Dexamethasone Intracanalicular Insert for Clinically Significant Aqueous-Deficient Dry Eye: A Randomized Controlled Trial.

PURPOSE: To evaluate a commercially available dexamethasone intracanalicular insert to treat dry eye. DESIGN: Single-center, double-masked randomized controlled trial. PARTICIPANTS: Patients with clinically significant aqueous-deficient dry eye (combined ocular surface staining score, ≥ 3 [0-12]; corneal fluorescein staining score, ≥ 2 [0-6]; and Schirmer's wetting, < 10 mm at 5 minutes in both eyes) with symptoms (dryness, eye discomfort, or visual fatigue, ≥ 30 [0-100]) despite treatment with at least 1 prescription drop and deemed candidates for topical steroid therapy. METHODS: Seventy-five adult patients were enrolled. A 1:1 randomization sequence was used to determine which eye of each patient would receive the treatment (dexamethasone 0.4-mg intracanalicular insert with 30-day elution time) or sham (collagen plug). The fellow eye received the opposite treatment. Patients were masked to treatment assignment. Follow-up visits (at weeks 2, 4, and 6) were performed by a masked investigator. MAIN OUTCOME MEASURES: Dry eye parameters and patient symptoms were used for efficacy, and intraocular pressure (IOP) was used for safety assessment. RESULTS: The severity of dry eye was comparable between the treatment arms (fellow eyes) at baseline. Eyes that received the dexamethasone insert showed significantly less corneal staining at week 4 (mean difference [MD], -0.55; 95% confidence interval [CI], -0.91 to -0.19) and conjunctival staining at week 4 (MD, -0.68; 95% CI, -1.05 to -0.30) and week 6 (MD, -0.34; 95% CI, -0.65 to -0.02). Schirmer's wetting was comparable between the two treatment arms. Although the patients reported less dryness in eyes that received the insert at week 4 (MD, -5.5; 95% CI, -11.4 to 0.4), no statistically significant differences were found in any patient-reported symptoms. At week 4, dexamethasone-treated eyes were more likely to show an IOP increase (by 5-10 mmHg; 9 eyes vs. 1 eye; relative risk, 9.00; 95% CI, 1.14-71.0). All cases of increased IOP were managed with short-term topical ß-blockers and subsided. CONCLUSIONS: The dexamethasone intracanalicular insert may be considered a dropless dual treatment for clinically significant aqueous-deficient dry eye when topical steroid treatment is deemed appropriate. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Sjögren's Working Group: The 2023 OMERACT meeting and provisional domain generation.

Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity.

Efficacy of a Novel Water-Free Topical Cyclosporine 0.1 % Solution for Optimizing the Ocular Surface in Patients with Dry Eye and Cataract.

This is a pooled analysis from two phase III clinical trials investigating a water-free topical cyclosporine 0.1% for the treatment of moderate to severe dry eye. The analyses included 1162 patients: 35% with cataract, 20% with pseudophakia and 45% without cataract. Demographics or baseline characteristics were comparable across groups except for age and vision. The cyclosporine treated patients achieved large mean improvements from baseline by day 15: -3.7 in patients without cataract, -3.2 in patients with cataract and -3.1 in pseudophakic patients. These improvements were statistically significantly higher compared to the respective vehicle groups. In the cataract subgroup, 59% of patients treated with cyclosporine achieved ≥3 grade improvements in corneal staining score, as early as day 15. The magnitude of the effect and early onset of action make this novel cyclosporine solution a promising candidate for pre-operative management of ocular surface in patients undergoing cataract surgery.

Sjögren's Versus Non-Sjögren's Ocular Features: Similar Symptoms, But Significantly Worse Signs.

Purpose: To examine the ocular signs and symptoms in participants of the Sjögren's International Collaborative Clinical Alliance cohort, and to compare them across Sjögren's disease (SjD) status. Methods: Our study population comprised 3380 Sjögren's International Collaborative Clinical Alliance participants who had no missing data relevant to this study. Participants' SjD status was assessed using the updated 2016 American College of Rheumatism/European League Against Rheumatism SjD classification criteria. Participants completed baseline questionnaires of ocular symptoms and underwent ocular examinations. Differences in the ocular signs and symptoms between SjD and non-SjD groups were assessed. We used multivariable linear and linear mixed-effects models to investigate the impact of SjD on Ocular Surface Disease Index-6 and OSS. Results: Among 1532 participants classified as SjD, their Ocular Surface Disease Index-6 did not clinically differ from those classified as non-SjD (adjusted difference, -0.97; 95% confidence interval, -1.52 to -0.41). However, SjD participants exhibited an elevated ocular staining score (adjusted difference, 3.47; 95% confidence interval, 3.36-3.57; P < 0.001) compared with non-SjD participants. In addition, SjD was associated with increased odds of ocular signs, such as reduced tear break-up time, abnormal Schirmer I test, and corneal abnormalities, and was strongly related to more intense corneal and conjunctival staining, as well as additional corneal staining points. Conclusions: SjD is associated with a higher risk of ocular signs and pathology compared with non-SjD, whereas ocular symptoms remain similar. In addition, corneal abnormalities and corneal staining patterns could serve as a potential biomarker in identifying SjD-related dry eye.

Usability of Patient Education-Oriented Cataract Surgery Websites.

PURPOSE: To assess the web accessibility and readability of patient-oriented educational websites for cataract surgery. DESIGN: Cross-sectional electronic survey. PARTICIPANTS: Websites with information dedicated to educating patients about cataract surgery. METHODS: An incognito search for "cataract surgery" was performed using a popular search engine. The top 100 patient-oriented cataract surgery websites that came up were included and categorized as institutional, private practice, or medical organization according to authorship. Each site was assessed for readability using 4 standardized reading grade-level formulas. Accessibility was assessed through multilingual availability, accessibility menu availability, complementary educational video availability, and conformance and adherence to the Web Content Accessibility Guidelines (WCAG) 2.0. A standard t test and chi-square analysis were performed to assess the significance of differences with regard to readability and accessibility among the 3 authorship categories. MAIN OUTCOME MEASURES: The main outcome measures were the website's average reading grade level, number of accessibility violations, multilingual availability, accessibility menu availability, complementary educational video availability, accessibility conformance level, and violation of the perceivable, operable, understandable, and robust (POUR) principles according to the WCAG 2.0. RESULTS: A total of 32, 55, and 13 sites were affiliated with institutions, private practice, and other medical organizations, respectively. The overall mean reading grade was 11.8 ± 1.6, with higher reading levels observed in private practice websites compared with institutions and medical organizations combined (12.1 vs. 11.4; P = 0.03). Fewer private practice websites had multiple language options compared with institutional and medical organization websites combined (5.5% vs. 20.0%; P = 0.03). More private practice websites had accessibility menus than institutions and medical organizations combined (27.3% vs. 8.9%; P = 0.038). The overall mean number of WCAG 2.0 POUR principle violations was 17.1 ± 23.1 with no significant difference among groups. Eighty-five percent of websites violated the perceivable principle. CONCLUSIONS: Available patient-oriented online information for cataract surgery may not be comprehensible to the general public. Readability and accessibility aspects should be considered when designing these resources. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

United States Regulatory Approval of Topical Treatments for Dry Eye.

PURPOSE: To report the heterogeneity in methodology of clinical trials submitted to the US Food and Drug Administration (FDA) for approval of topical dry eye treatments. DESIGN: Comparative analysis of clinical trials' methods. METHODS: We reviewed the online, publicly available FDA database, application review files, ClinicalTrials.gov registry records, and journal articles for each FDA-approved topical dry eye treatment. For each trial, we extracted information about the study, patient demographics, treatment names and doses, sample size in each arm, and the measurement instrument in a systematic fashion. RESULTS: Fourteen trials were included that assessed 5 topical treatments for dry eye (cyclosporine 0.05%, cyclosporine 0.09%, lifitegrast 5%, and loteprednol 0.25% eye drops and varenicline 0.03-mg nasal spray). Median treatment duration was 12 weeks (range, 2-24 weeks). In all trials, treatments, including varying concentrations of the same treatment, were compared with vehicle. Twelve trials (85.7%) evaluated a primary clinician-measured clinical sign, and 10 trials (71.4%) evaluated a primary patient-reported symptom. Corneal staining was the most frequently evaluated clinical sign primary outcome, reported in half (6 of 12) of the trials, and was graded using 4 different scoring systems. Conjunctival staining, conjunctival hyperemia, and tear production were each measured using 2 different scoring systems. Ocular discomfort, the only patient-reported symptom primary outcome, was measured using 5 different instruments. CONCLUSION: A variety of outcome measures were used in these clinical trials. Clinically meaningful dry eye outcome measures and standardized measurements can optimize the assessment of and comparison of therapeutic benefits.

Long-term outcomes of therapeutic corneal transplants performed in a tertiary eye care hospital in South India.

Purpose: This study aimed to review the demographics, clinical characteristics, and long-term outcomes of therapeutic penetrating keratoplasty (TPK) performed in a tertiary eye care hospital. Methods: Case records of 149 therapeutic transplants (135 patients) that were performed during the calendar year 2016 were retrospectively analyzed, and outcomes were measured until 3 years of follow-up. Information on demographics, presentation characteristics, keratoplasty indications, offending microbe, and secondary surgical interventions was studied. The final outcome was classified in terms of therapeutic, anatomical, and functional outcomes. Results: The median age of the recipients was 55 years with 61% men. The most common indications for TPK were perforated infectious ulcer (45.9%), nonhealing ulcers (29.9%), and graft infections (17.4%). Fungal etiology was noted in 61.2% and bacterial etiology in 17.4% of the eyes. Therapeutic success was achieved in 130 eyes (89%) at the end of 1 month. Anatomical success was achieved in 130 (98.5%) and 88 patients (86.3%) at the end of 1 and 6 months, respectively. At the 6-month time point, 78 patients (76.5%) attained functional success with vision better than light perception. Three-year follow-up data were available for 23.7% of recipients, of which only 12 patients (37.5%) retained a clear graft either after a primary therapeutic or secondary optical keratoplasty. Conclusion: Therapeutic keratoplasty is highly effective in eradicating infection and providing anatomical integrity. However, timely intervention can aid in achieving the best functional outcome.

Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease: The ESSENCE-2 Randomized Clinical Trial.

Importance: Dry eye disease (DED) is a common public health problem with significant impact on vision-related quality of life and well-being of patients. Medications with rapid onset of action and a good tolerability profile remain an unmet need. Objective: To assess efficacy, safety, and tolerability of a water-free cyclosporine ophthalmic solution, 0.1% (CyclASol [Novaliq GmbH]), applied twice daily in DED compared with vehicle. Design, Setting, and Participants: CyclASol for the Treatment of Signs and Symptoms of Dry Eye Disease (ESSENCE-2) was a phase 3, multicenter, randomized, double-masked, vehicle-controlled clinical study conducted from December 5, 2020, to October 8, 2021. Following a 14-day run-in period with an artificial tear administered 2 times per day, eligible participants were randomly assigned 1:1 to the treatment groups. Patients with moderate to severe DED were included in the study. Interventions: Cyclosporine solution vs vehicle administered 2 times per day for 29 days. Main Outcomes and Measures: The primary end points were changes from baseline in total corneal fluorescein staining (tCFS; 0-15 National Eye Institute scale) and in dryness score (0-100 visual analog scale) at day 29. Conjunctival staining, central corneal fluorescein staining, and tCFS responders were also assessed. Results: A total of 834 study participants were randomly assigned to cyclosporine (423 [50.7%]) or vehicle (411 [49.3%]) groups at 27 sites. Participants had a mean (SD) age of 57.1 (15.8) years, and 609 (73.0%) were female individuals. The majority of participants self-identified in the following race categories: 79 Asian (9.5 %), 108 Black (12.9%), and 635 White (76.1%). Participants treated with cyclosporine solution had greater improvement in tCFS (-4.0 grades) than the vehicle group (-3.6 grades) at day 29 (change [∆] = -0.4; 95% CI, -0.8 to 0; P = .03). The dryness score showed treatment benefits from baseline in both groups: -12.2 points for cyclosporine and -13.6 points for vehicle (∆ = 1.4; 95% CI, -1.8 to 4.6; P = .38). In the cyclosporine group, 293 participants (71.6%) achieved clinically meaningful reductions of 3 grades or higher in tCFS vs 236 (59.7%) in the vehicle group (∆ = 12.6%; 95% CI, 6.0%-19.3%; P < .001). These responders showed greater improvement in symptoms at day 29 including dryness (∆ = -4.6; 95% CI, -8.0 to -1.2; P = .007) and blurred vision (Δ = -3.5; 95% CI, -6.6 to -4.0; P = .03) compared with nonresponders. Conclusions and Relevance: The ESSENCE-2 trial confirmed that treatment with a water-free cyclosporine solution, 0.1%, results in early therapeutic effects on the ocular surface compared with vehicle. The responder analyses suggest that the effect is clinically meaningful in 71.6% of participants in the cyclosporine group. Trial Registration: ClinicalTrials.gov Identifier: NCT04523129.

Prospective, Randomized, Multicenter, Double-Masked, Clinical Trial of Corneal Cross-Linking for Boston Keratoprosthesis Carrier Tissue.

PURPOSE: To assess whether cross-linking the carrier donor cornea of the Boston Keratoprosthesis (BKPro) improves retention of the device in participants at high risk for keratolysis. DESIGN: Prospective, double-masked, randomized clinical trial. METHODS: In this multicenter study, 68 adult participants who were scheduled for BKPro implantation were enrolled. Masked participants were randomized to receive either a cross-linked (CXL) or non-cross-linked (non-CXL) donor corneal carrier. The Kaplan-Meier event-free survival was determined by the product-limit method and compared by the log-rank test to examine whether survival curves were different between the CXL and non-CXL groups. The primary outcome of the study was time from surgery to BKPro removal. The secondary endpoint was 12-month retention rate. RESULTS: A total of 68 participants were enrolled and randomized 1:1 to each group. The average age at the time of surgery was 62 (range = 24-89) years, and 42 participants (62%) were male. The overall BKPro retention rate was 70% during a mean follow-up time of 93 (range = 6-201) weeks. Twenty BKPros were removed, 10 in the CXL group and 10 in the non-CXL group, with 18 requiring removal because of sterile keratolysis. There was no difference in the time to removal between the groups during the study (P = .910). At 12 months, there was no significant difference in the retention rate in the CXL group (94%) vs the non-CXL group (82%, P = .150). CONCLUSIONS: In this prospective study, cross-linking of the carrier cornea prior to BKPro implantation did not reduce the incidence of sterile keratolysis or increase device retention among participants at high risk for retention failure.

Reduced tear thrombospondin-1/matrix metalloproteinase-9 ratio can aid in detecting Sjögren's syndrome etiology in patients with dry eye.

Differentiating patients with Sjögren's syndrome (SS)-associated dry eye from non-SS dry eye is critical for monitoring and appropriate management of possible sight- or life-threatening extraglandular complications associated with SS. We tested whether reduced tear levels of immunoregulatory thrombospondin (TSP)-1, which also inhibits matrix metalloproteinase (MMP)-9, would reflect SS pathogenesis aiding the identification of patients with SS-dry eye. Total of 61 participants, including healthy controls (n = 20), patients with non-SS dry eye (n = 20) and SS-dry eye (n = 21) were enrolled prospectively. Tear TSP-1 and MMP-9 levels were measured using a custom magnetic bead-based multi-plex assay in a masked manner. Analyte concentrations were assessed further according to ocular surface and tear film parameters. Relative to median tear TSP-1 (308 ng/ml) and MMP-9 (1.9 ng/ml) levels in the control group, significantly higher proportion of patients with SS-dry eye than non-SS had lower tear TSP-1 levels (55% vs. 29%, odds ratio [OR] = 3, 95% confidence interval [CI] = 1.64 to 5.35, p < 0.05) and higher tear MMP-9 levels (65% vs. 24%, OR = 5.8, 95% CI = 4.46 to 19.81, p < 0.05), respectively. The tear TSP-1/MMP-9 ratio was significantly reduced in patients with SS-dry eye compared to non-SS (B = -2.36, 95% CI = -3.94 to -0.0.79, p < 0.05), regardless of tear MMP-9 levels. Patients with a lower ratio were 2.3 times more likely to have SS (OR = 0.28, 95% CI = 0.1 to 0.75, p < 0.05). This ratio showed significant inverse correlations with clinical parameters (conjunctival and corneal staining scores). Our results denote that tear TSP-1/MMP-9 ratio can be useful in identifying patients with dry eye with underlying SS and used as a screening test.

Symptom-Based Cluster Analysis Categorizes Sjögren's Disease Subtypes: An International Cohort Study Highlighting Disease Severity and Treatment Discordance.

OBJECTIVE: Although symptom relief is a critical aspect for successful drug development in Sjögren's disease, patient experiences with Sjögren's-related symptoms are understudied. Our objective was to determine how pain, dryness, and fatigue, the cardinal symptoms of Sjögren's disease, drive cluster phenotypes. METHODS: We used data from the Sjögren's International Collaborative Clinical Alliance (SICCA) Registry and a Sjögren's Foundation survey. We performed hierarchical clustering of symptoms by levels of dryness, fatigue, and pain. Using international and US cohorts, we performed multiple logistic regression analysis to compare the clusters, which included comparisons of differences in symptoms, quality of life (QoL), medication use, and systemic manifestations. RESULTS: Four similar clusters were identified among 1,454 SICCA registrants and 2,920 Sjögren's Foundation survey participants: 1) low symptom burden in all categories (LSB); 2) dry with low pain and low fatigue (DLP); 3) dry with high pain and low to moderate fatigue (DHP); and 4) high symptom burden in all categories (HSB). Distribution of SICCA registrants matching the symptom profile for each cluster was 10% in the LSB cluster, 30% in the DLP cluster, 23% in the DHP cluster, and 37% in the HSB cluster. Distribution of survey participants matching the symptom profile for each cluster was 23% in the LSB cluster, 14% in the DLP cluster, 21% in the DHP cluster, and 42% in the HSB cluster. Individuals in the HSB cluster had more total symptoms and lower QoL but lower disease severity than those in the other clusters. Despite having milder disease as measured by laboratory tests and organ involvement, individuals in the HSB cluster received immunomodulatory treatment most often. CONCLUSION: We identified 4 symptom-based Sjögren's clusters and showed that symptom burden and immunomodulatory medication use do not correlate with Sjögren's end-organ or laboratory abnormalities. Findings highlight a discordance between objective measures and treatments and offer updates to proposed symptom-based clustering approaches.

A comprehensive overview of living with Sjögren's: results of a National Sjögren's Foundation survey.

To gain insight into the Sjögren's disease (SjD) patient experience using a survey generated by patients and providers. We evaluated the results of the 2016 Sjögren's Foundation survey, with 25 questions designed in a collaborative effort between the Foundation, patients with SjD, SjD provider experts, and a marketing research company. We used descriptive statistics to provide a thorough understanding of SjD demographics, symptoms, quality of life (QoL), cost, and treatments. Analyses revealed high symptoms, QoL, and financial burdens in SjD. Dry mouth and eye were the most commonly reported symptoms (94 and 93%, respectively). The most frequent extra-glandular symptoms included fatigue, dry or itchy skin, and morning stiffness. The top three aspects of QoL most impaired included (i) sex life (53%), (ii) participating in hobbies/social activities/extracurricular activities (52%), and (iii) job/career or ability to work (49%). SjD respondents commonly reported taking health food supplements/remedies, vitamin D, and exercising, in addition to taking treatments for symptomatic dryness. SjD costs were high, including a total yearly cost, on average, of $2026 for dental care. SjD respondents reported that dryness and risk factors for lymphoma and fatigue are essential to address with new therapies. In this comprehensive overview of the SjD experience, we demonstrated a high burden of disease to SjD respondents, including symptoms, QoL, and financial burden. We also identify the top goals of therapy for new systemic SjD therapies. Key Points • The top three symptoms or signs that patients with Sjögren's hope new treatments will address are dryness, fatigue, and reduction in lymphoma or blood cancer risk • The top aspects of quality of life reported to be impaired by Sjögren's are sex life, hobbies, social activities and extracurricular activities, job/career or ability to work, and finding the correct word during conversations • Patients with Sjögren's have a yearly mean dental cost of $2026 but also have high costs associated with prescription medications, healthcare appointments, over-the-counter medications, alternative therapies, and medical equipment.

Outcome Measures to Assess Dry Eye Severity: A Review.

Outcome measures used to assess efficacy of dry eye therapeutics have not been consistently applied in clinical settings, nor have they been shown to correlate with functional outcomes. We propose that corneal staining, a clinically meaningful dry eye parameter, should be used as a standard objective outcome measure across all clinical trials evaluating dry eye treatments. We justify this based on evidence regarding its relationship to vision and vision related quality-of-life. In addition, corneal staining has been shown to correlate with ocular surface inflammation, a well elucidated aspect of dry eye pathophysiology and an active area in therapeutics research. No one outcome measure explored herein correlates perfectly to this heterogenous disease. However, there is mounting evidence showing the correlation between corneal staining and functional visual indices. We hope that future clinical trials will standardize corneal staining as a measure to determine the efficacy of interventions and justify their clinical utility.

Reliability of Several Glaucoma Tests in Patients With Boston Type 1 Keratoprosthesis.

PURPOSE: Managing glaucoma after Boston type 1 keratoprosthesis (KPro) surgery remains challenging. We herein assessed the fitness of commonly used clinical tests to evaluate glaucoma in KPro eyes versus eyes with penetrating keratoplasty (PK) as controls. METHODS: Sixteen patients with KPro and 14 patients with PK tested in an identical manner. After the 10-2 visual field with size V stimulus, intraocular pressure (IOP) was estimated with palpation by the first observer. Then, retinal nerve fiber layer (RNFL) thickness analysis was performed twice using optical coherence tomography by an ophthalmic photographer, before and after a short break. After the second observer estimated the IOP, the visual field was repeated. Finally, color photographs of the optic disk were captured by an ophthalmic photographer. The cup-to-disk ratio was assessed by 2 masked observers, at 2 different time points, in a random manner. Agreements between and within observers and reliability of repeated measurements were evaluated using the intraclass correlation coefficient (ICC) and Bland-Altman plots. RESULTS: Inter-rater agreement of palpation IOP estimate was moderate for eyes with KPro (ICC = 0.47) and fair for eyes with PK (ICC = 0.27). Visual field and RNFL thickness showed high test-retest reliability in both KPro and PK eyes (ICC > 0.80 for both). Inter-rater agreement of cup-to-disk ratio assessments was substantial in eyes with both KPro (ICC = 0.62) and PK (ICC = 0.70). CONCLUSIONS: The 10-2 visual field and RNFL thickness seem sufficiently repeatable and might allow the detection of glaucoma progression in KPro eyes. Such testing is important, given limited inter-rater agreement regarding the palpation IOP estimate.

Antibodies to Both Ro52 and Ro60 for Identifying Sjögren's Syndrome Patients Best Suited for Clinical Trials of Disease-Modifying Therapies.

OBJECTIVE: To assess anti-Ro52 and anti-Ro60 serologic profiles as markers of clinically relevant phenotypic subsets of patients with Sjögren's syndrome (SS). METHODS: From a cohort of 839 consecutive patients with suspected or established SS seen in our multidisciplinary SS center, we compared the association of key phenotypic features in 390 patients who fulfilled SS classification criteria and in the parent cohort, stratifed by the presence of both anti-Ro60 and anti-Ro52, anti-Ro60 alone, and anti-Ro52 alone. RESULTS: The SS cohort included 227 patients (58%) with both anti-Ro60 and anti-Ro52, 65 (17%) with anti-Ro60 alone, 58 (15%) with anti-Ro52 alone, and 40 (10%) with neither antibody. Those with both anti-Ro60 and anti-Ro52 had a significantly increased prevalence of abnormal ocular surface staining, focal lymphocytic sialadenitis with focus score ≥1, antinuclear antibody ≥1:320, anti-SSB/La, rheumatoid factor, and IgG ≥15.6 gm/liter (P < 0.0016 for all). The groups with isolated anti-Ro52 and anti-Ro60 were equivalent to each other in their phenotypic associations, except for rheumatoid factor, which was higher in the anti-Ro52 alone group. The associations of these Ro antibody serologic profiles were similar in the parent cohort, except for additional associations with salivary gland enlargement and parotid gland ultrasound score. CONCLUSION: SS patients with both anti-Ro60 and anti-Ro52 antibodies are distinguished by a higher prevalence of markers of B-cell hyperactivity and glandular inflammation. Antibody reactivity to both Ro60 and Ro52 may thus serve as an important inclusion criterion for SS patients in clinical trials where the therapeutic agent targets pathways mediating these pathogenic abnormalities.

Associations Between Smoking and Primary Sjögren Syndrome Classification Using the Sjögren's International Collaborative Clinical Alliance Cohort.

OBJECTIVE: The objective of this study was to examine the association of smoking with Primary Sjögren syndrome (pSS) classification and pSS diagnostic test results. We hypothesized that past and current smokers would have lower odds of being classified as having Sjögren syndrome (SS) and lower odds of having abnormal individual SS diagnostic test results compared with nonsmokers. METHODS: Participants with suspected or established pSS were enrolled into the Sjögren's International Collaborative Clinical Alliance (SICCA) registry and had oral, ocular, and rheumatologic examinations performed; blood and saliva samples collected; and labial salivary gland biopsy examinations performed; they also completed questionnaires at baseline. Logistic regression was used to determine whether smoking status was associated with pSS classification and individual pSS diagnostic test results. RESULTS: A total of 3514 participants were enrolled in SICCA. A total of 1541 (52.9%) met classification criteria for pSS. Compared with never smokers, current smokers had reduced odds of being classified as having pSS, reduced odds of having a focus score ≥ 1 and serologic positivity for anti-SSA/anti-SSB antibodies, and lower odds of having abnormal signs or test results of dry eye disease. Compared with never smokers, past smokers did not have a statistically significant reduction in odds of being classified as having pSS and of having abnormal individual pSS diagnostic test results. CONCLUSION: Compared with never smokers, current smokers in the SICCA cohort had lower odds of being classified as having pSS, lower odds of exhibiting abnormal signs and test results for dry eye disease, and lower odds of having a labial salivary gland biopsy supportive of pSS classification. Such negative associations, however, do not suggest that current smoking is of any benefit with respect to pSS.

Autologous serum eye drops for ocular surface disorders.

PURPOSE OF REVIEW: Ocular surface disease is a prevalent, diverse group of conditions that cause patient discomfort and decreased visual acuity and present considerable expense to both patients and healthcare systems. Autologous serum eye drops are a topical treatment modality derived from the patient's own blood. Use of serum eye drops for ocular surface disease has been promising due to biochemical similarities to endogenous tears. RECENT FINDINGS: Use of serum eye drops for moderate to severe ocular surface diseases such as dry eye, corneal epithelial defects, and inflammatory conditions has become more prevalent. Recent studies have demonstrated that the use of serum eye drops is well-tolerated by patients and associated with improvement in patient-reported outcomes and objective dry eye parameters. Production of serum eye drops may vary, treatment costs can be significant, and the quality of evidence for serum eye drop use published from randomized controlled trials is modest, particularly for long-term treatment. Accessibility remains an area for improvement and may be complemented by allogeneic serum eye drops. SUMMARY: Serum eye drops are frequently used as a safe, well-tolerated, and effective treatment for ocular surface disease. Further research is needed to assess long-term outcomes and improve accessibility.

Impact of COVID-19 Pandemic on Infectious Keratitis Outcomes: A Retrospective Multicenter Study in Tertiary Eye Hospitals of South India.

PURPOSE: The purpose of this study was to report the adverse effects of the COVID-19 pandemic on the clinical outcomes of infectious keratitis in South India. METHODS: Two hundred fifty-eight patients presented with infectious keratitis at 6 tertiary care centers when strict travel restrictions were in place from March 24 to May 31, 2020. Case records were collected retrospectively and analyzed for demographics, type of initial treatment, length of delay in presentation, microbiological diagnosis, clinical course, and final treatment outcome. RESULTS: The mean age of the patients was 49.2 years, with most of them (61.2%) being male. Forty-one patients (15.9%) did not receive any treatment for at least a week after the onset of symptoms. One hundred eight patients (41.9%) presented with severe ulcer (32 had a frank perforation). Resolution of the infection was achieved only in 103 patients (45.6%). A total of 90 patients (39.8%) with ulcers had a perforation, yet only 29 patients (32.2%) could receive keratoplasty because of the unavailability of donor tissues. At the end of 6-month follow-up, 47 patients had anatomical failure (loss of globe) and 12 additional patients had functional failure (total permanent vision loss). CONCLUSIONS: Delay in presentation and acute shortage of donor corneal tissues for emergency keratoplasty because of the COVID-19 pandemic had a grave impact, resulting in irreversible blindness in a significant number of patients.

Impact of the COVID-19 pandemic on eye strain and dry eye symptoms.

PURPOSE: Among adult individuals with dry eye, assess the self-reported impact of the COVID-19 pandemic on (1) dry eye-related visual function, (2) reading efficiency, and (3) dry eye treatments used. METHODS: In June-July 2020, we conducted an online survey of adults with dry eye who spent at least somewhat more time at home during the pandemic than before. Consistent with TFOS DEWS II guidelines, we categorized respondents into mild, moderate, or severe dry eye based on treatment usage. RESULTS: We included 388 respondents: 97 respondents (25%) with mild, 80 (21%) with moderate, and 211 (54%) with severe dry eye. In all three groups, screen/reading time generally doubled during the pandemic. Reduced work-related efficiency was noted by a considerable proportion of respondents (moderate dry eye: 51%, mild: 39%, and severe: 38%). Compared with respondents with mild dry eye, respondents with moderate dry eye were considerably more likely to note worsening symptoms: eye pain (OR = 2.57, 95% CI 1.22-5.41), headache from eye symptoms (OR = 2.34, 95% CI 1.11-4.90), and difficulty concentrating because of eye symptoms (OR = 2.79, 95% CI 1.37-5.66). Respondents with moderate dry eye with Sjögren's syndrome were most likely to note these. Respondents with severe dry eye were more likely than respondents with mild dry eye to report losing access to dry eye-related treatments (OR = 2.62, 95% CI 1.36-5.03). CONCLUSIONS: The COVID-19 pandemic-related eye strain may be impacting symptoms, performance, and ultimately employment, especially for those with moderate dry eye. This may be compounding the already-high dry eye-related societal burden.

Neuropathic Pain in the Eyes, Body, and Mouth: Insights from the Sjögren's International Collaborative Clinical Alliance.

OBJECTIVE: To evaluate how ocular, oral, and bodily neuropathic pain symptoms, which characterize small fiber neuropathies, are associated with Sjögren's syndrome (SS) classification based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. METHODS: Participants enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) registry had ocular, rheumatologic, oral, and labial salivary gland (LSG) biopsy examinations, blood and saliva samples collected, and completed questionnaires at baseline. We used mixed effects modeling with age, country, gender, and depression being fixed effects and study site, a random effect, to determine if neuropathic pain indicators (assessed via questionnaires) were associated with being classified as SS. RESULTS: A total of 3,514 participants were enrolled into SICCA, with 1,541 (52.9%) meeting the 2016 ACR/EULAR classification criteria for SS. There was a negative association between being classified as SS and experiencing bodily neuropathic pain features of needle-like pain, prickling/tingling sensation, ocular neuropathic pain of constant burning, and constant light sensitivity, and having a presumptive diagnosis of neuropathic oral pain. CONCLUSIONS: We found that those classified as SS had lower scores/reports of painful neuropathies compared with those classified as non-SS. Non-SS patients with dry eye disease or symptoms could benefit from pain assessment as they may experience painful small-fiber neuropathies (SFNs). Pain questionnaires may help identify pain associated with SFNs in patients with SS and non-SS dry eye. Future studies would be helpful to correlate self-reports of pain to objective measures of SFNs in those with SS, non-SS dry eye, and healthy controls.