Design and Biocompatibility of a Novel, Flexible Artificial Cornea.

Purpose: We sought to introduce the materials, design, and biocompatibility of a flexible and suturable artificial corneal device. Methods: Single-piece, fully synthetic, optic-skirt design devices were made from compact perfluoroalkoxy alkane. The skirt and the optic wall surfaces were lined with a porous tissue ingrowth material using expanded polytetrafluoroethylene. Full-thickness macroapertures around the skirt perimeter were placed to facilitate nutrition of the recipient cornea. Material properties including the skirt's modulus of elasticity and bending stiffness, optic light transmission, wetting behavior, topical drug penetrance, and degradation profile were evaluated. Results: The final prototype suitable for human use has a transparent optic with a diameter of 4.60 mm anteriorly, 4.28 mm posteriorly, and a skirt outer diameter of 6.8 mm. The biomechanical and optical properties of the device closely align with the native human cornea with an average normalized device skirt-bending stiffness of 4.7 kPa·mm4 and light transmission in the visible spectrum ranging between 92% and 96%. No optical damage was seen in the 36 devices tested in fouling experiments. No significant difference was observed in topical drug penetrance into the anterior chamber of the device implanted eye compared with the naïve rabbit eye. Conclusions: The flexibility and biocompatibility of our artificial cornea device may offer enhanced tissue integration and decreased inflammation, leading to improved retention compared with rigid keratoprosthesis designs. Translational Relevance: We have developed a fully synthetic, flexible, suturable, optic-skirt design prototype artificial cornea that is ready to be tested in early human feasibility studies.

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.

Demographic and Psychiatric Associations With Dry Eye in a Medicare Population.

PURPOSE: The purpose of this study was to investigate the impact of demographic characteristics and psychiatric comorbidity on the prevalence of dry eye disease in the American geriatric population. METHODS: Data were collected from a 2011 nationwide sample of Medicare beneficiaries aged 65 years and older (N = 1,321,000). Age, sex, race/ethnicity, residential area, climate region, and income, along with psychiatric comorbidities including depression and anxiety, were collected. Multivariable logistic regression models were used to assess the relationship between demographic and psychiatric factors and the prevalence of dry eye disease. RESULTS: Among 21,059 patients with clinically significant dry eye, women had higher odds of having dry eye compared with men [odds ratio (OR) 2.03, 95% confidence interval (1.97-2.10)]. Asian and Native American patients had increased odds of having dry eye compared with White patients [OR 1.85 (1.69-2.02) and OR 1.51 (1.19-1.93)], while Black patients were less likely to have dry eye [OR 0.83 (0.79-0.87)]. Patients aged 75 to 84 years and 85+ were more likely to have dry eye compared with those aged 65 to 74 years [OR 1.49 (0.45-1.53) and OR 1.54 (1.48-1.60)]. Having both depression and anxiety were associated with higher odds of having dry eye [OR 2.38 (2.22-2.55)] compared with having depression alone [OR 1.95 (1.86-2.04)] or anxiety alone [OR 2.22 (2.10-2.35)]. CONCLUSIONS: Significant racial and regional disparities in dry eye prevalence were found. Psychiatric association with dry eye varied with age, sex, race, and residence region. Further research is needed to comprehend the underlying mechanisms, implications, and to address disparities in the diagnosis and management of dry eye.

Efficacy of a new 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 2 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 with 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 new cyclosporine solution a promising candidate for preoperative management of ocular surface in patients undergoing cataract surgery.

Ten-Year Outcome of Boston Type I Keratoprosthesis Surgery at a Tertiary Care Center.

PURPOSE: The aim of this study was to report long-term outcomes of patients who have undergone Boston type I keratoprosthesis (KPro) surgery. METHODS: This study was a retrospective review. Inclusion criteria were KPro surgery between 2006 and 2012 and at least 10 years of follow-up. Demographics, ocular history, surgery indication, clinical variables, and postsurgical outcomes were recorded. Descriptive statistical analysis was performed. RESULTS: We identified 75 patients with KPro implantation, and 17 patients with at least 10 years of follow-up (median = 11.1 years; range, 10.0-12.8 years) were included. Of 17 eyes, 11 (64.8%) had their original device in situ, 3 (17.6%) had their second device in situ, 1 (5.9%) had the device removed and replaced with a donor keratoplasty, and 2 (11.8%) were enucleated. At the last follow-up, 11 eyes (64.7%) were able to maintain improvement in vision, 5 (29.4%) had worsened vision, 1 (5.9%) had stable vision, and 9 (52.9%) had visual acuity

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.

Utilizing visual symptoms to distinguish dry eye from glaucoma, cataract, and suspect glaucoma patients: a cross-sectional study.

BACKGROUND: The diagnosis of dry eye and other common ophthalmological conditions can be supported using patient reported symptoms, which is increasingly useful in contexts such as telemedicine. We aim to ascertain visual symptoms that differentiate dry eye from cataract, glaucoma, or glaucoma suspects. METHODS: Adults with dry eye, glaucoma, cataract, and suspected glaucoma (controls) completed a questionnaire to rate the frequency and severity of 28 visual symptoms. Univariate, followed by multivariable logistic regression with backward stepwise selection (p < 0.05), determined the individual symptoms and set of symptoms best distinguishing dry eye from each of the other conditions. RESULTS: Mean age of 353 patients (94 glaucoma suspect controls, 79 glaucoma, 84 cataract, and 96 dry eye) was 64.1 years (SD = 14.1); 67% were female and 68% White. Dry eye patients reported more frequent light sensitivity (OR = 15.0, 95% CI = 6.3-35.7) and spots in vision (OR = 2.8, 95% CI = 1.2-6.3) compared to glaucoma suspect controls. Compared to glaucoma patients, dry eye patients experienced more frequent light sensitivity (OR = 9.2, 95% CI = 2.0-41.7), but less frequent poor peripheral vision (OR = 0.2, 95% CI = 0.06-0.7), difference in vision between eyes (OR = 0.09, 95% CI = 0.01-0.7), and missing patches of vision (OR = 0.06, 95% CI = 0.009-0.3). Compared to cataract patients, dry eye patients reported more frequent spots in vision (OR = 4.5, 95% CI = 1.5-13.4) and vision variability across the week (OR = 4.7, 95% CI = 1.2-17.7) and were less likely to report worsening vision (OR = 0.1, 95% CI = 0.03-0.4) and blindness (OR = 0.1, 95% CI = 0.02-0.8). CONCLUSION: Visual symptoms may serve as a complementary tool to distinguish dry eye from various ocular conditions, though the symptoms that best distinguish dry eye differ across comparisons. Differentiating how patients visually perceive common eye diseases may be used in a variety of clinical settings to rule out specific conditions.

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.

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.

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.

Cornea Classic: "Grading of Corneal and Conjunctival Staining in the Context of Other Dry Eye Tests," Bron, Evans, and Smith, 2003.

ABSTRACT: Dry eye is an increasingly common ocular condition with significant impact on quality of life due to eye discomfort and blurred vision complaints. In addition, the financial burden of dry eye on both patients and society is substantial. Although there has been a recent explosion of research in the field since 2002 with the approval of the first prescription topical treatment (Restasis, Allergan Inc, Irvine CA), dry eye lags behind other ophthalmic conditions where clinically meaningful outcome measures are closely tied with the metrics by which their therapeutics are evaluated. Unfortunately, current practice is such that physicians largely rely on patient symptoms to evaluate dry eye, and these do not always correlate with objective ocular surface and tear film parameters. In patients with severe dry eye, the patient-reported symptoms are likely dampened because of the neurotrophic state of the ocular surface, which accompanies any long-standing inflammatory ocular condition. Therefore, staining of the corneal and conjunctival surface using vital dyes is an invaluable dry eye test to provide information normally not visible during routine slit-lamp examination. The landmark article by Bron, Evans, and Smith published in Cornea in 2003 provides excellent guidance to clinicians to highlight and quantify ocular surface parameters in patients with dry eye. Validation studies correlating conjunctival or corneal staining with tangible quality-of-life parameters and metrics to measure those are needed to verify ocular surface staining as a clinically meaningful dry eye outcome to be used in clinical practice and clinical trials.

Twelve-Month Clinical and Histopathological Performance of a Novel Synthetic Cornea Device in Rabbit Model.

Purpose: To report the biological stability and postoperative outcomes of a second-generation, single-piece, flexible synthetic cornea in a rabbit model. Methods: Device materials and design were amended to enhance biointegration. Optic skirt design devices were made from compact perfluoroalkoxy alkane with porous expanded polytetrafluoroethylene ingrowth surface overlying the skirt and optic wall. Sixteen devices were implanted into intrastromal pocket in rabbit eyes. Rabbits were randomly assigned to 6- and 12-month follow-up cohorts (n = 8 in each) postoperatively. Monthly examinations and optical coherence tomography assessed cornea-device integration, iridocorneal angle, optic nerve, and retina. Results: There were no intraoperative complications. All devices were in situ at exit, with clear optics. No retroprosthetic membrane, glaucoma, cataract formation, or retinal detachment was observed. Two rabbits in the 6-month group had mild, focal anterior lamella thinning without retraction adjacent to the optic near tight sutures. Three postoperative complications occurred in the 12-month group. One rabbit diagnosed with endophthalmitis was euthanized on day 228. Mild sterile focal retraction of anterior lamella occurred in two rabbits, which were terminated on days 225 and 315. Light microscopic examination of enucleated globes demonstrated fibroplasia with new collagen deposition into the porous scaffold without significant inflammation, encapsulation, or granuloma formation. Conclusions: Clinical evaluations, imaging, and histopathological findings indicate favorable outcomes of this synthetic corneal device in a rabbit model. Early feasibility studies in humans are being planned. Translational Relevance: Favorable 12-month results of the device in rabbits demonstrate vision-restoring potential in corneally blind individuals at high risk of failure with donor keratoplasty.

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.

Combined Therapeutic Penetrating Keratoplasty and Pars Plana Vitrectomy for the Treatment of Infectious Keratitis Endophthalmitis: Mexican Endophthalmitis Study Group Protocol 4.

PURPOSE: The purpose of this study was to assess the role of combined surgical treatment of therapeutic penetrating keratoplasty and pars plana vitrectomy in the anatomical and functional outcome of infectious keratitis endophthalmitis. METHODS: This study reviewed the medical records of 4 participating centers in the United States and Mexico. This study included patients with a clinical diagnosis of infectious keratitis endophthalmitis who had been treated with an early therapeutic penetrating keratoplasty and pars plana vitrectomy as the main treatment for endophthalmitis. From each medical record, the study retrieved demographic data, relevant medical and drug history, baseline clinical manifestation of endophthalmitis, best-corrected visual acuity, and the need for enucleation/evisceration for the control of the infection or any other reason through the follow-up. RESULTS: The study included 48 patients (50.15 ± 20.6 years). The mean follow-up time was 13 ± 0.5 months. The mean best-corrected visual acuity at baseline was 2.1 ± 0.25 logarithm of the minimum angle of resolution. At month 12 was 2.09 ± 0.61 logarithm of the minimum angle of resolution ( P = 0.9). The overall prevalence of enucleation/evisceration was 8.3% (95% confidence interval: 2.32%-19.98%). The prevalence of a vision of no-light perception was 20.8% (95% confidence interval: 2.32%-19.98%). CONCLUSIONS: Combined surgery for severe cases of infectious keratitis endophthalmitis eradicates the infection in most cases, while significantly improving the overall outcomes.

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.

Racial and Ethnic Disparities in Dry Eye Diagnosis and Care.

PURPOSE: To investigate health disparities in racial and ethnic minorities with dry eye. METHODS: Medical records were reviewed for demographics, socioeconomic factors, treatments, and objective dry eye parameters. Race/ethnicity was self-reported as delineated by the U.S. Census. The reference group comprised of randomly selected White patients, with number equal to the largest minority group. RESULTS: The study included 465 patients (157 Black, 157 White, 85 Asian, and 66 Hispanic). Compared to White (3.2%) patients, larger proportion of minorities used Medicaid or lacked health insurance (Black 8.3%, P = .054; Asian 10.6%, P = .019; Hispanic 18.2%, P < .001). Black and Hispanic patients had lower estimated median household income than Whites (White $98,472, Black $75,554, P < .001; Asian $105,503, P = .088; Hispanic $86,839, P = .030). Prior to presentation, fewer minority patients received prescription treatments or procedures (White 61.8%; Black 30.6%, P < .001; Asian 43.5%, P = .006; Hispanic 43.9%, P = .014). Although at baseline visit minorities had worse mean conjunctival (White, 1.7; Black 2.2, P = .136, Asian 2.4, P = .022; Hispanic 2.6, P = .005) and corneal staining scores (White, 1.6; Black 2.5, P < .001; Asian 2.3, P = .003; Hispanic 2.4, P = .001), no differences were noted at final visit. CONCLUSION: Minorities presented with worse objective dry eye parameters, and less prior dry eye care. Income and health care access may not fully explain the observed undertreatment at presentation. Differential management by eye care providers and patient attitudes warrant further investigation.

Glaucoma and Ocular Surface Disease: More than Meets the Eye.

Understanding the association between ocular surface disease and glaucoma is important for improving adherence to treatment and introducing practical solutions. While topical antihypertensive medications for glaucoma are well tolerated according to short-term studies, there is little evidence on their long-term effects. Since they are often required for many years, the effects of these drops on the ocular surface become important in regard to quality of life and adherence. In this nonsystematic review performed in April 2022, we summarize what is known about the relationship between glaucoma and ocular surface disease. Specifically, we examine how each class of topical glaucoma drops affects the ocular surface. We then review the treatment of ocular surface disease for patients on topical glaucoma therapy. Finally, we discuss treatments that may reduce or eliminate the burden of topical medications.

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.