RESUMO
PURPOSE: A hallmark of albinism is foveal hypoplasia. However, literature suggests variable foveal development. This study evaluates the association between ocular phenotype and foveal morphology to demonstrate the broad structural and functional spectrum. METHODS: Best-corrected visual acuity (BCVA), nystagmus, angle kappa, stereoacuity, iris transillumination, macular melanin presence, foveal avascular zone, and annular reflex were recorded in 14 patients with albinism. Spectral-domain optical coherence tomography provided macular images. RESULTS: The clinical phenotype was broad, with BCVA varying from 20/20 to 20/100. Better BCVA was associated with a preserved foveal avascular zone, annular macular reflex, stereoacuity, and macular melanin. Imaging demonstrated a continuum of foveal development correlating with BCVA. Individuals with a rudimentary pit had normal inner and outer segment lengthening and better BCVA. CONCLUSIONS: The spectrum of ocular structure and visual function in albinism is broad, suggesting a possible diagnosis of albinism in a patient with an even more normal clinical presentation.
Assuntos
Albinismo Ocular/diagnóstico , Albinismo Oculocutâneo/diagnóstico , Anormalidades do Olho/diagnóstico , Fóvea Central/patologia , Adolescente , Adulto , Idoso de 80 Anos ou mais , Albinismo Ocular/genética , Albinismo Ocular/fisiopatologia , Albinismo Oculocutâneo/genética , Albinismo Oculocutâneo/fisiopatologia , Criança , Análise Mutacional de DNA , Percepção de Profundidade/fisiologia , Potenciais Evocados Visuais , Anormalidades do Olho/genética , Anormalidades do Olho/fisiopatologia , Proteínas do Olho/genética , Feminino , Fóvea Central/anormalidades , Humanos , Masculino , Proteínas de Membrana/genética , Nistagmo Patológico/diagnóstico , Fenótipo , Reação em Cadeia da Polimerase , Estudos Prospectivos , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Adulto JovemRESUMO
PURPOSE: Albinism is associated with disrupted foveal development, though intersubject variability is becoming appreciated. We sought to quantify this variability, and examine the relationship between foveal cone specialization and pit morphology in patients with a clinical diagnosis of albinism. METHODS: We recruited 32 subjects with a clinical diagnosis of albinism. DNA was obtained from 25 subjects, and known albinism genes were analyzed for mutations. Relative inner and outer segment (IS and OS) lengthening (fovea-to-perifovea ratio) was determined from manually segmented spectral domain-optical coherence tomography (SD-OCT) B-scans. Foveal pit morphology was quantified for eight subjects from macular SD-OCT volumes. Ten subjects underwent imaging with adaptive optics scanning light ophthalmoscopy (AOSLO), and cone density was measured. RESULTS: We found mutations in 22 of 25 subjects, including five novel mutations. All subjects lacked complete excavation of inner retinal layers at the fovea, though four subjects had foveal pits with normal diameter and/or volume. Peak cone density and OS lengthening were variable and overlapped with that observed in normal controls. A fifth hyper-reflective band was observed in the outer retina on SD-OCT in the majority of the subjects with albinism. CONCLUSIONS: Foveal cone specialization and pit morphology vary greatly in albinism. Normal cone packing was observed in the absence of a foveal pit, suggesting a pit is not required for packing to occur. The degree to which retinal anatomy correlates with genotype or visual function remains unclear, and future examination of larger patient groups will provide important insight on this issue.
Assuntos
Albinismo Oculocutâneo/diagnóstico , Fóvea Central/patologia , Células Fotorreceptoras Retinianas Cones/patologia , Acuidade Visual , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Albinismo Oculocutâneo/genética , Albinismo Oculocutâneo/fisiopatologia , Contagem de Células , Criança , DNA/genética , Eletrorretinografia , Proteínas do Olho/genética , Feminino , Fóvea Central/fisiopatologia , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Oftalmoscopia , Células Fotorreceptoras Retinianas Cones/metabolismo , Tomografia de Coerência Óptica , Adulto JovemRESUMO
Albinism, an inherited disorder of melanin biosynthesis, disrupts normal retinal development, with foveal hypoplasia as one of the more commonly associated ocular phenotypes. However the cellular integrity of the fovea in albinism is not well understood - there likely exist important anatomical differences that underlie phenotypic variability within the disease and that also may affect responsiveness to therapeutic intervention. Here, using spectral-domain optical coherence tomography (SD-OCT) and adaptive optics (AO) retinal imaging, we obtained high-resolution images of the foveal region in six individuals with albinism. We provide a quantitative analysis of cone density and outer segment elongation demonstrating that foveal cone specialization is variable in albinism. In addition, our data reveal a continuum of foveal pit morphology, roughly aligning with schematics of normal foveal development based on post-mortem analyses. Different albinism subtypes, genetic mutations, and constitutional pigment background likely play a role in determining the degree of foveal maturation.
