JP2016222563A - Ophthalmological composition for treating pigmentary degeneration of retina - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition for ophthalmological topical administration for treating pigmentary degeneration of the retina.SOLUTION: A composition for ocular topical administration for treating a patient of human pigmentary degeneration of the retina contains an effective dose of isopropyl unoprostone, and has an MD value of a Humphrey field analyzer 10-2 program is -15 dB or more.SELECTED DRAWING: None

Description

  The present application provides an ophthalmic composition for the treatment of patients with retinitis pigmentosa. More particularly, the present invention provides an ophthalmic composition for the treatment of patients with retinitis pigmentosa that is in metaphase or earlier.

  Retinitis pigmentosa is a group of inherited retinal diseases that cause abnormalities in the retina. Progressive night blindness, afferent visual field stenosis, and vision loss may occur, and severe vision loss or blindness may occur at the end. At present, an effective treatment method for retinitis pigmentosa has not been established.

  When retinal pigment degeneration progresses and the afferent visual field stenosis falls within 30 ° of the central visual field, the number of patients whose visual acuity decreases from 1.0 increases. At this time, most patients do not feel inconvenienced in their daily lives, but if the afferent visual field stenosis progresses to within 10 ° of the central visual field, or if the visual acuity becomes less than 0.5, inconvenience in daily life will occur. The patient who feels increases (nonpatent literature 1).

  The MD value of the Humphrey perimeter 10-2 program is a calculated value that takes into account the amount of deficiency from normal values by age of the same age in the Humphrey perimeter 68 that is large in the center and small in the periphery. It is. This is a value indicating how much the visual function of the central visual field is reduced from the normal value as a whole.

  It has been reported that the MD value of the Humphrey perimeter 10-2 program correlates well with the degree of progression of retinal pigment degeneration. Also, this value often decreases almost linearly with age in patients with retinitis pigmentosa, and the degree of progression of retinitis pigmentosa can be predicted to some extent based on the MD value of the Humphrey perimeter 10-2 program. It is.

  As a result of analyzing the course of visual function in patients with retinitis pigmentosa, it has been reported that the MD state of the Humphrey perimeter 10-2 program differs from -15 dB.

  In retinitis pigmentosa, it is common that relatively good central vision is preserved until the field of view is considerably narrowed, but as a field of view that can maintain a vision of 0.5 that does not interfere with daily life, The MD value of the Humphrey perimeter 10-2 program is set to -15 dB or more (Non-patent Documents 2-4).

  In recent years, detailed evaluation of the retinal structure has become possible by optical coherence tomography (OCT). The photoreceptor inscribed and circumscribed junction (IS / OS) line length depicted by OCT is used as an indicator of photoreceptor retention. The longer the IS / OS line length, the more retained the photoreceptor cells. When the IS / OS line length is 0 mm, the photoreceptor cells are almost dead.

  Prostones include intraocular pressure-lowering agents and glaucoma therapeutic agents (Patent Literatures 1-5), cataract treatment agents (Patent Literatures 6 and 7), choroidal blood flow increasing agents (Patent Literature 8), and optic neuropathy improving agents (Patent Literature 9). It is also known that it is useful as a pharmaceutical in the ophthalmic field such as (the disclosures of these documents are incorporated herein by reference). (+)-Isopropyl (Z) -7-[(1R, 2R, 3R, 5S) -3,5-dihydroxy-2- (3-oxodecyl) cyclopentyl] hept-5-enoate (generic name: isopropyl unoprostone) ) Is already marketed as a Rescula (registered trademark) ophthalmic solution as a pharmaceutical for the treatment of glaucoma and ocular hypertension. Isopropyl unoprostone is also known as a BK channel modulator (Non-patent Document 5).

  In Japan, several reports on clinical studies on patients with retinitis pigmentosa using isopropyl unoprostone have been made (for example, Non-Patent Documents 6-8 and Patent Document 10).

US Pat. No. 5,011,153 US Pat. No. 5,151,444 US Pat. No. 5,166,178 US Pat. No. 5,194,429 US Pat. No. 5,236,907 US Pat. No. 5,212,324 US Pat. No. 5,686,487 US Pat. No. 5,221,690 US Pat. No. 5,773,471 US Patent Application Publication No. 2011/0275715

The Reality of Low Vision Care To Improve QOL of Visually Impaired Patients Second Edition Medical School 2006 34-63 Ophthalmology vol. 50, No. 6, 2008 803-807 Jpn. J. Ophthalmol. (2002) 45 581-838 Jpn. J. Ophthalmol. (2012) 56 224-229 Biochimica et Biophysica Acta 1768 (2007) 1083-1092 Arch Ophthalmol.vol. 120, 348-352, 2002 IOVS 2008 49 abstract 2185 IOVS 2009 50 abstract 989

  The present invention provides a treatment method for preventing or delaying the progression of retinal pigment degeneration in patients with retinal pigment degeneration with a certain degree of progression or improving retinal sensitivity.

The present invention provides an ophthalmic topical composition for the treatment of human retinal pigment degeneration patients comprising an effective amount of isopropyl unoprostone and having an MD value of -15 dB or more in the center of the Humphrey perimeter 10-2 program. .
Furthermore, in the present invention, the MD value of the Humphrey perimeter 10-2 program center is -15 dB or more, and the photoreceptor inscribed / external junction (IS / OS) line length by optical coherence tomography (OCT) is other than 0 mm. A composition for topical ophthalmic administration for the treatment of human retinitis pigmentosa patients is provided.

  The present invention also relates to a method for treating human retinal pigment degeneration, wherein the MD value at the center of the Humphrey perimeter 10-2 program is -15 dB or more, which comprises administering an effective amount of a composition for topical ocular administration containing isopropyl unoprostone. A method for treating retinal pigment degeneration is provided.

  In the method of the present invention, for example, 0.15% by weight isopropyl unoprostone ophthalmic solution is administered twice a day, once twice as a daily dose, continuously over 24 weeks. For example, daily administration is performed for 32 weeks or more, 40 weeks or more, 52 weeks or more.

  The present invention further relates to a clinical trial for retinal pigment degeneration, wherein the target patient is a patient whose MD value of the Humphrey perimeter 10-2 program is -15 dB or more, or the Humphrey perimeter 10-2 program. Provided is a method for evaluating the effect of a test substance on retinal pigment degeneration, which comprises analyzing a test result for a patient group having an MD value of −15 dB or more.

  In another embodiment, in a clinical trial for retinal pigment degeneration, a target patient is treated as an inscribed and circumscribed joint by an optical coherence tomography (OCT) when the MD value of the Humphrey perimeter 10-2 program is -15 dB or more. (IS / OS) patients whose line length is other than 0 mm, or that the MD value of the Humphrey perimeter 10-2 program is -15 dB or more. / OS) Provided is a method for evaluating the effect of a test substance on retinal pigment degeneration, comprising analyzing test results for a group of patients whose line length is other than 0 mm.

  The composition and treatment method of the present invention can provide maintenance or improvement of visual function or delay of visual function in patients whose Hufrey 10-2 program center MD value is -15 dB or more.

The transition of the change value of the central 4-point average retinal sensitivity of the Humphrey perimeter 10-2 program of the UF-021 group and the placebo group is shown. The change of the change value of MD value of Humphrey perimeter 10-2 program of UF-021 group and placebo group is shown. The transition of the change value of the number of readable characters by the ETDRS visual acuity test table of the UF-021 group and the placebo group is shown. The change value of the total score of NEI VFQ-25 (Compo 8) at the end of 52 weeks from the start of administration in the UF-021 group and the placebo group or at the time of discontinuation is shown. The change value of the score of each subscale of NEI VFQ-25 (Compo 8) at the end of 52 weeks from the start of administration in the UF-021 group and placebo group or at the time of discontinuation is shown. The change rate of the visual field area by the Goldman perimeter at the end of 48 weeks from the start of administration of the UF-021 group and the placebo group at the time of termination or discontinuation is shown. Changes in the change in the central four-point average retinal sensitivity of the Humphrey perimeter 10-2 program of the UF-021 group and the placebo group, and the MD group of the Humphrey perimeter 10-2 program at the start of administration is -15 dB or more. , And the results of stratified analysis divided into patient groups of less than -15 dB. Changes in the measured values of the central four-point average retinal sensitivity of the Humphrey perimeter 10-2 program of the UF-021 group and the placebo group, and the MD value of the Humphrey perimeter 10-2 program at the start of administration is -15 dB or more. , And the results of stratified analysis divided into patient groups of less than -15 dB. Changes in the MD value of the Humphrey perimeter 10-2 program of the UF-021 group and the placebo group, the patient group in which the MD value of the Humphrey perimeter 10-2 program at the start of administration is −15 dB or more, and −15 dB The results of stratified analysis divided into patient groups of less than are shown. The change in the number of ETDRS readable characters in the UF-021 group and the placebo group is divided into a patient group in which the MD value of the Humphrey perimeter 10-2 program at the start of administration is -15 dB or more and a patient group in which the MD value is less than -15 dB. The results of stratified analysis are shown. The change in the total score of VFQ-25 (Compo 8) in the UF-021 group and the placebo group, the MD value of the Humphrey perimeter 10-2 program at the start of administration, a patient group with -15 dB or more, and less than -15 dB The results of stratified analysis divided into patient groups are shown. The change in each of the subscales of NEI VFQ-25 (Compo 8) in the UF-021 group and the placebo group, the patient group whose MD value of the Humphrey perimeter 10-2 program at the start of administration is -15 dB or more, and -15 dB The results of stratified analysis divided into less than patient groups are shown (less than -15 dB). The change in each of the subscales of NEI VFQ-25 (Compo 8) in the UF-021 group and the placebo group, the patient group whose MD value of the Humphrey perimeter 10-2 program at the start of administration is -15 dB or more, and -15 dB The result of stratified analysis divided into less than patient groups is shown (-15 dB or more). The change in the change value of the central 4-point average retinal sensitivity of the Humphrey perimeter 10-2 program of the UF-021 group and the placebo group, the MD value of the Humphrey perimeter 10-2 program at the start of administration is -15 dB or more and OCT The results of stratified analysis are shown for patient groups with IS / OS line lengths other than 0 mm and patient groups with less than −15 dB and OCT IS / OS line lengths other than 0 mm.

  The present invention is for treating a human retinitis pigmentosa patient with an MD of Humphrey perimeter 10-2 program of -15 dB or more, comprising administering a composition for topical ocular administration comprising an effective amount of isopropyl unoprostone. Provide a way.

  As used herein, the term “treatment” or “treating” refers to the management of any condition, including treatment of the subject disease, arrest of progression, delay of progression, relief of symptoms, and the like.

  In the present invention, the subject of treatment is a patient with retinitis pigmentosa, and the MD value of the Humphrey 10-2 program at the start of treatment is -15 dB or more. For example, with a Goldman perimeter, centripetal visual field stenosis (including a ring-shaped dark spot) extending to within 30 degrees in the center, the center 4-point average retinal sensitivity of the Humphrey vision meter 10-2 program is less than 30 dB, and the Humphrey perimeter Patients whose MD value of 10-2 program is -15 dB or more are targeted.

  When the MD value of the Humphrey 10-2 program is −15 dB or more, the corrected visual acuity is often kept at 0.5, which does not cause an abnormality in daily life. By starting the treatment at this stage, a better visual function as well as an effect of improving visual-related QOL can be obtained as compared with the case where the treatment is started at a further advanced stage.

  The ophthalmic composition of the present invention may include all ophthalmic preparations for topical ophthalmic administration used in the ophthalmic field, such as eye drops and eye ointments. Preferably, an ophthalmic solution, particularly preferably an ophthalmic solution containing 0.15% by weight of isopropyl unoprostone is used.

  Ophthalmic solutions may be prepared by dissolving the active ingredient in a sterile aqueous solution, such as saline and buffered solutions. Ophthalmic solutions may be provided as a powder composition that is dissolved prior to use or by combining powder compositions that are dissolved prior to use.

  The osmotic pressure adjusting agent may be any commonly used in the ophthalmic field. Examples of osmotic pressure regulators include sodium chloride, potassium chloride, calcium chloride, sodium bicarbonate, sodium carbonate, magnesium sulfate, sodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, boric acid, borax (Borax), sodium hydroxide, hydrochloric acid, mannitol, sorbitol, glucose, glycerin, propylene glycol, polyethylene glycol, and the like, but are not limited thereto. Preferably, the osmotic pressure regulating compound is a sugar alcohol such as mannitol or sorbitol and / or a polyol such as glycerin or propylene glycol.

  In the present invention, a solubilizer such as a surfactant can be used to improve the solubility of isopropyl unoprostone in a solvent. The surfactant used in the present invention is not limited as long as the object is achieved, but a nonionic surfactant is preferable. Examples of nonionic surfactants include polyoxyethylene sorbitan monooleate (polysorbate 80), polyoxyethylene sorbitan monostearate (polysorbate 60), polyoxyethylene sorbitan monopalmitate (polysorbate 40), polyoxyethylene sorbitan Polyoxyethylene sorbitan fatty acid esters such as monolaurate, polyoxyethylene sorbitan trioleate, polyoxyethylene sorbitan tristearate (polysorbate 65); polyoxyethylene castor oil 35, polyoxyethylene hydrogenated castor oil 10, polyoxyethylene cured Polyoxyethylene (hardened) castor oil such as castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60; (160) polyoxypropylene (30) glycol [Pluronic F68], polyoxyethylene (42) polyoxypropylene (67) glycol [Pluronic P123] and other polyoxyethylene polyoxypropylene glycols; polyoxyethylene 40 monostearate And polyoxyethylene alkyl ethers such as polyoxyl 10 oleyl ether (Bridge 97) and polyoxyl 20 oleyl ether (Bridge 98). Preferable examples include polyoxyethylene sorbitan monooleate (polysorbate 80), polyoxyethylene hydrogenated castor oil 60, polyoxyethylene 40 monostearate, polyoxyl 10 oleyl ether, and the like. Or two or more may be used in combination.

  Furthermore, additives commonly used in the ophthalmic field may be added to the composition of the present invention as desired. Such additives include buffers (e.g., boric acid, borax, sodium monohydrogen phosphate and sodium dihydrogen phosphate, sodium edetate), preservatives (e.g., benzalkonium chloride, benzethonium chloride and Chlorobutanol), thickeners (eg, sodium hyaluronate, chondroitin sulfate, guar gum, gellan gum, xanthan gum and sodium alginate; cellulose polymers such as methylcellulose, methylethylcellulose and hydroxypropylmethylcellulose; sodium polyacrylate, carboxy Vinyl polymers and cross-linked polyacrylic acid).

  In accordance with the present invention, preferred embodiments include that the ophthalmic composition is substantially free of benzalkonium chloride. As used herein, the term “the ophthalmic composition is substantially free of benzalkonium chloride” means that the composition does not contain benzalkonium chloride or the benzal chloride chloride of the composition. This means that the ruconium content is very low. The “ophthalmic composition substantially free of benzalkonium chloride” in the present invention contains 0.01% by weight or less, preferably 0.005% by weight or less, more preferably 0.003% by weight of benzalkonium chloride. It may be contained at a concentration of not more than%.

  The ophthalmic solution of the present invention may be formulated as a preservative, for example, as a sterile unit dose (daily or single unit dose) formulation substantially free of benzalkonium chloride.

  Furthermore, compositions for topical ophthalmic administration include sustained release dosage forms such as gel formulations, liposome formulations, lipid microemulsion formulations, microsphere formulations, to provide the active compound continuously to the back of the eye, Examples include nanosphere formulations and implant formulations.

  In the present invention, when 0.15 wt% isopropyl unoprostone ophthalmic solution is used, at least 3 drops per day may be administered. The administration time may be given at regular intervals (for example, every 5 hours) for each drop, or may be administered continuously. In the case of continuous administration, it is preferable to perform the next one drop instillation after an interval of at least 5 minutes after the first drop. Preferable usage examples include ophthalmic administration of at least 4 drops per day. In addition, two drops or more can be administered by eye drop twice a day. In this usage example, the second drop is applied 5 minutes after the first drop. If the number of drops further increases, one drop instillation can be performed every 5 minutes. The number of eye drops per day is about 2 to 12 times, and the number of eye drops per time is about 2 to 12 drops. For example, it is preferable to administer 2 drops once and twice daily (morning and evening) continuously every day.

  The drop volume of the ophthalmic composition used in the present invention may be at least about 20 μL or more, preferably about 30 μL or more, and usually about 20 to about 50 μL, preferably about 30 to about 40 μL. . When about 35 μL of a drop of isopropyl unoprostone (0.15 wt%) ophthalmic solution is used, the amount of compound per drop is about 52.5 μg. In the case of 4 drops per day, about 210 μg per day will be administered.

  The term “about” as used herein may mean an error of up to ± 30%, preferably ± 20%, more preferably ± 10% of a numerical value.

  In the methods of the invention, administration continues for at least 24 weeks. For example, administration is continued for 32 weeks, 40 weeks, 52 weeks or more.

As a phase III clinical trial of isopropyl unoprostone (UF-021) for retinitis pigmentosa, a multicenter double-blind study was conducted with a placebo group as a control.
Targeting patients with Goldman perimeter who have centripetal stenosis (including ring-shaped dark spots) within 30 degrees in the center (after mid-term) and whose center 4-point average retinal sensitivity of Humphrey perimeter 10-2 program is less than 30 dB did. The final number of patients that could be analyzed was 199 (99 in the placebo group, 100 in the active drug group).
Placebo or active drug was assigned by the double shielding method, 2 drops once, twice daily, for 52 weeks. As an evaluation by stage, a stratified analysis at the MD value of -15 dB of the Humphrey perimeter 10-2 program was planned in advance. There were 76 active drug groups and 82 placebo groups with MD values less than −15 dB, and 24 active drug groups and 17 placebo groups with MD values of −15 dB or more.

Test preparation Each component was dissolved in purified water so as to have the weight% shown below, filtered aseptically, and sealed in a sterilized low-density polyethylene container. The isopropyl unoprostone 0.15% ophthalmic solution was used. (1 drop volume: about 35 μL).
0.15% Isopropyl unoprostone (UF-021)
1.0% Polyoxyethylene sorbitan monooleate 1.0% Mannitol 1.9% Glycerin 0.05% Sodium edetate 0.003% Benzalkonium chloride.

The usage, dose, and administration timing in this study were as follows.
Daily, 2 drops once, 2 drops. Instillation around 7am (6-9am) and 20pm (19-22pm). One drop is instilled in one drop, and another drop is dropped about 5 minutes after that.
Administration period: 52 weeks

Before the start of administration, and after 4 weeks, 8 weeks, 16 weeks, 24 weeks, 32 weeks, 40 weeks, and 52 weeks after the start of administration, the following 1) and 2) are examined and effective for the placebo group Sex was evaluated. Moreover, about the case which stopped the test on the way, the same test | inspection was performed also at the time of cancellation, and it analyzed together with the data after 52 weeks.
1) Central four-point average retinal sensitivity and MD value of Humphrey perimeter 10-2 program 2) Examination by ETDRS eye chart

In addition, the following were also examined 3) The 25-Item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) Component 8 (total score after 52 weeks of administration before administration or discontinuation and scores of subscales) change of)
4) Field of view by Goldman perimeter (change rate of field of view after 48 weeks of administration from the start of administration or at the time of discontinuation)
5) Visual cell inscribed and circumscribed joint (IS / OS) line length by optical coherence tomography (OCT)

I Clinical Trial Results 1) Central 4-point average retinal sensitivity of Humphrey perimeter 10-2 program FIG. 1 shows changes in the change in central 4-point average retinal sensitivity of the Humphrey perimeter 10-2 program. In the UF-021 group, an improvement trend was observed up to 24 weeks after the start of administration, but thereafter it turned worse, and the change from 52 weeks after the start of administration or before administration at the time of discontinuation was There was no significant difference.

2) MD value of Humphrey perimeter 10-2 program Fig. 2 shows the change of the MD value of the Humphrey perimeter 10-2 program. In the UF-021 group, an improvement trend was observed up to 40 weeks after the start of administration, but no significant difference was observed with the placebo group.

3) Examination by ETDRS visual acuity test table FIG. 3 shows the transition of the change value of the number of ETDRS readable characters. The more ETDRS readable characters, the better the visual acuity. In the UF-021 group, significant improvement from the start of administration was observed 8 weeks after the start of administration, but the change value thereafter decreased, and the change value from 52 weeks after the start of administration or before the start of administration at the time of discontinuation There was no significant difference from the placebo group.

4) Assessment of patient's visual quality of life The original NEI VFQ-25 (The 25-item National Eye Institute Visual Function Questionnaire) that measures the visual quality of life (QOL) of patients It consists of 12 subscales (25 items) that measure function and the degree of physical, mental, and social life limitations depending on how you see them. In this test, a questionnaire of 8 components composed of 8 subscales excluding general health, driving, peripheral vision, and eye pain was used. The score change value (after 52 weeks or at the time of discontinuation-0 weeks) was evaluated at the end of the previous observation period (week 0) and at the end of administration (after 52 weeks or at the time of discontinuation). The total score change value of VFQ-25 (component 8) is shown in FIG. 4, and the change value of each subscale of VFQ-25 (component 8) is shown in FIG.

  It was confirmed that the UF-021 group significantly suppressed the decrease in visual-related quality of life compared to the placebo group.

5) Change rate of visual field area by Goldman perimeter Fig. 6 shows the change rate (%) of V / 4e isopter visual field area by Goldman perimeter before administration and after 48 weeks of administration or at the time of discontinuation. In the placebo group, visual field stenosis progressed significantly, but in the UF-021 group, no significant visual field stenosis progressed.

II Stratified analysis 1
The results obtained in the above phase III clinical trial were divided into patients with MD values of the Humphrey perimeter 10-2 program at the start of the trial of -15 dB or more and patient groups of less than -15 dB, and stratified analysis was performed. It was.

1) Central 4-point average retinal sensitivity of Humphrey perimeter 10-2 program FIG. 7 shows the stratified analysis results of the change value of the central 4-point average retinal sensitivity of the Humphrey perimeter 10-2 program. There was no difference between the two groups in the case group of less than -15 dB, but in the case group of -15 dB or more, it was found that the improvement of the central 4-point average retinal sensitivity continued in the UF-021 administration group.
FIG. 8 shows the result of stratified analysis of the transition of the measured value of the central 4-point average retinal sensitivity of the Humphrey perimeter 10-2 program. There was a clear difference in retinal sensitivity between the case group of less than -15 dB and the case group of -15 dB or more.

2) MD value of Humphrey perimeter 10-2 program The stratified analysis result of the change value of MD value of the Humphrey perimeter 10-2 program is shown in FIG. There was no difference between the two groups in the case group of less than -15 dB, but in the case group of -15 dB or more, it was found that the tendency to improve the MD value persisted in the UF-021 administration group.

3) Examination by ETDRS visual acuity test table FIG. 10 shows the stratified analysis result of the transition of the change value of the number of ETDRS readable characters. In the case group of less than -15 dB, no difference was observed between the two groups. However, in the case group of -15 dB or more, the improvement continued after 8 weeks in the UF-021 administration group.

4) Evaluation of patient's visual related quality of life For patient's visual related quality of life (QOL), the stratified analysis result of the change value of the total score of VFQ (component 8) is shown in FIG. 11, VFQ-25 (component 8). ) The change values of the lower scales are shown in FIGS. 12-1 and 12-2.
In the case group of less than -15 dB, there was no difference between the two groups, but in the case group of -15 dB or more, the UF-021 administration group showed a tendency to deteriorate in the placebo group, and the UF-021 group showed an improvement trend. There was a significant difference between the groups.

  From the results of the above stratified analysis, it was confirmed that isopropyl unoprostone is particularly effective in the treatment of retinal pigment degeneration with an MD value of the Humphrey perimeter 10-2 program of -15 dB or more.

  In addition, when analyzing the test results in a retinal pigment degeneration patient group with an MD value of the Humphrey perimeter 10-2 program of −15 dB or more, the effect of the test substance on retinal pigment degeneration compared to the case where no stratified analysis is performed. It was confirmed that it can be evaluated more clearly.

III Stratified analysis 2
The results obtained in the above phase III clinical trial were obtained by comparing the MD value of the Humphrey perimeter 10-2 program at the start of the trial with a value of −15 dB or more and the photoreceptor inscribed and circumscribed joint (IS) by optical coherence tomography (OCT) (IS / OS) Patients with line lengths other than 0 mm and patients with less than -15 dB optical coherence tomography (OCT) optical cell inscribed and circumscribed junction (IS / OS) line lengths other than 0 mm divided into stratified analysis Went.

1) Central four-point average retinal sensitivity of Humphrey perimeter 10-2 program FIG. 13 shows a stratified analysis result of change values of the central four-point average retinal sensitivity of the Humphrey perimeter 10-2 program. There was no difference between the two groups in cases less than −15 dB and IS / OS line length other than 0 mm, but in case groups other than −15 dB and IS / OS line length other than 0 mm, there was no difference in the UF-021 administration group. It was found that the 4-point average retinal sensitivity improvement persisted more significantly.

  Tests in patients with retinal pigment degeneration with an MD value of the Humphrey perimeter 10-2 program of -15 dB or more and an optical coherence tomography (IS / OS) line length other than 0 mm by optical coherence tomography (OCT) When the result was analyzed, it was confirmed that the effect of the test substance on retinal pigment degeneration can be more clearly evaluated as compared with the case of stratified analysis based only on the MD value of the Humphrey perimeter 10-2 program.

Claims (7)

  A composition for topical ocular administration for treating a human retinal pigment degeneration patient comprising an effective amount of isopropyl unoprostone and having an MD value at the center of the Humphrey perimeter 10-2 program of -15 dB or more.   The composition of claim 1, wherein the concentration of isopropyl unoprostone in the composition is 0.15 wt%.   The composition according to claim 1 or 2, wherein two drops of the ophthalmic composition per eye are instilled into a patient twice a day.   4. The composition according to any one of claims 1 to 3, wherein the administration is continued for a period of at least 24 weeks.   The composition according to any one of claims 1 to 4, wherein the composition is substantially free of benzalkonium chloride.   6. A composition according to any preceding claim, formulated as a sterile unit dose for single use.   Human retinitis pigmentosa has a MD value of -15 dB or more at the center of the Humphrey perimeter 10-2 program, and the optical cell inscribed and circumscribed junction (IS / OS) line length by optical coherence tomography (OCT) is 0 mm The composition according to any one of claims 1 to 6, which is other than the above.