Early onset retinal dystrophies: clinical clues to diagnosis for pediatricians.

INTRODUCTION: Inherited retinal dystrophies are major cause of severe progressive vision loss in children. Early recognition and diagnosis are essential for timely visual rehabilitation during the appropriate stages of the visual development, as well as for genetic diagnosis and possible gene therapy. The aim of this study is to characterize a pattern of the initial visual symptoms, which could help the pediatricians and the primary care providers to suspect an inherited retinal disorder in its early stage. METHODS: We analyzed the initial clinical symptoms, based on parental report during the first visit to specialist, in 50 children diagnosed with retinal dystrophy confirmed by full-field electroretinography. The analysis included the age of symptoms onset and the type of visual symptoms, both in the total population and in the following diagnostic subgroups: rod-cone dystrophy (n.17), cone-rod dystrophy (n.12), achromatopsia (n.13), congenital stationary night blindness (n.6) and Leber's congenital amaurosis (n.2). RESULTS: The majority of children (80%) had the onset of clinical symptoms before one year of age. The most frequent visual complaints reported by parents were nystagmus (76%), visual loss (28%) and photophobia (8%). Nystagmus was the first symptom reported by parents if the disease onset was before the age of six months, while the onset after the six months of age was more likely associated with the complain of vision loss. CONCLUSIONS: Low vision and nystagmus observed by parents, particularly in the first year of life, may represent a red flag, prompting an appropriate ophthalmological workup for inherited retinal dystrophy.

Non-syndromic isolated dominant optic atrophy caused by the p.R468C mutation in the AFG3 like matrix AAA peptidase subunit 2 gene.

Autosomal dominant optic atrophy (DOA) is the most frequent form of hereditary optic atrophy, a disease presenting with considerable inter- and intra-familial clinical variability. Although a number of mutations in different genes are now known to cause DOA, many cases remain undiagnosed. In an attempt to identify the underlying genetic defect, whole exome sequencing was performed in a 19-year-old male that had been affected by isolated DOA since childhood. The exome sequencing revealed a pathogenic mutation (p.R468C, c.1402C>T) in the AFG3 like matrix AAA peptidase subunit 2 (AFG3L2) gene, a gene known to be associated with spinocerebellar ataxia. The patient did not show any signs other than DOA. Thus, the result demonstrates the possibility that mutations in the AFG3L2 gene may be a cause of isolated autosomal DOA.

Long-term rearrangement of retinal structures in a novel mutation of X-linked retinoschisis.

The aim of the present study was to report a novel mutation in the retinoschisin 1 (RS1) gene in a Caucasian family affected by X-linked juvenile retinoschisis (XLRS) and to describe the long-term modification of retinal structure. Two brothers with an early onset maculopathy were diagnosed with XLRS. Fundus photography, fluorescein angiography, spectral domain optical coherence tomography and electroretinogram analyses were performed. Their sister was also examined. All subjects were screened for mutations in the RS1 gene. XLRS patients demonstrated a marked reduction of best-corrected visual acuity. SD-OCT scans reported a cystic degeneration primarily involving the inner nuclear layer, though some cysts were detected in the outer plexiform layer and in the ganglion cell layer. During the ten-year follow-up, a progressive retinal thickening and coalescence of the cysts was observed. Genetic testing revealed a novel mutation (p.Ile212Asn) in the RS1 gene in both XLRS patients, whereas their sister was not a genetic carrier. Several mutations of the RS1 gene were recognized to be responsible for XLRS. Although the correspondence between genotype and phenotype is still under debate, is reasonable that siblings affected by XLRS could share other genetic and/or epigenetic factors capable to influence clinical course of the disease.

Combination of photodynamic therapy and intraocular triamcinolone for exudative age-related macular degeneration and long-term chorioretinal macular atrophy.

OBJECTIVE: To evaluate the long-term effect of intravitreal triamcinolone acetonide (IVT) treatment combined with photodynamic therapy (PDT) vs PDT alone for neovascular age-related macular degeneration. METHODS: Prospective randomized study. Eighty-four patients were enrolled to receive PDT (n = 41) or IVT treatment followed by PDT (n = 43) within approximately a 7- to 15-day interval. All patients were naive to treatment. At baseline and each follow-up visit at 3, 6, 12, and 24 months, measurement of best-corrected visual acuity (VA), fluorescein angiography, indocyanine green angiography, and optical coherence tomography were performed. Mean changes in VA and retreatment rate were considered as primary outcome indicators. Analysis of vascular choroidal changes documented by indocyanine green angiography and fundus autofluorescence measurements were also performed. RESULTS: Mean VA increased at 1 month of follow-up but decreased progressively by the 24-month point in both groups (P = .74). The retreatment rate was significantly lower (P < .001) in the combined therapy group. Choroidal hypoperfusion/nonperfusion (P < .001) and areas with decreased/absent fundus autofluorescence within the PDT spot area were significantly greater with combined therapy (P < .001). CONCLUSIONS: Combination IVT treatment with PDT seemed to be more effective for managing neovascular age-related macular degeneration, but long-term analysis failed to demonstrate functional benefits.