Adalimumab in patients with vision-threatening uveitis: real-world clinical experience.

OBJECTIVES: Biologics are rapidly emerging as an effective vision saving addition to systemic uveitis therapy. The aim of this multicentre retrospective study is to review the outcomes of a large group of patients treated with adalimumab. METHODS: A retrospective chart review of patients with refractory non-infectious, active uveitis treated with adalimumab was conducted. The main outcome measures were ability to reduce prednisolone dose, ability to control uveitis, final visual acuity and time to treatment failure. RESULTS: Forty-six patients with uveitis, treated with adalimumab were included in the study. The most common anatomical uveitis phenotype was panuveitis (n=17, 37.0%). The most common diagnosis was idiopathic uveitis (n=19, 41.3%). At their latest review (mean: 4.46 years; median 4.40 years), 35 (76.1%) patients were able to discontinue corticosteroids, 11 (23.9%) patients were able to taper to <7.5 mg/day and only 1 (2.2%) patient required 10 mg of prednisone. The mean visual acuity at the latest follow-up of the worse eye was logarithm of the minimum angle of resolution (logMAR) 0.42 (SD 0.72), while the mean visual acuity of the better eye was logMAR 0.19 (SD 0.34). Of the 89 eyes, 21 (23.6%) eyes improved by at least 2 lines, 5 eyes (5.6%) deteriorated by ≥2 lines while vision was unchanged in the remaining 63 (70.8%) eyes. The time to recurrence was 1 in 12.47 person-years for adalimumab, with a 17.4% (8 patient) relapse rate. There were no serious adverse events. CONCLUSIONS: This study highlights the efficacy of adalimumab in patients with vision-threatening non-infectious uveitis, preserving vision and allowing reduction of corticosteroid dose.

Ethnic variation in early age-related macular degeneration lesions between white Australians and Singaporean Asians.

PURPOSE: We compared early age-related macular degeneration (AMD) lesion characteristics between white Australians and Singaporean Asians. METHODS: Participants of the Blue Mountains Eye Study (BMES; whites, n = 3508) and the Singapore Epidemiology of Eye Disease Study (SEED; Malay, n = 3280, Indian, n = 3400, and Chinese, n = 3353) underwent examinations, including retinal photography. The AMD lesions were assessed following the Wisconsin AMD grading protocol by the same photographic grader. Prevalence and characteristics of early AMD lesions were compared between the BMES and the SEED. The associations between ethnicity and early AMD lesion types were analyzed using logistic regression models adjusting for age, sex, smoking status, lipids, and genetic polymorphisms associated with AMD. RESULTS: After age-standardization to the BMES population, the prevalence of distinct soft drusen was significantly higher in Singaporeans compared to Australians (23.9%, 95% confidence interval [CI] 22.9-25.0 vs. 6.2%, 95% CI 5.3-7.0), with an adjusted odds ratio (OR) of 4.6 (95% CI 3.4-6.0). In contrast, the prevalence of indistinct soft or reticular drusen was significantly lower in Singaporeans compared to Australians (6.5%, 95% CI 5.9-7.1 vs. 8.3%, 95% CI 7.4-9.3, with nonsignificant adjusted OR of 1.2, 95% CI 0.8-1.7). Soft drusen of any type were present frequently at the inner and outer macula (within a zone ≥500 to <3000 µm radius from the foveal center) among Singaporeans, while among Australians soft drusen were present more frequently at the central macula (<500 µm radius). CONCLUSIONS: Singaporean Asians had a milder spectrum of early AMD lesions and lesion characteristics (predominantly distinct soft drusen and noncentral location) compared to white Australians.

Retrospective analysis of the natural history and management of serpiginous choroiditis in Australia and New Zealand.

BACKGROUND: To examine the prevalence of serpiginous choroidopathy in a predominantly Caucasian community, to examine associations between serpiginous choroiditis and other systemic diseases, and to report on the effect of immunosuppression on the long-term course of serpiginous choroiditis. DESIGN: Retrospective cohort study with patients from tertiary care centres and private practices. PARTICIPANTS: 18 patients, mean age 48 years at baseline. One patient was seen only once. Median follow-up was 69 months (5.8 years, range 0.4-29.7 years). METHODS: Patients were identified using the Australian and New Zealand Ophthalmic Surveillance Unit. A chart analysis was performed for all patients. Three treatment groups were identified: no treatment, prednisolone monotherapy, or combination of prednisolone and immunosuppression. Negative binomial regression was used to calculate incidence rate ratios for patient relapse. MAIN OUTCOME MEASURES: Patient demographics, clinical features, associated systemic diseases, treatments administered and dates of relapse. RESULTS: The disease prevalence in Australia and New Zealand is 1 case per 1.5 million people. Five cases (28%) had a positive QuantiFERON. A total of 32 relapses were observed: 14 while receiving no treatment, 11 on prednisolone and 7 on combination therapy. Compared with the no treatment group, the incidence rate ratio for prednisolone monotherapy and combination therapy was 1.29 and 2.92, respectively (95% confidence interval 0.40-4.14 and 0.96-8.88). CONCLUSION: Although the confidence intervals indicate that the difference in incidence rate ratios are not significant, these results suggest that there is a group of patients who have a benign course without long-term immunosuppression or corticosteroid treatment.

Impact of migration and acculturation on prevalence of type 2 diabetes and related eye complications in Indians living in a newly urbanised society.

BACKGROUND: Health of migrants is a major public health challenge faced by governments and policy makers. Asian Indians are among the fastest growing migration groups across Asia and the world, but the impact of migration and acculturation on diabetes and diabetes-related eye complications among Indians living in urban Asia remains unclear. METHODOLOGIES/PRINCIPAL FINDINGS: We evaluated the influence of migration and acculturation (i.e., migration status and length of residence) on the prevalence of type-2 diabetes mellitus (T2DM) and diabetes-related eye complications (diabetic retinopathy (DR) and cataract), among first-generation (defined as participant born in India with both parents born in India, n = 781) and second-generation (participants born in Singapore with both parents born in India, n = 1,112) Indian immigrants from a population-based study of Adult Indians in Singapore. Diabetes was defined as HbA1c≥6.5%, use of diabetic medication or a physician diagnosis of diabetes. Retinal and lens photographs were graded for the presence of DR and cataract. Compared to first generation immigrants, second generation immigrants had a higher age- and gender-standardized prevalence of T2DM (34.4% versus 29.0%, p<0.001), and, in those with T2DM, higher age- and gender-standardized prevalence of DR (31.7% versus 24.8%, p<0.001), nuclear cataract (13.6% versus 11.6%, p<0.001), and posterior sub-capsular cataract (6.4% versus 4.6%, p<0.001). Among first generation migrants, longer length of residence was associated with significantly younger age of diagnosis of diabetes and greater likelihood of having T2DM and diabetes-related eye complications. CONCLUSION: Second generation immigrant Indians and longer length of residence are associated with higher prevalence of diabetes and diabetes-related complications (i.e., DR and cataract) among migrant Indians living in Singapore. These data highlight potential worldwide impacts of migration patterns on the risk and burden of diabetes.

Prevalence and risk factors of epiretinal membrane in Asian Indians.

PURPOSE: To describe the prevalence of epiretinal membrane (ERM) and its risk factors in an Indian population and compare the findings with other populations. METHODS: The Singapore Indian Eye Study is a population-based survey of 3400 Asian Indians aged between 40 and 80 years. A comprehensive ophthalmic examination, standardized interviews, and laboratory blood tests were performed. Digital retinal fundus photographs were assessed for the presence of ERM following the definitions used in the Blue Mountains Eye Study (BMES). ERM was classified into a less severe form termed "cellophane macular reflex" (CMR) and a more severe form termed "preretinal macular fibrosis" (PMF) and also as primary and secondary (if it was associated with retinal pathology or cataract surgery). RESULTS: A total of 3328 persons (mean age 57.8 ± [SD] 10.1 years, and 50.2% male) provided data in this study. The age-standardized prevalence of ERM was 7.6% (95% confidence interval [CI], 6.8-8.6), CMR 4.1% (95% CI, 3.5-4.9), and PMF 3.5% (95% CI, 2.9-4.2). Older age (odds ratio [OR], 1.09; 95% CI, 1.07-1.11, per year increase), increasing myopic refraction (OR, 1.14; 95% CI, 1.07-1.22, per diopter decrease), and narrower retinal arteriolar diameter (OR, 1.02; 95% CI, 1.00-1.03, per µm decrease) were significantly associated with primary ERM. CONCLUSIONS: The age-standardized prevalence of ERM in the Indian population in Singapore was 7.6%. This is similar to Malays in Singapore (8.0%) and higher than the prevalence in whites in Australia (4.7%). Significant factors associated with primary ERM were older age, myopia, and narrower retinal arteriolar diameter.

Smoking and the long-term incidence of cataract: the Blue Mountains Eye Study.

PURPOSE: To assess the association between smoking and the long-term incidence of cataract and cataract surgery. METHODS: In a population-based cohort of Australians aged 49 years and over, 3654 participants were seen at baseline (1992-94) and 2406 were seen after 5- and/or 10-years and had photographs taken to assess incident cataract. Smoking status was recorded at interview. History, physical examination and fasting blood samples provided data on possible risk factors. Cataract incidence was calculated using the Kaplan-Meier survival approach. Discrete linear logistic models were used to assess risk of incident cataract. RESULTS: After controlling for age, sex and other factors, ever smokers had an increased risk of developing nuclear cataract compared to never smokers (relative risk (RR) 1.41; 95% confidence interval (CI) 1.09-1.83; RR 1.37, CI 1.04-1.81 for past smoking and RR 1.57, CI 1.06-2.31 for current smoking). The effect of smoking was strongest in ever smokers reporting 36 + pack-years of smoking compared to never smokers (RR 1.46; CI, 1.02-2.08). Current smokers also developed nuclear cataract slightly younger than non-smokers (mean age 65.2 versus 67.5 years, p = 0.049). No statistically significant associations were found between smoking status and the incidence of cortical or posterior subcapsular cataract, or cataract surgery. CONCLUSIONS: These epidemiological data confirm smoking as a modest risk factor for the development of nuclear cataract.

Cardiovascular disease, vascular risk factors and the incidence of cataract and cataract surgery: the Blue Mountains Eye Study.

PURPOSE: To assess whether an association exists between cardiovascular disease, vascular risk factors and incident cataract and cataract surgery. METHODS: The Blue Mountains Eye Study examined 3654 participants > or = 49 years of age during 1992-4, then 2335 survivors (75.1%) after five years. Trained interviewers administered a vascular history questionnaire; height, weight and blood pressure were measured. Lens photographs from both examinations were graded for presence of cortical, nuclear or posterior subcapsular cataract. RESULTS: Obesity (body mass index > or = 30 kg/m2) was significantly associated with increased incidence of both cortical [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.2-2.2] and posterior subcapsular cataract (OR 2.1, CI 1.2-3.7). Hypertensive participants using medication and aged less than 65 years at baseline had a higher incidence of posterior subcapsular cataract (OR 3.4, 95% CI 1.3-8.4) than normotensive subjects. A history of angina was associated with higher cataract surgery incidence (OR 2.1, 95% CI 1.3-3-5). CONCLUSIONS: These longitudinal data provide some evidence supporting a relationship between cardiovascular disease, vascular risk factors and incident cataract and cataract surgery. The findings confirm a number of associations previously documented in cross-sectional data.

Prevalence of undetected ocular conditions in a pilot sample of school children.

Parents of 134 children (age 5-18 years; 84% participation) attending a private school gave informed consent for their child's participation in a pilot study to demonstrate the feasibility and estimate sample size for a larger study of myopia prevalence, the Sydney Myopia Study. LogMAR visual acuity and other ocular assessments, including cycloplegic autorefraction (tropicamide 1%) and examination of the media and fundus, were performed. The prevalence of significant ocular conditions was 28.2%. Eleven children (8.4%) wore glasses. Five were referred for a change in their correction. Previously undetected ocular conditions (19.8%) included one child with ocular pathology and four children with strabismus. Uncorrected refractive error (16.8%) was the most common reason for referral and was more predominant in the senior students (25%), corresponding with an age-related shift in mean spherical equivalent refraction towards myopia (less than 7 years: +0.40 +/- 0.60 D; more than 15 years: -1.15 +/- 1.18 D). Three senior students were classified as having socially significant correctable vision impairment. These findings suggest that reliance on ad hoc referrals could result in delayed referral and that vision screening in both early and later school years may be desirable.

Myopia and incident cataract and cataract surgery: the blue mountains eye study.

PURPOSE: To assess whether an association exists between myopia and incident cataract and cataract surgery in an older population-based cohort study. METHODS: The Blue Mountains Eye Study examined 3654 participants aged 49 years or more during 1992 to 1994 and then 2334 (75.1%) of the survivors after 5 years. A history of using eyeglasses for clear distance vision was obtained. Objective refraction was performed with an autorefractor, followed by subjective refraction with a logarithm of minimum angle of resolution (logMAR) chart. Emmetropia was defined as a spherical equivalent refraction between +1 D and -1 D, hyperopia as more than +1 D, and myopia as less than -1 D. Slit lamp and retroillumination lens photographs were graded for presence of cortical, nuclear, or posterior subcapsular cataract, according to the Wisconsin Cataract Grading System. Generalized estimating equation models analyzed data by eye. RESULTS: There was a statistically significant association between high myopia (-6 D or less) and incident nuclear cataract (odds ratio [OR] 3.3, 95% confidence interval [CI] 1.5-7.4). Incident posterior subcapsular cataract was associated with any myopia (OR 2.1, 95% CI 1.0-4.8), moderate to high myopia (-3.5 D or less, OR 4.4, 95% CI 1.7-11.5), and use of distance glasses before age 20 (OR 3.0, 95% CI 1.0-9.3), after adjustment for multiple potential confounders, including severity of nuclear opacity. Incident cataract surgery was significantly associated with any myopia (OR 2.1, 95% CI 1.1-4.2) as well as moderate (-3.5 to more than -6D; OR 2.9, 1.2-7.3) and high myopia (OR 3.4, 95% CI 1.0-11.3). CONCLUSIONS: These epidemiologic data provide some evidence of an association between myopia and incident cataract and cataract surgery, after adjustment for multiple confounders and severity of nuclear opacity. These data support other cross-sectional and longitudinal population-based findings.

Iris color and incident cataract and cataract surgery: the Blue Mountains Eye Study.

PURPOSE: To assess whether an association exists between iris color and the incidence of cataract and cataract surgery. DESIGN: Population-based cohort study. METHODS: The Blue Mountains Eye Study examined 3654 predominantly Caucasian participants aged 49+ years during 1992-1994, and then 2335 survivors (75.1%) after 5 years. Iris color was determined by comparison with four standard photographs. Slit-lamp and retro-illumination lens photographs were graded for presence and severity of cortical, nuclear, or posterior subcapsular cataract. Incident cataract surgery was recorded by history and from the photographs. RESULTS: Participants with dark brown iris color had an increased incidence of nuclear cataract, odds ratio (OR) 1.8, 95% confidence interval (CI) 1.2 to 2.8, and cataract surgery (OR, 2.5; CI, 1.4-4.2) in multivariate models, compared with participants with blue iris color. CONCLUSION: Incidence data from this study support previous cross-sectional findings linking dark brown iris color with age-related cataract.

Hormone replacement therapy, reproductive factors, and the incidence of cataract and cataract surgery: the Blue Mountains Eye Study.

The authors aimed to assess the relation between endogenous and exogenous female hormones and the incidence of age-related cataract and cataract surgery. The Blue Mountains Eye Study examined 2,072 women aged 49 years or older during 1992-1994, of whom 1,343 (74.0% of survivors) were reexamined after 5 years, during 1997-1999. Information on reproductive factors and use of hormone replacement therapy was collected using an interviewer-administered questionnaire. Lens photographs were graded for the presence of cortical, nuclear, and posterior subcapsular cataract at baseline and follow-up. Women who had ever used hormone replacement therapy had a decreased incidence of cortical cataract affecting any eye compared with never users (odds ratio = 0.7, 95% confidence interval: 0.4, 1.0). However, this was not statistically significant (odds ratio = 0.7, 95% confidence interval: 0.4, 1.1) when using the first affected eye. Older age at menarche was associated with an increased incidence of cataract surgery (odds ratio = 2.6, 95% confidence interval: 1.2, 5.7) and a significant trend for increasing incidence of nuclear cataract (p = 0.04). There was also a significant trend for decreasing incidence of cataract surgery with increasing duration of reproductive years (p = 0.009). These epidemiologic data provide some evidence that estrogen may play a protective role in reducing the incidence of age-related cataract and cataract surgery.

Socioeconomic status and incident cataract surgery: the Blue Mountains Eye Study.

The aim of this study was to assess whether socioeconomic status influenced the incidence of cataract surgery in a defined population of older Australians. The Blue Mountains Eye Study examined 3654 residents during 1992-1994, then 2334 survivors (75.1%)during 1997-1999. Interviewers collected information on principal occupation, which was analysed using Australian Bureau of Statistics categories (stratified into four groups) and the Daniel Occupational Prestige Scale. Cataract surgical history was confirmed at both visits from clinical examinations. There were no statistically significant associations for any of the occupational categories with the 5-year incidence of cataract surgery. In summary, this study could not confirm any major socioeconomic associations with incident cataract surgery, supporting the view that cataract surgery is largely patient driven and that its primary incentive is patient benefit.