Relationship between nerve fiber layer hemorrhages and outcomes in central retinal vein occlusion

Copyright 2020 The Authors PURPOSE. To evaluate the depth and pattern of retinal hemorrhage in acute central retinal vein occlusion (CRVO) and to correlate these with visual and anatomic outcomes. METHODS. Retinal hemorrhages were evaluated with color fundus photography and fluorescein angiography at baseline and follow-up. Snellen visual acuity (VA), central foveal thickness (CFT), extent of retinal ischemia, and development of neovascularization were analyzed. RESULTS. 108 eyes from 108 patients were evaluated. Mean age was 63.6 ± 16.1 years with a predilection for the right eye (73.1%). Average follow-up was 17.2 ± 19.2 months. Mean VA at baseline was 20/126 and 20/80 at final follow-up. Baseline (P = 0.005) and final VA (P = 0.02) in eyes with perivascular nerve fiber layer (NFL) hemorrhages were significantly worse than in eyes with deep hemorrhages alone. Baseline CFT was greater in the group with perivascular hemorrhages (826 ± 394 μm) compared to the group with deep hemorrhages alone (455 ± 273 μm, P \u3c 0.001). The 10 disc areas of retinal ischemia was more common in patients with perivascular (80.0%) and peripapillary (31.3%) versus deep hemorrhages alone (16.1%, P \u3c 0.001). Neovascularization of the iris was more common, although this differrence was not significant, in the groups with peripapillary (14.3%) and perivascular (2.0%) NFL versus deep hemorrhages alone (0.0%). CONCLUSIONS. NFL retinal hemorrhages at baseline correlate with more severe forms of CRVO, with greater macular edema, poorer visual outcomes, and greater risk of ischemia and neovascularization. This may be related to the organization of the retinal capillary plexus. The depth and pattern of distribution of retinal hemorrhages in CRVO may provide an easily identifiable early biomarker of CRVO prognosis

ATM Gene Variants in Patients with Idiopathic Perifoveal Telangiectasia

PURPOSE. To investigate the prevalence of sequence variants in the ATM gene and to determine the frequency of major agerelated macular degeneration (AMD)-associated variants in CFH, CFB, and 10q26 loci in patients with idiopathic perifoveal telangiectasia (IPT). METHODS. Thirty patients with diagnoses of IPT underwent standard ophthalmologic evaluation that included visual acuity testing, fundus photography, and fluorescein angiography. DNA was screened for variations in the ATM gene by a combination of denaturing high-performance liquid chromatography and direct sequencing. Major AMD-associated alleles in CFH, CFB, and 10q loci were screened by PCR-restriction fragment-length polymorphism. RESULTS. Nineteen female and 11 male patients (average age, 59 years) with a median visual acuity of 20/50 were evaluated. Six patients were of Asian-Indian origin, one was Hispanic, and 23 were of European-American ancestry. Nine of 30 (30%) patients had diabetes mellitus, 18 of 30 (60%) patients had hypertension, and 12 of 30 (40%) patients had a history of smoking. Screening of the ATM gene revealed a null allele in 2 of 23 (8.7%) patients of European ancestry, previously disease-associated missense alleles in 4 of 23 (17.4%) patients, and common missense alleles in 7 of 23 (30.4%) patients. No variants were identified in the ATM gene in patients of Asian or Hispanic origin. Frequencies of major AMD-associated alleles in CFH, CFB, and 10q loci in the IPT cohort were similar to those in the ethnically matched general population. CONCLUSIONS. At least 26%, and maybe up to 57%, of IPT patients of European-American descent carried possibly diseaseassociated ATM alleles. Vascular risk factors such as hypertension, diabetes, and smoking may be associated with the pathogenesis of the disease. (Invest Ophthalmol Vis Sci. 2008; 49:3806 -3811

Anti-retinal IgG antibodies in patients with early and advanced type 2 macular telangiectasia

Type 2 idiopathic macular telangiectasia (MacTel-2) is a progressive adult-onset macular disease associated with bilateral perifoveal vascular changes, Muller cell degeneration and increased blood-retinal barrier permeability. The pathophysiological mechanisms of MacTel-2 remain unclear, however it was previously reported that anti-retinal antibodies in MacTel-2 patients are a significant feature of the disease. In this study, we aimed to compare the prevalence of anti-retinal antibodies in patients MacTel-2, healthy controls and patients with other retinal diseases. MacTel-2 patients diagnosed with multimodal imaging were enrolled and their disease severities were graded using spectral-domain optical coherence tomography. For comparison, patients with age-related macular degeneration (AMD), inherited retinal diseases (IRDs) or no retinal disease (healthy controls) were recruited as controls. Blood serum samples were screened for immunoglobulin G anti-retinal antibodies by western blotting, followed by densitometry analysis. Odds ratios (OR) with 95% confidence intervals (CI) were calculated and p < 0.05 considered statistically significant. Overall, anti-retinal antibody-positive cases were older (64 ± 15 vs 53 ± 17 years, p < 0.001) and females were more likely to develop anti-retinal antibodies (OR: 2.41, CI: 1.12–5.18). The frequency of anti-retinal antibody detection in MacTel-2 patients (n = 42, 36%) was not significantly different from healthy controls (n = 52, 25%) or IRD patients (n = 18, 25%) and the majority of MacTel-2 patients had no anti-retinal antibodies. In contrast, the frequency of anti-retinal antibody detection was significantly higher in patients with AMD (n = 15, 73%, p < 0.001). The lack of a greater anti-retinal antibody frequency or specificity in the MacTel-2 cohort suggests that antibody mediated immunological mechanisms may play a less significant role in MacTel-2 disease pathogenesis. © 2022 The Author

Cost analysis of childhood glaucoma surgeries using the US Medicaire allowable costs

AIM: To analyze and calculate the relative cost of various childhood glaucoma surgical interventions per mm Hg intraocular pressure (IOP) reduction ($/mm Hg). METHODS: Representative index studies were reviewed to quantitate the reduction of mean IOP and glaucoma medications for each surgical intervention in childhood glaucoma. A US perspective was adopted, using Medicare allowable costs to calculate cost/mm Hg IOP reduction ($/mm Hg) at 1y postoperatively. RESULTS: At 1y postoperatively, the cost/mm Hg IOP reduction was $226/mm Hg for microcatheter-assisted circumferential trabeculotomy,$284/mm Hg for cyclophotocoagulation, $288/mm Hg for conventional ab-externo trabeculotomy,$338/mm Hg for Ahmed glaucoma valve, $350/mm Hg for Baerveldt glaucoma implant,$351/mm Hg for goniotomy, and $400/mm Hg for trabeculectomy. CONCLUSION: Microcatheter-assisted circumferential trabeculotomy is the most cost-efficient surgical method to lower IOP in childhood glaucoma, while trabeculectomy is the least cost-efficient surgical method

Single-Dose Intravenous Toxicity Study of IRDye 800CW in Sprague-Dawley Rats

Objective: Fluorophore-labeled contrast imaging agents are moving toward clinical use for a number of applications. The near-infrared dye IRDye 800CW is frequently used in its N-hydroxysuccinamide (NHS) ester form for labeling these agents. Following conjugation or breakdown of a labeled ligand, excess NHS ester is converted to the carboxylate form. To prepare for clinical use as a near-infrared fluorophore, a toxicity study was conducted on IRDye 800CW carboxylate. Methods: Male and female Sprague–Dawley rats were given a single intravenous or intradermal administration of IRDye 800CW carboxylate; Indocyanine Green was used as a comparative control. Animals were injected with varying doses of the test and control articles and observed for up to 14 days. Clinical chemistry, hematological, and pharmacokinetic analyses were performed on subgroups of animals. Organs were analyzed for content of the test article. Tissues were analyzed microscopically for pathological changes. Results: Based on hematologic, clinical chemistry, and histopathologic evaluation, single administration of IRDye 800CW carboxylate intravenously at dose levels of 1, 5, and 20 mg/kg or 20 mg/kg intradermally produced no pathological evidence of toxicity. Conclusion: A dose of 20 mg/kg was identified as the no observed adverse effect level following IV or ID routes of administration of IRDye 800CW

Nanoceria Inhibit the Development and Promote the Regression of Pathologic Retinal Neovascularization in the Vldlr Knockout Mouse

Many neurodegenerative diseases are known to occur and progress because of oxidative stress, the presence of reactive oxygen species (ROS) in excess of the cellular defensive capabilities. Age related macular degeneration (AMD), diabetic retinopathy (DR) and inherited retinal degeneration share oxidative stress as a common node upstream of the blinding effects of these diseases. Knockout of the Vldlr gene results in a mouse that develops intraretinal and subretinal neovascular lesions within the first month of age and is an excellent model for a form of AMD called retinal angiomatous proliferation (RAP). Cerium oxide nanoparticles (nanoceria) catalytically scavenge ROS by mimicking the activities of superoxide dismutase and catalase. A single intravitreal injection of nanoceria into the Vldlr-/- eye was shown to inhibit: the rise in ROS in the Vldlr-/- retina, increases in vascular endothelial growth factor (VEGF) in the photoreceptor layer, and the formation of intraretinal and subretinal neovascular lesions. Of more therapeutic interest, injection of nanoceria into older mice (postnatal day 28) resulted in the regression of existing vascular lesions indicating that the pathologic neovessels require the continual production of excessive ROS. Our data demonstrate the unique ability of nanoceria to prevent downstream effects of oxidative stress in vivo and support their therapeutic potential for treatment of neurodegenerative diseases such as AMD and DR

Genome-wide analyses identify common variants associated with macular telangiectasia type 2

Idiopathic juxtafoveal retinal telangiectasis type 2 (macular telangiectasia type 2; MacTel) is a rare neurovascular degenerative retinal disease. To identify genetic susceptibility loci for MacTel, we performed a genome-wide association study (GWAS) with 476 cases and 1,733 controls of European ancestry. Genome-wide significant associations (P < 5 × 10−8) were identified at three independent loci (rs73171800 at 5q14.3, P = 7.74 × 10−17; rs715 at 2q34, P = 9.97 × 10−14; rs477992 at 1p12, P = 2.60 × 10−12) and then replicated (P < 0.01) in an independent cohort of 172 cases and 1,134 controls. The 5q14.3 locus is known to associate with variation in retinal vascular diameter, and the 2q34 and 1p12 loci have been implicated in the glycine/serine metabolic pathway. We subsequently found significant differences in blood serum levels of glycine (P = 4.04 × 10−6) and serine (P = 2.48 × 10−4) between MacTel cases and controls