Visual Dysfunction and Structural Correlates in Sorsby Fundus Dystrophy

Kristin Raming; Martin Gliem; Peter Charbel Issa; Johannes Birtel; Philipp Herrmann; Frank G Holz; Maximilian Pfau; Kristina Hess

doi:10.1016/j.ajo.2021.07.032

Visual Dysfunction and Structural Correlates in Sorsby Fundus Dystrophy

Am J Ophthalmol. 2022 Feb:234:274-284. doi: 10.1016/j.ajo.2021.07.032. Epub 2021 Aug 2.

Authors

Kristin Raming¹, Martin Gliem², Peter Charbel Issa³, Johannes Birtel⁴, Philipp Herrmann¹, Frank G Holz¹, Maximilian Pfau⁵, Kristina Hess⁶

Affiliations

¹ From the Department of Ophthalmology (K.R., J.B., P.H., F.G.H., M.P., K.H.), University of Bonn, Bonn, Germany; Center for Rare Diseases (K.R., P.H., F.G.H., K.H.), University of Bonn, Bonn, Germany.
² Boehringer Ingelheim GmbH (M.G.), Ingelheim am Rhein, Germany.
³ Oxford Eye Hospital (P.C.I., J.B.,), Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom; Nuffield Laboratory of Ophthalmology (P.C.I., J.B.), Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
⁴ From the Department of Ophthalmology (K.R., J.B., P.H., F.G.H., M.P., K.H.), University of Bonn, Bonn, Germany; Oxford Eye Hospital (P.C.I., J.B.,), Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom; Nuffield Laboratory of Ophthalmology (P.C.I., J.B.), Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
⁵ From the Department of Ophthalmology (K.R., J.B., P.H., F.G.H., M.P., K.H.), University of Bonn, Bonn, Germany; Ophthalmic Genetics and Visual Function Branch (M.P.), National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
⁶ From the Department of Ophthalmology (K.R., J.B., P.H., F.G.H., M.P., K.H.), University of Bonn, Bonn, Germany; Center for Rare Diseases (K.R., P.H., F.G.H., K.H.), University of Bonn, Bonn, Germany; Division of Epidemiology and Clinical Applications (K.H.), National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: Kristina.hess@ukbonn.de.

PMID: 34352251
DOI: 10.1016/j.ajo.2021.07.032

Abstract

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.

Keywords: Bruch's membrane; Dark adaptation; Fundus-controlled perimetry; Microperimetry; Outcome measures; Sorsby Fundus Dystrophy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cross-Sectional Studies
Dark Adaptation
Humans
Prospective Studies
Quality of Life*
Visual Acuity
Visual Field Tests / methods
Visual Fields*

Grants and funding

DH_/Department of Health/United Kingdom