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PURPOSE: To describe predominantly persistent intraretinal fluid (PP-IRF) and its association with visual acuity (VA) and retinal anatomic findings at long-term follow-up in eyes treated with pro re nata (PRN) ranibizumab or bevacizumab for neovascular age-related macular degeneration. DESIGN: Cohort within a randomized clinical trial. PARTICIPANTS: Participants in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) assigned to PRN treatment. METHODS: The presence of intraretinal fluid (IRF) on OCT scans was assessed at baseline and monthly follow-up visits by Duke OCT Reading Center. Predominantly persistent intraretinal fluid through week 12, year 1, and year 2 was defined as the presence of IRF at the baseline and in ≥ 80% of follow-up visits. Among eyes with baseline IRF, the mean VA scores (letters) and changes from the baseline were compared between eyes with and those without PP-IRF. Adjusted mean VA scores and changes from the baseline were also calculated using the linear regression analysis to account for baseline patient features identified as predictors of VA in previous CATT studies. Furthermore, outcomes were adjusted for concomitant predominantly persistent subretinal fluid. MAIN OUTCOME MEASURES: Predominantly persistent intraretinal fluid through week 12, year 1, and year 2; VA score and VA change; and scar development at year 2. RESULTS: Among 363 eyes with baseline IRF, 108 (29.8%) had PP-IRF through year 1 and 95 (26.1%) had PP-IRF through year 2. When eyes with PP-IRF through year 1 were compared with those without PP-IRF, the mean 1-year VA score was 62.4 and 68.5, respectively (P = 0.002), and was 65.0 and 67.4, respectively (P = 0.13), after adjustment. Predominantly persistent intraretinal fluid through year 2 was associated with worse adjusted 1-year mean VA scores (64.8 vs. 69.2; P = 0.006) and change (4.3 vs. 8.1; P = 0.01) as well as worse adjusted 2-year mean VA scores (63.0 vs. 68.3; P = 0.004) and changes (2.4 vs. 7.1; P = 0.009). Predominantly persistent intraretinal fluid through year 2 was associated with a higher 2-year risk of scar development (adjusted hazard ratio = 1.49; P = 0.03). CONCLUSIONS: Approximately one quarter of eyes had PP-IRF through year 2. Predominantly persistent intraretinal fluid through year 1 was associated with worse long-term VA, but the relationship disappeared after adjustment for baseline predictors of VA. Predominantly persistent intraretinal fluid through year 2 was independently associated with worse long-term VA and scar development.

PURPOSE: To determine effects of continued or discontinued use of omega-3 (ω3) fatty acid supplements through a randomized withdrawal trial among patients assigned to ω3 supplements in the first year of the DREAM study. METHODS: Patients who were initially assigned to ω3 (3000 mg) for 12 months in the primary trial were randomized 1:1 to ω3 active supplements or placebos (refined olive oil) for 12 more months. The primary outcome was change in the Ocular Surface Disease Index (OSDI) score. Secondary outcomes included change in conjunctival staining, corneal staining, tear break-up time, Schirmer test, and adverse events. RESULTS: Among 22 patients assigned to ω3 and 21 to placebo supplements, the mean change in OSDI score between month 12 and 24 was similar between treatment groups (mean difference in change -0.6 points, 95% confidence interval [CI], (-10.7, 9.5), p = 0.91). There were no significant differences between groups in mean change in conjunctival staining (difference in mean change -0.5 points; 95% CI (-1.2, 0.3)), corneal staining (-0.3 points; 95% CI (-1.2, 0.3)), tear break-up time (-0.8 s; 95% CI (-2.6, 0.9)) and Schirmer test (0.6 mm, 95% CI (-2.0, 3.2)). Rates of adverse events were similar in both groups. CONCLUSION: Among patients who received ω3 supplements for 12 months in the primary trial, those discontinuing use of ω3 for an additional 12 months did not have significantly worse outcomes compared to those who continued use of ω3. ClinicalTrials.gov number NCT02128763.

We report results from a multicenter, randomized clinical trial (N=535) of the effect of ω-3 supplementation, relative to placebo, on exploratory and minimally invasive outcome measures for moderate to severe dry eye disease.

BackgroundDry eye disease is a common chronic condition that is characterized by ocular discomfort and visual disturbances that decrease quality of life. Many clinicians recommend the use of supplements of n-3 fatty acids (often called omega-3 fatty acids) to relieve symptoms.MethodsIn a multicenter, double-blind clinical trial, we randomly assigned patients with moderate-to-severe dry eye disease to receive a daily oral dose of 3000 mg of fish-derived n-3 eicosapentaenoic and docosahexaenoic acids (active supplement group) or an olive oil placebo (placebo group). The primary outcome was the mean change from baseline in the score on the Ocular Surface Disease Index (OSDI; scores range from 0 to 100, with higher scores indicating greater symptom severity), which was based on the mean of scores obtained at 6 and 12 months. Secondary outcomes included mean changes per eye in the conjunctival staining score (ranging from 0 to 6) and the corneal staining score (ranging from 0 to 15), with higher scores indicating more severe damage to the ocular surface, as well as mean changes in the tear break-up time (seconds between a blink and gaps in the tear film) and the result on Schirmer's test (length of wetting of paper strips placed on the lower eyelid), with lower values indicating more severe signs.ResultsA total of 349 patients were assigned to the active supplement group and 186 to the placebo group; the primary analysis included 329 and 170 patients, respectively. The mean change in the OSDI score was not significantly different between the active supplement group and the placebo group (-13.9 points and -12.5 points, respectively; mean difference in change after imputation of missing data, -1.9 points; 95% confidence interval [CI], -5.0 to 1.1; P=0.21). This result was consistent across prespecified subgroups. There were no significant differences between the active supplement group and the placebo group in mean changes from baseline in the conjunctival staining score (mean difference in change, 0.0 points; 95% CI, -0.2 to 0.1), corneal staining score (0.1 point; 95% CI, -0.2 to 0.4), tear break-up time (0.2 seconds; 95% CI, -0.1 to 0.5), and result on Schirmer's test (0.0 mm; 95% CI, -0.8 to 0.9). At 12 months, the rate of adherence to treatment in the active supplement group was 85.2%, according to the level of n-3 fatty acids in red cells. Rates of adverse events were similar in the two trial groups.ConclusionsAmong patients with dry eye disease, those who were randomly assigned to receive supplements containing 3000 mg of n-3 fatty acids for 12 months did not have significantly better outcomes than those who were assigned to receive placebo. (Funded by the National Eye Institute, National Institutes of Health; DREAM ClinicalTrials.gov number, NCT02128763 .).

BackgroundDry eye disease is a common chronic condition that is characterized by ocular discomfort and visual disturbances that decrease quality of life. Many clinicians recommend the use of supplements of n-3 fatty acids (often called omega-3 fatty acids) to relieve symptoms.MethodsIn a multicenter, double-blind clinical trial, we randomly assigned patients with moderate-to-severe dry eye disease to receive a daily oral dose of 3000 mg of fish-derived n-3 eicosapentaenoic and docosahexaenoic acids (active supplement group) or an olive oil placebo (placebo group). The primary outcome was the mean change from baseline in the score on the Ocular Surface Disease Index (OSDI; scores range from 0 to 100, with higher scores indicating greater symptom severity), which was based on the mean of scores obtained at 6 and 12 months. Secondary outcomes included mean changes per eye in the conjunctival staining score (ranging from 0 to 6) and the corneal staining score (ranging from 0 to 15), with higher scores indicating more severe damage to the ocular surface, as well as mean changes in the tear break-up time (seconds between a blink and gaps in the tear film) and the result on Schirmer's test (length of wetting of paper strips placed on the lower eyelid), with lower values indicating more severe signs.ResultsA total of 349 patients were assigned to the active supplement group and 186 to the placebo group; the primary analysis included 329 and 170 patients, respectively. The mean change in the OSDI score was not significantly different between the active supplement group and the placebo group (-13.9 points and -12.5 points, respectively; mean difference in change after imputation of missing data, -1.9 points; 95% confidence interval [CI], -5.0 to 1.1; P=0.21). This result was consistent across prespecified subgroups. There were no significant differences between the active supplement group and the placebo group in mean changes from baseline in the conjunctival staining score (mean difference in change, 0.0 points; 95% CI, -0.2 to 0.1), corneal staining score (0.1 point; 95% CI, -0.2 to 0.4), tear break-up time (0.2 seconds; 95% CI, -0.1 to 0.5), and result on Schirmer's test (0.0 mm; 95% CI, -0.8 to 0.9). At 12 months, the rate of adherence to treatment in the active supplement group was 85.2%, according to the level of n-3 fatty acids in red cells. Rates of adverse events were similar in the two trial groups.ConclusionsAmong patients with dry eye disease, those who were randomly assigned to receive supplements containing 3000 mg of n-3 fatty acids for 12 months did not have significantly better outcomes than those who were assigned to receive placebo. (Funded by the National Eye Institute, National Institutes of Health; DREAM ClinicalTrials.gov number, NCT02128763 .).

To determine the correlations among symptoms and signs of dry eye disease (DED) in the Dry Eye Assessment and Management (DREAM) study. A total of 535 patients with moderate-to-severe DED were assessed for symptoms using the Ocular Surface Disease Index (OSDI) and four DED signs in both eyes (conjunctival lissamine green staining, corneal fluorescein staining, Schirmer's testing, and tear break-up time (TBUT)) following standardized protocols at baseline and follow-up visits (months 3, 6, and 12). Spearman correlation coefficients (rho) were calculated for correlations among symptoms and signs of DED at baseline and among changes in symptoms and signs from baseline at 12 months. The confidence intervals and p-values for correlation coefficients were calculated using a cluster bootstrapping to account for inter-eye correlation. At baseline, OSDI total score was not correlated with signs; however, OSDI subscale score of ocular symptoms was weakly correlated with corneal staining score (rho = 0.14, p =.002) and Schirmer test score (rho = 0.11, p =.01). There were statistically significant correlations among the four signs (p <.001), with absolute correlation coefficient ranging from 0.14 (conjunctival staining score vs. TBUT) to 0.33 (conjunctival staining score vs. cornea staining score). The correlations among changes in symptoms and signs were weaker, with the highest correlation between change in conjunctival staining and corneal staining (rho = 0.21, p <.001). Consistent with previous studies, among DREAM participants with moderate-to-severe DED at baseline, correlations of DED symptoms with signs were low and correlations among four objective signs were low to moderate. The correlations among changes in symptoms and signs were even weaker. [ABSTRACT FROM AUTHOR]

To determine incidence, risk factors for, and outcomes of dropped nucleus (DN) during cataract surgery. This is a matched case–control study at the Aravind Eye Hospital in Madurai, India. Out of 184 consecutive DN cases, 171 were included. The case immediately preceding the DN case by the same surgeon served as matched concurrent control. The proportion of cataract surgeries with DN was calculated with a 95% confidence interval (CI). Conditional logistic regression was used to generate odds ratios for potential risk factors. Among 415,487 consecutive cataract surgeries, incidence risk of DN was 0.044% [95% CI 0.038%, 0.051%], or 0.44 per 1,000 surgeries in 52 months. Significant preoperative risk factors were posterior polar cataract (adjusted odds ratio [aOR] 21.73, p =.003); suspected loose zonules (aOR 8.85, p <.001); older age (aOR 1.57, p =.001); and presence of diabetes mellitus (aOR 1.79, p =.03). Associated intraoperative complications included zonular dialysis (OR 34.49, p <.001), vitreous disturbance (OR 193.36, p <.001), and posterior capsule rent (OR 384.39, p <.001). Phacoemulsification and manual small incision cataract surgery did not significantly differ in DN incidence. DN most commonly occurred during nucleus removal (35.1%) or during/immediately following hydrodissection (24.0%). Visual outcomes of DN were worse than controls on average, but 51.9% achieved visual acuity 20/40 or better at 1 month. DN occurred rarely, with low absolute risk even when a strong risk factor was present. Nearly all cases followed posterior capsular rent or zonular dialysis, usually with observed vitreous loss. In spite of increased risk of postoperative complications in the DN group, the majority achieved favorable results. [ABSTRACT FROM AUTHOR]

Background: Prospective and longitudinal studies assessing the utility of spectral-domain optical coherence tomography (SD-OCT) to differentiate papilledema from pseudopapilledema are lacking. We studied the sensitivity and specificity of baseline and longitudinal changes in SD-OCT parameters with 3D segmentation software to distinguish between papilledema and pseudopapilledema in a cohort of patients referred for evaluation of undiagnosed optic disc elevation. Methods: Fifty-two adult patients with optic disc elevation were enrolled in a prospective longitudinal study. A diagnosis of papilledema was made when there was a change in the appearance of the optic disc elevation on fundus photographs as noted by an independent observer at or before 6 months. The degree of optic disc elevation was graded using the Frisen scale and patients with mild optic disc elevation (Frisen grades 1 and 2) were separately analyzed. SD-OCT parameters including peripapillary retinal nerve fiber layer (pRNFL), total retinal thickness (TRT), paracentral ganglion cell layer–inner plexiform layer (GCL-IPL) thickness, and optic nerve head volume (ONHV) at baseline and within 6 months of follow-up were measured. Results: Twenty-seven (52%) patients were diagnosed with papilledema and 25 (48%) with pseudopapilledema. Among patients with mild optic disc elevation (Frisen grades 1 and 2), baseline pRNFL (110.1 µm vs 151.3 µm) and change in pRNFL (ΔpRNFL) (7.3 µm vs 52.3 µm) were greater among those with papilledema. Baseline and absolute changes in TRT and ONHV were also significantly higher among patients with papilledema. The mean GCL-IPL thickness was similar at baseline, but there was a small reduction in GCL-IPL thickness among patients with papilledema. Receiver operator curves (ROCs) were generated; ΔpRNFL (0.93), ΔTRT (0.94), and ΔONHV (0.95) had the highest area under the curve (AUC). Conclusions: The mean baseline and absolute changes in SD-OCT measurements (pRFNL, TRT, and ONHV) were significantly greater among patients with papilledema, and remained significantly greater when patients with mild optic disc elevation were separately analyzed. ROCs demonstrated that ΔpRNFL, ΔTRT, and ΔONHV have the highest AUC and are best able to differentiate between papilledema and pseudopapilledema. [ABSTRACT FROM AUTHOR]

We evaluated the associations of clinical and demographic characteristics with visual acuity (VA) with over 5 years in a subspecialty noninfectious uveitis population. Retrospective data from 5,530 noninfectious uveitis patients were abstracted by expert reviewers, and contemporaneous associations of VA with demographic and clinical factors were modeled. Patients were a median of 41 years old, 65% female, and 73% white. Eyes diagnosed ≥5 years prior to cohort entry had worse VA (−1.2 lines) than those diagnosed <6 months prior, and eyes with cataract surgery performed prior to entry had worse VA (−5.9 lines) than those performed during follow-up. Vitreous haze (−4.2 lines for 3+ vs quiet), hypotony (−2.5 lines for ≤5 mm Hg vs 6–23 mm Hg), and CNV (−1.8 lines) all were strongly associated with reduced VA. Factors associated with reduced VA included well-known structural complications, and lack of subspecialty care during cataract surgery. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated visual acuity (VA) over 5 years in a subspecialty noninfectious uveitis population.Methods: Retrospective data from 5,530 noninfectious uveitis patients with anterior, intermediate, posterior or panuveitis were abstracted by expert reviewers. Mean VA was calculated using inverse probability of censoring weighting to account for losses to follow-up.Results: Patients were a median of 41 years old, 65% female, and 73% white. Initial mean VA was worse among panuveitis (20/84) than posterior (20/64), intermediate (20/47), and anterior (20/37) uveitides. On average, mean VA improved by 0.62, 0.51, 0.37, and 0.26 logMAR-equivalent lines over 2 years, respectively (each P < .001), then remained stable, except posterior uveitis mean VA worsened to initial levels.Conclusion: Mean VA of uveitic eyes improved and, typically, improvement was sustained under uveitis subspecialty care. Because VA tends to improve under tertiary care, mean VA change appears a better outcome for clinical studies than time-to-loss of VA. [ABSTRACT FROM AUTHOR]

To evaluate the association of dry eye disease (DED) severity with work productivity and activity impairment. Longitudinal, observational study within a randomized clinical trial. People with moderate to severe DED who enrolled in the multicenter Dry Eye Assessment and Management (DREAM) study. Participants completed the Work Productivity and Activity Impairment questionnaire at 0, 6, and 12 months and were assessed in parallel for symptoms and signs (conjunctival and corneal staining, tear film break-up time [TBUT], and Schirmer test) of DED. Associations of work productivity and activity impairment with symptom and signs were evaluated with linear regression models using generalized estimating equations and controlling for demographics and comorbidities. Work productivity (employment, absenteeism, presenteeism, overall work impairment) and activity impairment. Among 535 participants at baseline, 279 (52%) were employed, and mean activity impairment was 24.5%. Among those employed, the mean score was 2% for absenteeism, 18% for presenteeism, and 19.6% for overall work impairment. Higher Ocular Surface Disease Index (OSDI) symptom scores were associated with greater absenteeism, presenteeism, and activity impairment. Overall work impairment and activity impairment were greater by 4.3% and 4.8%, respectively, per 10-unit difference in OSDI score (P < 0.001). Longitudinal increases (worsening) in OSDI scores were associated with increasing impairment in work and non–work-related activity: 2.0% and 3.1% per 10 units in OSDI, respectively (P < 0.01). Worse corneal staining and TBUT were associated with higher overall work impairment and activity level (P ≤ 0.04). However, longitudinal changes in these two signs were not associated with changes in work productivity or activity impairment. Worse symptoms of DED are associated with decreased work productivity and activity level, both cross-sectionally (interindividually) and longitudinally within person (intraindividually). Corneal staining and TBUT are associated with interindividual differences but not intraindividual changes in work productivity and activity impairment. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association of quality of life (QoL) with ocular structure and function in glaucoma patients, and to identify which aspects of QoL are most closely tied to Visual Field (VF) and Visual Acuity (VA). Methods: We conducted a comprehensive review of studies on QoL in glaucoma patients using PubMed, Web of Science, and Google Scholar (from 1 January 1997 to 7 December 2019). A total of 21 studies in the United States that used the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ) or 51-item NEI VFQ were included. A descriptive analysis of data from the selected studies was conducted. The association between QoL scores and visual function and structure was investigated by ranking the strength of association on a scale from 1 (weakest) to 12 (strongest). Results: Studies reported correlations between QoL scores and Visual Structure. Associations were also reported between QoL and Visual Function both cross-sectionally and longitudinally, with a stronger association of VF and VA with distance activities (average ranking 9.1 and 9.6), vision-specific dependency (8.7 and 8.9), and driving (8.6 and 9.7). Vision-specific mental health (6.5 and 4.9), vision-specific social functioning (8.4 and 6.2), and vision-specific role difficulties (7.1 and 6.6) domains were more associated with VF than with VA. Conclusion: Our study was the first to quantify and rank the strength of association between visual function and QoL domains. Driving and psycho-social QoL domains tended to be most affected by glaucoma-related deterioration of visual function. QoL scores could be used for more patient-centered disease management. [ABSTRACT FROM AUTHOR]

Background: We prospectively evaluated the sensitivity and specificity of ocular ultrasonography (OUS) to distinguish papilledema from pseudopapilledema. Methods: Forty-nine study participants, with optic disc elevation, underwent neuro-ophthalmic evaluation, OUS, fundus photography, and optical coherence tomography (OCT) of the optic nerve head at the initial and follow-up visits (#6 months apart). Participants were classified as having papilledema if there was a change in optic nerve appearance on fundus photographs, as determined by a masked observer, between initial and follow-up visits #6 months apart. OUS was considered positive when the optic nerve sheath width was .3.3 mm and the 30° test was positive. Ocular ultrasonographic findings were correlated in patients who had papilledema vs patients who had pseudopapilledema. In a subanalysis, OUS findings were also correlated with change in peripapillary retinal nerve fiber layer thickness on OCT of the optic nerve head between initial and follow-up visits. Results: OUS was 68% (17/25) sensitive for papilledema and 54% (13/24) specific for pseudopapilledema. When using OCT parameters to define papilledema, the sensitivity of OUS to diagnose papilledema decreased to 62%. Positive OUS correlated with elevated opening pressure on lumbar puncture and with signs of increased intracranial pressure on MRI. Conclusion: OUS alone was less sensitive in diagnosing papilledema than previously thought. Therefore, OUS may not be helpful in distinguishing between papilledema and pseudopapilledema. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate associations between visual function and the level of uncorrected hyperopia in 4‐ and 5‐year‐old children without strabismus or amblyopia. Methods: Children with spherical equivalent (SE) cycloplegic refractive error of −0.75 to +6.00 on eligibility testing for the Vision in Preschoolers–Hyperopia in Preschoolers (VIP‐HIP) study were included. Children were grouped as emmetropic (<1D SE myopia or hyperopia), low hyperopic (+1 to <+3D SE) or moderate hyperopic (+3 to +6D SE). Children with anisometropia or astigmatism (≥1D), amblyopia or strabismus were excluded. Visual functions assessed were monocular distance visual acuity (VA) and binocular near VA with crowded HOTV charts, accommodative lag using the Monocular Estimation Method and near stereoacuity by 'Preschool Assessment of Stereopsis with a Smile'. Visual functions were compared as continuous measures among refractive error groups. Results: 554 children (mean age 58 months) were included in the analysis. Mean SE (SD) {N} for emmetropia, low and moderate hyperopia were +0.52D (0.49) {N = 270}, +2.18D (0.57) {N = 171} and +3.95D (0.78) {N = 113}, respectively. There was a consistent trend of poorer visual function with increasing hyperopia (p < 0.001). Although all children had age‐normal distance VA, logMAR (Snellen) VA of 0.00 (6/6) or better was achieved (distance, near) among more emmetropic (52%, 26%) and low hyperopic (47%, 15%) children than moderate hyperopes (25%, 9%). Mean (SD) distance logMAR VA declined from emmetropic 0.05 (0.10), to low hyperopic 0.06 (0.10) to moderately hyperopic children 0.12 (0.11) (p < 0.001); A mild progressive decrease in near VA also was observed from the emmetropic 0.13 (0.11) to low hyperopic 0.15 (0.10) to moderate hyperopic 0.19 (0.11) groups, (p < 0.001). Accommodative responses showed an increased lag with increasing hyperopia (ρ = 0.50, p < 0.001). Median near stereoacuity for emmetropes, low and moderate hyperopes was 40, 60 and 120 sec arc, respectively. The percentage of these groups with no reduced near visual functions was 83%, 61%, and 34%, respectively. Conclusions: Decreasing visual function was associated with increasing hyperopia in 4‐ and 5‐year‐olds without strabismus or amblyopia. As hyperopia with reduced visual function has been associated with early literacy deficits, near visual function should be evaluated in these children. [ABSTRACT FROM AUTHOR]

Purpose: Chronic kidney disease (CKD) patients often develop cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess the association between progression of retinopathy and concurrent incidence of CVD events in participants with CKD. Design: We assessed 1051 out of 1936 participants in the Chronic Renal Insufficiency Cohort Study that were invited to have fundus photographs obtained at two timepoints separated by 3.5 years, on average. Methods: Using standard protocols, presence and severity of retinopathy (diabetic, hypertensive or other) and vessel diameter calibre were assessed at a retinal image reading centre by trained graders masked to study participants' information. Participants with a self-reported history of CVD were excluded. Incident CVD events were physician adjudicated using medical records and standardised criteria. Kidney function and proteinuria measurements along with CVD risk factors were obtained at study visits. Results: Worsening of retinopathy by two or more steps in the EDTRS retinopathy grading scale was observed in 9.8% of participants, and was associated with increased risk of incidence of any CVD in analysis adjusting for other CVD and CKD risk factors (OR 2.56, 95% CI 1.25 to 5.22, p<0.01). After imputation of missing data, these values were OR=1.66 (0.87 to 3.16), p=0.12. Conclusion: Progression of retinopathy is associated with higher incidence of CVD events, and retinal-vascular pathology may be indicative of macrovascular disease even after adjustment for kidney diseases and CVD risk factors. Assessment of retinal morphology may provide important information when assessing CVD in patients with CKD. [ABSTRACT FROM AUTHOR]

To estimate the incidence of medication-free remission of chronic anterior uveitis and identify predictors thereof. Retrospective cohort study. Patients diagnosed with anterior uveitis of longer than 3 months' duration followed up at United States tertiary uveitis care facilities. Estimation of remission incidence and identification of associated predictors used survival analysis. Incidence of medication-free remission. For the primary analysis, remission was defined as inactive uveitis while off treatment at all visits spanning an interval of at least 90 days or—for patients who did not return for follow-up after 90 days—remaining inactive without receiving suppressive medications at all of the last visits. Association of factors potentially predictive of medication-free remission was also studied. Two thousand seven hundred ninety-five eyes of 1634 patients with chronic anterior uveitis were followed up over 7936 eye-years (4676 person-years). The cumulative medication-free, person-year remission incidence within 5 years was 32.7% (95% confidence interval [CI], 30.4%–35.2%). Baseline clinical factors predictive of reduced remission incidence included longer duration of uveitis at presentation (for 2 to 5 years vs. less than 6 months: adjusted hazard ratio [aHR], 0.61; 95% CI, 0.44–0.83), bilateral uveitis (aHR, 0.75; 95% CI, 0.59–0.96), prior cataract surgery (aHR, 0.70; 95% CI 0.56–0.88), and glaucoma surgery (aHR, 0.63; 95% CI, 0.45–0.90). Two time-updated characteristics were also predictive of reduced remission incidence: keratic precipitates (aHR, 0.36; 95% CI, 0.21–0.60) and synechiae (aHR, 0.62; 95% CI, 0.41–0.93). Systemic diagnosis with juvenile idiopathic arthritis and spondyloarthropathy were also associated with reduced remission incidence. Older age at presentation was associated with higher incidence of remission (for age ≥40 years vs. <40 years: aHR, 1.29; 95% CI, 1.02–1.63). Approximately one third of patients with chronic anterior uveitis remit within 5 years. Longer duration of uveitis, younger age, bilateral uveitis, prior cataract surgery, glaucoma surgery, presence of keratic precipitates and synechiae, and systemic diagnoses of juvenile idiopathic arthritis and spondyloarthropathy predict reduced remission incidence; patients with these factors should be managed taking into account the higher probability of a longer disease course. [ABSTRACT FROM AUTHOR]

Aims To determine the association of single nucleotide polymorphisms (SNPs) downstream from the TMCO1 gene with primary open-angle glaucoma (POAG) in African Americans (AA). Methods AA subjects were recruited for the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study from the Scheie Eye Institute and its satellite sites in Philadelphia. A region containing an AluJb repeat and seven SNPs, including rs4656461 near the TMCO1 gene, were PCR-Sanger sequenced from POAAGG cases (n=1537) and controls (n=1570). Association between POAG and SNPs near TMCO1 was investigated by logistic regression analysis. Phenotypic trait associations with these SNPs were assessed by analysis of variance. Electrophoretic mobility shift assay (EMSA) was performed to assess the affinity of human T-box 5 (TBX5) protein for a predicted binding motif in the TMCO1 region. Dual Luciferase assays were performed by transfecting recombinant plasmids containing the region surrounding the above SNPs in HEK293T and trabecular meshwork cells. Results The SNP rs4657473 (C>T) was associated with POAG; the TT genotype was protective (OR 0.20, 95% CI 0.09 to 0.42; p<0.001). No significant associations were found between the TMCO1 variants and phenotypic traits. EMSA confirmed the affinity of TBX5 for a predicted binding motif containing TMCO1 SNP rs4657475. Luciferase assays demonstrated a regulatory function for the genomic region around SNP rs4656561, located within AluJb repeat. Conclusion Our results demonstrate that a SNP downstream of TMCO1, rs4657473, is associated with POAG in an AA population. Our studies suggest a regulatory role for the previously POAG-associated locus near the TMCO1 gene that may affect gene expression. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the association between gender and primary open-angle glaucoma (POAG) among African Americans and to assess demographic, systemic, and behavioral factors that may contribute to differences between genders. The Primary Open-Angle African American Glaucoma Genetics (POAAGG) study had a case-control design and included African Americans 35 years and older, recruited from the greater Philadelphia, Pennsylvania. Diagnosis of POAG was based on evidence of both glaucomatous optic nerve damage and characteristic visual field loss. Demographic and behavioral information, history of systemic diseases and anthropometric measurements were obtained at study enrollment. Gender differences in risk of POAG were examined using multivariate logistic regression. A total of 2,290 POAG cases and 2,538 controls were included in the study. The percentage of men among cases was higher than among controls (38.6% vs 30.3%, P<0.001). The subjects’ mean age at enrollment was significantly higher for cases compared to controls (70.2±11.3 vs. 61.6±11.8 years, P<0.003). Cases had lower rates of diabetes (40% vs. 46%, P<0.001), higher rates of systemic hypertension (80% vs. 72%, P<0.001), and lower body mass index (BMI) (29.7±6.7 vs. 31.9±7.4, P<0.001) than controls. In the final multivariable model, male gender was significantly associated with POAG risk (OR, 1.64; 95% CI, 1.44–1.87; P<0.001), after adjusting for age, systemic hypertension, diabetes, and BMI. Within the POAAGG study, men were at higher risk of having POAG than women. Pending genetic results from this study will be used to better understand the underlying genetic variations that may account for these differences. [ABSTRACT FROM AUTHOR]

Abstract Mitochondrial dysfunction has been implicated in the pathogenesis of primary open-angle glaucoma (POAG). However, the potential significance of mitochondrial DNA (mtDNA) haplogroups to POAG has not been evaluated in the overaffected African American population. To investigate the association of mtDNA haplogroups with POAG and its phenotypic characteristics, genotyping data from 4081 African American subjects (1919 cases and 2162 controls) was analyzed using 1293 positions on mtDNA. The overall frequency of mtDNA haplogroups in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study cohort was 37% L3, 29% L2, 21% L1, 4% L0, and 10% non-African haplogroups (non-L). When all haplogroups (L0, L1, L2, and non-L) were compared against theL3 reference group, after adjusting by age and principal component of ancestry, the non-L3 haplogroups showed higher risk of POAG (OR-1.19, p = 0.02), with a particularly strong association among males (OR = 1.41, p = 0.003). More specifically the non-L group was associated with higher POAG risk than the L3 haplogroup (OR = 1.77, p = 0.007, Bonferroni adjusted p = 0.027) and to the L3e (n = 256, OR = 1.92, p = 0.007, Bonferroni adjusted p = 0.029). No significant association was found when genders were analyzed together or in female only analysis. There were no significant differences in various POAG endophenotypes across mtDNA haplogroups. This study expands our knowledge of mitochondrial genetics and mtDNA haplogroup associations in African American POAG. Further work is needed to better understand the functional role of mtDNA polymorphisms and their interactions with nuclear genes that affect POAG. [ABSTRACT FROM AUTHOR]

Background: Although giant cell arteritis (GCA) is a well-known cause of transient and permanent vision loss, diplopia as a presenting symptom of this condition is uncommon. We compared symptoms and signs of patients presenting with diplopia from GCA to those from other causes. Methods: This was a multicenter, retrospective study comparing the clinical characteristics of patients presenting with diplopia from GCA with age-matched controls. Demographic information, review of symptoms, ophthalmic examination, and laboratory data of biopsy-proven patients with GCA were compared with those of age-matched controls presenting with diplopia. Results: A total of 27 patients presented with diplopia from GCA, 19 with constant diplopia, and 8 with transient diplopia. All patients with constant diplopia from GCA were matched with 67 control subjects who had diplopia from other etiologies. Patients with GCA were more likely to describe other accompanying visual symptoms (58% vs 25%, P = 0.008), a greater number of systemic GCA symptoms (3.5, GCA vs 0.6, controls, P < 0.001) such as headache (94% [17/18] vs 39% [23/67]; P < 0.001), jaw claudication (80% [12/15] vs 0% [0/36]; P < 0.001), and scalp tenderness (44% [7/16] vs 7% [3/43]; P < 0.001). Ocular ischemic lesions (26% vs 1%, P < 0.001) were also common in patients with diplopia from GCA. Inflammatory markers were elevated significantly in patients with GCA vs controls (erythrocyte sedimentation rate: 91% [10/11] vs 12% [3/25], P < 0.001; C-reactive protein: 89% [8/9] vs 11% [2/19], P < 0.001). Conclusions: GCA is a rare but serious cause of diplopia among older adults and must be differentiated from other more common benign etiologies. Our study suggests that most patients with diplopia from GCA have concerning systemic symptoms and/or elevated inflammatory markers that should trigger further work-up. Moreover, careful ophthalmoscopic examination should be performed to look for presence of ocular ischemic lesions in older patients presenting with acute diplopia. [ABSTRACT FROM AUTHOR]