Pali P. Singh's research while affiliated with Duke University Medical Center and other places

Purpose: To compare features of endogenous endophthalmitis associated with injection drug use (IDU) to endogenous endophthalmitis from other etiologies. Methods: We retrospectively collected data on patients with endogenous endophthalmitis due to IDU or other causes from three academic tertiary care centers over a six-year period. Differences in presenting characteristics, culture results, treatment, and visual acuity (VA) were compared between groups. Results: Thirty-eight (34%) patients had IDU-associated endogenous endophthalmitis, while 75 (67%) had endogenous endophthalmitis from other causes. Compared to patients in the non-IDU group, IDU patients were significantly younger, more frequently male, had longer duration of symptoms at diagnosis, and were less likely to have bilateral disease (p<0.05 for all). IDU patients were less likely to have a systemic infection source identified (29% vs 71%, p<0.001) or have positive cultures (47% vs 80%, p<0.001). The IDU group was less likely to be admitted to the hospital (71% vs 92%, p=0.005) and less likely to receive treatment with intravenous antimicrobials (55% vs 83%, p=0.003). VA did not significantly differ between groups. Conclusions: Endophthalmitis related to IDU presents in younger patients with less comorbidities and frequently without positive cultures or an identifiable systemic source; therefore, a high index of suspicion is needed to identify this disease.

Background Plasma and cerebrospinal fluid (CSF) levels of neuronal biomarkers have been associated with Alzheimer’s disease (AD). The aqueous humor, which can be collected during routine cataract surgery, may have similar concentrations of neuronal biomarkers to CSF. Method This proof‐of‐concept study prospectively enrolled adults without a diagnosis of cognitive impairment undergoing cataract surgery at a tertiary academic medical center. Participants underwent Montreal Cognitive Assessment (MoCA blind version 7.1, “abnormal” < 18) at the time of study enrollment. Aqueous samples were collected during cataract surgery through a surgical paracentesis. Samples were analyzed using an ultrasensitive single‐molecule array (SiMoA). Assessed biomarkers included phosphorylated tau (pTau)‐181, amyloid‐beta (Aß)‐42, Aß‐40, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Correlations were assessed using Spearman’s rank correlation (rho). Result Sixteen eyes of 16 patients (average MoCA 19.2) underwent aqueous sampling to assess pTau‐181 and 7 eyes of 7 separate patients (average MoCA 20.0) underwent aqueous and plasma sampling to assess Aß‐42, Aß‐40, NfL, and GFAP. Aqueous pTau‐181 increased with increasing age (rho = 0.67, p = 0.0046). No aqueous or plasma biomarkers were significantly correlated with MoCA scores (all p > 0.05). Aqueous and plasma levels of biomarkers were not significantly correlated. Conclusion Neuronal biomarkers are measurable in aqueous humor using SiMoA analysis; however, these biomarkers did not significantly correlate with MoCA scores in a cognitively normal population. Further study in individuals with a known diagnosis of Alzheimer’s disease or mild cognitive impairment is indicated.

Background Diabetes mellitus is a risk factor for central retinal vein occlusion (CRVO); however, it is unclear whether certain commonly used medications among diabetics or glycemic control impact visual outcomes in diabetic eyes with CRVO. Purpose To evaluate the effect of select systemic medications and glycemic control on presenting features, treatment burden, and outcomes in patients with diabetes who develop a central retinal vein occlusion (CRVO). Methods Retrospective longitudinal cohort study at a single tertiary academic referral center from 2009–2017 investigating eyes of patients being treated for diabetes mellitus at CRVO onset. Eyes with a prior history of anti-vascular endothelial growth factor (anti-VEGF) therapy or laser treatment within the year prior to CRVO onset were excluded. Main outcomes and measures were visual acuity (VA), central subfield thickness (CST), cystoid macular edema (CME), and number of intravitreal injections and laser treatment throughout follow-up. Results We identified 138 eyes of 138 participants who were diabetic at CRVO onset. Of these, 49% had an ischemic CRVO. Median follow-up time was 25.5 months. Fifty-five eyes (40%) had a HbA1c within 6 months of CRVO presentation. HbA1c was positively correlated with both presenting CST (p = 0.04) and presence of CME (p < 0.01). In all 138 eyes, mean presenting VA was 20/246, and mean final VA was 20/364. Better-presenting VA was significantly associated with aspirin 325 mg use (p = 0.04). Lower CST at presentation was significantly associated with metformin use (p = 0.02). Sitagliptin use at CRVO onset was associated with a lower prevalence of CME at final follow-up (p < 0.01). Lower final CST was significantly associated with glipizide use at CRVO onset (p = 0.01). There were no significant associations between systemic medications or HbA1c and treatment burden or final VA (p > 0.05). Conclusion Although aspirin 325 mg, metformin, sitagliptin, and glipizide were associated with better-presenting VA, lower-presenting CST, lower prevalence of macular edema at final visit, and lower final CST, respectively, none of these systemic agents or glycemic control were associated with decreased treatment burden or improved visual outcomes in diabetics with CRVO.

Purpose: The purpose of this study was to investigate the effect of systemic antiplatelet agents and anticoagulants on the structural and functional outcomes of eyes with branch retinal vein occlusion (BRVO). Methods: A retrospective longitudinal cohort study was performed on BRVO patients evaluated at a single tertiary care referral center between 2009 and 2017. Medical records were reviewed for antiplatelet agent and anticoagulant use including aspirin, clopidogrel, warfarin, rivaroxaban, apixaban, or dabigatran prior to BRVO onset. In addition, optical coherence tomography (OCT) parameters, clinical outcomes, and treatment patterns were also recorded. Results: A total of 354 BRVO eyes were identified with a mean follow-up time of 36 months. Antiplatelet or anticoagulant use was associated with presence of cystoid macular edema (CME) at presentation after controlling for potential confounding variables in a multivariate logistic regression. Multivariate regression also revealed an association between foveal hemorrhage at presentation and use of antiplatelet or anticoagulant medications. There were no significant differences in visual acuity or prevalence of CME at the final visit in those with antiplatelet/anticoagulant use compared to those not on these agents. Conclusion: Although the use of systemic antiplatelet or anticoagulant agents was associated with increased prevalence of CME and foveal hemorrhage at presentation of BRVO, the use of these medications was not associated with different visual or structural outcomes at the final visit.

Purpose This work evaluates the effect of antiplatelet and anticoagulant agents on clinical outcomes, optical coherence tomography (OCT) parameters, and macular ischemia in eyes with central retinal vein occlusion (CRVO). Methods A retrospective longitudinal cohort study was performed to evaluate patients with CRVO. Demographics, OCT parameters before and after treatment, macular ischemia on fluorescein angiography, and clinical outcomes including the number of injections received were analyzed. Results A total of 365 patients with CRVO were identified. The average follow-up was 36 months. Antiplatelet or anticoagulant agent use was not associated with a significant difference in visual acuity (VA), prevalence of macular edema, or central subfield thickness on OCT at presentation or final visit. The use of 81-mg aspirin alone was associated with an increased prevalence of foveal hemorrhage at presentation. Patients who were taking an antiplatelet agent, an anticoagulation agent, or both and had an ischemic CRVO with logMAR VA of less than 1.0 experienced improved VA at the final study visit. Patients given antiplatelet or anticoagulant agents had a similar incidence of neovascular sequelae compared with patients not administered these agents. Conclusions In eyes with CRVO, the use of antiplatelet or anticoagulant agents at CRVO onset was not associated with significantly different functional outcomes, except in ischemic CRVO eyes with VA of less than 20/200. The use of 81-mg aspirin was associated with foveal hemorrhage at CRVO presentation. Otherwise, the use of any antiplatelet agent or anticoagulation was not associated with any CRVO structural outcomes.

Purpose The etiology of meibomian gland dysfunction (MGD) is incompletely understood, despite being a common ophthalmic condition and an area of unmet medical need. It is characterized by an insufficiency in glandular provision of specialized lipids (meibum) to the tear film and is a major cause of dry eye. Work in the allergic eye disease (AED) mouse model has revealed an immunopathogenic role in MGD causation, now raising interest in the applicability of immunomodulatory therapies. As such, we herein ask whether inhibition of lymphocyte function associated antigen (LFA)-1/intracellular adhesion molecules (ICAM)-1 signaling via topical lifitegrast administration has a therapeutic effect on MGD in AED mice. Methods Mice were induced with AED by i.p. injection of ovalbumin (OVA) mixed with alum and pertussis toxin, followed 2 weeks later by once daily topical OVA challenges for 7 days. Mice were treated topically with 5% lifitegrast ophthalmic solution or vehicle (PBS) 30 min prior to challenge. We developed a clinical ranking method to assess MGD severity, and also scored clinical allergy. Conjunctivae and draining lymph nodes were collected for flow cytometry. Results Topical lifitegrast significantly inhibited clinical MGD severity, which was associated with diminished pathogenic TH17 cell and neutrophil numbers in the conjunctiva. No significant change in conjunctival TH2 cells or eosinophils, and only marginal differences in ocular allergy were observed. Conclusions In AED mice, lifitegrast inhibited MGD severity marked by a reduction in select immune populations in the conjunctiva. Our findings warrant future examination of lifitegrast in the treatment of patients with forms of MGD.

Purpose This report describes the diagnosis of ocular toxocariasis presenting as endophthalmitis in an adult intravenous drug user. Methods A case is reported. Results Fundus imaging showed numerous white opacities obscuring the macula. Toxocara canis serology was reactive with an enzyme immunoassay titer of 1:2 (positive ≥ 1:32). Findings from bacterial and fungal cultures were negative, and vitrectomy cytology revealed no organisms. Postoperatively, serial optical coherence tomography imaging demonstrated a slight decrease in size of an intraretinal hyperreflective lesion in the macula. Conclusions Owing to a variety of presentations, ocular toxocariasis can be challenging to diagnose. In a patient with a history of intravenous drug use where fungal and bacterial organisms are more common causes of endophthalmitis, it is important to have a wide differential of causative organisms, particularly in the context of negative culture results and a worsening clinical examination.