Faculty Bibliography

Sjögren syndrome (SS) is a chronic inflammatory autoimmune disease characterized by destruction of mucosal glands resulting in dry eye and dry mouth. Ocular presentations can be heterogenous in SS with corneal nerves abnormalities that are structural, functional, or both. Some individuals present with corneal hyposensitivity, with a phenotype of decreased tear production and epithelial disruption. Others present with corneal hypersensitivity, with a phenotype of neuropathic pain including light sensitivity and pain out of proportion to signs of tear dysfunction. A similar correlate can be found outside the eye, with dry mouth predominating in some individuals while pain conditions predominate in others. Understanding how nerve status affects SS phenotype is an important first step to improving disease management by targeting nerve abnormalities, as well as inflammation.

BACKGROUND:To examine ocular symptoms and signs of veterans with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) diagnosis, ME/CFS symptoms, and controls. METHODS:This was a prospective, cross-sectional study of 124 South Florida veterans in active duty during the Gulf War era. Participants were recruited at an ophthalmology clinic at the Miami Veterans Affairs Hospital and evaluated for a diagnosis of ME/CFS, or symptoms of ME/CFS (intermediate fatigue, IF) using the Canadian Consensus criteria. Ocular symptoms were assessed via standardised questionnaires and signs via comprehensive slit lamp examination. Inflammatory blood markers were analysed and compared across groups. RESULTS:Mean age was 55.1 ± 4.7 years, 88.7% identified as male, 58.1% as White, and 39.5% as Hispanic. Ocular symptoms were more severe in the ME/CFS (n = 32) and IF (n = 48) groups compared to controls (n = 44) across dry eye (DE; Ocular Surface Disease Index [OSDI]: 48.9 ± 22.3 vs. 38.8 ± 23.3 vs. 19.1 ± 17.8, p < 0.001; 5 item Dry Eye Questionnaire [DEQ-5]: 10.8 ± 3.9 vs. 10.0 ± 4.6 vs. 6.6 ± 4.2, p < 0.001) and pain-specific questionnaires (Numerical Rating Scale 1-10 [NRS] right now: 2.4 ± 2.8 vs. 2.4 ± 2.9 vs 0.9 ± 1.5; p = 0.007; Neuropathic Pain Symptom Inventory modified for the Eye [NPSI-E]: 23.0 ± 18.6 vs. 19.8 ± 19.1 vs. 6.5 ± 9.0, p < 0.001). Ocular surface parameters and blood markers of inflammation were generally similar across groups. CONCLUSION/CONCLUSIONS:Individuals with ME/CFS report increased ocular pain but similar DE signs, suggesting that mechanisms beyond the ocular surface contribute to symptoms.

PURPOSE/OBJECTIVE:To investigate the cost-effectiveness (CE) of prophylactic laser peripheral iridotomy (LPI) in primary angle-closure (PAC) suspects (PACSs). DESIGN/METHODS:Cost-effectiveness analysis utilizing Markov models. SUBJECTS/METHODS:Patients with narrow angles (PACSs). METHODS:Progression from PACSs through 4 states (PAC, PAC glaucoma, blindness, and death) was simulated using Markov cycles. The cohort entered at 50 years and received either LPI or no treatment. Transition probabilities were calculated from published models, and risk reduction of LPI was calculated from the Zhongshan Angle Closure Prevention trial. We estimated costs of Medicare rates, and previously published utility values were used to calculate quality-adjusted life year (QALY). Incremental CE ratios (ICER) were evaluated at $50 000. Probabilistic sensitivity analyses (PSAs) addressed uncertainty. MAIN OUTCOME MEASURES/METHODS:Total cost, QALY, and ICER. RESULTS:Over 2 years, the ICER for the LPI cohort was > $50 000. At 6 years, the LPI cohort was less expensive with more accrued QALY. In PSA, the LPI arm was cost-effective in 24.65% of iterations over 2 years and 92.69% over 6 years. The most sensitive parameters were probability of progressing to PAC and cost and number of annual office visits. CONCLUSIONS:By 6 years, prophylactic LPI was cost-effective. The rate of progressing to PAC and differing practice patterns most impacted CE. With uncertainty of management of narrow angles, cost may be a decision management tool for providers. FINANCIAL DISCLOSURE(S)/BACKGROUND:The authors have no proprietary or commercial interest in any materials discussed in this article.

Purpose/UNASSIGNED:To validate and assess user satisfaction and usability of the New York University (NYU) Langone Eye Test application, a smartphone-based visual acuity (VA) test. Design/UNASSIGNED:Mixed-methods cross-sectional cohort study. Participants/UNASSIGNED:Two hundred forty-four eyes of 125 participants were included. All participants were adults 18 years of age or older. Participants' eyes with a VA of 20/400 (1.3 logarithm of the minimum angle of resolution [logMAR]) or worse were excluded. Methods/UNASSIGNED:Patients were tested using the clinical standard Rosenbaum near card and the NYU Langone Eye Test application on an iPhone and Android device. Each test was performed twice to measure reliability. Ten patients were selected randomly for subsequent semistructured qualitative interviews with thematic analysis. Main Outcome Measures/UNASSIGNED:Visual acuity was the parameter measured. Bland-Altman analysis was used to measure agreement between the results of the NYU Langone Eye Test application and Rosenbaum card, as well as test-retest reliability of each VA. The correlation between results was calculated using the intraclass correlation coefficient. Satisfaction survey and semistructured interview questions were developed to measure usability and acceptability. Results/UNASSIGNED:Bland-Altman analysis revealed an agreement between the application and the Rosenbaum near card of 0.017 ± 0.28 logMAR (iPhone) and 0.009 ± 0.29 logMAR (Android). The correlation between the application and the Rosenbaum near card was 0.74 for both the iPhone and Android. Test-retest reliability was 0.003 ± 0.22 logMAR (iPhone), 0.01 ± 0.25 logMAR (Android), and 0.01 ± 0.23 logMAR (Rosenbaum card). Of the 125 participants, 97.6% found the application easy to use, and 94.3% were overall satisfied with the application. Thematic analysis yielded 6 key themes: (1) weaknesses of application, (2) benefits of the application, (3) tips for application improvement, (4) difficulties faced while using the application, (5) ideal patient for application, and (6) comparing application with traditional VA testing. Conclusions/UNASSIGNED:The NYU Langone Eye Test application is a user-friendly, accurate, and reliable measure of near VA. The application's integration with the electronic health record, accessibility, and easy interpretation of results, among other features, make it ideal for telemedicine use.

PURPOSE/OBJECTIVE:Sphingolipids (SPL) are a class of lipid molecules that play important functional and structural roles in our body and are a component of meibum. Sphingomyelinases (SMases) are key enzymes in sphingolipid metabolism that hydrolyze sphingomyelin (SM) and generate ceramide (Cer). The purpose of this study was to examine relationships between ocular surface SMases, SPL composition, and parameters of Meibomian gland dysfunction (MGD). METHODS:Individuals were grouped by meibum quality (n = 25 with poor-quality, MGD, and n = 25 with good-quality, control). Meibum and tears were analyzed with LC-MS to quantify SPL classes: Cer, Hexosyl-Ceramide (Hex-Cer), SM, Sphingosine (Sph), and sphingosine 1-phosphate (S1P). SMase activity in tears were quantified using a commercially available 'SMase assay'. Statistical analysis included multiple linear regression analyses to assess the impact of SMase activity on lipid composition, as well as ocular surface symptoms and signs of MGD. RESULTS:Demographic characteristics were similar between the two groups. nSMase and aSMase levels were lower in the poor vs good quality group. aSMase activity in tears negatively correlated with SM in meibum and tears and positively with Sph in meibum and S1P in tears. Lower SMase activity were associated with signs of MGD, most notably Meibomian gland dropout. CONCLUSION/CONCLUSIONS:This study suggests that individuals with MGD have reduced enzymatic activity of SMases in tears. Specifically, individuals with poor vs good meibum quality were noted to have alterations in SMase activity and SPL composition of meibum and tears which may reflect deviations from normal lipid metabolism in individuals with MGD.

PURPOSE/OBJECTIVE:To investigate the costs and effects of implanting trabecular meshwork bypass stents during cataract surgery from a societal perspective in the United States. DESIGN/METHODS:Cost-utility analysis using Markov models and efficacy/safety data from published pivotal or randomized control trials (RCTs) of devices investigated. PARTICIPANTS/METHODS:Patients aged 65 years and older with mild to moderate primary open-angle glaucoma with or without visually significant cataract. METHODS:With the use of Markov models, glaucoma progression through 4 glaucoma states (mild, moderate, advanced, severe/blind) and death were simulated over 35 years. The cohort with cataract entered the model and received cataract surgery with or without device implantation. We included a medication management only reference group to calculate total costs and outcomes for those without cataract. Intraocular pressure (IOP) reductions from RCTs were converted to glaucoma state transition probabilities using visual field (VF) mean deviation (MD) decline rates from the Early Manifest Glaucoma Trial. Progressive thinning of the retinal nerve fiber layer (RNFL) on OCT imaging related to IOP control warranted further intervention, including adding medication, selective laser trabeculoplasty (SLT), or incisional glaucoma surgery. We estimated whole costs at Medicare rates and obtained utility values for glaucoma states from previous studies. Incremental costs per quality-adjusted life-year (QALY) gained were evaluated at a QALY threshold of $50 000. One-way deterministic sensitivity analysis, scenario analyses, and probabilistic sensitivity analyses addressed parameter uncertainty and demonstrated model robustness. MAIN OUTCOME MEASURES/METHODS:Total costs, QALY, and incremental cost-effectiveness ratio (ICER). RESULTS:Over 35 years in the base case, the Hydrus (Ivantis, Inc.) implanted with cataract surgery arm cost $48 026.13 and gained 12.26 QALYs. The iStent inject (Glaukos Corp.) implanted with cataract surgery arm cost $49 599.86 and gained 12.21 QALYs. Cataract surgery alone cost $54 409.25 and gained 12.04 QALYs. Initial nonsurgical management cost $57 931.22 and gained 11.74 QALY. The device arms dominated or were cost-effective compared with cataract surgery alone within 5 years and throughout sensitivity analyses. The iStent inject arm was cost-effective in 94.19% of iterations in probabilistic sensitivity analyses, whereas the Hydrus arm was cost-effective in 94.69% of iterations. CONCLUSIONS:Implanting the Hydrus Microstent or iStent inject during cataract surgery is cost-effective at a conservative QALY threshold.

Introduction: Ocular surface pain has been traditionally lumped under the umbrella term "˜dry eye"™ (DE) but is now understood as its own entity and can occur in the absence or presence of tear dysfunction. Identifying patients at risk for the development of chronic ocular surface pain, and factors contributing to its severity are important in providing precision medicine to patients. Areas covered: In this review, we discuss factors linked to the presence and severity of ocular surface pain, including eye-related features, systemic characteristics, and environmental findings. We discuss corneal nerves, whose anatomic and functional integrity can be characterized through in vivo confocal microscopy images and testing of corneal sensitivity. We review systemic diseases that are comorbid with ocular surface pain, including physical and mental health diagnoses. Finally, we identify environmental contributors, including air pollution, previous surgeries, and medications, associated with ocular surface pain. Expert opinion: Intrinsic and extrinsic factors contribute to ocular surface pain and must be considered when evaluating an individual patient. These factors can inform the suspected etiology of the pain, and guide management decisions such as tear replacement or medications targeting nerve pain.

PURPOSE/OBJECTIVE:Sphingolipids (SPL) play a role in cell signaling, inflammation, and apoptosis. The purpose of this study was to examine meibum and tear SPL composition in individuals with poor versus good meibum quality. METHODS:Individuals were grouped by meibum quality (n = 25 with poor quality, case group and n = 25 with good quality, control group). Meibum and tears were analyzed with liquid chromatography-mass spectrometry (LC-MS) to quantify SPL classes. Semiquantitative and relative composition (mole percent) of SPL and major classes, Ceramide (Cer), Hexosyl-Ceramide (Hex-Cer), Sphingomyelin (SM), Sphingosine (Sph), and sphingosine 1-phosphate (S1P) were compared between groups. RESULTS:Demographic characteristics were similar between the two groups. Overall, individuals with poor meibum quality had more SPL pmole in meibum and tears than controls. Relative composition analysis revealed that individuals with poor meibum quality had SPL composed of less Cer, Hex-Cer, and Sph and more SM compared to individuals with good quality meibum. This pattern was not reproduced in tears as individuals with poor meibum quality had SPL composed of a similar amount of Cer, but more Hex-Cer, Sph and SM compared to controls. In meibum, SPL pmole and relative composition most strongly correlated with MG metrics while in tears, SPL pmole and relative composition most strongly correlated with tear production. SPL in both compartments, specifically Cer pmole in meibum and S1P% in tears, correlated with DE symptoms. CONCLUSION/CONCLUSIONS:SPL composition differs in meibum and tears in patients with poor vs good meibum quality. These findings may be translated into therapeutic targets for disease.

PURPOSE/OBJECTIVE:To examine dry eye (DE) symptoms and signs in individuals with versus without Gulf War Illness (GWI). DESIGN/METHODS:Prospective cross-sectional study. METHODS:We performed a prospective, cross-sectional study of South Florida veterans who were active duty during the Gulf War Era (GWE; 1990-91) and seen at an eye clinic between October 1, 2020, and March 13, 2021. Veterans were split into two groups: those who met Kansas criteria for GWI (cases, N=30) and those who did not (controls, N=41). DE symptoms were assessed via standardized questionnaires while DE signs were assessed using a series of ocular surface parameters. Differences between groups were assessed via Mann-Whitney U test. Linear regressions analyses were used to examine which GWI symptoms most closely aligned with DE symptoms. RESULTS:Veterans with GWI had higher DE symptoms scores compared to controls (Ocular Surface Disease Index (OSDI) scores: mean 41.20±22.92 vs 27.99±24.03, p=0.01). In addition, veterans with GWI had higher eye pain scores compared to controls (average eye pain over past week: 2.63±2.72 vs 1.22±1.50, p=0.03), including on neuropathic ocular pain questionnaires (Neuropathic Pain Symptom Inventory- modified for the Eye (NPSI-E): 17.33±17.20 vs 9.63±12.64, p=0.03). DE signs were mostly similar between the groups. GWI symptoms "nausea or upset stomach" (β=14.58. SE=3.02, p<0.001) and "headache" (β=7.90, SE=2.91, p=0.011) correlated with higher OSDI scores. CONCLUSION/CONCLUSIONS:Individuals with GWI have more severe DE symptoms and ocular pain scores but similar tear and ocular surface parameters compared to controls without GWI. This finding suggests that mechanisms beyond tear dysfunction drive eye symptoms in GWI.