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To compare the 2-year outcome to antivascular endothelial growth factor therapy for myopic choroidal neovascularization (CNV) in the eyes with or without dome-shaped macula (DSM).Data from treatment-naive myopic CNV with a 2-year follow-up were retrospectively collected and divided into two groups according to the presence of DSM. The best-corrected visual acuity was acquired at baseline, 3, 12, and 24 months. The association between visual outcomes and CNV type and area, presence of scleral-derived feeder vessel, macular atrophy, and lacquer cracks at baseline was also evaluated.Fifty-four eyes of 54 patients were included; 18 eyes (33.4%) had DSM. Choroidal neovascularization was foveal in 10 DSM eyes (55.6%) and in 30 non-DSM eyes (83.9%), P = 0.033. At baseline, the mean best-corrected visual acuity was significantly higher in the DSM group (68.33 ± 12.04 Early Treatment Diabetic Retinopathy Study letters, 20/40 Snellen) compared with the non-DSM group (57.75 ± 13.46 Early Treatment Diabetic Retinopathy Study letters, 20/72 Snellen; P = 0.007). This difference disappeared after 3 months and did not reoccur afterward. All other parameters were not significantly associated with visual outcomes.Overall, DSM does not represent a negative prognostic factor in response to antivascular endothelial growth factor therapy in myopic CNVs after 2 years. However, in DSM eyes, CNVs tend to be extrafoveal, thus ensuring a good visual prognosis from the earliest stage of the disease.

Kyrieleis plaques (KP) represent a peculiar type of vasculitis affecting retinal arterial branches in a beaded segmental pattern that can be found in several posterior inflammatory ocular conditions. The nature and precise location of KP is unclear. Adaptive Optics (AO) provides an in vivo visualization of retinal vasculature on a microscopic level, thus permitting a more detailed characterization of KP as compared to traditional imaging techniques. This study aims to report AO imaging of KP in Varicella Zoster virus (VZV)-associated posterior uveitis and to correlate the findings with traditional imaging techniques. Three patients diagnosed with VZV posterior uveitis underwent adaptive optics (AO) imaging and traditional multimodal imaging techniques, including fundus photography, fluorescein angiography, indocyanine green angiography and optical coherence tomography. In all subjects, AO imaging revealed segmental hyporeflectivity confined to the vessel wall, with no evidence of arterial wall disruption or extravascular involvement. In our series, AO findings support the view that KP are localized within the inner arterial wall, possibly at the endothelial level.

Objective To assess the time course and risk factors for conversion of incomplete retinal pigment epithelium and outer retina atrophy (iRORA) to complete retinal pigment epithelium and outer retina atrophy (cRORA) in eyes with non-neovascular intermediate age-related macular degeneration (iAMD), using optical coherence tomography (OCT) analysis. Design Retrospective survival study. Participants Tracked structural Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) volume datasets from 2 retinal specialists at the University of California–Los Angeles were retrospectively screened to identify consecutive participants with non-neovascular iAMD without signs of atrophy or macular neovascularization in either eye at baseline. Methods In the first stage of selection, 321 consecutive iAMD eyes were screened for onset of iRORA. Eyes that developed iRORA within the first 24 months were followed for an additional 24 months to assess the rate of conversion to cRORA. A Kaplan-Meier survival curve was formulated to illustrate the conversion from iRORA to cRORA. Results Among 321 baseline participants with iAMD, 87 incident iRORA lesions (50 eyes, 42 participants) were included in the conversion analysis. Eighty-one iRORA lesions (93.1%) converted to cRORA within 24 months (median 14 months). Multivariate binary logistic regression analysis indicated that intraretinal hyperreflective foci and extrafoveal iRORA location at baseline were associated with a faster rate of progression to cRORA (model R2 = 0.816, p Conclusions The majority of incident iRORA lesions progress to cRORA within a 24-month period. These findings may be of value in the design of early intervention trials for risk stratification and prognostication but need to be validated with a prospective analysis.

Objective: To evaluate the effect of changing slab position on the correlation between choriocapillaris (CC) flow deficits (FD) in eyes with geographic atrophy (GA) and yearly enlargement rate (yER) of GA. Methods: OCT and OCTA images obtained on Cirrus HD-OCT device were collected from patients with GA. Each patient underwent OCTA scan at baseline and two OCT scans, one at baseline and one after at least 12 months. GA was delineated on en-face fundus image to calculate yER. OCTA images were generated from three 10 µm thick slabs 11, 21 and 31 µm posterior to RPE-fit line. A 100 µm-wide concentric rings were generated around GA to calculate FD% in each ring which was correlated with yER. Results: For the 11-21 µm slab, FD% was not significantly correlated with yER for any of the rings (p > 0.05). For the 21-31 and 31-41 µm slab, FD% of rings located in the 500 µm region around GA was significantly correlated with yER (p < 0.05). However, in all slab locations, there was no significant correlation between yER and CC FD% of rings located beyond the 500 µm region (p > 0.05). Conclusions: Slab selection for quantification of CC FD% may have a significant impact on quantitative results in eyes with GA.

Complete congenital stationary night blindness (cCSNB) due to mutations in TRPM1, GRM6, GPR179, NYX, or leucine-rich repeat immunoglobulin-like transmembrane domain 3 (LRIT3) is an incurable inherited retinal disorder characterized by an ON-bipolar cell (ON-BC) defect. Since the disease is non-degenerative and stable, treatment could theoretically be administrated at any time in life, making it a promising target for gene therapy. Until now, adeno-associated virus (AAV)-mediated therapies lead to significant functional improvements only in newborn cCSNB mice. Here we aimed to restore protein localization and function in adult Lrit3−/− mice. LRIT3 localizes in the outer plexiform layer and is crucial for TRPM1 localization at the dendritic tips of ON-BCs and the electroretinogram (ERG)-b-wave. AAV2-7m8-Lrit3 intravitreal injections were performed targeting either ON-BCs, photoreceptors (PRs), or both. Protein localization of LRIT3 and TRPM1 at the rod-to-rod BC synapse, functional rescue of scotopic responses, and ON-responses detection at the ganglion cell level were achieved in a few mice when ON-BCs alone or both PRs and ON-BCs, were targeted. More importantly, a significant number of treated adult Lrit3−/− mice revealed an ERG b-wave recovery under scotopic conditions, improved optomotor responses, and on-time ON-responses at the ganglion cell level when PRs were targeted. Functional rescue was maintained for at least 4 months after treatment., Graphical abstract, Zeitz and colleagues report in this study strong restoration of scotopic function in adult Lrit3−/− mice affected with complete congenital stationary night blindness as shown by a gene therapy approach targeting bipolar and/or photoreceptor cells. Findings were validated by immunolocalization studies, electroretinogram, multi-electrode array measurements, and optomotor response evaluation.

Purpose To evaluate the correlation between choriocapillaris (CC) flow alterations and scotopic macular sensitivity (sMS) in patients with early and intermediate age-related macular degeneration (AMD). Design Prospective cross-sectional study. Methods We acquired 2 3 × 3 mm and 2 6 × 6 mm swept-source optical coherence tomography angiography (OCTA) images of 1 eye of consecutive early or intermediate AMD patients at the Doheny UCLA Eye Centers. After 30 minutes of dark adaptation, the same eye underwent scotopic microperimetry with an 18-degree-wide grid (52 stimuli) centered on the fovea. The 2 en face CC angiograms obtained from each scan pattern were compensated for signal loss and averaged. The main outcome measures were correlation between percentages of flow deficits (FD3mm and FD6mm) and sMS in the central 10° (MS10) and the overall pattern (MS18). Results Thirty eyes of 30 patients were enrolled, with 14 (46.7%) having subretinal drusenoid deposits (SDD). In the averaged OCTA scans, the FD3mm was 12.56% ± 2.41% while the FD6mm was 9.33% ± 1.84%. The mean MS10 and MS18 were 13.84 ± 5.89 dB and 14.64 ± 5.21 dB, respectively. For the MS10, the multivariate regression analysis showed a significant association only with FD3mm (β: −0.628, P Conclusions Our study reports a significant correlation between the CC flow impairment and the sMS in eyes with early or intermediate AMD. If replicated in future longitudinal studies, the choriocapillaris FD may prove to be a useful parameter for evaluating the functional status and prognosis of these eyes.

Variants in the X-linked retinitis pigmentosa GTPase regulator gene (RPGR) and, specifically, in its retinal opening reading frame-15 isoform (RPGRORF15) may cause rod-cone (RCD), cone, and cone-rod dystrophies (CDs and CRDs). While RPGR-related RCDs have been frequently evaluated, the characteristics and progression of RPGR-related CD/CRDs are largely unknown. Therefore, the goal of our work was to perform genotype–phenotype correlations specifically in RPGRORF15-related CD/CRDs. This retrospective longitudinal study included 34 index patients and two affected relatives with a molecular diagnosis of RPGR-related CD/CRDs. Patients were recruited at the “Quinze-Vingts” Hospital, Paris, France and screened for mutations in RPGRORF15 at the Institut de la Vision, Paris, France. We identified 29 distinct variants, of which 27 were truncating. All were located in the 3′ half of the RPGRORF15 transcript. Twenty of them were novel. Fifteen subjects were affected by CD, the remaining had CRD. When analyzing the longitudinal data, a progressive decline in visual acuity (VA) was noted, with more than 60% of the patients reaching VA ≥ 1 LogMar in the best eye after the fifth decade of life. To our knowledge, this is the largest described study of a cohort of CD/CRD patients affected by RPGRORF15 variants. Longitudinal data showed a rapidly progressive disease, possibly locating an optimal window of intervention for future therapies in younger ages.

Inherited retinal diseases (IRD) are a group of heterogeneous disorders, most of which lead to blindness with limited therapeutic options. Pathogenic variants in RBP4, coding for a major blood carrier of retinol, retinol-binding protein 4, are responsible for a peculiar form of IRD. The aim of this study was to investigate if retinal function of an RBP4-related IRD patient can be improved by retinol administration. Our patient presented a peculiar white-dot retinopathy, reminiscent of vitamin A deficient retinopathy. Using a customized next generation sequencing (NGS) IRD panel we discovered a novel loss-of-function homozygous pathogenic variant in RBP4: c.255G >A, p.(Trp85*). Western blotting revealed the absence of RBP4 protein in the patient’s serum. Blood retinol levels were undetectable. The patient was put on a high-dose oral retinol regimen (50,000 UI twice a week). Subjective symptoms and retinal function markedly and sustainably improved at 5-months and 1-year follow-up. Here we show that this novel IRD case can be treated by oral retinol administration.

Biallelic variants in CLRN1 are responsible for Usher syndrome 3A and non-syndromic rod-cone dystrophy (RCD). Retinal findings in Usher syndrome 3A have not been well defined. We report the detailed phenotypic description of RCD associated with CLRN1 variants in a prospective cohort.Patients were clinically investigated at the National Reference Center for rare ocular diseases at the Quinze-Vingts Hospital, Paris, France. Best-corrected visual acuity (BCVA) tests, Goldmann perimetry, full-field electroretinography (ffERG), retinal photography, near-infrared reflectance, short-wavelength and near-infrared autofluorescence, and optical coherence tomography (OCT) were performed for all patients.Four patients from four unrelated families were recruited. Mean follow-up was 11 years for three patients, and only baseline data were available for one subject. Median BCVA at baseline was 0.2 logMAR (range, 0.3-0). ffERG responses were undetectable in all subjects. The III4e isopter of the Goldmann visual field was constricted to 10°. The retinal phenotype was consistent in all patients: small whitish granular atrophic areas were organized in a network pattern around the macula and in the midperiphery. OCT showed intraretinal microcysts in all patients. Upon follow-up, all patients experienced a progressive BCVA loss and further visual field constriction. Four distinct pathogenic variants were identified in our patients: two missense (c.144TG, p.(Asn48Lys) and c.368CA, p.(Ala123Asp)) and two frameshift variants (c.176del, p.(Gly59Valfs*13) and c.230dup, p.(Ala78Serfs*52)).RCD in Usher 3A syndrome has some distinctive features. It is a severe photoreceptor dystrophy with whitish granular posterior pole appearance and cystic maculopathy.

International audience; Purpose: To document the rod-cone dystrophy phenotype of patients with Usher syndrome type 1 (USH1) harboring MYO7A mutations.Methods: Retrospective cohort study of 53 patients (42 families) with biallelic MYO7A mutations who underwent comprehensive examination, including functional visual tests and multimodal retinal imaging. Genetic analysis was performed either using a multiplex amplicon panel or through direct sequencing. Data were analyzed with IBM SPSS Statistics software v. 21.0.Results: Fifty different genetic variations including 4 novel were identified. Most patients showed a typical rod-cone dystrophy phenotype, with best-corrected visual acuity and central visual field deteriorating linearly with age. At age 29, binocular visual field demonstrated an average preservation of 50 central degrees, constricting by 50% within 5 years. Structural changes based on spectral domain optical coherence tomography, short wavelength autofluorescence, and near-infrared autofluorescence measurements did not however correlate with age. Our study revealed a higher percentage of epiretinal membranes and cystoid macular edema in patients with MYO7A mutations compared with rod-cone dystrophy patients with other mutations. Subgroup analyses did not reveal substantial genotype-phenotype correlations.Conclusion: To the best of our knowledge, this is the largest French cohort of patients with MYO7A mutations reported to date. Functional visual characteristics of this subset of patients followed a linear decline as in other typical rod-cone dystrophy, but structural changes were variable indicating the need for a case-by-case evaluation for prognostic prediction and choice of potential therapies.

To correlate choriocapillaris (CC) flow deficits (FD) in eyes with geographic atrophy (GA) at various distances from the border of the GA lesion with yearly enlargement rate (yER) of GA. In this retrospective study, spectral domain optical coherence tomography (SD-OCT) and SD optical coherence tomography angiography (OCTA) images were collected from patients with GA, who were imaged at Doheny Eye Centers between 2016 and 2018, using the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA). All enrolled patients had one baseline 6 × 6 mm OCTA scan and two 6 × 6 mm SD-OCT cubes, one at baseline and one at a follow-up visit at least 12 months later. The border of the GA was manually outlined on the en face OCT fundus image and the yER was calculated after square root transformation. A grid composed of 100-μm-wide successive concentric rings was created around the GA lesion on the OCTA CC slab using ImageJ and the FD% was calculated from the binarized image. FD% from each ring was correlated with the yER of GA. Thirty eyes of 22 patients were included in the study. The mean yER was 0.2 ± 0.15 mm. The FD% in the first five rings (from 0 to 500 μm from the border of GA) was significantly correlated with the yER. However, there was no statistically significant correlation between the yER and CC FD% beyond 500 μm from the GA lesion. Only the choriocapillaris FD% in the 500-μm region immediately surrounding GA lesions appears to predict the rate of enlargement of these lesions.

Variants in the X-linked retinitis pigmentosa GTPase regulator gene (

We read with interest the paper by Chatziralli et al. which highlights the unique opportunities COVID-19 provides to embrace technologically driven teaching modalities in ophthalmic education [1]. We designed and implemented an e-learning tool to reduce extraneous cognitive overload in undergraduate ophthalmic teaching and would like to share our experience with readers. Beyond its evolving impact on postgraduate training, COVID-19 threatens undergraduate ophthalmic teaching, exposure to which is increasingly limited [2]. Cognitive load theory (CLT) is a well-established model of information processing, which assumes a limited working memory, whereby the reduction of superfluous knowledge improves retention [3]. Adherence to CLT principles in resource design may improve student satisfaction. We applied over a decade of course evaluations (n = 1109) to the design of an e-learning resource tailored to reduce extraneous cognitive load, and further studied its uptake amongst senior Edinburgh Medical School undergraduates through a non-randomised pretest/posttest study (n = 116 responses, 29% attrition) over an 8-week assessment period. Eight goal-free ophthalmic disease-specific factsheets were created, integrating basic and clinical sciences teaching across 30+ information sources (Fig. 1). Other strategies employed included coherence (exclusion of extraneous words), spatiotemporal contiguity (presenting corresponding words and pictures in close proximity and simultaneously), signalling (highlighting important words), and personalisation (employing a conversational style) [4]. Key facts were thematically arranged in comparative statements underscoring variations between differential diagnoses, and hyperlinked to online content. Clinical image courtesy of Jonathan Trobe, M.D., accessed at https://commons.wikimedia.org/wiki/File:Acute_Angle_Closure-glaucoma.jpg, no changes made (CC BY 3.0). Module satisfaction correlated with teaching quality (r2 = 0.61, P < 0.01), resource availability (r2 = 0.62, P < 0.01), and learning objective achievement (r2 = 0.64, P < 0.01). Compared to existing resources, the intervention received improved ratings for quality (36 percentage points increase, P < 0.001, 95% CI 28–45), utility (27 percentage points, P < 0.001, 95% CI 15–39), reliability (34 percentage points, P < 0.001, 95% CI 23–46), and satisfaction (44 percentage points, P < 0.001, 95% CI 34–53) (Fig. 2). All comparative responses were more favourable, and all associated descriptors were positive (144% increase). Error bars signify confidence intervals. POMS = [(observed − minimum)/(maximum − minimum)]. Our resources conferred rapid improvements in the perceived quality, utility, and reliability of, and overall satisfaction with, local ophthalmology teaching materials. We, therefore, support the authors’ conclusion that high-quality content remains an educational priority [1]. Face-to-face teaching restrictions post COVID-19 will require innovative and accessible learning materials [5]. Chatziralli I, Ventura CV, Touhami S, Reynolds R, Nassisi M, Weinberg T, et al. Transforming ophthalmic education into virtual learning during COVID-19 pandemic: a global perspective. Eye. 2020:1–8. https://doi.org/10.1038/s41433-020-1080-0. [Epub ahead of print] Hill S, Dennick R, Amoaku W. Present and future of the undergraduate ophthalmology curriculum: a survey of UK medical schools. Int J Med Educ. 2017;8:389–95. Article Google Scholar Van Merrienboer JJ, Sweller J. Cognitive load theory in health professional education: design principles and strategies. Med Educ. 2010;44:85–93. Article Google Scholar Mayer RE. Multimedia learning. In: Psychology of learning and motivation. Academic Press; 2002. Vol 41, p. 85–139. Dhillon N, Dhillon B. On-line lessons learned post Covid-19: mater artium necessitas [letter]. BMJ Stel. 2020. Available from: https://stel.bmj.com/content/6/4/196.responses. [Accessed 17 July 2020]. Download references Ophthalmology, Division of Health Sciences, The University of Edinburgh, Edinburgh, UK Nikolaos Tzoumas, Toby Boote, Jennie Higgs, Heather Ellis, Baljean Dhillon & Peter Cackett Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK Nikolaos Tzoumas You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to Nikolaos Tzoumas. The authors declare that they have no conflict of interest. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions Tzoumas, N., Boote, T., Higgs, J. et al. Comment on: Transforming ophthalmic education into virtual learning during COVID-19 pandemic: a global perspective. Eye (2020). https://doi.org/10.1038/s41433-020-01182-6 Download citation Received: 09 August 2020 Revised: 03 September 2020 Accepted: 04 September 2020 Published: 14 September 2020 DOI: https://doi.org/10.1038/s41433-020-01182-6

Purpose To quantify inner and outer retinal layer thicknesses and understand their relevance to visual function among young adults born extremely preterm (EP). Design Prospective observational study with 19 years of follow-up. Participants A total of 354 eyes (226 eyes of former EP infants and 128 age-matched full-term control eyes) from 177 young adults were evaluated. Among EP participants, 50% of eyes (112/226) were not previously diagnosed with neonatal retinopathy of prematurity (ROP), 38% of eyes (84) had ROP not deemed to require treatment in the neonatal period, and 13% of eyes (30) had neonatal cryotherapy or laser ablation for ROP. Methods Subjects underwent eye examinations including best-corrected visual acuity (BCVA) and Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) macular spectral-domain (SD) OCT imaging. Retinal layers were auto-segmented and thickness profiles were computed at the fovea by the instrument software. Main Outcome Measures Correlation between retinal sublayer thickness and BCVA. Results Compared with control eyes, the inner and outer retinal layers of EP eyes were significantly thicker and BCVA was significantly reduced. Retinal layer thicknesses and BCVA were similar for untreated EP eyes and those without neonatal ROP. In contrast, treated eyes had increased inner and outer retinal layer thickness and decreased vision. Inner retinal layer thickness was moderately correlated with worse BCVA (r = 0.30, P Conclusions Extremely premature birth influences maturation of the fovea and visual outcomes into early adult life. Increased ganglion cell layer thickness was associated with worse BCVA. Eyes requiring neonatal treatment for ROP had associated worse BCVA at the age of 19 years.

International audience; Cyclic nucleotide-gated channel β1 (CNGB1) encodes the 240-kDa β subunit of the rod photoreceptor cyclic nucleotide-gated ion channel. Disease-causing sequence variants in CNGB1 lead to autosomal recessive rod-cone dystrophy/retinitis pigmentosa (RP). We herein present a comprehensive review and analysis of all previously reported CNGB1 sequence variants, and add 22 novel variants, thereby enlarging the spectrum to 84 variants in total, including 24 missense variants (two of which may also affect splicing), 21 nonsense, 19 splicing defects (7 at noncanonical positions), 10 small deletions, 1 small insertion, 1 small insertion-deletion, 7 small duplications, and 1 gross deletion. According to the American College of Medical Genetics and Genomics classification criteria, 59 variants were considered pathogenic or likely pathogenic and 25 were variants of uncertain significance. In addition, we provide further phenotypic data from 34 CNGB1-related RP cases, which, overall, are in line with previous findings suggesting that this form of RP has long-term retention of useful central vision despite the early onset of night blindness, which is valuable for patient counseling, but also has implications for it being considered a priority target for gene therapy trials.

Purpose To characterize changes in retinal perfusion during pregnancy and the postpartum period using optical coherence tomography angiography (OCTA). Methods A nonmydriatic OCTA camera was used to image healthy women who were pregnant or in the postpartum period along with nonpregnant controls. Perfusion density (PD) and vessel length density (VLD) in the superficial capillary plexus (SCP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were evaluated. Results A total of 16, 15, and 13 eyes from nonpregnant, pregnant, and healthy postpartum subjects, respectively, were evaluated. When compared to controls, there were significant increases in ICP PD during the second and third trimester of pregnancy, along with significant decreases in both PD and VLD in SCP, ICP, and DCP up to 14 weeks postpartum. Conclusions During pregnancy, vascular changes consistent with retinal vasodilation were noted in the ICP. During the postpartum period, changes in retinal vasculature suggest relative vasoconstriction involving all three layers when compared to both the pregnant and nonpregnant states. Translational relevance Detecting postpartum changes in retinal vasculature could offer important insights into postpartum physiology throughout the body.

Age-related macular degeneration (AMD) is a progressive neuro-retinal disease and the leading cause of central vision loss among elderly individuals in the developed countries. Modern ocular imaging technologies constitute an essential component of the evaluation of these patients and have contributed extensively to our understanding of the disease. A challenge with any review of ocular imaging technologies is the rapid pace of progress and evolution of these instruments. Nonetheless, for proper and optimal use of these technologies, it is essential for the user to understand the technical principles underlying the imaging modality and their role in assessing the disease in various settings. Indeed, AMD, like many other retinal diseases, benefits from a multimodal imaging approach to optimally characterize the disease. In this chapter, we will review the various imaging technologies currently used in the assessment and management of AMD.

Thirty-eight patients from 37 families with retinitis pigmentosa (RP) underwent macular 6 × 6-mm swept-source optical coherence tomography angiography (SS-OCTA) and 30° near-infrared fundus autofluorescence (NIR-FAF) acquisitions in one eye. Superficial vascular complex (SVC), deep capillary complex (DCC) and choriocapillaris (CC) angiograms were registered with NIR-FAF acquisitions to comparatively assess subjects with and without central area of preserved NIR-FAF (APA). On the subset of patients showing an APA, the vessel densities for SVC and DCC and flow deficits for CC were assessed in three directions (superior, inferior and temporal) from the fovea and compared to healthy 1:1 age-matched controls. Nine patients with no APA had evidence of severe central OCTA alterations at all levels, especially in the DCC. In the other 29 subjects presenting APA, all OCTA parameters were similar to healthy eyes within the APA, where the retina preserves its structural integrity. Outside the APA, both the DCC and CC were significantly reduced in all directions. These alterations are probably related to the outer retinal atrophy outside the APA. Comparing OCTA to other imaging modalities is helpful to determine the potential interest of OCTA findings as an outcome measure for disease status and progression.

Aims To compare the biometric data from partial coherence interferometry (PCI) and swept-source OCT (SS-OCT) in patients with age-related cataract and epiretinal membrane (ERM): ERM, ERM with foveoschisis and macular pseudohole. Methods 49 eyes of 49 subjects including 36 ERM, 9 ERM foveoschisis and 4 macular pseudohole were analysed to evaluate the axial length (AL) measurements and the presence of AL measurement errors, defined basing on the shape of the biometric output graphs and on the concordance of AL values between instruments. Eyes with ERM were divided in four stages according to OCT features (i.e. presence/absence of the foveal pit, presence of ectopic inner foveal layers, disrupted retinal layers). Results The devices provided similar mean AL measurements in all subgroups, with differences Conclusion Both devices provide reliable biometric data in the majority of patients and can be used in the preoperative assessment of patients with age-related cataract and ERM. In eyes with ectopic inner foveal layers, attention should be paid as AL measurement and refractive prediction errors may occur, more frequently with the PCI device.

Age-related macular degeneration (AMD) is a progressive neuro-retinal disease and the leading cause of central vision loss among elderly individuals in the developed countries. Modern ocular imaging technologies constitute an essential component of the evaluation of these patients and have contributed extensively to our understanding of the disease. A challenge with any review of ocular imaging technologies is the rapid pace of progress and evolution of these instruments. Nonetheless, for proper and optimal use of these technologies, it is essential for the user to understand the technical principles underlying the imaging modality and their role in assessing the disease in various settings. Indeed, AMD, like many other retinal diseases, benefits from a multimodal imaging approach to optimally characterize the disease. In this chapter, we will review the various imaging technologies currently used in the assessment and management of AMD.

Choroideremia is an X-linked inherited retinal disorder (IRD) characterized by the degeneration of retinal pigment epithelium, photoreceptors, choriocapillaris and choroid affecting males with variable phenotypes in female carriers. Unlike other IRD, characterized by a large clinical and genetic heterogeneity, choroideremia shows a specific phenotype with causative mutations in only one gene, CHM. Ongoing gene replacement trials raise further interests in this disorder. We describe here the clinical and genetic data from a French cohort of 45 families, 25 of which carry novel variants, in the context of 822 previously reported choroideremia families. Most of the variants represent loss-of-function mutations with eleven families having large (i.e. ≥6 kb) genomic deletions, 18 small insertions, deletions or insertion deletions, six showing nonsense variants, eight splice site variants and two missense variants likely to affect splicing. Similarly, 822 previously published families carry mostly loss-of-function variants. Recurrent variants are observed worldwide, some of which linked to a common ancestor, others arisen independently in specific CHM regions prone to mutations. Since all exons of CHM may harbor variants, Sanger sequencing combined with quantitative polymerase chain reaction or multiplex ligation-dependent probe amplification experiments are efficient to achieve the molecular diagnosis in patients with typical choroideremia features.

PURPOSE To reappraise the presentation and the course of ITM2B-related retinal dystrophy and give further insights into ITM2B expression in the retina. METHODS The clinical data of nine subjects with ITM2B-related retinal dystrophy were retrospectively reviewed. The genetic mutation was assessed for its influence on splicing in cultured fibroblasts. The cellular expression of ITM2B within the inner retina was investigated in wild-type mice through mRNA in situ hybridization. RESULTS All patients complained of decreased vision and mild photophobia around their twenties-thirties. The peculiar feature was the hyperreflective material on optical coherence tomography within the inner retina and the central outer nuclear layer with thinning of the retinal nerve fiber layer. Although retinal imaging revealed very mild or no changes over the years, the visual acuity slowly decreased with about one Early Treatment Diabetic Retinopathy Study letter per year. Finally, full-field electroretinography showed a mildly progressive inner retinal and cone dysfunction. ITM2B mRNA is expressed in all cellular types of the inner retina. Disease mechanism most likely involves mutant protein misfolding and/or modified protein interaction rather than misplicing. CONCLUSION ITM2B-related retinal dystrophy is a peculiar, rare, slowly progressive retinal degeneration. Functional examinations (full-field electroretinography and visual acuity) seem more accurate in monitoring the progression in these patients because imaging tends to be stable over the years.

The study aims to analyze the changes produced by half-dose photodynamic therapy (HD-PDT) in the choroid of eyes with chronic central serous chorioretinopathy (CSC) applying the binarization method to spectral domain optical coherence tomography (SDOCT) and OCT Angiography (OCTA) images. SDOCT and OCTA were performed before, one hour, one week, and one month after HD-PDT. Binarization with a modified Niblack method and analysis by ImageJ were applied. An average ratio between luminal part and total structure was calculated. Twenty-two eyes of 21 patients (20 male and 1 female, mean age 54.8 years) were enrolled. A statistically significant reduction of the central choroidal thickness was observed one week (from 407 &micro, m to 362 &micro, m, p = 0.034) and one month (from 407 &micro, m to 341.5 &micro, m, p = 0.0004) after HD-PDT. The baseline average ratio between luminal part and total structure was 33.4% in SDOCT, and 61.1% in OCTA. These values were 35.3% and 61% one hour, 33.9% and 60.4% one week, and 34.5% and 60.6% one month after HD-PDT, respectively. Overall, PDT seems to produce short-term changes on the luminal component of both choriocapillaris and choroid, which return to baseline status after one month from treatment. However, choroid stays significantly thinner after one month, with both luminal and interstitial components significantly reduced.

PURPOSE To quantify the regional variation in choriocapillaris (CC) flow deficits percentage (FD%) surrounding treatment-naive Type 1 choroidal neovascularization (CNV) associated with age-related macular degeneration. METHODS Patients were imaged with swept-source optical coherence tomography angiography system (Carl Zeiss PLEX Elite 9000; Carl Zeiss Meditec AG, Jena, Germany). Two 6 × 6-mm volume scans were acquired. Boundary-specific segmentation was used to isolate the Type 1 CNV. For CC assessment, both structural and optical coherence tomography angiography CC slabs (10-µm thick, starting 21 µm below the retinal pigment epithelium fit reference) were exported for signal compensation and averaging using ImageJ. The resultant CC image was binarized to calculate the FD%, for para-CNV and peri-CNV rings (each 500-µm wide). In a subgroup of 20 eyes, the FD% was compared with similar regions of age-matched controls. The FD% was also analyzed in small 500 × 500-µm squares equidistant from the fovea to compensate for regional variation of CC FD% as a potential confounding factor. RESULTS Thirty-two eyes from 27 subjects were enrolled in this study. The CC FD% in the para-CNV ring was 26.58 ± 7.36, which was significantly higher than the peri-CNV ring (21.94 ± 6.31); P < 0.001. The FD% in para-CNV and peri-CNV rings was significantly greater than that of healthy controls (15.82 ± 1.29% and 15.53 ± 1.32%, respectively); P < 0.001. The FD% computed in the 500-µm squares equidistant from the fovea was also greater in the para-CNV ring (26.14 ± 7.11) than that in the peri-CNV ring (22.31 ± 6.21); P < 0.001. CONCLUSION Choriocapillaris FD% is the highest in the region immediately surrounding the CNV.

PReCIS:: Our study demonstrated that in low-tension glaucoma (LTG) patients, Microperimeter-3 (MP-3)-derived and Humphrey Field Analyzer (HFA)-derived retinal sensitivities were similar and strongly correlated, allowing the respective data to be interrelated. PURPOSE To compare and correlate retinal sensitivities obtained by Nidek MP-3 with those obtained from the HFA in eyes with LTG. MATERIALS AND METHODS In this prospective comparative study, 45 eyes of 24 LTG patients underwent retinal sensitivity assessments using the MP-3 (Nidek Technologies) and the HFA (Carl Zeiss Meditec) at the UCLA-Doheny Eye Center. Global and pointwise retinal sensitivity measurements were compared and correlated between the 2 devices. RESULTS No statistically significant differences (P=0.85) were noted between the mean retinal sensitivities determined by each device (MP-3: 26.33±4.31 dB; range, 13.05 to 31.60 vs. HFA: 26.42±3.98 dB; range, 17.17 to 30.96), and a strong correlation (r=0.66, P

Background/AimsTo assess the role of microperimetric retinal sensitivity (MPRS) and inner choroid flow deficits (IC FD) in predicting the development of incomplete retinal pigment epithelial and outer retinal atrophy (iRORA) in intermediate AMD (i-AMD).MethodsThirty eyes with i-AMD evaluated at the Doheny-UCLA Eye Centres were enrolled in this prospective IRB-approved study. Subjects underwent several diagnostic tests: (a) 6×6 mm swept-source optical coherence tomography angiography (SS-OCTA) with the IC slab used to quantify the FDs, (b) 20°×20° spectral-domain optical coherence tomography (SD-OCT) to monitor progression to iRORA and (c) scotopic MPRS within an area of 18° centred on the fovea. All subjects were followed-up for 24 months. The baseline IC FD and MPRS were correlated with the development of iRORA. At 24-month follow-up, the stage of AMD was re-assessed and the eyes were divided into two sub-groups based on the development of iRORA.ResultsTwenty-eight eyes completed the 2-year follow-up. At baseline, the mean MPRS was 13.40±4.66 dB and the mean IC FD was 27.55±8.67%. The morpho-functional regression showed a significant correlation between baseline MPRS and IC FD and the development of iRORA within 24 months (R2=0.744, pConclusionsA lower MPRS and greater IC FD at baseline were predictors of progression to iRORA in eyes with i-AMD. These parameters may be useful biomarkers for risk stratification and prognostication.

BackgroundAlzheimer's disease (AD) pathology precedes symptoms and its detection can identify at-risk individuals who may benefit from early treatment. Since the retinal nerve fiber layer (RNFL) is depleted in established AD, we tested whether its thickness can predict whether cognitively healthy (CH) individuals have a normal or pathological cerebrospinal fluid (CSF) Aß42 (A) and tau (T) ratio.MethodsAs part of an ongoing longitudinal study, we enrolled CH individuals, excluding those with cognitive impairment and significant ocular pathology. We classified the CH group into two sub-groups, normal (CH-NAT, n = 16) or pathological (CH-PAT, n = 27), using a logistic regression model from the CSF AT ratio that identified >85% of patients with a clinically probable AD diagnosis. Spectral-domain optical coherence tomography (OCT) was acquired for RNFL, ganglion cell-inner plexiform layer (GC-IPL), and macular thickness. Group differences were tested using mixed model repeated measures and a classification model derived using multiple logistic regression.ResultsMean age (± standard deviation) in the CH-PAT group (n = 27; 75.2 ± 8.4 years) was similar (p = 0.50) to the CH-NAT group (n = 16; 74.1 ± 7.9 years). Mean RNFL (standard error) was thinner in the CH-PAT group by 9.8 (2.7) μm; p < 0.001. RNFL thickness classified CH-NAT vs. CH-PAT with 87% sensitivity and 56.3% specificity.ConclusionsOur retinal data predict which individuals have CSF biomarkers of AD pathology before cognitive deficits are detectable with 87% sensitivity. Such results from easy-to-acquire, objective and non-invasive measurements of the RNFL merit further study of OCT technology to monitor or screen for early AD pathology.

PURPOSE: To evaluate the effect of averaging en-face optical coherence tomography angiography (OCTA) images on quantitative measurements of the retinal microvasculature and their correlation to diabetic retinopathy (DR) disease severity. DESIGN: Cross-sectional cohort study PARTICIPANTS: 105 eyes (65 patients) with 28 eyes from 19 healthy, aged-matched controls, 14 eyes from 9 diabetics without DR and 63 eyes from 37 diabetics with varying levels of DR. METHODS: Spectral-domain OCTA images with uniform illumination, good foveal centration, and no macular edema or significant motion artifact were acquired 5 times with the 3×3 mm scan pattern on the CIRRUS™ 5000 HD-OCT with AngioPlex (Carl Zeiss Meditec, Dublin, CA) software. En-face images of the superficial retinal layer (SRL) and deep retinal layer (DRL) were registered and averaged. Included eyes had a signal strength ≥7. Vessel length density (VLD), perfusion density (PD) and foveal avascular zone (FAZ) parameters were measured on averaged versus single OCTA images. Pearson correlation coefficient compared the two groups. Univariate and multivariate linear regression correlated quantitative metrics to DR severity and best corrected visual acuity (BCVA). RESULTS: 84 eyes (55 patients) met the inclusion criteria. Almost uniformly, lower VLD and PD parameters were significantly associated with worse DR severity and BCVA. Multivariable linear regression for DR severity resulted in an R(2) value of 0.82 and 0.77 for single and averaged groups, respectively. No variables remained significantly associated with DR severity in multivariate analysis with single images but in averaged images, increased superior SRL PD significantly predicted worse DR severity (coefficient 52.7, p=0.026). Multivariate linear regression for BCVA had an R(2) value of 0.42 and 0.47 for single and averaged groups, respectively. FAZ size was not associated with DR severity when single OCTA images (p=0.98) were considered, but was highly associated when using averaged images (coefficient 6.18, p

Optical coherence tomography angiography is evolving towards wider fields of view. As single widefield acquisitions have a lower resolution, preventing an accurate segmentation of vascular plexuses in the periphery, we examined the retinal vascularisation from the macula to the periphery in all retinal quadrants, using 3 × 3-mm volume scans, to obtain montages with sufficient image resolution up to 11 mm from the foveal centre. Images were qualitatively and quantitatively analysed, using C- and B-scan approaches to calculate the capillary density (CD) and the interplexus distance (IPD). Three vascular plexuses (i.e., superficial vascular plexus: SVP, intermediate capillary plexus: ICP, and deep capillary plexus: DCP) were observed up to the mid-periphery in all sectors. The CD of the SVP decreased from about 5 mm of eccentricity, along with ganglion cell density decrease. The CD of the ICP progressively decreased from the fovea towards the periphery, along with the retinal thinning and then vanished from 8 to 9 mm of eccentricity, becoming undetectable beyond. This ICP disappearance resulted in an increased IPD between the SVP and the DCP in an area known to be frequently affected by capillary drop-out in diabetic retinopathy. The DCP only showed a slightly decreased CD towards the retinal periphery.

AimsTo evaluate the choriocapillaris (CC) flow alterations around geographic atrophy (GA) in eyes with dry age-related macular degeneration.MethodsUsing a swept-source optical coherence tomography angiography (SS-OCTA) device, two volume 6×6 mm scans were acquired in patients with GA presenting between June and December 2017 at the Doheny-UCLA Eye Centers. The area of GA was delineated on the en face structural OCT fundus images. For each eye, the en face OCTA slabs at the level of the CC from the two acquisitions were averaged and compensated for signal loss using the corresponding structural en face images. The resulting images were binarised and analysed for the percentage of flow voids in the para-atrophy zone (a 500 µm wide ring around the immediate edge of the atrophy) and in the peri-atrophy zone (a 500 µm wide ring around the para-atrophy zone edge), the latter considered as a reference in the comparative analysis.ResultsThirty eyes of 20 patients were enrolled. The percentage of flow voids in the para-atrophy zone was 27.23%±6.29% and was significantly higher than in the surrounding peri-atrophy zone (23.4%±6.01%; pConclusionsA significant impairment of the CC flow is present in the zone immediately surrounding the GA lesions strengthening the hypothesis that CC alterations may be relevant to the progression of GA.

International audience; no abstract

We investigated the prevalence of reported deep-intronic variants in a French cohort of 70 patients with Stargardt disease harboring a monoallelic pathogenic variant on the exonic regions of ABCA4. Direct Sanger sequencing of selected intronic regions of ABCA4 was conducted. Complete phenotypic analysis and correlation with the genotype was performed in case a known intronic pathogenic variant was identified. All other variants found on the analyzed sequences were queried for minor allele frequency and possible pathogenicity by in silico predictions. The second mutated allele was found in 14 (20%) subjects. The three known deep-intronic variants found were c.5196+1137G&gt, A in intron 36 (6 subjects), c.4539+2064C&gt, T in intron 30 (4 subjects) and c.4253+43G&gt, A in intron 28 (4 subjects). Even though the phenotype depends on the compound effect of the biallelic variants, a genotype-phenotype correlation suggests that the c.5196+1137G&gt, A was mostly associated with a mild phenotype and the c.4539+2064C&gt, T with a more severe one. A variable effect was instead associated with the variant c.4253+43G&gt, A. In addition, two novel variants, c.768+508A&gt, G and c.859-245_859-243delinsTGA never associated with Stargardt disease before, were identified and a possible splice defect was predicted in silico. Our study calls for a larger cohort analysis including targeted locus sequencing and 3D protein modeling to better understand phenotype-genotype correlations associated with deep-intronic changes and patients&rsquo, selection for clinical trials.