Efficacy of Adalimumab in Non-Infectious Uveitis Across Different Etiologies: A Post Hoc Analysis of the VISUAL I and VISUAL II Trials.

Purpose: To assess efficacy of adalimumab versus placebo in patients with active or inactive noninfectious intermediate, posterior, or panuveitis across different etiologies.Methods: VISUAL I (V-I) and VISUAL II (V-II) clinical trials included adults with active or inactive uveitis, respectively, randomized to receive adalimumab or placebo. In a post hoc subgroup analysis, time to treatment failure (TTF) starting at week 6 (V-I) or week 2 (V-II) was analyzed using the Kaplan-Meier method. Hazard ratios (HR) for TTF with 95% CI were calculated with Cox proportional hazards regression.Results: The analysis included 217 V-I patients and 226 V-II patients. Treatment failure occurred later and risk was significantly lower in patients with idiopathic uveitis receiving adalimumab versus those receiving placebo in V-I (HR = 0.50 [CI, 0.30-0.84]; P = .006) and V-II (HR = 0.43 [CI, 0.22-0.83]; P = .010).Conclusions: Treatment failure risk was lower in patients with idiopathic noninfectious uveitis receiving adalimumab versus those receiving placebo.

Long-Term Safety and Efficacy of Adalimumab in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis.

PURPOSE: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Open-label, multicenter, phase 3 extension study (VISUAL III). PARTICIPANTS: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or who discontinued the study after meeting treatment failure criteria (active uveitis). METHODS: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤ 362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose. MAIN OUTCOME MEASURES: Long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related systemic corticosteroids. RESULTS: At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry. Mean daily dose of systemic corticosteroids was reduced from 9.4 ± 17.1 mg/day at week 0 (n = 359) to 1.5 ± 3.9 mg/day at week 150 (n = 181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest were infections (n = 275; 79 events/100 patient-years [PY]); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively. CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab.

New observations and emerging ideas in diagnosis and management of non-infectious uveitis: A review.

BACKGROUND: Non-infectious uveitis (NIU) is an immune-mediated disease with clinical symptoms such as eye pain, redness, floaters, and light sensitivity. NIU is one of the leading causes of preventable blindness. OBJECTIVE: This review describes current and emerging therapies for NIU. METHODS: PubMed searches were conducted using the terms uveitis, therapy, corticosteroids, immunomodulators, biologics, intravitreal injections, intraocular implants, and adverse events deemed relevant if they presented data relating to prevalence, diagnosis, and treatment of uveitis. RESULTS: Diagnosis and management of NIU may require collaboration among different healthcare providers, including ophthalmologists and rheumatologists. Although many patients with NIU respond to corticosteroid (CS) therapy, long-term CS use can be associated with potentially severe adverse events. Localized CS therapies have been developed to reduce adverse events; however, some intravitreal injections and intraocular implants were linked to elevated intraocular pressure and cataracts. CS-sparing therapies such as biologics have demonstrated efficacy and safety while reducing CS burden. Biologics targeting tumor necrosis factor provide CS-sparing options for patients with NIU. Additional studies are needed to address long-term efficacy and safety of biologics targeting IL-6 and inhibitors of JAK/STAT. CONCLUSION: Biologics, JAK/STAT inhibitors, and improved localized therapies may provide additional options for patients with NIU.

Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III.

PURPOSE: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Phase 3, open-label, multicenter clinical trial extension (VISUAL III). PARTICIPANTS: Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. METHODS: Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. MAIN OUTCOME MEASURES: Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. RESULTS: Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. CONCLUSIONS: Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.

Is HIV a model of accelerated or accentuated aging?

BACKGROUND: Antiretroviral therapy has reduced the incidence of adverse events and early mortality in HIV-infected persons. Despite these benefits, important comorbidities that increase with age (eg, diabetes, cardiovascular disease, cancer, liver disease, and neurocognitive impairment) are more prevalent in HIV-infected persons than in HIV-uninfected persons at every age, and geriatric syndromes such as falls and frailty occur earlier in HIV-infected persons. This raises a critical research question: Does HIV accelerate aging through pathways and mechanisms common to the aging process or is HIV simply an additional risk factor for a wide number of chronic conditions, thus accentuating aging? METHODS: Extensive literature review. RESULTS: The purpose of this review is to briefly outline the evidence that age-related clinical syndromes are exacerbated by HIV, examine the ways in which HIV is similar, and dissimilar from natural aging, and assess the validity of HIV as a model of premature aging. Specific biomarkers of aging are limited in HIV-infected hosts and impacted by antiretroviral therapy, and a high rate of modifiable life style confounders (eg, smoking, substance abuse, alcohol) and coinfections (eg, hepatitis) in HIV-infected participants. CONCLUSIONS: There is a need for validated biomarkers of aging in the context of HIV. Despite these differences, welldesigned studies of HIV-infected participants are likely to provide new opportunities to better understand the mechanisms that lead to aging and age-related diseases.

Retinal nerve fibre layer thickness and contrast sensitivity in HIV-infected individuals in South Africa: a case-control study.

BACKGROUND: Antiretroviral treatment (ART) has altered the spectrum of HIV-related eye disease, resulting in a lower prevalence of retinal opportunistic infections (OIs). However, abnormalities in visual function have been reported in HIV-infected individuals despite effective viral suppression and the absence of retinal OIs. These changes may be mediated by an HIV-associated 'neuroretinal disorder', characterized by changes in the retinal nerve fibre layer (RNFL). HIV infection may also be associated with accelerated biological aging. The aim of this study was to investigate the relationships between contrast sensitivity, RNFL thickness, HIV infection and frailty in South African adults. METHODS: Case-control study of 225 HIV-infected individuals without retinal OIs and 203 gender/age-matched HIV-seronegative individuals. Peri-papillary RNFL thickness was determined with spectral domain optical coherence tomography in four quadrants. CS was measured using a Pelli-Robson chart. Frailty was assessed using standard criteria. Multivariable linear and logistic regression were used to assess associations between HIV status and RNFL/CS and frailty. RESULTS: The median age of both groups was similar (41.2 vs. 41.9 years, p = 0.37). 88% of HIV-infected individuals were receiving ART and their median CD4 count was 468 cells/µl. Adjusted CS score was lower in HIV-infected participants compared to HIV-seronegative individuals (1.76 vs. 1.82, p = 0.002). Independent predictors of poor CS in the HIV-infected group were positive frailty status and current HIV viral load >2 log copies/ml. Lower CS score was also associated with thin temporal RNFL in HIV-infected individuals (p = 0.04). Superior quadrant RNFL thickness was greatest in ART-naïve participants relative to the HIV-uninfected group (p-trend = 0.04). Longer ART duration was associated with thinning of inferior and nasal RNFL quadrants (p-trend = 0.03 and 0.04, respectively). CONCLUSIONS: Contrast sensitivity is reduced in HIV-infected individuals and functionally associated with frailty and unsuppressed viraemia. This may reflect structural changes in the RNFL that are evident despite the absence of OIs.

Ocular parameters of biological ageing in HIV-infected individuals in South Africa: relationship with chronological age and systemic biomarkers of ageing.

HIV-infected individuals have an increased risk of age-related morbidity despite antiretroviral treatment (ART). Several anatomic and functional ophthalmological parameters are associated with increasing chronological age. These may, therefore, potentially serve as biomarkers of ageing. We investigated associations between ocular parameters (lens density, retinal vessel calibre, corneal endothelium and retinal nerve fibre layer thickness) and two 'cellular' biomarkers of ageing (leukocyte telomere length and CDKN2A expression) and with frailty in a cross-sectional study of 216 HIV-infected individuals. All ocular parameters, telomere length and frailty were associated with chronological age, whereas CDKN2A expression was not. Retinal venular calibre and lens density were associated with shorter telomere length (p-trend=0.04, and 0.08, respectively), whereas CDKN2A expression and frailty status were not associated with ocular parameters. Longitudinal studies are warranted to assess the integration of retinal vascular calibre and lens density with systemic markers to develop an overall index of biological ageing in HIV infection.

Burden of HIV-related cytomegalovirus retinitis in resource-limited settings: a systematic review.

BACKGROUND: Cytomegalovirus (CMV) is a late-stage opportunistic infection in people living with human immunodeficiency virus (HIV)/AIDS. Lack of ophthalmological diagnostic skills, lack of convenient CMV treatment, and increasing access to antiretroviral therapy have all contributed to an assumption that CMV retinitis is no longer a concern in low- and middle-income settings. METHODS: We conducted a systematic review and meta-analysis of published and unpublished studies reporting prevalence of CMV retinitis in low- and middle-income countries. Eligible studies assessed the occurrence of CMV retinitis by funduscopic examination within a cohort of at least 10 HIV-positive adult patients. RESULTS: We identified 65 studies from 24 countries, mainly in Asia (39 studies, 12 931 patients) and Africa (18 studies, 4325 patients). By region, the highest prevalence was observed in Asia with a pooled prevalence of 14.0% (11.8%-16.2%). Almost a third (31.6%, 95% confidence interval [CI], 27.6%-35.8%) had vision loss in 1 or both eyes. Few studies reported immune status, but where reported CD4 count at diagnosis of CMV retinitis was <50 cells/µL in 73.4% of cases. There was no clear pattern of prevalence over time, which was similar for the period 1993-2002 (11.8%; 95% CI, 8%-15.7%) and 2009-2013 (17.6%; 95% CI, 12.6%-22.7%). CONCLUSIONS: Prevalence of CMV retinitis in resource low- and middle-income countries, notably Asian countries, remains high, and routine retinal screening of late presenting HIV-positive patients should be considered. HIV programs must ensure capacity to manage the needs of patients who present late for care.

Accelerated biological ageing in HIV-infected individuals in South Africa: a case-control study.

OBJECTIVES: Little is known about the impact of HIV infection on biological ageing in sub-Saharan Africa. The study aimed to assess biological ageing in South African HIV-infected adults and HIV-seronegative individuals using two validated biomarkers, telomere length and CDKN2A expression (a mediator of cellular senescence). DESIGN: A case-control study. METHODS: Two hundred and thirty-six HIV-infected adults aged at least 30 years and 250 age and sex frequency matched HIV-seronegative individuals were recruited from clinics in township communities in Cape Town. Biological ageing was evaluated by measurement of telomere length and CDKN2A expression in peripheral blood leukocytes. RESULTS: The median ages of the HIV-infected and HIV-seronegative participants were 39 and 40 years, respectively. Among HIV-infected participants, 87.1% were receiving antiretroviral therapy (ART), their median CD4⁺ cell count was 468 cells/µl and 84.3% had undetectable viral load. Both biomarkers were validated against chronological age in HIV-seronegative individuals. Telomere length was significantly shorter in HIV-infected individuals than in HIV-seronegative individuals (mean relative T/S ratio ±SE:0.91 ± 0.007 vs. 1.07 ± 0.008, P < 0.0001). CD2NKA expression was higher in HIV-infected participants than in HIV-seronegative individuals (mean expression: 0.45 ± 0.02 vs. 0.36 ± 0.03, P = 0.003). Socioeconomic factors were not associated with biological ageing in HIV-infected participants. However, in participants on ART with undetectable viral load, biomarker levels indicated greater biological ageing in those with lower current CD4⁺ cell counts. CONCLUSION: Telomere length and CDKN2A expression were both consistent with increased biological ageing in HIV-infected individuals. Prospective studies of the impact of HIV on biological ageing in sub-Saharan Africa are warranted.

Assessment of candidate ocular biomarkers of ageing in a South African adult population: relationship with chronological age and systemic biomarkers.

Certain anatomic and functional parameters of the eye change with increasing chronological age. They may, therefore, serve as potential biomarkers of ageing. We investigated associations between four such ocular parameters (lens density, retinal vessel calibre, corneal endothelial cells and retinal nerve fibre layer thickness) and two 'cellular' biomarkers of ageing (leukocyte telomere length and CDKN2A expression), with frailty (a clinical correlate of biological ageing) in a population of South African adults. All ocular parameters revealed an association with either telomere length or CDKN2A expression. However, lens density was most strongly correlated with age, increased CDKN2A expression, and with frailty (p=0.05 and 0.03, respectively). Narrow retinal arteriolar diameter, associated with increased chronological age, was also associated with increased CDK2NA expression (0.42 vs. 0.31, p=0.02) but not with frailty. Ocular parameters may aid in determining biological age, warranting investigation in longitudinal studies.

Corneal endothelial cells provide evidence of accelerated cellular senescence associated with HIV infection: a case-control study.

BACKGROUND: Cellular senescence may be a key factor in HIV-related premature biological aging. We assessed features of the corneal endothelium that are known to be associated with biological aging, and cellular senescence markers in HIV-infected adults. METHODS: Case-control study of 242 HIV-infected adults and 249 matched controls. Using specular microscopy, the corneal endothelium was assessed for features of aging (low endothelial cell density [ECD], high variation in cell size, and low hexagonality index). Data were analysed by multivariable regression. CDKN2A expression (a cell senescence mediator) was measured in peripheral blood leukocytes and 8-hydroxy-2'-deoxyguanosine (8-OHDG; an oxidative DNA damage marker) levels were measured in plasma. RESULTS: The median age of both groups was 40 years. Among HIV-infected adults, 88% were receiving antiretroviral therapy (ART); their median CD4 count was 468 cells/µL. HIV infection was associated with increased odds of variation in cell size (OR = 1.67; 95% CI: 1.00-2.78, p = 0.04). Among HIV-infected participants, low ECD was independently associated with current CD4 count <200 cells/µL (OR = 2.77; 95%CI: 1.12-6.81, p = 0.03). In participants on ART with undetectable viral load, CDKN2A expression and 8-OHDG levels were higher in those with accelerated aging, as reflected by lower ECD. CONCLUSIONS: The corneal endothelium shows features consistent with HIV-related accelerated senescence, especially among those with poor immune recovery.

Increased ocular lens density in HIV-infected individuals with low nadir CD4 counts in South Africa: evidence of accelerated aging.

BACKGROUND: HIV infection is thought to be associated with an increased risk of age-related morbidity and premature aging. Lens density increases with age and may function as a biomarker of aging. The relationship of lens density measurements with clinical and demographic characteristics in HIV-infected individuals in comparison with a matched population of HIV-seronegative individuals was investigated. METHODS: Case-control study of 490 adults aged greater than or equal to 30 years composed of 242 HIV-infected adults and 248 age- and sex-matched HIV-seronegative individuals. Lens density was assessed using lens densitometry (Pentacam) imaging. Measurements were divided into quartiles, and comparison of HIV status and HIV-related factors was assessed by multivariate and multinomial logistic regression. RESULTS: The mean age was 41.2 years in HIV-infected adults and 42.3 years in HIV-seronegative individuals (P = 0.14). Of the HIV-infected adults, 88% were receiving antiretroviral therapy (ART) (median duration, 58 months), and within this group, their median CD4 count was 468 cells per microliter and 84% had undetectable viral load. Although adjusted lens densities were similar by HIV serostatus, participants on ART and who had nadir CD4 counts less than 200 cells per microliter had a higher risk of high lens density compared with HIV-seronegative individuals (P trend = 0.04). Lens density was weakly associated with detectable HIV viremia despite ART, but not with current CD4 count. CONCLUSIONS: HIV-infected individuals on ART with nadir CD4 counts <200 cells per microliter had increased risk of higher lens density. Lens density may represent a novel biomarker of aging, providing insight into accelerated aging trajectories in HIV infection.

The eye as a model of ageing in translational research--molecular, epigenetic and clinical aspects.

The eye and visual system are valuable in many areas of translational research such as stem cell therapy, transplantation research and gene therapy. Changes in many ocular tissues can be measured directly, easily and objectively in vivo (e.g. lens transparency; retinal blood vessel calibre; corneal endothelial cell counts) and so the eye may also be a uniquely useful site as a model of ageing. This review details cellular, molecular and epigenetic mechanisms related to ageing within the eye, and describes ocular parameters that can be directly measured clinically and which might be of value in ageing research as the translational "window to the rest of the body". The eye is likely to provide a valuable model for validating biomarkers of ageing at molecular, epigenetic, cellular and clinical levels. A research agenda to definitively establish the relationship between biomarkers of ageing and ocular parameters is proposed.

Frailty in HIV-infected adults in South Africa.

OBJECTIVES: Some evidence suggests that HIV infection is associated with premature frailty-a syndrome typically viewed as being related to ageing. We determined the prevalence and predictors of frailty in a population of HIV-infected individuals in South Africa. DESIGN: Case-control study of 504 adults more than the age of 30 years, composed of 248 HIV-infected adults and 256 age- and gender-matched, frequency-matched HIV-seronegative individuals. METHODS: Frailty was defined by standardized assessment comprised of ≥ 3 of weight loss, low physical activity, exhaustion, weak grip strength, and slow walking time. Independent predictors of frailty were evaluated using multivariable logistic regression. RESULTS: The mean ages of the HIV-infected and HIV-seronegative groups were 41.1 ± 7.9 years and 42.6 ± 9.6 years, respectively. Of the HIV-infected adults, 87.1% were receiving antiretroviral treatment (median duration, 58 months), their median CD4 count was 468 cells/µL (interquartile range = 325-607 cells/µL) and 84.3% had undetectable plasma viral load. HIV-infected adults were more likely to be frail than HIV-seronegative individuals (19.4% vs. 13.3%; P = 0.07), and this association persisted after adjustment for confounding variables [adjusted OR = 2.14; 95% confidence interval (95% CI): 1.16-3.92, P = 0.01]. Among HIV-infected individuals, older age was a strong predictor of frailty, especially among women (women: OR = 2.55 per 10-year age increase; men: OR = 1.29 per 10-year age increase, P-interaction = 0.01). Lower current CD4 count (<500 cells/µL) was also independently associated with frailty (OR = 2.84; 95% CI: 1.02 -7.92, P = 0.04). CONCLUSIONS: HIV infection is associated with premature development of frailty, especially in women. Since higher CD4 counts were associated with lower risk of frailty, earlier initiation of antiretroviral treatment may be protective.

Retinal arterioles narrow with increasing duration of anti-retroviral therapy in HIV infection: a novel estimator of vascular risk in HIV?

OBJECTIVES: HIV infection is associated with an increased risk of age-related morbidity mediated by immune dysfunction, atherosclerosis and inflammation. Changes in retinal vessel calibre may reflect cumulative structural damage arising from these mechanisms. The relationship of retinal vessel calibre with clinical and demographic characteristics was investigated in a population of HIV-infected individuals in South Africa. METHODS: Case-control study of 491 adults ≥30 years, composed of 242 HIV-infected adults and 249 age- and gender-matched HIV-negative controls. Retinal vessel calibre was measured using computer-assisted techniques to determine mean arteriolar and venular diameters of each eye. RESULTS: The median age was 40 years (IQR: 35-48 years). Among HIV-infected adults, 87.1% were receiving highly active antiretroviral therapy (HAART) (median duration, 58 months), their median CD4 count was 468 cells/µL, and 84.3% had undetectable plasma viral load. Unadjusted mean retinal arteriolar diameters were 163.67±17.69 µm in cases and 161.34±17.38 µm in controls (p = 0.15). Unadjusted mean venular diameters were 267.77±18.21 µm in cases and 270.81±18.98 µm in controls (p = 0.07). Age modified the effect of retinal arteriolar and venular diameters in relation to HIV status, with a tendency towards narrower retinal diameters in HIV cases but not in controls. Among cases, retinal arteriolar diameters narrowed with increasing duration of HAART, independently of age (167.83 µm <3 years of HAART vs. 158.89 µm >6 years, p-trend = 0.02), and with a HIV viral load >10,000 copies/mL while on HAART (p = 0.05). HIV-related venular changes were not detected. CONCLUSIONS: Narrowing of retinal arteriolar diameters is associated with HAART duration and viral load, and may reflect heightened inflammatory and pro-atherogenic states of the systemic vasculature. Measurement of retinal vascular calibre could be an innovative non-invasive method of estimating vascular risk in HIV-infected individuals.

Cytomegalovirus retinitis associated with HIV in resource-constrained settings: systematic screening and case detection.

Although cytomegalovirus (CMV) can cause a wide spectrum of multi-system disorders in HIV-infected patients, retinal disease is by far the most common clinical manifestation and may lead to blindness if untreated. We discuss the rationale for systematic case detection for CMV retinitis (CMVR) within the HIV-affected population, focusing particularly on resource-limited settings. The gold standard for detection of CMVR is indirect ophthalmoscopy performed by a trained ophthalmologist. However this is generally not feasible in resource-constrained settings. Alternative methods include fundus photography or the use of laboratory techniques to detect CMV infection. Training and deployment of non-ophthalmic personnel to detect CMVR by ophthalmoscopy or with novel strategies may be a paradigm shift that needs to occur in order to provide effective systematic case detection for those at risk of CMVR in resource-constrained settings. Further research is needed to determine the diagnostic accuracy and operational feasibility of different strategies in resource-limited settings.

Differing spectrum of HIV-associated ophthalmic disease among patients starting antiretroviral therapy in India and South Africa.

Differences in the prevalence and spectrum of HIV-associated ophthalmic disease in Africa and Asia are not well documented. We studied two comparable cohorts of patients initiating antiretroviral therapy in Mumbai, India, and Cape Town, South Africa. The prevalence of HIV-associated ophthalmic disease was higher in the Indian population (17.5%) than in the South African population (12.1%). This was largely because of vitreo-retinal opportunistic infections (11.4%vs. 2.6%, respectively), notably cytomegalovirus retinitis. This difference persisted after adjusting for confounding factors (adjusted odds ratio=11.32, 95% confidence interval: 2.67-48.13), confirming a marked geographical difference in the prevalence of HIV-associated retinal disease.

Prevalence of eye disease in early childhood and associated factors: findings from the millennium cohort study.

PURPOSE: To report the prevalence and distribution of eye conditions and visual impairment and associations with early social and biological factors using parental report of diagnosed eye conditions and additional chronic illnesses. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: We included 14 981 children, aged 3 years, participating in the United Kingdom Millennium Cohort Study. METHODS: Data on demographic, socioeconomic, and maternal and child health factors were obtained by maternal report through structured interview and verbatim reports of diagnosed eye problems and additional chronic illnesses were recorded. Multinomial regression analyses were used to calculate risk ratios of the association of eye disease (with or without associated visual impairment), with socioeconomic and early life factors. MAIN OUTCOME MEASURES: Parental report of diagnosed eye conditions and other chronic illnesses. RESULTS: Overall, at 3 years, 5.7% (95% confidence interval, 5.2-6.3%; n = 881) of children had ≥ 1 eye condition with 0.24% (0.15-0.3%; n = 45) reported to have associated visual impairment. In the majority, time of onset was reported to be the first year of life. Eye disorders without report of visual impairment were independently associated with lower socioeconomic status, decreasing birth weight, and prematurity. Visual impairment was more likely in those of low birthweight for gestational age and from an ethnic minority group. Maternal illnesses during pregnancy were associated with eye disease without reported visual impairment, as was white ethnicity. CONCLUSIONS: Good research opportunities exist within the context of population-based general health surveys to use parental report to estimate minimum prevalence, investigate associations of eye disease with a broad range of environmental factors, and as a mechanism for "flagging" individuals with eye disease in a population sample for further study. Our findings regarding the association of parentally reported childhood eye disease with early life factors such as modest degrees of prematurity, ethnicity and maternal ill-health warrant further investigation. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Prevalence of and early-life influences on childhood strabismus: findings from the Millennium Cohort Study.

BACKGROUND: Strabismus is a common disorder of largely unknown cause reported to occur more frequently in children with neurodevelopmental conditions and in children born prematurely or of low birth weight. Population-based investigation of other potential early-life influences has been limited. OBJECTIVE: To investigate the prevalence of and the early-life risk factors associated with childhood strabismus. DESIGN: Cross-sectional analytical study of a nationally representative sample of children participating in the Millennium Cohort Study. SETTING: United Kingdom. PARTICIPANTS: A population-based sample of 14 980 children aged 3 years. MAIN OUTCOME MEASURES: Parental report of "isolated" strabismus and "neurodevelopmental" strabismus (ie, in the context of neurologic disorders), considered separately. RESULTS: Three hundred forty-three children had strabismus (of whom 20 [5.8%] had neurodevelopmental/neurologic disorders), giving a total weighted prevalence of 2.1% (95% confidence interval, 1.8%-2.4%). In multivariable analysis, the risk of isolated strabismus was reduced in children of nonwhite maternal ethnicity and was increased in those born after an assisted or cesarean delivery and in those who were of low birth weight and preterm (in particular, late preterm). An increased risk of neurodevelopmental strabismus was independently associated with maternal smoking into later pregnancy, maternal illnesses in pregnancy, and decreasing birth weight for gestational age and sex. Socioeconomic status was associated with isolated (inverse relationship) and neurodevelopmental (U-shaped relationship) strabismus. CONCLUSIONS: Several early-life social and biological factors are associated with strabismus, with differences in patterns between isolated and neurodevelopmental forms. Further collaborative research could explore this hypothesis to identify modifiable risk factors.