Reviewing the Role of Ultra-Widefield Imaging in Inherited Retinal Dystrophies

Ophthalmol Ther https://doi.org/10.1007/s40123-020-00241-1 REVIEW Reviewing the Role of Ultra-Widefield Imaging in Inherited Retinal Dystrophies Maria Vittoria Cicinelli . Alessandro Marchese . Alessandro Bordato . Maria Pia Manitto . Francesco Bandello . Maurizio Battaglia Parodi Received: January 3, 2020 Ó The Author(s) 2020 ABSTRACT Inherited retinal dystrophies (IRD) are a heterogeneous group of rare chronic disorders caused by genetically determined degeneration of photoreceptors and retinal pigment epithelium cells. Ultra-widefield (UWF) imaging is a useful diagnostic tool for evaluating retinal integrity in IRD, including Stargardt disease, retinitis pigmentosa, cone dystrophies, and Best vitelliform dystrophy. Color or pseudocolor and fundus autofluorescence images obtained with UWF provide previously unavailable information on the retinal periphery, which correlates well with visual field measurement or electroretinogram. Despite unavoidable artifacts of the UWF device, the feasibility of investigations in infants and in patients with poor fixation makes UWF imaging a precious resource in the diagnostic armamentarium for IRD. Keywords: Best vitelliform disease; Fundus autofluorescence; Inherited retinal dystrophy; Enhanced digital features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.11882325. M. V. Cicinelli (&)
A. Marchese
A. Bordato
M. P. Manitto
F. Bandello
M. Battaglia Parodi Department of Ophthalmology, San Raffaele VitaSalute University, Ospedale San Raffaele, Milan, Italy e-mail: Retinitis pigmentosa; Stargardt Ultra-widefield imaging dystrophy; Key Summary Points Inherited retinal dystrophies (IRD) are a heterogeneous group of rare chronic disorders caused by genetically determined degeneration of photoreceptors or retinal pigment epithelium (RPE) cells. Color and fundus autofluorescence ultrawidefield (UWF) imaging have added novel insights in the interpretation of both macular and peripheral changes occurring in IRD. UWF imaging aids in the diagnosis and monitoring of patients with IRD; UWF changes correlate well with functional damage on visual field test and electroretinogram. Advantages of digital UWF imaging systems include enhanced resolution, easier acquisition with non-compliant patients (i.e., children), and avoidance of pupil dilation. Future investigations on structure–function and phenotype–genotype correlations using UWF will increase our understanding of the complex spectrum of IRD. Ophthalmol Ther INTRODUCTION Inherited retinal dystrophies (IRD) are a heterogeneous group of rare chronic disorders caused by genetically determined degeneration of photoreceptors or retinal pigment epithelium (RPE) cells. IRD are heterogeneous in terms of onset of symptoms and severity of clinical manifestations. IRD can be clinically categorized into four groups: rod-dominant diseases, cone-dominant diseases, generalized retinal degenerations, and vitreoretinal disorders [1, 2]. An additional group of IRD includes pure macular diseases, namely Stargardt disease (STGD1), pattern dystrophy, Best vitelliform dystrophy (BVD), Sorsby disease, North Carolina dystrophy, and Doyne honeycomb dystrophy [3]. Specific complaints, age of onset, inheritance pattern, and electro-functional tests (such as full-field electroretinogram (ERG) and multifocal ERG) may suggest the site of retinal dysfunction and, in specific cases, the gene defect. There is currently no specific treatment for any form of retinal dystrophy; antioxidant drugs, such as lutein, photoprotection, and lowvision aids are the only therapeutic alternatives offered nowadays. Nevertheless, early diagnosis and better characterization are important for accurate information on prognosis, genetic counseling, and gene-targeted therapeutic options available in the future. The aim of the present narrative review is to elucidate the role of non-invasive imaging in IRD, focusing on widefield (WF) and ultra-widefield (UWF) imaging devices. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. NON-INVASIVE IMAGING AND WIDEFIELD APPLICATION IN IRD Fundus autofluorescence (FAF) is one of the most informative techniques in patients with IRD. Two types of FAF are mostly used in clinical practice: short wavelength autofluorescence (SW-FAF), with an emitting light of 488 nm, is specific for lipofuscin, and near-infrared autofluorescence (NIR-FAF), with an emitting light of 787 nm, is specific for melanin. The changes on SW- and NIR-FAF provide useful information about the pathophysiology of IRD. SW-FAF shows hyper-autofluorescence in the case of lipofuscin buildup [4] or outer retinal disruption [5]; on the other hand, hypo-autofluorescence corresponds to areas of RPE loss (as RPE atrophy) or masquerading of normal RPE autofluorescence (such as pigment clumping) [6–8]. SW-FAF signal may also transiently increase after blue light exposure; this phenomenon has been called photobleaching. The optical pigments of photoreceptors normally absorb light in the same spectrum of SW-FAF; illumination with blue light induces an isomerization of the optical pigments from the 11-cis to all-trans conformation, resulting in a temporary loss of their absorption properties [9]. Photobleaching might differ between healthy and diseased eyes, including intermediate age-related macular degeneration [10] and IRD [11]. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) evaluate the retinal and choroidal perfusion [12] and the presence of rare complications of IRD, such as cystoid macular edema (CME) or choroidal neovascularization (CNV) [13]. While they are useful at the first diagnosis, they are poorly applicable in monitoring patients with IRD. Optical coherence tomography (OCT) assesses the state of the vitreoretinal interface, the inner retinal layers, the photoreceptors, and the RPE; OCT also confirms the presence of specific features, including vitelliform accumulation in Best disease, flecks in STGD1, and foveal cavitation in certain cone-rod dystrophies [14, 15]. OCT angiography (OCTA) has added novel insights in the interpretation of vascular changes occurring in the macula in patients with IRDs. OCTA combines information from morphology and perfusion at the level of the superficial capillary plexus and the deep capillary plexus of the inner retina, at the choriocapillaris, and the choroidal layer. OCTA has shown interesting changes in a wide variety of IRD, including STGD1 [16], retinitis pigmentosa (RP) [17], and BVD [18]. Whereas the scanning Ophthalmol Ther range of most commercially available OCTA devices is still limited to the posterior pole, technical advances now allow scanning of larger areas of the retina (up to 80°) by montage of multiple scans [19, 20]. A swept-source OCTA device (PlexElite, Carl Zeiss Meditec, Dublin, CA, (...truncated)