RESUMEN
Purpose: Choroidal thinning has been associated with reticular pseudodrusen (RPD) and ß-peripapillary atrophy (ß-PPA), which have been linked to normal-tension glaucoma (NTG). This analysis sought to determine whether RPD are independently associated with ß-PPA in early AMD patients. Secondary outcomes included the association of RPD and preexisting diagnosis of glaucoma, cup-to-disc ratio (CDR), subfoveal choroidal thickness (SFCT), and IOP. Methods: This prospective cross-sectional study examined 78 age- and sex-matched early AMD patients: 43 RPD patients (63 eyes) and 35 non-RPD patients (64 eyes). Exclusion criteria included advanced AMD, high myopia, and vitreoretinal conditions/surgery. RPD and non-RPD groups were identified by confocal scanning laser ophthalmoscopy. ß-PPA as well as CDR were graded on digital, nonstereoscopic fundus photos. SFCT was measured on spectral-domain optical coherence tomography for 69 patients (35 RPD and 34 non-RPD). IOP and glaucoma diagnosis were extracted from charts. Results: ß-PPA had a greater prevalence in RPD than non-RPD (44% vs. 19%, P = 0.002); however, this relationship was not significant when SFCT was added to the model (P = 0.150). A preexisting diagnosis of glaucoma (P = 0.156), CDR (P = 0.176), and IOP (P = 0.98) was not different between groups. Conclusions: RPD in early AMD are associated with presence of ß-PPA, but choroidal thickness is a confounder in this relationship. Because ß-PPA is a common finding in NTG, focusing on a potential shared pathway between RPD and NTG could improve the understanding of pathophysiology and expand therapies for each condition.
Asunto(s)
Atrofia Geográfica/diagnóstico , Glaucoma/diagnóstico , Atrofia Óptica/diagnóstico , Drusas Retinianas/diagnóstico , Anciano , Anciano de 80 o más Años , Neovascularización Coroidal/patología , Estudios Transversales , Femenino , Angiografía con Fluoresceína , Humanos , Presión Intraocular , Masculino , Oftalmoscopía , Disco Óptico/patología , Estudios Prospectivos , Tomografía de Coherencia Óptica/métodos , Agudeza VisualRESUMEN
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.
Asunto(s)
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
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.
Asunto(s)
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
PURPOSE: To compare choroidal thickness (CT) measurements in early AMD between patients with and without reticular pseudodrusen (RPD) using spectral-domain optical coherence tomography (SD-OCT). METHODS: This cross-sectional study examined 84 age- and sex-matched AMD patients (40 RPD [63 eyes], 44 non-RPD [75 eyes]). Fundus photographs and scanning laser ophthalmoscopy images were graded to identify RPD and non-RPD groups by three retinal specialists (MO, SY, SB) who were masked to corresponding SD-OCTs. CT at the fovea and 2400 to 3000 µm superior and inferior to the fovea was measured on SD-OCT by a grader (AG) and reviewed by a retinal specialist (SB). Only images with a clear posterior choroidal margin were analyzed (six eyes excluded due to poor image quality), and enhanced depth imaging SD-OCT was used when available (20 of 138 eyes). Greatest retinal thickness (RT) on horizontal foveal SD-OCT was also recorded. RESULTS: Mean CTs in the superior, foveal, and inferior macula in RPD (191.3 µm ± 57.9 SD, 176.3 µm ± 60.5 SD, 179.7 µm ± 56.24 SD) were significantly less than that of non-RPD (228.0 µm ± 66.1 SD, 216.5 µm ± 70.3 SD, 224.4 µm ± 71.9 SD; P = 0.0010, P = 0.0005, P = 0.0001, respectively), as was greatest RT (P = 0.0301). CONCLUSIONS: CT was thinner throughout the macula in the RPD group as compared with the non-RPD group. The current analysis supports an association between RPD and a thinned choroidal layer and is consistent with a choroidal etiology of RPD. CT may be integral to understanding RPD, and may be helpful in stratifying AMD progression risk.