OCULAR HYPERTENSION AFTER INTRAVITREAL DEXAMETHASONE (OZURDEX) SUSTAINED-RELEASE IMPLANT.

PURPOSE: To evaluate ocular hypertension (OHT) after Ozurdex injection to determine the incidence of OHT, therapy for OHT, and any associative factors such as diagnosis, underlying glaucoma and therapy, or sequential Ozurdex injection(s). METHODS: Retrospective consecutive case series with patients receiving one or more intravitreal Ozurdex implantations at a tertiary care academic center. Ocular hypertension was defined as a single measurement of ≥30 mmHg or an increase of ≥10 mmHg from baseline. RESULTS: Ninety-four injections in 52 patients (59 eyes) were reviewed. Forty eyes received a single injection, and 19 eyes received multiple injections. Ocular hypertension developed in 14 patients (26.9%). Thirteen patients (25%) had preexisting glaucoma or suspicion of glaucoma, and 6 of these developed OHT. Glaucoma eye drops were initiated after 13 injections (13.8%). Invasive surgery for glaucoma was required in 3 patients (3.2%): all had glaucoma or suspicion of glaucoma (one case was related to neovascular glaucoma and unlikely related to steroid response after Ozurdex). There was no difference in relative intraocular pressure increase (i.e., difference between final follow-up or subsequent intravitreal injection vs. baseline) between single versus multiple Ozurdex injections (P = 0.883). CONCLUSION: Patients (26.9%) who received Ozurdex developed OHT. Glaucoma or glaucoma-suspicion factors were present in all patients who required invasive surgery for glaucoma. A greater proportion of patients who received multiple injections had an intraocular pressure elevation, but the relative intraocular pressure increase was not significant.

Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration.

PURPOSE: Unhealthy lifestyles have been associated with increased odds for age-related macular degeneration (AMD). Whether this association is modified by genetic risk for AMD is unknown and was investigated. DESIGN: Interactions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalence of AMD, assessed 6 years later. PARTICIPANTS: Women 50 to 79 years of age in the Carotenoids in Age-Related Eye Disease Study with exposure and AMD data (n=1663). METHODS: Healthy lifestyle scores (0-6 points) were assigned based on Healthy Eating Index scores, physical activity (metabolic equivalent of task hours/week), and smoking pack years assessed in 1994 and 1998. Genetic risk was based on Y402H in complement factor H (CFH) and A69S in age-related maculopathy susceptibility locus 2 (ARMS2). Additive and multiplicative interactions in odds ratios were assessed using the synergy index and a multiplicative interaction term, respectively. MAIN OUTCOME MEASURES: AMD presence and severity were assessed from grading of stereoscopic fundus photographs taken in 2001-2004. AMD was present in 337 women, 91% of whom had early AMD. RESULTS: The odds of AMD were 3.3 times greater (95% confidence interval [CI], 1.8-6.1) in women with both low healthy lifestyle score (0-2) and high-risk CFH genotype (CC), relative to those who had low genetic risk (TT) and high healthy lifestyle scores (4-6). There were no significant additive (synergy index [SI], 1.08; 95% CI, 0.70-1.67) or multiplicative (Pinteraction=0.94) interactions in the full sample. However, when limiting the sample to women with stable diets before AMD assessment (n=728) the odds for AMD associated with low healthy lifestyle scores and high-risk CFH genotype were strengthened (odds ratio, 4.6; 95% CI, 1.8-11.6) and the synergy index was significant (SI, 1.34; 95% CI, 1.05-1.70). Adjusting for dietary lutein and zeaxanthin attenuated, and therefore partially explained, the joint association. There were no significant additive or multiplicative interactions for ARMS2 and lifestyle score. CONCLUSIONS: Having unhealthy lifestyles and 2 CFH risk alleles increased AMD risk (primarily in the early stages), in an or additive or greater (synergistic) manner. However, unhealthy lifestyles increased AMD risk regardless of AMD risk genotype.

Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration.

Age-related macular degeneration (AMD) is the most common form of irreversible blindness in developed countries. Variants in the factor H gene (CFH, also known as HF1), which encodes a major inhibitor of the alternative complement pathway, are associated with the risk for developing AMD. Here we test the hypothesis that variation in genes encoding other regulatory proteins of the same pathway is associated with AMD. We screened factor B (BF) and complement component 2 (C2) genes, located in the major histocompatibility complex class III region, for genetic variation in two independent cohorts comprising approximately 900 individuals with AMD and approximately 400 matched controls. Haplotype analyses identify a statistically significant common risk haplotype (H1) and two protective haplotypes. The L9H variant of BF and the E318D variant of C2 (H10), as well as a variant in intron 10 of C2 and the R32Q variant of BF (H7), confer a significantly reduced risk of AMD (odds ratio = 0.45 and 0.36, respectively). Combined analysis of the C2 and BF haplotypes and CFH variants shows that variation in the two loci can predict the clinical outcome in 74% of the affected individuals and 56% of the controls. These data expand and refine our understanding of the genetic risk for AMD.

Inclusion of genotype with fundus phenotype improves accuracy of predicting choroidal neovascularization and geographic atrophy.

PURPOSE: The accuracy of predicting conversion from early-stage age-related macular degeneration (AMD) to the advanced stages of choroidal neovascularization (CNV) or geographic atrophy (GA) was evaluated to determine whether inclusion of clinically relevant genetic markers improved accuracy beyond prediction using phenotypic risk factors alone. DESIGN: Cohort study. PARTICIPANTS: White, non-Hispanic subjects participating in the Age-Related Eye Disease Study (AREDS) sponsored by the National Eye Institute consented to provide a genetic specimen. Of 2415 DNA specimens available, 940 were from disease-free subjects and 1475 were from subjects with early or intermediate AMD. METHODS: DNA specimens from study subjects were genotyped for 14 single nucleotide polymorphisms (SNPs) in genes shown previously to associate with CNV: ARMS2, CFH, C3, C2, FB, CFHR4, CFHR5, and F13B. Clinical demographics and established disease associations, including age, sex, smoking status, body mass index (BMI), AREDS treatment category, and educational level, were evaluated. Four multivariate logistic models (phenotype; genotype; phenotype + genotype; and phenotype + genotype + demographic + environmental factors) were tested using 2 end points (CNV, GA). Models were fitted using Cox proportional hazards regression to use time-to-disease onset data. MAIN OUTCOME MEASURES: Brier score (measure of accuracy) was used to identify the model with the lowest prediction error in the training set. The most accurate model was subjected to independent statistical validation, and final model performance was described using area under the receiver operator curve (AUC) or C-statistic. RESULTS: The CNV prediction models that combined genotype with phenotype with or without age and smoking revealed superior performance (C-statistic = 0.96) compared with the phenotype model based on the simplified severity scale and the presence of CNV in the nonstudy eye (C-statistic = 0.89; P<0.01). For GA, the model that combined genotype with phenotype demonstrated the highest performance (AUC = 0.94). Smoking status and ARMS2 genotype had less of an impact on the prediction of GA compared with CNV. CONCLUSIONS: Inclusion of genotype assessment improves CNV prediction beyond that achievable with phenotype alone and may improve patient management. Separate assessments should be used to predict progression to CNV and GA because genetic markers and smoking status do not equally predict both end points. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

The Ocular Trauma Score Underestimates Visual Recovery for the Most Severe Open-Globe Injuries.

PURPOSE: To compare visual outcomes after open-globe injury (OGI) with those predicted by the Ocular Trauma Score (OTS), and to investigate the effect of treatment with pars plana vitrectomy (PPV). DESIGN: Retrospective cohort study. SUBJECTS: Patients presenting with OGI to an academic United States ophthalmology department from 2017 to 2020. METHODS: Best-corrected visual acuity (VA) measurements at the most recent follow-up were compared with final VA predicted by the OTS, based on preoperative injury characteristics. The most recently measured VA of patients treated with PPV during initial OGI repair (primary PPV group) was compared with patients treated with PPV after initial OGI repair (secondary PPV group) and patients never treated with PPV (No PPV group). MAIN OUTCOME MEASURES: Best-corrected VA in the injured eye at last follow-up; secondary outcome measures included the occurrence of vitreous hemorrhage at any time, occurrence of retinal detachment at any time, rates of additional surgery, and rates of enucleation. RESULTS: One-hundred and thirty-three subjects with OGI were identified and analyzed. The overall rate of PPV was 32%. Predictors of worse VA at last follow-up included older age (P = 0.047) and worse presenting VA (P < 0.001). Visual acuity outcomes for eyes in OTS categories 2 to 5 did not significantly differ from OTS predictions. However, eyes in OTS category 1 had a higher likelihood of last follow-up VA of light perception (LP) to hand motion (46% in the study cohort vs. 15% predicted by the OTS, P = 0.004) and a lower likelihood of no LP (33% vs. 74%, P < 0.001). The secondary PPV group had the worst VA at presentation among the 3 groups (P = 0.016), but VA at last follow-up did not significantly differ between the study groups (P = 0.338). CONCLUSIONS: The most severe OGIs (i.e., OTS category 1) had better visual outcomes than predicted by the published OTS expectations, and secondary PPV was associated with significant visual improvement despite poor prognostic predictions. Evaluation by a vitreoretinal surgeon should be considered for all patients with severe OGI, especially those in OTS category 1. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

A survey study of musculoskeletal disorders among eye care physicians compared with family medicine physicians.

PURPOSE: To evaluate the prevalence of musculoskeletal disorders among eye care physicians compared with family medicine physicians. DESIGN: Case control study. PARTICIPANTS AND CONTROLS: Ophthalmologists and optometrists at the University of Iowa and Mayo Clinic (participants) and family medicine physicians at the University of Iowa and Mayo Clinic (controls). METHODS: An electronic survey was e-mailed to all subjects. MAIN OUTCOME MEASURES: The prevalence of musculoskeletal symptoms between eye care providers and family medicine physicians (control group). RESULTS: One hundred eight-six surveys were completed by 94 eye care physicians and 92 family medicine physicians with a response rate of 99% and 80%, respectively. There were no significant differences between the 2 groups with regard to mean age, gender, body mass index, years with current employer, or years in practice. Eye care providers, compared with their family medicine colleagues, reported a higher prevalence of neck (46% vs 21%; P<0.01), hand/wrist pain (17% vs 7%; P = 0.03), and lower back pain (26% vs 9%; P<0.01). A greater proportion of eye care physicians classified their job as a high-strain job (high demand, low control; 31% vs 20%) and a lower proportion classified their job as an active job (high demand, high control; 24% vs 47%; p = 0.01). Several job factors reported by eye care providers to contribute to musculoskeletal symptoms included performing the same task repeatedly, working in awkward/cramped positions, working in the same position for long periods, and bending/twisting the back (all P<0.01). CONCLUSIONS: In this survey, the study group, composed of ophthalmologists and optometrists, had a higher prevalence of neck, hand/wrist, and lower back pain compared with family medicine physicians; repetitive tasks, prolonged or awkward/cramped positions, and bending/twisting were contributory factors. Given the ramifications of these findings, future efforts should concentrate on modifications to the eye care providers' work environment to prevent or alleviate musculoskeletal disorders and their personal and socioeconomic burden.

Clinical validation of a genetic model to estimate the risk of developing choroidal neovascular age-related macular degeneration.

Predictive tests for estimating the risk of developing late-stage neovascular age-related macular degeneration (AMD) are subject to unique challenges. AMD prevalence increases with age, clinical phenotypes are heterogeneous and control collections are prone to high false-negative rates, as many control subjects are likely to develop disease with advancing age. Risk prediction tests have been presented previously, using up to ten genetic markers and a range of self-reported non-genetic variables such as body mass index (BMI) and smoking history. In order to maximise the accuracy of prediction for mainstream genetic testing, we sought to derive a test comparable in performance to earlier testing models but based purely on genetic markers, which are static through life and not subject to misreporting. We report a multicentre assessment of a larger panel of single nucleotide polymorphisms (SNPs) than previously analysed, to improve further the classification performance of a predictive test to estimate the risk of developing choroidal neovascular (CNV) disease. We developed a predictive model based solely on genetic markers and avoided inclusion of self-reported variables (eg smoking history) or non-static factors (BMI, education status) that might otherwise introduce inaccuracies in calculating individual risk estimates. We describe the performance of a test panel comprising 13 SNPs genotyped across a consolidated collection of four patient cohorts obtained from academic centres deemed appropriate for pooling. We report on predictive effect sizes and their classification performance. By incorporating multiple cohorts of homogeneous ethnic origin, we obtained >80 per cent power to detect differences in genetic variants observed between cases and controls. We focused our study on CNV, a subtype of advanced AMD associated with a severe and potentially treatable form of the disease. Lastly, we followed a two-stage strategy involving both test model development and test model validation to present estimates of classification performance anticipated in the larger clinical setting. The model contained nine SNPs tagging variants in the regulators of complement activation (RCA) locus spanning the complement factor H (CFH), complement factor H-related 4 (CFHR4), complement factor H-related 5 (CFHR5) and coagulation factor XIII B subunit (F13B) genes; the four remaining SNPs targeted polymorphisms in the complement component 2 (C2), complement factor B (CFB), complement component 3 (C3) and age-related maculopathy susceptibility protein 2 (ARMS2) genes. The pooled sample size (1,132 CNV cases, 822 controls) allowed for both model development and model validation to confirm the accuracy of risk prediction. At the validation stage, our test model yielded 82 per cent sensitivity and 63 per cent specificity, comparable with metrics reported with earlier testing models that included environmental risk factors. Our test had an area under the curve of 0.80, reflecting a modest improvement compared with tests reported with fewer SNPs.

Proteomic analysis of vitreous biopsy techniques.

PURPOSE: To compare vitreous biopsy methods using analysis platforms used in proteomics biomarker discovery. METHODS: Vitreous biopsies from 10 eyes were collected sequentially using a 23-gauge needle and a 23-gauge vitreous cutter instrument. Paired specimens were evaluated by UV absorbance spectroscopy, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: The total protein concentration obtained with a needle and vitrectomy instrument biopsy averaged 1.10 mg/mL (standard error of the mean = 0.35) and 1.13 mg/mL (standard error of the mean = 0.25), respectively. In eight eyes with low or medium viscidity, there was a very high correlation (R = 0.934) between the biopsy methods. When data from 2 eyes with high viscidity vitreous were included, the correlation was reduced (R = 0.704). The molecular weight protein sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles of paired needle and vitreous cutter samples were similar, except for a minority of pairs with single band intensity variance. Using LC-MS/MS, equivalent peptides were identified with similar frequencies (R ≥ 0.90) in paired samples. CONCLUSION: Proteins and peptides collected from vitreous needle biopsies are nearly equivalent to those obtained from a vitreous cutter instrument. This study suggests both techniques may be used for most proteomic and biomarker discovery studies of vitreoretinal diseases, although a minority of proteins and peptides may differ in concentration.

Age-Related Macular Degeneration Masquerade: A Review of Pentosan Polysulfate Maculopathy and Implications for Clinical Practice.

ABSTRACT: Pentosan polysulfate (PPS) sodium (Elmiron) is the only Food and Drug Administration (FDA)-approved oral medication to treat interstitial cystitis, also known as bladder pain syndrome. A symptomatic pigmentary maculopathy associated with PPS was reported in 2018. Since then, recognition of this unique drug toxicity has increased rapidly. This potentially sight-threatening side effect prompted the FDA in June 2020 to update the label for PPS to warn about "retinal pigmentary changes." A challenging feature of pentosan maculopathy is its ability to mimic many other retinal conditions, including inherited retinal dystrophies such as pattern dystrophy, mitochondrially inherited diabetes and deafness, and Stargardt disease, and age-related macular degeneration. In this review, we discuss the history of PPS maculopathy and its implications for thousands of at-risk interstitial cystitis patients. We use published literature and an illustrative case from our institution to highlight the importance of diagnosing PPS maculopathy. We also compare PPS maculopathy to age-related macular degeneration, explain why differentiating between the 2 is clinically important, and highlight avenues for further research. Finally, we highlight the paucity of data on patients of color and why this lack of understanding may impact patient care.

Bilateral intravitreal injection of antivascular endothelial growth factor therapy.

PURPOSE: The purpose of this study was to review adverse events and patient preference after bilateral intravitreal injection of antibodies to vascular endothelial growth factor. METHODS: A retrospective case-control study. Patients with exudative age-related macular degeneration who received intravitreal antivascular endothelial growth factor agent injections in both eyes (bilateral group) on the same day over a 23-month period were compared with patients who received injections in only 1 eye. The occurrence of endophthalmitis, cerebrovascular accident, myocardial infarction, death, patient discomfort, and patient preference was compared between the two groups. RESULTS: One hundred and two patients received an average of 4.43 bilateral injections (range 1-13). A case-control group of 102 patients received an average of 10.2 unilateral injections, (range 2-28). Bevacizumab was injected 45.5%, ranibizumab 45.5%, and a combination of bevacizumab and ranibizumab 9% of the time for bilateral injections. Bevacizumab was used 50.3% and ranubizumab 49.7% of the time in unilateral injections. The follow-up of both groups averaged 18.4 months (range 4.7-36.5 months). There were no cases of endophthalmitis or cerebrovascular accident in either group. There was a single case of myocardial infarction in each group. There were two deaths in the bilateral group and three deaths in the unilateral group. More than 90% strongly preferred bilateral injections to unilateral injections. CONCLUSION: Bilateral injections of antivascular endothelial growth factor agents on the same day did not increase the rate of adverse events and was preferred by the majority of patients.

Reticular Pseudodrusen Characteristics and Associations in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2), an Ancillary Study of the Women's Health Initiative.

PURPOSE: To determine the prevalence and morphologic features of reticular pseudodrusen (RPD) and their association with participant demographics and age-related macular degeneration (AMD) status in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2) sample, an ancillary study of the Women's Health Initiative Observational Study. DESIGN: Cross-sectional, multicenter, natural history study. PARTICIPANTS: Nine hundred and twenty-seven eyes from 466 postmenopausal women 69 to 101 years of age. METHODS: Multimodal imaging, including spectral-domain (SD) OCT and infrared reflectance (IR), were used to identify RPD characteristics, including location (within or outside the 6-mm diameter circle centered at the macula), presence of peripapillary RPD, pattern of RPD, and RPD area. Age-related macular degeneration features from SD OCT, IR, and color photographs also were assessed and AMD severity was categorized. MAIN OUTCOME MEASURES: Reticular pseudodrusen prevalence using SD OCT and IR imaging and AMD status. RESULTS: Reticular pseudodrusen were present in 130 eyes (14% of eyes, 16% of participants), with increasing prevalence with age: 7% in those younger than 78 years, 14% in those 78 to 83 years of age, and 30% in those older than 83 years. Using clinical classification of AMD with color photography, RPD were seen in 2.4% of eyes with no AMD or aging changes, 11.5% in early AMD, 25.1% in intermediate AMD, and 51.1% in late AMD. Mean RPD area was 17.4 mm2 (standard deviation, 14.7 mm2). Ribbon morphologic RPD (53%) was more common than dot morphologic RPD (36%). Reticular pseudodrusen mostly were located both within and outside the 6-mm circle with primarily superior retinal distribution. Reticular pseudodrusen were visualized with corresponding color fundus photography in only 38 eyes (4% of total eyes). Participants with and without RPD had a visual acuity±standard error of 77.9 ± 1.4 letters and 81.3 ± 0.4 letters, respectively (P = 0.02). CONCLUSIONS: The prevalence of RPD in CAREDS2 increased with age and was associated with AMD severity. Reticular pseudodrusen were detected in eyes without other features of AMD and could represent an earlier disease state. Multimodal imaging with SD OCT and IR has significantly greater sensitivity for visualizing RPD than color fundus photography.

Association of Macular Thickness With Age and Age-Related Macular Degeneration in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2), An Ancillary Study of the Women's Health Initiative.

Purpose: To evaluate the relationship of retinal layer thickness with age and age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study 2. Methods: Total retinal thickness within the macular area, and individual layer thickness was determined for CAREDS2 participants (n = 906 eyes, 473 women) from the Women's Health Initiative using Heidelberg optical coherence tomography (OCT). Mean measurements within the OCT grid were compared across age tertiles (69-78, 78-83, and 83-101 years) and AMD outcomes. Results: Mean retinal thickness in the central circle, inner ring, and outer ring were 277 ± 34 µm, 326 ± 20 µm, and 282 ± 15 µm, respectively. Thickness did not vary by age in the central circle, but decreased with age in the inner and outer circles (P ≤ 0.004). Specifically, ganglion cell (GCL), inner plexiform, and outer nuclear (ONL) layer thickness decreased with age (P ≤ 0.003). Age-adjusted retinal thickness in all three circles did not vary by AMD outcomes (486 without AMD and 413 with AMD). However, individual layers showed changes with GCL and photoreceptor thinning and retinal pigment epithelial thicknening in eyes with late AMD. After controlling for age and AMD, higher ONL thickness was associated with better visual acuity. Conclusions: In this cohort of older women, a decrease in perifoveal thickness was associated with increasing age, particularly in the inner retinal layers. Variabilty in thickness in AMD eyes was primarily due to outer retinal layers. Among all retinal layers, the ONL plays an important role in preserving visual acuity. Translational Relevance: The study provides a deeper understanding of age related changes to the retinal layers and their effect on visual loss.

Attaining functional levels of visual acuity after vitrectomy for retinal detachment secondary to proliferative diabetic retinopathy.

Most patients needing diabetic tractional retinal detachment (TRD) surgery are working-age adults that drive and participate in other vision-dependent activities of daily living. We sought to determine the proportion of patients that achieve functional visual acuity (VA) based on the World Health Organization (WHO) definition of 'low vision' (≤ 20/80) and US driving standards (≥ 20/40) after vitrectomy for diabetic TRD. In this 10-year retrospective review, consecutive patients who underwent primary vitrectomy for TRD from proliferative diabetic retinopathy were studied. 240 eyes in 203 patients met criteria for analysis (38 eyes were lost to follow up at 3 months; 68 at 12 months; 146 at 60 months). While most patients (nearly 80%) having TRD surgery had low vision pre-op, almost half attained VA that was > 20/80 five years post-op. Those most likely to achieve significant visual improvement (p < 0.0001) had concomitant vitreous hemorrhage pre-op. Only 6% of eyes met the US minimum driving standard before surgery based on VA compared to 28% after vitrectomy however this study did not examine visual fields which could warrant additional assessment depending on local requirements. In summary, significant gains in visual acuity are seen after vitrectomy for diabetic TRD that can result in functional improvement in activities of daily living.

Orally Administered Alpha Lipoic Acid as a Treatment for Geographic Atrophy: A Randomized Clinical Trial.

PURPOSE: Alpha lipoic acid (ALA) is a nutraceutical and potent antioxidant that has shown efficacy in the retina light damage mouse model and in humans for multiple sclerosis. Our objective was to evaluate the efficacy and safety of oral ALA for the treatment of geographic atrophy (GA). DESIGN: Randomized, controlled, double-masked, multicenter phase 2 clinical trial of ALA versus placebo. PARTICIPANTS: Participants with unilateral or bilateral GA from age-related macular degeneration. METHODS: Participants were randomized to 1200 mg daily of ALA or placebo. Fundus autofluorescence, fundus color photography, and spectral-domain OCT were conducted and best-corrected visual acuity (BCVA) was obtained at baseline and every 6 months through month 18. MAIN OUTCOME MEASURES: Annual rate of change over 18 months in square root-transformed area of GA in study eyes as measured on fundus autofluorescence. Secondary outcomes included the number of adverse events (AEs), change in BCVA, and annual rate of change in area of GA measured on color photographs. RESULTS: Fifty-three participants (mean age, 80 years) were randomized (April 2016-August 2017). Twenty-seven participants (37 eyes) were in the placebo group, and 26 participants (36 eyes) were in the ALA group. Unadjusted mean (standard error) annual change in GA area was 0.28 (0.02) mm and 0.31 (0.02) mm for the placebo and ALA groups, respectively (difference, 0.04 mm; 95% confidence interval [CI], -0.03 to 0.11 mm; P = 0.30). Adjusting for baseline GA area, number of GA lesions, and presence of subfoveal GA, the mean annual change in GA area was 0.27 (0.04) mm and 0.32 (0.05) mm for the placebo and ALA groups, respectively (difference, 0.05 mm; 95% CI, -0.02 to 0.12 mm; P = 0.14). At 18 months, the percent of eyes losing 15 letters or more of BCVA was 22% (8 of 36) and 14% (5 of 36) in the placebo and ALA groups, respectively (P = 0.54). No difference was found in the percentage of participants with nonserious AEs (P = 0.96) or serious AEs (P = 0.28) between the placebo and ALA groups. CONCLUSIONS: Results do not support ALA having beneficial effects on GA or BCVA. This trial design may be useful for other GA repurposing drug trials.

Management of sympathetic ophthalmia with the fluocinolone acetonide implant.

OBJECTIVE: We examined whether implantation of the fluocinolone acetonide (Retisert) implant achieved control of inflammation and a reduced need for oral corticosteroids or immunosuppressives in patients with sympathetic ophthalmia (SO). DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Eight patients with active SO. METHODS: The results of fluocinolone acetonide implantation in 8 patients with active SO were studied with a follow-up period of 6 months to 2 years. MAIN OUTCOME MEASURES: Presence or absence of intraocular inflammation, visual acuity, intraocular pressure, need for further surgery, and the need for additional use of oral or locally injected corticosteroids and/or immunosuppressives. RESULTS: All patients demonstrated a significant reduction in the systemic medication required to maintain control of inflammation. Two patients had recurrent inflammatory episodes requiring the resumption of an oral immunosuppressive. Vision improved or was stabilized in all 8 patients. CONCLUSIONS: The fluocinolone acetonide implant provides inflammatory control and reduces the dependence on systemic immunosuppression in patients with SO.

Associations between age-related nuclear cataract and lutein and zeaxanthin in the diet and serum in the Carotenoids in the Age-Related Eye Disease Study, an Ancillary Study of the Women's Health Initiative.

OBJECTIVE: To evaluate associations between nuclear cataract (determined from slitlamp photographs between May 2001 and January 2004) and lutein and zeaxanthin in the diet and serum in patients between 1994 and 1998 and macula between 2001 and 2004. DESIGN: A total of 1802 women aged 50 to 79 years in Iowa, Wisconsin, and Oregon with intakes of lutein and zeaxanthin above the 78th (high) and below the 28th (low) percentiles in the Women's Health Initiative Observational Study (1994-1998) were recruited 4 to 7 years later (2001-2004) into the Carotenoids in Age-Related Eye Disease Study. RESULTS: Women in the group with high dietary levels of lutein and zeaxanthin had a 23% lower prevalence of nuclear cataract (age-adjusted odds ratio, 0.77; 95% confidence interval, 0.62-0.96) compared with those with low levels. Multivariable adjustment slightly attenuated the association (odds ratio, 0.81; 95% confidence interval, 0.65-1.01). Women in the highest quintile category of diet or serum levels of lutein and zeaxanthin as compared with those in the lowest quintile category were 32% less likely to have nuclear cataract (multivariable-adjusted odds ratio, 0.68; 95% confidence interval, 0.48-0.97; P for trend = .04; and multivariable-adjusted odds ratio, 0.68; 95% confidence interval, 0.47-0.98; P for trend = .01, respectively). Cross-sectional associations with macular pigment density were inverse but not statistically significant. CONCLUSIONS: Diets rich in lutein and zeaxanthin are moderately associated with decreased prevalence of nuclear cataract in older women. However, other protective aspects of such diets may in part explain these relationships.

Choroidal Features of Acute Macular Neuroretinopathy via Optical Coherence Tomography Angiography and Correlation With Serial Multimodal Imaging.

Importance: Acute macular neuroretinopathy (AMN) is a rare, idiopathic condition resembling other acute maculopathies such as paracentral acute middle maculopathy. The pathophysiology of AMN is not well understood, and the role of the choroid in the pathogenesis of AMN remains controversial. Objective: To describe initial and serial multimodal imaging findings in AMN, with attention to choroidal vascular changes. Design, Setting, and Participants: Retrospective case series at a single institution, tertiary referral center. The case series included 7 patients with clinical diagnosis of AMN. Main Outcomes and Measures: Multimodal imaging findings, including fundus photography, fluorescein angiography, spectral-domain optical coherence tomography (OCT), en face near-infrared imaging, fundus autofluorescence, optical coherence tomography angiography (OCTA), and automated quantification of the regional structural context of choroidal flow interest between different imaging modalities, using an automatic algorithm. Results: Nine eyes from 7 patients (5 women and 2 men; mean age, 40.1 years) with a diagnosis of AMN were included. Mean duration of follow-up was 11 weeks (range, 1-25 weeks). All eyes had inner choroidal flow void on OCTA that topographically corresponded to regions of abnormal hyperreflectance of the outer retinal layers on spectral-domain OCT and hyporeflectance on en face near-infrared imaging (dice similarity coefficient, 0.76). For each patient, these areas of choroidal flow void on OCTA persisted during the follow-up period, while the abnormal hyperreflectance of outer plexiform layer and inner nuclear layer on spectral-domain OCT was observed to improve. Conclusions and Relevance: These findings suggest that areas of inner choroidal vascular flow void on OCTA are seen in patients with AMN. These areas may persist weeks after the onset of symptoms and suggest that vascular compromise of the inner choroid may be involved in the pathogenesis of AMN.