Exploring a Structural Basis for Delayed Rod-Mediated Dark Adaptation in Age-Related Macular Degeneration Via Deep Learning

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Purpose Subretinal drusenoid deposits (SDD) first appear in the rod-rich perifovea and can extend to the cone-rich fovea. To refine the spatial relationship of visual dysfunction with SDD burden, we determined the topography of mesopic and scotopic light sensitivity in participants with non-neovascular AMD with and without SDD. Methods Thirty-three subjects were classified into three groups: normal ( n = 9), AMD–Drusen (with drusen and without SDD; n = 12), and AMD–SDD (predominantly SDD; n = 12). Mesopic and scotopic microperimetry were performed using 68 targets within the Early Treatment Diabetic Retinopathy Study grid, including points at 1.7° from the foveal center (rod:cone ratio, 0.35). Age-adjusted linear regression was used to compare mesopic and scotopic light sensitivities across groups. Results Across the entire Early Treatment Diabetic Retinopathy Study grid and within individual subfields, the three groups differed significantly for mesopic and scotopic light sensitivities (all P < 0.05). The AMD–SDD group exhibited significantly decreased mesopic and scotopic sensitivity versus both the normal and the AMD–Drusen groups (all P < 0.05), while AMD–Drusen and normal eyes did not significantly differ (all P > 0.05). The lowest relative sensitivities were recorded for scotopic light levels, especially in the central subfield, in the AMD–SDD group. Conclusions SDD-associated decrements in rod-mediated vision can be detected close to the foveola, and these deficits are proportionately worse than functional loss in the rod-rich perifovea. This finding suggests that factors other than the previously hypothesized direct cytotoxicity to photoreceptors and local transport barrier limitations may negatively impact vision. Larger prospective studies are required to confirm these observations.

Section: Discussionmentioning

confidence: 82%

mentioning

confidence: 96%

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Spatial Dissociation of Subretinal Drusenoid Deposits and Impaired Scotopic and Mesopic Sensitivity in AMD

Zhang

Sadda

Sarraf

et al. 2022

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“…Delayed RMDA is a functional biomarker for AMD onset. 75 A recent study 76 agnostically revealed via deep learning that structural OCT features predictive for delayed RMDA fall within a circular foveal-centered oil spill, defined by epidemiology, 3 clinical imaging, 74 and the current histology. This entire sequence plausibly unfolds under the lifetime systemic and intraocular influence of HDL genes 77,78 (APOE, CETP, LIPC, ABCA1), the second largest pathway implicated by AMD genetics after complement.…”

Section: Discussionmentioning

confidence: 99%

Biometrics, Impact, and Significance of Basal Linear Deposit and Subretinal Drusenoid Deposit in Age-Related Macular Degeneration

Chen

Messinger

Kar

et al. 2021

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Basal linear deposit (BLinD) is a thin layer of soft drusen material. To elucidate the biology of extracellular deposits conferring age-related macular degeneration (AMD) progression risk and inform multimodal clinical imaging based on optical coherence tomography (OCT), we examined lipid content and regional prevalence of BLinD, soft drusen, pre-BLinD, and subretinal drusenoid deposit (SDD) in AMD and non-AMD aged eyes. We estimated BLinD volume and illustrated its relation to type 1 macular neovascularization (MNV).METHODS. Donor eyes were classified as early to intermediate AMD (n = 25) and agematched controls (n = 54). In high-resolution histology, we assessed BLinD/soft drusen thickness at 836 and 1716 locations in AMD and control eyes, respectively. BLinD volume was estimated using solid geometry in donor eyes, one clinically characterized. RESULTS.BLinD, drusen, type 1 MNV, and fluid occupy the sub-RPE-basal laminar space. BLinD volume in a 3-mm diameter circle may be as much as 0.0315 mm 3 . Osmophilic lipid was more concentrated in BLinD/drusen than SDD. In the fovea, BLinD/drusen was prevalent in AMD eyes; pre-BLinD was prevalent in control eyes. SDD was low in the fovea and high in perifovea, especially in AMD eyes. CONCLUSIONS.Although invisible, BLinD may presage type 1 MNV. BLinD volume approaches the criterion OCT drusen volume of 0.03 mm 3 for AMD progression risk. BLinD culminates years of subfoveal lipid accumulation. SDD is detected relatively late in life, with currently unknown precursors. Deposit topography suggests one outer retinal lipid recycling system serving specialized cone and rod physiology, and its dysregulation in AMD is due to impaired transfer to the circulation.

“…The contradiction with regard to the central regional relationship of rod-mediated dysfunction has been explained as compromised transport through the choriocapillaris and BrM being more prominent in this anatomical location, thus affecting the retinoid resupply route. 24 , 61 …”

Section: Discussionmentioning

confidence: 99%

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

Fragiotta

Costanzo

Viggiano

et al. 2022

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.