Novel USH1G homozygous variant underlying USH2-like phenotype of Usher syndrome.

PURPOSE: Usher syndrome (USH) is an autosomal recessive disorder characterized by congenital sensorineural hearing impairment and retinitis pigmentosa. Classification distinguishes three clinical types of which type I (USH1) is the most severe, with vestibular dysfunction as an added feature. To date, 15 genes and 3 loci have been identified with the USH1G gene being an uncommon cause of USH. We describe an atypical USH1G-related phenotype caused by a novel homozygous missense variation in a patient with profound hearing impairment and relatively mild retinitis pigmentosa, but no vestibular dysfunction. METHODS: A 26-year-old female patient with profound congenital sensorineural hearing loss, nyctalopia and retinitis pigmentosa was studied. Audiometric, vestibular and ophthalmologic examination was performed. A panel of 13 genes was tested by next-generation sequencing (NGS). RESULTS: While the hearing loss was confirmed to be profound, the vestibular function resulted normal. Although typical retinitis pigmentosa was present, the age at onset was unusually late for USH1 syndrome. A novel homozygous missense variation (c.1187T>A, p.Leu396Gln) in the USH1G gene has been identified as causing the disease in our patient. CONCLUSIONS: Genetic and phenotypic heterogeneity are very common in both isolated and syndromic retinal dystrophies and sensorineural hearing loss. Our findings widen the spectrum of USH allelic disorders and strength the concept that variants in genes that are classically known as underlying one specific clinical USH subtype might result in unexpected phenotypes.

Choriocapillary vascular density in central serous chorioretinopathy complicated by choroidal neovascularization.

BACKGROUND: To evaluate choriocapillary vascular density (CVD) in eyes with central serous chorioretinopathy (CSC) complicated by choroidal neovascularization (CNV), at baseline and after intravitreal injections (IVR) of Ranibizumab, using optical coherence tomography angiography (OCTA). METHODS: Twelve eyes of 12 patients were enrolled as group 1 and 12 unaffected fellow eyes formed group 2. Twelve eyes of 12 healthy controls were the control group. RESULTS: CVD in Group 1 did not differ before and after treatment. CVD of Group 1 was significantly lower compared with controls at baseline (whole, parafovea and fovea p < 0.05). CVD of controls resulted significantly higher than Group 2 at baseline (whole, parafovea and fovea p < 0.05). There were not significant differences in CVD between Groups 1 and 2 at baseline (p > 0.05). CONCLUSIONS: OCTA revealed a choriocapillary hypoperfusion that may be responsable for the beginning of this disease and the late development of CNV.

Optical coherence tomography angiography to assess vascular remodeling of the choriocapillaris after low-fluence photodynamic therapy for chronic central serous chorioretinopathy.

BACKGROUND: To evaluate the efficacy of optical coherence tomography angiography (OCTA) in identifying changes in the choriocapillaris layer after low-fluence verteporfin photodynamic therapy (vPDT) in patients affected by chronic central serous chorioretinopathy (CSCR). METHODS: Low-fluence vPDT was performed on 28 eyes of 27 patients with CSCR. All patients underwent the following tests at baseline and 6 months after treatment: best corrected visual acuity (BCVA), fluorescein angiography, indocyanine green angiography, enhanced depth imaging OCT and OCTA. RESULTS: Subretinal fluid was completely absorbed in 18 of the 28 affected eyes (64.3%) after low-fluence vPDT ("responders"), and incompletely absorbed in 10 eyes (35.7%) ("non responders"). BCVA was significantly improved (p = 0.006) whereas central foveal thickness and choroidal foveal thickness were significantly decreased (p = 0.001 and p = 0.00 respectively) 6 months after treatment in responders. CONCLUSIONS: OCTA revealed a different pattern of vascular remodeling of the choriocapillaris between CSC patients who responded and those who did not respond to low-fluence vPDT.

The Relationship between Macular Pigment and Vessel Density in Patients with Type 1 Diabetes Mellitus.

AIM: Macular pigment density and microvascular density on optical coherence tomography angiography (OCTA) were measured in a cohort of type 1 diabetes mellitus (T1DM) patients with retinopathy in the attempt to shed light on the pathophysiology of this condition. METHODS: Eighty-two consecutive eyes of 59 patients with diabetic retinopathy examined at the Eye Clinic of the University of Naples Federico II from November 2016 to April 2017 were enrolled in this prospective study. Eighty normal eyes of 40 age-matched subjects without diabetes mellitus, without a history of glaucoma or evidence of intraocular surgery, and without retinal pathologic features constituted the control group. All patients and controls underwent a complete ophthalmic examination, best corrected visual acuity evaluation according to the ETDRS visual logMAR scale, measurement of intraocular pressure, OCTA, and evaluation of macular pigment. RESULTS: There were no significant age differences between patients and controls. Both macular pigment measurements and vessel density measured by OCTA were significantly lower in patients than in controls. A moderate correlation was found between vessel density in all ETDRS sectors and macular pigment parameters. CONCLUSIONS: There was a reduction in macular pigment and in OCTA vessel density in T1DM patients with retinopathy, which may have prognostic value in determining disease progression.

Optical coherence tomography angiography in myopic choroidal neovascularization after intravitreal ranibizumab.

PURPOSE:: To describe the optical coherence tomography angiography characteristics of myopic patients with choroidal neovascularization secondary to pathologic myopia during ranibizumab therapy. METHODS:: Nineteen patients were enrolled in this prospective study (13 females, 6 males, mean age 55.25 ± 9.63 years) for a total of 20 eyes examined (14 right eyes, 6 left eyes). Images were analyzed independently by two examiners. RESULTS:: Mean follow-up was 5.75 ± 1.88 months, with a mean intravitreal injections of 1.90 ± 0.44. Mean best-corrected visual acuity at baseline was 0.39 ± 0.18 logMAR versus 0.26 ± 0.16 logMAR 6 months after treatment. The neovascular area (Z = -2.091, p = 0.037) was significantly reduced after treatment, whereas vessel density was not (Z = -1.848, p = 0.065). Moreover, the best-corrected visual acuity was increased (Z = -3.055, p = 0.002). Neovascular area was significantly correlated with best-corrected visual acuity, at both baseline and follow-up (p < 0.05). CONCLUSION:: Our data suggest that optical coherence tomography angiography is a reproducible non-invasive examination with which to monitor changes in the neovascular area in patients with pathologic myopia treated with ranibizumab.

Evaluation of Vascular Changes with Optical Coherence Tomography Angiography after Plaque Radiotherapy of Choroidal Melanoma.

AIM: The purpose of this paper was to evaluate whether optical coherence tomography angiography (OCT-A) can be used to quantify the vascular changes in radiation maculopathy, and changes in the tumor vasculature in eyes treated with plaque radiotherapy for choroidal melanoma. METHODS: In this prospective study, we evaluated 39 Caucasian patients with choroidal melanoma (39 eyes) treated with ruthenium-106 plaque radiotherapy. The patients underwent complete ophthalmic examination, bulbar echography, and OCT-A before and 1 year after treatment. RESULTS: At baseline, the mean best-corrected visual acuity (BCVA) in the affected eyes was 0.35 ± 0.40 logMAR, and the mean tumor thickness was 2.68 ± 0.25 mm at A-scan echography. After treatment, the mean BCVA increased to 0.41 logMAR, the mean tumor thickness decreased to 1.66 ± 0.23 mm, and the tumor basal diameter was significantly reduced (U = 108, p = 0.001). Moreover, the capillary vessel density was significantly lower in all Early Treatment of Diabetic Retinopathy Study sectors, and both the vessel and flow areas were significantly reduced (p = 0.030 and p = 0.001, respectively). CONCLUSIONS: OCT-A is a noninvasive, reliable method with which to quantify the vessel changes in radiation maculopathy and, given the association between vascularization and malignancy, this procedure may be an aid in treatment decision-making and in monitoring the efficacy of treatment.

Multimodal Imaging in Autosomal Dominant Cone-Rod Dystrophy Caused by Novel CRX Variant.

AIM: To characterize by multimodal approach the phenotype of patients from a 3 generations pedigree, affected by autosomal dominant cone-rod dystrophy (CRD), found to carry a novel pathogenic variant in the cone-rod homeobox-containing (CRX) gene. METHODS: Examination of the adult patients included the following tests: visual acuity, multicolour imaging, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) and OCT angiography (OCT-A) recordings. In a 2.5-year-old child, cycloplegic refraction, fundoscopy, ocular motility evaluation and electrophysiological exams were performed. Next Generation Sequencing of patients' DNA has been carried out. RESULTS: A novel CRX pathogenic variant has been identified in our patients. The 2.5-year-old child in the third generation was found to have inherited the variant, with no clinical signs of the condition, but electroretinographic abnormalities in the scotopic component. In the adult patients, diffuse atrophy of the retinal pigment epithelium/photoreceptor complex in the macular region was evident at the OCT and FAF, while OCT-A showed choriocapillaris density reduction. CONCLUSIONS: Multimodal study allowed the characterization of a peculiar form of CRD. The novel pathogenic variant seems to have a different effect on the phenotype if compared with a previously described similar one, giving an insight into the pathogenic mechanism of CRX-related retinal dystrophies and offering valuable information that could lead to the development of possible future therapies.

Study of the Radial Peripapillary Capillary Network in Congenital Optic Disc Anomalies With Optical Coherence Tomography Angiography.

PURPOSE: To evaluate the radial peripapillary capillary network with optical coherence tomography angiography (angio-OCT) in morning glory syndrome (MGS), optic disc colobomas, and optic disc pits, and to explore possible correlations between the neural vascular structure and the pathogenesis of congenital optic disc anomalies. DESIGN: Prospective observational comparative case series. METHODS: Fifteen eyes of 15 patients with congenital optic disc anomalies were enrolled in this study. All patients underwent angio-OCT. The scans were centered on optic discs. RESULTS: The mean age at presentation was 33 years (range: 19-50 years). Congenital optic disc anomalies were identified in all 15 eyes. Three eyes had the characteristic funduscopic signs of MGS, and angio-OCT scans of the peripapillary retina revealed a dense microvascular network. Optic disc colobomas were found in 5 eyes, and the characteristic funduscopic signs of optic pits were found in 7 eyes. Angio-OCT showed the absence of a radial peripapillary microvascular network in these 12 eyes. CONCLUSION: The finding that angio-OCT scans confirmed the presence of a peripapillary microvascular network only in MGS cases supports the hypothesis that a primary neuroectodermal abnormality and a secondary mesenchymal abnormality leads to MGS. Angio-OCT is a safe, rapid imaging technique that could shed light on the pathogenesis of rare diseases of the optic disc.

Optical coherence tomography angiography versus fluorescein angiography in the diagnosis of ischaemic diabetic maculopathy.

PURPOSE: To evaluate the efficacy of optical coherence tomography (OCT) angiography versus fluorescein angiography (FA) in terms of retinal vessel imaging in ischaemic diabetic maculopathy defined according to the Early Treatment Diabetic Retinopathy Study (ETDRS) classification. METHODS: Twenty patients (31 eyes) with ischaemic diabetic maculopathy and 17 control subjects (27 eyes) were enrolled in this prospective study. Patients and control subjects underwent complete ophthalmic examination, including best-corrected visual acuity (BCVA), intraocular pressure, FA, Fourier domain optical coherence tomography (FD-OCT) and OCT angiography. Fluorescein angiograms and OCT angiography images were graded according to the foveal avascular zone (FAZ) of the ETDRS group. Ganglion cell complex (GCC) thickness was evaluated with FD-OCT. RESULTS: Optical coherence tomography (OCT) angiography images closely correlated with FA in terms of FAZ parameters. The correlation was strongest with OCT angiography deep imaging. The average GCC thickness was smaller in patients than in controls. Neither GCC parameters nor FAZ was correlated to BCVA. CONCLUSIONS: Given the correlation between FA and OCT angiography in terms of FAZ parameters, the newer method can be considered a valid, reliable and easy-to-perform method with which to evaluate ischaemic diabetic maculopathy without contrast injection, and thus to visualize and quantify non-perfusion areas without risks of anaphylactic reactions.

Evaluation of ischemic diabetic maculopathy with Fourier-domain optical coherence tomography and microperimetry.

OBJECTIVE: To evaluate the efficacy of high-speed Fourier-domain optical coherence tomography (FD-OCT) and fundus microperimetry (MP-1) in identifying the anatomic and functional features of ischemic diabetic maculopathy. DESIGN: Prospective noninterventional study. PARTICIPANTS: Forty-two consecutive eyes (23 patients) with ischemic diabetic maculopathy and 40 normal eyes (25 control subjects) were included in this study. METHODS: Best corrected visual acuity, ganglion cell complex (GCC) thickness measured with FD-OCT, and central light sensitivity recorded with MP-1 were evaluated. RESULTS: GCC thickness and light sensitivity were significantly reduced in all affected eyes versus control eyes. logMAR BVCA was significantly correlated with mean macular sensitivity (R=0.783, R(2)=0.611). CONCLUSIONS: GCC thickness and microperimetry integrated with fluorescein angiography could be a marker of retinal vascular abnormalities that is useful for the diagnosis of ischemic diabetic maculopathy.

A randomized trial of intravitreal bevacizumab vs. ranibizumab for myopic CNV.

AIMS: The aim was to compare the efficacy of intravitreal therapy with bevacizumab and ranibizumab for choroidal neovascularization (CNV) in pathologic myopia (PM). METHODS: This was a prospective multicenter randomized nonblinded trial. RESULTS: In seven centers, 78 eyes were randomized 1:1 to treatment with bevacizumab (group B, 40 eyes) or ranibizumab (group R, 38 eyes) given with an "on demand" regimen (PRN). The mean follow-up was 19 months (SD 2, range 12-24). The mean BCVA at baseline was 0.60 logMAR (20/80 Snellen equivalent, Seq) and 50 letter score (ls). Mean final BCVA was 0.51 LogMAR (20/63 Seq) and 57 ls (p = 0.0009 and p = 0.0002, respectively). In group B, mean basal BCVA was 0.52 logMAR (20/63 Seq) and 54 ls, and final BCVA was 0.51 logMar (20/63 Seq) and 57 ls. In group R, mean basal BCVA was 0.62 logMAR (20/80 Seq) and 45 ls, and the final values were 0.50 logMAR (20/63 Seq) and 58 ls. Statistical comparison of the two groups showed no significant difference (logMAR p = 0.90 and letters p = 0.78). Multivariate analysis showed no influence of age or previous photodynamic treatment (PDT) on final visual changes. The mean number of treatments in the first year was 2.7 in group B and 2.3 in group R (p = 0.09). CONCLUSION: Myopic CNV equally benefits from on-demand intravitreal injection of either bevacizumab or ranibizumab; the therapeutic effect is independent of previous PDT and age.