Stefania Miotto

Combined effects of genetic and non-genetic risk factors affect response to ranibizumab in exudative age-related macular degeneration.

To investigate whether genetic and non‐genetic risk factors influence 12‐month response to ranibizumab treatment for exudative age‐related macular degeneration (AMD).

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.

Occult macular dystrophy in an Italian family carrying a mutation in the RP1L1 gene.

Occult macular dystrophy (OMD) is an inherited macular disease characterized by progressive visual decline with the absence of visible retinal abnormalities. Typical alterations of the retinal structure are detectable by spectral domain optical coherence tomography (SD‑OCT). Mutations in the RP1L1 gene have been identified to be responsible for the disease in Asian subjects. The present study assessed the role of mutations in the RP1L1 gene in an Italian family with OMD. One patient with OMD and five related subjects (two male offspring affected by progressive visual decline and three asymptomatic siblings of the patient) were subjected to complete ophthalmological examination. SD‑OCT was also performed. All subjects were screened for OMD‑associated genetic mutations in the RP1L1 gene. The OMD patient and the two symptomatic offspring presented with a reduced best‑corrected visual acuity. Although no fundus abnormalities were observed, SD‑OCT examination showed that the external limiting membrane and the inner segment/outer segment band were not clearly identifiable and a focal disruption of the photoreceptor layer was present. The degree of photoreceptor alterations was correlated with the severity of visual impairment. Clinical and tomographic results in the three asymptomatic relatives were normal. A p.Arg45Trp mutation in the RP1L1 gene was identified in the OMD patient, in the two symptomatic offspring and also in two of the asymptomatic siblings of the patient. The identification of RP1L1 mutations in subjects with OMD may improve the accuracy of diagnosis of this rare condition and may aid in enhancing the efficacy of genetic counseling.

Morphologic Criteria of Lesion Activity in Neovascular Age-Related Macular Degeneration: A Consensus Article

Abstract Intravitreal antivascular endothelial growth factor drugs represent the current standard of care for neovascular age-related macular degeneration (nAMD). Individualized treatment regimens aim at obtaining the same visual benefits of monthly injections with a reduced number of injections and follow-up visits, and, consequently, of treatment burden. The target of these strategies is to timely recognize lesion recurrence, even before visual deterioration. Early detection of lesion activity is critical to ensure that clinical outcomes are not compromised by inappropriate delays in treatment, but questions remain on how to effectively monitor the choroidal neovascularization (CNV) activity. To assess the persistence/recurrence of lesion activity in patients undergoing treatment for nAMD, an expert panel developed a decision algorithm based on the morphological features of CNV. After evaluating all current retinal imaging techniques, the panel identified optical coherent tomography as the most reliable tool to ascertain lesion activity when funduscopy is not obvious.

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.

Relief of macular traction after laser puncture for an intraretinal hemorrhagic pseudocyst.

Relief of Macular Traction After Laser Puncture for an Intraretinal Hemorrhagic Pseudocyst A 44-year-old man complained of floaters in his right eye. The fundus examination revealed a large multilayered hemorrhage, adjacent to the macula, which was associated with an arterial macroaneurysm (Figure 1A). Hard exudates and aneurysms were also evident in midperiphery where angiography showed telangiectasia surrounded by the areas of capillary dropout. The left eye was normal. Clinical and angiographic features were consistent with the diagnosis of adult-onset Coats’ disease. Laser photocoagulation of vascular abnormalities was performed and retinal exudates were gradually reabsorbed. The large retinal hemorrhage spontaneously cleared in 4 months, leaving a dome-shaped pseudocystic lesion, filled with serous fluid (Figure 1B) and covered with a taut membrane, which strongly adhered to the vitreous cortex. Retinal traction from the edge of the cyst extended to the macula contributing, along with vascular leakage, to foveal distortion and thickening (Figure 2A). Because of persistent metamorphopsia, a neodymium-doped yttrium aluminum garnet (Nd:YAG) laser puncture, near the inferior edge of the dome-shaped lesion (4 bursts, 4 mJ), was performed. Immediately after treatment, spectral domain optical coherence tomography showed bloodstained cyst fluid pouring into the vitreous cavity through an aperture on the cyst wall (Figure 2B). During the next days, there was an evident progressive flattening of the lesion, with the relief of traction on the macula that gradually recovered normal shape and thickness (Figures 1C and 2, C and D). As the cyst wall became less rigid, it appeared to be composed by 2 layers, the vitreous cortex and the internal limiting membrane (Figure 2D). Superficial intraretinal hemorrhagic pseudocysts are an uncommon complication of Coats’ disease. Although laser treatment of subhayloidal hemorrhages has been previously reported, we are original in