Abstract
Purpose :
Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) poses significant challenge with progressive loss of vision due to outer retinal degeneration. Developing GA model in NHPs provides the opportunity to recapitulate human disease pathology owing to similar retinal anatomy, however, the progression needs to be accelerated to screen efficacy of different drugs. Here, we report utilization of OCT-guided, spatially targeted visible laser irradiation platform for localizing the injury while inducing layer-specific retinal degeneration and enabling real-time monitoring.
Methods :
The integrated laser and OCT beam, facilitates the identification of a microirradiation target region and real-time monitoring. To ensure specific layer irradiation, the beam’s spot focal plane was dynamically adjusted, focusing on the retinal pigment epithelium (RPE) layer. To emulate localized photoreceptor degeneration akin to GA, OCT-guided laser microirradiation was performed surrounding the fovea of NHP retina. Structural and functional changes post-irradiation were assessed using OCT imaging and multifocal electroretinogram (mfERG) recording.
Results :
Sequential measurements, post-laser injury, revealed progressive RPE layer degradation, followed by photoreceptor layer thinning and reduced mfERG signal. Average retinal thickness in perifovea area reduced from 351.25±21.3, 317.3±16.55, 296.7±22.4 microns for -2, 0, and 4 weeks post laser damage, which corresponded to a reduction in mfERG signal. This methodology demonstrated high spatiotemporal precision in inducing retinal degeneration. This approach minimized collateral damage to surrounding retinal layers unlike non-scanning laser irradiation method. The induction of GA model did not lead to choroidal damage, neovascularization, hemorrhage or show any evidence of inflammation.
Conclusions :
Our results demonstrate successful establishment of an OCT-guided laser microirradiation for precise, spatially targeted retinal injury with minimal collateral damage or inflammation. This establishes the anatomical defects of GA in NHP model and provides an ideal platform for evaluating myriad of therapies in development prior to clinical translation.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.