008% by weight. In yet other embodiments, the copper-containing agent can be present in an amount of from about 0.01% to about 0.1% by weight, or from about 0.03% to about 0.08% by weight.

[0018] The amount of copper in the composition can alternatively be expressed as weight per volume (e.g., mg / mL). In some embodiments, the weight per volume measurements provided herein are calculated based on the total copper weight per volume unit in the ophthalmic composition. For example, an amount of 0.0025 mg / ml of copper(II) perchlorate hexahydrate provides a composition with a copper content of about 0.000428 mg / ml. This is because the atomic weight of copper(II) perchlorate hexahydrate is about 370.54 g / mol, but only about 63.5 g / mol or about 17% of the agent is copper itself. As an alternative example, an amount of 0.0018 mg / ml of anhydrous copper(II) acetate provides a composition with a copper content of about 0.00063 mg / ml. Thus, in some embodiments, the concentration of the copper-containing agent can be determined based on the total copper content provided by the copper-containing agent, rather than the amount of the copper-containing agent itself.

[0019] Thus, in some embodiments, the compositions comprise a copper-containing agent in an amount from about 0.0001 mg / mL or about 0.0005 mg / mL to about 5 mg / mL or about 50 mg / mL. In some embodiments, the composition comprises a copper-containing agent in an amount of about 0.001 mg / mL to about 50 mg / mL, about 0.001 mg / mL to about 40 mg / mL, about 0.001 mg / mL to about 30 mg / mL, about 0.001 mg / mL to about 20 mg / mL, about 0.001 mg / mL to about 10 mg / mL, about 0.001 mg / mL to about 7.5 mg / mL, about 0.001 mg / mL to about 5 mg / mL, about 0.001 mg / mL to about 2.5 mg / mL, about 0.001 mg / mL to about 1 mg / mL, about 0.001 mg / mL to about 0.75 mg / mL, about 0.001 mg / mL to about 0.5 mg / mL, about 0.001 mg / mL to about 0.25 mg / mL, or about 0.001 mg / mL to about 0.2 mg / mL.

[0020] Alternatively, in some embodiments, the copper-containing agent can be present at about 0.005 mg / mL to about 50 mg / mL, about 0.005 mg / mL to about 40 mg / mL, about 0.005 mg / mL to about 30 mg / mL, about 0.005 mg / mL to about 20 mg / mL, about 0.005 mg / mL to about 10 mg / mL, about 0.005 mg / mL to about 7.5 mg / mL, about 0.005 mg / mL to about 5 mg / mL, about 0.005 mg / mL to about 2.5 mg / mL, about 0.005 mg / mL to about 1 mg / mL, about 0.005 mg / mL to about 0.75 mg / mL, about 0.005 mg / mL to about 0.5 mg / mL, about 0.005 mg / mL to about 0.25 mg / mL, or about 0.005 mg / mL to about 0.2 mg / mL.

[0021] Alternatively, in some embodiments, the copper-containing agent can be present at about 0.01 mg / mL to about 50 mg / mL, about 0.01 mg / mL to about 40 mg / mL, about 0.01 mg / mL to about 30 mg / mL, about 0.01 mg / mL to about 20 mg / mL, about 0.01 mg / mL to about 10 mg / mL, about 0.01 mg / mL to about 7.5 mg / mL, about 0.01 mg / mL to about 5 mg / mL, about 0.01 mg / mL to about 2.5 mg / mL, about 0.01 mg / mL to about 1 mg / mL, about 0.01 mg / mL to about 0.75 mg / mL, about 0.01 mg / mL to about 0.5 mg / mL, about 0.01 mg / mL to about 0.25 mg / mL, or about 0.01 mg / mL to about 0.2 mg / mL.

[0022] Alternatively, in some embodiments, the copper-containing agent can be present at about 0.03 mg / mL to about 50 mg / mL, about 0.03 mg / mL to about 40 mg / mL, about 0.03 mg / mL to about 30 mg / mL, about 0.03 mg / mL to about 20 mg / mL, about 0.03 mg / mL to about 10 mg / mL, about 0.03 mg / mL to about 7.5 mg / mL, about 0.03 mg / mL to about 5 mg / mL, about 0.03 mg / mL to about 2.5 mg / mL, about 0.03 mg / mL to about 1 mg / mL, about 0.03 mg / mL to about 0.75 mg / mL, about 0.03 mg / mL to about 0.5 mg / mL, about 0.03 mg / mL to about 0.25 mg / mL, or about 0.03 mg / mL to about 0.2 mg / mL.

[0023] Alternatively, in some embodiments, the copper-containing agent is from about 0.05 mg / mL to about 50 mg / mL, from about 0.05 mg / mL to about 40 mg / mL, from about 0.05 mg / mL to about 30 mg / mL, from about 0.05 mg / mL to about 20 mg / mL, from about 0.05 mg / mL to about 10 mg / mL, from about 0.05 mg / mL to about 7.5 mg / mL, from about 0.05 mg / mL to about 5 mg / mL, from about 0.05 mg / mL to about 2.5 mg / mL , about 0.05 mg / mL to about 1 mg / mL, about 0.05 mg / mL to about 0.75 mg / mL, about 0.05 mg / mL to about 0.5 mg / mL, about 0.05 mg / mL to about 0.4 mg / mL, about 0.05 mg / mL to about 0.3 mg / mL, about 0.05 mg / mL to about 0.25 mg / mL, about 0.05 mg / mL to about 0.2 mg / mL, or about 0.05 mg / mL to about 0.2 mg / mL.

[0024] Alternatively, in some embodiments, the copper-containing agent may be from about 0.075 mg / mL to about 50 mg / mL, from about 0.075 mg / mL to about 40 mg / mL, from about 0.075 mg / mL to about 30 mg / mL, from about 0.075 mg / mL to about 20 mg / mL, from about 0.075 mg / mL to about 10 mg / mL, from about 0.075 mg / mL to about 7.5 mg / mL, from about 0.075 mg / mL to about 5 mg / mL, from about 0.075 mg / mL to about 2.5 mg / mL, mL, about 0.075 mg / mL to about 1 mg / mL, about 0.075 mg / mL to about 0.75 mg / mL, about 0.075 mg / mL to about 0.5 mg / mL, about 0.075 mg / mL to about 0.4 mg / mL, about 0.075 mg / mL to about 0.3 mg / mL, about 0.075 mg / mL to about 0.25 mg / mL, about 0.075 mg / mL to about 0.2 mg / mL, or about 0.075 mg / mL to about 0.2 mg / mL.

[0025] Alternatively, in some embodiments, the copper-containing agent may be from about 0.1 mg / mL to about 50 mg / mL, from about 0.1 mg / mL to about 40 mg / mL, from about 0.1 mg / mL to about 30 mg / mL, from about 0.1 mg / mL to about 20 mg / mL, from about 0.1 mg / mL to about 10 mg / mL, from about 0.1 mg / mL to about 7.5 mg / mL, from about 0.1 mg / mL to about 5 mg / mL, or from about 0.1 mg / mL to about 10 mg / mL. The active ingredient can be present at about 0.1 mg / mL to about 2.5 mg / mL, about 0.1 mg / mL to about 1 mg / mL, about 0.1 mg / mL to about 0.75 mg / mL, about 0.1 mg / mL to about 0.5 mg / mL, about 0.1 mg / mL to about 0.4 mg / mL, about 0.1 mg / mL to about 0.3 mg / mL, about 0.1 mg / mL to about 0.25 mg / mL, or about 0.1 mg / mL to about 0.2 mg / mL.

[0026] However, just because a particular amount of copper-containing agent is included in a composition does not mean that all of the copper content is bioavailable upon administration, or that it is bioavailable in the same proportion. Copper bioavailability may vary to some extent from one copper-containing component to another. In addition, copper bioavailability may be affected by pH, viscosity, solubility, and other compositional factors. For a given patient, the appropriate dosage of the copper-containing agent may be determined based on the type of delivery vehicle, the type of copper-containing agent, the desired delivery period, and the like. Thus, the appropriate dosage of the copper-containing agent may also be adjusted based on the bioavailability of copper for a particular copper carrier, pH, formulation, and the like. Furthermore, the release rate of the copper content from a particular dosage form may be adjusted based on the particular copper-containing agent employed in the dosage form. For example, in some cases, a less soluble copper-containing agent (e.g., copper fluoride, copper hydroxide, copper carbonate, and the like) may be used to prolong the release of the copper-containing agent from the composition. In some further embodiments, the release rate may additionally or alternatively be controlled by a particular pharmaceutical carrier or formulation type.

[0027] In some embodiments, the copper-containing agent can be administered with a second active or therapeutic agent, such as an additional crosslinking agent. The second active agent can act by another mechanism of action that works in concert with the crosslinking induced by the copper-containing agent and / or another crosslinking agent. For example, the second active agent can reduce axial elongation, reduce accommodation (i.e., the process by which the eye changes its refractive power to maintain a clear focus on an image as its distance changes), and the like, or a combination thereof. Such additional agents can include riboflavin, rose bengal, hydroxylysine, calcium-containing agents, magnesium-containing agents, silver-containing agents, aluminum-containing agents, zinc-containing agents, iron-containing agents, acai extract, decorin, biglycan, keratocan, lumican, mimican, fibromodulin, collagen type VI, collagen type X, collagen type XII, collagen type XIV, atropine, homatopine, cyclopentolate, pirenzepine, 7-methylxanthanine, and the like, or a combination thereof. In some embodiments, the additional or second active agent can include atropine, homatropine, cyclopentolate, pirenzepine, 7-methylxanthanine, and the like, or combinations thereof. In certain embodiments, the second active agent can include atropine. In some additional embodiments, the second active agent can include homatropine. In yet additional embodiments, the second active agent can include cyclopentolate. In further embodiments, the second active agent can include pirenzepine. In further embodiments, the second active agent can include 7-methylxanthanine. The second active agent can generally be present in an amount of about 0.001% to about 0.1% by weight. In other embodiments, the second active agent can be present in an amount of about 0.005% to about 0.05% by weight, or about 0.007% to about 0.02% by weight.

[0028] In other embodiments, the composition does not include an additional active ingredient, i.e., the copper-containing agent is the only active ingredient in the composition, hi some embodiments, the composition does not include an anti-inflammatory agent, an antihistamine, a vasoconstrictor, an antibiotic, an analgesic, or a steroid.

[0029] In certain embodiments, the composition does not include an amine. In some embodiments, the composition does not include an amine-copper complex, e.g., a coordination complex in which a copper cation is complexed to one or more amine ligands.

[0030] The copper-containing agent can be provided in a pharma- ceutically acceptable carrier. The pharma- ceutically acceptable carrier can be formulated in a variety of ways to deliver the copper-containing agent. Non-limiting examples can include solutions, suspensions, emulsions, gels, hydrogels, thermoresponsive gels, formulations for subconjunctival injection, formulations for sub-Tenon's injection, depots, films, sustained delivery matrices, contact lenses, pledgets, punctal plugs, gelling suspensions, and the like, or combinations thereof. The composition can be formulated for passive delivery to the eye. Alternatively, the composition can be formulated for active delivery to the eye, such as iontophoresis, electroporation, sonoporation, and the like. In certain embodiments, the formulation can be an eye drop. In some embodiments, the composition can be formulated as a copper-eluting contact lens, such as a soft lens, a toric lens, a hard lens, a scleral lens, and the like, or a combination thereof. The contact lens can be a daily disposable lens or an extended wear lens (e.g., a lens for use from 2 days to 2 weeks or more). In some embodiments, the composition can be formulated as a sustained delivery or depot matrix or device for placement in contact with an ocular surface, such as the cul-de-sac, conjunctiva, subconjunctival, Tenon's capsule, or sub-Tenon's space. In some embodiments, the composition can be formulated as a biodegradable device, such as a lens, film, capsule, punctal plug, or the like, or a combination thereof. The biodegradable device can be configured to biodegrade at a rate of about 1 week to about 6 months, or about 2 weeks to about 4 months, or about 1 month to about 2 months.

[0031] The composition comprising a copper-containing agent may further comprise an excipient selected from a tonicity agent, a solubilizer, a viscosity enhancing agent, a polymer, a buffer, a pH adjusting agent, a preservative, and water, In certain such embodiments, the composition comprises two or more of the excipients.

[0032] Non-limiting examples of solubilizing agents can include phosphate buffered saline (PBS), Dulbecco's PBS, Alsever's solution, Tris-buffered saline (TBS), water, balanced salt solutions (BSS) such as Hank's BSS, Earle's BSS, Gray's BSS, Puck's BSS, Simm's BSS, Tyrode's BSS, BSS Plus, Ringer's lactate solution, normal saline (i.e., 0.9% saline), ½ normal saline, or combinations thereof. Solubilizing agents can be present in the pharma- ceutically acceptable carrier in varying amounts depending on the particular formulation, method of treatment, and the like.

[0033] Non-limiting examples of tonicity agents can include the solubilizers listed above, as well as sodium chloride, potassium chloride, calcium chloride, magnesium chloride, mannitol, sorbitol, dextrose, glycerin, propylene glycol, ethanol, trehalose, and the like, or combinations thereof. Tonicity agents can be used to provide the appropriate isotonicity of the formulation. In certain embodiments, the tonicity of the formulation is about 200 to about 800 milliosmoles per liter (mOsm / L). In other embodiments, the tonicity of the formulation can be about 200 mOsm / L to about 700 mOsm / L. In other embodiments, the tonicity of the formulation can be about 200 mOsm / L to about 650 mOsm / L. In yet other embodiments, the tonicity of the formulation can be about 200 mOsm / L to about 600 mOsm / L. In other embodiments, the tonicity of the formulation can be from about 250 mOsm / L to about 700 mOsm / L. In still other embodiments, the tonicity of the formulation can be from about 250 mOsm / L to about 650 mOsm / L, from about 250 mOsm / L to about 600 mOsm / L, from about 270 mOsm / L to about 700 mOsm / L, from about 270 mOsm / L to about 650 mOsm / L, or from about 270 mOsm / L to about 600 mOsm / L. The tonicity agent can be present in the pharma- ceutically acceptable carrier in various amounts, depending on the particular formulation, method of treatment, etc.

[0034] Non-limiting examples of pH adjusters include many acids, bases, and combinations thereof, such as hydrochloric acid, phosphoric acid, citric acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, etc. The pH adjuster can be used to provide the appropriate pH to the formulation. In certain embodiments, the pH of the composition can be about 5.0 to about 8.5. In certain embodiments, the pH can be about 5.0 to about 8.0. Alternatively, the pH can be about 5.2 to about 8.0, about 5.3 to about 8.0, about 5.4 to about 7.9, about 5.5 to about 7.8. The pH adjuster can be present in a pharma- ceutically acceptable carrier in various amounts, depending on the particular formulation, method of treatment, etc.

[0035] Non-limiting examples of viscosity enhancing agents can include glycerol, propylene glycol, polyethylene glycol, polyvinyl alcohol, cellulose derivatives (such as methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, etc.), ethylvinyl alcohol, hyaluronic acid, etc., or combinations thereof. Viscosity enhancing agents can be present in a pharma- ceutically acceptable carrier in varying amounts, depending on the particular formulation, method of treatment, etc.

[0036] Non-limiting examples of polymers that can be used to prepare polymeric matrices for films, contact lenses, and the like can include biodegradable or non-biodegradable polymers. Non-limiting examples of polymers or combinations of polymers can include poly(methyl methacrylate), polyorthoesters, hydroxyethyl methacrylate, polysiloxanes, poly(lactic-co-glycolic acid) (with different ratios of lactic acid and glycolide content, and end groups such as acid or ester ends), polyvinyl alcohol, polyvinyl acetate, ethylene vinyl acetate, polyethylene glycol, polylactic acid, polyglycolic acid, hydroxypropyl methylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose, croscamellose, polycaprolactone, hyaluronic acid, albumin, sodium chloride block copolymers thereof, salts thereof, and the like, or combinations thereof. Certain copolymers, such as polylactic acid-polyglycolic acid block copolymer (PLGA), polyglycolic acid-polyvinyl alcohol block copolymer (PGA / PVA), hydroxypropyl methylcellulose (HPMC), polycaprolactone-polyethylene glycol block copolymer, and croscarmellose, can be particularly effective for biodegradable matrices, if desired.

[0037] In certain embodiments, the composition can include a thermoresponsive polymer. Non-limiting examples of thermoresponsive polymers include poly(N-isopropylacrylamide), poly[2-(dimethylamino)ethyl methacrylate], hydroxypropyl cellulose, poly(vinylcaprolactam), polyvinyl methyl ether, polyethylene oxide, polyhydroxyethyl methacrylate, ABCBA type pentablock polymer, chitosan, etc., or combinations thereof. Such thermoresponsive polymers can bind or function with a specific copper-containing agent within a certain temperature range, and release the copper-containing agent when the temperature of the surrounding environment is changed, such as contacting the composition with the eye or applying a heat source to the eye after administration of the composition.

[0038] Non-limiting examples of preservatives can include benzalkonium chloride (BAK), cetrimonium, sodium perborate, ethylenediaminetetraacetic acid (EDTA) and its various salt forms, chlorobutanol, etc. Preservatives can be present in the pharma- ceutically acceptable carrier in varying amounts depending on the particular formulation, method of treatment, etc.

[0039] In certain preferred embodiments, the composition is administered topically. The composition for topical administration to the eye includes an ophthalmic composition. The composition for topical administration is formulated as an ointment, gel, thin film, or eye drop composition.

[0040] In a particularly preferred embodiment, the composition can be formulated as an eye drop, for example, the pharma- ceutically acceptable carrier can include PBS, BSS, or other suitable solubility or tonicity agent. For example, the composition can be formulated as an eye drop, for example, the pharma-ceutically acceptable carrier can include artificial tears (e.g., RefreshTears®, Genteal®, OasisTears®, etc.). Alternatively, the composition can be formulated as a thin film, an ointment, a gelling suspension, a punctal plug, or a contact lens.

[0041] The ophthalmic composition can be used as an ophthalmic dosage form for administering a therapeutically effective amount of a copper-containing agent. In some embodiments, an amount of about 1 μl to about 500 μl of the composition is administered per administration event. In still other embodiments, about 1 μl to about 250 μl, about 1 μl to about 200 μl, about 1 μl to about 100 μl, about 2 μl to about 250 μl, about 2 μl to about 200 μl, about 2 μl to about 100 μl, about 3 μl to about 250 μl, about 3 μl to about 200 μl, about 3 μl to about 100 μl, about 4 μl to about 250 μl, about 4 μl to about 200 μl, about 4 μl to about 100 μl, or about 5 μl to about 250 μl, about 5 μl to about 200 μl, or about 5 μl to about 100 μl is administered per administration event. In the case of eye drops, this amount is preferably administered in, for example, 1 to 3 drops of the ophthalmic composition.

[0042] In some embodiments, the ophthalmic composition can be formulated to biodegrade or otherwise provide controlled or sustained release of the copper-containing agent over a predetermined period of time. In still other embodiments, the ophthalmic composition can be formulated to release the copper-containing agent from a non-biodegradable matrix in a controlled or sustained manner. In certain such embodiments, the dosage form can be formulated to release the copper-containing agent over a period of hours, days, or weeks, as needed. In some specific embodiments, the composition can be formulated to deliver about 0.005mcg to about 250mcg of copper per week. In still other embodiments, the dosage form can be formulated to deliver about 0.008mcg to about 200mcg per week, about 0.01mcg to about 150mcg per week, or about 0.1mcg to about 100mcg per week. In certain embodiments, the ophthalmic composition can be formulated to have zero-order drug release kinetics.

[0043] In some embodiments, the dosage form can be held or stored in a container as a premixed composition ready to be administered without further dilution or preparation. In some embodiments, a single container can hold a volume or amount of a composition suitable for a single administration, but less than the amount suitable for multiple administrations. In yet other embodiments, a single container can hold a volume or amount of a composition suitable for multiple administrations.

[0044] Many suitable containers can be used. The container can be, for example, an amber container. In some embodiments, the container can be made of glass, polypropylene, polyethylene, polycarbonate, polyvinyl chloride, or the like, or combinations thereof. In some embodiments, the container can have a volume of about 0.5 ml to about 50 ml. In other embodiments, the container can have a volume of about 1 ml to about 30 ml, about 5 ml to about 20 ml, or about 3 ml to about 15 ml. In other embodiments, the container can hold a single dose of the dosage form. Alternatively, the container can hold multiple doses of the dosage form. The container can be, for example, a vial, a bottle, a blister pack, a sachet.

[0045] In some embodiments, the container can contain from about 0.005 mg to about 1 mg of the copper-containing agent. In yet other embodiments, the container can contain from about 0.01 mg to about 5 mg of the copper-containing agent. In some embodiments, the container can contain from about 0.001 mg to about 5 mg of copper. In some embodiments, the container can contain from about 0.005 mg to about 2 mg of copper.

[0046] In certain embodiments, the dosage form may be a topical ophthalmic dosage form formulated as an eye drop and placed in a container adapted to dispense the composition dropwise in drops of about 5 μl to about 100 μl. Alternatively, the container may be adapted to dispense the ophthalmic composition in a drop volume of about 1 μl to about 250 μl, about 1 μl to about 200 μl, about 1 μl to about 100 μl, about 2 μl to about 250 μl, about 2 μl to about 200 μl, about 2 μl to about 100 μl, about 3 μl to about 250 μl, about 3 μl to about 200 μl, about 3 μl to about 100 μl, about 4 μl to about 250 μl, about 4 μl to about 200 μl, about 4 μl to about 100 μl, or about 5 μl to about 250 μl, about 5 μl to about 200 μl, or about 5 μl to about 100 μl.

[0047] When the composition is formulated as an eye drop, the container can include a suitable nozzle or tip that can dispense the composition.Thus, the container can usually be at least partially flexible or collapsible to dispense the composition.However, in some cases, after the composition is dispensed, air may be sucked back into the container, thereby contaminating the composition.Therefore, the nozzle or tip can include a valve mechanism, a filter, etc., or a combination thereof, to prevent or minimize the introduction of bacteria and other contaminants into the container.

[0048] In certain embodiments, the container or dosage form can include or be associated with an administration mechanism, such as a syringe, dropper, or other mechanism. In some embodiments, the package can be configured to provide, for example, in a single integrated system, the composition, the container, and instructions for its use, and optionally, the administration mechanism.

[0049] There are numerous options for the manner in which the compositions described herein can be administered, for example, by air-gun delivery or ballistic air delivery.

[0050] In certain embodiments, the composition or dosage form can be administered at least once a week to each eye in need of treatment, at least once a day to each eye in need of treatment, 1 to 4 times a day to each eye in need of treatment, or twice a day to each eye in need of treatment. In some embodiments, at each time point, the composition is administered in an amount of about 1 μl to about 250 μl, about 1 μl to about 200 μl, about 1 μl to about 100 μl, about 2 μl to about 250 μl, about 2 μl to about 200 μl, about 2 μl to about 100 μl, about 3 μl to about 250 μl, about 3 μl to about 200 μl, about 3 μl to about 100 μl, about 4 μl to about 250 μl, about 4 μl to about 200 μl, about 4 μl to about 100 μl, or about 5 μl to about 250 μl, about 5 μl to about 200 μl, or about 5 μl to about 100 μl.

[0051] The duration of treatment may depend on several factors, such as the severity of the condition, the age of the subject at the time of diagnosis, etc. In some embodiments, the composition is administered for a treatment period of at least about 1 week, at least about 6 weeks, or at least about 6 months. In further embodiments, the composition is administered for a treatment period of about 1 week to about 5 years, or about 6 months to about 5 years, or about 6 months to about 1 year.

[0052] In some embodiments, the ophthalmic composition can be administered as eye drops. Alternatively, the ophthalmic composition can be administered as a subconjunctival injection. In alternative embodiments, the ophthalmic composition can be administered as a sub-Tenon injection. In further alternative embodiments, the ophthalmic composition can be administered in the form of a topical film, a topical gel, a contact lens, a punctal plug, and the like. In some embodiments, the topical film, the topical gel, the contact lens, the punctal plug, and the like can be configured to biodegrade over time to provide a controlled, sustained release of the copper-containing agent.

[0053] In some embodiments, the subject is a human who is at least about 3 years old, at least about 5 years old, at least about 10 years old, or at least about 25 years old. In further embodiments, the subject is a human who is about 3 years old to about 60 years old, about 3 years old to about 40 years old, about 3 years old to about 25 years old, about 25 years old to about 60 years old, or 25 years old to about 40 years old.

[0054] In certain embodiments, the myopia is progressive myopia, hi other embodiments, the myopia is non-progressive myopia.

[0055] The methods disclosed herein are useful for treating myopia and its associated symptoms.Thus, the methods of the present invention can stabilize, improve, or correct the distorted or blurred vision of a patient, relieve eye strain, reduce squinting of the patient, reduce fatigue, and / or improve night vision.In severe cases of myopia, the methods of the present invention can slow the progression of retinal detachment, cataracts, glaucoma, and / or blindness.The methods of the present invention can reduce or prevent headaches or migraines associated with myopia.

[0056] Pharmaceutical Compositions In certain embodiments, the copper-containing agents used in the methods of the present invention are formulated in a pharmaceutical composition, e.g., the pharmaceutical composition comprises one or more copper-containing agents and a pharma- ceutically acceptable carrier.

[0057] The compositions and methods of the present invention are utilized to treat individuals in need thereof.In certain embodiments, the individual is a mammal, such as a human, or a non-human mammal.When administered to an animal, such as a human, the compositions or compounds are preferably administered as pharmaceutical compositions, for example, comprising the compounds of the present invention and a pharmaceutically acceptable carrier.Pharmaceutically acceptable carriers are well known in the art, and include, for example, aqueous solutions, such as water or physiologically buffered saline, or other solvents or solvents, such as glycols, glycerol, oils, such as olive oil, or organic esters.

[0058] Pharmaceutically acceptable carriers can include, for example, physiologically acceptable agents that act to stabilize, increase solubility, or increase absorption of a compound such as a compound of the present invention. Such physiologically acceptable agents include, for example, carbohydrates such as glucose, sucrose, or dextran, antioxidants such as ascorbic acid or glutathione, chelating agents, low molecular weight proteins, or other stabilizers or excipients.

[0059] Further examples of pharma- ceutically acceptable antioxidants include: (1) water-soluble antioxidants, such as ascorbic acid, cysteine ​​hydrochloride, sodium bisulfate, sodium disulfite, sodium sulfite, and the like; (2) oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, α-tocopherol, and the like; and (3) metal chelators, such as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like.

[0060] The phrase "pharmacologically acceptable" as used herein refers to compounds, materials, compositions, and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0061] The phrase "pharmacologically acceptable carrier" as used herein means a pharma- ceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not harmful to the patient. Examples of substances that can function as pharma-ceutically acceptable carriers include: (1) sugars, such as lactose, glucose, sucrose, and the like; (2) starches, such as corn starch, potato starch, and the like; (3) cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose, cellulose acetate, and the like; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter, suppository wax, and the like; and (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, soybean oil. (10) glycols, such as propylene glycol, (11) polyols, such as glycerin, sorbitol, mannitol, polyethylene glycol, and the like; (12) esters, such as ethyl oleate, ethyl laurate, and the like; (13) agar; (14) buffers, such as magnesium hydroxide, aluminum hydroxide, and the like; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) phosphate buffer solution; and (21) other non-toxic compatible substances used in pharmaceutical formulations.

[0062] Methods of preparing these formulations or compositions include the step of bringing into association an active compound, such as a compound of the present invention, with the carrier and, optionally, one or more accessory ingredients. Generally, the formulations are prepared by uniformly and intimately bringing the active compound into association with one or more liquid carriers.

[0063] Suspensions may contain, in addition to the active compound(s), suspending agents such as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar, and tragacanth, and mixtures thereof.

[0064] These compositions may also contain auxiliary agents such as preservatives, wetting agents, emulsifying agents, and dispersing agents. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, etc. It is also preferable to include isotonic agents, such as sugars, sodium chloride, etc., in the compositions.

[0065] Actual dosage levels of the active ingredients in pharmaceutical compositions can be varied to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, and which is not toxic to the patient.

[0066] The selected dosage level will depend on a variety of factors, including the activity of the particular compound or combination of compounds employed, the route of administration, the time of administration, the rate of elimination or excretion of the particular compound employed, the duration of treatment, other drugs, compounds, and / or materials used in combination with the particular compound employed, the age, sex, weight, condition, general health, and previous medical history of the patient being treated, as well as factors well known in the medical art.

[0067] A physician or veterinarian of ordinary skill in the art can easily determine and prescribe the required therapeutically effective amount of the pharmaceutical composition. For example, the physician or veterinarian can begin administering the pharmaceutical composition or compound at a level lower than that required to achieve the desired therapeutic effect, and gradually increase the dosage until the desired effect is achieved. By "therapeutically effective amount" is meant the concentration of the compound sufficient to elicit the desired therapeutic effect. It is generally understood that the effective amount of the compound varies according to the subject's weight, sex, age, and medical history. Other factors that affect the effective amount include, but are not limited to, the severity of the patient's condition, the disease being treated, the stability of the compound, and other types of therapeutic agents that are optionally administered together with the compound of the present invention. A larger total dose can be delivered by administering the agent multiple times. Methods for determining efficacy and dosage are known to those skilled in the art (Isselbacher et al. (1996) Harrison's Principles of Internal Medicine 13 ed., 1814-1882, incorporated herein by reference).

[0068] In general, a suitable daily dose of an active compound used in the compositions and methods of the present invention is that amount of the compound that is the lowest dose effective to produce a therapeutic effect. Such an effective amount will generally depend on the factors mentioned above.

[0069] Optionally, the effective daily dose of active compound is administered as 1, 2, 3, 4, 5, 6 or more subdoses administered separately at appropriate intervals throughout the day, optionally in unit dosage form.In certain embodiments of the present invention, active compound is administered 2 or 3 times a day.In certain embodiments, active compound is administered once a day.

[0070] The patient to receive this treatment may be any animal in need thereof, including primates, particularly humans, as well as other mammals, such as horses, cattle, pigs, and sheep, as well as poultry and pets in general.

[0071] In certain embodiments, the compounds of the present invention are used alone or are administered in combination with another type of therapeutic agent. As used herein, the phrase "conjoint administration" refers to any form of administration of two or more different therapeutic compounds, such that the second compound is administered while the previously administered therapeutic compound is still effective in the body (e.g., the two compounds are effective in the patient at the same time, and a synergistic effect of the two compounds may be involved). For example, the different therapeutic compounds can be administered simultaneously or sequentially in the same formulation or in separate formulations. In certain embodiments, the different therapeutic compounds can be administered within 1 hour, 12 hours, 24 hours, 36 hours, 48 ​​hours, 72 hours, or within 1 week of each other. Thus, an individual undergoing such treatment can benefit from the combined effect of the different therapeutic compounds.

[0072] In certain embodiments, the combined administration of a compound of the invention with one or more additional therapeutic agent(s) (e.g., one or more additional chemotherapeutic agent(s)) results in improved efficacy compared to the separate administration of the compound of the invention or the one or more additional therapeutic agent(s). In certain such embodiments, the combined administration results in an additive effect, where additive effect refers to the sum of the respective effects of the separate administration of the compound of the invention and the one or more additional therapeutic agent(s).

[0073] The term "treating" includes preventative and / or therapeutic treatments. The term "prophylactic or therapeutic" treatments is art-recognized and includes administration of one or more of the subject compositions to a host. When administered prior to the clinical manifestation of an undesirable condition (e.g., a disease or other undesirable condition of a host animal), the treatment is prophylactic (i.e., protects the host against the manifestation of the undesirable condition), whereas when administered after the manifestation of an undesirable condition, the treatment is therapeutic (i.e., intended to reduce, ameliorate, or stabilize an existing undesirable condition or its side effects). Treatment also encompasses eliminating the undesirable condition or side effects. As used herein, treating a disease, disorder, or condition includes treating a complication(s) of the disease, disorder, or condition, including, for example, treating the underlying pathophysiology specific to the complication(s) of the disease, disorder, or condition. The subject to whom the therapeutic agent is administered may be asymptomatic or symptomatic. EXAMPLES

[0074] Example 1 - Copper perchlorate increases lysyl oxidase (LOX) activity in human corneal cells To examine LOX activity in normal corneal cells using copper perchlorate and compare it with activity using copper sulfate, corneal stromal cells (n=3 each) taken from normal corneas were cultured in 10% fetal bovine serum (FBS) DMEM and exposed to copper sulfate or copper perchlorate in BSS, then filtered through a 0.25 μm filter. The conditioned culture medium was subjected to peroxidase-linked fluorescent activity measurement of LOX using Amplex red. In parallel, 500 uM aminopropionitrile (BAPN), which completely reduces LOX activity, was added. The fluorescence of oxidized Amplex red was recorded every 10 min using a fluorescent plate reader. After subtraction of background fluorescence, the fluorescence intensity was plotted against the incubation time (Figure 1).

[0075] The results showed that copper perchlorate dramatically increased LOX enzyme activity in a dose-response manner (Figure 1a). Furthermore, at a low concentration of 100 nM, copper perchlorate increased LOX activity more than copper sulfate at the same molar concentration. Without wishing to be bound by theory, it is believed that copper perchlorate enhances activity because the perchlorate anion releases oxygen, thereby enhancing the oxidase activity of LOX more than copper ions administered together with anions such as sulfate. EXAMPLES

[0076] Example 2 - Copper perchlorate increases scleral lysinonorleucine (LNL) in guinea pig pups. Lysyl oxidase converts lysine to allysine, which spontaneously conjugates to lysine or hydroxylysine to become lysinonorleucine (LNL), an established biomarker of collagen cross-linking. To test the hypothesis that copper enhances LOX activity in the sclera and increases the amount of LNL in the sclera (indicating scleral cross-linking), guinea pig pups (3–7 days old) were instilled with 0.08 mg / mL copper perchlorate hexahydrate twice daily for 6–8 weeks (n=5 each). After 6 weeks, sclera were dissected and analyzed for LNL content using a mass spectrometer (LC-MS). Semiquantitative mass spectrometry was performed using a Sciex 6500Q-Trap (Sciex, Framingham, MA, USA).

[0077] In guinea pig studies, treated sclera showed 6.9 × 10 -4 ug / mg LNL response was observed, compared with 3.9 × 10 -4 A LNL response of ug / mg was observed (Figure 2). Although the standard deviation is large due to baseline variability between guinea pigs, an increase in LNL was observed in treated eyes compared to untreated eyes in each of the n=5 guinea pigs. A paired samples T-test showed a statistically significant difference with a p-value of 0.036, indicating that copper perchlorate induces scleral cross-linking in vivo. EXAMPLES

[0078] Example 3 - Copper perchlorate increases the biomechanical stiffness of the sclera in treated guinea pig pups. To test the hypothesis that copper perchlorate enhances scleral LOX activity, leading to increased scleral cross-linking and scleral biomechanics, guinea pig pups (age 3-7 days) were instilled with 0.08 mg / mL copper perchlorate hexahydrate twice daily for 8 weeks (n=3 each). After 8 weeks, the sclera were peeled for creep compliance testing. Compliance was tested using an Instrong 5943 mechanical testing system equipped with custom grips and a 5 N Futek load cell. Six specimens were each loaded with a load of 0.005 kgf, corresponding to an equivalent pressure of 12.0-16.6 mmHg depending on specimen dimensions.

[0079] Experimental myopia studies in animals have shown that scleral tissue in myopic eyes has reduced mechanical stiffness and increased creep compliance compared to normal sclera. In contrast, copper perchlorate decreased creep compliance, i.e., increased scleral stiffness (Figure 3). Less compliance results in less elongation when pressure is applied (hence, the sclera is stiffer after copper perchlorate treatment). EXAMPLES

[0080] Example 4 - Copper perchlorate was well tolerated and slowed the progression of spontaneous myopia in guinea pig pups. Spontaneous myopic albino guinea pigs were used as a model of pediatric myopia. Spontaneous myopia is of great potential interest because this type of myopia closely resembles myopia in humans. Albino guinea pig pups were used as a pediatric model from 4-7 days of age. In this group of n=5 pups, all left eyes were untreated (internal control). The other eye (right eye) was treated with 0.22 mg / mL copper perchlorate hexahydrate twice daily. Treatment began approximately 1 week after birth and continued for approximately 2 months. Measurements were performed between 5 and 7 days after birth (baseline, untreated) and every other week thereafter. Refractive error was measured by streak retinoscopy after pupil dilation, and axial length was measured by Lenstar biometry (Haag-Streit). Cycloplegic refractive error and corneal inflammation were also measured by an anonymous pediatric ophthalmologist. Preliminary clinical observations showed no toxicity or discoloration in the rabbit corneas during the study period. Copper perchlorate slowed the progression of myopic refractive error by 48% within 9 weeks of treatment (Figure 4). A trend toward decreased axial length and vitreous chamber depth was observed in treated eyes (OD) compared to control eyes (OS) (Figure 5). EXAMPLES

[0081] Example 5 - Copper perchlorate inhibits axial elongation, vitreous chamber elongation, and myopia in a genetic model of myopia in guinea pigs. Copper perchlorate was administered to guinea pigs at 0.35 mg / ml. The results (Figure 6) showed that copper perchlorate treatment (eye drops administered twice daily) significantly reduced axial elongation and vitreous chamber depth elongation in treated eyes compared to control eyes. At the end of the experiment, copper perchlorate-treated eyes had significantly reduced myopia compared to control eyes. Days with significant differences between treated and control eyes are marked with an * in Figure 6. EXAMPLES

[0082] Example 6 - Low concentrations of copper perchlorate administered once daily reduce myopia in a genetic model of myopia in guinea pigs. Copper perchlorate, 0.22 mg / ml, was administered once daily for approximately 3 months to the right eye only. Cycloplegic refraction was measured biweekly by an anonymous pediatric ophthalmologist. The results (Figure 7) show that the slope analysis (left-to-right difference, pairwise difference within animals) showed that the refractive error decreased by 0.027 (sd=0.011) more per day in the left eye than in the right eye (i.e., the difference between eyes has a negative slope), with a p-value of 0.0189. The left-right change from baseline to day 81 was 2.27 units lower from baseline, i.e., the left eye decreased on average by -2.27 relative to the right eye, indicating that over the 81 days of treatment, the untreated left eye progressed 2.27 diopters more myopia than the treated right eye. EXAMPLES

[0083] Example 7 - Copper perchlorate increases lysyl oxidase activity in scleral fibroblasts. Copper perchlorate increased LOX activity in scleral cells. Copper perchlorate was found to dramatically increase LOX enzyme activity in a dose-response manner at specific concentrations comparable to the effective levels of topical eye drops (Figure 8).

[0084] Incorporation by Reference All publications and patents mentioned herein are herein incorporated by reference in their entirety as if each individual publication or patent was specifically and individually indicated to be incorporated by reference. In case of conflict, the present application, including definitions herein, will control.

[0085] Equivalent While specific embodiments of the subject invention have been described, the above specification is illustrative and not restrictive. Many variations of the invention will become apparent to those skilled in the art upon review of this specification and the claims that follow. The full scope of the invention, along with such variations, along with its full scope of equivalents, should be determined by reference to the claims and the specification.

Claims

1. A composition comprising a copper-containing agent selected from copper perchlorate, copper perbromate, copper periodate, and copper permanganate, for use in treating myopia in the eye of a subject in need thereof.

2. Use of an agent selected from copper perchlorate, copper perbromate, copper periodate, and copper permanganate in the preparation of a composition for the treatment of myopia in the eye of a subject in need thereof.

3. 3. The composition of claim 1 or 2, wherein the copper-containing agent is copper perchlorate.

4. 3. The composition of claim 1, wherein the composition comprises from about 0.001% to about 0.1% by weight of the copper-containing agent.

5. 3. The composition of claim 1, wherein the composition comprises from about 0.01 mg / mL to about 1.0 mg / mL of the copper-containing agent.

6. 3. The composition of claim 1, further comprising an excipient selected from a tonicity agent, a solubilizer, a viscosity agent, a polymer, a buffer, a pH adjuster, a preservative, and water.

7. 3. The composition of claim 1, wherein the composition does not contain any additional active ingredients.

8. 3. The composition of claim 1, wherein the composition has a tonicity of about 200 mOsm / kg to about 600 mOsm / kg.

9. 3. The composition of claim 1, wherein the composition has a pH of about 5.0 to about 7.

8.

10. 3. The composition of claim 1 or 2, wherein the composition is formulated for topical delivery.

11. 3. The composition of claim 1 or 2, wherein the composition is an ointment, gel, thin film, or eye drop composition.

12. The composition of claim 11, wherein the composition is adjusted for delivery to the sclera.

13. The composition of claim 12, wherein the composition is further adjusted for delivery to the cornea.

14. 3. The composition of claim 1 or 2, wherein the composition is a sustained delivery or depot matrix.

15. 15. The composition of claim 14, wherein the composition is prepared for placement in the cul-de-sac, conjunctiva, subconjunctival, Tenon's capsule, or sub-Tenon's space, or is placed periorbitally.

16. 3. The composition of claim 1, wherein the composition is prepared for delivery by air-gun delivery or ballistic air delivery.

17. 3. The composition of claim 1 or 2, wherein the composition is prepared for administration at least once a week to each eye in need thereof.

18. 3. The composition of claim 1, wherein the composition is formulated for administration at least once daily to each eye in need thereof.

19. 3. The composition of claim 1, wherein the composition is prepared for administration to each eye in need thereof from 1 to 4 times daily.

20. 3. The composition of claim 1, wherein the myopia is progressive myopia.

21. 3. The composition of claim 1, wherein the myopia is non-progressive myopia.

22. 3. The composition of claim 1 or 2, wherein the subject is a human at least about 3 years of age, or a human between about 3 and about 25 years of age, or a human at least about 25 years of age.

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