Methods for the treatment and prevention of age-related retinal dysfunction
A method of treating or preventing age-related retinal dysfunction involves administering to a patient a pharmaceutically effective amount of a synthetic retinal derivative repeatedly over a duration of at least about 3 months. Effective synthetic retinal derivatives include 9-cis-retinyl esters, 11-cis-retinyl esters, derivatives and congeners thereof, and combinations thereof. Suitable ester substituents include carboxylates of C 1 -C 10 monocarboxylic acids and C 2 -C 22 polycarboxylic acids.
1. A method of treating age-related macular degeneration (AMD) in a human subject in need thereof, comprising:
administering a pharmaceutically effective amount of a synthetic retinal derivative to the human subject, wherein the synthetic retinal derivative supplements or replaces endogenous 11-cis-retinal in the eye, and wherein the synthetic retinal derivative is administered intermittently about once a month over a period of at least four months, and wherein the synthetic retinal derivative has a structure represented by Formula I:
wherein A is CH 2 OR, wherein R is the ester forming portion of a C 1 to C 10 monocarboxylic acid or a C 2 to C 22 polycarboxylic acid.
2. The method of claim 1 , wherein the synthetic retinal derivative is administered to the subject intermittently over a period of at least 6 months.
3. The method of claim 1 , wherein the administering synthetic retinal derivative restores or stabilizes photoreceptor function in the human subject with age-related macular degeneration (AMD).
4. The method of claim 1 , wherein the administering synthetic retinal derivative increases or stabilizes dark adaptation in the human subject with age-related macular degeneration (AMD).
5. The method of claim 1 , wherein the administering synthetic retinal derivative increases or stabilizes contrast sensitivity in the human subject with age-related macular degeneration (AMD).
6. The method of claim 1 , wherein the ester substituent is a carboxylate radical of a polycarboxylic acid of C 3 to C 10 .
7. The method of claim 1 , wherein the synthetic retinal derivative is 9-cis-retinyl acetate, 9-cis-retinyl succinate, 9-cis-retinyl citrate, 9-cis-retinyl ketoglutarate, 9-cis-retinyl fumarate, 9-cis-retinyl malate or 9-cis-retinyl oxaloacetate.
8. The method of claim 1 , wherein the synthetic retinal derivative is 9-cis-retinyl acetate or 9-cis-retinyl succinate.
9. The method of claim 1 , wherein the synthetic retinal derivative is administered orally.
10. The method of claim 1 , wherein the synthetic retinal derivative is administered locally.
11. The method of claim 1 , wherein the synthetic retinal derivative is administered by eye drops, intraocular injection or periocular injection.
12. The method of claim 1 , wherein the long term dosage regimen comprises administering an individual dosage greater than an effective daily dose.