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PURPOSE: To investigate the clinical, functional, and imaging characteristics in patients affected by inherited retinal diseases associated with RDH5 and RLBP1 gene variants, and to report novel genotype-phenotype correlations. DESIGN: Retrospective single-center cohort study. METHODS: Twenty-two patients with molecularly confirmed RLBP1-associated retinopathy and 5 with RDH5-associated retinopathy. Medical records were reviewed to obtain data on family history and ophthalmologic examinations, including retinal imaging and full-field electroretinography (ffERG). Genotype was determined by targeted next-generation sequencing followed by confirmation and familial segregation by Sanger sequencing. RESULTS: The median (interquartile ranges) age at baseline for the RDH5 and RLBP1 cohort was 44.6 (38.2-67.9) years and 36.9 (23.1-45.2) years, respectively. Macular atrophy (MA) was found in approximately 80% of eyes from both cohorts. The RLBP1 genotype was associated with a lower macular volume by 0.28 mm3 (95% CI, -0.46 to -0.11; P = .005) compared to the RDH5 genotype. In both genotypic cohorts, we found a significant annual rate of macular volume loss, estimated at -0.007 mm3/y (95% CI, -0.012 to -0.001; P = .02), without any significant difference between the two genotypes. Three unrelated patients homozygous for the c.361C>T p.(Arg121Trp) RLBP1 variant showed minimal impairment of both the rod and cone systems function on ffERG and absence of MA. CONCLUSIONS: Progressive MA in addition to congenital night blindness can be identified in adult patients with RDH5-associated retinopathy. Vice versa, hypomorphic RLBP1 variants may cause milder retinal phenotypes rather than the typical severe rod-cone dystrophy with MA. These findings could prove beneficial to improve the prognostication of patients and help in designing future interventional trials.
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PURPOSE: To compare non-syndromic and syndromic forms of USH2A-related retinitis pigmentosa (RP) by means of structural optical coherence tomography (OCT) and OCT-angiography (OCTA). METHODS: Observational, cross-sectional, multicenter study. All patients underwent best corrected visual acuity (BCVA) measurement, OCT (Spectralis HRA + OCT, Heidelberg Engineering) and OCTA (OCT DRI Topcon Triton, Topcon Corporation). We compared subfoveal choroidal thickness (SCT), choroidal vascularity index (CVI), presence of cystroid macular edema (CME), macular vessel density (VD) at the superficial and deep capillary plexa, as well as VD of the radial peripapillary capillary (RPC) network, between syndromic and non-syndromic patients with USH2A-associated retinopathy. RESULTS: Thirty-four eyes from 18 patients (7 females) were included. Thirteen patients (72.2%) were affected by Usher syndrome type 2, whereas the remaining 5 subjects (27.8%) had non-syndromic retinitis pigmentosa (nsRP). Syndromic patients were younger than nsRP (p = 0.01) and had a worse visual acuity than those with the exclusively retinal phenotype. Patients with Usher syndrome type 2 had a higher prevalence of CME and a thicker choroid compared to nsRP, although these results were not statistically significant (p = 0.775 and p = 0.122, respectively). Similarly, none of the other quantitative OCT and OCTA parameters was statistically different between the two groups. CONCLUSIONS: Despite their younger age, patients with Usher syndrome type 2 displayed similar choroidal and microvascular changes compared to those with nsRP.
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PURPOSE: To describe the clinical outcome and late-stage findings of extensive macular atrophy with pseudodrusen-like appearance (EMAP). DESIGN: Retrospective cohort study. PARTICIPANTS: Seventy-eight patients (156 eyes) affected by EMAP. METHODS: We collected data on best-corrected visual acuity, kinetic perimetry, OCT, short-wavelength autofluorescence, and near-infrared autofluorescence findings. Genetic testing for the TIMP3 and C1QTNF5 genes was performed via Sanger sequencing for 58 patients, with no pathogenic variants identified. MAIN OUTCOME MEASURES: The primary outcomes were best-corrected visual acuity at the last examination, visual field at the last examination, and incidence rates and time-to-event curves for blindness with the United States Social Security Administration and World Health Organization (WHO) criteria, foveal involvement, and atrophy enlargement beyond the 30° and 55° field of view. Imaging findings at the last examination were secondary outcomes. RESULTS: At the most recent visit, mean age was 70.9 ± 5.2 years. Using United States criteria, 58.1% of the patients were blind, and 25.8% were blind according to WHO criteria. All eyes showed large central scotomas, which were associated with visual field constriction in 22.2% of eyes. We detected focal openings or large dehiscences of Bruch's membrane (BM) in 25.4% of eyes. Near-infrared autofluorescence showed increased visibility of the choroidal vessels beyond the atrophy in 87.2% of eyes. The incidence rates for blindness were 3.95 per 100 patient-years with United States criteria and 1.54 per 100 patient-years according to WHO criteria. The incidence rates were 22.8 per 100 eye-years for foveal involvement, 12.0 per 100 eye-years for atrophy enlargement beyond 30°, and 6.6 per 100 eye-years for atrophy enlargement beyond 55°. The estimates were not influenced by the age at onset. CONCLUSIONS: We identified characteristic imaging findings, including BM ruptures, in elder patients with EMAP and calculated incidence rates for different functional and anatomic outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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PURPOSE: Vitreoretinal lymphoma (VRL) is a rare lymphoma affecting the vitreous and the retina. Clinical diagnosis is challenging and often delayed and may lead to aggravated prognosis. This study aims to review multimodal imaging findings in VRL. METHODS: We performed a comprehensive narrative review of the multimodal imaging findings that might be useful in the detection of VRL lesions. RESULTS: The most frequent ocular manifestations of VRL are vitritis, and retinal and sub-retinal Pigmented Epithelium (RPE) infiltrations. Color Fundus Photography (CFP) detects vitreous haze, optic nerve, retinal and sub-RPE infiltration. Ultra-wide field imaging allows visualization of different patterns of vitreous haze and monitoring of VRL evolution through the detection of chorio-retinal atrophy (CRA). Fundus Autofluorescence shows granular hypo- and hyper-autofluorescent pattern. Optical Coherence Tomography (OCT) reveals vitreous cells, vertical hyper-reflective lesions and sub-RPE infiltrates. Fluorescein Angiography (FA) shows hypo or hyperfluorescent round lesions at the late stages of the examination, while Indocyanine Green Angiography (ICGA) detects round areas of focal hypo-fluorescence in the early phases that gradually enlarge in the late phases. B-scan ultrasonography detects vitreous opacities and homogeneous hyperreflective corpuscular material in the vitreous, and is a strongly recommended tool in suspecting VRL and is particularly useful when vitreous haze is impeding retinal examination. CONCLUSION: Diagnostic vitrectomy with cytopathological analysis remains the gold standard for VRL diagnosis, however multimodal imaging allows the identification of suggestive retinal and vitreal lesions for early suspicion, diagnosis, and treatment and monitoring disease progression and response to treatment.
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PURPOSE: To analyze the alterations at the level of the inner retina in patients affected by Stargardt disease (STGD1). METHODS: Cross-sectional investigation involving STGD1 patients with genetically confirmed diagnosis, who underwent optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), and microperimetry. RESULTS: Overall, 31 patients (62 eyes) with genetically confirmed STGD1 were included in the study. Mean inner retinal thickness, vessel density of plexa, and retinal sensitivity resulted significantly reduced in STGD patients, compared with healthy controls (p < 0.05), both in the outer and in the inner ETDRS rings. Overall, 43% of eyes revealed an inner retinal thinning, whereas 21% and 35% showed a thicker or within normal range inner retina. CONCLUSIONS: Inner retina is irregularly altered in STGD1, showing variable quantitative alterations as detected on OCT. Inner retinal status might represent a useful biomarker to better characterize STGD1 and to ascertain the effects of new treatment approaches.
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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 â¼4000 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.
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Distrofias de Conos y Bastones , Linaje , Pez Cebra , Humanos , Distrofias de Conos y Bastones/genética , Distrofias de Conos y Bastones/patología , Masculino , Femenino , Pez Cebra/genética , Animales , Genes Recesivos , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/patología , Mutación/genética , Células Fotorreceptoras Retinianas Conos/patología , Células Fotorreceptoras Retinianas Conos/metabolismo , Retina/patología , Retina/metabolismo , Adulto , Túnez , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/patología , Fenotipo , Células Fotorreceptoras Retinianas Bastones/metabolismo , Células Fotorreceptoras Retinianas Bastones/patologíaRESUMEN
Retinitis pigmentosa (RP) is a group of inherited rod-cone dystrophies, noted for a high genotypical and phenotypical heterogeneity.Traditionally, VA, visual field, and electroretinography have been used to assess RP progression. However, visual acuity and visual field tests are essentially subjective and, especially in the late stages of the disease, are unable to confidently reveal minor progression. Therefore, there is a need for novel examination modalities that rely on quantitative, structural measurements. In this regard, several non-invasive imaging techniques have been studied, including spectral-domain optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence. By correlating surrogate biomarkers with functional measurements of the disease, these techniques may be able to develop reliable outcome meters that can be used to gain a deeper understanding of the underlying causes of the disease and to assess the effectiveness of therapy even before an actual loss of vision occurs.In this review, we will summarize the recent imaging findings and biomarkers that have been identified in RP patients. Our goal is to provide information that can promptly aid in selecting patients for clinical trials and new gene therapies, monitoring the disease progression, and evaluating treatment outcomes.
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Retinitis Pigmentosa , Humanos , Retinitis Pigmentosa/diagnóstico por imagen , Retinitis Pigmentosa/genética , Electrorretinografía , Campos Visuales , Tomografía de Coherencia Óptica , Biomarcadores , Imagen Multimodal , RetinaRESUMEN
Best Vitelliform Macular Dystrophy (BVMD) is a dominantly inherited retinal disease caused by dominant variants in the BEST1 gene. The original classification of BVMD is based on biomicroscopy and color fundus photography (CFP); however, advancements in retinal imaging provided unique structural, vascular, and functional data and novel insights on disease pathogenesis. Quantitative fundus autofluorescence studies informed us that lipofuscin accumulation, the hallmark of BVMD, is unlikely to be a primary effect of the genetic defect. It could be due to a lack of apposition between photoreceptors and retinal pigment epithelium in the macula with subsequent accumulation of shed outer segments over time. Optical Coherence Tomography (OCT) and adaptive optics imaging revealed that vitelliform lesions are characterized by progressive changes in the cone mosaic corresponding to a thinning of the outer nuclear layer and then disruption of the ellipsoid zone, which are associated with a decreased sensitivity and visual acuity. Therefore, an OCT staging system based on lesion composition, thus reflecting disease evolution, has been recently developed. Lastly, the emerging role of OCT Angiography proved a greater prevalence of macular neovascularization, the majority of which are non-exudative and develop in late disease stages. In conclusion, effective diagnosis, staging, and clinical management of BVMD will likely require a deep understanding of the multimodal imaging features of this disease.
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Mácula Lútea , Distrofia Macular Viteliforme , Humanos , Distrofia Macular Viteliforme/diagnóstico por imagen , Distrofia Macular Viteliforme/genética , Retina/patología , Epitelio Pigmentado de la Retina/patología , Mácula Lútea/patología , Tomografía de Coherencia Óptica/métodos , Angiografía con Fluoresceína/métodos , Imagen Multimodal , Bestrofinas/genéticaRESUMEN
PURPOSE: To describe the retinal phenotype associated with the p.Pro101Thr BEST1 variant. DESIGN: Retrospective, observational case series. PARTICIPANTS: Patients diagnosed with bestrophinopathies in which molecular genetic testing identified the p.Pro101Thr BEST1 as well as healthy carriers among their first-degree relatives. METHODS: Medical records were reviewed to obtain data on family history and ophthalmic examinations, including retinal imaging. The imaging protocol included OCT and fundus autofluorescence using Spectralis HRA + OCT (Heidelberg Engineering). Genetic analysis was performed by next-generation sequencing. MAIN OUTCOME MEASURES: Results of ophthalmic examinations and multimodal imaging features of retinal phenotypes. RESULTS: The c.301C>A, p.Pro101Thr BEST1 missense variant was identified as the causative variant in 8 individuals (all men) from 5 families, accounting for 13% of cases (8/61) and 10% of pathogenic alleles (9/93) in our cohort of patients affected by bestrophinopathies. Seven individuals (14 eyes) had the variant in heterozygous status: all eyes had a hyperopic refractive error (median spherical equivalent of + 3.75 diopters [D]) and 4 individuals had a macular dystrophy with mildly reduced visual acuity (median of 20/25 Snellen), whereas the other 3 were asymptomatic carriers. On multimodal retinal imaging, 5 (36%) out of 14 eyes had subclinical bestrophinopathy, 4 (29%) had typical findings of adult-onset foveomacular vitelliform dystrophy (AOFVD), and the remaining 5 (36%) displayed a pattern dystrophy-like phenotype. Follow-up data were available for 6 subjects, demonstrating clinical stability up to 11 years, in both subclinical and clinical forms. An additional patient with autosomal recessive bestrophinopathy was found to harbor the p.Pro101Thr variant in homozygosity. CONCLUSIONS: The p.Pro101Thr BEST1 variant is likely a frequent cause of bestrophinopathy in the Italian population and can result in autosomal dominant macular dystrophies with incomplete penetrance and mild clinical manifestations as well as autosomal recessive bestrophinopathy. The spectrum of autosomal dominant maculopathy includes the typical AOFVD and a pattern dystrophy-like phenotype. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Enfermedades Hereditarias del Ojo , Enfermedades de la Retina , Distrofias Retinianas , Distrofia Macular Viteliforme , Adulto , Masculino , Humanos , Estudios Retrospectivos , Mutación , Linaje , Análisis Mutacional de ADN , Distrofia Macular Viteliforme/diagnóstico , Distrofia Macular Viteliforme/genética , Distrofia Macular Viteliforme/patología , Fenotipo , Bestrofinas/genéticaRESUMEN
PURPOSE: To study peripheral capillary non-perfusion (PCN-P) in branch retinal vein occlusion (BRVO) by means of ultra wide-field fluorescein angiography (UWFFA), and to correlate its extent and severity with optical coherence tomography (OCT) and OCT-angiography (OCTA) parameters and best corrected visual acuity (BCVA). METHODS: Prospective case series with 2 years of planned follow-up. We recruited patients from June 2019 to December 2019. Ophthalmologic examination included BCVA, UWFFA, OCT and OCTA. Partial (p) and complete (c) ischemic index (ISI) were evaluated on UWFFA images. Vessel density (VD) in both the macular region and the optic nerve head (ONH) was calculated. RESULTS: Twelve BRVO subjects and 12 healthy controls were recruited. Mean age was 63.8 ± 8.74 years. Mean BCVA improved from 0.43 ± 0.25 logMAR to 0.15 ± 0.18 after two years (p < 0.01), while mean central macular thickness (CMT) decreased from 463.83 ± 200.85â µm to 353.17 ± 108.85â µm (p > 0.05). Mean cISI, pISI and total ISI were 25.2 ± 13.0%, 6.3 ± 5.0% and 31.5 ± 12.0%, respectively. Except for VDs of the superficial capillary plexus and choriocapillaris in the macular region, all VDs were lower in the BRVO group (p < 0.01). cISI and tISI negatively correlated with mDCP (p < 0.01), whereas only pISI correlated with CMT at baseline (p < 0.05). Additionally, cISI also negatively correlated with VD at the ONH (p < 0.05). CONCLUSION: The amount of complete and partial ischemia may have different implications in BRVO, with the former being more associated with microvascular impairment and the latter with macular edema.
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Oclusión de la Vena Retiniana , Humanos , Persona de Mediana Edad , Anciano , Oclusión de la Vena Retiniana/complicaciones , Oclusión de la Vena Retiniana/diagnóstico , Fondo de Ojo , Estudios Retrospectivos , Estudios de Seguimiento , Angiografía con Fluoresceína/métodos , Vasos Retinianos , Tomografía de Coherencia Óptica/métodosRESUMEN
BACKGROUND: Autosomal Recessive Bestrophinopathy (ARB) is an inherited retinal disease caused by biallelic mutations in the BEST1 gene. Herein, we report the multimodal imaging findings of ARB presenting with cystoid maculopathy and investigate the short-term response to combined systemic and topical carbonic anhydrase inhibitors (CAIs). MATERIAL AND METHODS: An observational, prospective, case series on two siblings affected by ARB is presented. Patients underwent genetic testing and optical coherence tomography (OCT), blue-light fundus autofluorescence (BL-FAF), near-infrared fundus autofluorescence (NIR-FAF), fluorescein angiography (FA), MultiColor imaging, and OCT angiography (OCTA). RESULTS: Two male siblings, aged 22 and 16, affected by ARB resulting from c.598C>T, p.(Arg200*) and c.728C>A, p.(Ala243Glu) BEST1 compound heterozygous variants, presented with bilateral multifocal yellowish pigment deposits scattered through the posterior pole that corresponded to hyperautofluorescent deposits on BL-FAF. Vice versa, NIR-FAF mainly disclosed wide hypoautofluorescent areas in the macula. A cystoid maculopathy and shallow subretinal fluid were evident on structural OCT, albeit without evidence of dye leakage or pooling on FA. OCTA demonstrated disruption of the choriocapillaris throughout the posterior pole and sparing of intraretinal capillary plexuses. Six months of combined therapy with oral acetazolamide and topical brinzolamide resulted in limited clinical benefit. CONCLUSIONS: We reported two siblings affected by ARB, presenting as non-vasogenic cystoid maculopathy. Prominent alteration of NIR-FAF signal and concomitant choriocapillaris rarefaction on OCTA were noted in the macula. The limited short-term response to combined systemic and topical CAIs might be explained by the impairment of the RPE-CC complex.
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Enfermedades Hereditarias del Ojo , Degeneración Macular , Enfermedades de la Retina , Humanos , Masculino , Tomografía de Coherencia Óptica , Antagonistas de Receptores de Angiotensina , Estudios Prospectivos , Canales de Cloruro/genética , Proteínas del Ojo/genética , Inhibidores de la Enzima Convertidora de Angiotensina , Enfermedades de la Retina/diagnóstico por imagen , Enfermedades de la Retina/genética , Angiografía con Fluoresceína , Bestrofinas/genéticaRESUMEN
PURPOSE: To report the acute onset of macular atrophy soon after photobiomodulation (PBM) administration in a patient with intermediate age-related macular degeneration (AMD). METHODS: Optical coherence tomography (OCT) was performed in the study eye before and after PBM. RESULTS: A patient with drusenoid pigment epithelium detachment (D-PED) underwent PBM. A few weeks after PBM the D-PED collapsed, resulting in incomplete retinal pigment epithelium and outer retinal atrophy with visual acuity worsening. CONCLUSION: Thinning of the outer retinal layers over a D-PED and posterior hypertrasmission may represent bad prognostic factors for PBM, accelerating the lesion's natural history towards atrophic evolution.
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Purpose: To determine if circulating antiretinal antibodies (ARAs) differ between patients affected by retinitis pigmentosa (RP) and control participants and to assess whether ARAs are associated with clinical outcomes in patients with RP. Methods: Cross-sectional study involving a group of patients clinically diagnosed with RP and a control group of healthy participants. Serum autoantibodies against enolase, heat shock protein 70 (HSP70), and carbonic anhydrase II (CAII) were tested in all participants using Jess capillary Western blot. We compared ARA prevalence between the RP and control groups and investigated the association of serum ARA positivity with macular edema and vitreomacular disorders in patients affected by RP. Results: Thirty-six patients affected by RP and a control group of 39 healthy individuals were included. Overall, at least one ARA positivity was detected in 89% and 80% of participants in the RP and control groups, respectively. We observed a similar prevalence of anti-CAII and anti-enolase ARA between patients and controls (P = 0.87 and P = 0.35, respectively). Sera from patients with RP tested positive for anti-HSP70 ARAs more frequently than those from controls (53% vs. 36%), albeit without reaching statistical significance (P = 0.29). Among the 72 eyes with RP, 25% presented with macular edema (most often bilateral) and 33% with epiretinal membrane and/or lamellar macular hole. None of the three ARAs was associated with an increased risk of any macular complications in eyes affected by RP (all P > 0.05). Conclusions: The prevalence of circulating ARAs against enolase, HSP70, and CAII is similar between patients affected by RP and healthy individuals. Our results provide evidence against the association of ARAs with macular edema and vitreomacular interface disorders in RP.
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Edema Macular , Retinitis Pigmentosa , Humanos , Edema Macular/diagnóstico , Edema Macular/etiología , Estudios Transversales , Retinitis Pigmentosa/diagnóstico , Retinitis Pigmentosa/complicaciones , Retina , Fosfopiruvato Hidratasa , Tomografía de Coherencia Óptica/métodosRESUMEN
Pigmented paravenous chorioretinal atrophy (PPCRA) is an uncommon form of chorioretinal atrophy characterized by perivenous aggregations of pigment clumps associated with peripapillary and radial zones of retinal pigment epithelial atrophy that are distributed along the retinal veins. Most patients are asymptomatic, and evidence suggest that PPCRA is slowly progressing. Unless macular involvement is present, the majority of patients usually retain a normal visual function. Our ability to diagnose PPCRA has recently improved thanks to multimodal imaging, especially with the advent of ultra-widefield (UWF) imaging. Blood tests and functional and genetic testing can help with the correct differential diagnosis of pseudo-PPCRA or other disorders with similar characteristics. Although the cause of PPCRA is unknown, it is possible that it has a genetic basis. In this review we provide a summary of the multimodal imaging characteristics of PPCRA, and discuss its possible pathogenesis, based on the genes that have been associated with this disease.
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Purpose: To investigate the clinical utility of choroidal quantitative assessment associated with the presence of macular neovascularization (MNV) or atrophy in high myopia. Methods: The study was designed as a retrospective case series with two-year follow-up. We measured choroidal thickness (CT) and the presence and subtype of dome-shaped macula (DSM). In DSM eyes we also calculated the presence and type of choroidal deepening (CD). The eyes were categorized as Subgroup 1 (high myopia without complications), Subgroup 2 (high myopia complicated by MNV), and Subgroup 3 (high myopia complicated by macular or posterior pole atrophy). Main outcome measures were the detection of significant CT cutoffs associated with the three subgroups of eyes and the clinical impact of DSM and CD subtypes. Results: Our cohort (190 eyes affected by high myopia) was categorized as Subgroup 1 (66 eyes), Subgroup 2 (72 eyes) and Subgroup 3 (52 eyes). Baseline CT values allowed to separate the subgroups with myopic-related complications (area under the curve = 0.85; P < 0.05). In Subgroup 1, vertical DSM was the most frequent (54%), with CD absence characterizing the 46% of cases. Round DSM was the most represented subtype in Subgroup 2 (49%), with 55% of sub-dome CD subtypes; in these cases, MNV resulted always localized in the fovea. Subgroup 3 equally shown horizontal or vertical DSM (53% and 47%, respectively), with 80% of cases showing peri-dome CD. Conclusions: Choroidal quantitative assessment can categorize three high myopia subgroups. MNV subgroup is characterized by intermediate choroidal thinning and higher prevalence of round DSM with sub-dome CD.
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Miopía , Humanos , Estudios Retrospectivos , Miopía/complicaciones , Miopía/diagnóstico , Coroides , Atrofia , Fóvea Central , Neovascularización PatológicaRESUMEN
Purpose: The purpose of this study was to investigate the relation among hyperautofluorescent ring patterns, visual acuity (VA), and optical coherence tomography (OCT) features in patients with retinitis pigmentosa (RP), and to describe its modifications over time. Methods: This was a retrospective, longitudinal, and observational study. Clinical and imaging data from the first and last available visits of patients with a clinical diagnosis of RP were reviewed. The ellipsoid zone (EZ) width was measured on OCT acquisitions. Short-wavelength autofluorescence (SW-AF) images were classified based on the hyperautofluorescent ring pattern as absent, regular, and irregular, and their modifications over the follow-up were described. The VA, EZ width, and progression rate were compared among the three groups. Results: One hundred eight eyes from 54 subjects were included in the study. The hyperautofluorescent ring was not present in 28 eyes (25.9%), appeared regular in 45 eyes (41.7%), and had an irregular pattern in 35 eyes (32.4%). The three groups differed in terms of age, VA, and EZ width (all P < 0.05). Additionally, the absence of a hyperautofluorescent ring indicated a faster rate of progression (P < 0.001). Throughout the follow-up period, 17 eyes (15.7%) experienced a change in the AF pattern, with irregular rings being more commonly affected. Conclusions: The hyperautofluorescent ring is a useful tool to frame patients based on their EZ width and VA. We described its possible modifications over time, the knowledge of which can aid clinicians in the interpretation of imaging finding changes of their patients.
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Ojo , Retinitis Pigmentosa , Tomografía de Coherencia Óptica , Humanos , Ojo/diagnóstico por imagen , Estudios Longitudinales , Retinitis Pigmentosa/diagnóstico , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Masculino , Femenino , AdultoRESUMEN
OBJECTIVE: To assess the relationship between ≥ 1 localizations of intraretinal fluid (IRF) within retinal layers and the 2-year outcome in a cohort of neovascular age-related macular degeneration (AMD) eyes. DESIGN: Retrospective case series. PARTICIPANTS: Two hundred forty-three eyes of 243 AMD patients affected by type 1 and type 2 macular neovascularization (MNV). METHODS: We analyzed data considering MNV onset, 1-year, and 2-year timepoints. Optical coherence tomography images were used to classify MNV types, distinguish different types of fluids and assess IRF localization within retinal layers. A subcohort of eyes were also analyzed by OCT angiography. MAIN OUTCOME MEASURES: The association between IRF cyst localization and both visual outcome and onset of outer retinal atrophy at 2-year follow-up. RESULTS: Macular neovascularizations were distributed as type 1 (69%) and type 2 (31%). The mean number of intravitreal injections was 7 ± 2 at 1-year follow-up and 5 ± 2 at 2-year follow-up. Baseline best-corrected visual acuity was 0.4 ± 0.3 logarithm of the minimum angle of resolution, improving to 0.3 ± 0.4 at 2-year follow-up (P < 0.01). Outer retinal atrophy occurred in 24% of cases at 1 year and 39% of cases at 2-year follow-up. Intraretinal fluid localizations at the level of IPL-INL and OPL-ONL at baseline were associated with the worst functional and anatomical outcome. Moreover, the presence of IRF at baseline was associated with greater impairment of the intraretinal vascular network. CONCLUSIONS: The localization of IRF at the level of IPL-INL and OPL-ONL retinal layers represents a negative prognostic biomarker for the morphologic and functional outcomes of neovascular AMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Quistes , Degeneración Macular Húmeda , Humanos , Inhibidores de la Angiogénesis/uso terapéutico , Ranibizumab , Factor A de Crecimiento Endotelial Vascular , Estudios Retrospectivos , Agudeza Visual , Degeneración Macular Húmeda/diagnóstico , Retina , Quistes/diagnóstico , AtrofiaRESUMEN
PURPOSE: To describe the alterations of the peripheral retina in extensive macular atrophy with pseudodrusen-like deposits (EMAP) by means of ultrawidefield fundus photography (UWFFP) and ultrawidefield fundus autofluorescence (UWF-FAF). STUDY DESIGN: Prospective, observational case series. PARTICIPANTS: Twenty-three patients affected by EMAP. METHODS: Each patient underwent best-corrected visual acuity (BCVA) measurement, UWFFP, and UWF-FAF. The area of macular atrophy, as well as the pseudodrusen-like deposits and peripheral degeneration, were assessed using UWF images, at baseline and over the follow-up. MAIN OUTCOME MEASURES: The assessment of the clinical patterns of both pseudodrusen-like deposits and peripheral retinal degeneration. Secondary outcomes included assessing macular atrophy by means of UWFFP and UWF-FAF, and tracking progression over the follow-up. RESULTS: Twenty-three patients (46 eyes) were included, of whom 14 (60%) were female. Mean age was 59.0 ± 5 years. Mean BCVA at baseline was 0.4 ± 0.4, declining at a mean rate of 0.13 ± 0.21 logarithm of the minimum angle of resolution/year. Macular atrophy at baseline was 18.8 ± 14.2 mm2 on UWF-FAF, enlarging at a rate of 0.46 ± 0.28 mm/year, after the square root transformation. Pseudodrusen-like deposits were present in all cases at baseline, and their detection decreased over the follow-up. Three main types of peripheral degeneration were identified: retinal pigment epithelium alterations, pavingstone-like changes, and pigmented chorioretinal atrophy. Peripheral degeneration progressed in 29 eyes (63.0%), at a median rate of 0.7 (interquartile range, 0.4-1.2) sectors/year. CONCLUSIONS: Extensive macular atrophy with pseudodrusen-like deposits is a complex disease involving not only the macula, but also the midperiphery and the periphery of the retina. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Importance: ABCA4-associated retinopathy is a common inherited retinal disease, and its phenotype spans from late-onset macular dystrophy to extensive cone-rod degeneration. Over 2000 disease-causing variants in the ABCA4 gene have been identified. Objective: To investigate genotype-phenotype correlations in ABCA4-associated retinopathy. Design, Setting, and Participants: This cohort study took place at a single referral center for inherited retinal diseases in Italy. Data were prospectively acquired from January 2015 to June 2022. Patients diagnosed with an inherited retinal disease related to biallelic ABCA4 variants were included for analysis. Exposure: Genotype, classified into 4 groups according to the presence of the (1) p.Gly1961Glu allele, (2) a hypomorphic allele, (3) at least 1 moderate variant (moderate genotypes), or (4) 2 biallelic severe variants (severe genotypes). Main Outcomes and Measures: Total decreased autofluorescence (TDAF) and definitely decreased autofluorescence (DDAF) areas, inner and outer retinal volumes, and the respective progression rate. Results: A total of 71 patients (median [IQR] age, 34 [22.4-47.2] years; 40 [56%] female) were included in the study, and 54 (76%) were followed up for a median (IQR) of 3.5 (1.6-4.7) years. Compared with moderate genotypes, those with the p.Gly1961Glu allele had smaller TDAF lesions by 61% (95% CI, -78% to -33%; P < .001) and DDAF lesions by 77% (95% CI, -93% to -18%; P = .02), along with slower growth rates for both TDAF (0.05 mm/y; 95% CI, 0.01-0.07; P < .001) and DDAF (0.06 mm/y; 95% CI, 0-0.12; P = .004). Hypomorphic alleles were associated with a thicker inner (+0.19 mm3; 95% CI, +0.02 to +0.36; P = .03) and outer retinal volume (+0.16 mm3; 95% CI, +0.03 to +0.28; P = .01) compared with moderate genotypes as well as a slower TDAF growth rate (0.05 mm/y; 95% CI, 0.01-0.08; P = .007). Severe genotypes had a 7-fold larger TDAF area (95% CI, 3.4-14.7; P < .001) and 11-fold larger DDAF area (95% CI, 2.9-42.1; P < .001) compared with moderate genotypes, along with faster growth rates estimated at 0.16 mm/y for TDAF (95% CI, 0.12-0.20; P < .001) and 0.17 mm/y for DDAF (95% CI, 0.12-0.23; P < .001). Conclusions and Relevance: In this study of ABCA4-associated retinopathy, a 4-tier classification of genotypes was found to capture substantial variation in disease phenotype severity. These findings could prove beneficial for the prognostication of patients and warrant consideration of genotype in the design of future clinical trials.
Asunto(s)
Transportadoras de Casetes de Unión a ATP , Humanos , Femenino , Adulto , Masculino , Enfermedad de Stargardt , Estudios de Cohortes , Transportadoras de Casetes de Unión a ATP/genética , Genotipo , Fenotipo , MutaciónRESUMEN
Purpose: To analyze fixation location and stability in best vitelliform macular dystrophy (BVMD) and test their association with best-corrected visual acuity (BCVA). Design: Observational, cross-sectional study. Participants: Thirty patients (55 eyes) affected by genetically confirmed BVMD were followed up at the Retinal Heredodystrophies Unit of IRCCS San Raffaele Scientific Institute, Milan. Methods: Patients underwent testing with macular integrity assessment (MAIA) microperimeter. Fixation location was measured as distance in degrees (°) between preferred retinal locus (PRL) and estimated fovea location (EFL); fixation was defined as eccentric when the distance between PRL and EFL exceeded 2°. Fixation stability was graded as stable, relatively unstable, or unstable and expressed as bivariate contour ellipse area (BCEA, °2). Main Outcome Measures: Fixation location and stability. Results: The median distance of the PRL from the anatomic fovea was 0.7°, and fixation location was eccentric in 27% of eyes. Fixation was graded as stable in 64% of eyes, relatively unstable in 13%, and unstable in 24%, with a median 95% BCEA of 6.2°2. The atrophic/fibrotic stage was associated with worse fixation parameters (all P < 0.01). Both PRL eccentricity and fixation stability were linearly associated with BCVA: every 1° increase in PRL eccentricity was associated with a 0.07 logarithm of the minimum angle of resolution (logMAR) worse BCVA (P < 0.0001) while every 1°2 increase in 95% BCEA was associated with a 0.01 logMAR worse BCVA (P < 0.001). No significant intereye correlation was found for PRL eccentricity and fixation stability, as well as no association between the patient's age and fixation parameters. Conclusions: We demonstrated that most eyes affected by BVMD retain a central stable fixation and provided evidence that both fixation eccentricity and stability are strongly associated with visual acuity in BVMD. These parameters may serve as secondary end points for future clinical trials. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.