Abstract
Purpose :
To compare the visual deficit in NHPs with blue light induced macular injury to a cohort of AMD patients using similar imaging and vision psychophysics testing.
Methods :
For the NHP study, 8 cynomolgus monkeys were unilaterally irradiated (study eye, SE) with blue light centered on the macula (8 mm diameter) for 20 to 30 min; contralateral eye (non-study eye, NSE) remained naïve. For the human study, 10 AMD patients with simplified Age-Related Eye Disease Study (AREDS) scores 3 or 4 and 8 age-matched Controls were enrolled. Both, NHP and human subjects were evaluated with fundus autofluorescence (FAF) and optical coherence tomography (OCT) to quantify retinal pigment epithelium (RPE) disruption and outer nuclear layer thickness (ONL). Contrast sensitivity functions (CSF) were used to evaluate visual function using the same custom software suite. NHPs were placed in a primate chair in a custom-made testing chamber. They were trained to hold and then release a lever when a visual stimulus was detected (i.e., “hit”); otherwise non-response was considered a “miss”. Threshold was operationally defined as two successive misses in a descending method of limits (1.5 to 24 cycles per degree (cpd); 5 steps). For the human subjects, a descending method of limits was combined with a 2 Alternate Forced Choice technique (0.75 – 18.50 cpd; 8 steps). The CSF was fit with a double exponential function.
Results :
The clinical presentation of the lesions between NHPs and humans was different. In the NHPs, the lesion was diffuse (late stage AMD; GA); in the humans it was multi-focal (early stage AMD). In NHPs, mean log contrast sensitivity (CS) was 1.27 ± 0.06 (NSE) and 0.73 ± 0.08 (SE). Peak reduction was 0.68 log units at 6 cpd. In the human study, mean log CS in the control subjects was 1.34 ± 0.07 while in AMD patients it was 1.28 ± 0.06. Peak reduction was 0.16 log units at 3 cpd.
Conclusions :
Using similar instrumentation, we found a reduction in CS in the NHP model and human AMD patients. The reduction in CS correlated with the severity of the damage. These results demonstrate that vision psychophysics can be used as a valuable tool in evaluating disease models and efficacy prior to clinical study initiation and inform the best selection of sensitive vision endpoints to use with patients.
This is a 2021 ARVO Annual Meeting abstract.