Abstract
Purpose :
We evaluated the efficacy of genipin sustained-release formulation (GSRF) in guinea pig and its safety in rabbit. The efficacy was evaluated by measuring GSRF inhibition on axial length (AL) elongation caused by form-deprivation myopia (FD).
Methods :
For the efficacy study, monocular FD was induced in three-week-old pigmented guinea pigs by placing a diffuser over one eye for 21 days. GSRF was injected on Day 0 into the nasal and temporal sides of the Tenon capsule in the FD-affected eye. The guinea pigs were assigned to a control group (n = 9) or one of four GSRF dosing groups (15, 45, 90, and 225 µg/site dose; n = 10/group). AL was measured by using A-scan ultrasonography both before placement of the diffuser and on Day 21. Dunnett’s test was used to compare results between the GSRF dose groups and the control group.
To assess ocular toxicity, ten-week-old Japanese white rabbits were treated with GSRF injected into the nasal and temporal sides of the Tenon capsule in the left eye. The rabbits were assigned to a control group (n = 6) or one of three GSRF dosing groups (180, 375, and 1050 µg/site dose; n = 3/group). Toxicological findings were evaluated by slit lamp biomicroscopy, fundus examination, tonometry, and histologic examination in Weeks 1, 2, and 4 after injection.
Results :
In the efficacy study, AL elongation was significantly (p <0.05) inhibited in GSRF groups (≧45 µg/site dose) compared with the control group. However, AL elongation in the 15-µg/site GSRF group was comparable with that in the control group.
In the ocular toxicity assessment, blue discoloration and thickening were observed in the conjunctiva (≧375 µg/site dose). In contrast, no toxicologically important drug-related findings were noted in the GSRF group dosed at 180 µg/site.
Conclusions :
These results show that the safe dose of GSRF in rabbit was 180 µg/site. Given the area ratio of the ocular surface, the safe dose in rabbit is equivalent to the 45-µg/site dose in guinea pig, which was an efficacious dose level in that species.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.