Inner Retinal Thickness and Vasculature in Patients with Reticular Pseudodrusen

Introduction: The aim of this study was to investigate retinal layer thickness and vessel density differences between patients with reticular pseudodrusen (RPD) and intermediate dry age-related macular degeneration (iAMD). Methods: Participants included in the study were patients diagnosed by retinal specialists with RPD, iAMD, and both RPD and iAMD at our academic referral center, seen from May 2021 until February 2022. The central 3 mm retinal thickness was measured using spectral-domain optical coherence tomography (Heidelberg Spectralis HRA+OCT System; Heidelberg Engineering, Heidelberg, Germany). Individual retinal thickness measurements were obtained from the innermost layer (nerve fiber layer) until the outermost layer (retinal pigment epithelium [RPE]). Each thickness measurement was subdivided into nine Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. For the vessel density, OCT angiography from the Heidelberg Spectralis System was measured using proprietary third-party software (AngioTool; National Institutes of Health, National Cancer Institute, Bethesda, MD). Clinical and demographic characteristics were compared across the three groups (iAMD, RPD, iAMD and RPD) and analyzed with necessary adjustments. Linear mixed-effects models with necessary corrections were employed to compare continuous eye-level measurements between our three groups as well as in pairwise fashion using the R statistical programming software (R version 4.2.1). Results: A total of 25 eyes of 17 patients with RPD, 20 eyes of 15 patients with iAMD, and 14 eyes of 9 patients with both iAMD and RPD were analyzed. Retinal thickness analysis identified that the superior inner (p = 0.028) and superior outer (p = 0.027) maculas of eyes with both iAMD and RPD were significantly thinner than those with iAMD alone. In eyes with RPD, the superior inner and superior outer RPE (p = 0.011 and p = 0.05, respectively), outer plexiform layer (p = 0.003 and p = 0.013, respectively), and inner nuclear layer (p = 0.034 and p = 0, respectively) were noted to be thinner compared to eyes with iAMD alone. In addition, the macular deep capillary plexus vessel density was significantly reduced in eyes with RPD compared to eyes with iAMD (p = 0.017). Conclusion: Patients with RPD had inner retinal structural as well as vascular changes compared to iAMD patients. Inner retinal vascular attenuation should be investigated further to see if there is a causal association with retinal thinning.