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Although rare, inherited retinal degenerations (IRDs) are the most common reason for blind registration in the working age population. They are highly genetically heterogeneous (>300 known genetic loci), and confirmation of a molecular diagnosis is a prerequisite for many therapeutic clinical trials and approved treatments. First-tier genetic testing of IRDs with panel-based next-generation sequencing (pNGS) has a diagnostic yield of ≈70-80%, leaving the remaining more challenging cases to be resolved by second-tier testing methods. This study describes the phenotypic reassessment of patients with a negative result from first-tier pNGS and the rationale, outcomes, and cost of second-tier genetic testing approaches. Removing non-IRD cases from consideration and utilizing case-appropriate second-tier genetic testing techniques, we genetically resolved 56% of previously unresolved pedigrees, bringing the overall resolve rate to 92% (388/423). At present, pNGS remains the most cost-effective first-tier approach for the molecular assessment of diverse IRD populations Second-tier genetic testing should be guided by clinical (i.e., reassessment, multimodal imaging, electrophysiology), and genetic (i.e., single alleles in autosomal recessive disease) indications to achieve a genetic diagnosis in the most cost-effective manner.
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Pruebas Genéticas/métodos , Degeneración Retiniana/genética , Análisis de Secuencia de ADN/métodos , Adulto , Anciano , Femenino , Fondo de Ojo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Degeneración Retiniana/diagnóstico por imagenRESUMEN
PURPOSE: The purpose of our study was to investigate morpho-functional features of the preferred retinal location (PRL) and the transition zone (TZ) in a series of patients with recessive Stargardt disease (STGD1). METHODS: Fifty-two STGD1 patients with at least one ABCA4 mutation, atrophy of the central macula (MA) and an eccentric PRL were recruited for the study. Microperimetry, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT) were performed. The location and stability of the PRL along with the associated FAF pattern and visual sensitivities were determined and compared to the underlying retinal structure. RESULTS: The mean visual sensitivity of the PRLs for the 52 eyes was 10.76 +/- 3.70 dB. For the majority of eyes, PRLs were associated with intact ellipsoid zone (EZ) bands and qualitatively normal FAF patterns. In 17 eyes (32.7%) the eccentric PRL was located at the edge of the MA. In 35 eyes (67.3%) it was located at varying distances from the border of the MA with a TZ between the PRL and the MA. The TZ was associated with decreased sensitivity values (5.92 +/- 4.69 dB) compared to PRLs (p<0.05), with absence/disruption of the EZ band and abnormal FAF patterns (hyper or hypo-autofluorescence). CONCLUSIONS: In STGD1 eccentric PRLs are located away from the border of MA and associated with intact EZ bands and normal FAF. The TZ is characterized by structural and functional abnormalities. The results of multimodal imaging of the PRL and TZ suggest a possible sequence of retinal and functional changes with disease progression that may help in the planning of future therapies; RPE dysfunction appears to be the primary event leading to photoreceptor degeneration and then to RPE loss.
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Mácula Lútea/patología , Degeneración Macular/congénito , Imagen Multimodal/métodos , Epitelio Pigmentado de la Retina/patología , Adulto , Anciano , Femenino , Angiografía con Fluoresceína/métodos , Fondo de Ojo , Humanos , Degeneración Macular/diagnóstico , Degeneración Macular/fisiopatología , Masculino , Persona de Mediana Edad , Oftalmoscopía/métodos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Enfermedad de Stargardt , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Campos Visuales , Adulto JovenRESUMEN
OBJECTIVE: To report a new phenotype caused by mutations in the CRB1 gene in a family with 2 affected siblings. DESIGN: Molecular genetics and observational case studies. PARTICIPANTS: Two affected siblings and 3 unaffected family members. METHODS: Each subject received a complete ophthalmic examination together with color fundus photography, fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (SD-OCT). Microperimetry 1 (MP-1) mapping and electroretinogram (ERG) analysis were performed on the proband. Screening for disease-causing mutations was performed by whole exome sequencing in 3 family members followed by segregation analyses in the entire family. MAIN OUTCOME MEASURES: Appearance of the macula as examined by clinical examination, fundus photography, FAF imaging, SD-OCT, and visual function by MP-1 and ERG. RESULTS: The proband and her affected brother exhibited unusual, previously unreported, findings of a macular dystrophy with relative sparing of the retinal periphery beyond the vascular arcades. The FAF imaging showed severely affected areas of hypoautofluorescence that extended nasally beyond the optic disc in both eyes. A central macular patch of retinal pigment epithelium (RPE) sparing was evident in both eyes on FAF, whereas photoreceptor sparing was documented in the right eye only using SD-OCT. The affected brother presented with irregular patterns of autofluorescence in both eyes characterized by concentric rings of alternating hyper- and hypoautofluorescence, and foveal sparing of photoreceptors and RPE, as seen on SD-OCT, bilaterally. After negative results in screening for mutations in candidate genes including ABCA4 and PRPH2, DNA from 3 members of the family, including both affected siblings and their mother, was screened by whole exome sequencing resulting in identification of 2 CRB1 missense mutations, c.C3991T:p.R1331C and c.C4142T:p.P1381L, which segregated with the disease in the family. Of the 2, the p.R1331C CRB1 mutation has not been described before and the p.P1381L variant has been described in 1 patient with Leber congenital amaurosis. CONCLUSIONS: This report illustrates a novel presentation of a macular dystrophy caused by CRB1 mutations. Both affected siblings exhibited a relatively well-developed retinal structure and preservation of generalized retinal function. An unusual 5-year progression of macular atrophy alone was observed that has not been described in any other CRB1-associated phenotypes.
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Proteínas del Ojo/genética , Degeneración Macular/genética , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Análisis de Secuencia de ADN/métodos , Adulto , Análisis Mutacional de ADN , Femenino , Humanos , Degeneración Macular/patología , Masculino , Persona de Mediana Edad , Mutación Missense , Fenotipo , HermanosRESUMEN
(1) Background: Inherited retinal degenertions are rare conditions which may have a dramatic impact on the daily life of those affected and how they interact with their environment. Coordination of clinical services via an ophthalmic genetics multidisciplinary team (OG-MDT) allows better efficiency of time and resources to reach diagnoses and facilitate patient needs. (2) Methods: This clinical case series was conducted by a retrospective review of patient records for patients enrolled in the Target 5000 programme and managed by the OG-MDT, at the Mater Hospital Dublin, Ireland (n = 865) (3) Results: Herein we describe clinical cases and how the use of the OG-MDT optimizes care for isolated and syndromic IRD pedigrees. (4) Conclusions: this paper demonstrates the benefits of an OG-MDT to patients with IRDs resulting in the holistic resolution of complex and syndromic cases. Furthermore, we demonstrate that this format can be adopted/developed by similar centres around the world, bringing with it the myriad benefits.
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BACKGROUND: Non-infectious uveitis affecting the posterior segment of the eye (NIU-PS) is an inflammatory disease, which can significantly impair visual acuity if not adequately treated. Fluocinolone-acetonide sustained-release-0.2 µg/day intravitreal (FAc) implants are indicated for prevention of relapse in recurrent NIU-PS. The aim here was to provide treating clinicians with some consensus-based-recommendations for the clinical management of patients with NIU-PS with 0.2 µg/day FAc implants. METHODS: A European-clinical-expert-group agreed to develop a consensus report on different issues related to the use of FAc implants in patients with NIU-PS. RESULTS: The Clinical-expert-panel provided specific recommendations focusing on clinical presentation (unilateral/bilateral) of the NIU-PS; systemic involvement of NIU-PS and the lens status. Treatment algorithms were developed; one that refers to the management of patients with NIU-PS in clinical practice and another that establishes the best clinical scenarios for the use of FAc implants, both as monotherapy and as adjuvant therapy. Additionally, the Clinical-expert-panel has provided recommendations about the use of the FAc implants in a clinical-setting. The Clinical-expert-panel also considered the safety profile of FAc implants and their possible implications in the daily practice. CONCLUSIONS: As more clinical experience has been gained using FAc implants, it was necessary to update the clinical recommendations that guide patient management in the clinic. The current consensus document addresses relevant issues related to the use of FAc implants on different types of patients with various etiologies of NIU-PS, and was conducted to standardize approaches to help specialists obtain better clinical outcomes.
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BACKGROUND/AIMS: To establish a consensus in the nomenclature for reporting optical coherence tomography angiography (OCTA findings in uveitis. METHODS: The modified Delphi process consisted of two rounds of electronic questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-one items were included for discussion. The three main areas of discussion were: wide field OCTA (WF-OCTA), nomenclature of OCTA findings and OCTA signal attenuation assessment and measurement. Seventeen specialists in uveitis and retinal imaging were selected by the executive committee to constitute the OCTA nomenclature in Uveitis Delphi Study Group. The study endpoint was defined by the degree of consensus for each question: 'strong consensus' was defined as >90% agreement, 'consensus' as 85%-90% and 'near consensus' as >80% but <85%. RESULTS: There was a strong consensus to apply the term 'wide field' to OCTA images measuring over 70° of field of view, to use the terms 'flow deficit' and 'non-detectable flow signal' to describe abnormal OCTA flow signal secondary to slow flow and to vessels displacement respectively, to use the terms 'loose' and 'dense' to describe the appearance of inflammatory choroidal neovascularisation, and to use the percentage of flow signal decrease to measure OCTA ischaemia with a threshold greater than or equal to 30% as a 'large area'. CONCLUSIONS: This study sets up consensus recommendations for reporting OCTA findings in uveitis by an expert panel, which may prove suitable for use in routine clinical care and clinical trials.
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Tomografía de Coherencia Óptica , Uveítis , Humanos , Angiografía con Fluoresceína/métodos , Tomografía de Coherencia Óptica/métodos , Uveítis/diagnóstico por imagen , Vasos Retinianos/diagnóstico por imagen , RetinaRESUMEN
PURPOSE: To report genetic and phenotypic discordance across two generations of a family with autosomal recessive Stargardt disease (STGD1) and to compare pathogenicities of the G1961E and A1038V alleles of the ATP-binding cassette transporter, subfamily A, member 4 (ABCA4) gene. METHODS: Five members of a family with STGD1 (patients 1-4, affected; patient 5, carrier) were included. Clinical assessment was performed together with fundus autofluorescence and spectral domain-optical coherence tomography. Patients were stratified based on the results of electroretinogram testing. Genotyping of the ABCA4 gene was performed with the ABCR500 microarray. RESULTS: STGD1 was diagnosed in the male proband and his female sibling (patients 1 and 2, respectively). Two children of patient 2 (patients 3 and 4) were also affected. Genotyping revealed the W663X stop mutation in all affected patients. Patients 3 and 4, who were compound heterozygous for the G1961E mutation, had earlier ages of onset than patients 1 and 2, who were compound heterozygous for the A1038V mutation. Patient 1 had an age of onset 28 years younger than patient 2, whose delayed onset can be explained by relative foveal sparing, while patient 4 had an age of onset 44 years younger than patient 2. CONCLUSIONS: The G1961E mutation, which has been considered "mild," yields a more severe phenotype in this family than the A1038V mutation, which has been considered "severe." Marked intrasibship discordance in clinical course is described, suggesting an additional role for modifying factors in ABCA4 pleiotropism.
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Transportadoras de Casetes de Unión a ATP/genética , Degeneración Macular/genética , Mutación , Adulto , Alelos , Análisis Mutacional de ADN , Electrorretinografía , Femenino , Genes Recesivos , Genotipo , Heterocigoto , Humanos , Degeneración Macular/congénito , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Estructura Terciaria de Proteína , Índice de Severidad de la Enfermedad , Enfermedad de Stargardt , Tomografía de Coherencia ÓpticaRESUMEN
We report the case of a 78-year old man with a delayed diagnosis of syphilis and an advanced phenotype of acute syphilitic posterior placoid chorioretinopathy after receiving 5 months of high dose steroids prior to anti-treponemal treatment. Bilateral choroidal neovascular membranes were present at the time of diagnosis and were successfully treated with intravitreal aflibercept, following completion of anti-treponemal therapy.
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PURPOSE: To present the observation of multifocal evanescent white dot syndrome (MEWDS)-like phenotypes developing in association with the onset of choroidal neovascularization (CNV) in a series of patients. METHODS: Patients presenting to tertiary-care centers with MEWDS-like phenotypes and CNV were identified. RESULTS: Five patients presented for the management of CNV in the context of previous diagnoses of punctate inner choroidopathy (PIC) and/or myopia. In time-periods ranging from 0 days to 12 weeks from the diagnosis of active CNV, MEWDS-like changes were observed. Treatment with anti-VEGF agents were instituted in four cases, in an as-required protocol. 1 patient received systemic steroid. CONCLUSIONS: The development of MEWDS-like phenotypes in association with CNVM can occur in eyes with either inflammatory or non-inflammatory CNVM, and in those who were or were not treated with anti-VEGF therapy. The association suggests an inflammatory event, which causes RPE changes and probably induces the development of the CNV.
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Síndromes de Puntos Blancos , HumanosRESUMEN
Persistent anterior uveitis causing cystoid macular oedema may necessitate either intraocular or systemic immunosuppression. This case report highlights how a newly licenced treatment, fluocinolone acetonide (Iluvien®, Alimera Sciences Ltd., England, UK) achieves quiescence in refractory and steroid-dependent disease and in the presence of an acute relapse.
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The aim of this study was to assess peripapillary sparing in patients with non-group I Stargardt disease. We suggest this as a useful clinical sign for formulating disease severity. Patients with a diagnosis of Stargardt disease were grouped by electroretinogram (ERG). Fundus autofluorescence was used to assess the peripapillary area for involvement in the Stargardt disease process. From a cohort of 32 patients (64 eyes), 17 patients (33 eyes) demonstrated loss of peripapillary sparing. One of 15 patients in Group I, six of 7 patients in group II and 9 of 10 patients in group III demonstrated peripapillary atrophy. One patient in group II had peripapillary flecks. All patients had at least one mutation detected in the ABCA4 gene. Both mutations were detected in 21 patients. Patients in groups II and III had the earliest ages of onset and the poorest visual acuities. Two novel disease causing mutation in the ABCA4 gene were detected. Our data supports the observation that peripapillary sparing is not universal finding for Stargardt disease and peripapillary atrophy is a useful clinical sign for identifying patients with Stargardt disease who fall into the more severe ERG groups, i.e. groups II and III. The presence of atrophy suggests a continuum of disease between groups II and III. Loss of peripapillary sparing is likely associated with the more deleterious mutations of the ABCA4 gene.
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Degeneración Macular/diagnóstico , Atrofia Óptica/diagnóstico , Disco Óptico/patología , Transportadoras de Casetes de Unión a ATP/genética , Adolescente , Adulto , Edad de Inicio , Anciano , Electrorretinografía , Femenino , Humanos , Degeneración Macular/genética , Masculino , Persona de Mediana Edad , Mutación , Análisis de Secuencia por Matrices de Oligonucleótidos , Atrofia Óptica/genética , Segmento Interno de las Células Fotorreceptoras Retinianas/patología , Segmento Externo de las Células Fotorreceptoras Retinianas/patología , Estudios Retrospectivos , Agudeza Visual/fisiología , Adulto JovenRESUMEN
BACKGROUND/OBJECTIVES: To determine if the presence of sub-retinal fluid (SRF) was associated with reduced vision in dome-shaped macula (DSM), and to assess its effect and response to treatment during follow-up. METHODS: Patients were identified retrospectively. Baseline and follow-up data were recorded. The diagnosis of DSM, and presence or absence of SRF and intra-retinal fluid (IRF) was confirmed using Spectral Domain-Optical Coherence Tomography (SD-OCT). Decisions to treat oedema were based on clinician preference. RESULTS: 193 eyes of 106 patients (71 female) were confirmed to have DSM. Overall mean duration of follow-up for this cohort was 3.5 years. Mean BRVA for all eyes at baseline was 0.38 (range: -0.20 to 'light perception'). A significant difference was noted in mean baseline BRVA between those eyes with SRF compared with those without SRF at baseline (0.48 vs. 0.31, p < 0.001). Intra-retinal fluid moderately correlated with poorer baseline BRVA (r = 0.31, p < 0.003). No significant change in BRVA was noted during follow-up. No significant effect of treatment on BRVA was observed. CONCLUSIONS: The presence of SRF at baseline was associated with poorer vision. Vision appears to remain stable irrespective of the presence or absence of SRF at baseline. The treatments administered in this cohort did not affect final vision or SRF.
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Mácula Lútea , Femenino , Estudios de Seguimiento , Humanos , Estudios Retrospectivos , Líquido Subretiniano/diagnóstico por imagen , Tomografía de Coherencia ÓpticaRESUMEN
A 58-year-old Afro-Caribbean gentleman with a diagnosis of quiescent systemic lupus erythematosus- (SLE-) related occlusive retinal vasculitis was previously treated with sector pan-retinal photocoagulation in his right eye to control temporal retinal neovascularization. At routine review he was found to have a focal area of subretinal fluid in the temporal macula sparing an ischaemic fovea. Fundus fluorescein angiography and indocyanine green angiography confirmed a branching vascular network (BVN) and terminal polys (i.e., polypoidal choroidal vasculopathy (PCV)). Interestingly, the BVN arose within an old laser scar. To our knowledge this is the first report of PCV in uveitis in an Afro-Caribbean patient and of the lesions arising within a laser scar.
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Acute macular neuroretinopathy (AMN) is a rare disease, the etiology of which remains unclear. An ischemic event at the level of the deep capillary plexus has been proposed. The authors present three cases of AMN in the context of active systemic Behçet's disease, with the support of multimodal imaging. All patients were known to have Behçet's disease before the diagnosis of AMN. AMN was confirmed in all three cases on spectral domain optical coherence tomography (SD-OCT), near infrared reflectance and OCT angiography. Behçet's disease is known to be a prothrombotic disease. The presentation of AMN in this context supports the presumed ischemic etiology of AMN. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:634-638.].
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Síndrome de Behçet/complicaciones , Enfermedades de la Retina/patología , Neuronas Retinianas/patología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , FenotipoRESUMEN
PURPOSE: To determine whether intraocular lens (IOL) exchange with insertion of a sulcus-fixated IOL is an effective treatment for the management of pseudophakic negative dysphotopsia. SETTING: Department of Ophthalmology, Stoke Mandeville Hospital, Buckinghamshire, United Kingdom. DESIGN: Case series. METHODS: Participants in the study were recruited prospectively from the clinic at the time of diagnosis or retrospectively from the operating room logs by identifying all patients who had IOL exchanges over a 4-year period (2009 to 2012). RESULTS: Five eyes of 5 women with negative dysphotopsia were treated with IOL exchange and replacement with a 3-piece IOL (Acrysof MA60AC) inserted in the ciliary sulcus. All patients had a resolution of the negative dysphotopsia symptoms. One patient had primary insertion of a sulcus IOL in the fellow eye and did not develop negative dysphotopsia symptoms. CONCLUSION: Intraocular lens exchange with insertion of a 3-piece IOL in the ciliary sulcus appears to be a safe and effective treatment for the management of pseudophakic negative dysphotopsia. FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in any material or method mentioned.
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Segmento Anterior del Ojo/cirugía , Remoción de Dispositivos , Implantación de Lentes Intraoculares/métodos , Trastornos de la Visión/rehabilitación , Campos Visuales/fisiología , Anciano , Femenino , Humanos , Persona de Mediana Edad , Facoemulsificación , Estudios Prospectivos , Reoperación , Tomografía de Coherencia Óptica , Trastornos de la Visión/etiología , Trastornos de la Visión/fisiopatologíaRESUMEN
BACKGROUND: A 71-year-old female presented on 3 occasions with escalating pain in a congenitally blind eye. Examination revealed hypertensive uveitis with morning glory optic disc dysplasia and absence of a crystalline lens. There was no previous intraocular surgery or trauma. Intensive anti-hypertensive agents and topical steroids did not control intraocular pressure (IOP) or inflammation. RESULTS: Dilated fundus examination on the third clinical review revealed a luxated cataractous lens on the retina. Pars plana vitrectomy and fragmatome lensectomy controlled inflammation and IOP, with resolution of ocular pain. DISCUSSION: This is an exceptional case of phacogenic uveitis with secondary glaucoma occurring years after spontaneous crystalline lens luxation in a patient with morning glory syndrome. The embryological pathogenesis of morning glory syndrome and the significance of accelerated cataractogenesis and zonular weakness are discussed. Hypertensive uveitis with unexplained absence of a crystalline lens in a blind eye must prompt suspicion of delayed phacogenic uveitis following asymptomatic lens luxation.
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Glaucoma/etiología , Subluxación del Cristalino/complicaciones , Cristalino/anomalías , Uveítis/etiología , Anciano , Diagnóstico Diferencial , Femenino , Glaucoma/diagnóstico , Glaucoma/fisiopatología , Humanos , Presión Intraocular , Subluxación del Cristalino/diagnóstico , Síndrome , Uveítis/diagnósticoRESUMEN
PURPOSE: To describe pathologic changes of the external limiting membrane (ELM) in young patients with early-onset Stargardt (STGD1) disease. METHODS: Twenty-six STGD1 patients aged younger than 20 years with confirmed disease-causing adenosine triphosphate-binding cassette, subfamily A, member 4 (ABCA4) alleles and 30 age-matched unaffected individuals were studied. Spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (AF), and color fundus photography (CFP) images, as well as full-field electroretinograms were obtained and analyzed for one to four visits in each patient. RESULTS: The ELM in all patients exhibited a distinct thickening that was not observed in unaffected individuals. In addition, accumulations of reflective deposits were noted in the outer nuclear layer in every patient. Four patients exhibited a concave protuberance or bulging of a thickened and hyperreflective ELM band within the fovea containing preserved photoreceptors. Longitudinal SD-OCT data in several patients revealed the persistence of this ELM abnormality over a period of time (1-4 years). Furthermore, the edges of the inner segment ellipsoid band appeared to recede earlier than the ELM band in active lesions. CONCLUSIONS: Structural changes seen in the ELM of this cohort may reflect a gliotic response to cellular stress at the photoreceptor level in early-onset STGD1.
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Transportadoras de Casetes de Unión a ATP/genética , ADN/genética , Células Ependimogliales/patología , Degeneración Macular/congénito , Mutación , Células Fotorreceptoras de Vertebrados/patología , Transportadoras de Casetes de Unión a ATP/metabolismo , Adolescente , Adulto , Niño , Preescolar , Análisis Mutacional de ADN , Electrorretinografía , Células Ependimogliales/metabolismo , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Fondo de Ojo , Humanos , Degeneración Macular/genética , Degeneración Macular/metabolismo , Degeneración Macular/patología , Masculino , Fenotipo , Células Fotorreceptoras de Vertebrados/metabolismo , Estudios Retrospectivos , Enfermedad de Stargardt , Tomografía de Coherencia Óptica , Adulto JovenRESUMEN
PURPOSE: To quantify fundus autofluorescence (qAF) in patients with recessive Stargardt disease (STGD1). METHODS: A total of 42 STGD1 patients (ages: 7-52 years) with at least one confirmed disease-associated ABCA4 mutation were studied. Fundus AF images (488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Texture factor (TF) was calculated to characterize inhomogeneities in the AF image and patients were assigned to the phenotypes of Fishman I through III. RESULTS: Quantified fundus autofluorescence in 36 of 42 patients and TF in 27 of 42 patients were above normal limits for age. Young patients exhibited the relatively highest qAF, with levels up to 8-fold higher than healthy eyes. Quantified fundus autofluorescence and TF were higher in Fishman II and III than Fishman I, who had higher qAF and TF than healthy eyes. Patients carrying the G1916E mutation had lower qAF and TF than most other patients, even in the presence of a second allele associated with severe disease. CONCLUSIONS: Quantified fundus autofluorescence is an indirect approach to measuring RPE lipofuscin in vivo. We report that ABCA4 mutations cause significantly elevated qAF, consistent with previous reports indicating that increased RPE lipofuscin is a hallmark of STGD1. Even when qualitative differences in fundus AF images are not evident, qAF can elucidate phenotypic variation. Quantified fundus autofluorescence will serve to establish genotype-phenotype correlations and as an outcome measure in clinical trials.
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Degeneración Macular/congénito , Oftalmoscopía/métodos , Epitelio Pigmentado de la Retina/patología , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Femenino , Fluorescencia , Fondo de Ojo , Humanos , Lipofuscina , Degeneración Macular/genética , Degeneración Macular/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Enfermedad de Stargardt , Adulto JovenRESUMEN
Stargardt disease (STGD1) is caused by mutations in the ABCA4 gene. It has previously been reported that abnormalities in STGD1 may be detectable in the photoreceptors using spectral domain-optical coherence tomography (SD-OCT) prior to the detection of retinal pigment epithelium abnormalities. We present a 5-year-old asymptomatic girl with normal appearing fundi who possessed pathogenic ABCA4 variants on both chromosomes and where thickening of the external limiting membrane was the only abnormality detected on SD-OCT.