Two novel compound heterozygous SAG mutations in an Italian patient with Oguchi disease: A genetic and multimodal retinal imaging study.

BACKGROUND: Oguchi disease is a rare autosomal recessive retinal dystrophy, characterized by congenital stationary blindness and caused by pathogenic variants in SAG and GRK1 genes. The present study aimed to report an Italian patient affected by Oguchi disease, evaluated by means of a multimodal retinal imaging study and harboring two novel heterozygous pathogenic variants in the SAG gene. MATERIALS AND METHODS: A 60-year-old female complaining congenital stationary night blindness was investigated through fundus photograph, optical coherence tomography (OCT), electroretinography (ERG), and genetic testing. RESULTS: Fundus examination showed a golden-grayish fundus aspect. The rod response of the scotopic ERG was undetectable and mixed rod-cone response was electronegative. Fundus photographs obtained in light and in prolonged dark-adapted conditions allowed to detect the Mizuo-Nakamura phenomenon. Light condition OCT over the abnormal retinal regions showed high-intensity areas in the outer photoreceptor segment layer, that reduced with prolonged dark adaption. Genetic testing identified two rare heterozygous sequence variants in the SAG gene: NM_000541.5:c.807delA p.(Glu270Lysfs*9) and NM_000541.5:c.1047-1G>C confirming the diagnosis of Oguchi disease. CONCLUSIONS: We identified the first Italian compound heterozygous patient harboring two novel alterations in the SAG gene (a frameshift deletion and a splicing variant). The involvement of the SAG gene in Oguchi disease is a common finding in Japanese population, but rarely identified in Caucasians. Clinical suspicion should prompt the molecular analysis of genes associated with this condition.

Severe retinopathy of prematurity is associated with early post-natal low platelet count.

Pathophysiology of retinopathy of prematurity (ROP) still presents a gap. Lately blood tests parameters of premature infants have been measured at different times of ROP, attempting to detect correlations with ROP development and progression. So far, very early post-natal biomarkers, predictive of ROP outcome, have not been detected. Our purpose is to evaluate, in the earliest post birth blood sample, the correlation between routinely dosed blood parameters and ROP outcome. 563 preterm babies, screened according to ROP guidelines, were included and classified in conformity with ET-ROP study in "Group 1" (ROP needing treatment), "Group 2" (ROP spontaneously regressed) and "noROP" group (never developed ROP). The earliest (within an hour after delivery) blood test parameters routinely dosed in each preterm infant were collected. Platelet count was decreased in Group 1 versus noROP group (p = 0.0416) and in Group 2 versus noROP group (p = 0.1093). The difference of thrombocytopenic infants among groups was statistically significant (p = 0.0071). CRP was higher in noROP versus all ROPs (p = 0.0331). First post-natal blood sample revealed a significant thrombocytopenia in ROP needing treatment, suggesting a role of platelets in the pathophysiology and progression of ROP, possibly considering it as a predictive parameter of ROP evolution.

Structural and microvascular changes of the peripapillary retinal nerve fiber layer in Von Hippel-Lindau disease: an OCT and OCT angiography study.

Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic disease caused by VHL gene mutation. Retinal hemangioblastomas (RH) are vascularized tumors and represent the main ocular manifestation of the disease. Histopathologically, RH are composed of capillary vessels and stromal cells, the neoplastic population of the lesion. The origin of these stromal cells remains controversial, even if they are hypothesized to be glial cells. The aim of the present study was to investigate neuronal and microvascular changes of the peripapillary retinal nerve fiber layer, in which glial cells, neurons and capillaries (the radial peripapillary capillary plexus) interact. VHL patients with or without peripheral RH were enrolled and compared to healthy controls. Mean peripapillary retinal nerve fiber layer (pRNFL) thickness was measured by means of optical coherence tomography (OCT). The following vascular parameters of the radial peripapillary capillary plexus were quantified using OCT angiography: Vessel Area Density,Vessel Length Fraction, Vessel Diameter Index and Fractal Dimension. One hundred and nine eyes of 61 patients, and 56 eyes of 28 controls were consecutively studied. Mean pRNFL was significantly thinner in VHL eyes without RH versus eyes with RH and controls. Mean pRNFL thickness did not differ between VHL eyes with RH and controls. All OCTA vascular parameters were reduced in VHL eyes with or without RH versus controls, with significative difference for Vessel Diameter Index. The same OCTA parameters did not significantly differ between VHL eyes with or without RH. In VHL eyes without RH, pRNFL thinning may be the consequence of impaired perfusion of the radial peripapillary capillary plexus, while the increase of pRNFL thickness in VHL eyes with RH may depend on possible activation and proliferation of the other RNFL resident cells, the glial cells.

Macular Perfusion Impairment in Von Hippel-Lindau Disease Suggests a Generalized Retinal Vessel Alteration.

BACKGROUND: To evaluate macular perfusion in patients with Von Hippel-Lindau (VHL) disease. METHODS: VHL patients with or without peripheral retinal hemangioblastomas (RHs) were consecutively enrolled. A group of healthy subjects served as controls. Macular perfusion was analyzed by means of OCT angiography (OCTA) in the superficial vascular plexus (SVP), and in the intermediate (ICP) and deep retinal capillary (DCP) plexuses. The following OCTA parameters were measured: Vessel Area Density (VAD), Vessel Length Fraction (VLF), Vessel Diameter Index (VDI) and Fractal Dimension (FD). RESULTS: Sixty-three VHL patients (113 eyes) and 28 healthy controls (56 eyes) were enrolled. All OCTA quantitative parameters were reduced in VHL patients vs. controls, reaching statistical significance for VAD of the SVP (0.348 ± 0.07 vs. 0.369 ± 0.06, p = 0.0368) and VDI of all plexuses (p < 0.03 for all). No significant differences were detected between eyes without or with peripheral RHs. CONCLUSIONS: Macular perfusion is reduced in VHL patients demonstrating retinal vessel changes that are independent of the presence of peripheral RHs. VHL gene mutations disrupt the hypoxia-induced (HIF)/vascular endothelium growth factors (VEGF) pathway and the Notch signaling, both essential for the normal retinal vasculogenesis and angiogenesis. Therefore, an anomalous generalized retinal vascular development may be hypothesized in VHL disease.