Visual Dysfunction and Structural Correlates in Sorsby Fundus Dystrophy

TY - JOUR

T1 - Visual Dysfunction and Structural Correlates in Sorsby Fundus Dystrophy

AU - Raming, Kristin

AU - Gliem, Martin

AU - Charbel Issa, Peter

AU - Birtel, Johannes

AU - Herrmann, Philipp

AU - Holz, Frank G

AU - Pfau, Maximilian

AU - Hess, Kristina

N1 - Copyright © 2021 Elsevier Inc. All rights reserved.

PY - 2022/2

Y1 - 2022/2

N2 - PURPOSE: To elucidate morphological determinants of rod and cone dysfunction in Sorsby fundus dystrophy (SFD), and to systematically compare visual function tests for interventional trials.DESIGN: Prospective cross-sectional study.METHODS: Patients with SFD (n = 16) and controls (n = 20) underwent visual function testing (best-corrected visual acuity [BCVA] and low luminance visual acuity [LLVA], contrast sensitivity, mesopic and dark-adapted (DA) fundus-controlled perimetry [FCP], rod-mediated dark adaptation [RMDA]), and multimodal imaging. Vision-related quality of life was evaluated. FCP and RMDA thresholds were analyzed using mixed models and structure-function correlation using machine learning (ML). Longitudinal data of 1 patient with high-dose vitamin A supplementation were available.RESULTS: Although photopic BCVA was normative in SFD, LLVA was impaired (0.30 LogMAR [0.20; 0.45] vs 0.20 LogMAR [0.03; 0.28], P < .05). Scotopic visual function exhibited a delayed rod-intercept time (21 minutes [12.15; 21] vs 4.05 minutes [3.22; 5.36], P < .001), and marked DA cyan mean sensitivity loss (-11.80 dB [-3.47; -19.85]), paralleled by a reduced vision-related quality of life. ML-based structure-function correlation allowed prediction of mesopic, DA cyan, and red sensitivity with high accuracy (cross-validated mean absolute error: 4.36, 7.77, and 5.31 dB, respectively), whereas RMDA could be slowed even in the absence of fundus alterations on multimodal imaging. After high-dose vitamin A supplementation, RMDA and DA thresholds improved markedly.CONCLUSIONS: Patients with SFD exhibit severely impaired scotopic visual function even in the absence of funduscopic alterations on multimodal imaging. In contrast to BCVA, scotopic visual function tests are suitable to quantify dysfunction in the early stages. Improvement of scotopic dysfunction after (off-label) high-dose vitamin A intake, as observed in one patient in our study, is compatible with the hypothesized local deficiency of vitamin A secondary to Bruch's membrane alterations.

AB - PURPOSE: To elucidate morphological determinants of rod and cone dysfunction in Sorsby fundus dystrophy (SFD), and to systematically compare visual function tests for interventional trials.DESIGN: Prospective cross-sectional study.METHODS: Patients with SFD (n = 16) and controls (n = 20) underwent visual function testing (best-corrected visual acuity [BCVA] and low luminance visual acuity [LLVA], contrast sensitivity, mesopic and dark-adapted (DA) fundus-controlled perimetry [FCP], rod-mediated dark adaptation [RMDA]), and multimodal imaging. Vision-related quality of life was evaluated. FCP and RMDA thresholds were analyzed using mixed models and structure-function correlation using machine learning (ML). Longitudinal data of 1 patient with high-dose vitamin A supplementation were available.RESULTS: Although photopic BCVA was normative in SFD, LLVA was impaired (0.30 LogMAR [0.20; 0.45] vs 0.20 LogMAR [0.03; 0.28], P < .05). Scotopic visual function exhibited a delayed rod-intercept time (21 minutes [12.15; 21] vs 4.05 minutes [3.22; 5.36], P < .001), and marked DA cyan mean sensitivity loss (-11.80 dB [-3.47; -19.85]), paralleled by a reduced vision-related quality of life. ML-based structure-function correlation allowed prediction of mesopic, DA cyan, and red sensitivity with high accuracy (cross-validated mean absolute error: 4.36, 7.77, and 5.31 dB, respectively), whereas RMDA could be slowed even in the absence of fundus alterations on multimodal imaging. After high-dose vitamin A supplementation, RMDA and DA thresholds improved markedly.CONCLUSIONS: Patients with SFD exhibit severely impaired scotopic visual function even in the absence of funduscopic alterations on multimodal imaging. In contrast to BCVA, scotopic visual function tests are suitable to quantify dysfunction in the early stages. Improvement of scotopic dysfunction after (off-label) high-dose vitamin A intake, as observed in one patient in our study, is compatible with the hypothesized local deficiency of vitamin A secondary to Bruch's membrane alterations.

KW - Cross-Sectional Studies

KW - Dark Adaptation

KW - Humans

KW - Prospective Studies

KW - Quality of Life

KW - Visual Acuity

KW - Visual Field Tests/methods

KW - Visual Fields

U2 - 10.1016/j.ajo.2021.07.032

DO - 10.1016/j.ajo.2021.07.032

M3 - SCORING: Journal article

C2 - 34352251

VL - 234

SP - 274

EP - 284

JO - AM J OPHTHALMOL

JF - AM J OPHTHALMOL

SN - 0002-9394

ER -