Predominantly Persistent Intraretinal Fluid in the Comparison of Age-related Macular Degeneration Treatments Trials.

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.

Corneal Endothelial Transplantation in Uveitis: Incidence and Risk Factors.

PURPOSE: To estimate the incidence of corneal endothelial transplantation (CET) and identify risk factors among patients with noninfectious ocular inflammation. DESIGN: Retrospective cohort study. METHODS: Adult patients attending United States tertiary uveitis care facilities diagnosed with noninfectious ocular inflammation were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Time-to-event analysis was used to estimate the incidence of CET, including penetrating keratoplasty, Descemet stripping endothelial keratoplasty, or Descemet membrane endothelial keratoplasty procedures. The incidence of CET was calculated. Potential risk factors for CET were also evaluated using Cox regression, accounting for correlation between eyes of the same patient. RESULTS: Overall, 14,264 eyes met eligibility criteria for this analysis, with a median follow-up of 1.8 eye-years. The Kaplan-Meier estimated incidence of CET within 10 years was 1.10% (95% CI, 0.68%-1.53%). Risk factors for CET included age >60 years vs <40 years (adjusted hazard ratio [aHR], 16.5; 95% CI, 4.70-57.9), anterior uveitis and scleritis vs other types (aHR, 2.97; 95% CI, 1.46-6.05; and aHR, 4.14; 95% CI,1.28-13.4, respectively), topical corticosteroid treatment (aHR, 2.84; 95% CI, 1.32-6.13), cataract surgery (aHR, 4.44; 95% CI, 1.73-11.4), tube shunt surgery (aHR, 11.9; 95% CI, 5.30-26.8), band keratopathy (aHR, 5.12; 95% CI, 2.34-11.2), and hypotony (aHR, 7.38; 95% CI, 3.14-17.4). Duration of uveitis, trabeculectomy, peripheral anterior synechia, and ocular hypertension had no significant association after multivariate adjustment. CONCLUSIONS: In patients with ocular inflammation, CET occurred infrequently. Tube shunt surgery, hypotony, band keratopathy, cataract surgery, and anterior segment inflammation were associated with increased risk of undergoing CET; these factors likely are associated with endothelial cell damage.

Dropped Nucleus during Cataract Surgery in South India: Incidence, Risk Factors, and Outcomes.

PURPOSE: To determine incidence, risk factors for, and outcomes of dropped nucleus (DN) during cataract surgery. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A Precise Method to Evaluate 360 Degree Measures of Optic Cup and Disc Morphology in an African American Cohort and Its Genetic Applications.

(1) Background: Vertical cup-to-disc ratio (CDR) is an important measure for evaluating damage to the optic nerve head (ONH) in glaucoma patients. However, this measure often does not fully capture the irregular cupping observed in glaucomatous nerves. We developed and evaluated a method to measure cup-to-disc ratio (CDR) at all 360 degrees of the ONH. (2) Methods: Non-physician graders from the Scheie Reading Center outlined the cup and disc on digital stereo color disc images from African American patients enrolled in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. After converting the resultant coordinates into polar representation, the CDR at each 360-degree location of the ONH was obtained. We compared grader VCDR values with clinical VCDR values, using Spearman correlation analysis, and validated significant genetic associations with clinical VCDR, using grader VCDR values. (3) Results: Graders delineated outlines of the cup contour and disc boundaries twice in each of 1815 stereo disc images. For both cases and controls, the mean CDR was highest at the horizontal bisector, particularly in the temporal region, as compared to other degree locations. There was a good correlation between grader CDR at the vertical bisector and clinical VCDR (Spearman Correlation OD: r = 0.78 [95% CI: 0.76-0.79]). An SNP in the MPDZ gene, associated with clinical VCDR in a prior genome-wide association study, showed a significant association with grader VCDR (p = 0.01) and grader CDR area ratio (p = 0.02). (4) Conclusions: The CDR of both glaucomatous and non-glaucomatous eyes varies by degree location, with the highest measurements in the temporal region of the eye. This method can be useful for capturing innate eccentric ONH morphology, tracking disease progression, and identifying genetic associations.

Predominantly Persistent Subretinal Fluid in the Comparison of Age-Related Macular Degeneration Treatments Trials.

OBJECTIVE: To describe predominantly persistent subretinal fluid (SRF) in eyes receiving ranibizumab or bevacizumab for neovascular age-related macular degeneration and to compare visual acuity (VA) to eyes with nonpersistent SRF. DESIGN: Cohort within randomized clinical trial. PARTICIPANTS: Comparison of Age-related Macular Degeneration Treatments Trials patients assigned to pro re nata treatment. METHODS: Graders evaluated monthly OCT scans for SRF. Predominantly persistent SRF through week 12 was defined as SRF at baseline and weeks 4, 8, and 12. Predominantly persistent SRF through 1 or 2 years was defined as SRF in 80% or more of visits by years 1 or 2, respectively. Linear regression models including baseline predictors of VA and predominantly persistent intraretinal fluid (IRF) were used to evaluate mean differences in vision outcomes. PRIMARY OUTCOME MEASURES: Predominantly persistent SRF through year 1, adjusted VA score and VA change, and foveal SRF thickness. RESULTS: Among 406 eyes with baseline SRF, SRF persisted in 108 eyes (26.6%) through week 12, in 94 eyes (23.2%) through year 1, and in 77 eyes (19.0%) through year 2. Adjusted VA means at year 1 were similar between eyes with predominantly persistent versus non persistent SRF by week 12 (68.1 vs. 70.2 letters; P = 0.18), year 1 (67.6 vs. 70.2 letters; P = 0.11), and year 2 (71.4 vs. 70.9 letters; P = 0.78). Adjusted changes in mean VA at year 1 were similar between eyes with predominantly persistent versus nonpersistent SRF by week 12 (6.3 vs. 7.6 letters; P = 0.38), year 1 (5.5 vs. 7.8 letters; P = 0.14), and year 2 (8.1 vs. 7.7 letters; P = 0.78). Among eyes with predominantly persistent SRF through year 1, foveal SRF was absent in 46 eyes (48.9%), thickness was 1 to 200 µm in 48 eyes (50.0%) and more than 200 µm in 1 eye (1.1%) at year 1. CONCLUSIONS: Eyes with predominantly persistent and nonpersistent SRF through week 12, year 1, or year 2 showed similar VA outcomes after adjustment for baseline covariates and persistent IRF. At the foveal center, predominantly persistent SRF was most commonly absent or present in small quantities.

Risk of Cataract in Intermediate Uveitis.

PURPOSE: To determine the incidence of and predictive factors for cataract in intermediate uveitis. DESIGN: Retrospective cohort study. METHODS: Patients were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study, in which medical records were reviewed to determine demographic and clinical data of every eye/patient at every visit at 5 participating US tertiary care uveitis centers. The primary outcome was development of vision-compromising cataract as defined by a decrease in visual acuity to 20/40 or less, or requiring cataract surgery. Survival analysis assessed visually defined cataract to avoid bias due to timing of surgery vis-à-vis inflammatory status. RESULTS: Among 2,190 eyes of 1,302 patients with intermediate uveitis, the cumulative incidence of cataract formation was 7.6% by 1 year (95% confidence interval [CI] = 6.2%-9.1%), increasing to 36.6% by 10 years (95% CI = 31.2%-41.6%). Increased cataract risk was observed in eyes with concurrent anterior uveitis causing posterior synechiae (hazard ratio = 2.68, 95% CI = 2.00-3.59, P < .001), and in eyes with epiretinal membrane formation (hazard ratio = 1.54, 95% CI = 1.15-2.07, P = .004). Higher dose corticosteroid therapy was associated with significantly higher incidence of cataract, especially time-updated use of topical corticosteroids ≥2 times/d or ≥4 periocular corticosteroid injections. Low-dose corticosteroid medications (oral prednisone 7.5 mg daily or less, or topical corticosteroid drops <2 times/d) were not associated with increased cataract risk. CONCLUSIONS: Our study found that the incidence of clinically important cataract in intermediate uveitis is moderate. The risk is higher with markers of severity and with higher doses of corticosteroid medications, the latter being potentially modifiable.

Contemporaneous Risk Factors for Visual Acuity in Non-Infectious Uveitis.

INTRODUCTION: We evaluated the associations of clinical and demographic characteristics with visual acuity (VA) with over 5 years in a subspecialty noninfectious uveitis population. METHODS: 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. RESULTS: 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. CONCLUSION: Factors associated with reduced VA included well-known structural complications, and lack of subspecialty care during cataract surgery.

Evaluating TNF-α and Interleukin-2 (IL-2) Levels in African American Primary Open-Angle Glaucoma Patients.

PURPOSE: To establish if SNPs in TNF-α and IL-2 genes are associated with Primary Open-Angle Glaucoma (POAG) in African Americans (AA). We also determined whether plasma TNF-α and IL-2 levels could serve as biomarkers for POAG in African Americans using sandwich enzyme-linked immunosorbent assay. METHODS: A single SNP association analysis was performed to investigate the association between potential gene variants in TNF-α and IL-2 genes and POAG in the AA population. Plasma samples from 190 African Americans (72 from normal subjects and 118 POAG cases) were obtained for TNF- α studies and 367 samples (135 from normal subjects and 232 from POAG cases) were obtained for IL-2 studies. TNF-α levels and IL-2 levels were measured by sandwich enzyme-linked immunosorbent assays (ELISA) and analyzed to see if they reached significance in cases with POAG and endophenotypes when compared to normal subjects. RESULTS: The SNP, rs1800630, in TNF-α gene was found to be marginally associated with POAG. SNPs in IL-2 gene were not associated with POAG in the case-control analysis. No significant difference was found between TNF-α levels and IL-2 levels in normal and POAG case subjects in our study. IL-2 levels were inversely correlated with high IOP in POAG cases. CONCLUSIONS: Although we found a marginal SNP association of TNF-α, assessing the expression levels of TNF-α and IL-2 may serve as promising biomarkers for African American POAG. Further investigation is needed to determine if POAG can be subdivided into more specified cohorts of the disease, which may affect plasma cytokine levels differently.

Localized Optical Coherence Tomography Precursors of Macular Atrophy and Fibrotic Scar in the Comparison of Age-Related Macular Degeneration Treatments Trials.

PURPOSE: To identify precursors of macular atrophy (MA) and of fibrotic scar (FS) in eyes treated with anti-vascular endothelial growth factor through pixel-mapping analysis of baseline optical coherence tomography (OCT). METHODS: Design: Cross-sectional analysis. SETTING: Multicenter clinical trial. PATIENT POPULATION: 68 eyes from the Comparison of Age-Related Macular Degeneration Treatments Trials. INTERVENTION: Treatment with anti-vascular endothelial growth factor agents. MAIN OUTCOME MEASURE: The percentage of MA or FS pixels with each OCT feature at baseline, and the odds ratio for baseline pixels with an OCT feature to develop MA or FS. RESULTS: Retinal pigment epithelium atrophy and photoreceptor loss on OCT were highly predictive of MA at that location at years 2 and 5 (P < .0001), but accounted for only 22.5% of the ensuing atrophy at year 2 and less at year 5. Among pixels of MA at year 2, 78% were preceded by thick drusen, 54% by subretinal macular neovascularization (MNV), and 22.5% by no detectable OCT features. MNV, subretinal hyperreflective material, pigment epithelial detachment, intraretinal fluid, and sub-retinal pigment epithelium fluid were predictive of FS at that location (P values <.05). More than 75% of the pixels of FS at years 2 and 5 were preceded by pixels of baseline MNV. CONCLUSIONS: Most pixels of FS were preceded by components of neovascularization. Although one-quarter of MA was accounted for by pre-existing evidence of atrophy on OCT alone, the development of MA in areas of thick drusen, areas with and without subretinal MNV lesion, and areas without detectable OCT precursors argues that the development of MA is multifactorial and may follow, in part, a non-neovascular pathway.

Remission of Non-Infectious Anterior Scleritis: Incidence and Predictive Factors.

PURPOSE: To assess how often non-infectious anterior scleritis remits and identify predictive factors. METHODS: Our retrospective cohort study at four ocular inflammation subspecialty centers collected data for each affected eye/patient at every visit from center inception (1978, 1978, 1984, 2005) until 2010. Remission was defined as inactivity of disease off all suppressive medications at all visits spanning at least three consecutive months or at all visits up to the last visit (to avoid censoring patients stopping follow-up after remission). Factors potentially predictive of remission were assessed using Cox regression models. RESULTS: During 1,906 years' aggregate follow-up of 832 affected eyes, remission occurred in 214 (170 of 584 patients). Median time-to-remission of scleritis = 7.8 years (95% confidence interval [CI]: 5.7, 9.5). More remissions occurred earlier than later during follow-up. Factors predictive of less scleritis remission included scleritis bilaterality (adjusted hazard ratio [aHR] = 0.46, 95% CI: 0.32-0.65); and diagnosis with any systemic inflammatory disease (aHR = 0.36, 95% CI: 0.23-0.58), or specifically with Rheumatoid Arthritis (aHR = 0.22), or Granulomatosis with Polyangiitis (aHR = 0.08). Statin treatment (aHR = 1.53, 95% CI: 1.03-2.26) within ≤90 days was associated with more remission incidence. CONCLUSIONS: Our results suggest scleritis remission occurs more slowly in anterior scleritis than in newly diagnosed anterior uveitis or chronic anterior uveitis, suggesting that attempts at tapering suppressive medications is warranted after long intervals of suppression. Remission is less frequently achieved when systemic inflammatory diseases are present. Confirmatory studies of whether adjunctive statin treatment truly can enhance scleritis remission (as suggested here) are needed.

Factors Predictive of Remission of Chronic Anterior Uveitis.

PURPOSE: To estimate the incidence of medication-free remission of chronic anterior uveitis and identify predictors thereof. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients diagnosed with anterior uveitis of longer than 3 months' duration followed up at United States tertiary uveitis care facilities. METHODS: Estimation of remission incidence and identification of associated predictors used survival analysis. MAIN OUTCOME MEASURES: 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. RESULTS: 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). CONCLUSIONS: 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.

Outcomes After Transcervical Thymectomy for Ocular Myasthenia Gravis: A Retrospective Cohort Study With Inverse Probability Weighting.

BACKGROUND: The benefit of thymectomy in reducing requirement for corticosteroids, symptom severity, need for immunosuppression, and hospitalization rates in patients with seropositive generalized myasthenia has recently been established. It is unclear whether this benefit applies to patients with myasthenia and purely ocular manifestations (ocular myasthenia gravis [OMG]). METHODS: We conducted a retrospective single-center cohort study of patients with OMG. Patients were included if their diagnosis was confirmed by acetylcholine receptor or muscle-specific kinase antibodies, abnormal electrophysiology, or a positive edrophonium test and at least 1 year of clinical follow-up. At each visit, the presence and severity of ocular and generalized symptoms was ascertained using a 4-point scale. Prednisone dose, steroid-sparing agent use, and need for intravenous immunoglobulin or plasmapheresis were recorded. The effect of thymectomy on time-weighted prednisone dose and symptom severity score was assessed using linear regression models. To adjust for nonrandomization of thymectomy, we used inverse probability weighting using a propensity score model derived from the prethymectomy observation period for thymectomy patients and a 6-month lead-in period for nonthymectomy patients that incorporated age, sex, acetylcholine receptor antibody seropositivity, disease severity (as defined by both symptom severity and treatment requirement), and treating physician preferences. RESULTS: Eighty-two patients (30 with thymectomy and 52 nonthymectomy) were included. In unadjusted analyses, time-weighted daily prednisone dose was 2.9 mg higher with thymectomy compared with nonthymectomy (95% CI: 0.2-5.7), but after inverse probability weighting, this was no longer statistically significant (difference = 1.7 mg, 95% CI: -0.8 to 4.2). There was no statistically significant difference in symptom severity score (adjusted difference = 0.35, 95% CI: -0.02 to 0.72) or risk of generalization (P = 0.22). CONCLUSIONS: In this retrospective study that used statistical techniques to account for nonrandomization, no significant differences in prednisone dose or symptom severity after thymectomy in ocular myasthenia were demonstrated.

Distribution of OCT Features within Areas of Macular Atrophy or Scar after 2 Years of Anti-VEGF Treatment for Neovascular AMD in CATT.

PURPOSE: Macular atrophy and scar increase in prevalence during treatment for neovascular age-related macular degeneration and are associated with poor visual acuity. We sought to identify the distribution of spectral-domain OCT (SD-OCT)-determined features and subretinal lesion thicknesses at sites of macular scar or atrophy after 2 years of treatment in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). DESIGN: Cross-sectional analysis. PARTICIPANTS: CATT participants with SD-OCT, color photographic (CP) and fluorescein angiogram (FA; CP/FA) images at year 2. METHODS: Sixty-eight study eyes at year 2 in CATT were selected based on image quality and CP/FA-determined predominant presence of the following: geographic atrophy (GA, n = 25), non-GA (NGA, n = 44), fibrotic scar (FS, n = 26), or non-FS (NFS, n = 7). The CP/FA components were delineated by CP/FA readers; SD-OCT morphologic features and thicknesses were delineated by OCT readers. Using custom software and graphic user interfaces, images were registered, overlaying features and components per pixel; differences were analyzed across groups. MAIN OUTCOME MEASURES: OCT features, CP/FA components, and retinal and subretinal lesion thicknesses at each pixel of regional overlays. RESULTS: SD-OCT assessment of registered areas of pathology revealed the following: (1) retinal pigment epithelium atrophy (with or without residual lesion material) covered 75% of pixels designated as GA, 22% of NGA, 24% of NFS, and 46% of FS (P < 0.001). (2) Photoreceptor layer thinning covered 85% of GA, 42% of NGA, 33% of NFS, and 59% of FS (P < 0.001). (3) Subretinal lesion features covered 31% of GA, 42% of NGA, 85% of NFS, and 92% of FS (P < 0.001). Mean thickness of the subretinal lesion complex (measured in microns ± standard deviation) differed among GA (48±25 µm), NGA (61±35 µm), NFS (83±17 µm), and FS (151±74 µm) (P < 0.001). In eyes with GA, the thickness was greater in areas with residual lesion (51.4±27 µm) than in those without (27.2±9 µm). CONCLUSIONS: Retinal pigment epithelium atrophy and photoreceptor layer thinning are common not only in areas of macular atrophy but also in areas of FS. Photoreceptor loss extends beyond the areas of clinically apparent atrophy and FS. Subretinal lesion components were common in areas of scar, but they were also present in nearly one-third or more of areas of macular atrophy.

Association of secondhand tobacco smoke exposure during childhood on adult cardiovascular disease risk among never-smokers.

PURPOSE: Adult secondhand tobacco smoke (SHS) exposure is related to stroke and coronary heart disease (CHD) risk, but long-term effects are less clear. We evaluated whether childhood SHS exposure affects subsequent stroke or CHD risk among adult black and white never-smokers followed for stroke and CHD. METHODS: In this prospective cohort study, inverse probability weights were calculated to correct for bias due to attrition and survey nonresponse. Cox proportional hazards models were used to assess hazard ratios and 95% confidence intervals for stroke or CHD, separately, by number of childhood household smokers. RESULTS: Of 13,142 eligible participants, 6136 had childhood SHS exposure assessed. Baseline mean (SD) age was 63.5 (9.0), 65% were female, 30% black, 46% reported 0 childhood household smokers, 36% reported 1, and 18% reported 2+. In 60,649 person-years, 174 strokes were observed (2.9% of participants), and in 45,195 person-years, 114 CHD events were observed (2.1% of participants). The weighted and adjusted hazard ratios (95% confidence intervals) of stroke for 2+ versus 0 childhood household smokers was 1.66 (1.29-2.13) and was 1.15 (0.82-1.59) for CHD. CONCLUSIONS: We observed a significant association between childhood SHS exposure and stroke, but not CHD, after age 45 years and adjusting for missing information.

Fluorometholone 0.1% as Ancillary Therapy for Trachomatous Trichiasis Surgery: Randomized Clinical Trial.

PURPOSE: To assess the hypothesis that fluorometholone 0.1% eye drops are safe and effective as adjunctive therapy for trachomatous trichiasis (TT) surgery; determining the most promising dose. DESIGN: Randomized, placebo-controlled, double-masked parallel dose-ranging clinical trial. METHODS: Patients undergoing upper lid TT surgery at a rural Ethiopian hospital were randomized to fluorometholone 0.1% twice daily for 4 weeks, 4 times daily for 4 weeks, 4 times daily for 8 weeks, or matching frequency placebo in a 3:1:3:1:3:1 ratio for 1 eye. Randomization was stratified by TT severity (1-4 vs ≥5 lashes touching the globe). Safety outcomes (intraocular pressure [IOP] elevation, cataract, and other dose-limiting toxicities) and postoperative TT incidence were assessed over 1 year. RESULTS: Subjects randomized were 39:13:39:13:38:13 in the respective groups, and 1 subject in the 8-weeks fluorometholone group was withdrawn. Of 154 subjects, 148 (96.1%) completed 1 year's follow-up. Among 76 eyes receiving fluorometholone 4 times daily, 1 developed IOP elevation ≥ 30 mm Hg (to 37 mm Hg) and 1 had an allergic reaction attributed to the study drug; each resolved upon drug cessation without sequelae. No cataract or other dose-limiting toxicity events occurred. Postoperative TT within 1 year occurred in 29.3% of placebo eyes vs 17.7%, 19.6%, and 23.2% among the respective fluorometholone groups (P = .29 comparing placebo vs all active treatments combined). CONCLUSIONS: The results suggest fluorometholone 0.1% is likely to be safe and efficacious to reduce postoperative TT following TT surgery, and 1 drop twice daily for 4 weeks is the most promising dose. Confirmation in a full-scale clinical trial is needed before programmatic implementation.

Retrospective, Multicenter Comparison of the Clinical Presentation of Patients Presenting With Diplopia From Giant Cell Arteritis vs Other Causes.

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.

Family History in the Primary Open-Angle African American Glaucoma Genetics Study Cohort.

PURPOSE: To determine the relationship between positive family history (FH) and primary open-angle glaucoma (POAG) diagnosis and clinical presentation in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) cohort. METHODS: FH of POAG in first-degree relatives was assessed in 2365 subjects in the POAAGG cohort. A standardized interview was used to assess FH of glaucoma, demographic characteristics, lifestyle choices, and medical and ocular comorbidities. RESULTS: Positive FH was associated with increased risk of POAG (age-adjusted odds ratio and 95% confidence interval 3.4 [2.8, 4.1]). In age-adjusted analysis among POAG cases, positive FH was associated with younger age (P < .001), female sex (P < .001), hypertension (P = .006), use of hypertension medication (P = .03), and prior glaucoma surgery (P = .02). Cases with positive FH also had thicker retinal nerve fiber layers (P = .03). CONCLUSIONS: The risk conferred by positive FH suggests strong genetic underpinnings for some patients with this disease, which will be investigated by genome-wide association studies and whole exome sequencing. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Orbital ultrasonography in the diagnosis of neoplastic extraocular muscle enlargement.

Neoplastic infiltration of the extraocular muscle (EOM) is a rare condition which can pose a diagnostic dilemma due to its rarity and overlapping ultrasonographic features with orbital myositis. The ultrasonographic features of neoplastic enlargement of EOM have not been systematically studied and previously have been described in only a few case reports. Orbital ultrasonography, in conjunction with the pattern of ocular misalignment, was assessed for its potential role in identifying patients with neoplastic EOM enlargement. Retrospective chart review of patients with neoplasm and myositis. The clinical features of 8 patients with neoplastic infiltration of the EOM were compared to 15 patients with myositis. In the neoplastic group the width of the EOM was (10.5 mm) almost twice the normal width of the muscle with myositis (p < 0.001). All the muscles in the neoplastic category were low to medium reflective. Paretic deviation was seen in 4/8(50%), purely restrictive in 2/8 (25%) and combined pattern in 2/8 (25%) were noted. In the myositis group the average EOM enlargement was 5.8 mm and all muscles showed low reflectivity. Although ultrasonographic features overlapped between the 2 groups paretic deviations were more common in the neoplastic group versus the myositis group (50% versus 7%). Neoplastic muscle enlargement tends to be larger with paretic deviations of ocular motility seen clinically. These findings in a patient with EOM enlargement should raise the suspicion of neoplasm as the etiology and further work up should be considered.

Tolerability of Topical Tocilizumab Eyedrops in Dogs: A Pilot Study.

PURPOSE: The aim of this study was to examine the tolerability of topical tocilizumab eyedrops in normal dogs and to assess whether this preparation alters tear film cytokine levels or conjunctival cytokine mRNA expression. METHODS: Two percent tocilizumab eyedrops were administered to the right eyes and artificial tears to the left eyes of 10 dogs with no anterior segment pathology 3 times daily for 4 weeks. Portable slit-lamp examinations and Schirmer tear testing were performed at baseline and day 1 week 4, as well as 2 weeks after treatment (week 6). Schirmer strips were also used to collect tears for analyses of cytokine levels using multiplex bead array. Median levels of 8 cytokines in the tear film [interferon gamma (IFN-γ), tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1ß, IL-2, IL-6, IL-8, and IL-10] were compared among tocilizumab-treated and control eyes. Conjunctival biopsies from both eyes were collected at week 4, and mRNA levels of cytokines were also evaluated. Blood samples were collected at baseline and at the end of treatment to monitor for changes in complete blood count, basic metabolic panel, or liver function tests. RESULTS: At week 4, conjunctival biopsies and tear samples showed no significant differences in either tear cytokine or mRNA levels for IFN-γ, TNF-α, IL-2, IL-6, IL-8, and IL-10. There was no evidence of local irritation or changes in bloodwork results from the topical tocilizumab formulation. CONCLUSIONS: Topical application of tocilizumab eyedrops was well tolerated when used on healthy dog eyes in this pilot study.

Risk of Ocular Hypertension in Adults with Noninfectious Uveitis.

PURPOSE: To describe the risk and risk factors for ocular hypertension (OHT) in adults with noninfectious uveitis. DESIGN: Retrospective, multicenter, cohort study. PARTICIPANTS: Patients aged ≥18 years with noninfectious uveitis seen between 1979 and 2007 at 5 tertiary uveitis clinics. METHODS: Demographic, ocular, and treatment data were extracted from medical records of uveitis cases. MAIN OUTCOME MEASURES: Prevalent and incident OHT with intraocular pressures (IOPs) of ≥21 mmHg, ≥30 mmHg, and increase of ≥10 mmHg from documented IOP recordings (or use of treatment for OHT). RESULTS: Among 5270 uveitic eyes of 3308 patients followed for OHT, the mean annual incidence rates for OHT ≥21 mmHg and OHT ≥30 mmHg are 14.4% (95% confidence interval [CI], 13.4-15.5) and 5.1% (95% CI, 4.7-5.6) per year, respectively. Statistically significant risk factors for incident OHT ≥30 mmHg included systemic hypertension (adjusted hazard ratio [aHR], 1.29); worse presenting visual acuity (≤20/200 vs. ≥20/40, aHR, 1.47); pars plana vitrectomy (aHR, 1.87); history of OHT in the other eye: IOP ≥21 mmHg (aHR, 2.68), ≥30 mmHg (aHR, 4.86) and prior/current use of IOP-lowering drops or surgery in the other eye (aHR, 4.17); anterior chamber cells: 1+ (aHR, 1.43) and ≥2+ (aHR, 1.59) vs. none; epiretinal membrane (aHR, 1.25); peripheral anterior synechiae (aHR, 1.81); current use of prednisone >7.5 mg/day (aHR, 1.86); periocular corticosteroids in the last 3 months (aHR, 2.23); current topical corticosteroid use [≥8×/day vs. none] (aHR, 2.58); and prior use of fluocinolone acetonide implants (aHR, 9.75). Bilateral uveitis (aHR, 0.69) and previous hypotony (aHR, 0.43) were associated with statistically significantly lower risk of OHT. CONCLUSIONS: Ocular hypertension is sufficiently common in eyes treated for uveitis that surveillance for OHT is essential at all visits for all cases. Patients with 1 or more of the several risk factors identified are at particularly high risk and must be carefully managed. Modifiable risk factors, such as use of corticosteroids, suggest opportunities to reduce OHT risk within the constraints of the overriding need to control the primary ocular inflammatory disease.