Abstract.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. IntroductionAutosomal dominant optic atrophy (DOA) is a disorder that results from the degeneration of the optic nerve fibers (1). It is one of the most prevalent forms of inherited optic neuropathies, which are genetic conditions affecting the retinal ganglion cells whose axons constitute the optic nerve (2). DOA is an important cause of inherited visual failure and occurs equally among males and females (1). Its prevalence is estimated to be 1 per 30,000 worldwide with higher frequencies in Denmark (1 per 10,000) due to a founder effect (3). It is generally diagnosed during childhood and is characterized by loss of visual acuity, dyschromatopsia, visual field defects and optic nerve pallor with optic disc excavation (4).The majority of DOA cases (80%) are isolated (non-syndromic) while the remaining (20%) are syndromic (2). DOA that presents clinically as an isolated optic neuropathy is caused by mutations in OPA1, mitochondrial dynamin like GTPase (OPA1) (4), OPA3, outer mitochondrial membrane lipid metabolism regulator (OPA3; also associated with cataracts) (5), aconitase 2 (ACO2) (6) and transmembrane protein 126A (TMEM126A) (7) genes, while syndromic DOA forms show greater genetic heterogeneity (8). To date, 224 genes associated with optic atrophy are listed in the Human Phenotype Ontology (HPO) database, the majority presenting with neurological symptoms, such as ataxia, mental retardation and spastic paraplegia (9). Increasing evidence also indicates that other genes, in addition to yet unidentified genes, are involved (10). Yet, despite these advancements, more than half of DOA patients still await a genetic diagnosis (11). This shortcoming may be overcome using whole exome sequencing, which has the potential to define the molecular diagnosis of patients presenting with a negative result for mutations in the OPA1, OPA3, ACO2 and TMEM126A genes.In the current study, the exome of an Italian patient affected by isolated DOA was analyzed. By combining exome sequencing with phenotype-driven variant analysis, a heterozygous mutation was identified in the AFG3 like matrix AAA peptidase subunit 2 (AFG3L2) gene. Notably, the p.R468C (c.1402C>T) mutation was recently described in a family ex...

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 15day 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 outcomeindicators.Analysisofvascularchoroidalchangesdocumented 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 Ͻ .001) in the combined therapy group. Choroidal hypoperfusion/nonperfusion (PϽ.001) and areas with decreased/absent fundus autofluorescence within the PDT spot area were significantly greater with combined therapy (PϽ .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.

Aims: To evaluate, with fundus perimetry, the peripapillary differential light threshold (DLT) in eyes with glaucoma and ocular hypertension (OHT), and compare it with peripapillary retinal nerve fibre layer (RNFL) thickness. Methods: 35 glaucomatous, 29 OHT and 24 control eyes were included. Peripapillary DLT at 1˚from the optic nerve head was quantified with fundus perimetry; peripapillary RNFL thickness was measured over the same area by optical coherence tomography. Results: Mean (SD) peripapillary DLT was 19.2 (1.7), 17.6 (4.2) and 10.1 (6.9) dB in control, OHT and glaucomatous eyes, respectively (p,0.001). Mean (SD) RNFL thickness was 98.4 (35.3), 83.9 (35.1) and 55.8 (28.2) mm, respectively (p,0.001). Mean peripapillary DLT showed higher sensitivity and specificity in differentiating the three groups compared with RNFL thickness. Conclusion: Progressive, significant reduction of peripapillary DLT was documented in OHT and glaucomatous eyes compared with controls (p,0.001). DLT reduction parallels RNFL reduction.

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