Effect of Preoperative Trabecular Meshwork Pigmentation and Other Eye Characteristics on Outcomes of Combined Phacoemulsification/Minimally Invasive Glaucoma Surgery.

PURPOSE: To investigate associations between pigmentation of the trabecular meshwork (PTM) and other preoperative eye characteristics and outcomes of minimally invasive glaucoma surgery combined with phacoemulsification (Phaco/MIGS). DESIGN: Retrospective interventional case series. PARTICIPANTS: Academic glaucoma clinic patients with symptomatic cataract and glaucoma treated with combined Phaco/MIGS. METHODS: Analyzing preoperative PTM, intraocular pressure (IOP), IOP-lowering medications and visual acuity (VA) data in relation to Phaco/MIGS outcomes. MAIN OUTCOME MEASURES: Pigmentation of the trabecular meshwork and other preoperative eye characteristics in relation to Phaco/MIGS success defined as postoperative IOP between 5 and 21 mmHg and IOP reduction of ≥ 20% and/or a reduction of ≥ 1 IOP-medications compared to baseline, and final IOP, IOP-lowering medications and VA. RESULTS: A total of 265 eyes (172 patients, mean age, 73.5 [standard deviation, 10.0], range 35-95 years, male 40.0%) were identified and categorized with high PTM (108 eyes, 40.8%) or low PTM (157 eyes, 59.2%). The high PTM group, compared with the low PTM group, demonstrated higher preoperative IOP (16.7 [standard error 0.4] vs. 15.2 [0.4] mmHg, P = 0.009), included more eyes with primary open-angle glaucoma (POAG, P = 0.03), fewer eyes with normal-tension glaucoma (NTG, P = 0.01), and fewer eyes with mild stage glaucoma (P = 0.001). Compared to baseline, final IOP decreased by 6.5 [2.4]% and 13.4 [3.0]% (P = 0.075) to 13.5 [0.3] mmHg and 13.6 [0.4] mmHg (P = 0.77) in the low and high PTM groups, respectively, and IOP-lowering medications decreased by 34.6 [4.9]% (n = 116) and 18.1 [7.3]% (n = 85), respectively (P = 0.062). Surgical success was 59.9% and 58.3%, respectively (P = 0.87). It was positively associated with higher preoperative IOP (hazard ratio 1.08 [95% confidence interval 1.04-1.12] P < 0.0001) and higher number of preoperative IOP-medications (1.20 [1.05-1.37] P = 0.007), negatively associated with history of selective laser trabeculoplasty (SLT, 0.40 [0.23-0.68] P = 0.0009) and longer axial length (0.87 [0.80-0.94], P = 0.0006), but was not associated with PTM. CONCLUSIONS: Higher PTM was associated with POAG rather than NTG, with more severe glaucoma and higher preoperative IOP, but not with Phaco/MIGS success. Surgical success was positively associated with higher preoperative IOP and number of IOP-medications and negatively associated with history of SLT and longer axial length. These findings may help guide glaucoma surgeons in surgical planning and patient counseling. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

An All-in-One Highly Multiplexed Diagnostic Assay for Rapid, Sensitive, and Comprehensive Detection of Intraocular Pathogens.

PURPOSE: Intraocular infections are sight-threatening conditions that can lead to vision loss. Rapid identification of the etiologies plays a key role in early initiation of effective therapy to save vision. However, current diagnostic modalities are time consuming and lack sensitivity and inclusiveness. We present here a newly developed comprehensive ocular panel designed to improve diagnostic yields and provide a tool for rapid and sensitive pathogen detection. DESIGN: Experimental laboratory investigation. METHODS: A panel containing 46 pathogens and 2 resistance/virulence markers that are commonly detected in intraocular infections was developed. Genomic targets were scrutinized for stretches predicted to be specific for a particular species while being conserved across different strains. A set of primers for sample enrichment, and two 50mer NanoString compatible probes were then designed for each target. Probe-target hybrids were detected and quantified using the NanoString nCounter SPRINT Profiler. Diagnostic feasibility was assessed in a pilot clinical study testing samples from infectious retinitis (n = 15) and endophthalmitis (n = 12) patients, for which the etiologies were confirmed by polymerase chain reaction (PCR) or culture. RESULTS: Analytical studies demonstrated highly sensitive detection of a broad spectrum of pathogens, including bacteria, viruses, and parasites, with limits of detection being as low as 2.5 femtograms per reaction. We also found excellent target specificity, with minimal cross-reactivity detected. The custom-designed NanoString ocular panel correctly identified the causative agent from all clinical specimens positive for a variety of pathogens. CONCLUSION: This highly multiplexed panel for pathogen detection offers a sensitive, comprehensive, and uniform assay run directly on ocular fluids that could significantly improve diagnostics of sight-threatening intraocular infections.

Mendelian Randomization Shows a Causal Effect of Low Vitamin D on Non-infectious Uveitis and Scleritis Risk.

PURPOSE: To investigate a causal relationship between Vitamin D levels and non-infectious uveitis and scleritis using Mendelian randomization (MR) techniques. DESIGN: Two-sample Mendelian randomization case-control study. METHODS: The study setting was a biobank of an academic, integrated health care system. The patient population comprised 375 case patients with a non-infectious uveitis and/or scleritis diagnosis and no diagnosis of infectious, trauma-related, or drug-induced uveitis/scleritis. In addition, there were 4167 controls with no uveitis or scleritis diagnosis. Causal effect estimates of low 25-hydroxy Vitamin D (25OHD) on uveitis/scleritis risk were calculated. RESULTS: We found an association of genetically decreased 25OHD with uveitis/scleritis risk (odds ratio [OR] = 2.16, 95% CI = 1.01-4.64, P = .049, per SD decrease in log25OHD). In a first sensitivity MR analysis excluding the genetic variants that are unlikely to have a role in biologically active 25OHD, effect estimates were consistent with those from the primary analysis (OR = 2.38, 95% CI =1.06-5.36, P = 0.035, per SD of log25OHD). Furthermore, in a second sensitivity analysis using only the 6 variants within the CYP2R1 locus (which encodes 25OHD hydroxylase, the liver enzyme responsible for converting Vitamin D to 25OHD), genetically decreased 25OHD was strongly associated with increased uveitis/scleritis risk (OR = 6.42, 95% CI = 3.19-12.89, P = 1.7 × 10-7, per SD of log25OHD). CONCLUSIONS: Our findings suggest a causal relationship between low Vitamin D levels and higher risk of non-infectious uveitis and scleritis. Vitamin D supplementation may be a low-cost, low-risk intervention to mitigate non-infectious uveitis and scleritis risk, and should be explored in a prospective trial.

Younger Age and Albuminuria are Associated with Proliferative Diabetic Retinopathy and Diabetic Macular Edema in the South Indian GeNetics of DiAbeTic Retinopathy (SIGNATR) Study.

Purpose: The purpose of the South Indian GeNetics of DiAbeTic Retinopathy (SIGNATR) Study is to identify non-genetic and genetic risk factors associated with diabetic retinopathy (DR). This report examines the non-genetic risk factors for DR in South Indian patients.Methods: Participants with South Indian ancestry and type 2 diabetes (T2D) were included from two sources: the Sankara Nethralaya Diabetic Retinopathy and Molecular Genetics Study (SN-DREAMS) and prospective recruitment at Sankara Nethralaya affiliates. Fundus photography and optical coherence tomography (OCT) were obtained on participants. Fundus images were graded for DR severity and OCTs were graded for center-involved diabetic macular edema (ciDME). Multivariate analyses were performed using stepwise logistic regression to assess effects of the demographic and clinical factors on proliferative DR (PDR) and DME.Results: Among the 2941 participants with DR grading, participants with PDR were more likely to be younger [odds ratio (OR)=0.95], men (OR = 1.83), have a longer duration of diabetes (OR = 1.10), have a higher hemoglobin A1c (OR = 1.12), have albuminuria (OR = 5.83), have hypertension (OR = 1.69), have a higher HDL (OR = 1.02) and a lower total cholesterol (OR = 0.99) (all p < 0.05). Among the 483 participants with gradable OCT scans, participants who had ciDME were more likely to be younger (OR = 0.97), men (OR = 2.80), have a longer duration of diabetes (OR = 1.06), have lower triglycerides (OR = 0.99), and have albuminuria (OR = 3.12) (all p < 0.05).Conclusions: Younger age, male sex, longer duration of diabetes, higher HbA1c, and presence of albuminuria were identified as risk factors for PDR and DME in a South Indian population with T2D.

Correlation of Immunological Markers with Disease and Clinical Outcome Measures in Patients with Autoimmune Retinopathy.

Purpose: To determine if immunological markers (1) are significantly different between autoimmune retinopathy (AIR) patients and controls and (2) correlate with disease progression in AIR patients. Methods: We enrolled patients with a possible AIR diagnosis, as well as control participants without eye disease, autoimmunity, or cancer. Immunological markers were tested in all participants. In addition, AIR patients had up to three blood draws for testing over their disease course. For AIR patients, clinical measures, including visual acuity (VA) and Goldmann visual field (GVF) area, were recorded at each draw. We used the Mann-Whitney U test to compare the immunological markers between AIR patients and controls. We used multilevel mixed-effect regression to investigate the correlation between markers and clinical parameters over time in AIR patients. Results: Seventeen patients with AIR and 14 controls were included. AIR patients had a higher percent of monocytes (Z = 3.076, P = 0.002). An increase in immunoglobulin G against recoverin was correlated with a VA decrease (ß = 0.0044, P < 0.0001). An increase in monocyte proportion was correlated with a decrease in GVF area (ß = -7.27, P = 0.0021). Several markers of B-cell depletion were correlated with GVF improvement. Conclusions: Monocytes may play a role in AIR pathophysiology and be a disease activity marker. B-cell depletion markers correlated with clinical parameter improvement, particularly GVF. Translational Relevance: This work elucidates immunologic markers that may improve the accuracy of diagnosis and treatment of AIR.

Risk of Noninfectious Uveitis with Female Hormonal Therapy in a Large Healthcare Claims Database.

PURPOSE: To determine if female hormonal therapy (FHT) increases the incidence of noninfectious uveitis. DESIGN: Retrospective cohort study. PARTICIPANTS: Women exposed to FHT and matched women unexposed to FHT enrolled in a national insurance plan. METHODS: Estimation of noninfectious uveitis incidence used multivariable Cox proportional hazards regression. To account for differences between the exposed and unexposed cohorts, a propensity score for being prescribed FHT was created using logistic regression, and inverse probability of treatment weighting was performed. MAIN OUTCOME MEASURES: Incidence of noninfectious uveitis. For the primary outcome, incident noninfectious uveitis was defined as a new diagnosis code for noninfectious uveitis followed by a second instance of a noninfectious uveitis code within 120 days. For the alternative outcome definition, a corticosteroid prescription or code for an ocular corticosteroid injection within 120 days of the uveitis diagnosis code was used instead of the second uveitis diagnosis code. RESULTS: There were 217 653 women exposed to FHT and 928 408 women not unexposed to FHT. For the primary outcome, the hazard ratio (HR) for incident noninfectious uveitis was not significantly different between the FHT and unexposed cohorts (HR, 0.99; 95% confidence interval [CI], 0.83-1.17; P = 0.87). With the alternative outcome definition, the FHT cohort was more likely to develop uveitis (HR, 1.21; 95% CI, 1.04-1.41; P = 0.01). When examined by anatomic subtype, for anterior uveitis there was a greater likelihood of incident uveitis in the exposed cohort (HR, 1.23; 95% CI, 1.05-1.45; P = 0.01) for the alternative outcome definition but not for the primary outcome. With age stratification, women exposed to FHT aged ≥45 years at the time of FHT prescription were more likely to develop uveitis (HR, 1.23; 95% CI, 1.03-1.47; P = 0.03) for the alternative outcome definition. A similar HR (1.22) was seen for women aged ≤44 years at the time of prescription, but this association did not meet statistical significance (P = 0.20). CONCLUSIONS: Exposure to FHT increases the rate of incident noninfectious uveitis when uveitis is defined on the basis of both diagnostic codes and documentation of corticosteroid treatment. However, the risk is modest and FHT is likely safe with regard to noninfectious uveitis risk in the majority of patients exposed to these drugs.

The Genetic Influence on Corticosteroid-Induced Ocular Hypertension: A Field Positioned for Discovery.

PURPOSE: To provide evidence that corticosteroid-induced ocular hypertension has a genetic component. DESIGN: Evidence-based perspective. METHODS: We conducted a comprehensive literature search for studies exploring genetic influences on intraocular pressure responses to corticosteroid treatment. RESULTS: Studies demonstrating increased risk of corticosteroid-induced ocular hypertension among first-degree relatives of affected individuals support a genetic contribution to the disease. Family and personal history of primary open-angle glaucoma also increases the risk of corticosteroid-induced intraocular pressure elevation, suggesting common genetic etiologies. A number of studies have attempted to identify predisposing genetic factors; however, reproducible findings have not yet been reported. The recent availability of large data sets with clinical and genetic data for patients affected by corticosteroid-induced ocular hypertension and glaucoma provides new opportunities to study the genetic underpinnings of this important condition. CONCLUSIONS: There is substantial evidence suggesting a genetic component to corticosteroid-related ocular hypertension and glaucoma, but specific genetic risk factors have yet to be identified. The current confluence of large genetic data sets and affordable genetic sequencing technologies has great potential for discovering the genes that increase risk for this blinding complication of corticosteroid therapy.