Risk factors for the development of intraretinal hyper-reflective foci overlying drusen in eyes with intermediate age-related macular degeneration

Abstract

Purpose : To assess the baseline characteristics of drusen preceding the development of intraretinal hyperreflective foci over 36 months in eyes with intermediate age-related macular degeneration (AMD)

Methods : Longitudinal optical coherence tomography (OCT) volume data from eyes with iAMD were screened for the presence of drusen with overlying intraretinal hyperreflective foci (IHRF). OCT data for 36 months prior to the visit with evidence of IHRF were evaluated, and eyes without evidence of IHRF at the baseline visit were selected as control for this analysis. Eyes that had evidence of macular neovascularization (MNV), vitreoretinal surgery, and/or intravitreal injection were excluded. All drusen (> 35µm in height and >88 µm in width) at the baseline visit were annotated with a sequential numerical label on the infrared reflectance (IR) image. A random number generator was used to randomly select three drusen that did not develop IHRF and up to three drusen which developed IHRF for further grading. At the baseline visit, quantitative and qualitative structural OCT features were assessed.

Results : A total of 90 eyes (72 patients) were annotated, including 140 drusen with overlying IHRF and 270 control drusen. Several baseline OCT features, including increased apical drusen height, basal drusen width, and overlying EZ and ELM disruption were associated with a significantly greater risk of developing IHRF (p-value £ 0.001 for all the features). Regression analysis revealed that EZ disruption over the drusen increased the odds for IHRF development by 3.47 times (p-value £ 0.001). Each 10-micron increase in drusen height and width increased the odds of developing IHRF by 32 % (p-value £ 0.001) and 3% (p-value: 0.005), respectively. Moreover, for each 10 microns increase in distance from the fovea, the odds for IHRF development decreased by 1% (p-value: 0.013).

Conclusions : The presence of overlying EZ disruption and a greater drusen height substantially increase the risk for the development of IHRF over that drusen within the next 3 years, whereas drusen further from the fovea appear at reduced risk for IHRF development. Given the importance of IHRF as a biomarker for AMD progression, these findings may be of value in defining patient populations for inclusion in future early intervention trials aimed at preventing progression to IHRF.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.