Disease-Causing TIMP3 Variants and Deep Phenotyping of Two Czech Families with Sorsby Fundus Dystrophy Associated with Novel p.(Tyr152Cys) Mutation.

We aim to report the ocular phenotype and molecular genetic findings in two Czech families with Sorsby fundus dystrophy and to review all the reported TIMP3 pathogenic variants. Two probands with Sorsby fundus dystrophy and three first-degree relatives underwent ocular examination and retinal imaging, including optical coherence tomography angiography. The DNA of the first proband was screened using a targeted ocular gene panel, while, in the second proband, direct sequencing of the TIMP3 coding region was performed. Sanger sequencing was also used for segregation analysis within the families. All the previously reported TIMP3 variants were reviewed using the American College of Medical Genetics and the Association for Molecular Pathology interpretation framework. A novel heterozygous variant, c.455A>G p.(Tyr152Cys), in TIMP3 was identified in both families and potentially de novo in one. Optical coherence tomography angiography documented in one patient the development of a choroidal neovascular membrane at 54 years. Including this study, 23 heterozygous variants in TIMP3 have been reported as disease-causing. Application of gene-specific criteria denoted eleven variants as pathogenic, eleven as likely pathogenic, and one as a variant of unknown significance. Our study expands the spectrum of TIMP3 pathogenic variants and highlights the importance of optical coherence tomography angiography for early detection of choroidal neovascular membranes.

Outcome of Cataract Surgery in Patients With Retinitis Pigmentosa.

PURPOSE: To assess the visual outcome of cataract surgery in patients with retinitis pigmentosa (RP). DESIGN: Retrospective, noncomparative clinical study. METHODS: Preoperative, intraoperative, and postoperative data of patients with RP who were undergoing cataract surgery were collected from several expertise centers across Europe. RESULTS: In total, 295 eyes of 226 patients were included in the study. The mean age at surgery of the first eye was 56.1 ± 17.9 years. Following surgery, best-corrected visual acuity (BCVA) improved significantly from 1.03 to 0.81 logMAR (ie, 20/214 to 20/129 Snellen) in the first treated eye (-0.22 logMAR; 95% CI = -0.31 to -0.13; P < .001) and from 0.80 to 0.56 logMAR (ie, 20/126 to 20/73 Snellen) in the second treated eye (-0.24 logMAR; 95% CI = -0.32 to -0.15; P < .001). Marked BCVA improvements (postoperative change in BCVA of ≥0.3 logMAR) were observed in 87 of 226 patients (39%). Greater odds for marked visual improvements were observed in patients with moderate visual impairment or worse. The most common complications were zonular dialysis (n = 15; 5%) and (exacerbation of) cystoid macular edema (n = 14; 5%), respectively. Postoperative posterior capsular opacifications were present in 111 of 295 eyes (38%). CONCLUSION: Significant improvements in BCVA are observed in most patients with RP following cataract surgery. Baseline BCVA is a predictor of visual outcome. Preoperative evaluation should include the assessment of potential zonular insufficiency and the presence of CME, as they are relatively common and may increase the risk of complications.

Novel noninvasive biomarkers of prodromal Alzheimer disease: The role of optical coherence tomography and optical coherence tomography-angiography.

BACKGROUND AND PURPOSE: A reduction of retinal thickness and an alteration of retinal perfusion have been found in Alzheimer disease (AD). Nowadays, retinal layers and retinal perfusion can be evaluated by means of noninvasive imaging techniques, namely, optical coherence tomography (OCT) and OCT-angiography (OCT-A). Here, we have compared the retinal thickness and the perfusion index, measured by means of OCT and OCT-A, in patients with mild cognitive impairment due to AD (MCI-AD) and in age- and sex-matched cognitively healthy controls. METHODS: Twenty-four MCI-AD patients and 13 control subjects were enrolled. MCI-AD patients underwent lumbar puncture; all of them showed a cerebrospinal fluid (CSF) profile compatible with AD. OCT was used for evaluating retinal volumes and thicknesses, whereas with OCT-A we measured fractal dimension (FD), vascular perfusion density (VPD), and vessel length density (VLD) of superficial capillary plexus (SCP), intermediate capillary plexus (ICP), deep capillary plexus (DCP), and choriocapillaris. The comparisons between groups were made after adjustment for age, diabetes, and hypertension. RESULTS: A significant reduction of SCP-VLD (p = 0.012), ICP-VPD (p = 0.015), ICP-VLD (p = 0.004), DCP-VPD (p = 0.012), and DCP-VLD (p = 0.009) was found in MCI-AD patients compared to controls. Conversely, FD was higher in MCI-AD than in controls (p = 0.044). CSF Aß42/total tau negatively correlated with FD (r = -0.51, p = 0.010). CONCLUSIONS: OCT-A might have a potential role in detecting new noninvasive biomarkers for early AD detection. Retinal VPD might identify amyloid angiopathy-related chronic injury, and FD could show early vessel recruitment as a compensative mechanism at disease onset. Further studies will be needed to confirm these findings.

Associations of Alzheimer's disease with macular degeneration.

There is growing evidence of epidemiological, genetic, molecular and clinical links between Alzheimer's disease (AD) and age-related macular degeneration (AMD). Major interest in the relationship between AD and AMD has derived from the evidence that beta-amyloid, the main component of senile plaques, the hallmark of AD, is also an important component of drusen, the hallmark of AMD. This finding has a great potential in the present era of anti-amyloid agents for the treatment of AD. The connection between AD and AMD is also supported by the evidence that the two diseases share other pathophysiological factors, such as oxidative stress and neuroinflammation. Accordingly, a few clinical trials have evaluated the efficacy of antioxidants on visual and cognitive performance in patients presenting both disorders. In this review, we summarize the pathophysiological and clinical evidence of the relationship between these two age-related disorders. Considering the increasing prevalence of both conditions along with the aging of the population, further investigations of this important issue are highly needed.