the terms “ about ”, “ approximate ” and “ approximately ” are used herein to modify a numerical value and indicate a defined range around that value . if “ x ” were the value , “ about x ” or “ approximately equal to x ” would generally indicate a value from 0 . 90x to 1 . 10x . any reference to “ about x ” minimally indicates at least the values x , 0 . 90x , 0 . 91x , 0 . 92x , 0 . 93x , 0 . 94x , 0 . 95x , 0 . 96x , 0 . 97x , 0 . 98x , 0 . 99x , 1 . 01x , 1 . 02x , 1 . 03x , 1 . 04x , 1 . 05x , 1 . 06x , 1 . 07x , 1 . 08x , 1 . 09x , and 1 . 10x . thus , “ about x ” is intended to disclose , e . g ., “ 0 . 98x .” when “ about ” is applied to the beginning of a numerical range , it applies to both ends of the range . thus , “ from about 6 to 8 . 5 ” is equivalent to “ from about 6 to about 8 . 5 .” when “ about ” is applied to the first value of a set of values , it applies to all values in that set . thus , “ about 7 , 9 , or 11 %” is equivalent to “ about 7 %, about 9 %, or about 11 %.” about may also refer to a number close to the cited number that would result in a bioequivalent therapeutic effect by a regulatory agency such as the fda or the emea . the terms “ active ”, “ active agent ”, “ active pharmaceutical ingredient ”, “ api ” and “ drug ” refer to the active ingredient of a composition . an api is typically a chemical substance or mixture of chemical substances . such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis , cure , mitigation , treatment or prevention of disease of the eye . the term “ daily ” means every day and may refer to once a day or multiple times a day such as bid or tid dosing . the terms “ effective amount ,” “ therapeutically effective amount ” or “ pharmaceutically effective amount ” refer to an amount of an active agent effective to treat ocular pain or ocular discomfort or other ophthalmic diseases , including a range of effects , from a detectable amount of improvement to substantial relief / improvement of symptoms or a cure of the disease or condition . the result can be reduction and / or alleviation of the signs , symptoms , or causes of a disease , or any other desired alteration of a biological system . for example , an “ effective amount ” for therapeutic uses is the amount of the composition comprising an agent as set forth herein required to provide a clinically significant decrease in an ophthalmic disease . for example , for the given aspect ( e . g ., length of incidence ), a therapeutically effective amount will show an increase or decrease of at least 5 %, 10 %, 15 %, 20 %, 25 %, 40 %, 50 %, 60 %, 75 %, 80 %, 90 %, or 100 %. therapeutic efficacy can also be expressed as “- fold ” increase or decrease . for example , a therapeutically effective amount can have at least a 1 . 2 - fold , 1 . 5 - fold , 2 - fold , 5 - fold , or more effect over a control . an appropriate “ effective ” amount in any individual case may be determined using techniques , such as a dose escalation study . “ emulsion ” means , but is not limited to , an oil - in - water emulsion , a water - in - oil emulsion , a micro emulsion referring to particle sizes of 10 − 9 . “ formulation ” and “ composition ,” are intended to be equivalent and refer to a composition of matter suitable for pharmaceutical use ( i . e ., producing a therapeutic effect as well as possessing acceptable pharmacokinetic and toxicological properties ). “ mechanoreceptors ” a sense organ or cell that responds to mechanical stimuli such as touch or sound . “ polymodal nociceptors ”: a receptor that responds to several different forms of sensory stimulation ( as heat , touch , and chemicals ) “ ocular pain ” is an unpleasant intolerable sensation located to the globe and eye socket “ ocular surface ” is the cornea and sclera and its associated bulbar conjunctiva “ ocular surface injury ” refers to damage to the corneal surface caused by physical injury or disease . “ ophthalmic acceptable composition ” is a composition that can be administered to the eye . “ pharmaceutically acceptable ” is used as equivalent to physiologically acceptable . in certain embodiments , a pharmaceutically acceptable composition or preparation will include agents for buffering and preservation in storage , and can include buffers and carriers for appropriate delivery , depending on the route of administration . the terms “ subject ,” “ patient ,” “ individual ,” are not intended to be limiting and can be generally interchanged . that is , an individual described as a “ patient ” does not necessarily have a given disease , but may be merely seeking medical advice . the term “ subject ” as used herein includes all members of the animal kingdom prone to suffering from the indicated disorder . in some aspects , the subject is a mammal , and in some aspects , the subject is a human . “ significant reduction in ocular pain ” a statistically significant reduction according to student &# 39 ; s non - paired t test . “ thermoreceptors ” are sensory receptors , usually a nerve ending in the skin that is stimulated by heat or cold . “ treating ” or “ treatment ” as used herein includes any approach for obtaining beneficial or desired results in a subject &# 39 ; s condition , including clinical results . beneficial or desired clinical results can include , but are not limited to , alleviation or amelioration of one or more symptoms or conditions , diminishment of the extent of a disease or treatment of ocular pain or ocular discomfort , stabilizing ( i . e ., not worsening ) the state of disease , delay or slowing of disease progression , amelioration , diminishment of the reoccurrence of disease . treatment may prevent the disease from occurring ; relieve the disease &# 39 ; s symptoms , fully or partially remove the disease &# 39 ; s underlying cause , shorten a disease &# 39 ; s duration , or do a combination of the above . “ treating ” and “ treatment ” as used herein may also include prophylactic treatment . treatment methods include administering to a subject a therapeutically effective amount of an active agent . the administering step may consist of a single administration or may include a series of administrations . the length of the treatment period depends on a variety of factors , such as the severity of the condition , the age of the patient , the concentration of active agent , the activity of the compositions used in the treatment , or a combination thereof . it will also be appreciated that the effective dosage of an agent used for the treatment or prophylaxis may increase or decrease over the course of a particular treatment or prophylaxis regime . changes in dosage may result and become apparent by standard diagnostic assays known in the art . in some instances , chronic administration may be required . for example , the compositions are administered to the subject in an amount and for duration sufficient to treat the patient . as used herein , “ topical ”, “ topical application ,” “ topical administration ,” and “ topically administering ” are used interchangeably herein and include the administration to the front of the eye of a subject . topical application or administering may result in the delivery of an active agent to the eye . “ topical formulation ” and “ topical pharmaceutical composition ” are used interchangeably herein and include a formulation that is suitable for topical application to the eye . a topical formulation may , for example , be used to confer a therapeutic benefit to its user . as used herein , the phrase “ pharmaceutically acceptable salts ” refers to salts of the active compound ( s ) which possess the same pharmacological activity as the active compound ( s ) and which are neither biologically nor otherwise undesirable . a salt can be formed with , for example , organic or inorganic acids . non - limiting examples of suitable acids include acetic acid , acetylsalicylic acid , adipic acid , alginic acid , ascorbic acid , aspartic acid , benzoic acid , benzenesulfonic acid , bisulfic acid , boric acid , butyric acid , camphoric acid , camphorsulfonic acid , carbonic acid , citric acid , cyclopentanepropionic acid , digluconic acid , dodecylsulfic acid , ethanesulfonic acid , formic acid , fumaric acid , glyceric acid , glycerophosphoric acid , glycine , glucoheptanoic acid , gluconic acid , glutamic acid , glutaric acid , glycolic acid , hemisulfic acid , heptanoic acid , hexanoic acid , hippuric acid , hydrobromic acid , hydrochloric acid , hydroiodic acid , hydroxyethanesulfonic acid , lactic acid , maleic acid , malic acid , malonic acid , mandelic acid , methanesulfonic acid , mucic acid , naphthylanesulfonic acid , naphthylic acid , nicotinic acid , nitrous acid , oxalic acid , pelargonic , phosphoric acid , propionic acid , saccharin , salicylic acid , sorbic acid , succinic acid , sulfuric acid , tartaric acid , thiocyanic acid , thioglycolic acid , thiosulfuric acid , tosylic acid , undecylenic acid , naturally and synthetically derived amino acids . non - limiting examples of base salts include ammonium salts ; alkali metal salts , such as sodium and potassium salts ; alkaline earth metal salts , such as calcium and magnesium salts ; salts with organic bases , such as dicyclohexylamine salts ; methyl - d - glucamine ; and salts with amino acids , such as arginine , lysine , and so forth . also , the basic nitrogen - containing groups can be quaternized with such agents as lower alkyl halides , such as methyl , ethyl , propyl , and butyl chlorides , bromides , and iodides ; dialkyl sulfates , such as dimethyl , diethyl , dibutyl , and diamyl sulfates ; long chain halides , such as decyl , lauryl , myristyl , and stearyl chlorides , bromides , and iodides ; asthma halides , such as benzyl and phenethyl bromides ; and others . the compositions can be administered prior to , concurrently with , and / or after the development of ocular discomfort or ocular pain or any other eye disease or condition . the compositions may be administered for a period of time necessary to achieve the desired results , which may be several days to several months or continuously . the compositions can be administered once or several times ( 2 , 3 , 4 , or more times ) a day depending on the desired effect . in certain embodiments , the compositions can be administered every 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 and 30 days or until the ocular pain or discomfort disappears . in another embodiment , the compositions can be administered one or more times every 1 , 2 , 3 or 4 weeks . the administration can be on an occasional basis such as monthly or bi - monthly basis or when needed by the patient . further , the compositions can be administered for 1 , 2 , 3 , 6 , 9 or 12 months or continuously . in certain embodiments , the compositions can be administered on an ongoing basis to maintain a desired result . the compositions can be administered once a day , twice a day , three times a day and up to four times a day . the compounds and compositions described herein may be administered at least in the minimum dose necessary to achieve the desired therapeutic effect . generally , such doses may be in the range of 50 - 100 μl / clay or per dosing or about 0 . 005 mg / day to about 1 mg / day . in another example embodiment , the compound or active agents may be present in a composition or formulation in a range of about 50 - 1000 μl / week or 0 . 005 - 10 mg / week . however , the actual amount of the compound to be administered in any given case will be determined by a physician taking into account the relevant circumstances , such as the age and weight of a patient , patient &# 39 ; s general physical condition , severity of the ocular pain or other eye condition or disease . in some instances , dosing is evaluated on a case - by - case basis . the ph of the disclosed compositions can be about 3 to about 8 . 0 , or about 6 . 5 to about 7 . 5 . in certain embodiments , the ph of the formulation is about 7 . 0 to about 7 . 4 or about 7 . 1 to about 7 . 3 . additionally , compositions may be designed to delay release of the compound over a given period of time such as in an ocular implant , or to carefully control the amount of compound released at a given time during the course of treatment . table 1 lists possible aqueous vehicle formulations in the form of solutions of 4 , 5 - dihydro - n -[ 4 -[[ 4 -( 1 - methylethoxy ) phenyl ] methyl ] phenyl ]- 1h - imadazol - 2 - amine but it is intended that any drug referenced in the specification or any prostanoid ip receptor antagonist may be included (“ active agent ”). table ii lists possible compositions of creams and gels for ocular administration . table ii lists possible vehicle compositions in the form of creams or gels of 4 , 5 - dihydro - n -[ 4 -[[ 4 -( 1 - methylethoxy ) phenyl ] methyl ] phenyl ]- 1h - imadazol - 2 - amine but it is intended that any drug referenced in the specification of any prostanoid ip receptor antagonist may be included (“ active agent ”): preservatives of the vehicles of tables 1 and 2 and in compositions throughout the application may be substituted with the following preservatives expressed in % w / v or % w / w : na - borate / boric acid 1 . 5 %- 1 . 9 %; polyhexamthethylene biguanide ( phmb ) from 0 . 0001 %- 0 . 02 %; parabens ( parahydroxy benzoic acid derivatives ; phenyl mercuric nitrate ; benzalkonium chloride 0 . 004 %- 0 . 02 % benzelthonium chloride up to 0 . 01 % chlorhexidine 0 . 005 % to 0 . 01 % chlorbutanol up to 0 . 5 % methyl paraben 0 . 03 - 0 . 1 % phenylethyl alcohol up to 0 . 5 % phenylmercuric acetate 0 . 002 - 0 . 004 % phenylmercuric nitrate 0 . 002 - 0 . 004 % propyl paraben up to 0 . 01 % thimerosol up to 0 . 01 % the active agent , which may be any drug referenced in the specification , may be present in the following concentrations from a percent w / v or w / w of about 0 . 01 to about 0 . 15 , from about 0 . 02 to about 0 . 15 , from about 0 . 03 to about 0 . 15 , from about 0 . 04 to about 0 . 15 , from about 0 . 05 to about 0 . 15 , from about 0 . 06 to about 0 . 15 , from about 0 . 07 to about 0 . 15 , from about 0 . 08 to about 0 . 15 , from about 0 . 09 to about 0 . 15 , from about 0 . 1 to about 0 . 15 , from about 0 . 11 to about 0 . 15 , from about 0 . 115 to about 0 . 15 , from about 0 . 120 to about 0 . 15 , and from about 0 . 125 to about 0 . 15 , from about 0 . 125 to about 0 . 145 , from about 0 . 125 to about 0 . 14 , from about 0 . 02 to about 0 . 08 , from about 0 . 03 to about 0 . 08 , from about 0 . 04 to about 0 . 08 , from about 0 . 05 to about 0 . 08 , from about 0 . 06 to about 0 . 08 , from about 0 . 07 to about 0 . 08 , from about 0 . 02 to about 0 . 07 , from about 0 . 03 to about 0 . 07 , from about 0 . 04 to about 0 . 07 , from about 0 . 05 to about 0 . 07 , from about 0 . 06 to about 0 . 07 , from about 0 . 02 to about 0 . 06 , from about 0 . 03 to about 0 . 06 , from about 0 . 04 to about 0 . 06 , from about 0 . 05 to about 0 . 06 , from about 0 . 02 to about 0 . 05 , from about 0 . 03 to about 0 . 05 , from about 0 . 04 to about 0 . 05 , from about 0 . 02 to about 0 . 04 , from about 0 . 03 to about 0 . 04 , or from about 0 . 02 to about 0 . 03 %. in other embodiments , the active agent may be present at about 0 . 01 , 0 . 02 , 0 . 03 , 0 . 04 , 0 . 05 , 0 . 06 , 0 . 07 , 0 . 08 , 0 . 09 , or 0 . 1 , 0 . 11 , 0 . 12 , 0 . 121 , 0 . 122 , 0 . 125 , 0 . 13 , 0 . 135 , 0 . 140 , 0 . 145 , 0 . 150 , 0 . 155 , 0 . 160 , 0 . 165 , 0 . 170 , 0 . 175 , 0 . 180 , 0 . 185 , 0 . 190 , 0 . 195 , 0 . 2 , 0 . 25 , 0 . 30 , 0 . 35 , 0 . 4 , 0 . 45 , 0 . 5 , 0 . 55 , 0 . 6 , 0 . 65 , 0 . 7 , 0 . 75 , 0 . 8 , 0 . 85 , 0 . 9 , 0 . 95 , 1 . 0 , 1 . 5 , 2 . 0 , 2 . 5 , 3 . 0 , 3 . 5 , 4 . 0 , 4 . 5 , 5 . 0 , 5 . 5 , 6 . 0 , 6 . 5 , 7 . 0 , 7 . 5 , 8 . 0 , 8 . 5 , 9 . 0 , 9 . 5 and 10 . 0 (% w / v ) or (% w / w ). a prostanoid ip receptor antagonist ( 4 , 5 - dihydro - n -[ 4 -[[ 4 -( 1 - methylethoxy ) phenyl ] methyl ] phenyl ]- 1h - imadazol - 2 - amine ro - 1138452 , cay 10441 ), at a dose of 0 . 3 % w / v in an aqueous 1 % polysorbate 80 in tris - hcl ( a standard ocular vehicle used in testing of ophthalmic drugs ), was administered topically to the ocular surface of twelve cynomolgus monkeys . cynomologus monkeys are the closest animal model for humans . a model that replicates an actual clinically encountered ocular condition , namely corneal abrasion , was employed . as an animal model indicative of both ocular discomfort and pain , mild corneal scarification and measurement of the resultant increased blinking ( nictation ) rate was employed . the species chosen was the cynomologous monkey and here are reasons for this selection . the cynomologus monkeys have similar vision to humans , its eye is structurally similar to humans , and it is the closest species phylogenetically to man . although superior to common laboratory animal species for ocular nociceptive studies , the monkey has the disadvantage of being incapable of communicating perceived ocular sensations and it is necessary to rely on behaviors indicative of pain , irritation , and discomfort . increased rate of blinking ( nictation ) is recognized as a reliable end - point indicative of discomfort and pain and was , therefore , used in the studies described herein . there is a linear correlation between ocular surface sensory - evoked stimulation and blink rate in humans ( wu et al ., 2014 ). increased blinking frequency is associated with a diverse variety of conditions that elicit ocular discomfort and pain such as air borne noxious contaminants ( lang et al ., 2008 ), acidic solutions ( conejo et al , 2015 ), dry eye conditions and wearing contact lenses ( wu et al ., 2014 ). thus , increased blinking rate is a universal indicator of ocular surface nociception resulting in discomfort and pain . the drug formulation was administered post - scarification of the cornea , and at identical time points on two subsequent days . ocular discomfort was monitored as the nictation ( blinking ) rate . blinking is an established human behavioral response to corneal discomfort and irritation ( lang et al ., 2008 ; wu et al ., 2014 ; callejo et al ., 2015 ). in setting up the monkey model of ocular surface discomfort , it was noted that increased blink rate remained part of a greater response to increased scarification width or topical capsaicin , where eye closure / squinting and scleral redness presented as additional symptoms . this degree of nociception was part of preliminary “ sighting ” experiments and was unintended and involved few animals . the detailed and final experimental protocol is provided as follows , with activities on each day detailed . a total of eight naïve cynomolgus monkeys were used . they were divided into two groups of four . the nictation rate ( blinking rate ) was measured to provide quantification of discomfort . the daily study protocol was as follows . the monkeys were not permanently harmed and were treated according to the highest standard of ethics . time 0 hr ( e . g . 8 : 00 am ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . time 10 hr ( e . g . 6 : 00 pm ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . time 0 hr ( e . g . 8 : 00 am ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . time 10 hr ( e . g . 6 : 00 pm ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . time 0 hr ( e . g . 8 : 00 am ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . then scarify the left cornea of each of the 8 monkeys . time 1 hr ( e . g . 9 : 00 am ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . time 2 hr ( e . g . 10 : 00 am ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . time 4 hr ( e . g . 12 : 00 am ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . time 10 hr ( e . g . 6 : 00 pm ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . time 0 hr ( e . g . 8 : 00 am ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . then apply the drug 4 , 5 - dihydro - n -[ 4 -[[ 4 -( 1 - methylethoxy ) phenyl ] methyl ] phenyl ]- 1h - imadazol - 2 - amine ) ( 0 . 3 % w / v ) to the left cornea of each of the 4 monkeys . then apply vehicle to the left cornea of each of the other 4 animals . time 1 hr ( e . g . 9 : 00 am ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . time 2 hr ( e . g . 10 : 00 am ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . time 4 hr ( e . g . 12 : 00 am ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . time 10 hr ( e . g . 6 : 00 pm ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . time 0 hr ( e . g . 8 : 00 am ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . then apply the drug ( 4 , 5 - dihydro - n -[ 4 -[[ 4 -( 1 - methylethoxy ) phenyl ] methyl ] phenyl ]- 1h - imadazol - 2 - amine , 0 . 3 % w / v ) to the left cornea of each of the 4 monkeys . then apply the vehicle to the left cornea of each of the other 4 monkeys . time 1 hr ( e . g . 9 : 00 am ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . time 2 hr ( e . g . 10 : 00 am ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . time 4 hr ( e . g . 12 : 00 am ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . time 10 hr ( e . g . 6 : 00 pm ): measure nictation rate and assess clarity of cornea , lacrimation , and conjunctival congestion . fig1 shows the effect of topically applied ip antagonist drug ( 4 , 5 - dihydro - n -[ 4 -[[ 4 -( 1 - methylethoxy ) phenyl ] methyl ] phenyl ]- 1h - imadazol - 2 - amine ), at a 0 . 3 % w / v concentration , on the discomfort associated with mild corneal abrasion . monkeys that received vehicle are represented by the black line , monkeys that received drug are represented by the gray line . drug and vehicle were given at 8 : 00 am of each experimental day depicted . values are mean % blink rate following drug or vehicle treatment compared to day 4 , 8 : 00 am baseline ( 100 %): n = 4 per group , p & lt ; 0 . 01 comparing vehicle and drug treated groups . the effect of topically applied ip antagonist drug ( 4 , 5 - dihydro - n -[ 4 -[[ 4 -( 1 - methylethoxy ) phenyl ] methyl ] phenyl ]- 1h - imadazol - 2 - amine ), given once daily at a 0 . 3 % w / v concentration , on the discomfort associated with mild corneal abrasion is shown in fig1 . animals that received vehicle showed a clinically significant rate of increase in nictation rate over the two day period , the nictation rate was statistically significantly lower in the drug treated eyes . nictation rate ( blinking ) demonstrates the extent of ocular pain , which is a standard method in showing relief of ocular pain in animals . during days 1 - 3 , there was no difference in terms of handling / treatment in control vs . treated group in day 1 - 3 . during day 1 and day 2 , the pre - surgical blinking baseline was measured in these two days . day 3 was the day of surgery , then wait 24 hours to get the blinking rate stabilize before treatment . comparing to the baseline in day 1 - 2 ( mean = 83 %), there was an increase in blinking rate after the surgery ( data not shown in slide # 1 ) and the post - surgery blinking baseline (= 100 %). the actual study started on day 4 . day 4 at 8 am nictation / blinking rate = 100 %, i . e . the blinking rate at 24 hour after scarification of the cornea is set as 100 %, all blinking rates are normalized to this control point . the ocular scarification was controlled at a degree that it should not cause the animals severe pain and visible inflammation , so the discomfort from the lesion did not last too long . this is why two days after the surgery ( day 5 - 16 : 00 ), the difference in blinking rate is minimal in the control vs . treated group . the results show that the ip antagonist drug ( 4 , 5 - dihydro - n -[ 4 -[[ 4 -( 1 - methylethoxy ) phenyl ] methyl ] phenyl ]- 1h - imadazol - 2 - amine ) significantly reduced ocular surface nociception induced by scarification ( p ≦ 0 . 01 non - paired t - test ) and therefore controls ocular pain . a 55 - year old caucasian male was suffering from extreme ocular discomfort which was associated with pain . the 55 year old caucasian male adds a 0 . 3 % w / v solution of 4 , 5 - dihydro - n -[ 4 -[[ 4 -( 1 - methylethoxy ) phenyl ] methyl ] phenyl ]- 1h - imadazol - 2 - amine and experiences an immediate reduction of ocular pain . the 55 - year old caucasian male continues to add the 0 . 3 % w / v solution twice a day and then all pain is reduced and eventually disappears . a 36 - year old hispanic female suffers a grade 2 chemical eye burn from an acidic substance . despite being administered prednisolone acetate 1 % every two hours , severe ocular pain persists . the physician will administer formula 3 from table i , three times a day . within twelve hours of administration , the patient feels a significant reduction in ocular pain , which leads to less nictation and rubbing of her eyes and faster healing . after 7 - 21 days , the patient experiences corneal / conjunctival epithelium and keratocytes proliferate . collagen synthesis begins . a 41 - year old african american construction worker is struck by debris while working , some of which implants into his cornea and he suffers from a corneal foreign body . unfortunately , the patient does not receive prompt medical attention . the foreign body entered into the anterior chamber of the eye , resulting in slight ocular necrosis , resulting in long - term pain . the patient will be administered formula 5 from table 1 up to 4 times a day for treatment of chronic pain until the patient &# 39 ; s eye is healed . a 78 - year old caucasian female , living in a very dry and arid climate , develops autoimmune positive dry eye needing prompt medical attention . the doctor prescribes composition 3 from table 2 which will be given 4 times daily for treatment of autoimmune dry eye . within a week the autoimmune dry eye symptoms disappear . a 60 - year old hispanic female suffers from aqueous tear deficient dry eye associated occasionally with moderate to severe sharp ocular pain . the doctor prescribes formulation 7 of table 1 twice a day and the dry eye and ocular pain improves immediately and the symptoms disappear completely after 7 days . a 35 - year old caucasian female lives in an arid region and frequently suffers from evaporative dry eye associated with occasional sharp pains that use of artificial tears does not prevent . after being prescribed once a day use of formulation 6 from table i , the 35 year old caucasian patient &# 39 ; s eyes no longer experience sharp pains and the dry eye symptoms improve . a 62 year old asian male has laser in - situ keratomileusis (′ lasik ″) surgery to correct near sightedness and after the surgery suffers from severe ocular pain and dry eye , which are common side effects with lazik surgery . the patient &# 39 ; s ophthalmologist prescribes composition 5 of table 2 tid until the patient &# 39 ; s symptoms improve and then administered bid . an 81 year old caucasian female patient undergoes an operation to remove cataracts . after the surgery the patient experiences intolerable ocular pain . the patient &# 39 ; s ophthalmologist prescribes formulation 8 of table 1 tid until the patient &# 39 ; s ocular pain symptoms improve . a 73 year old caucasian male undergoes conical transplant surgery . after the surgery , the patient experiences severe ocular pain . the patient &# 39 ; s ophthalmologist prescribes formulation 9 bid until the patient &# 39 ; s ocular pain symptoms improve .
the present invention relates generally to the use of compositions and methods for treating nociceptive events that occur on the ocular surface in association with dryness , injury , environmental pollutants , and infectious and non - infectious diseases . specifically , the present invention is directed to the use of certain compounds for treating for treating ocular pain or ocular discomfort .