Administration of keratolytics to ocular and periocular surfaces

Abstract

Provided herein are methods for treating conditions in or around the eye with a pharmaceutical composition comprising a keratolytic agent by spreading the pharmaceutical composition prior to administering the pharmaceutical composition to an ocular or periocular surface (e.g., eyelid) of an individual in need thereof.

Description

ADMINISTRATION OF KERATOLYTICS TO OCULAR AND PERIOCULARSURFACESCROSS REFERENCE

[0001] The present application claims the benefit of U. S. Provisional Application No. 63 / 525,551, filed July 7, 2023, which is entirely incorporated herein by reference.BACKGROUND OF THE INVENTION

[0002] Selenium sulfide (SeS2) is indicated for the treatment of dermatological condition such as seborrheic dermatitis, tinea versicolor and dandruff. It is typically used as shampoo, foam or lotion at commercially available concentrations of 1% and 2.5% and is applied for several minutes, then rinsed off. The use of SeS2 can be associated with known side effects that are listed in the drug insert and which may include irritation, burning, and on rare occasion, loss and discoloration of hair. Contact of a significant amount of preparations containing high-concentration SeS2 with mucous membranes of the eye may cause irritation (e.g., stinging) and prolonged contact (e.g., overnight application) of preparations containing SeS2 with the skin may cause local irritation.

[0003] Adverse events reported following topical ocular use of SeS2 containing products include: superficial punctate keratitis, punctate keratitis, eye irritation, eye pain, eye inflammation, and (increased) lacrimation. Adverse reactions reported for administration site conditions include: instillation / application site pain and application site irritation. The adverse events can resolve upon cessation of treatment. When SeS2 is applied topically for the treatment of tinea versicolor, skin irritation may occur in the genital areas and / or folds of the skin. SeS2 lotions can also cause rebound oiliness of the scalp. AHFS Drug Information 2010.

[0004] In the 1950s and early 1960s, several investigators attempted to use ophthalmic preparation of SeS2 to treat seborrheic blepharitis, typically associated with scaling at the eyelid margin and which affects many of those patients suffering from seborrheic dermatitis. These clinicians treated hundreds of patients over a course of time ranging between 1 month and 1 year using different methods including in-office application, home application, daily application, or application on alternating days. Mixed results were observed in these various studies.

[0005] Different means of application were described by the investigators including from careful application in the office with rinsing of excess material as well as at-home application with complete rinsing after a short period. It was clearly stated that careful application and rinsing were important to avoid harmful effects. It was further understood that patients who developed severe reactions were improperly applying the treatment to the eye or failed to observe thorough rinsing procedures.

[0006] Lavyel 1960, described the use of Selsunef® ointment, a 0.5% SeS2 ointment produced by Abbott. Selsunef® was used in the clinic in 80 subjects, where gentle and controlled application was performed by a physician who also removed the ointment after 30 min by a swab of cotton wool. Great care was always taken not to introduce any of the ointment into the conjunctival sac. In one case, where the patient administered Selsunef® to himself, contrary to medical advice, a rather severe keratitis promptly developed.SUMMARY OF THE INVENTION

[0007] In certain instances, administration of a SeS2 to an ocular or periocular surface can lead to undesirable results, including poor efficacy and / or poor tolerability, such as leading to discontinued use. In some instances, high concentrations and / or high volume of a selenium sulfide leads to poor tolerability in some individuals when administered to an ocular or periocular surface. Further, in certain instances, inadequate delivery and / or poor distribution of a SeS2 to a target location on an ocular and / or periocular surface leads to poor efficacy and / or poor tolerability. In specific instances, for example, uneven or misapplied administration of a SeS2 (or composition comprising a SeS2) leads to a large droplet or globule of a pharmaceutical composition comprising a SeS2 to a highly discrete area, such as within the target area, or even outside of the target area. For example, in some instances, application of a pharmaceutical composition (e.g., ointment comprising a SeS2) to a finger or other administration surface and subsequent administration to an ocular or periocular location leads to a globule of the ointment being applied to the eyelid, which may then sit in a single location, or may even migrate to an undesired location, such as the lower fornix of the eye associated with the ocular or periocular surface to which the pharmaceutical composition was administered. In other instances, the globule can be placed by error directly on the cornea or directly into the lower fornix, or directly onto the conjunctiva.

[0008] Provided in certain embodiment herein is a method for treating a disease or disorder in or around the eye in an individual in need thereof. In some embodiments, a method provided herein comprises providing a pharmaceutical composition comprising about 0.1 wt. % to about 10 wt. % (e.g., about 0.5 wt. % to about 5 wt. %) of selenium disulfide. In some embodiments, a method provided herein comprises administering about 2 pL or less (e.g., about 0.2 pL to about 2 pL) of the pharmaceutical composition to an eyelid of the individual. In certain instances, administration of 2 pL or less of the composition provides good therapeutic efficacy with good tolerability. In certain instances, administration of higher amounts of the composition may lead to lower tolerability, such as because of eye or skin irritation. In some instances, good tolerability leads to improved patient compliance and further improved therapeutic efficacy over time. In some embodiments, any suitable method is used to administer the composition in the amount describedherein. For example, in some embodiments, about 5 pL or less of a composition described herein is dispensed onto a finger of the individual being treated and then about 2 pL or less (e.g., about 0.2 pL to about 2 pL) of the composition is administered to the eyelid (e.g., eyelid margin) of the individual. In other embodiments, about 2 pL or less (e.g., about 0.2 pL to about 2 pL) of the composition is administered directly to the eyelid (e.g., eyelid margin) of the individual, such as from a device configured for direct administration of a composition to the eyelid (e.g., eyelid margin) of the individual.

[0009] Provided in certain embodiment herein is a method for treating a disease or disorder in or around the eye in an individual in need thereof. In some embodiments, a method provided herein comprises providing a pharmaceutical composition comprising about 0.5 wt. % to about 5 wt. % of selenium disulfide. In some embodiments, a method provided herein comprises administering about 0.2 pL to about 2 pL of the pharmaceutical composition to an eyelid of the individual.

[0010] Provided in certain embodiment herein is a method for treating a disease or disorder in or around the eye in an individual in need thereof. In some embodiments, a method provided herein comprises providing a pharmaceutical composition comprising about 0.1 wt. % to about 10 wt. % (e.g., about 0.5 wt. % to about 5 wt. %) of selenium disulfide. In some embodiments, a method provided herein comprises administering about 2 mg or less (e.g., about 1.6 mg or less) of the pharmaceutical composition to an eyelid of the individual. In certain instances, administration of 2 mg or less (e.g., about 1.6 mg or less) of the composition provides good therapeutic efficacy with good tolerability. In certain instances, administration of higher amounts of the composition may lead to lower tolerability, such as because of eye or skin irritation. In some instances, good tolerability leads to improved patient compliance and further improved therapeutic efficacy over time. In some embodiments, any suitable method is used to administer the composition in the amount described herein. For example, in some embodiments, about 5 pL or less of a composition described herein is dispensed onto a finger of the individual being treated and then about 2 mg or less (e.g., about 1.6 mg or less) of the composition is administered to the eyelid (e.g., eyelid margin) of the individual. In other embodiments, about 2 mg or less (e.g., about 1.6 mg or less) of the composition is administered directly to the eyelid (e.g., eyelid margin) of the individual, such as from a device configured for direct administration of a composition to the eyelid (e.g., eyelid margin) of the individual.

[0011] Provided in certain embodiment herein is a method for treating a disease or disorder in or around the eye in an individual in need thereof. In some embodiments, a method provided herein comprises providing a pharmaceutical composition comprising about 0.5 wt. % to about 5 wt. % of selenium disulfide. In some embodiments, a method provided herein comprises administering about 0.2 mg to about 1.6 mg of the pharmaceutical composition to an eyelid of the individual.

[0012] In some embodiments, a method provided herein comprises dispensing the pharmaceutical composition from a dispensing device.

[0013] In some embodiments, a method provided herein comprises applying the pharmaceutical composition onto a finger of the individual.

[0014] In some embodiments, a method provided herein comprises spreading the pharmaceutical composition over at least a portion of a surface of the finger (e.g., forming a thin film).

[0015] In some embodiments, a pharmaceutical composition provided herein is administered to the eyelid using the finger.

[0016] Provided in certain embodiment herein is a method for treating a disease or disorder in or around the eye in an individual in need thereof. In some embodiments, a method provided here comprises dispensing a pharmaceutical composition provided herein from a dispensing device. In some embodiments, the pharmaceutical composition comprises an effective amount of a keratolytic agent (e.g., selenium disulfide (SeS2)). In some embodiments, a method provided here comprises applying the pharmaceutical composition onto a finger of the individual. In some embodiments, a method provided here comprises spreading the pharmaceutical composition over at least a portion of a surface of the finger (e.g., forming a thin film). In some embodiments, a method provided here comprises using the finger, administering the pharmaceutical composition to an eyelid of the individual.

[0017] Provided in certain embodiment herein is a method for treating a disease or disorder in or around an eye in an individual (e.g., in need thereof). In some embodiments, the method comprises dispensing a pharmaceutical composition, such from a device described herein. In some embodiments, the method comprises dispensing a pharmaceutical composition comprising a keratolytic agent (e.g., SeS2). In specific embodiments, the pharmaceutical composition is dispensed (or applied following being dispensed) onto any suitable object (e.g., finger or piece of paper, or the back of the palm) or surface (e.g., finger surface, paper surface, back of the palm surface). To avoid placing a globule or lump of the pharmaceutical agent onto the ocular surface or the fornix, there is a need to first thin the pharmaceutical agent onto the applying finger surface. In some embodiments, the pharmaceutical composition is spread (e.g., by pressing or rubbing the pharmaceutical composition with a second finger) or softened (e.g., by heating the composition, such as with body heat or with the device used to extract the drug out or with a dedicated device). In some embodiments, the pharmaceutical composition is thinned by spreading or softening to create a thin layer of the pharmaceutical composition. In specific embodiments, spreading or softening of the pharmaceutical composition results in the pharmaceutical composition being spread over a surface of a finger (e.g., over at least a portion of the surface of the finger), such as the finger to which the pharmaceutical composition was applied. In some embodiments, followingadministration of the pharmaceutical composition to the finger (e.g., and following thinning, spreading, or softening the pharmaceutical composition on the finger), the pharmaceutical composition is administered to an ocular or periocular surface (e.g., eyelid) of the individual. In some embodiments, following administration of the pharmaceutical composition to the finger (e.g., and following thinning, spreading, or softening the pharmaceutical composition on the finger), the pharmaceutical composition is administered to an ocular or periocular surface (e.g., eyelid) of the individual and rubbed on the ocular or periocular surface (e.g., eyelid) of the individual multiple times (e.g., to ensure complete coverage).

[0018] Provided in some embodiments herein is a method for treating a disease or disorder in or around the eye in an individual in need thereof, the method comprising: dispensing a pharmaceutical composition from a dispensing device, the pharmaceutical composition comprising an effective amount of a keratolytic agent (e.g., selenium disulfide (SeS2)); applying the pharmaceutical composition onto a finger of the individual; spreading the pharmaceutical composition over at least a portion of a surface of the finger (e.g., forming a thin film); and using the finger, administering the pharmaceutical composition to an eyelid of the individual.

[0019] In some instances, larger volumes of keratolytic agents on the eye increase the likelihood of adverse events. In some instances, use of small volume (e.g., <25 pL) of keratolytic agents can reduce the likelihood of adverse event.

[0020] In some embodiments, application of a pharmaceutical composition (e.g., comprising a keratolytic agent) described herein according to a method provided herein reduces the likelihood of adverse event upon administration. In some embodiments, small volumes (e.g., <25 pL) of a pharmaceutical composition described herein are dispensed or administered according to a method provided herein. In other embodiments, larger volumes (e.g., >500 pL) of a pharmaceutical composition described herein are dispensed and can be used with a method provide herein, which will not increase the likelihood of adverse event (e.g., relative to other methods, such as those not involving spreading, thinning, and / or softening of the composition prior to periocular administration). In some instances, such as following an initial application of a large or small volume of the pharmaceutical composition over the finger, the pharmaceutical composition is rubbed (e.g., between at least two fingers multiple times) and thinned on the tip of the finger, such as using an index or middle finger and a thumb of the individual described herein. In some instances, the thickness of the pharmaceutical composition at the tip of the finger after rubbing and thinning is the same regardless of the initial amount or volume of the pharmaceutical composition dispensed on the finger. In some instances, only a small and safe amount or volume of the pharmaceutical composition is delivered onto the lid margin.

[0021] Provided in certain embodiment herein is a method for treating a disease or disorder in or around an eye in an individual (e.g., in need thereof). In some embodiments, a method provided herein comprises dispensing an amount of a pharmaceutical composition (e.g., provided herein) from a dispensing device. In some embodiments, a method provided herein comprises dispensing a predetermined amount of a pharmaceutical composition (e.g., provided herein) from a dispensing device. In some embodiments, the predetermined amount is about 100 microliters (pL) or less. In specific embodiments, the predetermined amount is about 1 pL to about 50 pL. In specific embodiments, the predetermined amount is about 2 pL to about 25 pL. In specific embodiments, the predetermined amount is about 2.5 pL to about 20 pL. In some embodiments, the predetermined amount is any volume described herein as being administered or dispensed. In some embodiments, the method comprises using a dispensing device to determine a proper amount (e.g., about 25 microliters (pL) or less) of a pharmaceutical composition comprising a keratolytic agent (e.g., SeS2) to dispense. In some embodiments, the dispensing device comprises a snap-on visual guide configured to provide a visual cue for the appropriate length of the pharmaceutical composition to dispense. In some embodiments, the dispensing device comprises dosing aid comprising a syringe device configured to provide a precise volume of the pharmaceutical composition to dispense.

[0022] In some embodiments, the method comprises dispensing a pharmaceutical composition comprising a keratolytic agent (e.g., SeS2). In specific embodiments, a pharmaceutical composition is dispensed until it reaches a virtual line of a visual guide (e.g., of a guide or snap- on visual guide provided herein). In some embodiments, a pharmaceutical composition is dispensed from an outlet of a barrel chamber of a syringe device by exerting force on a plunger of the syringe device. In some embodiments, a pharmaceutical composition is dispensed as a ribbon. In certain embodiments, the pharmaceutical composition is dispensed (or applied following being dispensed) onto any clean suitable object or surface (e.g., index finger).

[0023] In some embodiments, a pharmaceutical composition is thinned on the suitable surface by spreading as described herein (e.g., by rubbing the pharmaceutical composition on the washed index finger with a thumb) or by softening (e.g., by heating the composition, such as with the body heat of the index finger and thumb or with a device used to extract the drug out or with a dedicated device). In specific embodiments, spreading or softening of the pharmaceutical composition results in a thin layer of the pharmaceutical composition being spread over a surface of the finger (e.g., over at least a portion of the surface of the finger), such as the finger to which the pharmaceutical composition was applied. In some embodiments, following dispensing and applying a pharmaceutical composition onto a finger (e.g., and following spreading or softeningthe pharmaceutical composition on the finger), the pharmaceutical composition is administered to an ocular or periocular surface (e.g., eyelid) of an individual in need thereof.

[0024] In some embodiments, a method comprises pulling an eyelid away from an eye. In some embodiments, a method comprises administering a pharmaceutical composition over one eyelid margin of the affected eye. In some instances, administering a pharmaceutical composition comprises going over (e.g., rubbing the pharmaceutical composition to) the eyelid margin (e.g., with the surface of the finger where the ointment was spread) a few times to ensure complete coverage. In some embodiments, the individual blinks several times to transfer a portion of the keratolytic agent (e.g., selenium sulfide) from one eyelid to the other eyelid of the same affected eye.

[0025] In some embodiments, a method comprises administering a pharmaceutical composition to an affected eye twice a week at bedtime. In some embodiments, a method comprises administering a pharmaceutical composition to an affected eye twice a week before bedtime. In some embodiments, a method comprises administering a pharmaceutical composition to a lower eyelid margin of the affected eye twice a week at bedtime. In some embodiments, a method comprises administering a pharmaceutical composition to a lower eyelid margin of the affected eye twice a week before bedtime. In some embodiments, a method comprises administering a pharmaceutical composition to the affected eye with at least 1 day between instillations. In some embodiments, a method comprises not administering a pharmaceutical composition to the affected eye more than once daily before bedtime.

[0026] In some embodiments, when an individual wears contact lenses, a method comprises removing the contact lenses prior to administering a composition. In some embodiments, an individual does not remove the contact lenses prior to administering a composition. In some embodiments, when an individual wears contact lenses, a method comprises reinserting the contact lenses after administering a composition. In some embodiments, the individual reinserted the contact lenses 15 minutes after administering a composition.

[0027] Provided in some embodiments herein is a method for treating a disease or disorder in or around the eye in an individual in need thereof, the method comprising: dispensing a pharmaceutical composition comprising an effective amount of a keratolytic agent (e.g., selenium disulfide (SeS2)); applying the pharmaceutical composition onto a finger of the individual; spreading the pharmaceutical composition over at least a portion of a surface of the finger (e.g., forming a thin film); and using the finger, administering the pharmaceutical composition to an eyelid of the individual.

[0028] Provided in some embodiments herein is a method for treating a disease or disorder in or around the eye in an individual in need thereof, the method comprising: dispensing apharmaceutical composition comprising an effective amount of a keratolytic agent (e.g., selenium disulfide (SeS2)); applying the pharmaceutical composition onto a finger (e.g., fingertip) of the individual; thinning the pharmaceutical composition over at least a portion of a surface of the finger (e.g., forming a thin film); and using the finger (e.g., fingertip), administering the pharmaceutical composition to an eyelid of the individual.

[0029] In some embodiments, the pharmaceutical composition is a semi-solid, wherein the semisolid is an ointment, a gel, a cream, or a paste.

[0030] In some embodiments, the pharmaceutical composition is an ointment.

[0031] In some embodiments, the pharmaceutical composition comprises an oleaginous base.

[0032] In some embodiments, the pharmaceutical composition comprises an anhydrous base.

[0033] In some embodiments, the pharmaceutical composition comprises a petrolatum.

[0034] In some embodiments, the pharmaceutical composition is dispensed in a predetermined amount from the dispensing device.

[0035] In some embodiments, the pharmaceutical composition is dispensed onto the finger (e.g., fingertip) using a dispensing device.

[0036] In some embodiments, the pharmaceutical composition is dispensed and applied onto the finger (e.g., fingertip) as a strip.

[0037] In some embodiments, the pharmaceutical composition is applied onto the finger (e.g., fingertip) as a globule or droplet.

[0038] In some embodiments, the pharmaceutical composition is spread by increasing the surface area of the (e.g., globule or droplet) pharmaceutical composition on the finger (e.g., fingertip).

[0039] In some embodiments, the pharmaceutical composition is spread by decreasing the thickness of the (e.g., globule or droplet) pharmaceutical composition on the finger (e.g., fingertip).

[0040] In some embodiments, the pharmaceutical composition is spread over the finger (e.g., fingertip) using a device (e.g., lip balm, eye liner).

[0041] In some embodiments, the pharmaceutical composition is spread between two fingers (e.g., fingertips), such as a forefinger and a thumb of the individual.

[0042] In some embodiments, the pharmaceutical composition is administered to an eyelid of the individual.

[0043] In some embodiments, the pharmaceutical composition is administered to an upper eyelid of the individual.

[0044] In some embodiments, the pharmaceutical composition is administered to a lower eyelid of the individual.

[0045] In some embodiments, the pharmaceutical composition is administered to both upper and lower eyelid of the individual.

[0046] In some embodiments, the pharmaceutical composition is administered to an eyelid of the individual in a manner suitable to deliver the keratolytic agent to an eyelid margin of the individual.

[0047] In some embodiments, the pharmaceutical composition is administered to an eyelid margin of the individual.

[0048] In some embodiments, the pharmaceutical composition is administered to a lower eyelid margin of the individual.

[0049] In some embodiments, the pharmaceutical composition is administered to an upper eyelid margin of the individual.

[0050] In some embodiments, the individual self-administers the pharmaceutical composition.

[0051] In some embodiments, spreading the pharmaceutical composition comprises evenly spreading the pharmaceutical composition on the finger (e.g., fingertip), such as to create a thin film of the pharmaceutical composition.

[0052] In some embodiments, spreading the pharmaceutical composition comprises rubbing the pharmaceutical composition between two fingers (e.g., fingertips) before administering the pharmaceutical composition to the periocular surface (e.g., to create a thin film of the pharmaceutical composition).

[0053] In some embodiments, the individual rubs the pharmaceutical composition between two fingers (e.g., a forefinger or middle finger (fingertip) and a thumb) before administering the pharmaceutical composition to the periocular surface.

[0054] In some embodiments, the individual administers the pharmaceutical composition with a finger (e.g., a forefinger or middle finger (fingertip) and a thumb).

[0055] In some embodiments, the individual pulls a lower eyelid away from an eye (e.g., eye with disease or disorder) prior to administering the pharmaceutical composition over the lower eyelid margin of the eye.

[0056] In some embodiments, the individual pulls an upper eyelid away from an eye (e.g., eye with disease or disorder) prior to administering the pharmaceutical composition over the upper eyelid margin of the eye.

[0057] In some embodiments, the individual pulls both upper and lower eyelid away from an eye (e.g., eye with disease or disorder) prior to administering the pharmaceutical composition over both upper and lower eyelid margins of the eye.

[0058] In some embodiments, the individual administers the pharmaceutical composition by going over (e.g., rubbing) the lower eyelid margin (e.g., with the surface of the finger (e.g., fingertip) where the ointment was spread) a few times (e.g., to ensure complete coverage).

[0059] In some embodiments, the individual administers the pharmaceutical composition by going over (e.g., rubbing) the upper eyelid margin (e.g., with the surface of the finger (e.g., fingertip) where the ointment was spread) a few times (e.g., to ensure complete coverage).

[0060] In some embodiments, the individual administers the pharmaceutical composition by going over (e.g., rubbing) both lower and upper eyelid margins (e.g., with the surface of the finger (e.g., fingertip) where the ointment was spread) a few times (e.g., to ensure complete coverage).

[0061] In some embodiments, the individual repeats dispensing, spreading, applying, and administering the pharmaceutical composition to the other eye.

[0062] In some embodiments, the individual wears contact lenses.

[0063] In some embodiments, the contact lenses are removed prior to administering the pharmaceutical composition.

[0064] In some embodiments, the contact lenses are not removed prior to administering the pharmaceutical composition.

[0065] In some embodiments, the contact lenses are reinserted after administering the pharmaceutical composition.

[0066] In some embodiments, the pharmaceutical composition is administered at home.

[0067] In some embodiments, the disease or disorder in or around the eye is meibomian gland dysfunction (MGD), blepharitis, seborrheic blepharitis, Demodex infestation, dry eye disease (DED), dry eye syndrome, hyperkeratosis, dermatitis, keratitis, contact lens discomfort, lid wiper epitheliopathy (LWE), Keratoconjunctivitis Sicca, Sjogren's Syndrome, ocular rosacea, conjunctival ulcerations, sloughing of surface epithelium at the lid margin, conjunctival scarring / deficiency, or keratinization over the lid wiper zone and / or conjunctiva.

[0068] In some embodiments, the disease or disorder in or around the eye is Blepharitis or Seborrheic Blepharitis.

[0069] In some embodiments, the disease or disorder in or around the eye is meibomian gland dysfunction (MGD).

[0070] In some embodiments, the disease or disorder in or around the eye is dry eye syndrome.

[0071] In some embodiments, the disease or disorder in or around the eye is dry eye disease.

[0072] In some embodiments, the disease or disorder in or around the eye is keratitis or hyperkeratosis.

[0073] In some embodiments, the disease or disorder in or around the eye is contact lens discomfort.

[0074] In some embodiments, the disease or disorder in or around the eye is LWE.

[0075] In some embodiments, the keratolytic agent is selected from the group consisting of benzoyl peroxide, coal tar, dithranol, salicylic acid, selenium disulfide, alpha-hydroxy acid, urea, lactic acid, boric acid, retinoic acid, sodium thioglycolate, allantoin, zinc pyrithione, zinc L- pyrrolidone carboxylate, seleocysteine, selenomethionine, captopril, zofenopril, tiopronin, penicillamine, L-cysteine, N-acetyl cysteine (NAC), gluthatione, dithiothreitol, thiorphan, cysteamine, bucillamine, dimercaprol, 1,1 -ethanedi thiol, dimercaptosuccinic acid, furan-2- ylmethanethiol, omapatrilat, ovothiol A, rentiapril, thiosalicylic acid, tixocortol, mycothiol, coenzyme A, coenzyme B, disulfiram, psammaplin A, dixanthogen, pantethine, fursultiamine, octotiamine, sulbutiamine, prosultiamine, thiram, lipoic acid, lenthionine, ajoene, allicin, gemopatrilat, thioethanol, thiophospholipid, thiocholesterol, 12-mercaptododecanoic acid, 23-(9- mercaptononyl)-3,6,9,12,15,18,21-heptaoxatricosanoic acid, and sulfanegen.

[0076] In some embodiments, the keratolytic agent is selected from the group consisting of benzoyl peroxide, coal tar, dithranol, salicylic acid, selenium disulfide, N-acetyl cysteine (NAC), bucillamine, captopril, alpha-hydroxy acid, urea, lactic acid, sodium thioglycolate, zinc pyrithione, or zinc L-pyrrolidone carboxylate.

[0077] In some embodiments, the keratolytic agent is selenium disulfide.

[0078] In some embodiments, the pharmaceutical composition comprises the keratolytic agent in a therapeutically effective concentration.

[0079] In some embodiments, the therapeutically effective concentration of the keratolytic agent is greater than or equal to about 0.1% by weight (wt. %).

[0080] In some embodiments, the therapeutically effective concentration of the keratolytic agent is about 0.1 wt. % to about 10 wt. %.

[0081] In some embodiments, the therapeutically effective concentration of the keratolytic agent is about 0.1 wt. % to about 2 wt. %.

[0082] In some embodiments, the therapeutically effective concentration of the keratolytic agent is about 0.5 wt. % to about 5 wt. %.

[0083] In some embodiments, the therapeutically effective concentration of the keratolytic agent is about 0.5 wt. % to about 2 wt. %.

[0084] In some embodiments, the therapeutically effective concentration of the keratolytic agent is about 0.5 wt. % to about 1 wt. %.

[0085] In some embodiments, the therapeutically effective concentration of the keratolytic agent is less than or equal to about 1 wt. %.

[0086] In some embodiments, the therapeutically effective concentration of the keratolytic agent is about 1 wt. %.

[0087] In some embodiments, the therapeutically effective concentration of the keratolytic agent is about 0.5 wt. %.

[0088] In some embodiments, the volume of the pharmaceutical composition dispensed onto the finger (e.g., fingertip) is 25 pL or less.

[0089] In some embodiments, the volume of the pharmaceutical composition dispensed onto the finger (e.g., fingertip) is 500 pL or less.

[0090] In some embodiments, the volume of the pharmaceutical composition dispensed onto the finger (e.g., fingertip) is 100 pL or less.

[0091] In some embodiments, the predetermined amount is 25 pL or less.

[0092] In some embodiments, the predetermined amount is 500 pL or less.

[0093] In some embodiments, predetermined amount is 100 pL or less.

[0094] In some embodiments, the administered amount of the pharmaceutical composition is about 2 pL or less.

[0095] In some embodiments, the administered amount of the pharmaceutical composition is about 0.2 pL to about 2 pL.

[0096] In some embodiments, the administered amount of the pharmaceutical composition is about 1 pL to about 2 pL.

[0097] In some embodiments, the administered amount of the pharmaceutical composition is about 2 mg or less.

[0098] In some embodiments, the administered amount of the pharmaceutical composition is about 0.2 mg to about 2 mg.

[0099] In some embodiments, the administered amount of the pharmaceutical composition is about 0.2 mg to about 1.6 mg.

[0100] In some embodiments, the administered amount of the pharmaceutical composition is about 0.5 mg to about 1.5 mg.

[0101] In some embodiments, the method significantly improves compliance of the pharmaceutical composition.

[0102] In some embodiments, the method significantly reduces adverse events (e.g., application site pain (e.g., burning and / or stinging), keratitis (e.g., superficial punctate keratitis), eye pain, or the like, and / or as indicated by corneal staining or conjunctival staining) and / or the severity thereof.

[0103] In some embodiments, the method eliminates adverse events.

[0104] In some embodiments, a (significant) improvement in opening meibomian glands of the individual is observed after providing the keratolytic agent (e.g., selenium sulfide) to or around the eye of the individual.

[0105] In some embodiments, the method eliminates the need for a specific measured dose of administration onto the finger (e.g., fingertip).

[0106] In some embodiments, a (significant) improvement in meibum quality and / or quantity of the individual is observed after providing the keratolytic agent (e.g., selenium sulfide) to or around the eye of the individual.

[0107] In some embodiments, a (significant) improvement in opening meibomian glands, meibum quality, and / or meibum quantity of the individual is observed within about 5 months or less (e.g., 3 months or less or 1.5 months or less) after providing the keratolytic agent (e.g., selenium sulfide) to or around the eye of the individual.

[0108] In some embodiments, the individual has an improvement in lipid secretion.

[0109] In some embodiments, the any one or more of the following improves in the individual: meibomian glands yielding liquid secretion score (MGYLS), total ocular surface disease index (OSDI) score, standard patient evaluation of eye dryness (SPEED), meibomian gland score (MGS), and tear breakup time (TBUT).

[0110] In some embodiments, a symptom or symptom score improves after spreading and administering the pharmaceutical composition.[OHl] In some embodiments, a symptom score is determined by a (average) visual analogue scale (VAS) (e.g., pain VAS, photophobia VAS, burning / stinging VAS, itching VAS, foreign body VAS, or eye discomfort VAS), SPEED, contact lens dry eye questionnaire-8 (CLDQ8), or any sub scales of any such symptom questionnaire.

[0112] In some embodiments, the symptom (being evaluated) is eye dryness, pain, photophobia, burning, stinging, itching, grittiness (e.g., feeling like a foreign body is in the eye), or eye discomfort.

[0113] In some embodiments, the keratolytic agent (e.g., selenium sulfide) is administered to the individual monthly, bi-weekly, or once-weekly.

[0114] In some embodiments, the keratolytic agent (e.g., selenium sulfide) is administered to the individual once-weekly.

[0115] In some embodiments, the keratolytic agent (e.g., selenium sulfide) is administered to the individual for at least one month (e.g., one month or more, two months or more, three months or more, five months or more, or six months or more).

[0116] In some embodiments, the keratolytic agent (e.g., selenium sulfide) is administered to the individual twice a week.

[0117] In some embodiments, the keratolytic agent (e.g., selenium sulfide) is administered to the individual twice a week at bedtime.

[0118] In some embodiments, the keratolytic agent (e.g., selenium sulfide) is administered to the individual twice a week before bedtime.

[0119] In some embodiments, the keratolytic agent (e.g., selenium sulfide) is administered to the individual in the evening before bedtime.

[0120] In some embodiments, the keratolytic agent (e.g., selenium sulfide) is administered to the individual with at least 1 day between instillations.

[0121] In some embodiments, the keratolytic agent (e.g., selenium sulfide) is not administered to the individual more than once daily before bedtime.

[0122] In some embodiments, the individual blinks several times to transfer a portion of the keratolytic agent (e.g., selenium sulfide) from the lower eyelid to the upper eyelid.

[0123] In some embodiments, the individual blinks several times to transfer a portion of the keratolytic agent (e.g., selenium sulfide) from the upper eyelid to the lower eyelid.

[0124] Provided herein, in some embodiments, is a system comprising a dispensing device (e.g., any dispensing device provided herein) and a pharmaceutical composition (e.g., any pharmaceutical composition provided herein). In some embodiments, the dispensing device is configured to dispense a predetermined amount of a pharmaceutical composition (e.g., any pharmaceutical composition provided herein). In some embodiments, the system is for use in treating a disease or disorder in or around the eye in an individual in need thereof. In some embodiments, the system is used for implementing any method provided herein.

[0125] In some embodiments, provided herein is the use of a composition (e.g., any composition provided herein) for implementing any method provided herein.

[0126] In some embodiments, a system provided herein comprises a dispensing device, and a pharmaceutical composition comprising an effective amount of a keratolytic agent (e.g., selenium disulfide (SeS2)). In some embodiments, the dispensing device is configured to dispense a predetermined amount of a pharmaceutical composition (e.g., any pharmaceutical composition provided herein). In some embodiments, the system is for treating a disease or a disorder (e.g., in or around the eye). In some embodiments, the system is for treating a disease or a disorder (e.g., in or around the eye) using any method provided herein. In some embodiments, the method comprises applying the pharmaceutical composition onto a finger of the individual. In some embodiments, the method comprises spreading the pharmaceutical composition over at least a portion of a surface of the finger (e.g., forming a thin film). In some embodiments, the method comprises using the finger, administering the pharmaceutical composition in or around the eye of the individual. In some embodiments, the method comprises using the finger, administering the pharmaceutical composition to an eyelid of the individual.BRIEF DESCRIPTION OF THE DRAWINGS

[0127] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also “Figure” and “FIG.” herein), of which:

[0128] FIG. 1 illustrates disease improved results in treating an ocular disorder (using sodium fluorescein corneal staining) in the same individual when spreading the pharmaceutical composition provided herein (see months 1.5 and 3) to create a thin layer of the pharmaceutical composition on the index finger versus when administering the same composition without first spreading the pharmaceutical composition (see day 14).

[0129] FIG. 2 illustrates substantially improved MGYLS scoring in the same individual when spreading the pharmaceutical composition provided herein (see months 1.5 and 3) to create a thin layer of the pharmaceutical composition on the index finger versus when administering the same composition without first spreading the pharmaceutical composition (see day 14).

[0130] FIG. 3 illustrates substantially improved MGS scoring in the same individual when spreading the pharmaceutical composition provided herein (see months 1.5 and 3) to create a thin layer of the pharmaceutical composition on the index finger versus when administering the same composition without first spreading the pharmaceutical composition (see day 14).

[0131] FIG. 4 illustrates substantial decrease in symptoms in the same individual when spreading the pharmaceutical composition provided herein (see months 1.5 and 3) to create a thin layer of the pharmaceutical composition on the index finger versus when administering the same composition without first spreading the pharmaceutical composition (see day 14).

[0132] FIG. 5 illustrates disease improved results in treating an ocular disorder (using sodium fluorescein corneal staining) in the same individual when spreading the pharmaceutical composition provided herein (see months 1.5 and 3) to create a thin layer of the pharmaceutical composition on the index finger versus when administering the same composition without first spreading the pharmaceutical composition (see day 14).

[0133] FIG. 6 illustrates substantially improved MGYLS scoring in the same individual when spreading the pharmaceutical composition provided herein (see months 1.5 and 3) to create a thin layer of the pharmaceutical composition on the index finger versus when administering the same composition without first spreading the pharmaceutical composition (see day 14).

[0134] FIG. 7 illustrates substantially improved MGS scoring in the same individual when spreading the pharmaceutical composition provided herein (see months 1.5 and 3) to create a thinlayer of the pharmaceutical composition on the index finger versus when administering the same composition without first spreading the pharmaceutical composition (see day 14).

[0135] FIG. 8 illustrates substantial decrease in symptoms in the same individual when spreading the pharmaceutical composition provided herein (see months 1.5 and 3) to create a thin layer of the pharmaceutical composition on the index finger versus when administering the same composition without first spreading the pharmaceutical composition (see day 14).DETAILED DESCRIPTION OF THE INVENTIONCertain Definitions

[0136] As used herein and in the appended claims, the singular forms "a," "and," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "an agent" includes a plurality of such agents, and reference to "the cell" includes reference to one or more cells (or to a plurality of cells) and equivalents thereof known to those skilled in the art, and so forth. When ranges are used herein for physical properties, such as molecular weight, or chemical properties, such as chemical formulae, all combinations and subcombinations of ranges and specific embodiments therein are intended to be included. The term "about" when referring to a number or a numerical range means that the number or numerical range referred to is an approximation within experimental variability (or within statistical experimental error), and thus the number or numerical range may vary between 1% and 15% of the stated number or numerical range.

[0137] As used herein, the term “comprise” or variations thereof such as “comprises” or “comprising” are to be read to indicate the inclusion of any recited feature but not the exclusion of any other features. Thus, as used herein, the term “comprising” is inclusive and does not exclude additional, unrecited features. Any disclosure of “comprising” provided herein is understood to separately include a disclosure of “consisting of’ and a disclosure of “consisting essentially of.” In some embodiments of any of the compositions and methods provided herein, “comprising” may be replaced with “consisting essentially of’ or “consisting of.” The phrase “consisting essentially of’ is used herein to require the specified feature(s) as well as those which do not materially affect the character or function of the claimed disclosure. As used herein, the term “consisting" is used to indicate the presence of the recited feature alone.

[0138] The terms “treat,” “treating,” or “treatment” as used herein, include reducing, alleviating, abating, ameliorating, managing, relieving, or lessening the symptoms associated with a disease, disease state, condition, or indication (e.g., provided herein) in either a chronic or acute therapeutic scenario. Also, treatment of a disease or disease state described herein includes the disclosure ofuse of such compound or composition for the treatment of such disease, disease state, disorder, or indication.

[0139] The terms “individual,” “patient,” or “subj ecf ’ are used interchangeably. None of the terms require or are limited to situation characterized by the supervision (e.g., constant or intermittent) of a health care worker (e.g., a doctor, a registered nurse, a nurse practitioner, a physician’s assistant, an orderly, or a hospice worker).

[0140] The term “keratolytic agent” as used herein refers to an agent that softens, disrupts, dissolves, solubilizes, or loosens a keratinized obstruction, or prevents the formation of a keratinized obstruction. In some instances, keratolytic agents are used to promote softening and dissolution of keratin.

[0141] Concentrations of agents provided herein are based on any suitable measurement, such as wt. %, w / w %, or w / v%. In specific instances, the concentration is wt. % (e.g., w / w % or w / v%).

[0142] The term “cream” describes an emulsion semisolid dosage form, usually containing >20% water and volatiles and / or <50% hydrocarbons, waxes or polyols as the vehicle. A cream is more viscous than a lotion. This dosage form is generally for external application to the skin (US FDA Drug Nomenclature Monograph, number C-DRG-00201).

[0143] The term “ointment” describes a semisolid dosage form, usually containing <20% water and volatiles and / or >50% hydrocarbons, waxes or polyols as the vehicle. This dosage form is generally for external application to the skin or mucous membranes (US FDA Drug Nomenclature Monograph, number C-DRG-00201).

[0144] The term, “meibomian gland dysfunction,” as used herein, refers to chronic, diffuse abnormality of the meibomian glands, that is characterized by terminal duct obstruction or qualitative or quantitative changes in the glandular secretion, or both. MGD may result in alteration of the tear film, eye irritation symptoms, inflammation, or ocular surface disease. The most prominent aspects of MGD are obstruction of the meibomian gland orifices and terminal ducts and changes in the meibomian gland secretions.

[0145] Provided in certain embodiment herein is a method for treating a disease or disorder in or around the eye in an individual (e.g., in need thereof). In some embodiments, the method comprises dispensing a pharmaceutical composition described herein, such as using a device described herein. In some embodiments, the method comprises dispensing a pharmaceutical composition comprising a keratolytic agent (e.g., SeS2). In specific embodiments, the pharmaceutical composition is dispensed (or applied following being dispensed) onto any suitable object (e.g., finger) or surface (e.g., finger surface). In some embodiments, the pharmaceutical composition is spread (e.g., by pressing or rubbing the pharmaceutical composition with a second finger) or softened (e.g., by heating the composition, such as with the body heat of the finger). Insome embodiments, the pharmaceutical composition is thinned by spreading or softening to create a thin layer of the pharmaceutical composition. In specific embodiments, spreading or softening of the pharmaceutical composition results in a thin layer of the pharmaceutical composition being spread over a surface of the finger (e.g., over at least a portion of the surface of the finger), such as the finger to which the pharmaceutical composition was applied. In specific embodiments, spreading or softening of the pharmaceutical composition described herein results in a thin layer of the pharmaceutical composition being spread over a fingertip (e.g., an index finger fingertip or a middle finger fingertip). In some embodiments, following administration of the pharmaceutical composition to the finger (e.g., and following spreading or softening the pharmaceutical composition on the finger), the pharmaceutical composition is administered to an ocular or periocular surface (e.g., eyelid) of the individual. In some embodiments, following administration of the pharmaceutical composition to the finger (e.g., and following thinning, spreading, or softening the pharmaceutical composition on the finger), the pharmaceutical composition is administered to an ocular or periocular surface (e.g., eyelid) of the individual and rubbed on the ocular or periocular surface (e.g., eyelid) of the individual multiple times (e.g., to ensure complete coverage).

[0146] Provided in certain embodiment herein is a method for treating a disease or disorder in or around an eye in an individual (e.g., in need thereof). In some embodiments, the method comprises using a dispensing device to determine a proper amount (e.g., about 25 microliters (pL) or less) of a pharmaceutical composition comprising a keratolytic agent (e.g., SeS2) being dispensed. In some embodiments, the dispensing device comprises a snap-on visual guide that comprises two front tips (e.g., connected by a virtual line that is provided as a visual cue for the appropriate length of product to dispense). In some embodiments, the dispensing device comprises a dosing aid (e.g., a syringe device).

[0147] Provided in certain embodiment herein is a method of a disease or disorder in or around an eye comprising administering any agent describe in any of U.S. Patent Number 11,643,429, U.S. Patent Application Number 18 / 117,759, U.S. Patent Number 10,875,845, U.S. Patent Number 11,634,411, U.S. Patent Application Number 18 / 119,248, U.S. Patent Application Number 18 / 033,053, U.S. Patent Number 11,459,351, U.S. Patent Publication Number US2022 / 0332749, U.S. Patent Application 18 / 033,055, all of which are incorporated herein by reference for the agents described therein. In some instances, the agent is or serves as a keratolytic, such as used in any method or composition provided herein.

[0148] Provided in certain embodiment herein is a method of a disease or disorder in or around an eye comprising administering any agent describe in any of U.S. Patent Number 11,643,429, U.S. Patent Application Number 18 / 117,759, U.S. Patent Number 10,875,845, U.S. PatentNumber 11,634,411, U.S. Patent Application Number 18 / 119,248, U.S. Patent Application Number 18 / 033,053, U.S. Patent Number 11,459,351, U.S. Patent Publication Number US2022 / 0332749, U.S. Patent Application 18 / 033,055, PCT Publication number WO 2023 / 067387, all of which are incorporated herein by reference for the agents described therein. In some instances, the agent is or serves as a keratolytic, such as used in any method or composition provided herein.

[0149] In some embodiments, the method comprises dispensing a pharmaceutical composition comprising a keratolytic agent (e.g., SeS2). In specific embodiments, a pharmaceutical composition is dispensed until it reaches a virtual line of a visual guide (e.g., of a guide or snap- on visual guide provided herein). In some embodiments, a pharmaceutical composition is dispensed using a dosing aid as provided herein. In certain embodiments, the pharmaceutical composition is dispensed (or applied following being dispensed) onto any clean suitable object or surface (e.g., index finger). In certain embodiments, the pharmaceutical composition is dispensed (or applied following being dispensed) onto a fingertip. In certain embodiments, the pharmaceutical composition is dispensed (or applied following being dispensed) onto an index finger fingertip. In certain embodiments, the pharmaceutical composition is dispensed (or applied following being dispensed) onto an middle finger fingertip.

[0150] In some embodiments, a pharmaceutical composition is spread (e.g., by rubbing the pharmaceutical composition on the washed index finger with a thumb) or softened (e.g., by heating the composition, such as with the body heat of the index finger and thumb). In some embodiments, a pharmaceutical composition is thinned. In some embodiments, the pharmaceutical composition is rubbed between two fingers (e.g., a forefinger (fingertip) or a middle finger (fingertip) and a thumb) multiple times to spread or soften the pharmaceutical composition. In some embodiments, the pharmaceutical composition is rubbed between two fingers (e.g., a forefinger (fingertip) or a middle finger (fingertip) and a thumb) several times to spread or soften the pharmaceutical composition. In specific embodiments, spreading or softening of the pharmaceutical composition results in a thin layer of the pharmaceutical composition being spread over a surface of the finger (e.g., over at least a portion of the surface of the finger), such as the finger to which the pharmaceutical composition was applied. In some embodiments, following dispensing and applying a pharmaceutical composition onto a finger (e.g., and following spreading or softening the pharmaceutical composition on the finger), the pharmaceutical composition is administered to an ocular or periocular surface (e.g., eyelid) of an individual in need thereof. In some embodiments, following dispensing and applying a pharmaceutical composition onto a fingertip (e.g., and following spreading or softening the pharmaceutical composition on the fingertip), thepharmaceutical composition is administered to an ocular or periocular surface (e.g., eyelid) of an individual in need thereof.

[0151] In some embodiments, a method comprises pulling an eyelid away an eye. In some embodiments, a method comprises administering a pharmaceutical composition over the eyelid margin of the affected eye. In some embodiments, a method comprises pulling an upper eyelid away an eye. In some embodiments, a method comprises administering a pharmaceutical composition over the upper eyelid margin of the affected eye. In some embodiments, a method comprises pulling a lower eyelid away an eye. In some embodiments, a method comprises administering a pharmaceutical composition over the lower eyelid margin of the affected eye. In some embodiments, a method comprises pulling both upper and lower eyelids away an eye. In some embodiments, a method comprises administering a pharmaceutical composition over the upper and lower eyelid margins of the affected eye. In some embodiments, administering a pharmaceutical composition comprises going over (e.g., rubbing the pharmaceutical composition to) the lower eyelid margin a few times to ensure complete coverage. In some embodiments, administering a pharmaceutical composition comprises going over (e.g., rubbing the pharmaceutical composition to) the upper and lower eyelid margins a few times to ensure complete coverage. In some embodiments, a method comprises administering a pharmaceutical composition to an eye twice a week at bedtime. In some embodiments, a method comprises administering a pharmaceutical composition to an eye twice a week before bedtime. In some embodiments, a method comprises administering a pharmaceutical composition to an eye with at least 1 day between instillations. In some embodiments, a method comprises not administering a pharmaceutical composition to an eye more than once daily before bedtime.

[0152] In some embodiments, when an individual wears contact lenses, a method comprises removing the contact lenses prior to administering a composition. In some embodiments, when an individual wears contact lenses, a method comprises not removing the contact lenses prior to administering a composition. In some embodiments, when an individual wears contact lenses, a method comprises reinserting the contact lenses after administering a composition. In some embodiments, when an individual wears contact lenses, a method comprises reinserting the contact lenses 15 minutes after administering a composition.

[0153] In some embodiments, provided herein are methods for treating a disease or disorder in or around the eye in an individual (e.g., in need thereof), the method comprising: dispensing a pharmaceutical composition comprising an effective amount of a keratolytic agent (e.g., selenium disulfide (SeS2)); applying the pharmaceutical composition onto a finger of the individual; spreading the pharmaceutical composition over at least a portion of a surface of the finger (e.g.,forming a thin film); and using the finger, administering the pharmaceutical composition to an eyelid of the individual.

[0154] In some embodiments, provided herein are methods for treating a disease or disorder in or around the eye in an individual (e.g., in need thereof), the method comprising: dispensing a pharmaceutical composition comprising an effective amount of a keratolytic agent (e.g., selenium disulfide (SeS2)); applying the pharmaceutical composition onto a fingertip of the individual; spreading the pharmaceutical composition over at least a portion of a surface of the fingertip (e.g., forming a thin film); and using the fingertip, administering the pharmaceutical composition to an eyelid of the individual.

[0155] In some embodiments, provided herein are methods for treating a disease or disorder in or around the eye in an individual (e.g., in need thereof), the method comprising: dispensing a pharmaceutical composition comprising an effective amount of a keratolytic agent (e.g., selenium disulfide (SeS2)); applying the pharmaceutical composition onto a finger of the individual; thinning the pharmaceutical composition over at least a portion of a surface of the finger (e.g., forming a thin film); and using the finger, administering the pharmaceutical composition to an eyelid of the individual.

[0156] In some embodiments, provided herein are methods for treating a disease or disorder in or around the eye in an individual (e.g., in need thereof), the method comprising: dispensing a pharmaceutical composition comprising an effective amount of a keratolytic agent (e.g., selenium disulfide (SeS2)); applying the pharmaceutical composition onto a fingertip of the individual; thinning the pharmaceutical composition over at least a portion of a surface of the fingertip (e.g., forming a thin film); and using the fingertip, administering the pharmaceutical composition to an eyelid of the individual.

[0157] Provided in certain embodiments herein, are methods for treating conditions in or around an eye. In some embodiments, the method comprises administering a pharmaceutical (e.g., ophthalmically acceptable) composition to an ocular and / or periocular surface of an individual. In certain embodiments, the method comprises dispensing the pharmaceutical composition onto an administration surface (e.g., prior to administration to the ocular and / or periocular surface). In specific embodiments, the administration surface is a surface of a digit (e.g., finger) of the individual. In some embodiments, the method comprises softening (e.g., by raising the temperature of the composition, such as with body temperature) or otherwise spreading (e.g., increasing the surface area of) the pharmaceutical composition. In some embodiments, the method comprises thinning the pharmaceutical composition. In some embodiments, the method comprises thinning the pharmaceutical composition before administering to the ocular or periocular region of an individual. In some embodiments, the method comprises softening (e.g., by raising thetemperature of the composition, such as with body temperature of the finger or with the device used to extract the drug out or with a dedicated device) of the pharmaceutical composition. In some embodiments, softening or spreading the pharmaceutical composition results in a thin layer of the pharmaceutical composition before administering to the ocular or periocular region of an individual.

[0158] In certain embodiments, any method provided herein comprises dispensing, such as, from where a pharmaceutical composition provided herein is stored, (e.g., squeezing out of a tube) a pharmaceutical composition provided herein onto any suitable object (e.g., finger or swab) or surface (e.g., finger surface, such as a fingertip, or swab surface). In some instances, a suitable surface is a surface from which the pharmaceutical composition is administered to an ocular or periocular surface of an individual (e.g., described herein). In some embodiments, a method provided herein comprises dispensing the pharmaceutical composition onto a suitable surface (e.g., a swab) prior to applying the pharmaceutical composition onto another suitable surface (e.g., finger). In some embodiments, a method provided herein comprises dispensing the pharmaceutical composition onto a suitable surface prior to administering to an ocular area and / or a periocular area of the individual. In certain embodiments, a method provided comprises dispensing a pharmaceutical composition onto a finger prior to administering to the ocular area and / or the periocular area of the individual. In certain embodiments, a method provided comprises dispensing a pharmaceutical composition onto a fingertip prior to administering to the ocular area and / or the periocular area of the individual.

[0159] In some embodiments, a pharmaceutical composition is dispensed manually (e.g., using a hand to squeeze the pharmaceutical composition out of a tube). In some embodiments, a composition is dispensed onto a suitable surface (e.g., described herein) as a solid, a semi-solid (e.g., globule), or a (e.g., thick) liquid. In some embodiments, a (e.g., solid or semi-solid) composition is dispensed onto a suitable surface (e.g., described herein) as a globule. In some embodiments, the globule is dispensed and applied onto a finger of an individual (by using an index finger or a swab to pick up the globule). In some embodiments, a (e.g., solid or semi-solid) composition is dispensed onto a suitable surface (e.g., described herein) as a strip. In some embodiments, a (e.g., solid or semi-solid) composition is dispensed onto a suitable surface (e.g., described herein) as a strip using a dosing aid as described herein. In some embodiments, the strip is dispensed and applied onto a finger of an individual (by using an index finger or a swab to pick up the strip). In some embodiments, the strip is dispensed and applied onto a fingertip of an individual (by using an index finger or a swab to pick up the strip). In some embodiments, a (e.g., liquid) composition is dispensed onto a suitable surface (e.g., as described herein) as a droplet. In some embodiments, the droplet is dispensed and applied onto a finger of an individual (by usingan index finger or a swab to pick up the droplet). In some embodiments, the droplet is dispensed and applied onto a fingertip of an individual (by using an index finger or a swab to pick up the droplet).

[0160] In certain embodiments, a pharmaceutical composition is dispensed by a dispensing device. In some embodiments, the dispensing device exacts a pharmaceutical composition from where a pharmaceutical composition is stored (e.g., a tube).

[0161] In some embodiments, the dispensing device comprises a snap-on visual guide (e.g., guiding a proper amount of the pharmaceutical composition to dispense). In certain embodiments, the snap-on visual guide is snapped onto where the pharmaceutical composition is stored (e.g., a tube). In some embodiments, the snap-on guide comprises two front tips connected by a virtual line that is used to determine the proper amount of the pharmaceutical composition being dispensed. In some embodiments, the pharmaceutical composition is dispensed until it reaches the virtual line. For example, in some instances, if the dispensed composition (such as a strip) touches the snap-on visual guide, the dispensed composition should be discarded and a new dose of the pharmaceutical composition should be dispensed.

[0162] In some embodiments, the dispensing device comprises a dosing aid. In some embodiments, the dosing aid comprises a syringe device configured to provide precise secretion of the pharmaceutical composition to the suitable surface as described here in (e.g., a finger surface). In some embodiments, the syringe device comprises a barrel chamber having an outlet and a plunger configured to dispense the pharmaceutical composition from the chamber through the outlet. In some embodiments, the outlet of the syringe dispenses a thinner strip of the pharmaceutical composition with smaller diameter compared with the strip of the pharmaceutical composition being dispensed directly from the medication tube of the pharmaceutical composition. In some embodiments, the individual uses a finger to pick up the ointment strip from the tip of the syringe device. In some embodiments, the individual uses a fingertip to pick up the ointment strip from the tip of the syringe device. In some embodiments, the individual uses an index finger to pick up the ointment strip from the tip of the syringe device. In some embodiments, the individual uses an index finger fingertip to pick up the ointment strip from the tip of the syringe device. In some embodiments, the individual uses a middle finger fingertip to pick up the ointment strip from the tip of the syringe device.

[0163] In certain embodiments, any method provided herein comprises spreading a pharmaceutical (e.g., ophthalmically acceptable) composition provided herein. In specific embodiments, spreading the pharmaceutical composition comprises increasing the surface area of the pharmaceutical composition (e.g., a globule or a droplet) on a suitable surface (e.g., a finger and / or a palm), such as to create a thin film of the composition. In further or alternativeembodiments, spreading the pharmaceutical composition comprises decreasing the thickness of the pharmaceutical composition (e.g., a globule or a droplet) on a suitable surface (e.g., a finger and / or a palm), such as to create a thin film of the composition. In some embodiments, spreading the pharmaceutical composition comprises evenly spreading the pharmaceutical composition on any finger or any suitable surface, such as to create a thin film of the composition. In some embodiments, the thin film comprises a thin layer of a pharmaceutical composition described herein with a decreased thickness (e.g., ranging from nanometer to several micrometers) that may result from softening or spreading the pharmaceutical composition by two fingers and / or a device. In some embodiments, the spreading comprises mechanical spreading, such as with a device or a finger.

[0164] In certain embodiments, any method provided herein comprises thinning a pharmaceutical (e.g., ophthalmically acceptable) composition provided herein. In specific embodiments, thinning the pharmaceutical composition comprises increasing the surface area of the pharmaceutical composition (e.g., a globule or a droplet) on a suitable surface (e.g., a finger and / or a palm), such as to create a thin film of the composition. In further or alternative embodiments, thinning the pharmaceutical composition comprises decreasing the thickness of the pharmaceutical composition (e.g., a globule or a droplet) on a suitable surface (e.g., a finger and / or a palm), such as to create a thin film of the composition. In some embodiments, thinning the pharmaceutical composition comprises evenly spreading the pharmaceutical composition on any finger or any suitable surface, such as to create a thin film of the composition. In some embodiments, the thin film comprises a thin layer of a pharmaceutical composition described herein with a decreased thickness (e.g., ranging from nanometer to several micrometers) that may result from thinning the pharmaceutical composition by two fingers and / or a device.

[0165] In some embodiments, the thin layer described herein is about 400 pm or less. In some embodiments, the thin layer described herein is about 300 pm or less. In some embodiments, the thin layer described herein is about 200 pm or less. In some embodiments, the thin layer described herein is about 10 pm to 200 pm. In some embodiments, the thin layer described herein is about 10 pm to 100 pm. In some embodiments, the thin layer described herein is about 25 pm to 75 pm. In some embodiments, the thin layer described herein is about 50 pm.

[0166] In certain embodiments, spreading the pharmaceutical composition is achieved by any suitable method. In some instances, spreading is achieved by heating (e.g., using the individual’s body temperature). In some instances, spreading is achieved by applying force (e.g., between fingers or fingertips) to the pharmaceutical composition (e.g., prior to administration to the ocular and / or periocular surface). In some embodiments, the pharmaceutical composition is spread over the finger using a device (e.g., lip balm, eye liner). In some embodiments, the pharmaceuticalcomposition is spread over the fingertips using a device (e.g., lip balm, eye liner). In specific embodiments, spreading the pharmaceutical composition results in the pharmaceutical composition being spread over a surface of the finger (e.g., over at least a portion of the surface of the finger), such as the finger to which the pharmaceutical composition was applied. In some instances, spreading is achieved by a dispensing machine as described herein.

[0167] In further or alternative embodiments, spreading the pharmaceutical composition comprises rubbing the pharmaceutical composition between two suitable surfaces (e.g., two fingers, a finger and a palm, two palms, two swabs), such as to use the body temperature to melt and create a thin film of the composition. In some embodiments, spreading the pharmaceutical composition comprises rubbing the pharmaceutical composition between any of the fingers. In some embodiments, spreading the pharmaceutical composition comprises rubbing the pharmaceutical composition between any of the fingertips. In some embodiments, spreading the pharmaceutical composition comprises rubbing the pharmaceutical composition between any one of the fingers and a suitable surface. In some embodiments, spreading the pharmaceutical composition comprises rubbing the pharmaceutical composition between any one of the fingertips and a suitable surface. In some embodiments, spreading the pharmaceutical composition comprises rubbing the pharmaceutical composition between two suitable surfaces. In specific embodiments, spreading the pharmaceutical composition comprises rubbing the pharmaceutical composition between a forefinger and a thumb. In specific embodiments, spreading the pharmaceutical composition comprises rubbing the pharmaceutical composition between a forefinger fingertip and a thumb fingertip. In specific embodiments, spreading the pharmaceutical composition comprises rubbing the pharmaceutical composition between a middle finger fingertip and a thumb fingertip.

[0168] In some embodiments, any method provided herein comprises spreading a (e.g., pharmaceutically or ophthalmically acceptable) composition provided herein prior to administering the pharmaceutical composition to an ocular area (e.g., surface) and / or a periocular area (e.g., surface) of an individual (e.g., having a disease or condition affecting the periocular area and / or ocular area associated with the periocular area to which the pharmaceutical composition is administered).

[0169] In certain embodiments, thinning the pharmaceutical composition is achieved by any suitable method. In some instances, thinning is achieved by heating (e.g., using the individual’s body temperature). In some instances, thinning is achieved by applying force (e.g., between fingers or fingertips) to the pharmaceutical composition (e.g., prior to administration to the ocular and / or periocular surface). In some embodiments, the pharmaceutical composition is thinned over the finger using a device (e.g., lip balm, eye liner). In some embodiments, the pharmaceuticalcomposition is thinned over the fingertips using a device (e.g., lip balm, eye liner). In specific embodiments, thinning the pharmaceutical composition results in the pharmaceutical composition being thinned over a surface of the finger (e.g., over at least a portion of the surface of the finger, such as the fingertip), such as the finger to which the pharmaceutical composition was applied. In some instances, thinning is achieved by a dispensing machine as described herein.

[0170] In further or alternative embodiments, thinning the pharmaceutical composition comprises rubbing the pharmaceutical composition between two suitable surfaces (e.g., two fingers, a finger and a palm, two palms, two swabs), such as to use the body temperature to melt and create a thin film of the composition. In some embodiments, thinning the pharmaceutical composition comprises rubbing the pharmaceutical composition between any of the fingers. In some embodiments, thinning the pharmaceutical composition comprises rubbing the pharmaceutical composition between any of the fingertips. In some embodiments, thinning the pharmaceutical composition comprises rubbing the pharmaceutical composition between any one of the fingers and a suitable surface. In some embodiments, thinning the pharmaceutical composition comprises rubbing the pharmaceutical composition between any one of the fingertips and a suitable surface. In some embodiments, thinning the pharmaceutical composition comprises rubbing the pharmaceutical composition between two suitable surfaces. In specific embodiments, thinning the pharmaceutical composition comprises rubbing the pharmaceutical composition between a forefinger and a thumb. In specific embodiments, thinning the pharmaceutical composition comprises rubbing the pharmaceutical composition between a forefinger fingertip and a thumb fingertip. In specific embodiments, thinning the pharmaceutical composition comprises rubbing the pharmaceutical composition between a middle fingertip and a thumb fingertip.

[0171] In some embodiments, any method provided herein comprises thinning a (e.g., pharmaceutically or ophthalmically acceptable) composition provided herein prior to administering the pharmaceutical composition to an ocular area (e.g., surface) and / or a periocular area (e.g., surface) of an individual (e.g., having a disease or condition affecting the periocular area and / or ocular area associated with the periocular area to which the pharmaceutical composition is administered).

[0172] When the pharmaceutical composition is not spread or thinned on a suitable surface prior to administering to the ocular or periocular area of an individual in need thereof, undesirable results, such as poor efficacy and / or poor tolerability, can be observed and may lead to discontinued use. In some instances, high concentrations and / or high volume of a SeS2 (or composition comprising a SeS2) lead to poor tolerability in some individuals when administered to an ocular or periocular surface. Further, in certain instances, inadequate delivery and / or poor distribution of a SeS2 (or composition comprising a SeS2) to a target location on an ocular and / orperiocular surface leads to poor efficacy and / or poor tolerability. In specific instances, for example, uneven or misapplied administration of a SeS2 (or composition comprising a SeS2) leads to a large droplet or globule of a pharmaceutical composition comprising a SeS2 to a highly discrete area, such as within the target area, or even outside of the target area. For example, in some instances, application of a pharmaceutical composition (e.g., ointment comprising a SeS2) to a finger, a fingertip, or other administration surface and subsequent administration to a ocular or periocular location leads to a globule of the ointment being applied to the eyelid, which may then sit in a single location, or may even migrate to an undesired location, such as a caruncle of the eye associated with the ocular or periocular surface to which the pharmaceutical composition was administered.

[0173] Without spreading or thinning the pharmaceutical composition on a suitable surface prior to administering to the ocular or periocular area of the patients, detrimental results can be observed. For example, FIG. 1 and FIG. 5 illustrates a moderate to severe inflammation of an ocular disease (e.g., indicated by sodium fluorescein corneal staining having an Oxford score equal to 3) at day 14 when the patients did not spread a pharmaceutical composition comprising SeS2 provided herein on their fingers before administration compared with baseline level (before any treatment with the composition) where the inflammation of the ocular disease was early to moderate (e.g., indicated by sodium fluorescein corneal staining having an Oxford score between 1 and 2). This moderate to severe inflammation at day 14 was also associated with a poor MGYLS and MGS scoring in the same patients as illustrated in FIG. 2, FIG. 3, FIG. 6, and FIG. 7. One of the patients also exhibited a worse total OSDI and SPPED scoring (e.g., indicating worsening symptoms) at day 14 as illustrated in FIG. 5.

[0174] When the pharmaceutical composition is spread or thinned on a suitable surface prior to administering to the ocular or periocular area of the patients, improved efficacy and / or tolerability can be observed. For example, FIG.1-8 illustrates improved efficacy and / or tolerability after day 14 when the same patients spread or thin a pharmaceutical composition on the fingers provided herein versus when administering the same composition without first spreading or thinning the same composition on the fingers prior to administration before day 14. For instance, MGYLS and MGS scoring were substantially improved in the same patients in months 1.5 and 3 compared with day 14 after the patients spread the pharmaceutical composition prior to administering to the ocular or periocular area as illustrated in FIG. 2, FIG. 3, FIG. 6, and FIG. 7. In addition, total OSDI and SPPED scoring were substantially improved in the same patients in months 1.5 and 3, indicating the symptoms were also improved (FIG. 4 and FIG. 8). In another instance, when a patient spread or thin a pharmaceutical composition provided herein on their finger first and then administer the same composition to the ocular or periocular area of the patient since the treatmentstarted, an improved MGYLS, MGS, and total OSDI were observed (data not shown). This patient exited the study early after substantial improvement of eye conditions.

[0175] In certain embodiments, any method provided herein comprises self-administering a (e.g., pharmaceutically or ophthalmically acceptable) composition provided herein to an individual (one’s self) in need thereof (e.g., having a disease or condition affecting the periocular area and / or ocular area associated with the periocular area to which the pharmaceutical composition is administered). In some embodiments, any method provided herein comprises self-administering the pharmaceutical composition at home. In further or alternative embodiments, any method provided herein comprises administering the pharmaceutical composition to the individual by a medical practitioner (e.g., a doctor, a nurse, a skilled medical technician, etc.). In some embodiments, the pharmaceutical composition is administered to the individual by another individual or by a machine. In some embodiments, the individual blinks several times to transfer a portion of the keratolytic agent (e.g., selenium sulfide) from the lower eyelid to the upper eyelid. In some embodiments, the individual blinks several times to transfer a portion of the keratolytic agent (e.g., selenium sulfide) from the upper eyelid to the lower eyelid.

[0176] In some embodiments, the administration of the pharmaceutical composition is via a finger (e.g., a forefinger, a middle finger, or a ring finger). In some embodiments, the administration of the pharmaceutical composition is via a fingertip. In specific embodiments, the administration of the pharmaceutical composition is via a forefinger. In specific embodiments, the administration of the pharmaceutical composition is via a forefinger fingertip. In specific embodiments, the administration of the pharmaceutical composition is via a middle finger. In specific embodiments, the administration of the pharmaceutical composition is via a middle finger fingertip. In specific embodiments, the administration of the pharmaceutical composition is via a ring finger. In specific embodiments, the administration of the pharmaceutical composition is via a ring finger fingertip. In some embodiments, the administration of the pharmaceutical composition is via a swab. In some embodiments, finger administration is preferred.

[0177] In some instances, administration of a pharmaceutical composition provided herein after dispensing the pharmaceutical composition manually or via a dispensing device, applying the pharmaceutical composition onto a finger (e.g., as a globule, strip, or droplet), spreading the pharmaceutical composition (e.g., increasing the surface area and / or decreasing the thickness of a composition) with a finger, rather than without such steps (e.g., by administration of a glob with a swab), results in improved efficacy, improved safety and tolerability of the compound, decreased discomfort or adverse event, and / or improved compliance with repeated administration protocols.

[0178] In some instances, administration of a pharmaceutical composition provided herein after dispensing the pharmaceutical composition manually or via a dispensing device, applying thepharmaceutical composition onto a fingertip (e.g., as a globule, strip, or droplet), spreading the pharmaceutical composition (e.g., increasing the surface area and / or decreasing the thickness of a composition) with a finger, rather than without such steps (e.g., by administration of a glob with a swab), results in improved efficacy, improved safety and tolerability of the compound, decreased discomfort or adverse event, and / or improved compliance with repeated administration protocols.

[0179] In certain embodiments, any method provided herein comprises administering a pharmaceutical (e.g., ophthalmically acceptable) composition provided herein to any suitable area. In some embodiments, the suitable area is an area affected by a disorder described herein and / or an area wherein administration of a pharmaceutical composition provided herein would provide efficacious treatment of a disorder described herein, such as according to a method provided herein.

[0180] In some embodiments, a method provided herein comprises administering a pharmaceutical composition provided herein to an ocular area (e.g., surface) and / or a periocular area (e.g., surface) of an individual (e.g., having a disease or condition affecting the periocular area and / or ocular area associated with the periocular area to which the pharmaceutical composition is administered). In specific embodiments, a method provided herein comprises administering the pharmaceutical composition to a periocular area of an individual (e.g., having a disease or condition affecting the periocular area and / or ocular area associated with the periocular area to which the pharmaceutical composition is administered).

[0181] In certain embodiments, a method provided herein comprises administering a pharmaceutical composition provided herein to the ocular surface, surrounding ocular tissues, eyelid, eyelid margin, lid wiper, meibomian gland, mucocutaneous margin, eyelashes, lash line, lash follicle, tarsal glands, palpebral border, medial angle, lacrimal papilla and punctum, dermal or epidermal tissue within 1 cm of the ocular surface, dermal or epidermal tissue within 2 cm of the ocular surface, or any combination thereof.

[0182] In certain embodiments, a method provided herein comprises administering a pharmaceutical composition provided herein to an eyelid (e.g., upper and / or lower eyelid) of the individual. In some embodiments, the pharmaceutical composition is administered to a lower eyelid of the individual. In some embodiments, the pharmaceutical composition is administered to an upper eyelid of the individual. In some embodiments, the pharmaceutical composition is administered to both upper and lower eyelid of the individual. In some embodiments, the pharmaceutical composition is administered to an eyelid margin (e.g., upper and / or lower eyelid margin). In some embodiments, the pharmaceutical composition is administered to a lower eyelid margin. In some embodiments, the pharmaceutical composition is administered to an upper eyelidmargin. In some embodiments, the pharmaceutical composition is administered to both upper and lower eyelid margin.

[0183] In some embodiments, administration of a pharmaceutical composition provided herein to an eyelid comprises administration to an ocular or periocular area, such that the pharmaceutical composition is delivered to the eyelid. In some embodiments, administration of a pharmaceutical composition provided herein to an eyelid margin comprises administration to an ocular or periocular area (e.g., eyelid), such that the pharmaceutical composition is delivered to the eyelid margin.

[0184] In some embodiments, an individual in need there of pulls a lower eyelid away from an eye (e.g., eye with disease or disorder) prior to administering the pharmaceutical composition over the lower eyelid margin of the eye. In some embodiments, pulling a lower eyelid exposes a bigger and / or wider ocular or periocular area surface for better coverage when administering a pharmaceutical composition provided herein. In some embodiments, an individual in need there of administers a pharmaceutical composition (after spreading and applying the pharmaceutical composition on the finger or fingertip as described herein) by spreading the pharmaceutical composition over the lower eyelid margin several times (e.g., to ensure better and / or complete coverage than spreading the pharmaceutical composition only once).

[0185] In some embodiments, an individual in need there of pulls an upper eyelid away from an eye (e.g., eye with disease or disorder) prior to administering the pharmaceutical composition over the upper eyelid margin of the eye. In some embodiments, pulling an upper eyelid exposes a bigger and / or wider ocular or periocular area surface for better coverage when administering a pharmaceutical composition provided herein. In some embodiments, an individual in need there of administers a pharmaceutical composition (after spreading and applying the pharmaceutical composition on the finger or fingertip as described herein) by spreading the pharmaceutical composition over the upper eyelid margin several times (e.g., to ensure better and / or complete coverage than spreading the pharmaceutical composition only once).

[0186] In some embodiments, an individual in need there of pulls both upper and lower eyelids away from an eye (e.g., eye with disease or disorder) prior to administering the pharmaceutical composition over the upper and lower eyelid margins of the eye. In some embodiments, pulling both upper and lower eyelids exposes a bigger and / or wider ocular or periocular area surface for better coverage when administering a pharmaceutical composition provided herein. In some embodiments, an individual in need there of administers a pharmaceutical composition (after spreading and applying the pharmaceutical composition on the finger or fingertip as described herein) by spreading the pharmaceutical composition over the upper and lower eyelid marginsseveral times (e.g., to ensure better and / or complete coverage than spreading the pharmaceutical composition only once).

[0187] In some embodiments, an individual in need there of washes hands before dispensing a pharmaceutical composition provided herein. In some embodiments, an individual in need there of washes hands before dispensing a pharmaceutical composition to one eye. In some embodiments, an individual in need there of washes hands before dispensing a pharmaceutical composition to the other eye. In some embodiments, an individual in need there of washes hands after finishing administering a pharmaceutical composition provided herein. In some embodiments, an individual in need there of washes hands after finishing administering the pharmaceutical composition to one eye. In some embodiments, an individual in need there of washes hands after finishing administering the pharmaceutical composition to other eye. In some embodiments, an individual in need there of washes hands between administering the pharmaceutical composition to both eyes (e.g., when both eyes have disease or disorder). In some embodiments, an individual in need there of repeats dispensing, spreading, applying, and administering the pharmaceutical composition to the other eye.

[0188] In some embodiments, an individual in need thereof wears contact lenses. In further embodiments, the contact lenses are removed prior to administering the pharmaceutical composition. In some embodiments, an individual does not remove the contact lenses prior to administering a composition. In some embodiments, the contact lenses are reinserted after administering the pharmaceutical composition. In some embodiments, the contact lenses are reinserted 15 minutes after administering the pharmaceutical composition.

[0189] In certain embodiments, any methods provided herein comprises treating conditions in or around an eye. In specific embodiments, the conditions in or around the eye comprises a disease or disorder in or around the eye. In specific embodiments, the disease or disorder comprises one or more conditions selected from the group comprising meibomian gland dysfunction (MGD), blepharitis, seborrheic blepharitis, Demodex infestation, dry eye disease (DED), dry eye syndrome (DES), hyperkeratosis, dermatitis, keratitis, contact lens discomfort, lid wiper epitheliopathy (LWE), Keratoconjunctivitis Sicca, Sjogren's Syndrome, ocular rosacea, conjunctival ulcerations, sloughing of surface epithelium at the lid margin, conjunctival scarring / deficiency, or keratinization over the lid wiper zone and / or conjunctiva. In some embodiments, the disease or disorder in or around the eye is Blepharitis or Seborrheic Blepharitis. In some embodiments, the disease or disorder in or around the eye is meibomian gland dysfunction (MGD). In some embodiments, the disease or disorder in or around the eye is dry eye disease (e.g., also known as the dry eye syndrome). In some embodiments, the disease or disorder in or around the eye is dry eye syndrome. In some embodiments, the disease or disorder in or around the eye is keratitis orhyperkeratosis. In some embodiments, the disease or disorder in or around the eye is contact lens discomfort. In some embodiments, the disease or disorder in or around the eye is LWE. In some embodiments, the disease or disorder in or around the eye is a condition characterized by insufficient secretion of lipids.

[0190] In some embodiments, a method provided herein comprises administering a pharmaceutical composition provided herein to an individual in need thereof. In some embodiments, the individual in need thereof has conditions in or around an eye. In specific embodiments, the conditions in or around the eye comprises a disease or disorder in or around the eye described herein.

[0191] In certain embodiments, a (e.g., pharmaceutically or ophthalmically acceptable) composition provided herein is formulated in any suitable manner. In some embodiments, the pharmaceutical composition is a semi-solid. In specific embodiments, the semi-solid is an ointment, a gel, a cream, or a paste. In some embodiments, the semi-solid is an ointment.

[0192] In some embodiments, the pharmaceutical composition is an ointment. In some embodiments, the ointment is, for example, hydrocarbon based, absorption based, water-soluble based, emulsifying based, or vegetable based. In some embodiments, the ointment comprises, for example, a hard paraffin, a soft paraffin, a microcrystalline wax, a ceresin, a wool fat, a beeswax, a macrogol, an emulsifying wax, olive oil, coconut oil, sesame oil, almond oil, peanut oil, or any combination thereof. In some embodiments, the ointment is a soft paraffin, such as, for example, petroleum jelly or petrolatum.

[0193] In some embodiments, a (e.g., pharmaceutically or ophthalmically acceptable) composition provided herein is a solid form that either melts or has flow at a temperature at a physiologically acceptable temperature, such about 37°C or less. In further or alterative embodiments, the pharmaceutical composition is a semi-solid or fluid (e.g., liquid or suspension) that has decreased viscosity when at a physiologically acceptable temperature, such as about 37°C or less (e.g., compared to at a refrigerated or room temperature, such as about 4°C or 20°C, respectively).

[0194] In some embodiments, a (e.g., pharmaceutically or ophthalmically acceptable) composition provided herein comprises a keratolytic agent. In specific embodiments, the keratolytic agent is selected from the group consisting of benzoyl peroxide, coal tar, dithranol, salicylic acid, selenium disulfide, alpha-hydroxy acid, urea, lactic acid, boric acid, retinoic acid, sodium thioglycolate, allantoin, zinc pyrithione, zinc L-pyrrolidone carboxylate, seleocysteine, selenomethionine, captopril, zofenopril, tiopronin, penicillamine, L-cysteine, N-acetyl cysteine (NAC), gluthatione, dithiothreitol, thi orphan, cysteamine, bucillamine, dimercaprol, 1,1- ethanedithiol, dimercaptosuccinic acid, furan-2-ylmethanethiol, omapatrilat, ovothiol A,rentiapril, thiosalicylic acid, tixocortol, mycothiol, coenzyme A, coenzyme B, disulfiram, psammaplin A, dixanthogen, pantethine, fursultiamine, octotiamine, sulbutiamine, prosultiamine, thiram, lipoic acid, lenthionine, ajoene, allicin, gemopatrilat, thioethanol, thiophospholipid, thiocholesterol, 12-mercaptododecanoic acid, 23-(9-mercaptononyl)-3,6,9,12,15,18,21- heptaoxatricosanoic acid, and sulfanegen. In some embodiments, the keratolytic agent is selected from the group consisting of benzoyl peroxide, coal tar, dithranol, salicylic acid, selenium disulfide, N-acetyl cysteine (NAC), bucillamine, captopril, alpha-hydroxy acid, urea, lactic acid, sodium thioglycolate, zinc pyrithione, or zinc L-pyrrolidone carboxylate. In some embodiments, the keratolytic agent is selenium disulfide.

[0195] In some embodiments, a pharmaceutical (e.g., ophthalmically acceptable) composition provided herein is any compound described in any of U.S. Patent Number 11,643,429, U.S. Patent Application Number 18 / 117,759, U.S. Patent Number 10,875,845, U.S. Patent Number 11,634,411, U.S. Patent Application Number 18 / 119,248, U.S. Patent Application Number 18 / 033,053, U.S. Patent Number 11,459,351, U.S. Patent Publication Number US2022 / 0332749, U.S. Patent Application 18 / 033,055, all of which are incorporated herein by reference for the agents described therein.

[0196] In some embodiments, a pharmaceutical (e.g., ophthalmically acceptable) composition provided herein is any compound described in any of U.S. Patent Number 11,643,429, U.S. Patent Application Number 18 / 117,759, U.S. Patent Number 10,875,845, U.S. Patent Number 11,634,411, U.S. Patent Application Number 18 / 119,248, U.S. Patent Application Number 18 / 033,053, U.S. Patent Number 11,459,351, U.S. Patent Publication Number US2022 / 0332749, U.S. Patent Application 18 / 033,055, PCT Publication number WO 2023 / 067387, all of which are incorporated herein by reference for the agents described therein.

[0197] In some embodiments, a pharmaceutical (e.g., ophthalmically acceptable) composition provided herein comprises a keratolytic agent (e.g., SeS?) described herein with a therapeutically effective concentration. In some embodiments, the pharmaceutical composition comprises SeS2 in a therapeutically effective concentration. In some embodiments, the pharmaceutical composition comprises SeS2 in less than a therapeutically effective concentration. In some embodiments, the pharmaceutical composition comprises SeS? in a homeopathic concentration. In some embodiments, the pharmaceutical composition comprises SeS? in greater than a therapeutically effective concentration.

[0198] In some embodiments, the therapeutically effective concentration is about 0.1 wt. % to about 2.5 wt. % (e.g., about 0.5 wt. % to about 1 wt. %). In some embodiments, the therapeutically effective concentration comprises at least about 0.01 wt. %, about 0.05 wt. %, about 0.1 wt. %, about 0.15 wt. %, about 0.2 wt. %, about 0.25 wt. %, about 0.3 wt. %, about 0.35 wt. %, about 0.4wt. %, about 0.45 wt. %, about 0.5 wt. %, about 0.55 wt. %, about 0.6 wt. %, about 0.65 wt. %, about 0.7 wt. %, about 0.75 wt. %, about 0.8 wt. %, about 0.85 wt. %, about 0.9 wt. %, about 0.95 wt. %, about 1.0 wt. %, about 1.25 wt. %, about 1.5 wt. %, about 1.75 wt. %, about 2.0 wt. %, about 2.5 wt. %, about 3.0 wt. %, about 4.0 wt. %, about 4.5 wt. %, about 5.0 wt. %, about 5.5 wt. %, about 6.0 wt. %, about 6.5 wt. %, about 7.0 wt. %, about 7.5 wt. %, about 8.0 wt. %, about 8.5 wt. %, about 9.0 wt. %, about 9.5 wt. %, about 10.0 wt. %, about 10.5 wt. %, about 11.0 wt. %, about 11.5 wt. %, about 12.0 wt. %, about 15.0 wt. % or more of the keratolytic agent (e.g., selenium disulfide (SeS2) described herein.

[0199] In some embodiments, the therapeutically effective concentration comprises at most about 15.0 wt. %, about 14.0 wt. %, about 13.0 wt. %, about 12.0 wt. %, about 11.0 wt. %, about 10.0 wt. %, about 9.0 wt. %, , about 8.0 wt. %, about 7.0 wt. %, about 6.0 wt. %, about 5.0 wt. %, about 4.0 wt. %, about 3.0 wt. %, about 2.5 wt. %, about 2.0 wt. %, about 1.75 wt. %, about 1.5 wt. %, about 1.25 wt. %, about 1.0 wt. %, about 0.95 wt. %, about 0.9 wt. %, about 0.85 wt. %, about 0.8 wt. %, about 0.75 wt. %, about 0.70 wt. %, about 0.65 wt. %, about 0.60 wt. %, about 0.55 wt. %, about 0.5 wt. %, about 0.45 wt. %, about 0.4 wt. %, about 0.35 wt. %, about 0.3 wt. %, about 0.25 wt. %, or less of the keratolytic agent (e.g., SeS?) described herein.

[0200] In some embodiments, the therapeutically effective concentration comprises about 0.01 wt. % to about 15.0 wt. %, about 0.01 wt. % to about 10.0 wt. %, about 0.01 wt. % to about 9.0 wt. %, about 0.01 wt. % to about 8.0 wt. %, about 0.01 wt. % to about 7.0 wt. %, about 0.01 wt. % to about 6.0 wt. %, about 0.01 wt. % to about 5.0 wt. %, about 0.01 wt. % to about 4.0 wt. %, about 0.01 wt. % to about 3.0 wt. %, about 0.01 wt. % to about 2.0 wt. %, about 0.01 wt. % to about 1.5 wt. %, about 0.01 wt. % to about 1.0 wt. %, about 0.01 wt. % to about 0.5 wt. %, about 0.01 wt. % to about 0.1 wt. %, about 0.01 wt. % to about 0.05 wt. %, about 0.05 wt. % to about 4.0 wt. %, about 0.05 wt. % to about 3.0 wt. %, about 0.05 wt. % to about 2.0 wt. %, about 0.05 wt. % to about 1.5 wt. %, about 0.05 wt. % to about 1.0 wt. %, about 0.05 wt. % to about 0.5 wt. %, about 0.05 wt. % to about 0.1 wt. %, about 0.1 wt. % to about 4.0 wt. %, about 0.1 wt. % to about 3.0 wt. %, about 0.1 wt. % to about 2.0 wt. %, about 0.1 wt. % to about 1.5 wt. %, about 0.1 wt. % to about 1.0 wt. %, about 0.1 wt. % to about 0.5 wt. %, about 0.5 wt. % to about 4.0 wt. %, about 0.5 wt. % to about 3.0 wt. %, about 0.5 wt. % to about 2.0 wt. %, about 0.5 wt. % to about 1.5 wt. %, about 0.5 wt. % to about 1.0 wt. %, about 1.0 wt. % to about 4.0 wt. %, about 1.0 wt. % to about 3.0 wt. %, about 1.0 wt. % to about 2.5 wt. %, about 1.0 wt. % to about 2.0 wt. %, about 1.0 wt. % to about 1.5 wt. %, or any combination thereof. In some instances, administration or use of lower concentrations of SeS2 (e.g., 0.5 wt. %) results in fewer adverse effects. In some instances, administration or use of lower concentrations of SeS2 (e.g., 0.5 wt. %) results in feweradverse effects when light is avoided after administration, such as administration in the evening or at night.

[0201] In some embodiments, the pharmaceutical composition is administered in a volume of less than 25 pL (e.g., 1-25 pL). In some embodiments, the pharmaceutical composition is administered in a volume of about 1 pL to about 20 pL (e.g., about 2 pL to about 15 pL, or about 3 pL to about 10 pL). In some embodiments, the volume of the pharmaceutical composition or the volume of pharmaceutical composition administered using a method provided herein (e.g., using a swab or a finger) is at most about 30 pL, at most about 25 pL, at most about 20 pL, at most about 15 pL, at most about 10 pL, or at most about 5 pL. In some embodiments, the volume is at least about 0.01 microliters (pL), at least about 0.05 pL, at least about 0.1 pL, at least about 0.5 pL, at least about 1 pL, at least about 5 pL, at least about 10 pL, at least about 15 pL, at least about 20 pL, or more. In some embodiments, the volume is from about 0.01 pL to about 50 pL, about 0.1 pL to about 30 pL, about 0.5 pL to 25 pL, about 1 pL to 25 pL, about 10 pL to 25 pL, or about 2.5 pL to about 10 pL.

[0202] In some embodiments, the therapeutically effective amount of SeS2 is at least about 0.1 milligrams (mg), at least about 0.2 mg, at least about 0.3 mg, at least about 0.5 mg, at least about 1 mg, at least about 2 mg, at least about 2.5 mg, or the like. In some embodiments, the therapeutically effective amount of selenium disulfide (SeS2) is about 25 mg or less, about 15 mg or less, about 10 mg or less, 7.5 mg or less, about 5 mg or less. In some embodiments, the therapeutically effective amount of SeS2 is about 0.5 mg, about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 8 mg, about 10 mg, or the like. In some embodiments, the therapeutically effective amount of SeS2 is about 4 mg.

[0203] In some embodiments, a pharmaceutical (e.g., ophthalmically acceptable) composition provided herein is dispensed (e.g., squeezed and / or applied) onto an administration surface described herein (e.g., a finger, a fingertip, or a swab) in any suitable amount, such as an amount of less than about 10 milligrams (mg). In some embodiments, the pharmaceutical composition is dispensed onto a finger and / or administered to an ocular and / or periocular surface in an amount of less than about 100 mg. In some embodiments, the pharmaceutical composition is dispensed onto a finger and / or administered to an ocular and / or periocular surface in an amount of less than about 50 mg. In some embodiments, the pharmaceutical composition is dispensed onto a finger and / or administered to an ocular and / or periocular surface in an amount of about 0.1 mg to about 50 mg. In some embodiments, the pharmaceutical composition is dispensed onto a finger and / or administered to an ocular and / or periocular surface in an amount of about 1 mg to about 50 mg. In some embodiments, the pharmaceutical composition is dispensed onto a finger and / or administered to an ocular and / or periocular surface in an amount of about 5 mg to about 30 mg.In some embodiments, the pharmaceutical composition is dispensed onto a finger and / or administered to an ocular and / or periocular surface in an amount of about 5 mg. In some embodiments, the pharmaceutical composition is dispensed onto a finger and / or administered to an ocular and / or periocular surface in an amount of about 10 mg. In some embodiments, the pharmaceutical composition is dispensed onto a finger and / or administered to an ocular and / or periocular surface in an amount of about 20 mg. In some embodiments, the pharmaceutical composition is dispensed onto a finger and / or administered to an ocular and / or periocular surface in an amount of about 30 mg.

[0204] In some embodiments, a pharmaceutical (e.g., ophthalmically acceptable) composition provided herein is dispensed (e.g., squeezed and / or applied) onto an administration surface described herein (e.g., a finger, a fingertip, or a swab) in any suitable volume, such as a volume of less than 25 pL. In specific embodiments, the pharmaceutical composition is dispensed onto a finger and / or administered to an ocular and / or periocular surface in a volume less than 500 pL. In specific embodiments, the pharmaceutical composition is dispensed onto a fingertip and / or administered to an ocular and / or periocular surface in a volume less than 500 pL. In specific embodiments, the pharmaceutical composition is dispensed onto a finger and / or administered to an ocular and / or periocular surface in a volume less than 100 pL. In specific embodiments, the pharmaceutical composition is dispensed onto a fingertip and / or administered to an ocular and / or periocular surface in a volume less than 100 pL. In specific embodiments, the pharmaceutical composition is dispensed onto a finger and / or administered to an ocular and / or periocular surface in a volume less than 25 pL. In specific embodiments, the pharmaceutical composition is dispensed onto a fingertip and / or administered to an ocular and / or periocular surface in a volume less than 25 pL. In some embodiments, the volume is from about 0.01 pL to about 50 pL, about 0.1 pL to about 30 pL, about 0.5 pL to about 25 pL, about 1 pL to about 25 pL, about 0.1 pL to about 10 pL, or about 2.5 pL to about 10 pL. In specific embodiment, the volume of composition dispensed onto an administration surface is (e.g., a therapeutically effective volume and) about 0.1 pL to about 10 pL.

[0205] In some embodiments, the volume of the pharmaceutical composition dispensed onto the finger is about 500 pL or less. In some embodiments, the volume of the pharmaceutical composition dispensed onto the fingertip is about 500 pL or less. In some embodiments, the volume of the pharmaceutical composition dispensed onto the finger is about 100 pL or less. In some embodiments, the volume of the pharmaceutical composition dispensed onto the fingertip is about 100 pL or less. In some embodiments, the volume of the pharmaceutical composition dispensed onto the finger is about 25 pL or less. In some embodiments, the volume of the pharmaceutical composition dispensed onto the fingertip is about 25 pL or less.

[0206] In some embodiments, the method provided herein eliminates the need for a specific measured dose of administration onto the finger. In some embodiments, the method provided herein eliminates the need for a specific measured dose of administration onto the fingertip.

[0207] In some embodiments, the volume of the pharmaceutical composition dispensed onto the finger or fingertip is spread, thinned, or the like to provide a thin layer of the pharmaceutical composition on the finger or fingertip of the individual described herein. In some embodiments, the thin layer is about 400 micrometers (pm) or less. In some embodiments, the thin layer is about 300 pm or less. In some embodiments, the thin layer is about 200 pm or less. In some embodiments, the thin layer is about 10 pm to 200 pm. In some embodiments, the thin layer is about 100 pm or less. In some embodiments, the thin layer is about 10 pm to 100 pm. In some embodiments, the thin layer is about 25 pm to 75 pm. In some embodiments, the thin layer is about 50 pm.

[0208] In some embodiments, the volume or amount of the pharmaceutical composition dispensed onto the finger is spread or thinned to a suitable thickness. In some embodiments, the thickness of the pharmaceutical composition spread on the finger is the same regardless of the volume dispensed to the finger (e.g., fingertip). In some embodiments, the thickness of the pharmaceutical composition spread on the finger is at most about 200 micrometers (pm). In some embodiments, the thickness of the pharmaceutical composition spread on the finger is at most about 100 micrometers (pm). In some embodiments, the thickness of the pharmaceutical composition spread on the finger is about 1 pm to about 100 pm. In some embodiments, the thickness of the pharmaceutical composition spread on the finger is about 25 pm to about 75 pm. In some embodiments, the thickness of the pharmaceutical composition spread on the finger is about 50 pm.

[0209] In some embodiments, a pharmaceutical (e.g., ophthalmically acceptable) composition provided herein is dispensed (e.g., squeezed and / or applied) onto an administration surface described herein (e.g., a finger or a swab) as a ribbon in any suitable length, such as a length of less than about 30 millimeters (mm). In some embodiments, the length is at most about 100 mm. In some embodiments, the length is at most about 50 mm. In some embodiments, the length is at most about 30 mm. In some embodiments, the length is at least about 0.5 mm. In some embodiments, the length is about 1 mm to about 20 mm, about 1 mm to about 10 mm, about 1 mm to about 5 mm. In specific embodiment, the length dispensed onto an administration surface is (e.g., a therapeutically effective volume and) about 3 mm. In specific embodiment, the length dispensed onto an administration surface is (e.g., a therapeutically effective volume and) about 5 mm.

[0210] In some embodiments, any method provided herein comprises administering to an individual in need thereof a pharmaceutical composition (e.g., a keratolytic agent, such as SeS2) provided herein. In specific embodiments, the administration of the pharmaceutical composition comprising a keratolytic agent provided herein (e.g., SeS2) occurs monthly, bi-weekly, once- weekly, multiple times a week, daily, or multiple times a day. In some embodiments, the administration of the pharmaceutical composition comprising the keratolytic agent (e.g., SeS2) occurs monthly, bi-weekly, or once-weekly. In some embodiments, the administration of the pharmaceutical composition comprising the keratolytic agent (e.g., SeS2) occurs once-weekly. In specific embodiments, administration is done at least once a week. In more specific embodiment, administration is done at least twice a week. In still more specific embodiments, administration is done at least once a day. In some embodiments, administration is done twice a week. In some embodiments, administration is not more than once daily before bedtime.

[0211] In some embodiments, the individual limits, avoids, or is instructed in a manner such as to limit or avoid exposure to light following administration by administering or being instructed to administer the pharmaceutical composition at a specific time of day. In some embodiments, the specific time of day is later than about an hour before dusk. In some embodiments, the specific time of day is later than about two hours before dusk. In some embodiments, the specific time of day is later than about dusk. In some embodiments, the specific time of day is later than about an hour after dusk. In some embodiments, the specific time of day is later than about two hours after dusk. In some embodiments, the specific time of day is after dusk (nighttime). In some embodiments, the specific time of day is more than about an hour before bedtime. In some embodiments, the specific time of day is less than about an hour before bedtime. In some embodiments, the specific time of day is less than about 30 minutes before bedtime. In some embodiments, administration is performed at night. In specific embodiments, night time administration is a time after 4:00 PM, after 5:00 PM, after 6:00 PM, or the like. In some embodiments, administration is performed twice a week at bedtime. In some embodiments, administration is performed twice a week before bedtime. In some embodiments, administration is performed not more than once daily before bedtime.

[0212] In some embodiments, administration is performed with at least 1 day between instillations. In some embodiments, administration is performed with at least 2 days between instillations. In some embodiments, administration is performed with at least 3 days between instillations.

[0213] In some embodiments, the method reduces adverse events (e.g., application site pain (e.g., burning and / or stinging), keratitis (e.g., superficial punctate keratitis), eye pain, or the like, and / or as indicated by corneal staining or conjunctival staining) and / or the severity thereof. In specificembodiments, the method moderately reduces adverse events (e.g., application site pain (e.g., burning and / or stinging), keratitis (e.g., superficial punctate keratitis), eye pain, or the like, and / or as indicated by corneal staining or conjunctival staining) and / or the severity thereof. In some embodiments, the method significantly reduces adverse events (e.g., application site pain (e.g., burning and / or stinging), keratitis (e.g., superficial punctate keratitis), eye pain, or the like, and / or as indicated by corneal staining or conjunctival staining) and / or the severity thereof. In some embodiments, the method eliminates adverse events.

[0214] In some embodiments, an improvement in opening meibomian glands of the individual is observed after providing the pharmaceutical composition (e.g., keratolytic agent, such as SeS2) to or around an eye of an individual in need thereof. In specific embodiments, a significant improvement in opening meibomian glands of the individual is observed after providing the pharmaceutical composition (e.g., keratolytic agent, such as SeS2) to or around the eye of the individual. In specific embodiments, a moderate improvement in opening meibomian glands of the individual is observed after providing the pharmaceutical composition (e.g., keratolytic agent, such as SeS2) to or around the eye of the individual.

[0215] In some embodiments, an improvement in meibum quality and / or quantity of an individual in need thereof is observed after providing the keratolytic agent (e.g., SeS2) to or around the eye of the individual. In some embodiments, a moderate improvement in meibum quality and / or quantity of the individual is observed after providing the keratolytic agent (e.g., SeS2) to or around the eye of the individual. In some embodiments, a significant improvement in meibum quality and / or quantity of the individual is observed after providing the keratolytic agent (e.g., SeS2) to or around the eye of the individual.

[0216] In some embodiments, an improvement in opening meibomian glands, meibum quality, and / or meibum quantity of an individual in need thereof is observed within about 5 months or less (e.g., 3 months or less or 1.5 months or less) after providing the keratolytic agent (e.g., SeS2) to or around the eye of the individual. In some embodiments, a significant improvement in the initial objective score is observed within about 5 months or less after providing the keratolytic agent (e.g., SeS2) to or around the eye of the individual. In some embodiments, a significant improvement in the initial objective score is observed within about 3 months or less after providing the keratolytic agent (e.g., SeS2) to or around the eye of the individual. In some embodiments, a significant improvement in the initial objective score is observed within about 1.5 months or less after providing the keratolytic agent (e.g., SeS2) to or around the eye of the individual. In some embodiments, a significant improvement in the initial objective score is observed within about 14 days or less after providing the keratolytic agent (e.g., SeS2) to or around the eye of the individual.

[0217] In some embodiments, an individual in need thereof has an improvement in lipid secretion. In some embodiments, the individual has a moderate improvement in lipid secretion. In some embodiments, the individual has a significant improvement in lipid secretion.

[0218] In some embodiments, an individual in need thereof has an improvement in meibomian glands yielding liquid secretion score (MGYLS) (e.g., compared to baseline and / or vehicle). In some embodiments, the individual has an improvement in MGYLS of three or more (e.g., five or more). In some embodiments, the individual has an improvement in MGYLS five months or less (e.g., three months) after receiving the keratolytic agent (e.g., SeS2).

[0219] In some embodiments, an individual in need thereof has an improvement in total ocular surface disease index (OSDI) score (e.g., compared to baseline and / or vehicle). In some embodiments, the individual has an improvement in total OSDI of fifteen or less (e.g., thirteen or less). In some embodiments, the individual has an improvement in total OSDI five months or less (e.g., three months) after receiving the keratolytic agent (e.g., selenium sulfide).

[0220] In some embodiments, an individual in need thereof has an improvement in standard patient evaluation of eye dryness (SPEED) (e.g., compared to baseline and / or vehicle). In some embodiments, the individual has an improvement from baseline and / or vehicle in SPEED five months or less (e.g., three months) after receiving the keratolytic agent (e.g., SeS2).

[0221] In some embodiments, an individual in need thereof has an improvement in average visual analogue scale (VAS) (e.g., compared to baseline and / or vehicle). In some embodiments, the individual has an improvement VAS five months or less (e.g., three months) after receiving the keratolytic agent (e.g., SeS2). In some embodiments, the individual has a significant improvement in eye dryness VAS within three months or less (e.g., 1.5 months) of receiving the keratolytic agent (e.g., SeS2). In some embodiments, the individual has a significant improvement in itching VAS within five months or less (e.g., three months) of receiving the keratolytic agent (e.g., SeS2).

[0222] In some embodiments, an individual in need thereof has an improvement in meibomian gland score (MGS) (e.g., compared to baseline and / or vehicle). In some embodiments, the individual has an improvement in MGS from baseline and / or vehicle of ten or more (e.g., twelve or more). In some embodiments, the individual has an improvement in MGS from baseline and / or vehicle five months or less (e.g., three months) after receiving the keratolytic agent (e.g., SeS2).

[0223] In some embodiments, an individual in need thereof has an improvement in tear breakup time (TBUT) (e.g., compared to baseline and / or vehicle). In some embodiments, the individual has an improvement in TBUT from baseline and / or vehicle of eight or more (e.g., ten or more). In some embodiments, the individual has an improvement in TBUT from baseline and / or vehicle five months or less (e.g., three months) after receiving the keratolytic agent (e.g., SeS2).

[0224] In some embodiments, an individual in need thereof has an improvement in TBUT and total OSDI (from baseline and / or vehicle) about three months after receiving the keratolytic agent (e.g., SeS2). In some embodiments, the individual has a moderate improvement in TBUT and total OSDI (from baseline and / or vehicle) about three months after receiving the keratolytic agent (e.g., SeS2). In some embodiments, the individual has a significant improvement in TBUT and total OSDI (from baseline and / or vehicle) about three months after receiving the keratolytic agent (e.g., SeS2).

[0225] In some embodiments, an individual in need thereof has an improvement in a symptom or symptom score improves after spreading and administering the pharmaceutical composition provided herein. In some embodiments, the individual has a moderate improvement in a symptom or symptom score improves after spreading and administering the pharmaceutical composition provided herein. In some embodiments, the individual has a significant improvement in a symptom or symptom score improves after spreading and administering the pharmaceutical composition provided herein.

[0226] In some embodiments, the symptom score is determined by a (average) visual analogue scale (VAS) (e.g., pain VAS, photophobia VAS, buming / stinging VAS, itching VAS, foreign body VAS, or eye discomfort VAS), SPEED, contact lens dry eye questionnaire-8 (CLDQ8), or any sub scales of any such symptom questionnaire.

[0227] In some embodiments, the symptom (being evaluated) is eye dryness, pain, photophobia, burning, stinging, itching, grittiness (e.g., feeling like a foreign body is in the eye), or eye discomfort.

[0228] In some embodiments, the pharmaceutical composition is administered to the lower eyelid margin of the affected eye(s) twice a week at bedtime. In some embodiments, there is at least 1 day between instillations.

[0229] In some embodiments, the pharmaceutical composition is administered to the lower eyelid margin of the affected eye(s) twice a week before bedtime. In some embodiments, there is at least 1 day between instillations.

[0230] In some embodiments, the recommended dose of the pharmaceutical composition is one ribbon of ointment (approximately 5 mg or 3 mm long) to the lower eyelid margin of the affected eye(s) in the evening just before bedtime. In some embodiments, the pharmaceutical composition is applied twice a week using a washed index finger allowing at least 1 day between instillations. In some embodiments, a dosing aid is used with the tube storing the pharmaceutical composition to visualize the amount of ointment applied.

[0231] In some embodiments, the recommended dose of the pharmaceutical composition is one ribbon of ointment (approximately 5 mg or 3 mm long) to the lower eyelid margin of the affectedeye(s) in the evening just before bedtime. In some embodiments, the pharmaceutical composition is applied twice a week using a washed index finger fingertip allowing at least 1 day between instillations. In some embodiments, a dosing aid is used with the tube storing the pharmaceutical composition to visualize the amount of ointment applied.

[0232] In some embodiments, the recommended dose of the pharmaceutical composition is one ribbon of ointment (approximately 5 mg or 3 mm long) to the lower eyelid margin of the affected eye(s) in the evening just before bedtime. In some embodiments, the pharmaceutical composition is applied twice a week using a washed index finger allowing at least 1 day between instillations. In some embodiments, the individual blinks several times to transfer a portion of the pharmaceutical composition from the lower eyelid to the upper eyelid. In some embodiments, a dosing aid is used with the tube storing the pharmaceutical composition to visualize the amount of ointment applied. In some embodiments, the dosage of the pharmaceutical composition should not exceed once daily just before bedtime. It has been shown that administration of drug in excess of this amount or in the daytime may increase the incidence to local tolerability findings and result in paradoxical reductions in efficacy findings. In some embodiments, contact lenses are removed prior to the administration of the pharmaceutical composition and may be reinserted 15 minutes following administration.

[0233] In some embodiments, the recommended dose of the pharmaceutical composition is one ribbon of ointment (approximately 5 mg or 3 mm long) to the lower eyelid margin of the affected eye(s) in the evening just before bedtime. In some embodiments, the pharmaceutical composition is applied twice a week using a washed index finger fingertip allowing at least 1 day between instillations. In some embodiments, the individual blinks several times to transfer a portion of the pharmaceutical composition from the lower eyelid to the upper eyelid. In some embodiments, a dosing aid is used with the tube storing the pharmaceutical composition to visualize the amount of ointment applied. In some embodiments, the dosage of the pharmaceutical composition should not exceed once daily just before bedtime. It has been shown that administration of drug in excess of this amount or in the daytime may increase the incidence to local tolerability findings and result in paradoxical reductions in efficacy findings. In some embodiments, contact lenses are removed prior to the administration of the pharmaceutical composition and may be reinserted 15 minutes following administration.

[0234] In some embodiments, the pharmaceutical composition is dispensed from the tube using the snap-on visual guide to provide a visual cue for the appropriate length of product to dispense. In some embodiments, the individual uses an index finger to pick up the ointment strip. In some embodiments, the individual spreads the pharmaceutical composition evenly on the forefinger by rubbing the thumb on the forefinger. In some embodiments, the individual uses the other hand topull the lower lid away from the eye and spreads the ointment over the lower eyelid margin of the affected eye, going over the lower eyelid margin a few times to ensure complete coverage. In some embodiments, the individual repeats the process to apply the product to the other eye. In some embodiments, the individual administers the product to each eye twice a week at bedtime. In some embodiments, there is at least 1 day between instillations. In some embodiments, contact lenses are removed prior to the administration of the pharmaceutical composition and may be reinserted 15 minutes following administration.

[0235] In some embodiments, the pharmaceutical composition is dispensed from the tube using the snap-on visual guide to provide a visual cue for the appropriate length of product to dispense. In some embodiments, the individual uses an index finger to pick up the ointment strip. In some embodiments, the individual spreads the pharmaceutical composition evenly on the forefinger fingertip by rubbing the thumb fingertip on the forefinger fingertip. In some embodiments, the individual uses the other hand to pull the lower lid away from the eye and spreads the ointment over the lower eyelid margin of the affected eye, going over the lower eyelid margin a few times to ensure complete coverage. In some embodiments, the individual repeats the process to apply the product to the other eye. In some embodiments, the individual administers the product to each eye twice a week at bedtime. In some embodiments, there is at least 1 day between instillations. In some embodiments, contact lenses are removed prior to the administration of the pharmaceutical composition and may be reinserted 15 minutes following administration. While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.EXAMPLESExample 1: Spreading Compound 1 (SeSi 1.0 wt%) to create a thin layer of the compound on the finger prior to administering the compound to the ocular and / or periocular surface of patients resulted in substantial improvements in ocular disease.Method

[0236] Study treatment consisted of Compound 1 (SeS2 1.0 wt%) using the method provided herein was conducted for 3 months. Patients with ocular disease were asked to spread Compound 1 using their washed index finger and thumb to create a thin layer of Compound 1 on their index finger prior to administering to the study eye (e.g., the eye receiving the drug) with the same indexfinger twice weekly, such as immediately before sleep and on the lower eyelids of the study eye. Subsequent blinking transferred drug to the upper eyelid. Study visits occurred at screening (Visit 1, Day -14), baseline (Visit 2, Day 0), Day 14 (Visit 3), Month 1.5 (Visit 4), and Month 3 (Visit 5, primary endpoint). Patients were provided with a dispensing aid and trained on appropriate dispensing and application at the baseline visit to ensure consistent dosing between individuals and between applications.

[0237] Sodium fluorescein corneal staining (Oxford scale) and meibomian gland (MGD) evaluation were assessed at all study visits. Meibomian gland evaluations were performed by the same investigator for all visits by a patient. The signs of MGD were measured by the number of meibomian glands yielding liquid secretion (MGYLS) and MGS scores; the symptoms of MGD were assessed using the Ocular Surface Disease Index (OSDI), and Standard Patient Evaluation of Eye Dryness (SPEED).

[0238] The Oxford grading scale divides corneal staining into six groups according to severity from 0 (absent) to 5 (severe). The same investigator compares the overall appearance of the patient's corneal staining with a reference figure, simulating the pattern of staining encountered in an ocular disease. The same investigator selects the appropriate grade that best represents the state of corneal staining intuitionally.

[0239] The signs of MGD were assessed by the number of open meibomian glands (i.e., MGYLS score) and quality of meibum (i.e., MGS score). The number of MGYLS is based on a technique for meibomian gland expression, where secretion in the lower eyelid of each eye was measured for five consecutive glands in each of three regions (temporal, central, and nasal). Expression was performed using a Meibomian Gland Evaluator on the 15 glands individually, with a binary score of 0 (none observed) or 1 (liquid observed) recorded following expression. The MGYLS is scored from 0-15, where lower scores indicate more severe disease. For the study, a MGYLS responder is someone who has an increase of >5 MGLYS from baseline, which lies between a score consistent with symptomatic disease (<4 responding glands) and non-symptomatic disease (>6 responding glands).

[0240] The MGS is based on visual evidence of meibum quality. Using the same methodology as MGYLS assessment, secretion in the lower eyelid of each eye is measured on a total score scale of 0-45 per eye for which lower scores indicate more severe disease. Each gland is scored using a four-point scale where 0=no secretion, l=inspissated / toothpaste consistency, 2=cloudy liquid secretion, and 3=clear liquid secretion. For the study, a MGS responder is someone who has a MGS score >12, indicating normal meibum quality.

[0241] The impacts of MGD were evaluated by symptoms (OSDI and SPEED). The OSDI questionnaire comprises 12 questions regarding ocular symptoms, environmental triggers, andvi si on-related functioning. The OSDI total score ranges 0-100, with higher scores representing greater disability; scores <13 represent normal, 13 to <23 represent mild, 23-33 represent moderate, and >33 represent severe dry eye disease. For the study, a OSDI responder is someone who has an OSDI total score <13, which is considered normal or asymptomatic for dry eye disease.

[0242] The SPEED total score is calculated based on occurrence, frequency, and severity of the four symptoms of eye dryness — grittiness or scratchiness, soreness or irritation, burning or watering, and eye fatigue — with the individual recording the time / occurrence of symptoms (at this visit, within past 72 hours, or within past 3 months). Derived from the frequency and severity scores across the four symptoms, SPEED total score ranges 0-28, with higher scores indicate increasing severity. For the study, scores from 0-4 are classified as ‘mild’ disease, 5-7 as ‘moderate’ disease, and >8 as ‘severe’ disease.Results

[0243] No serious adverse event related to treatment was observed. Most patients exhibited a substantial improvement in total OSDI, SPEED, MGS, MGYLS by month 3 (Data not shown). One patient exited the study by day 14 after total OSDI, MGS, and MGYLS was improved.

[0244] Superficial punctate keratitis adverse event was observed in two patients as described below related to improper spreading prior to administering Compound 1 to the ocular or periocular surface.

[0245] One patient exhibited minimal ocular surface staining (Oxford scale =1) in both eyes at baseline (day 0) and increased ocular surface staining (Oxford scale =3) in the right eye at day 14 (FIG. 1). This asymmetrical increase in Oxford staining noted at day 14 was also associated with a slight increase (worsening) in total OSDI and SPEED (FIG. 4). It was found that the patient did not properly spread and / or soften Compound 1 prior to administration before the day 14 visit. Instead, the patient applied Compound 1 directly into the eye before it melt and became a thin layer on the index finger. After patient was retained for training on how to spread Compound 1 prior to administration, total OSDI, SPEED, MGS, and MGYLS scoring were substantially improved in months 1.5 and 3 (FIG. 2, FIG. 3, and FIG. 4). These results suggest without spreading Compound 1 prior to administering to the ocular or periocular area of the patient can lead to detrimental results. However, when the pharmaceutical composition is spread properly (as described herein) prior to administering to the ocular or periocular area of the patients, improved efficacy and / or tolerability can be observed.

[0246] The other patient exhibited minimal ocular surface staining (Oxford scale =1) in the left eye and no staining in the right eye at baseline (day 0) and increased ocular surface staining (Oxford scale =3) in both eyes at day 14 (FIG. 5). This patient also did not properly spread and / or soften Compound 1 prior to administration before the day 14 visit. After patient was retained fortraining on how to spread Compound 1 prior to administration, total OSDI, SPEED, MGS, and MGYLS scoring were substantially improved in months 1.5 and 3 (FIG. 6, FIG. 7, and FIG. 8). Although the ocular surface staining remained moderate in month 1.5, the staining became mild by month 3.Example 2: Evaluation of effective and well tolerated amount of pharmaceutical composition administered to the eyelid margin.

[0247] Following determination of certain exemplary effective administration techniques (e.g., dispensing a controlled amount of a composition provided herein onto a finger, rubbing the composition between fingers, and administering an effective amount to the eyelid margin), amounts of effective and well-tolerated pharmaceutical compositions administered were evaluated using such techniques. Experimental designs included the following steps: a. after wearing a glove, a standard dose of 4 mg (5 pL) SeS2 was dispensed over a gloved finger; b. the ointment was spread between the dosing finger and the thumb, forming a thin layer of ointment over the dosing finger; c. the dosing finger and the thumb of the gloves were cut and weighed using an analytical scale; d. the gloves fingers were worn again, and the compound was applied over the lower eyelid margins using the effective administration techniques described herein; e. the gloves fingers were weighed again using the analytical scale; f. the weight difference between the pre and post application was calculated; and g. the process was repeated.

[0248] Below is the calculated amount of the applied ointment:Amount of Ointment over the eyelid

[0249] Based on the instant determination of effective and well tolerated amounts of composition administered, other suitable techniques and devices can be used to deliver a comparable amount of the composition to the eyelid margin of an individual treated according to a method described herein.

Claims

CLAIMSWe claim:

1. A method for treating a disease or disorder in or around the eye in an individual in need thereof, the method comprising: providing a pharmaceutical composition comprising about 0.1 wt. % to about 10 wt. % (e.g., about 0.5 wt. % to about 5 wt. %) of selenium disulfide, administering about 2 pL or less (e.g., about 0.2 pL to about 2 pL) of the pharmaceutical composition to an eyelid of the individual.

2. A method for treating a disease or disorder in or around the eye in an individual in need thereof, the method comprising: providing a pharmaceutical composition comprising about 0.1 wt. % to about 10 wt. % (e.g., about 0.5 wt. % to about 5 wt. %) of selenium disulfide, administering about 1.6 mg or less (e.g., about 0.2 mg to about 1.6 mg) of the pharmaceutical composition to an eyelid of the individual.

3. The method of any one of the preceding claims, further comprising dispensing the pharmaceutical composition from a dispensing device.

4. The method of any one of the preceding claims, further comprising applying the pharmaceutical composition onto a finger of the individual.

5. The method of any one of the preceding claims, further comprising spreading the pharmaceutical composition over at least a portion of a surface of the finger (e.g., forming a thin film).

6. The method of any one of the preceding claims, wherein the pharmaceutical composition is administered to the eyelid using the finger.

7. A method for treating a disease or disorder in or around the eye in an individual in need thereof, the method comprising: dispensing a pharmaceutical composition from a dispensing device, the pharmaceutical composition comprising an effective amount of a keratolytic agent (e.g., selenium disulfide (SeS?)); applying the pharmaceutical composition onto a finger of the individual; spreading the pharmaceutical composition over at least a portion of a surface of the finger (e.g., forming a thin film); and using the finger, administering the pharmaceutical composition to an eyelid of the individual.

8. The method of any one of the preceding claims, wherein the pharmaceutical composition is a semi-solid, wherein the semi-solid is an ointment, a gel, a cream, or a paste.

9. The method of any one of the preceding claims, wherein the pharmaceutical composition is an ointment.

10. The method of any one of the preceding claims, wherein the pharmaceutical composition further comprises an oleaginous base.

11. The method of any one of the preceding claims, wherein the pharmaceutical composition further comprises an anhydrous base.

12. The method of any one of the preceding claims, wherein the pharmaceutical composition further comprises a petrolatum.

13. The method of any one of the preceding claims, wherein the pharmaceutical composition is dispensed in a predetermined amount from the dispensing device.

14. The method of any one of the preceding claims, wherein the pharmaceutical composition is dispensed and applied onto the finger (e.g., fingertip) as a strip.

15. The method of any one of the preceding claims, wherein the pharmaceutical composition is applied onto the finger (e.g., fingertip) as a globule or droplet.

16. The method of any one of the preceding claims, wherein the pharmaceutical composition is spread by increasing the surface area of the (e.g., globule or droplet) pharmaceutical composition on the finger (e.g., fingertip).

17. The method of any one of the preceding claims, wherein the pharmaceutical composition is spread by decreasing the thickness of the (e.g., globule or droplet) pharmaceutical composition on the finger (e.g., fingertip).

18. The method of any one of the preceding claims, wherein the pharmaceutical composition is spread over the finger (e.g., fingertip) using a device (e.g., lip balm, eye liner).

19. The method of any one of the preceding claims, wherein the pharmaceutical composition is spread between two fingers (e.g., fingertips), such as a forefinger and a thumb of the individual.

20. The method of any one of the preceding claims, wherein the pharmaceutical composition is administered to an eyelid of the individual.

21. The method of any one of the preceding claims, wherein the pharmaceutical composition is administered to an upper eyelid of the individual.

22. The method of any one of the preceding claims, wherein the pharmaceutical composition is administered to a lower eyelid of the individual.

23. The method of any one of the preceding claims, wherein the pharmaceutical composition is administered to upper and lower eyelid of the individual.

24. The method of any one of the preceding claims, wherein the pharmaceutical composition is administered to an eyelid of the individual in a manner suitable to deliver the keratolytic agent to an eyelid margin of the individual.

25. The method of any one of the preceding claims, wherein the pharmaceutical composition is administered to an eyelid margin of the individual.

26. The method of any one of the preceding claims, wherein the pharmaceutical composition is administered to a lower eyelid margin of the individual.

27. The method of any one of the preceding claims, wherein the pharmaceutical composition is administered to an upper eyelid margin of the individual.

28. The method of any one of the preceding claims, wherein the individual self-administers the pharmaceutical composition.

29. The method of any one of the preceding claims, wherein spreading the pharmaceutical composition comprises evenly spreading the pharmaceutical composition on the finger (e.g., fingertip), such as to create a thin film of the pharmaceutical composition.

30. The method of any one of the preceding claims, wherein spreading the pharmaceutical composition comprises rubbing the pharmaceutical composition between two fingers (e.g., fingertips) before administering the pharmaceutical composition to the periocular surface (e.g., to create a thin film of the pharmaceutical composition).

31. The method of any one of the preceding claims, wherein the individual rubs the pharmaceutical composition between two fingers (e.g., fingertips, such as a forefinger fingertip and a thumb fingertip) before administering the pharmaceutical composition to the periocular surface.

32. The method of any one of the preceding claims, wherein the individual administers the pharmaceutical composition with a finger (e.g., fingertip, such as a forefinger fingertip or index finger fingertip).

33. The method of any one of the preceding claims, wherein the individual pulls a lower eyelid away from an eye (e.g., eye with disease or disorder) prior to administering the pharmaceutical composition over the lower eyelid margin of the eye.

34. The method of any one of the preceding claims, wherein the individual pulls an upper eyelid away from an eye (e.g., eye with disease or disorder) prior to administering the pharmaceutical composition over the upper eyelid margin of the eye.

35. The method of any one of the preceding claims, wherein the individual pulls both upper and lower eyelids away from an eye (e.g., eye with disease or disorder) prior to administering the pharmaceutical composition over both upper and lower eyelid margin of the eye.

36. The method of claim 33, wherein the individual administers the pharmaceutical composition by going over (e.g., rubbing) the lower eyelid margin (e.g., with the surface of the finger (e.g., fingertip) where the ointment was spread) a few times (e.g., to ensure complete coverage).

37. The method of claim 34, wherein the individual administers the pharmaceutical composition by going over (e.g., rubbing) the upper eyelid margin (e.g., with the surface of the finger (e.g., fingertip) where the ointment was spread) a few times (e.g., to ensure complete coverage).

38. The method of claim 35, wherein the individual administers the pharmaceutical composition by going over (e.g., rubbing) both lower and upper eyelid margins (e.g., with the surface of the finger (e.g., fingertip) where the ointment was spread) a few times (e.g., to ensure complete coverage).

39. The method of any one of the preceding claims, wherein the individual repeats dispensing, spreading, applying, and administering the pharmaceutical composition to the other eye.

40. The method of any one of the preceding claims, wherein the individual wears contact lenses.

41. The method of claim 40, wherein the contact lenses are removed prior to administering the pharmaceutical composition.

42. The method of claim 40, wherein the contact lenses are not removed prior to administering the pharmaceutical composition.

43. The method of claim 35 or 36, wherein the contact lenses are reinserted after administering the pharmaceutical composition.

44. The method of any one of the preceding claims, wherein the pharmaceutical composition is administered at home.

45. The method of any one of the preceding claims, wherein the disease or disorder in or around the eye is meibomian gland dysfunction (MGD), blepharitis, seborrheic blepharitis, Demodex infestation, dry eye disease (DED), dry eye syndrome, hyperkeratosis, dermatitis, keratitis, contact lens discomfort, lid wiper epitheliopathy (LWE), Keratoconjunctivitis Sicca, Sjogren's Syndrome, ocular rosacea, conjunctival ulcerations, sloughing of surface epithelium at the lid margin, conjunctival scarring / deficiency, or keratinization over the lid wiper zone and / or conjunctiva.

46. The method of any one of the preceding claims, wherein the disease or disorder in or around the eye is Blepharitis or Seborrheic Blepharitis.

47. The method of any one of the preceding claims, wherein the disease or disorder in or around the eye is meibomian gland dysfunction (MGD).-SO-48. The method of any one of the preceding claims, wherein the disease or disorder in or around the eye is dry eye syndrome.

49. The method of any one of the preceding claims, wherein the disease or disorder in or around the eye is dry eye disease.

50. The method of any one of the preceding claims, wherein the disease or disorder in or around the eye is keratitis or hyperkeratosis.

51. The method of any one of the preceding claims, wherein the disease or disorder in or around the eye is contact lens discomfort.

52. The method of any one of the preceding claims, wherein the disease or disorder in or around the eye is LWE.

53. The method of any one of the preceding claims, wherein the keratolytic agent is selected from the group consisting of benzoyl peroxide, coal tar, dithranol, salicylic acid, selenium disulfide, alpha-hydroxy acid, urea, lactic acid, boric acid, retinoic acid, sodium thioglycolate, allantoin, zinc pyrithione, zinc L-pyrrolidone carboxylate, seleocysteine, selenomethionine, captopril, zofenopril, tiopronin, penicillamine, L-cysteine, N-acetyl cysteine (NAC), gluthatione, dithiothreitol, thiorphan, cysteamine, bucillamine, dimercaprol, 1,1 -ethanedithiol, dimercaptosuccinic acid, furan-2-ylmethanethiol, omapatrilat, ovothiol A, rentiapril, thiosalicylic acid, tixocortol, mycothiol, coenzyme A, coenzyme B, disulfiram, psammaplin A, dixanthogen, pantethine, fursultiamine, octotiamine, sulbutiamine, prosultiamine, thiram, lipoic acid, lenthionine, ajoene, allicin, gemopatrilat, thioethanol, thiophospholipid, thiocholesterol, 12-mercaptododecanoic acid, 23-(9-mercaptononyl)-3,6,9,12,15,18,21-heptaoxatricosanoic acid, and sulfanegen.

54. The method of any one of the preceding claims, wherein the keratolytic agent is selected from the group consisting of benzoyl peroxide, coal tar, dithranol, salicylic acid, selenium disulfide, N-acetyl cysteine (NAC), bucillamine, captopril, alpha-hydroxy acid, urea, lactic acid, sodium thioglycolate, zinc pyrithione, or zinc L-pyrrolidone carboxylate.

55. The method of any one of the preceding claims, wherein the keratolytic agent is selenium disulfide.

56. The method of any one of the preceding claims, wherein the pharmaceutical composition comprises the keratolytic agent in a therapeutically effective concentration.

57. The method of claim 56, wherein the therapeutically effective concentration of the keratolytic agent is greater than or equal to about 0.1% by weight (wt. %).

58. The method of claim 57, wherein the therapeutically effective concentration of the keratolytic agent is about 0.1 wt. % to about 10 wt. %.

59. The method of claim 58, wherein the therapeutically effective concentration of the keratolytic agent is about 0.1 wt. % to about 2 wt. %.

60. The method of claim 58, wherein the therapeutically effective concentration of the keratolytic agent is about 0.5 wt. % to about 5 wt. %.

61. The method of claim 58, wherein the therapeutically effective concentration of the keratolytic agent is about 0.5 wt. % to about 2 wt. %.

62. The method of claim 58, wherein the therapeutically effective concentration of the keratolytic agent is about 0.5 wt. % to about 1 wt. %.

63. The method of claim 56, wherein the therapeutically effective concentration of the keratolytic agent is less than or equal to about 1 wt. %.

64. The method of claim 56, wherein the therapeutically effective concentration of the keratolytic agent is about 1 wt. %.

65. The method of claim 56, wherein the therapeutically effective concentration of the keratolytic agent is about 0.5 wt. %.

66. The method of any one of the preceding claims, wherein the predetermined amount is 500 pL or less.

67. The method of any one of the preceding claims, wherein the predetermined amount is 100 pL or less.

68. The method of any one of the preceding claims, wherein the predetermined amount is 25 pL or less.

69. The method of any one of the preceding claims, wherein the administered amount of the pharmaceutical composition is about 2 pL or less.

70. The method of any one of the preceding claims, wherein the administered amount of the pharmaceutical composition is about 0.2 pL to about 2 pL.

71. The method of any one of the preceding claims, wherein the administered amount of the pharmaceutical composition is about 1 pL to about 2 pL.

72. The method of any one of the preceding claims, wherein the administered amount of the pharmaceutical composition is about 2 mg or less.

73. The method of any one of the preceding claims, wherein the administered amount of the pharmaceutical composition is about 0.2 mg to about 2 mg.

74. The method of any one of the preceding claims, wherein the administered amount of the pharmaceutical composition is about 0.2 mg to about 1.6 mg.

75. The method of any one of the preceding claims, wherein the administered amount of the pharmaceutical composition is about 0.5 mg to about 1.5 mg.

76. The method of any one of the preceding claims, wherein the method significantly improves compliance of the pharmaceutical composition.

77. The method of any one of the preceding claims, wherein the method significantly reduces adverse events (e.g., application site pain (e.g., burning and / or stinging), keratitis (e.g., superficial punctate keratitis), eye pain, or the like, and / or as indicated by corneal staining or conjunctival staining) and / or the severity thereof.

78. The method of any one of the preceding claims, wherein the method eliminates adverse events.

79. The method of any one of the preceding claims, wherein a (significant) improvement in opening meibomian glands of the individual is observed after providing the keratolytic agent (e.g., selenium sulfide) to or around the eye of the individual.

80. The method of any one of the preceding claims, wherein the method eliminates the need for a specific measured dose of administration onto the finger.

81. The method of any one of the preceding claims, wherein a (significant) improvement in meibum quality and / or quantity of the individual is observed after providing the keratolytic agent (e.g., selenium sulfide) to or around the eye of the individual.

82. The method of any one of the preceding claims, wherein a (significant) improvement in opening meibomian glands, meibum quality, and / or meibum quantity of the individual is observed within about 5 months or less (e.g., 3 months or less or 1.5 months or less) after providing the keratolytic agent (e.g., selenium sulfide) to or around the eye of the individual.

83. The method of any one of the preceding claims, wherein the individual has an improvement in lipid secretion.

84. The method of any one of the preceding claims, wherein the any one or more of the following improves in the individual: meibomian glands yielding liquid secretion score (MGYLS), total ocular surface disease index (OSDI) score, standard patient evaluation of eye dryness (SPEED), meibomian gland score (MGS), and tear breakup time (TBUT).

85. The method of any one of the preceding claims, wherein a symptom or symptom score improves after spreading and administering the pharmaceutical composition.

86. The method of any one of the preceding claims, wherein a symptom score is determined by a (average) visual analogue scale (VAS) (e.g., pain VAS, photophobia VAS, buming / stinging VAS, itching VAS, foreign body VAS, or eye discomfort VAS), SPEED, contact lens dry eye questionnaire-8 (CLDQ8), or any sub scales of any such symptom questionnaire.

87. The method of any one of the preceding claims, wherein the symptom (being evaluated) is eye dryness, pain, photophobia, burning, stinging, itching, grittiness (e.g., feeling like a foreign body is in the eye), or eye discomfort.

88. The method of any one of the preceding claims, wherein the keratolytic agent (e.g., selenium sulfide) is administered to the individual monthly, bi-weekly, or once-weekly.

89. The method of any one of the preceding claims, wherein the keratolytic agent (e.g., selenium sulfide) is administered to the individual once-weekly.

90. The method of any one of the preceding claims, wherein the keratolytic agent (e.g., selenium sulfide) is administered to the individual for at least one month (e.g., one month or more, two months or more, three months or more, five months or more, or six months or more).

91. The method of any one of the preceding claims, wherein the keratolytic agent (e.g., selenium sulfide) is administered to the individual twice a week.

92. The method of any one of the preceding claims, wherein the keratolytic agent (e.g., selenium sulfide) is administered to the individual twice a week at bedtime.

93. The method of any one of the preceding claims, wherein the keratolytic agent (e.g., selenium sulfide) is administered to the individual twice a week before bedtime.

94. The method of any one of the preceding claims, wherein the keratolytic agent (e.g., selenium sulfide) is administered to the individual in the evening before bedtime.

95. The method of any one of the preceding claims, wherein the keratolytic agent (e.g., selenium sulfide) is administered to the individual with at least 1 day between instillations.

96. The method of any one of the preceding claims, wherein the keratolytic agent (e.g., selenium sulfide) is not administered to the individual more than once daily before bedtime.

97. The method of any one of the preceding claims, wherein the individual blinks several times to transfer a portion of the keratolytic agent (e.g., selenium sulfide) from the lower eyelid to the upper eyelid.

98. The method of any one of the preceding claims, wherein the individual blinks several times to transfer a portion of the keratolytic agent (e.g., selenium sulfide) from the upper eyelid to the lower eyelid.

99. A system for use in treating a disease or disorder in or around the eye in an individual in need thereof, the system comprising: a dispensing device;a pharmaceutical composition comprising an effective amount of a keratolytic agent (e.g., selenium disulfide (SeS?)); wherein the dispensing device is configured to dispense a predetermined amount of the pharmaceutical composition from the dispensing device, and wherein treating the disease or disorder comprises applying the pharmaceutical composition onto a finger of the individual; spreading the pharmaceutical composition over at least a portion of a surface of the finger (e.g., forming a thin film); and using the finger, administering the pharmaceutical composition to an eyelid of the individual.

100. The system of claim 99, wherein treating the disease or disorder comprises using the steps of any of claims 7-98.

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