Foveal Sparing in Central Retinal Dystrophies

Abstract

PURPOSE. To describe foveal sparing (FS) in central retinal dystrophies (RD). METHODS. Participants for this retrospective study were identified from the retinal dystrophy database of the Department of Ophthalmology at Radboud University Medical Center. FS was defined as an intact foveal structure surrounded by at least 1808 of chorioretinal atrophy, and a best-corrected visual acuity (BCVA) of <1.0 logMAR (>20/200 Snellen). Eligible eyes were identified using fundus autofluorescence (FAF) images, and FS was confirmed using nearinfrared reflectance (NIR) imaging and spectral-domain optical coherence tomography when available. Clinical and demographic data were extracted from medical records. We performed quantification of FS and chorioretinal atrophic areas using semiautomated software on fundus autofluorescence and NIR images. We calculated the chronologic change using eye-wise linear regression. RESULTS. We identified 36 patients (56 eyes) with FS. RDs included: Stargardt disease (STGD1;20 patients), central areolar choroidal dystrophy (CACD; 7 patients), mitochondrial retinal dystrophy (MRD; 6 patients), pseudo-Stargardt pattern dystrophy (PSPD; 3 patients). Median age at first presentation was 60 (interquartile range [IQR] 54-63) years. Median BCVA at first presentation ranged from 20/25 Snellen in STGD1, to 20/38 Snellen in MRD. Progression of the chorioretinal atrophic area ranged from 0.26 (0.25-0.28) mm/year in PSPD, to 0.14 (0.11-0.22) in CACD. Change in FS area over time was similar between the different dystrophies. CONCLUSIONS. The presence of FS in different RDs suggests a disease-independent mechanism that prolongs the survival of the fovea. The associated preservation of BCVA is important for the individual prognosis and has implications for the design of therapeutic trials for RDs. Keywords: foveal sparing, retinal dystrophy, Stargardt disease, central areolar choroidal dystrophy, mitochondrial retinal dystrophy (STGD1), 8,10-13 central areolar choroidal dystrophy (CACD), 14 and maternally inherited diabetes and deafness (MIDD). 15,16 Geographic atrophy and reticular pseudo-drusen in age-related macular degeneration may also show a tendency to spare the fovea for a prolonged period of time. 7,9,17-20 Although there is no consensus definition of the term ''foveal sparing,'' it could be distinguished from a perimacular ring scotoma, which is located more peripherally in the macula, resulting in a central visual island frequently observed in retinitis pigmentosa (RP). 21 Bull's eye maculopathy is another separate entity, where an intact fovea is surrounded by ausually oval shaped-area of outer retinal atrophy. Historically, the term ''foveal sparing'' was coined by Hart et al. 22 to describe the sparing of the fovea from hemifield defects. In the context of macular disorders, Hart et al. 22 were the first

Clinical spectrum, genetic complexity and therapeutic approaches for retinal disease caused by ABCA4 mutations

“…However, the age of onset varies extensively, where a proportion of individuals start experiencing delayed vision loss between the 4th and 7th decades of life ( Gerber et al, 1995 ; Lambertus et al, 2016 ; Runhart et al, 2018 ; Runhart et al, 2019 ; Westeneng-van Haaften et al, 2012 ; Yatsenko et al, 2001 ; Zernant et al, 2017 ; Zernant et al, 2018 ). The exact age of disease onset is often difficult to determine, as many patients—particularly children—may be unaware of their visual impairment or have preserved central vision due to functional sparing of the fovea ( Bax et al, 2019b ; Fujinami et al, 2013b ; Nakao et al., 2012 ; Runhart et al, 2019 ; van Huet et al, 2014 ). In general, ABCA4 -associated retinopathy subtypes that manifest early in life tend to progress more rapidly, while a later age of onset is associated with a milder prognosis ( Fujinami et al., 2015 ; Tanaka et al, 2018 ; Zernant et al, 2017 ).…”

“…Numerous systematic protocols have been developed and this is the standard used by all clinical trials ( Table 6 ). Many studies have documented broad trends in BCVA progression and its relationship to other clinical features in ABCA4 -associated retinopathy ( Birch et al, 2001 ; Collison and Fishman, 2018 ; Ergun et al, 2005 ; Kong et al, 2016 ; Parodi et al, 2015 ; Querques et al, 2008 ; Testa et al, 2012 , 2014 ), however as a method, it is perhaps most susceptible to technical limitations such as measurement bias, repeatability as well as confounders that are specific to ABCA4 -associated retinopathy such as the variable status of the fovea ( Bax et al, 2019b ; Collison et al, 2019 ; Nakao et al., 2012 ; van Huet et al, 2014 ) and shifting of the preferred retinal locus (PRL) into consideration ( Bethlehem et al, 2014 ; Greenstein et al, 2008 ; Krishnan and Bedell, 2018 ; Schonbach et al, 2017a , 2018 ).…”

Phenotypic Differences in a PRPH2 Mutation in Members of the Same Family Assessed with OCT and OCTA

“…The following are available online at , Figure S1: Location of macular components in OCT images; Figure S2: Infrared images of right (upper) and left (down) eyes of control (A,B) and patients with PRPH2 gene mutation (C-I); Figure S3: Three-dimensional reconstruction from a dense OCT scan of some study patients associated to p.Arg195Leu mutation; Figure S4: Volume scan of the GCL thickness map (right) at 1, 2, and 3 circle diameters from the foveola. References [ 32 , 42 , 45 , 46 , 49 , 50 ] are cited in the Supplementary Materials.…”

Genotypes Predispose Phenotypes—Clinical Features and Genetic Spectrum of ABCA4-Associated Retinal Dystrophies

“…Among these variants, c.4519G>A, c.71G>A has been reported in late-onset STGD1 [29,30], but no foveal sparing pattern was reported in patients carrying c.1804C>T and c.4070C>A. To the best of our knowledge, the foveal sparing phenotype has been described in several retinal dystrophies, including STGD1 and age-related macular dystrophy [31,32], but not in patients with CRD. Here, we described a case of late-onset CRD (P09) with a foveal sparing pattern and preserved initial VA, which may provide a new aspect of the phenotype of CRD.…”