Solar retinopathy: a new setting of red, green, and blue channels

PURPOSE: To introduce a new color imaging technique using improved settings of red, green, and blue channels for improved delineation of retinal damage in patients with solar retinopathy. METHODS: A retrospective case series of patients with poor vision secondary to solar retinopathy were analyzed. All patients underwent visual acuity, refraction, and dilated fundus examination. A spectral domain–optical coherence tomography of the macula and color fundus imaging using optimized red, green, and blue color setting was performed. Patients were reviewed over a 6-month period. The data were analyzed for statistical significance using an independent t test and a receiver operating characteristic curve. RESULTS: In total, 20 eyes of 10 patients were included between 2009 and 2017. The mean age was 24.9 ± 18.1 years. Best corrected visual acuity at first consultation was 0.78 ± 0.11 and after 6 months was 0.83 ± 0.09. Spectral domain–optical coherence tomography demonstrated retinal abnormalities at the myoid zone, ellipsoid zone, and the outer segment of photoreceptors. Receiver operating characteristic curve analysis showed an improving effect (area under the curve = 0.62; 95% confidence interval = 0.42–0.79). The color channels parameters, which improve visualization of the lesions were found to be 67-0.98-255 for the R-guided setting, 19-0.63-121 for the B-guided setting, and 7-1.00-129 for the G-guided setting. The ideal red, green, and blue setting was in 24-0.82-229. CONCLUSIONS: The use of a new setting of red, green, and blue channels could improve the diagnosis and monitoring of solar retinopathy, hence improving patient care

Evidence of impaired mitochondrial cellular bioenergetics in ocular fibroblasts derived from glaucoma patients

Glaucoma is a progressive optic neuropathy characterized by the neurodegeneration of the retinal ganglion cells (RGCs) resulting in irreversible visual impairment and eventual blindness. RGCs are extremely susceptible to mitochondrial compromise due to their marked bioenergetic requirements and morphology. There is increasing interest in therapies targeting mitochondrial health as a method of preventing visual loss in managing glaucoma. The bioenergetic profile of Tenon's ocular fibroblasts from glaucoma patients and controls was investigated using the Seahorse XF24 analyser. Impaired mitochondrial cellular bioenergetics was detected in glaucomatous ocular fibroblasts including basal respiration, maximal respiration and spare capacity. Spare respiratory capacity levels reflect mitochondrial bio-energetic adaptability in response to pathophysiological stress. Basal oxidative stress was elevated in glaucomatous Tenon's ocular fibroblasts and hydrogen peroxide (H2O2) induced reactive oxygen species (ROS) simulated the glaucomatous condition in normal Tenon's ocular fibroblasts. This work supports the role of therapeutic interventions to target oxidative stress or provide mitochondrial energetic support in glaucoma

Corneal biomechanics and biomechanically corrected intraocular pressure in primary open-angle glaucoma, ocular hypertension and controls.

AIMS: To compare the biomechanically corrected intraocular pressure (IOP) estimate (bIOP) provided by the Corvis-ST with Goldmann applanation tonometry (GAT-IOP) in patients with high-tension and normal-tension primary open-angle glaucoma (POAG; HTG and NTG), ocular hypertension (OHT) and controls. Moreover, we compared dynamic corneal response parameters (DCRs) of the Corvis-ST in POAG, OHT and controls, evaluated the correlation between global visual field parameters mean deviation and pattern SD (MD and PSD) and DCRs in the POAG group. METHODS: 156 eyes of 156 patients were included in this prospective, single-centre, observational study, namely 41 HTG and 33 NTG, 45 OHT cases and 37 controls. Central corneal thickness (CCT), GAT-IOP and bIOP were measured, GAT-IOP was also adjusted for CCT (GATAdj). DCRs provided by Corvis-ST were evaluated, MD and PSD were recorded by 24-2 full-threshold visual field. To evaluate the difference in DCRs between OHT, HTG and NTG, a general linear model was used with sex, medications and group as fixed factors and bIOP and age as covariates. RESULTS: There was a significant difference between GAT-IOP, GATAdj and bIOP in NTG and HTG, OHT and controls. NTG corneas were significantly softer and more deformable compared with controls, OHT and HTG as demonstrated by significantly lower values of stiffness parameters A1 and highest concavity and higher values of inverse concave radius (all p<0.05). There was a significant correlation (p<0.05) between MD, PSD and many DCRs with POAG patients with softer or more compliant corneas more likely to show visual field defects. CONCLUSIONS: Corneal biomechanics might be a significant confounding factor for IOP measurement that should be considered in clinical decision-making. The abnormality of corneal biomechanics in NTG and the significant correlation with visual field parameters might suggest a new risk factor for the development or progression of NTG

Solar retinopathy: a new setting of red, green, and blue channels

9siPurpose: To introduce a new color imaging technique using improved settings of red, green, and blue channels for improved delineation of retinal damage in patients with solar retinopathy. Method: A retrospective case series of patients with poor vision secondary to solar retinopathy were analyzed. All patients underwent visual acuity, refraction, and dilated fundus examination. A spectral domain–optical coherence tomography of the macula and color fundus imaging using optimized red, green, and blue color setting was performed. Patients were reviewed over a 6-month period. The data were analyzed for statistical significance using an independent t test and a receiver operating characteristic curve. Results: In total, 20 eyes of 10 patients were included between 2009 and 2017. The mean age was 24.9 ± 18.1 years. Best corrected visual acuity at first consultation was 0.78 ± 0.11 and after 6 months was 0.83 ± 0.09. Spectral domain–optical coherence tomography demonstrated retinal abnormalities at the myoid zone, ellipsoid zone, and the outer segment of photoreceptors. Receiver operating characteristic curve analysis showed an improving effect (area under the curve = 0.62; 95% confidence interval = 0.42–0.79). The color channels parameters, which improve visualization of the lesions were found to be 67-0.98-255 for the R-guided setting, 19-0.63-121 for the B-guided setting, and 7-1.00-129 for the G-guided setting. The ideal red, green, and blue setting was in 24-0.82-229. Conclusion: The use of a new setting of red, green, and blue channels could improve the diagnosis and monitoring of solar retinopathy, hence improving patient care.reservedmixedBorroni D.; Erts R.; Vallabh N.A.; Bonzano C.; Sepetiene S.; Krumina Z.; Romano V.; Parekh M.; Iannetta D.Borroni, D.; Erts, R.; Vallabh, N. A.; Bonzano, C.; Sepetiene, S.; Krumina, Z.; Romano, V.; Parekh, M.; Iannetta, D

The mutational constraint spectrum quantified from variation in 141,456 humans

Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes critical for an organism’s function will be depleted for such variants in natural populations, while non-essential genes will tolerate their accumulation. However, predicted loss-of-function (pLoF) variants are enriched for annotation errors, and tend to be found at extremely low frequencies, so their analysis requires careful variant annotation and very large sample sizes1. Here, we describe the aggregation of 125,748 exomes and 15,708 genomes from human sequencing studies into the Genome Aggregation Database (gnomAD). We identify 443,769 high-confidence pLoF variants in this cohort after filtering for sequencing and annotation artifacts. Using an improved human mutation rate model, we classify human protein-coding genes along a spectrum representing tolerance to inactivation, validate this classification using data from model organisms and engineered human cells, and show that it can be used to improve gene discovery power for both common and rare diseases