A Decade Of Diagnosing Inherited Retinal Dystrophies and Optic Atrophies: The Evolution Towards An Advanced Standardized Retinal Imaging and Molecular Genetic Approach

Abstract

Purpose: An early diagnosis of inherited retinal or optic nerve disorders (IROD) is frequently delayed due to unspecific clinical signs, variability of clinical manifestations and the underlying genetic defects. The present study evaluates the impact of non-invasive retinal imaging techniques (fundus autofluorescence (FAF), near-infrared autofluorescence (NIA), spectral domain OCT (SD-OCT), three wavelength MultiColor spectral reflectance imaging (MC)) and molecular genetic analysis on the diagnostic process of IROD.

Methods: In a single specialized center 1045 patients with IROD were examined and confirmed based on electrophysiological, retinal imaging or molecular genetic data between 2004 and 2014. Follow-up was available in 378 patients (median 3.9 y.). In addition to the basic ophthalmological examination electrophysiological testing (ERG n=358; EOG n=53; VEP n=102; mfERG n=283) and non-invasive retinal imaging (FAF n=947; NIA n=698; SD-OCT n=621; MC n=242) were performed at least once. Molecular genetic analysis was performed in 545 patients.

Results: The combination of non-invasive retinal imaging with molecular genetic analysis has continuously replaced electrophysiological testing as a primary tool for the diagnosis of IROD. Multiple novel imaging phenomena have been observed specific for IROD, although frequently not specific for certain associated genes. Early phenomena in retinal imaging modalities frequently precede ophthalmoscopic visible alterations and therefore facilitate early diagnosis. Mostly in cone dysfunction and congenital stationary night blindness ERG is superior to retinal imaging. Molecular genetic testing confirmed disease-causing mutations (1 in dominant or x-linked disorders, 2 in recessive disorders) in 229 patients (44.4%).

Conclusions: Non-invasive retinal imaging techniques advanced towards the primary tool for the diagnostic approach in suspected IROD and serve as the basis for planning of molecular genetic analysis. Multiple novel characteristic retinal imaging phenomena have been observed and increased our understanding of IROD. Patients have the advantage that imaging techniques are more widespread available than electrophysiological testing. A targeted diagnostic strategy reduces the diagnostic delay, enables an earlier counselling and therapy and avoids unnecessary diagnostic tests.