Variants in UBAP1L lead to autosomal recessive rod-cone and cone-rod dystrophy.

PURPOSE: Progressive inherited retinal degenerations (IRDs) affecting rods and cones are clinically and genetically heterogeneous and can lead to blindness with limited therapeutic options. The major gene defects have been identified in subjects of European and Asian descent with only few reports of North African descent. METHODS: Genome, targeted next-generation, and Sanger sequencing was applied to cohort of ∼4000 IRDs cases. Expression analyses were performed including Chip-seq database analyses, on human-derived retinal organoids (ROs), retinal pigment epithelium cells, and zebrafish. Variants' pathogenicity was accessed using 3D-modeling and/or ROs. RESULTS: Here, we identified a novel gene defect with three distinct pathogenic variants in UBAP1L in 4 independent autosomal recessive IRD cases from Tunisia. UBAP1L is expressed in the retinal pigment epithelium and retina, specifically in rods and cones, in line with the phenotype. It encodes Ubiquitin-associated protein 1-like, containing a solenoid of overlapping ubiquitin-associated domain, predicted to interact with ubiquitin. In silico and in vitro studies, including 3D-modeling and ROs revealed that the solenoid of overlapping ubiquitin-associated domain is truncated and thus ubiquitin binding most likely abolished secondary to all variants identified herein. CONCLUSION: Biallelic UBAP1L variants are a novel cause of IRDs, most likely enriched in the North African population.

Predictors of lack of response to methotrexate in juvenile idiopathic arthritis associated uveitis.

OBJECTIVES: To investigate clinical features associated with lack of response to MTX in juvenile idiopathic arthritis associated uveitis (JIA-U). METHODS: Clinical records of JIA-U patients were retrospectively reviewed. Differences among variables were assessed by Mann-Whitney and χ 2 or Fisher's exact tests as appropriate. Association between predictors and requirement of a biological disease modifying antirheumatic drug (bDMARD) was evaluated by univariate Cox regression analysis and Kaplan-Meier curves. A multivariable logistic model was applied to estimate strength of association, adjusting for potential confounders. RESULTS: Data from 99 JIA-U patients treated with MTX were analysed (82.8% female), with a mean follow up of 9.2 years and a mean age at uveitis onset of 5.7 years. In 65 patients (65.7%) at least one bDMARD to control uveitis was required. Children requiring a bDMARD for uveitis had lower age at JIA and uveitis onset, more frequent polyarticular course, higher frequency of bilateral uveitis at onset and higher prevalence of systemic steroids' use. Despite similar frequency of ocular damage at onset, MTX non responders showed a higher percentage of ocular damage at last visit. Younger age at JIA onset, polyarticular course and a history of systemic steroids' use resulted independent factors associated to lack of response to MTX at Cox regression analysis. Kaplan-Meier curves and the multivariate model confirms the independent role of both polyarticular course and systemic steroids' use. CONCLUSIONS: Younger age at JIA onset, polyarticular course and a history of systemic steroids' use are predictors of a worse response to MTX in JIA-U.

Optical coherence tomography angiography findings in Williams-Beuren syndrome.

PURPOSE: Williams-Beuren syndrome (WBS) is a rare genetic disease characterized by psychomotor delay, cardiovascular, musculoskeletal, and endocrine problems. Retinal involvement, which is not well characterized, has also been described. The purpose of this cross-sectional study is to describe the characteristics in optical coherence tomography (OCT) and OCT-angiography (OCTA) of patients with WBS. METHODS: We included patients with WBS confirmed by genetic analysis. The patients underwent OCT (30° × 25°, 61 B-scans) and OCTA (10° × 10° and 20° × 20°) examinations, all centered on the. Data on retinal thickness (total, inner and outer layers) and foveal morphology on OCT and vessel and perfusion density in OCTA (VD and PD, respectively) were collected. These data were compared with an age-matched control group. RESULTS: 22 eyes of 22 patients with WBS (10 females, mean age 31.5 years) were included. Retinal thickness (and specifically inner retinal layers) in OCT was significantly reduced in all sectors (central, parafoveal, and perifoveal) compared to the control group (p < 0.001 in all sectors). Fovea in WBS eyes was broader and shallower than controls. The PD and VD in both 10 and 20 degrees of fields in OCTA was significantly reduced in patients with WBS, in all vascular plexa (all p < 0.001). CONCLUSIONS: This study is the first to quantify and demonstrate retinal structural and microvascular alterations in patients with WBS. Further studies with longitudinal data will reveal the potential clinical relevance of these alterations.

Ocular features in Williams-Beuren syndrome: a review of the literature.

PURPOSE OF REVIEW: The current review will discuss the pathophysiology, work-up and clinical relevance of the ocular phenotype in Williams-Beuren syndrome in detail. RECENT FINDINGS: Few case reports, case series and retrospective studies reported the ophthalmic features in Williams-Beuren syndrome, focusing on specific aspects of the ocular involvement. Recently, novel retinal findings have been described in association with the disease. SUMMARY: Numerous ocular features have been described in Williams-Beuren syndrome. Some of them, such as the stellate pattern of the iris or the retinal arteriolar tortuosity may be helpful for the diagnosis but have no significant clinical implications; others, such as strabismus and refractive errors require early treatment to reduce the risk of irreversible visual impairment. Finally, some features, such as a broad foveal pit and thinner retina still have unknown significance and require further longitudinal and multimodal studies.

Relationship between the distribution of intra-retinal hyper-reflective foci and the progression of intermediate age-related macular degeneration.

PURPOSE: To assess the relationship between the distribution of intra-retinal hyper-reflective foci (IHRF) on optical coherence tomography (OCT) and progression of intermediate age-related macular degeneration (iAMD) over 2 years. METHODS: Cirrus OCT volumes of the macula of subjects enrolled in the Amish Eye Study with 2 years of follow-up were evaluated for the presence of iAMD and IHRF at baseline. The IHRF were counted in a series of 5 sequential en face slabs from outer to inner retina. The number of IHRF in each slab at baseline and the change in IHRF from baseline to year 2 were correlated with progression to late AMD at 2 years. RESULTS: Among 120 eyes from 71 patients with iAMD, 52 eyes (43.3%) of 42 patients had evidence of both iAMD and IHRF at baseline. Twenty-three eyes (19.0%) showed progression to late AMD after 2 years. The total IHRF count increased from 243 at baseline to 604 at 2 years, with a significant increase in the IHRF number in each slab, except for the innermost slab 5 which had no IHRF at baseline or follow-up. The IHRF count increased from 121 to 340 in eyes that showed progression to late AMD. The presence of IHRF in the outermost retinal slabs 1 and 2 was independently associated with a significant risk of progression to late AMD. A greater increase in IHRF count over 2 years in these same slabs 1 and 2 was also associated with a higher risk of conversion to late AMD. CONCLUSIONS: The risk of progression to late AMD appears to be significantly associated with the distribution and extent of IHRF in the outermost retinal layers. This observation may point to significant pathophysiologic differences of IHRF in inner versus outer layers of the retina.

Delaying anti-VEGF therapy during the COVID-19 pandemic: long-term impact on visual outcomes in patients with neovascular age-related macular degeneration.

OBJECTIVES: To evaluate the outcomes of delayed intravitreal injections (IVIs) caused by the outbreak of coronavirus disease 2019 (COVID-19), in patients with neovascular age-related macular degeneration (nAMD). METHODS: nAMD patients with scheduled IVIs between March 1st and April 30th, 2020 were stratified through a risk-based selection into a non-adherent group (NA-group) if they skipped at least one IVI and an adherent group (A-group) if they followed their treatment schedule. During the pandemic visit (v0), if a significant worsening of the disease was detected, a rescue therapy of three-monthly IVIs was performed. Multimodal imaging and best-corrected visual acuity (BCVA) findings were evaluated after 6 months (v6), compared between groups and with the visit prior the lockdown (v-1). RESULTS: Two hundred fifteen patients (132 females, mean age: 81.89 ± 5.98 years) delayed their scheduled IVI while 83 (53 females, mean age: 77.92 ± 6.06 years) adhered to their protocol. For both groups, BCVA at v0 was significantly worse than v-1 (mean 4.15 ± 7.24 ETDRS letters reduction for the NA-group and 3 ± 7.96 for the A-group) but remained stable at v6. The two groups did not significantly differ in BCVA trends after 6 months and neither for development of atrophy nor fibrosis. CONCLUSIONS: A risk-based selection strategy and a rescue therapy may limit the long-term outcomes of an interruption of the treatment protocol in patients with nAMD.

Twenty-four-month real-life treatment outcomes of polypoidal choroidal vasculopathy versus type 1 macular neovascularization in Caucasians.

BACKGROUND: To compare 24-month real-world outcomes of Vascular Endothelial Growth Factor (VEGF) inhibitors for Polypoidal Choroidal Vasculopathy (PCV) and type 1 Macular Neovascularization (MNV) in a Caucasian population. METHODS: Retrospective analysis from a prospectively designed observational database. Data from Italian centres participating in the Fight Retinal Blindness! (FRB!) project were collected. Treatment-naïve PCV or type 1 MNV commencing treatment after January 2009 were included. The primary outcome was 24-month visual acuity (VA) change; other outcomes included baseline characteristics, number of anti-VEGF injections, time to lesion inactivation and proportion of active visits. RESULTS: A total of 322 eyes (114 PCVs) from 291 patients were included. Median [Q1, Q3] VA at baseline was comparable (70 [55, 75.8] vs. 70 [58.8, 75] letters, p = 0.95). Adjusted VA change at 2 years was higher in PCV (mean [95% CI], +1.2 [-1.6, 4.1] vs. -3.6 [-6, -1.2] letters, p = 0.005). PCV received fewer anti-VEGF injections over the first 24 months of treatment than type 1 MNV (median [Q1, Q3], 8 [5, 10] vs. 9 [7, 12.2] injections, p = 0.001), inactivated earlier (median [Q1, Q3], 235 [184, 308] vs. 252 [169, 343] days, p = 0.04) and was less frequently graded 'active' (62% vs. 68% of visits, p = 0.001). CONCLUSIONS: PCV had slightly better VA outcomes over 24 months of treatment than type 1 MNV after receiving less anti-VEGF injections. These results suggest a possible overlap of the two clinical entities with similar visual prognosis in Caucasians.

RESPONSE TO TREATMENT OF CHOROIDAL NEOVASCULARIZATION IN HIGHLY MYOPIC EYES WITH DOME-SHAPED MACULA: Two Years of Follow-Up.

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Retrospective Natural History Study of RPGR-Related Cone- and Cone-Rod Dystrophies While Expanding the Mutation Spectrum of the Disease.

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.

Large Benefit from Simple Things: High-Dose Vitamin A Improves RBP4-Related Retinal Dystrophy.

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.

CHM mutation spectrum and disease: An update at the time of human therapeutic trials.

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.

CNGB1-related rod-cone dystrophy: A mutation review and update.

Cyclic nucleotide-gated channel ß1 (CNGB1) encodes the 240-kDa ß 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.

DEEP PHENOTYPING AND FURTHER INSIGHTS INTO ITM2B-RELATED RETINAL DYSTROPHY.

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.

Ocular Imaging for Enhancing the Understanding, Assessment, and Management of Age-Related Macular Degeneration.

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.

Relationship between proximity of choriocapillaris flow deficits and enlargement rate of geographic atrophy.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Only the choriocapillaris FD% in the 500-µm region immediately surrounding GA lesions appears to predict the rate of enlargement of these lesions.

QUANTITATIVE ASSESSMENT OF CHORIOCAPILLARIS FLOW DEFICITS SURROUNDING CHOROIDAL NEOVASCULAR MEMBRANES.

PURPOSE: To quantify the regional variation in choriocapillaris (CC) flow deficits percentage (FD%) surrounding treatment-naïve 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.

CORRELATION OF EN FACE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AVERAGING VERSUS SINGLE-IMAGE QUANTITATIVE MEASUREMENTS WITH RETINAL VEIN OCCLUSION VISUAL OUTCOMES.

PURPOSE: To demonstrate the effect of averaging multiple en face optical coherence tomography angiography images on the correlation between retinal microvasculature quantitative metrics and best-corrected visual acuity (BCVA) in eyes with retinal vein occlusion. METHODS: A cross-sectional cohort with unilateral retinal vein occlusion was imaged in both eyes. Five 3 mm × 3-mm spectral domain optical coherence tomography angiography images were averaged, and quantitative parameters from averaged versus single images were correlated with logMAR BCVA. Regression analyses were performed to correlate quantitative metrics with BCVA. RESULTS: Ten patients (5 male, average age 64.3 years) were included. Among retinal vein occlusion eyes, vessel length density was significantly less in averaged versus a single image for both the superficial retinal layer (15.5 ± 2.5 vs. 17.8 ± 2.4/mm, P = 0.05) and deep retinal layer (16.2 ± 1.4 vs. 18.5 ± 1.6/mm, P = 0.003). Multivariate linear regression showed an increased R value with averaging (0.93 to 0.95, for single and averaged groups, respectively). Foveal avascular zone circularity was associated with BCVA on single images (coefficient = -0.96, P = 0.002), but not with averaged images (P = 0.063). CONCLUSION: Scan averaging of en face optical coherence tomography angiography images improves the clarity of vessels and may allow for more accurate quantification of vessel metrics. Quantitative metrics are significantly associated with BCVA, and averaging does not further improve this association compared with single-scan analysis.

PHENOTYPIC CHARACTERISTICS OF ROD-CONE DYSTROPHY ASSOCIATED WITH MYO7A MUTATIONS IN A LARGE FRENCH COHORT.

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.

Relationship between Retinal Thickness Profiles and Visual Outcomes in Young Adults Born Extremely Preterm: The EPICure@19 Study.

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 < 0.001), but outer retinal layer thickness was not (r = -0.01, P = 0.80). Multivariate regression indicated ganglion cell layer thickness was a significant independent predictor of BCVA. 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.

OCT Risk Factors for Development of Late Age-Related Macular Degeneration in the Fellow Eyes of Patients Enrolled in the HARBOR Study.

PURPOSE: To evaluate the relationship between OCT features and progression to late age related-macular degeneration (AMD) in the fellow eyes of patients enrolled in the Study of Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular AMD (HARBOR) (ClinicalTrials.gov identifier, NCT00891735). DESIGN: Post hoc analysis of a phase 3 multicenter, prospective, randomized, double-masked, active treatment-controlled clinical trial. PARTICIPANTS: Evaluable patients (n = 501) with macular neovascularization (MNV) secondary to neovascular AMD and early or intermediate AMD in the fellow eye. METHODS: Volume OCT scans from 501 fellow eyes of 501 patients with MNV were reviewed. Baseline OCT features that were assessed included intraretinal hypereflective foci (IHRF), hyporeflective foci (hRF) within drusenoid lesions (DLs), subretinal drusenoid deposits (SDDs), and drusen volume (DV) of 0.03 mm3 or more. OCT images obtained at months 6, 12, 18, and 24 were graded by masked graders for late AMD (defined as MNV, complete retinal pigment epithelium and photoreceptor atrophy [cRORA], or both). Participant demographic characteristics (age, gender, and smoke exposure) and baseline OCT features were correlated with progression to late AMD. MAIN OUTCOME MEASURES: Incidence of late AMD, hazard ratio (HR) for demographics, and OCT risk factors. RESULTS: At month 24, 33.13% of eyes (166/501) demonstrated late AMD: 20.96% (105/501) demonstrated cRORA, whereas 12.18% (61/501) demonstrated MNV. Baseline demographic factors were not associated significantly with development of late AMD, whereas significant associations were identified for all OCT features. Intraretinal hypereflective foci had an HR of 5.21 (95% confidence interval [CI], 3.29-8.26), hRF within DLs had an HR of 2.42 (95% CI, 1.74-3.38), SDD had an HR of 1.95 (95% CI, 1.34-2.82), and DV of 0.03 mm3 or more had an HR of 1.46 (95% CI, 1.03-2.07). The correlation remained significant when considering only the progression to cRORA and MNV alone, except for DV, which was not associated significantly with progression to MNV. CONCLUSIONS: We confirmed that 4 previously reported OCT risk factors were associated with progression to late AMD in the fellow eyes of patients newly diagnosed with MNV. Although outcomes of more than 2 years were not evaluated, these findings may help to identify high-risk AMD patients.