Phd in EXPERIMENTAL MEDICINE

Thesis title: Drusen remodeling in intermediate age-related macular degeneration: functional and morphological correlates.

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 the automatic segmentation of 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. Microperimetry obtained under mesopic conditions was overlaid with the corresponding thickness maps through Fiji software. 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 an 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 an ORL thickening at 1-year (r=0.61, p=0.008). Conclusions: Progressive degeneration of the ONL is related to a photoreceptor irreversible dysfunction in iAMD. Likewise, choroidal vascular modifications are associated with a significant functional decline in the central region and diffusely. Longitudinal evaluation of drusen remodeling reveals functional implications for the drusen resorption, describing an end-stage drusen lifecycle with irreversible changes in cellular activity and critical photoreceptor loss.