Abstract
Purpose :
To evaluate changes in minimum rim width (MRW), retinal nerve fiber layer (RNFL), macular ganglion cell inner plexiform layer thickness (GCIPL), photopic negative response (PhNR) and retinal ganglion cell (RGC) count in non-human primates over a 24-week period following the induction of a chronic ocular hypertension (cOHT) model of glaucoma.
Methods :
Eight animals induced with unilateral cOHT were imaged every 2 weeks using the Glaucoma Module Premium Edition (GMPE; Spectralis; Heidelberg Engineering) to quantify MRW, RNFL, and GCIPL thickness. Retinal function was quantified using PhNR amplitude. Animals were euthanized at the end of the in-live portion (24 weeks) for histology and RGC count. A linear mixed effects (LME) model was used to analyze the change in structure (MRW, RNFL, GCIPL) and function (PhNR) across time. A generalized linear model (GLM) was used to analyze RGC counts. Time of onset of change was determined using Kaplan-Meir (KM) survival analysis and compared using Log Rank test.
Results :
Intraocular pressure was significantly elevated in the study eye (SE; 53.28 ± 6.76 mmHg) post- induction compared to baseline (20.9 ± 0.9 mmHg) and the elevation was sustained for the 24-week evaluation period (p〈0.05). In the SE at 2 weeks post-induction, MRW was significantly reduced relative to baseline (182.08 ± 15.8 μm vs. 269 ± 11.4 μm), as was PhNR amplitude (1.9 ± 0.6 μV vs. 26.5 ± 3.2 μV). Similarly, in the SE at 4 weeks post-induction, GCIPL was significantly reduced relative to baseline (66.83 ± 1.3 μm vs. baseline 68.8 ± 0.7 μm), as was RNFL (72.3 ± 2.8 μm vs. baseline 84.2 ± 3.3 μm). Reductions in all four measures were sustained throughout the 24-week evaluation period. Time of onset of change in MRW and PhNR amplitude preceded GCIPL and RNFL (KM; p〈0.05). The macular RGC count was significantly reduced in the SE (306 ± 110) compared to the contralateral eye (1270 ± 68) at 24-weeks. Induction of cOHT was not achieved in 2 animals, which were excluded from analysis.
Conclusions :
Changes in MRW and PhNR preceded reductions in RNFL and GCIPL in the non-human primate cOHT model. Significant loss of RGC count was observed and is consistent with the in-vivo imaging data. This suggests that the cOHT model closely mimics human glaucoma and could be used for evaluating therapeutics that may prevent optic nerve and inner retinal degeneration.
This is a 2020 ARVO Annual Meeting abstract.