City Research Online

Abstract

Inherited retinal diseases are the leading cause of irreversible visual impairment in the working-age population in the United Kingdom, with rod-cone degenerations a common subphenotype. Treatments are limited, but research to develop new therapies is ongoing. This critical analysis synthesises eleven published research papers that investigate alternative visual function assessments for use as clinical trial outcome measures in such patients. The aim is to provide outcome measure evidence-based recommendations to support ongoing translational research.

Chapter 1 introduces inherited retinal diseases and provides an overview of the visual function tests explored in this critical analysis. Chapter 2 outlines the critical analysis and evidence synthesis structure, data collection and outcome measure evaluation approaches, including test standardisation, reliability and repeatability. Chapter 3 synthesises and evaluates the key publication results grouped by test type: acuity tests, mesopic microperimetry and scotopic microperimetry. This includes five publications that evaluate measures of visual acuity; they explore sources of variability, test performance, reliability and sensitivity. One publication focuses on microperimetry central retinal sensitivity testing, exploring sensitivity indices and endpoint selection. A further three publications evaluate a modified version of microperimetry, called scotopic microperimetry, for use in patients with inherited retinal disease and healthy controls. Chapter 4 makes recommendations for the use of these alternative vision tests based on disease severity and identifies future research directions.

This critical analysis emphasises that outcome measures selection should consider clinical phenotype as well as stage of disease. Scotopic microperimetry testing showed poor reliability and significant floor effects in patients with moderate-stage choroideremia. Further validation is required to determine its suitability for patients with very early-stage disease with preserved central function. Mesopic microperimetry appears to be suitable for most patients with early-to-moderate rod-cone degeneration. Testing has been standardised, and evidence is provided to support the use of volumetric hill-of-vision sensitivity indices. Standardisation recommendations were made for low luminance visual acuity testing. However, its ability to detect subtle sensitivity changes appears limited; low luminance visual acuity may instead be a useful pre-screening tool to determine the onset of late-stage disease. The Moorfields Acuity Chart did not show any clinically significant improvements in reliability compared to other visual acuity testing and so is not recommended. Further research is needed to determine whether low-contrast visual acuity testing provides a more sensitive marker of disease progression, to evaluate the utility of electronic letter charts, and to clarify how different vision assessments relate to everyday visual function.

Publication Type:	Thesis (Doctoral)
Subjects:	Q Science > Q Science (General) R Medicine > RE Ophthalmology
Departments:	School of Health & Medical Sciences > Department of Optometry & Visual Science School of Health & Medical Sciences > School of Health & Medical Sciences Doctoral Theses Doctoral Theses

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