Extrahepatic Manifestations of Chronic Hepatitis C Virus (HCV) Infection.

Hepatitis C virus (HCV) is a well-recognized, major cause of various liver-related conditions such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Apart from liver disease, chronic HCV infection is also associated with several extrahepatic manifestations that can lead to significant morbidity and mortality. These extrahepatic manifestations include essential mixed cryoglobulinemia (EMC), lymphomas, porphyria cutanea tarda, lichen planus, necrolytic acral erythema, glomerulonephritis, subclinical autoantibody formation, immune thrombocytopenia, thyroid disease, Sjögren's disease/sicca symptoms, diabetes mellitus, ocular diseases, musculoskeletal disorders, cardiovascular diseases, neurocognitive dysfunction, and leukocytoclastic vasculitis. We are presenting a case of chronic HCV infection linked to the extrahepatic manifestations of the disease which can be directly related to HCV or indirectly related to EMC from HCV. An awareness and knowledge of these extrahepatic manifestations will highlight the importance of recognizing the symptoms for an early diagnosis and effective anti-viral treatment in order to improve or resolve the long-term complications of chronic HCV infection.

Chronic Alcoholism and Its Health Implications: A Case Report.

Individuals with chronic alcohol use can be asymptomatic for a prolonged period of time and then exhibit signs of advanced heart and liver diseases with an abrupt onset. Herein, we present a case of a 60-year-old male with severe alcohol use disorder who presented with newly diagnosed atrial fibrillation (AF) with rapid ventricular response (RVR), dilated cardiomyopathy (DCM), and alcohol-associated cirrhosis following an episode of binge drinking.

Four-year Surgical Outcomes of Gonioscopy-assisted Transluminal Trabeculotomy in Patients with Open-Angle Glaucoma.

PURPOSE: To provide 4-year data on the efficacy and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in patients with open-angle glaucoma. DESIGN: Retrospective case series. PARTICIPANTS: Eyes of patients > 18 years of age who underwent GATT by a single surgeon at Wills Eye Hospital with at least 36 months follow-up. METHODS: Postoperative changes in outcome measures including intraocular pressure (IOP), medication use and visual acuity were recorded. Failure was defined as IOP > 21 mmHg or less than 20% reduction below baseline at any postoperative visit after 3 months or need for further glaucoma surgery. MAIN OUTCOME MEASURES: Main outcome measures were failure rate, IOP, number of glaucoma medications, and visual acuity at 4 years. RESULTS: Fifty-nine patients (74 eyes), age 57.1 ± 18.5 years (37.8% female) underwent the GATT procedure. Average follow-up was 47.0 ± 6.7 months (range 35.6-76.5 months). Mean IOP was 27.0 ± 10.0 mmHg preoperatively and 14.8 ± 6.5 mmHg at 4 years (45% IOP decrease; P < 0.01). Mean number of medications decreased from 3.2 ± 1.0 preoperatively to 2.3 ± 1.0 at 4 years (P < 0.01). The cumulative failure rate at 4 years was 53.9%, and the cumulative reoperation rate was 42.0%. No significant differences between patients with primary open-angle glaucoma and other types of glaucoma were found. CONCLUSIONS: Gonioscopy-assisted transluminal trabeculotomy can be a safe and effective conjunctival-sparing surgery for treating various forms of open-angle glaucoma at 4 years. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Systemic side effects of glaucoma medications.

Glaucoma is a progressive loss of retinal ganglion cells leading to visual field loss. Lowering intraocular pressure is currently the only modifiable risk factor to slow glaucoma progression. Intraocular pressure-lowering options include topical and systemic medications, lasers, and surgical procedures. Glaucoma eye drops play a major role in treating this blinding disease. Similar to all medications, the glaucoma medications have their own adverse effects. The majority of glaucoma medications work by stimulating or inhibiting adrenergic, cholinergic, and prostaglandin receptors, which are distributed all over the body. Therefore, the glaucoma medications can affect organs other than the eye. This review will discuss the systemic adverse effects of carbonic anhydrase inhibitors, sympathomimetics, para-sympathomimetics, beta blockers, prostaglandin analogs, hyperosmotic agents, and novel glaucoma medications with a stress on pregnant patients, breastfeeding mothers, and paediatric patients.

Sociodemographic and Economic Factors in Outcomes of Tube Shunts for Neovascular Glaucoma.

IMPORTANCE: Few studies have analyzed associations between sociodemographic factors and neovascular glaucoma (NVG) outcomes. AIM AND BACKGROUND: To determine the potential impact of sociodemographic and economic factors on the NVG tube shunt surgery outcomes. DESIGN: Retrospective, single-center, comparative case series. PARTICIPANTS: Consecutive patients who underwent tube shunt surgery for NVG and had ≥6 months of follow-up. MATERIALS AND METHODS: Regional average adjusted gross income (AGI) was determined by cross-referencing self-reported residential zip codes with average AGI per zip code supplied by the Internal Revenue Service. Two groups were created: (1) lower-income: individuals from neighborhoods with the lowest 10% of AGI (near the United States poverty line), (2) higher-income: the remaining 90% of individuals. MAIN OUTCOME MEASURES: Visual acuity (VA), intraocular pressure (IOP), and glaucoma medication number at 6 months and the most recent visit. RESULTS: The mean annual AGI in the higher-income group (130 patients) was $69,596 ± 39,700 and the lower-income group (16 patients) was $27,487 ± 1,600 (p < 0.001). Age, sex, distance to the clinic, language, and all baseline clinical variables (including VA and IOP) were comparable between groups. Lower-income was associated with non-white race (81.3 vs 52.3%; p = 0.024). At month 6, VA in the lower-income group [median: HM (20/70-NLP)] was worse than the higher-income group [median: CF (20/25-NLP)] (log MAR VA: 2.32 ± 0.8 vs 1.77 ± 1.1; p = 0.02); these trends persisted through the most recent visit (p = 0.043). Follow-up IOP and medications were similar between groups. CONCLUSIONS AND RELEVANCE: Lower-income may be associated with worse VA outcomes following NVG tube shunt surgery. HOW TO CITE THIS ARTICLE: Shalaby WS, Arbabi A, Myers JS, et al. Sociodemographic and Economic Factors in Outcomes of Tube Shunts for Neovascular Glaucoma. J Curr Glaucoma Pract 2021;15(2):70-77.

iStent versus iStent inject implantation combined with phacoemulsification in open angle glaucoma.

PURPOSE: To compare the outcomes of iStent vs. iStent inject implantation combined with phacoemulsification. METHODS: This single center retrospective comparative case series included subjects with open angle glaucoma who underwent iStent or iStent inject implantation combined with phacoemulsification with ≥1 year follow-up. The main outcome measures were in-group and between-group changes in intraocular pressure (IOP) and medication number, proportion of eyes that achieved IOP ≤15 mmHg, and surgical success defined as 20% IOP reduction from baseline at 6/12 months. Univariate/multivariate regression analyses were done to identify predictors of surgical failure. RESULTS: One hundred ninety-seven eyes of 148 patients were included (122 iStent, 75 iStent inject). Both groups achieved significant IOP and medication reduction at months 6/12 (P < 0.05). At month 6, IOP was significantly lower in iStent inject vs. iStent eyes (P = 0.003), but the difference was insignificant by month 12 (P = 0.172). Medication number was comparable in both groups at months 6/12 (P > 0.05). More iStent inject eyes achieved IOP ≤15 mmHg at month 6 (P = 0.003) and 12 (P = 0.047). Surgical success was comparable in both groups at months 6/12 (P > 0.05). Kaplan-Meier survival analysis showed similar cumulative rate of surgical failure at year-1 in both groups (P = 0.644). The multivariate model identified older age (P = 0.017) and lower baseline IOP (P = 0.002) as the strongest predictors of surgical failure. CONCLUSION: Compared to iStent, iStent inject achieved lower IOP at month 6 and higher proportion of eyes achieved IOP ≤15 mmHg at month 6/12. However, surgical success was similar in both groups. Predictors of surgical failure were older age and lower baseline IOP rather than the stent type.

Association of the Pattern of Retinal Capillary Non-Perfusion and Vascular Leakage with Retinal Neovascularization in Proliferative Diabetic Retinopathy.

PURPOSE: To explore the correlation between retinal capillary non-perfusion and the distribution of retinal neovascularization and vascular leakage (VL) in patients with proliferative diabetic retinopathy (PDR). METHODS: Ultra-widefield angiograms of 96 eyes of 69 patients with PDR were reviewed for the proportion of non-perfused area to total gradable area, and for the presence of neovascularization and VL. RESULTS: Retinal neovascularization was distributed as such: neovascularization elsewhere (NVE), 57.3%; neovascularization of the disc (NVD), 11.5%; both neovascularization of the disc and elsewhere (NVED), 31.3%. The proportion of non-perfused retina, so-called ischemic index, was greater in eyes with NVED compared to eyes with NVE only, but not when compared to NVD only. Overall, 83% of eyes had VL. The presence and the extent of VL correlated with the proportion of the ischemic index. While VL and ischemic index were more severe in the mid-periphery and far-periphery, the majority of NVE was located in the posterior pole. CONCLUSIONS: The presence of both NVD and NVE is associated with a greater ischemic index than NVE alone. Although both VL and ischemic index is significantly higher in peripheral zones, the majority of neovascularization occurs at the posterior pole.

Reduced Expression of VEGF-A in Human Retinal Pigment Epithelial Cells and Human Muller Cells Following CRISPR-Cas9 Ribonucleoprotein-Mediated Gene Disruption.

Purpose: To evaluate the effects of vascular endothelial growth factor-A (VEGF-A) gene editing in human retinal pigment epithelial (RPE) cells and human Muller cells, which are the main VEGF-A producing cells in the eye. Methods: CRISPR-Cas9 ribonucleoprotein was used to target exon 1 in VEGF-A gene. Lipofectamine CRISPRMAX was used as a vehicle. In vitro gene editing efficiency was assessed on oligonucleotides and genomic DNAs. Sanger sequencing was performed to detect indels. VEGF-A messenger RNA and protein expressions were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Results: In vitro cleavage assay on a 60-nucleotide DNA duplex showed 88% cleavage of the precursor. The cleavage efficiency was 40% in RPE cells and 32% in Muller cells. Sanger sequencing in the CRISPR-Cas9 treated RPE and Muller cells showed indels at the predicted cut site in both cells. After the VEGF-A gene disruption, VEGF-A protein levels decreased 43% in RPE cells (P < 0.0001) and 38% in Muller cells (P < 0.0001). Conclusions: CRISPR-Cas9-mediated gene disruption resulted in a significant decrease in the VEGF-A gene protein expression in human RPE and Muller cells. CRISPR-Cas9 ribonucleoprotein may allow simultaneous targeting of multiple VEGF-A producing cells. Translational Relevance: VEGF-A gene disruption using CRISPR-Cas9 ribonucleoprotein has a potential in treating retinal vascular diseases.

Retinal Gene Distribution and Functionality Implicated in Inherited Retinal Degenerations Can Reveal Disease-Relevant Pathways for Pharmacologic Intervention.

The advent of genetic therapies for inherited retinal diseases (IRDs) has spurred the need for precise diagnosis and understanding of pathways for therapeutic targeting. The majority of IRDs that are clinically diagnosed, however, lack an identifiable mutation in established disease-causing loci and thus can be investigated with limited rational drug discovery methods. Transcriptome profiling of the retina can reveal the functional state of the tissue, and geographic profiling can uncover the various clinical phenotypic presentations of IRDs and aid in pharmaceutical intervention. In this investigation, we detail the retinal geographic expression of known retinal disease-causing genes in the primate retina and functional targetable pathways in specific IRDs. Understanding the genetic basis as well as the resulting functional consequences will assist in the discovery of future therapeutic interventions and provide novel insights to medicinal chemists. Herein, we report that, despite the genetic heterogeneity of retinal diseases, potential functional pathways can be elucidated for therapeutic targeting and be used for predictive phenotypic and genotypic modeling of novel IRD presentations.

Gene Therapy for Inherited Retinal Degeneration.

Inherited retinal degeneration (IRD), a group of rare retinal diseases that primarily lead to the progressive loss of retinal photoreceptor cells, can be inherited in all modes of inheritance: autosomal dominant (AD), autosomal recessive (AR), X-linked (XL), and mitochondrial. Based on the pattern of inheritance of the dystrophy, retinal gene therapy has 2 main strategies. AR, XL, and AD IRDs with haploinsufficiency can be treated by inserting a functional copy of the gene using either viral or nonviral vectors (gene augmentation). Different types of viral vectors and nonviral vectors are used to transfer plasmid DNA both in vitro and in vivo. AD IRDs with gain-of-function mutations or dominant-negative mutations can be treated by disrupting the mutant allele with (and occasionally without) gene augmentation. This review article aims to provide an overview of ocular gene therapy for treating IRDs using gene augmentation with viral or nonviral vectors or gene disruption through different gene-editing tools, especially with the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system.

Assessment of C-reactive Protein and C3 as Inflammatory Markers of Insulin Resistance in Women with Polycystic Ovary Syndrome: A Case-Control Study.

BACKGROUND: Polycystic ovary syndrome (PCOS), a common endocrine disorder, is associated with infertility, menstrual dysfunction, hirsutism and frequent miscarriages. Insulin resistance, as a major cause of PCOS, represents a disorder with increase in inflammatory markers and risk of type 2 diabetes. We aimed to investigate whether inflammatory markers, including C-reactive protein and C3 (Complement), are related and altered in polycystic ovary syndrome. METHODS: A case-control study including forty-two women diagnosed with PCOS, according to Rotterdam criteria, and forty-two healthy controls, matched for body mass index (BMI) and age, was conducted in 2012. C-Reactive protein (CRP) and C3 were assessed as possible determinants of the homeostasis model assessment (HOMA) index. Independent-sample t-test was used to compare the means of the groups in age, BMI, C3, FBS and BS 2hpp (2 hr postprandial glucose) and for CRP, Fasting Insulin and 2 hr Plasma Insulin and HOMA index. Mann-Whitney test and Pearson correlation were used for analyzing the data. The p<0.05 was considered as statistically significant. RESULTS: Levels of plasma CRP (p=0.039), 2 hr pp (p=0.045), Fasting Insulin (p=0.002), 2 hr Plasma Insulin (p=0.002) and HOMA index (p=0.002) were significantly higher in PCOS patients. But C3 was not significantly higher in cases (p=0.885). There was no significant correlation between C3 and CRP with HOMA index. CONCLUSION: CRP increased significantly in patients with PCOS and was associated with insulin resistance, the most probable cause of PCOS. However, such an association was not found in C3.