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.

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.

Intense pulse light therapy treatment for refractory dry eye disease due to meibomian gland dysfunction.

PURPOSE: To assess the effect of the intense pulse light (IPL) therapy for the treatment of meibomian gland dysfunction (MGD) and dry eye parameters. METHODS: Patients who underwent an IPL therapy for the treatment of MGD were included in this retrospective study. Ocular Surface Disease Index (OSDI) scores, the frequency of daily lubricant use, non-invasive tear break-up time (NIBUT), meibomian glad dropout scores, corneal staining scores, and Schirmer test results were collected from patient charts that recorded at baseline and follow-up visits at 1 month, 3 months, and 12 months. For the analysis, patients were grouped based on the severity of their baseline meibomian gland dropout score as mild, moderate, and severe atrophy. RESULTS: Forty-three patients (mild atrophy = 22, moderate atrophy = 17, and severe atrophy = 4) were included for analysis. Except for the Schirmer test, all dry eye parameters significantly improved in patients with mild and moderate atrophy following the treatment and this effect lasted until the 12-month follow-up visit (p < 0.001). No significant improvement in any parameter was observed in patients with severe atrophy at any time point (p > 0.05). In the mild and moderate atrophy groups, OSDI scores, as well as NIBUT, started improving at 1 month (p < 0.01), while corneal staining and meibomian gland dropout scores showed earliest improvements at 3 months (p < 0.01). No adverse events were observed, except for temporary redness in 4 patients. CONCLUSION: The IPL treatment seems an effective and safe treatment for patients with MGD. This study shows that the IPL resulting in an earlier improvement in symptoms and signs with long-lasting beneficial effect on the meibomian glands.

Effects of Prolonged Reading on Dry Eye.

PURPOSE: To demonstrate the effects of prolonged silent reading on tear film and ocular surface parameters. DESIGN: Prospective, observational clinical study. PARTICIPANTS: A total of 177 patients with dry eye and 34 normal controls aged 50 years and older. METHODS: After evaluating symptoms using the Ocular Surface Disease Index (OSDI) questionnaire, the following tests were performed in consecutive order: automated noninvasive tear break-up time (TBUT), surface asymmetry and regularity indices, Schirmer's testing without anesthesia, corneal staining using fluorescein, and conjunctival staining using lissamine green. The participants were then asked to read a 30-minute validated passage silently. The tests were repeated after the reading task. MAIN OUTCOME MEASURES: Changes in tear film and ocular surface parameters after reading. RESULTS: All parameters, with the exception of surface asymmetry index, worsened after the reading task in patients with dry eye and in controls. The worsening reached a statistical significance for corneal and conjunctival staining in the dry eye group (P < 0.001) and for corneal staining in the control group (P < 0.01). At baseline, OSDI scores correlated only with corneal and conjunctival staining scores (r = 0.19, P = 0.006 and r = 0.27, P < 0.001). Among postreading measurements, baseline OSDI scores correlated with TBUT (r = -0.15, P = 0.03) in addition to corneal and conjunctival staining (r = 0.25, P < 0.001 and r = 0.22, P = 0.001). Changes in TBUT and Schirmer's test correlated significantly with their respective baseline values (r = -0.61, P < 0.001 and r = -0.44, P < 0.001), indicating that the more unstable the tear film and the lower the aqueous tear secretion, the worse they became after the prolonged reading task. Worsening in corneal staining directly correlated with the baseline conjunctival staining (r = 0.17, P = 0.02) and surface regularity index (r = 0.21, P = 0.01). CONCLUSIONS: Evaluating tear film and ocular surface parameters at rest may miss clinical findings brought about by common everyday tasks such as reading, leading to discordance between patient-reported symptoms and clinician-observed signs. Quantifying dry eye after visually straining activities such as prolonged silent reading may help better understand patient symptomatology.

Impact of Dry Eye on Prolonged Reading.

SIGNIFICANCE: Patients with dry eye frequently report difficulty with reading. However, the impact of dry eye on reading has not been studied in detail. This study shows the unfavorable effect of dry eye on reading speed and offers mechanisms that may be responsible. PURPOSE: The purpose of this study was to evaluate the impact of dry eye signs as well as symptoms on both short-duration out-loud and prolonged silent reading. METHODS: This study included 116 patients with clinically significant dry eye, 39 patients with dry eye symptoms only, and 31 controls, 50 years or older. After the Ocular Surface Disease Index (OSDI) questionnaire, objective testing of dry eye (tear film stability studies, Schirmer's test, and ocular surface staining) was performed. Total OSDI score and two subscores (vision related and discomfort related) were calculated. A short-duration out-loud reading test and a 30-minute sustained silent reading test were performed. Reading speed for each test was calculated as words per minute (wpm) and compared across the three groups. RESULTS: Patients with clinically significant dry eye read slower than controls measured with sustained silent reading test (240 vs. 272 wpm, P = .04), but not with short-duration out-loud reading test (146 vs. 153 wpm, P = .47). Patients with dry eye symptoms only did not have slower reading speed measured using either reading test as compared with controls. However, vision-related OSDI subscore independently was associated with slower reading speed (P = .02). Multivariable regression models demonstrated that each 1-point (between 0 and 6) increase in corneal staining score led to a 10-wpm decrease in sustained silent reading speed (P = .01). CONCLUSIONS: This study demonstrates a significant negative impact of dry eye (particularly presence of corneal staining) on prolonged reading. Prolonged reading task may serve as an objective clinically relevant test to measure the impact of dry eye on vision-related quality of life.

The Icare HOME (TA022) Study: Performance of an Intraocular Pressure Measuring Device for Self-Tonometry by Glaucoma Patients.

PURPOSE: To evaluate the Icare HOME (TA022) device (Icare Oy, Vanda, Finland) for use by glaucoma patients for self-tonometry. DESIGN: Prospective performance evaluation of a medical device. PARTICIPANTS: One hundred eighty-nine participants with glaucoma or suspected glaucoma were recruited from the Wilmer Eye Institute, Baltimore, Maryland, between July 2014 and April 2015. METHODS: Participants had standardized training and had to be able use the Icare HOME device independently. Subjects also had to be able to obtain the first intraocular pressure (IOP) measurement within 5 mmHg of Goldmann applanation tonometry (GAT). Those certified obtained 3 IOP measures using the HOME device, and these were compared with Icare TA01i and GAT IOP measurements. MAIN OUTCOME MEASURES: The agreement between Icare HOME and reference tonometers was used to assess precision. The intraclass correlation coefficient was used to assess within-patient reliability for the HOME device. RESULTS: Eighteen of 189 recruited patients were ineligible to take part in the study. Forty-four of 171 patients (25.7%) started but failed to complete the study: 7 stopped because of time concerns, 10 of 171 patients (6%) stopped because of difficulty using the device during certification, and 27 of 171 patients (16%) failed to be certified based on IOP. The HOME and GAT measurements agreed within 5 mmHg in 116 of 127 participants (91.3%); 2 participants (1.6%) had a difference of more than 7 mmHg. The mean difference between the Icare HOME and GAT measurements was -0.33 mmHg (standard deviation, 3.11 mmHg). The overall intraclass correlation coefficient for the HOME device was 0.92 (95% confidence interval, 0.89-0.95). CONCLUSIONS: Not all participants could learn how to use the Icare HOME device, but for those who could, most were able to obtain measurements similar to those obtained by GAT. The Icare HOME device is safe and reliable for self-tonometry, but nearly 1 in 6 individuals may fail to certify in use of the device based on large differences in IOP when comparing GAT with the Icare HOME measurements. The device has the potential to address an unmet need by providing more frequent IOP measurements in a patient's day to day life.

Sarcoidosis Presenting with Cicatrizing Conjunctivitis.

PURPOSE: To report two patients with sarcoidosis initially presenting with cicatrizing conjunctivitis. CASE REPORTS: Both patients with chronic conjunctivitis were referred for further management. The first patient had conjunctival granulomas, subepithelial fibrosis, and forniceal foreshortening. The second patient had extensive upper and lower conjunctival scarring with forniceal foreshortening and symblepharon formation of both eyes. Conjunctival biopsy specimens revealed noncaseating granulomas. Immunofluorescein studies were negative for immunoreactant deposition in the basement membrane. Because of further diagnostic evaluations, sarcoidosis was determined to be the final cause of the cicatrizing conjunctivitis. CONCLUSIONS: Sarcoidosis should be included in the differential diagnosis of cicatrizing conjunctivitis. Recognition of the characteristic noncaseating granulomas in the conjunctival biopsy and initiation of the appropriate evaluations are essential in establishing the diagnosis and determining the extent of systemic involvement.

Effect of Topical Recombinant Human Nerve Growth Factor on Corneal Epithelial Regeneration in Refractory Epithelial Keratopathy.

PURPOSE: To report the effect of topical application of recombinant human nerve growth factor (rhNGF) eye drops on corneal epithelial regeneration in patients with refractory epitheliopathy. METHODS: A retrospective chart review was conducted on patients treated with topical rhNGF for refractory epithelial keratopathy due to stage I neurotrophic keratitis (NK). Data regarding demographics and ocular/systemic past medical history was extracted from patient charts. Visual acuity and corneal staining scores were recorded at baseline and subsequent follow-up visits at 8 weeks and 3 months. Measurements from the worse eye were used to compare before and after treatment values. RESULTS: We identified 14 patients (median age 68 years, 21% male) who received rhNGF treatment for refractory epithelial keratopathy. After an 8-week treatment with topical rhNGF, the median corneal staining score in the worse eye improved from 4 to 1 (p = 0.001). All patients showed at least one-grade improvement in corneal staining at 8 weeks, with sustained effect in seven patients at 3 months. A better response was observed in eyes with post-radiation epithelial keratopathy, LASIK, and Sjogren's disease. Those with chronic use of other topical treatments and uncontrolled diabetes mellitus demonstrated incomplete responses. Eight patients reported mild-to-moderate ocular discomfort from drop application that fully resolved after completion of treatment. CONCLUSIONS: Topical rhNGF was effective and safe for refractory epithelial keratopathy in our small cohort, but sustained effects were seen only in certain etiologies for up to 3 months. Further studies are needed for optimal dosing and duration based on underlying causes.

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.

Cost and Prescriber and Patient Characteristics of Cenegermin Use in the Medicare Population.

PURPOSE: To assess the cost and prescriber and patient characteristics associated with the early use of cenegermin (OXERVATE) after its approval among Medicare beneficiaries to better define resource use and areas for improvement in the treatment of neurotrophic keratopathy. DESIGN: Retrospective, cross-sectional study. METHODS: Medicare Part D claims data of all cenegermin prescriptions from January 1, 2019, to December 31, 2020, were identified using its National Drug Code. Patients younger than 65 years and those with missing demographic characteristics were excluded. Information on patient and prescriber demographic characteristics, quantity of cenegermin prescription, gross drug costs, and patient out-of-pocket costs were extracted from each claim. RESULTS: In 2019-2020, a total of 2410 Medicare beneficiaries aged 65 years or older were prescribed cenegermin. The mean (standard deviation [SD]) age of these patients was 77.3 (7.6) years. Most patients were female (63.6%), White (87.3%), and lived in urban areas (86.9%). The majority (72%) received a standard 8-week course. A total of 1025 clinicians prescribed cenegermin. Most were male (68.2%), in an urban setting (90.8%). The median (interquartile range [IQR]) duration of cenegermin therapy prescribed per patient by each clinician was 8 (7.5-8) weeks. Total gross drug cost of all cenegermin therapy over the study period was $287 million. Median (IQR) out-of-pocket patient cost was $5791 (180-7179). CONCLUSIONS: Despite the clinical benefits of cenegermin therapy, the associated significant cost warrants further analysis of its cost-effectiveness in patient care, especially in comparison with alternative novel management options.

Prevalence of SARS-CoV-2 in Conjunctival Swab Samples Among Patients Presenting with Conjunctivitis During the COVID-19 Pandemic.

PURPOSE: To investigate the prevalence of SARS-CoV-2-associated conjunctivitis among patients presenting with conjunctivitis to ophthalmology clinics in the absence of respiratory symptoms suggesting COVID-19 during the first year of the pandemic. PATIENTS AND METHODS: This prospective, observational, cross-sectional study enrolled patients aged 18 years and older who presented with acute conjunctivitis between May 2020 and May 2021. After reviewing demographics, ocular and systemic symptoms, a slit lamp examination was performed. Five samples were collected (conjunctival swab from each eye, nasal swab from each nostril, and a nasopharyngeal swab) in separate tubes for a reverse transcription-polymerase chain reaction test for SARS-CoV-2. Patients were called at 1 and 2 weeks to follow up on their ocular and systemic symptoms and collect information about conjunctival adenovirus test results and COVID-19 test results if performed outside of the study. RESULTS: A total of 36 patients were enrolled. The most common ocular symptom was redness (35/36, 97%), and 14 patients (39%) had symptoms in both eyes at the time of the presentation. SARS-CoV-2 RNA was not detected in any samples collected during the study visit (95% confidence interval [CI] from 0 to 0.08). None of the study participants were diagnosed with COVID-19 following conjunctivitis during the 2-week follow-up period. We found that 25 patients had a conjunctival adenovirus test done on the day of their study visit, 9 of which reported positive results. CONCLUSION: Our data suggest that it may not be valuable to obtain routine testing of SARS-CoV-2 in patients presenting with conjunctivitis in the absence of COVID-19.

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.

Refractive and visual outcomes after Intacs vs ferrara intrastromal corneal ring segment implantation for keratoconus: a comparative study.

PURPOSE: To evaluate the refractive, topographic, optical, visual acuity, and quality outcomes of two types of intrastromal corneal ring segments (ICRS) in the treatment of keratoconus. METHODS: In this retrospective study, 16 eyes that had been implanted with Intacs ICRS (Addition Technology Inc) (Intacs group) and 17 eyes implanted with Ferrara ICRS (Ferrara Ophthalmics Ltda) (Ferrara group) were evaluated. Pre- and postoperative examinations included uncorrected and corrected distance visual acuities (UDVA and CDVA, respectively), manifest refraction, slit-lamp examination, topography, and ocular wavefront analysis. Contrast sensitivity measurements under photopic, scotopic, and scotopic with glare conditions were performed 1 year postoperatively. RESULTS: One year postoperatively, a significant decrease was noted in spherical equivalent refractive error of 3.76 ± 0.39 diopters (D) and 3.42 ± 0.88 D and keratometry of 3.43 ± 0.24 D and 3.28 ± 0.78 D in the Intacs and Ferrara groups, respectively; and increase in mean UDVA and CDVA in Snellen lines of 0.18 ± 0.04 and 0.21 ± 0.05, respectively, in the Intacs group and 0.21 ± 0.09 and 0.26 ± 0.08, respectively, in the Ferrara group (P<.01 for all). The postoperative increase in UDVA and CDVA and decrease in keratometry readings were not significantly different between groups (P>.05 for all). Mean higher order aberrations decreased in the Intacs group and increased in the Ferrara group (P>.05 for both). Postoperatively, a significant decrease was noted in scotopic contrast sensitivity when glare was introduced in the Ferrara group, which was positively correlated with pupil diameter (r(15)=0.50, P=.04). CONCLUSIONS: Both ICRS types provided comparable refractive, topographic, and optical quality outcomes. Eyes with Ferrara ICRS experienced greater decrease in scotopic contrast sensitivity under glare, which was significantly correlated with pupil diameter.

Characterization of Progressive Cicatrizing Conjunctivitis With Negative Immunofluorescence Staining.

PURPOSE: To characterize the clinical features of patients with direct immunofluorescence (DIF)-negative mucous membrane pemphigoid (MMP). DESIGN: Retrospective case series. METHODS: Thirty-six patients who underwent a conjunctival biopsy for suspected MMP were included. Demographic and clinical information was collected. Main outcome measures included visual acuity, Foster stages, presence of extraocular involvement, history of autoimmune disease, and durations of follow-up. RESULTS: Thirty-two patients had a negative DIF. Of those, 2 had a positive DIF on repeat biopsy. Eleven showed progression of conjunctival scarring during a median follow-up of 42 months (range, 8-100 months) and were diagnosed with biopsy-negative MMP. Another 11 patients with a median follow-up of 54 months (range, 15-138 months) were diagnosed with cicatrizing conjunctivitis of other causes. The median visual acuity of patients with biopsy-negative MMP at presentation was significantly lower compared to patients with cicatrizing conjunctivitis of other causes (20/400 vs 20/40, P = .02). Conjunctival scarring score at presentation in both biopsy-positive and biopsy-negative MMP groups was significantly higher compared to patients with cicatrizing conjunctivitis of other causes (median Foster stage, 3 vs 1, P = .009; and 3 vs 1, P = .01, respectively). CONCLUSIONS: Patients with progressive cicatrizing conjunctivitis likely have MMP in the absence of alternate diagnoses. Our findings emphasize that suspicion for MMP must remain high for patients who have Foster stage 3 conjunctival scarring on presentation or worsening of scarring during follow-up, even in the setting of negative DIF.

Sustained Gazing Causes Measurable Decline in Visual Function of Patients with Dry Eye.

PURPOSE: To assess the effects of sustained gazing on visual function of dry eye patients. DESIGN: Prospective, comparative before-and-after study. METHODS: A total of 176 patients with dry eye and 33 control subjects ≥50 years old were included. Dry eye symptomatology along and clinical parameters were assessed. Out-loud reading speed was measured using the International Reading Speed Test (IReST) as words per minute (wpm). Reading speed was repeated using different IReST excerpts following 30-minute silent reading. RESULTS: At baseline, there were no differences between dry eye patients and control subjects with respect to reading speed (172 vs 180 wpm, respectively; P = 0.21) or the time to read the excerpt (33 vs 30 seconds, respectively; P = 0.17). After silent reading, the dry eye patients had decreased reading speed and increases in the length of time to read the passage compared to baseline (161 vs 172 wpm, respectively; P = 0.002; and 38 vs 33 seconds, respectively; P < 0.001). The control subjects did not show significant differences for either parameter. There were significant differences with respect to both parameters between the dry eye and control groups after sustained gazing (161 vs 188 wpm, respectively; P = 0.006; and 38 vs 31 seconds, respectively; P = 0.003). Each 1-point increase in baseline corneal staining score (0-6) led to a 5-wpm reduction in reading speed (95% confidence interval, -8 to -1; P = 0.01). CONCLUSIONS: Sustained gazing, such as in silent reading, has a measurable negative impact on visual performance of dry eye patients. Corneal staining represents a clinical parameter relevant to visual function.

Differential Diagnosis of Sjögren Versus Non-Sjögren Dry Eye Through Tear Film Biomarkers.

PURPOSE: Systemic implications necessitate the identification of dry eye patients with Sjögren syndrome (SS). This study aims to explore the utility of tear MUC5AC and inflammatory cytokine levels in the differential diagnosis of SS-related dry eye. METHODS: A prospective, observational, case-control study was conducted on 62 patients (those with a definitive diagnosis of SS dry eye, non-SS dry eye, and age-matched healthy controls with no dry eye). Clinical evaluations included the following tests in the order listed here: noninvasive tear break-up time, osmolarity, tear sampling, Schirmer test without anesthesia, and ocular surface staining (lissamine green for conjunctiva and fluorescein for cornea). Tear MUC5AC levels were assessed with enzyme-linked immunosorbent assay, and cytokines [interferon-gamma, tumor necrosis factor alpha, interleukin (IL)-6, IL-17a, IL-1ß, IL-8, IL-10, and IL-12p70] were measured using a Luminex assay in a masked fashion. RESULTS: The Bulbar conjunctival lissamine green staining score was significantly greater in patients or controls with SS versus non-SS dry eye. This greater conjunctival staining was associated with a reduction in tear MUC5AC (B = -17.8 ng/mL, 95% confidence interval = -31.8 to -3.9, P = 0.01). Among the tear cytokines, a significant association was found between IL-8 levels (hazard ratio [HR] = 1.002, 95% confidence interval = 1.000-1.003, P = 0.03) and SS diagnosis. When patients were stratified based on tear MUC5AC levels, significantly increased tear IL-8 levels were detected in patients with SS dry eye but not with non-SS dry eye, in comparison with healthy controls. CONCLUSIONS: Tear levels of goblet cell-specific MUC5AC combined with IL-8 can potentially serve as a useful biomarker for differential diagnosis of SS dry eye from non-SS dry eye.

Clinical Outcomes Of Descemet Membrane Endothelial Keratoplasty Using The Bonfadini-Todd Injector For Graft Insertion.

PURPOSE: To evaluate the clinical outcomes of using an Alcon intraocular lens (IOL) B cartridge for graft insertion during Descemet membrane endothelial keratoplasty (DMEK). PATIENTS AND METHODS: We retrospectively reviewed medical charts of patients who underwent DMEK using the Bonfadini-Todd injector, composed of an Alcon IOL B cartridge connected to plastic tubing and a syringe, for graft insertion between May 2016 and August 2018. Patient demographics, diagnoses, donor information, visual acuity, intraocular pressure (IOP), graft position and attachment status, pachymetry, and postoperative complications were recorded. RESULTS: Twenty-four eyes of 23 patients with an average age of 72.8 ± 10.0 years (range, 48-87 years) were included. Mean follow-up duration was 13.3 ± 6.6 months (range, 3-26 months). Twenty-one (87.5%) patients had a primary diagnosis of Fuchs endothelial dystrophy, two (8.3%) patients had bullous keratopathy and one (4.2%) had Peter's anomaly. Sixteen (66.7%) cases combined phacoemulsification and IOL implantation. Best-corrected visual acuity improved from a median of 0.398 logMAR preoperatively to 0.097 logMAR (P <0.001) at last follow-up examination, and central corneal thickness decreased from a median of 651 µm to 533.5 µm (P <0.001). Nine of 24 patients (37.5%) required re-bubbling due to partial graft detachment with a mean time of 12.1 ± 9.2 days (range, 5-35 days). One patient (4.2%) developed graft failure after re-bubbling and underwent Descemet stripping endothelial keratoplasty. CONCLUSION: The Alcon IOL B cartridge for DMEK graft insertion is safe and simple.

Clinical Correlations of Novel Autoantibodies in Patients with Dry Eye.

BACKGROUND: Diagnostic criteria for Sjögren's syndrome (SS) are continually being updated in pursuit of more precise and earlier diagnosis to prevent its complications. Owing to the high rate of false negative traditional serological markers, the need for better serological testing remains. OBJECTIVE: To investigate the clinical significance of three recently discovered novel autoantibodies, anti-salivary gland protein 1 (SP1), anti-carbonic anhydrase 6 (CA6), and anti-parotid secretory protein (PSP), in a cohort of dry eye patients with suspected underlying inflammatory/autoimmune disease. METHODS: Medical records of 136 patients with a primary diagnosis of dry eye who underwent laboratory testing between April 2014 and July 2017 were reviewed retrospectively. Data regarding demographic information, ocular and systemic symptoms, previous medical diagnoses, serological test results, and minor salivary gland biopsy results were collected. Dry eye evaluations included tear osmolarity, Schirmer test without anesthesia, conjunctival lissamine green staining, and corneal fluorescein staining in the order listed here. RESULTS: Of the 136 patients, 9 (9/136, 6.6%) presented with a history of SS, and 9 additional patients (9/127, 7%) received a new diagnosis of SS as a result of evaluations. Fifty-six patients (56/136, 41%) tested positive for at least one of the novel autoantibodies. Fifty-four percent (6/11) of patients with primary SS who underwent the novel serological testing had a positive anti-PSP. Of those, 2 (2/11, 18%) had negative traditional serology and had to undergo minor salivary gland biopsy for definitive diagnosis. Anti-CA6 was associated with increased corneal and conjunctival staining after adjusting for age, sex, and other serologic markers (HR = 1.5, 95% CI = 1.20-1.97, and p = 0.009 and HR = 1.4, 95% CI = 1.04-1.76, and p = 0.02, respectively). CONCLUSIONS: This cross-sectional study demonstrated that anti-CA6 is seen in patients with severe aqueous-deficient dry eye. Whether these patients have an early stage of SS or a different type of autoimmune condition may be determined through longitudinal studies.

Monoclonal gammopathy of "ocular" significance.

PURPOSE: Diagnostic criteria for monoclonal gammopathy of undetermined significance (MGUS) do not currently include ocular phenotypic changes. Here, we offer a new diagnostic approach that is useful in patients with posteriorly located corneal depositions and present evidence to support the theory that the aqueous humor is a source for monoclonal proteins accumulated in the cornea. OBSERVATIONS: A 77-year-old woman presented to the clinic with a gradual decrease in visual acuity over 6 months. Slit lamp examination revealed bilateral central guttae consistent with Fuchs corneal dystrophy, peripheral circular band-like corneal opacities in the deep stroma, and bilateral nuclear sclerotic and cortical cataracts. Anterior segment optical coherence tomography confirmed corneal opacities in the posterior stroma and Descemet membrane. Immunological studies revealed increased serum IgG levels of 3220 mg/dL and serum electrophoresis showed an abnormal monoclonal band of 2.4 g/dL identified as IgG lambda by immunofixation electrophoresis. The patient was referred to the hematology clinic where she underwent further systemic workup and was diagnosed with MGUS. Immunofixation electrophoresis of aqueous sampling, which was performed at the time of cataract surgery, confirmed the presence of the IgG lambda gammopathy in the anterior chamber. CONCLUSIONS AND IMPORTANCE: Monoclonal gammopathy, although rare, should be included in the differential diagnosis of corneal opacities, as the ocular finding can be the initial manifestation of a systemic disease that can potentially be life-threatening. When corneal biopsy is not feasible due to the location of corneal pathology, aqueous sampling may be an alternative approach towards a clinical diagnosis. We propose a new terminology, "monoclonal gammopathy of ocular significance," for patients diagnosed with MGUS, however, their only significant clinical finding is ocular manifestation.