Thyroid Eye Disease: Pilot Study Comparison Between Patients in United States-Based and India-Based Practices.

PURPOSE: Thyroid eye disease (TED) phenotype varies by ethnicity/race and genetic/environmental factors. This study compared demographic and clinical characteristics of TED patients from the US and India. DESIGN: Observational pilot study . METHODS: Sixty-four patients with TED ages ≥18 years old with active disease (onset of symptoms ≤18 months or presenting clinical activity score (CAS) ≥4) were recruited between March and October 2021 from clinical practices in the United States (Philadelphia, PA) (n = 30) and India (Hyderabad, India) (n = 34). Data collection at baseline and 3 months included clinical measurements, thyroid disease history, and photographs. Ocular symptoms and quality of life data were obtained by phone interview. CAS was calculated using the standard 7-point scale. RESULTS: There was no statistically significant difference in age, TED duration, or smoking status between patient groups. Both groups had good vision, a low rate of optic neuropathy, and comparable exophthalmometry. US patients were predominantly female (86.7% [26/30]), with a history of hyperthyroidism (96% 29/30). In comparison, Indian patients were 52.9% (18/34, P = .004) female; underlying thyroid disease was distributed between hyperthyroidism (52%), hypothyroidism (17.6%) and euthyroid (9.7%). Mean (SD) CAS in the US cohort was double the score in the India cohort (4.2 (1.7) vs 1.65 (1.7), respectively) (P < .0001). However, patients at both sites experienced subjective symptoms of TED at a similar frequency. CONCLUSIONS: Observed differences in TED between US and Indian patients warrant further investigation to elucidate differences in pathogenesis, disease expression, or other factors that may influence TED in diverse populations.

Prevalence of Novel Candidate Sjogren Syndrome Autoantibodies in the Dry Eye Assessment and Management (DREAM) Study.

PURPOSE: To evaluate the prevalence of novel candidate Sjogren syndrome (SS) autoantibodies [salivary protein-1 (SP-1), parotid secretory protein, carbonic anhydrase 6] in the DRy Eye Assessment and Management (DREAM) cohort, a study evaluating the effectiveness of omega-3 fatty acid supplements for the treatment of dry eye. METHODS: Participants underwent ocular surface examinations and serological testing for traditional and novel SS autoantibodies. Dry eye assessment and management participants were categorized into the following 3 groups: 1) no history of SS or other autoimmune diseases and negative traditional SS autoantibodies (n = 352); 2) no history of SS but a history of other autoimmune diseases (n = 66); and 3) those who met the 2012 American College of Rheumatology SS classification criteria (n = 52). RESULTS: Eleven percent had a history of SS, and 6% of those without a history of SS most likely had undiagnosed SS. The SS group had a higher prevalence of SP-1 autoantibodies than the group without SS or other autoimmune diseases (33% vs. 19%; P = 0.02) but had no difference in carbonic anhydrase 6 (P = 0.31) or parotid secretory protein autoantibodies (P = 0.33). Participants who were positive for the traditional autoantibodies alone or positive for both traditional and novel autoantibodies had the highest scores for corneal (P = 0.002) and conjunctival staining (P < 0.001). CONCLUSIONS: Data from this multicenter, prospective study demonstrated that one of the novel candidate autoantibodies, SP-1, is associated with underlying SS and that novel autoantibodies may be associated with worse ocular surface disease. Future longitudinal studies are needed to evaluate their utility in screening patients with dry eye for SS.

Dry Eye Assessment and Management (DREAM©) Study: Study design and baseline characteristics.

PURPOSE: Describe trial design and baseline characteristics of participants in the DRy Eye Assessment and Management (DREAM©) Study. DESIGN: Prospective, multi-center, randomized, double-masked "real-world" clinical trial assessing efficacy and safety of oral omega-3 (ω3) supplementation for the treatment of dry eye disease (DED). METHODS: RESULTS: Mean age of participants was 58.0 ±â€¯13.2 years. Mean OSDI score at baseline was 44.4 ±â€¯14.2. Mean conjunctival staining score (scale 0-6) was 3.0 ±â€¯1.4, corneal staining score (scale 0-15) was 3.9 ±â€¯2.7, tear break-up time was 3.1 ±â€¯1.5 s, and Schirmer test was 9.6 ±â€¯6.5 mm/5 min. CONCLUSIONS: DREAM© participants mirror real world patients who seek intervention for their DED-related symptoms despite their current treatments. Results regarding the efficacy of omega-3 supplementation will be helpful to clinicians and patients with moderate to severe DED who are considering omega-3 as a treatment. This trial design may be a model for future RCT's on nutritional supplements and DED treatments seeking to provide useful information for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02128763.

Iontophoretic delivery of dexamethasone phosphate for non-infectious, non-necrotising anterior scleritis, dose-finding clinical trial.

Currently available treatment options for non-infectious scleritis, including non-steroidal anti-inflammatory drugs, systemic corticosteroids and immunosuppressive therapies, have both efficacy and side effect limitations. Iontophoretic delivery of corticosteroids has been demonstrated to be effective for anterior uveitis and represents a potential new approach to scleritis therapy. We hypothesised that iontophoretic delivery would provide effective and precise medication delivery to the sclera, while limiting systemic exposure and side effects. This first-in-human randomised, double-masked, dose-escalating study of iontophoretic administration of dexamethasone phosphate for scleritis suggests the treatment to be well tolerated and safe (within the limitations of the 18 patients sample size). There was a suggestion of efficacy in the lowest (1.2 mA/min at 0.4 mA) dose group (corresponding to the superficial location of scleritis compared with anterior uveitis), with 5/7 eyes meeting the primary efficacy outcome within 28 days. Our results suggest iontophoretic delivery of corticosteroids is a promising potential treatment for scleritis, with favourable safety and preliminary efficacy results in this phase 1 trial. TRIAL REGISTRATION NUMBER: NCT01059955.

Postinjection endophthalmitis in the comparison of age-related macular degeneration treatments trials (CATT).

OBJECTIVE: To describe the incidence and outcomes of endophthalmitis after intravitreal injections of anti-vascular endothelial growth factor agents in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and to assess the effect of prophylactic topical antimicrobials on incidence. DESIGN: Cohort study within a randomized clinical trial. PARTICIPANTS: Patients enrolled in CATT. METHODS: Patients with neovascular age-related macular degeneration received intravitreal injections of ranibizumab or bevacizumab under 1 of 3 dosing regimens. The study protocol specified preinjection preparation to include use of a sterile lid speculum and povidone iodine (5%). Use of preinjection and postinjection antibiotics was at the discretion of the treating ophthalmologist. Patients were followed up monthly for 2 years. MAIN OUTCOME MEASURES: Development of endophthalmitis and visual acuity. RESULTS: Endophthalmitis developed after 11 of 18 509 injections (1 per 1700 [0.06%]; 95% confidence interval, 0.03%-0.11%), and in 11 of 1185 patients (0.93%; 95% confidence interval, 0.52-1.66). Incidence of endophthalmitis was 0.15% among injections with no antibiotic use, 0.08% among injections with preinjection antibiotics only, 0.06% among injections with postinjection antibiotics only, and 0.04% among injections with preinjection and postinjection antibiotics (P = 0.20). All eyes were treated with intravitreal antibiotics and 4 underwent vitrectomy. Among the 11 affected eyes, the final study visual acuity was 20/40 or better in 4 eyes (36%), 20/50 to 20/80 in 2 eyes (18%), 20/100 to 20/160 in 3 eyes (27%), and worse than 20/800 in 2 eyes (18%). The final visual acuity was within 2 lines of the visual acuity before endophthalmitis in 5 eyes (45%). CONCLUSIONS: Rates of endophthalmitis were low and similar to those in other large-scale studies. Use of topical antibiotics either before or after injection does not seem to reduce the risk for endophthalmitis.

Red blood cell fatty acid analysis for determining compliance with omega3 supplements in dry eye disease trials.

PURPOSE: To evaluate pill counts and red blood cell (RBC) membrane fatty acid profiles as measures of compliance with oral omega3 polyunsaturated fatty acids (ω3 PUFAs) and to compare the two techniques. METHODS: Sixteen dry eye disease subjects were given oral ω3 PUFA or placebo for 3 months. Compliance was measured by pill counts and blood tests at baseline and 3 months. The Wilcoxon signed-rank tests and rank-sum tests were used to compare changes from baseline and the difference between the two groups; Spearman correlation coefficients were used to assess the relationship of pill counts to changes in blood FAs. RESULTS: Pill counts for the ω3 (n=7) and placebo (n=9) groups showed a mean consumption of 4.39 and 4.76 pills per day, respectively. In the ω3 group, the median change from baseline was +1.46% for eicosapentaenoic acid (EPA) (P=0.03), +1.49% for docosahexaenoic acid (DHA) (P=0.08), and -1.91% for arachidonic acids (AA) (P=0.02). In the placebo group, median changes in all measured FAs were small and not statistically significant. The difference in change in FA levels between the two groups was significantly greater for EPA (P=0.01) and AA (P=0.04). The correlations between pill counts and changes in EPA (r=0.36, P=0.43) and DHA (r=0.17, P=0.70) were not strong. CONCLUSIONS: RBC FA analysis can be used to measure compliance in the active group and also monitor the placebo group for nonstudy ω3 intake. Low correlation of pill counts with blood levels suggests that pill counts alone may be inaccurate and should be replaced or supplemented with objective measures.

The age-related macular degeneration radiotherapy trial (AMDRT): one year results from a pilot study.

PURPOSE: To assess the short-term safety and efficacy of treating subfoveal choroidal neovascularization (CNV) with external beam radiation delivered in 5 x 4 Gy fractions among patients having age-related macular degeneration (AMD). DESIGN: A multicenter prospective randomized controlled pilot study. METHODS: Eighty-eight patients were enrolled through 10 sites and were randomized to radiotherapy (20 Gy delivered in 5 daily fractions of 4 Gy each; 6 MV [N = 41]) or no radiotherapy (sham radiotherapy [N = 22] or observation [N = 25]). Eligibility criteria included visual acuity of at least 20/320 and subfoveal CNV not amenable to treatment. Randomization was stratified by lesion type (new or recurrent CNV) and blood (<50% or >/=50% of the lesion [N = 13]). The primary outcome measure was loss of >/=3 lines of visual acuity. Secondary outcome measures were angiographic response and side effects. RESULTS: At baseline, patient and ocular characteristics were similar between treatment groups. At six months, 9 radiated eyes (26%) and 17 eyes not radiated (49%) lost >/=3 lines of visual acuity (P = .04; stratified chi(2) test). At 12 months, 13 radiated eyes (42%) and 9 observed eyes (49%) lost >/=3 visual acuity lines (P = .60). The radiated group demonstrated smaller lesions and less fibrosis than the nonradiated group (P = .05 and .004, respectively) at 12 months. Radiation-induced complications were not observed except for one radiated eye with numerous cotton wool spots and possible radiation retinopathy. CONCLUSIONS: External beam radiation at 5 x 4 Gy may have a modest and short-lived (six month) benefit in preserving visual acuity.

The electronic visual acuity tester: testability in preschool children.

PURPOSE: To evaluate the ability of preschool children to have their threshold visual acuity assessed using a standardized, computer-based letter test. METHODS: Participants were 1195 3.5- to 5-year-old children enrolled in the Vision in Preschoolers Study. Monocular visual acuity was assessed by licensed eye care professionals (optometrists and pediatric ophthalmologists experimented in the examination of children), using the Electronic Visual Acuity tester, which uses the letters H, O, T, and V with a crowded surround. RESULTS: Overall, 99.1% of children passed the training that consisted of identifying the letters H, O, T, and V by naming or matching the letters at 60 cm. Among those who passed the training, 99.6% completed the binocular pretest at 3 m, and 97.6% of those passing the training and the pretest completed monocular threshold visual acuity testing of each eye with the Electronic Visual Acuity tester. Testability increased with age for training (p = 0.03), pretesting (p = 0.04), and acuity testing (p = 0.07). Overall, 93.3% of 3.5-year-olds, 96.7% of 4-year-olds, and 98.8% of 5-year-olds completed training, pretesting, and monocular threshold acuity testing of each eye using standard letter optotypes. CONCLUSION: Using the computer-based Electronic Visual Acuity system, nearly all 3.5- to 5-year-old children can complete monocular acuity testing of each eye.