Common clinical features of unilateral retinal pigment epithelium dysgenesis and combined hamartoma of the retina and retinal pigment epithelium

Background Herein, we report two cases of unilateral retinal pigment epithelium dysgenesis (URPED) in Chinese patients and explore the relationship between URPED and combined hamartoma of the retina and retinal pigment epithelium (CHRRPE). Case presentation The lesion margins in the two cases showed pathognomonic clinical features of URPED, namely, a scalloped reticular margin in hyperplastic retinal pigment epithelium and mild fibrosis. The hypoautofluorescence observed by fundus autofluorescence was inverted compared with that observed by fundus fluorescence angiography. A large amount of fibroglial proliferation and disorganization of the retina involving the whole layer, which are also found in peripapillary CHRRPE, were found in the lesions. Conclusions URPED appears to share some clinical features with CHRRPE, and the relationship between URPED and CHRRPE needs further study.

Twelve-year follow up of a case of autosomal recessive bestrophinopathy with transient resolution of retinal edema in one eye

Purpose To report 12-year follow-up of a patient with ARB. Case report A 25-year-old man presented with blurred vision in his both eyes (OU). Best-corrected visual acuity (BCVA) was 20/63 Snellen equivalent in the right eye (OD) and 20/32 Snellen equivalent in the left eye. The intraocular pressures and anterior segment examination were unrevealing in OU. Posterior segment examination revealed multiple yellowish flecks and dots in the posterior pole in OU. Optical coherence tomography (OCT) showed subretinal fluid (SRF), intraretinal hyporeflective spaces, elongated and shaggy photoreceptors and outer retinal defects. Fundus autofluorescence demonstrated mottling hyperautofluorescence and hypoautofluorescence in the posterior pole in OU. Fluorescein angiography illustrated hyperfluorescence in the posterior pole and surrounding the arcades in OU. Multifocal electroretinography objectified mild to markedly abnormal responses in all ring areas in OU. Molecular genetic testing confirmed two heterozygous sequence variations in the BEST1 gene. At 4 years of follow-up, OCT revealed a complete resolution of SRF and a partial resolution of intraretinal hyporeflective spaces in the OD with corresponding improvement in the BCVA to 20/23 Snellen equivalent in the OD, even though outer retinal defects persisted. Our patient denied recent changes in his alimentary habits and medical history at that time. Posteriorly, SRF and intraretinal hyporeflective spaces reappeared in the OD. Conclusion To the best of our knowledge, this is the first case report of ARB with a transient resolution of retinal edema in one eye without medical treatment and dietary therapy.

An integrated analysis of clinical and morphometric indications of atrophic forms of age-related macular degeneration

The atrophic form of late age-related macular degeneration (AMD) is a common cause of severe vision loss. Recently, a new classification system has been proposed, which identifies two types of atrophy in the late stage of AMD that require a more detailed study: (1) drusenassociated geographic atrophy (GA), which is the final stage of progression of dry AMD, and (2) macular atrophy (MA), which occurs in wet AMD, including the period of AMD treatment with angiogenesis inhibitors. Purpose: an integrated analysis of clinical and morphometric signs of atrophic AMD forms. Material and methods. 48 people (61eyes) aged 48–84 with GA (group 1) and MA (group 2) and a control group, recruited from age-matching 25 healthy volunteers (35 eyes), underwent standard ophthalmological examinations, fundus autofluorescence (FAF) with lesion area measurement, fundus photography, optical coherence tomography (OCT) in the standard mode and Enhanced Depth Imagine Mode, Multicolor, and OCT angiography. Results. The comparative analysis of two atrophic AMD forms showed that in GA eyes, foci of atrophy capturing the fovea were significantly more common, while, contrariwise in MA eyes atrophic foci not capturing the fovea were more frequent (p < 0.05). Photoreceptor tubulation was diagnosed mainly in eyes with GA (p < 0.05). The morphometric analysis showed a significant decrease in the subfoveal thickness of the choroid in the groups with GA and MA as compared to the control (p < 0.05), whilst no significant differences between two groups were noted. The assessment of the frequency of occurrence of types of fundus AF patterns in groups 1 and 2 followed by a comparative analysis, showed the presence of all types of patterns in GA patients, including the heterogeneous and the bordering pattern (p < 0.05). In the MA group, diffuse and focal types of patterns were revealed, while the frequency of the diffuse pattern turned out to be significantly more frequent (p < 0.05). Conclusion. The integrated analysis revealed the main semiological signs and morphometric parameters, their features and prevalence in GA and MA, which may have diagnostic and prognostic importance for the management and treatment of patients with AMD.

Subthreshold Laser Treatment for Serous Retinal Detachment Associated with Tilted Disc Syndrome

Persistent serous retinal detachment (SRD) is a common complication of tilted disc syndrome (TDS). The purpose of this study is to evaluate the efficacy of subthreshold laser photocoagulation for SRD associated with TDS. This retrospective, single-center study included 5 eyes of 5 patients with TDS-associated SRD treated by subthreshold laser treatment. SRD was completely absorbed in 4 eyes within 4 months after initial treatment. However, it recurred in 2 eyes; one required additional laser treatment and one showed spontaneous resolution. Eventually, all 4 eyes showed complete SRD resorption. The mean visual acuities at enrollment and 1 and 3 months showed no significant differences. The mean central macular thickness showed a significant decrease at 3 months. Two eyes showed changes in fundus autofluorescence findings at the laser ablation site. However, there were no instances of laser scotoma and no laser-induced retinal scarring on color fundus photography performed at the end of treatment. In conclusion, subthreshold laser photocoagulation is an effective treatment for SRD associated with TDS. Thus, the clinical indications of subthreshold laser photocoagulation may be extended to SRD in patients with TDS.

Retinal Progression Biomarkers of Early and Intermediate Age-Related Macular Degeneration

Early and intermediate AMD patients represent a heterogeneous population with an important but variable risk of progression to more advanced stages of the disease. The five-year progression from early and intermediate AMD to late disease is known to range from 0.4% to 53%. This wide variation explains the particular interest in searching predictive AMD biomarkers. Clinical parameters such as drusen size, presence of pigmentary abnormalities, and fellow eye status were, traditionally, the more important predictive elements. Multimodal retinal assessment (Color Fundus Photography, Optical Coherence Tomography, Optical Coherence Angiography and Fundus Autofluorescence) is providing new and accurate image biomarkers, useful in research and in daily practice. If individual progression risk could be anticipated, then management plans should be adapted accordingly, considering follow-up intervals and therapeutic interventions. Here, we reviewed the most important image progression biomarkers of early and intermediate AMD with relevant interest in clinical practice.

Genotype-Specific Lesion Growth Rates in Stargardt Disease

Reported growth rates (GR) of atrophic lesions in Stargardt disease (STGD1) vary widely. In the present study, we report the longitudinal natural history of patients with confirmed biallelic ABCA4 mutations from five genotype groups: c.6079C>T, c.[2588G>C;5603A>T], c.3113C>T, c.5882G>A and c.5603A>T. Fundus autofluorescence (AF) 30° × 30° images were manually segmented for boundaries of definitely decreased autofluorescence (DDAF). The primary outcome was the effective radius GR across five genotype groups. The age of DDAF formation in each eye was calculated using the x-intercept of the DDAF effective radius against age. Discordance between age at DDAF formation and symptom onset was compared. A total of 75 eyes from 39 STGD1 patients (17 male [44%]; mean ± SD age 45 ± 19 years; range 21–86) were recruited. Patients with c.3113C>T or c.6079C>T had a significantly faster effective radius GR at 0.17 mm/year (95% CI 0.12 to 0.22; p < 0.001 and 0.14 to 0.21; p < 0.001) respectively, as compared to those patients harbouring c.5882G>A at 0.06 mm/year (95% CI 0.03–0.09), respectively. Future clinical trial design should consider the effect of genotype on the effective radius GR and the timing of DDAF formation relative to symptom onset.

Peeling of Epiretinal Membrane: Analysis of Prognostic Factors and Surgical Complications, Impacting Visual Outcome

An epiretinal membrane (ERM) is the most common pathology of the vitreoretinal interface. First-line therapy for a symptomatic ERM is vitrectomy with ERM peeling. Clinical prognostic factors for postoperative visual acuity improvement include baseline visual acuity, age, duration of symptoms, and baseline pseudophakia. Postoperative optical coherence tomography (OCT) shows improvement in the integrity of the inner/outer segment junction and a reduction in the thickness of the ganglion cell complex and foveola. Retinal changes after ERM peel are also described using OCT angiography, fluorescein angiography, fundus autofluorescence, and multifocal retinography. Complications of ERM peeling include cataract formation, retinal breaks/detachments, ERM recurrence, and macular holes.

Multimodal Imaging of Torpedo Maculopathy With Fluorescence Adaptive Optics Imaging of Individual Retinal Pigmented Epithelial Cells

Torpedo maculopathy (TM) is a rare congenital defect of the retinal pigment epithelium (RPE). The RPE is often evaluated clinically using fundus autofluorescence (AF), a technique that visualizes RPE structure at the tissue level from the intrinsic AF of RPE fluorophores. TM lesions typically emit little or no AF, but this macroscopic assessment is unable to resolve the RPE cells, leaving the organization of the RPE cell mosaic in TM unknown. We used fluorescence adaptive optics scanning laser ophthalmoscopy (AOSLO) to show here for the first time the microscopic cellular-level structural alterations to the RPE cell mosaic in TM that underlie the tissue-level changes seen in conventional clinical imaging. We evaluated two patients with TM using conventional clinical imaging techniques and adaptive optics (AO) infrared autofluorescence (IRAF) in AOSLO. Confocal AOSLO revealed relatively normal cones outside the TM lesion but altered cone appearance within it and along its margins in both patients. We quantified cone topography and RPE cell morphometry from the fovea to the margin of the lesion in case 1 and found cone density to be within the normal range across the locations imaged. However, RPE morphometric analysis revealed disrupted RPE cells outside the margin of the lesion; the mean RPE cell area was greater than two standard deviations above the normative range up to approximately 1.5 mm from the lesion margin. Similar morphometric changes were seen to individual RPE cells in case 2. Multi-modal imaging with AOSLO reveals that RPE cells are abnormal in TM well beyond the margins of the characteristic TM lesion boundary defined with conventional clinical imaging. Since the TM fovea appears to be fully formed, with normal cone packing, it is possible that the congenital RPE defect in TM occurs relatively late in retinal development. This work demonstrates how cellular level imaging of the RPE can provide new insight into RPE pathologies, particularly for rare conditions such as TM.

Deep Learning to Distinguish ABCA4-Related Stargardt Disease from PRPH2-Related Pseudo-Stargardt Pattern Dystrophy

(1) Background: Recessive Stargardt disease (STGD1) and multifocal pattern dystrophy simulating Stargardt disease (“pseudo-Stargardt pattern dystrophy”, PSPD) share phenotypic similitudes, leading to a difficult clinical diagnosis. Our aim was to assess whether a deep learning classifier pretrained on fundus autofluorescence (FAF) images can assist in distinguishing ABCA4-related STGD1 from the PRPH2/RDS-related PSPD and to compare the performance with that of retinal specialists. (2) Methods: We trained a convolutional neural network (CNN) using 729 FAF images from normal patients or patients with inherited retinal diseases (IRDs). Transfer learning was then used to update the weights of a ResNet50V2 used to classify the 370 FAF images into STGD1 and PSPD. Retina specialists evaluated the same dataset. The performance of the CNN and that of retina specialists were compared in terms of accuracy, sensitivity, and precision. (3) Results: The CNN accuracy on the test dataset of 111 images was 0.882. The AUROC was 0.890, the precision was 0.883 and the sensitivity was 0.883. The accuracy for retina experts averaged 0.816, whereas for retina fellows it averaged 0.724. (4) Conclusions: This proof-of-concept study demonstrates that, even with small databases, a pretrained CNN is able to distinguish between STGD1 and PSPD with good accuracy.