Functional Correlates of Outer Retina Remodeling in Intermediate Age-Related Macular Degeneration Using Microperimetry

PURPOSE: To assess the effect of drusen morphometric changes and choroidal vascular modifications on retinal sensitivity (RS) evaluated through microperimetry in intermediate age-related macular degeneration (iAMD). METHODS: A retrospective review of 18 iAMD patients (18 eyes) with a 12-month follow-up was performed. Eye-tracked spectral-domain optical coherence tomography was obtained, with automatic segmentation of the outer retinal layer (ORL) delineating the drusen area from the external limiting membrane to Bruch's membrane and outer nuclear layer (ONL) thickness maps adjusted manually, as needed. Advanced retinal pigment epithelium analysis was also performed with a ZEISS PLEX Elite 900. Microperimetry obtained under mesopic conditions was overlaid with the corresponding thickness maps with Fiji software. The choroidal vascularity index (CVI) was calculated in the subfoveal b-scan and volumetric in the central 1-mm subfield. RESULTS: A reduced central ONL thickness was strongly associated with RS decline at the same region (r = 0.69, P = 0.002) and globally (r = 0.80, P < 0.001) at baseline, but also at 1 year in the central subfield (central: r = 0.70, P = 0.001). One-year subfoveal CVI variation, differently from volumetric CVI, directly influenced the central (r = 0.64, P = 0.004) and global RS (r = 0.59, P = 0.009), indicating that a CVI reduction negatively affected RS. A greater volumetric CVI within central 1-mm was associated with ORL thickening at 1 year (r = 0.61, P = 0.008). CONCLUSIONS: Progressive degeneration of the ONL is related to irreversible photoreceptor dysfunction in iAMD. Likewise, choroidal vascular modifications are associated with a significant functional decline in the central region and diffusely.