Retinal perfusion is linked to cognition and brain MRI biomarkers in Black Americans.

INTRODUCTION: We investigated whether retinal capillary perfusion is a biomarker of cerebral small vessel disease and impaired cognition among Black Americans, an understudied group at higher risk for dementia. METHODS: We enrolled 96 Black Americans without known cognitive impairment. Four retinal perfusion measures were derived using optical coherence tomography angiography. Neurocognitive assessment and brain magnetic resonance imaging (MRI) were performed. Multiple linear regression analyses were performed. RESULTS: Lower retinal capillary perfusion was correlated with worse Oral Symbol Digit Test (P < = 0.005) and Fluid Cognition Composite scores (P < = 0.02), but not with the Crystallized Cognition Composite score (P > = 0.41). Lower retinal perfusion was also correlated with higher free water and peak width of skeletonized mean diffusivity, and lower fractional anisotropy (all P < 0.05) on MRI (N = 35). DISCUSSION: Lower retinal capillary perfusion is associated with worse information processing, fluid cognition, and MRI biomarkers of cerebral small vessel disease, but is not related to crystallized cognition.

Visual Field Loss Impacts Vision-Specific Quality of Life by Race and Ethnicity: The Multiethnic Ophthalmology Cohorts of California Study.

PURPOSE: To assess the impact of visual field loss (VFL) on vision-specific quality of life (VSQOL) by race, ethnicity, and age. DESIGN: Pooled analysis of cross-sectional data from 3 population-based, prospective cohort studies. PARTICIPANTS: The Multiethnic Ophthalmology Cohorts of California Study (MOCCaS) participants included 6142 Latinos, 4582 Chinese Americans, and 6347 Black Americans from Los Angeles County. METHODS: A total of 17 071 adults aged 40 years and older completed comprehensive interviews and ophthalmic examinations from 2000 to 2018. VFL was measured using the Humphrey Swedish Interactive Threshold Algorithm Standard 24-2 test as decibels (dB) of mean deviation (MD). Multivariable linear regression was used to evaluate the impact of VFL in the better-seeing eye on self-reported VSQOL scores, adjusting for sociodemographic and clinical covariables. Hierarchical modeling was performed to determine the best-fit model after considering main effects and interactions by race, ethnicity, and age. MAIN OUTCOME MEASURES: The VSQOL scores were measured using the 25 Item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). Item response theory was used to model vision-related task and well-being composite scores, and classical test theory was used to calculate 11 vision subscales. RESULTS: The impact of VFL on VSQOL varied by race and ethnicity. Five-point reductions in task and well-being scores were reached after mild-to-moderate VFL for Latinos (6.7 dB and 7.5 dB), mild-to-moderate VFL for Chinese Americans (7.0 dB and 8.7 dB), and moderate-to-severe VFL for Black Americans (10.1 dB and 12.9 dB), respectively. Differences met statistical significance when comparing Latinos and Black Americans (P < 0.001). Visual field loss had the largest effect on driving among all participants. Driving difficulties were the only VSQOL outcome modified by age; participants aged 65 years and older scored 0.487 lower points per MD of VFL (P < 0.001). Subscales most affected by VFL included role function, mental health, and dependency. CONCLUSIONS: Race and ethnicity modified the impact of VFL on VSQOL, even after adjusting for sociodemographic covariates. In MOCCaS, Latinos and Chinese Americans reported a greater change in VSQOL than Black Americans for the same level of VFL. Future work should assess whether findings were due to socioeconomic or cultural differences in perception of visual function.

Retinal Nerve Fiber Layer Thickness in Healthy Eyes of Black, Chinese, and Latino Americans: A Population-Based Multiethnic Study.

PURPOSE: To compare peripapillary retinal nerve fiber layer (RNFL) thickness among healthy adults by race and ethnicity and to identify determinants of RNFL thickness. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Data from 6133 individuals (11 585 eyes) from 3 population-based studies in Los Angeles County, California, 50 years of age or older and of self-described African, Chinese, or Latin American ancestry. METHODS: We measured RNFL thickness and optic nerve head parameters using the Cirrus HD-OCT 4000. Multivariate linear mixed regression was used to evaluate factors associated with RNFL thickness among participants without ocular diseases. MAIN OUTCOME MEASURES: Determinants and modifiers of RNFL thickness. RESULTS: The mean age of the participants was 60.1 years (standard deviation, 7.4 years). Black Americans showed the lowest RNFL thickness and smallest cup-to-disc ratio (CDR), and Chinese Americans showed the largest CDR and disc area after adjusting for age and gender (all P < 0.05). Per each 10-year older age group, the average RNFL thickness was 2.5 µm (95% confidence interval [CI], 1.8-3.1 µm), 2.8 µm (95% CI, 2.3-3.3 µm), and 3.5 µm (95% CI, 2.9-4.1 µm) thinner for Black, Chinese, and Latino Americans, respectively (age trend P < 0.05 and interaction P = 0.041). Black Americans compared with Chinese Americans, older age, male gender, hypertension, diabetes, greater axial length (AL), bigger disc area, and lower scan signal strength were associated with thinner average RNFL. Race, age, AL, disc area, and scan signal strength consistently were associated with RNFL thickness in all quadrants, whereas gender, hypertension, and diabetes were associated with RNFL thickness in select quadrants. Age and race explained the greatest proportion of variance of RNFL thickness. CONCLUSIONS: Clinically important differences in RNFL thickness are present in healthy adults 50 years of age or older from different racial and ethnic groups of the same age, with the thinnest measures observed in Black Americans. This difference remains after accounting for disc size and AL. Furthermore, age-related RNFL thinning differs by race and ethnicity. Longitudinal studies are needed to verify our findings and to assess the influence of race and ethnicity in the clinical application of RNFL thickness.

Influence of Distance and Near Visual Impairment on Self-Reported Near Visual Functioning in a Multinational Study.

PURPOSE: To assess the influence of distance and near visual impairment on self-reported near visual functioning (VF) in a multinational study. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Participants aged 35 years or older were selected randomly with cluster sampling at 7 sites: rural sites in Nepal (Kaski) and India (Madurai), a semirural site in China (Shunyi), semiurban sites in South Africa (Durban) and Niger (Dosso), and urban sites in the United States (Los Angeles) and China (Guangzhou). METHODS: Binocular presenting distance and near visual acuity (VA) were measured with a logarithm of the minimum angle of resolution tumbling E chart at 4 m and 40 cm, respectively. A 12-item near VF questionnaire interview was administered by trained local interviewers, with responses scored from 100 to 0 as visual disability increased. Multiple linear regression was used to investigate the association of age, gender, education, and VA with overall eyesight, difficulty with activities, and social functioning subscale scores. MAIN OUTCOME MEASURES: Visual functioning subscale scores. RESULTS: The study sample consisted of 6851 questionnaire respondents. The VF subscale scores decreased significantly with worse distance and near VA, and even mildly impaired VA could result in reduced VF. Lower VF subscale scores were associated with older age at 4 sites, female gender at 3 sites, and greater education at 2 sites. The influence of near VA was greater than distance VA at 3 sites, and at 1 site, distance VA was more influential than near VA. With study site included in the regression modeling, lower scores for the overall eyesight subscale (compared with the Shunyi reference site) were found in Guangzhou, Kaski, and Durban; lower difficulty in activities scores were found in Kaski and Durban, but better scores were found in Guangzhou and Madurai; and social functioning scores were lower in Kaski, Durban, and Dosso. CONCLUSIONS: Along the entire VA spectrum, lower levels of distance and near VA led to significant reductions in VF subscale scores, with wide variation both within and between study sites. The impact of near vision on VF should receive greater emphasis with further investigation in various socioeconomic and cultural settings.

Assessment of retinal vascular oxygenation and morphology at stages of diabetic retinopathy in African Americans.

BACKGROUND: Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of blindness in working-age adults. The likelihood of visual impairment associated with DR is two-fold higher in the African-American (AA) compared to non-Hispanic white. Although alterations in retinal vessel oxygenation and morphology have been reported in DR, there is limited knowledge about these vascular changes in AA subjects. The purpose of the current study was to investigate alterations in retinal vascular oxygen saturation (SO2), vessel diameter (D) and tortuosity at severity stages of DR in AA subjects. METHODS: A nested case-control study of 56 AA subjects was conducted. Right eyes were grouped as non-diabetic (ND) (N = 26), no clinical DR (NDR) (N = 19), or moderate/severe non-proliferative DR (NPDR) (N = 11). Imaging was performed using a commercially available scanning laser ophthalmoscope. Images were analyzed to determine retinal arterial and venous SO2 (SO2A and SO2V), diameter (DA and DV), and vessel tortuosity index (VTI) (VTIA and VTIV). RESULTS: SO2V and DV were higher in NPDR compared to ND and NDR groups (P < 0.05). There were no significant differences in SO2A and DA among ND, NDR, and NPDR groups (P > 0.8). Maximum VTIA was higher in diabetics (NDR and NPDR) compared to non-diabetics (P < 0.03). There was no significant difference in maximum VTIV among the 3 groups (P = 0.5). CONCLUSIONS: The findings advance our understanding of DR pathophysiology in the AA population and may propel identification of race-specific retinal vascular biomarkers for improved diagnosis and monitoring of DR.

Prevalence, Characteristics, and Risk Factors of Moderate or High Hyperopia among Multiethnic Children 6 to 72 Months of Age: A Pooled Analysis of Individual Participant Data.

PURPOSE: To describe the prevalence, ocular characteristics, and associated risk factors of moderate to high hyperopia in early childhood. DESIGN: Pooled analysis of individual participant data from population-based studies. PARTICIPANTS: Six- to 72-month-old multiethnic children who participated in 4 population-based studies of pediatric eye diseases. METHODS: The pooled studies conducted comparable parental interviews and ocular examinations including cycloplegic autorefraction. Presence of hyperopia was defined based on cycloplegic refractive error in the worse eye. Multivariate analyses were performed to evaluate the association of potential risk factors with hyperopia risk. MAIN OUTCOME MEASURES: Prevalence and odds ratios of moderate to high hyperopia (≥4.0 diopters [D]). RESULTS: Cycloplegic refraction was completed in 15 051 children 6 to 72 months of age. Among these children, the overall prevalence of moderate to high hyperopia (≥4.0 D) in the worse eye was 3.2% (95% confidence interval, 2.9%-3.5%), accounting for 15.6% of all hyperopia (≥2.0 D). Among children with moderate to high hyperopia, both eyes were affected in 64.4%, 28.9% showed spherical anisometropia of 1.0 D or more, and 19.5% showed astigmatism of 1.5 D or more. Among 36- to 72-month-old children with moderate to high hyperopia, 17.6% wore glasses. Prevalence of moderate to high hyperopia was slightly less in 12- to 23-month-old children and was relatively stable in children 24 months of age and older. Non-Hispanic and Hispanic white race and ethnicity, family history of strabismus, maternal smoking during pregnancy, and being a participant in the United States studies were associated with a higher risk of moderate to high hyperopia (P < 0.05). CONCLUSIONS: By assembling similarly designed studies, our consortium provided robust estimates of the prevalence of moderate to high hyperopia in the general population and showed that in 6- to 72-month-old children, moderate to high hyperopia is not uncommon and its prevalence does not decrease with age. Risk factors for moderate to high hyperopia differ from those for low to moderate hyperopia (2.0-<4.0 D) in preschool children, with family history of strabismus and maternal smoking during pregnancy more strongly associated with moderate to high hyperopia than low to moderate hyperopia.

Surgical options in the management of landmine blast injuries of lower limb: a randomised prospective study.

Landmine blast injuries are high velocity shattering injuries that produce ghastly and gory wounds, presenting a dilemma to the treating surgeon, especially when the literature on this subject is limited. The aim of the present study is to enlist various surgical procedures that can be explored to treat such complex injuries. 60 cases having varied degrees of involvement of the lower limb from mine blasts were managed. Surgical treatment was tailored to the individual requirement depending on the extent and severity of injury. Serial surgical wound debridement was an integral part of all these procedures. Limb length preservation was possible in 70% cases. A combination of surgical approaches and procedures from fixation to different types of amputations can be employed for treating mine blast injuries to maximise residual limb function.

Modeling topographic regularity in structural brain connectivity with application to tractogram filtering.

Topographic regularity is an important biological principle in brain connections that has been observed in various anatomical studies. However, there has been limited research on mathematically characterizing this property and applying it in the analysis of in vivo connectome imaging data. In this work, we propose a general mathematical model of topographic regularity for white matter fiber bundles based on previous neuroanatomical understanding. Our model is based on a novel group spectral graph analysis (GSGA) framework motivated by spectral graph theory and tensor decomposition. The GSGA provides a common set of eigenvectors for the graphs formed by topographic proximity of nearby tracts, which gives rises to the group graph spectral distance, or G2SD, for measuring the topographic regularity of each fiber tract in a tractogram. Based on this novel model of topographic regularity in fiber tracts, we then develop a tract filtering algorithm that can generally be applied to remove outliers in tractograms generated by any tractography algorithm. In the experimental results, we show that our novel algorithm outperforms existing methods in both simulation data from ISMRM 2015 Tractography Challenge and real data from the Human Connectome Project (HCP). On a large-scale dataset from 215 HCP subjects, we quantitatively show our method can significantly improve the retinotopy in the reconstruction of the optic radiation bundle. The software for the tract filtering algorithm developed in this work has also been publicly released on NITRC (https://www.nitrc.org/projects/connectopytool).

Genome-wide association study identifies WNT7B as a novel locus for central corneal thickness in Latinos.

The cornea is the outermost layer of the eye and is a vital component of focusing incoming light on the retina. Central corneal thickness (CCT) is now recognized to have a significant role in ocular health and is a risk factor for various ocular diseases, such as keratoconus and primary open angle glaucoma. Most previous genetic studies utilized European and Asian subjects to identify genetic loci associated with CCT. Minority populations, such as Latinos, may aid in identifying additional loci and improve our understanding of the genetic architecture of CCT. In this study, we conducted a genome-wide association study (GWAS) in Latinos, a traditionally understudied population in genetic research, to further identify loci contributing to CCT. Study participants were genotyped using either the Illumina OmniExpress BeadChip (∼730K markers) or the Illumina Hispanic/SOL BeadChip (∼2.5 million markers). All study participants were 40 years of age and older. We assessed the association between individual single nucleotide polymorphisms (SNPs) and CCT using linear regression, adjusting for age, gender and principal components of genetic ancestry. To expand genomic coverage and to interrogate additional SNPs, we imputed SNPs from the 1000 Genomes Project reference panels. We identified a novel SNP, rs10453441 (P = 6.01E-09), in an intron of WNT7B that is associated with CCT. Furthermore, WNT7B is expressed in the human cornea. We also replicated 11 previously reported loci, including IBTK, RXRA-COL5A1, COL5A1, FOXO1, LRRK1 and ZNF469 (P < 1.25E-3). These findings provide further insight into the genetic architecture of CCT and illustrate that the use of minority groups in GWAS will help identify additional loci.

Does time of surgery and complication have any correlation in the management of hip fracture in elderly and can early surgery affect the outcome?

OBJECTIVE: Hip fractures in the elderly are usually associated with a high rate of morbidity and mortality and affect quality of life. On review of published data, the current guidelines in the literature indicate that early surgery should be performed within 24 h of injury because it is associated with better functional outcomes and lower rates of perioperative complications and mortality. The aim of this study was to evaluate whether any correlation exists between early surgical intervention and functional outcomes. METHODS: In a retrospective study, we analyzed the records between January 2010 and December 2016 and 550 elderly patients between the age group of 65-95 were included. RESULTS: The results of early surgery were promising, 451 (82%) patients did not have any complication, 42 (7.6%) has developed bed sore, 23 (4%) developed a hospital-acquired infection, 13 (2.3%) developed wound infection, 08 (1.4%) developed DVT, 04 (0.7%) developed implant failure, and 09 (01%) died of some or other complications. CONCLUSION: Still, there is conflicting evidence in the published data that early surgery would improve mortality and function. However, early surgery definitively improves outcome and reduces morbidity, bed sores, infection, and the length of hospital stay could be improved by reducing the waiting time of hip surgery following fracture. We concluded that it is beneficial to the elderly patients to receive surgical treatment as early as possible.

RESPONSIVENESS OF THE NATIONAL EYE INSTITUTE VISUAL FUNCTION QUESTIONNAIRE-25 TO VISUAL ACUITY GAINS IN PATIENTS WITH DIABETIC MACULAR EDEMA: Evidence From the RIDE and RISE Trials.

PURPOSE: To evaluate the responsiveness of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) in patients with diabetic macular edema using data from the RIDE and RISE trials. METHODS: Patients were randomized to monthly intravitreal ranibizumab 0.3 mg, 0.5 mg, or sham injections for 2 years. The NEI VFQ-25 was administered at baseline and at Months 6, 12, 18, and 24. The least-squares mean change in NEI VFQ-25 for ≥15 letters gained or lost was derived from analysis of covariance models. RESULTS: The mean improvement in NEI VFQ-25 composite score associated with a ≥15-letter gain in best-corrected visual acuity over 24 months was 9.0 (95% confidence interval, 6.3-11.7) points in RIDE and 7.1 (95% confidence interval, 4.7-9.6) points in RISE. In patients who lost ≥15 letters, the mean worsening in overall NEI VFQ-25 composite score was -6.6 (95% confidence interval, -13.6 to 0.5) in RIDE and -2.7 (95% confidence interval, -8.9 to 3.5) in RISE. CONCLUSION: This exploratory analysis of data from the RIDE and RISE studies supports the responsiveness of the NEI VFQ-25 to changes in best-corrected visual acuity over time in patients with diabetic macular edema.

Development and Validation of a Deep Learning System for Diabetic Retinopathy and Related Eye Diseases Using Retinal Images From Multiethnic Populations With Diabetes.

Importance: A deep learning system (DLS) is a machine learning technology with potential for screening diabetic retinopathy and related eye diseases. Objective: To evaluate the performance of a DLS in detecting referable diabetic retinopathy, vision-threatening diabetic retinopathy, possible glaucoma, and age-related macular degeneration (AMD) in community and clinic-based multiethnic populations with diabetes. Design, Setting, and Participants: Diagnostic performance of a DLS for diabetic retinopathy and related eye diseases was evaluated using 494 661 retinal images. A DLS was trained for detecting diabetic retinopathy (using 76 370 images), possible glaucoma (125 189 images), and AMD (72 610 images), and performance of DLS was evaluated for detecting diabetic retinopathy (using 112 648 images), possible glaucoma (71 896 images), and AMD (35 948 images). Training of the DLS was completed in May 2016, and validation of the DLS was completed in May 2017 for detection of referable diabetic retinopathy (moderate nonproliferative diabetic retinopathy or worse) and vision-threatening diabetic retinopathy (severe nonproliferative diabetic retinopathy or worse) using a primary validation data set in the Singapore National Diabetic Retinopathy Screening Program and 10 multiethnic cohorts with diabetes. Exposures: Use of a deep learning system. Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUC) and sensitivity and specificity of the DLS with professional graders (retinal specialists, general ophthalmologists, trained graders, or optometrists) as the reference standard. Results: In the primary validation dataset (n = 14 880 patients; 71 896 images; mean [SD] age, 60.2 [2.2] years; 54.6% men), the prevalence of referable diabetic retinopathy was 3.0%; vision-threatening diabetic retinopathy, 0.6%; possible glaucoma, 0.1%; and AMD, 2.5%. The AUC of the DLS for referable diabetic retinopathy was 0.936 (95% CI, 0.925-0.943), sensitivity was 90.5% (95% CI, 87.3%-93.0%), and specificity was 91.6% (95% CI, 91.0%-92.2%). For vision-threatening diabetic retinopathy, AUC was 0.958 (95% CI, 0.956-0.961), sensitivity was 100% (95% CI, 94.1%-100.0%), and specificity was 91.1% (95% CI, 90.7%-91.4%). For possible glaucoma, AUC was 0.942 (95% CI, 0.929-0.954), sensitivity was 96.4% (95% CI, 81.7%-99.9%), and specificity was 87.2% (95% CI, 86.8%-87.5%). For AMD, AUC was 0.931 (95% CI, 0.928-0.935), sensitivity was 93.2% (95% CI, 91.1%-99.8%), and specificity was 88.7% (95% CI, 88.3%-89.0%). For referable diabetic retinopathy in the 10 additional datasets, AUC range was 0.889 to 0.983 (n = 40 752 images). Conclusions and Relevance: In this evaluation of retinal images from multiethnic cohorts of patients with diabetes, the DLS had high sensitivity and specificity for identifying diabetic retinopathy and related eye diseases. Further research is necessary to evaluate the applicability of the DLS in health care settings and the utility of the DLS to improve vision outcomes.

African Ancestry Is Associated with Higher Intraocular Pressure in Latinos.

PURPOSE: Intraocular pressure (IOP) is a major risk factor, as well as the only modifiable risk factor, for glaucoma. Racial differences have been observed in IOP measurements with individuals of African descent experiencing the highest IOP when compared with other ethnic groups. The purpose of this study was to examine the relationship between genetic ancestry and IOP in Latinos. DESIGN: Population-based genetic association study. PARTICIPANTS: A total of 3541 participants recruited from the Los Angeles Latino Eye Study. METHODS: Study participants were genotyped using the Illumina OmniExpress BeadChip (∼730K markers). We used STRUCTURE to estimate individual genetic ancestry. Simple and multiple linear regression, as well as quantile regression, analyses were performed to investigate the relationship between genetic ancestry and IOP. MAIN OUTCOME MEASURES: The relationship between genetic ancestry and IOP in Latinos. RESULTS: African ancestry was significantly associated with higher IOP in Latinos in our simple linear regression analysis (P = 0.002). After adjusting for age, gender, body mass index, systolic blood pressure, central corneal thickness, and type 2 diabetes, this association remained significant (P = 0.0005). The main association was modified by a significant interaction between African ancestry and hypertension (P = 0.037), with hypertensive individuals experiencing a greater increase in IOP with increasing African ancestry. CONCLUSIONS: To our knowledge, we demonstrate for the first time that African ancestry and its interaction with hypertension are associated with higher IOP in Latinos.

Visual Impairment and Blindness Avoided with Ranibizumab in Hispanic and Non-Hispanic Whites with Diabetic Macular Edema in the United States.

OBJECTIVE: To estimate visual impairment (VI) and blindness avoided with intravitreal ranibizumab 0.3 mg treatment for central-involved diabetic macular edema (DME) among Hispanic and non-Hispanic white individuals in the United States. DESIGN: Population-based model simulating visual acuity (VA) outcomes over 2 years after diagnosis and treatment of DME. PARTICIPANTS: Visual acuity changes with and without ranibizumab were based on data from the RISE, RIDE, and DRCR Network trials. METHODS: For the better-seeing eye, VA outcomes included VI, defined as worse than 20/40 in the better-seeing eye, and blindness, defined as VA of 20/200 or worse in the better-seeing eye. Incidence of 1 or both eyes with central-involved DME in 2010 were estimated based on the 2010 United States population, prevalence of diabetes mellitus, and 1-year central-involved DME incidence rate. Sixty-one percent of incident individuals had bilateral DME and 39% had unilateral DME, but DME could develop in the fellow eye. MAIN OUTCOMES MEASURES: Cases of VI and blindness avoided with ranibizumab treatment. RESULTS: Among approximately 102 million Hispanic and non-Hispanic white individuals in the United States 45 years of age and older in 2010, an estimated 37 274 had central-involved DME and VI eligible for ranibizumab treatment. Compared with no ranibizumab treatment, the model predicted that ranibizumab 0.3 mg every 4 weeks would reduce the number of individuals with VI from 11 438 (95% simulation interval [SI], 7249-16 077) to 6304 (95% SI, 3921-8981), a 45% (95% SI, 36%-53%) reduction at 2 years. Ranibizumab would reduce the number of incident eyes with VA worse than 20/40 from 16 910 (95% SI, 10 729-23 577) to 9361 (95% SI, 5839-13 245), a 45% (95% SI, 38%-51%) reduction. Ranibizumab was estimated to reduce the number of individuals with legal blindness by 75% (95% SI, 58%-88%) and the number of incident eyes with VA of 20/200 or worse by 76% (95% SI, 63%-87%). CONCLUSIONS: This model suggests that ranibizumab 0.3 mg every 4 weeks substantially reduces prevalence of VI and legal blindness 2 years after initiating treatment among Hispanic and non-Hispanic white individuals in the United States with central-involved DME that has caused vision loss.

The primary open-angle african american glaucoma genetics study: baseline demographics.

PURPOSE: To describe the baseline characteristics of the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study cohort, the largest African American population with primary open-angle glaucoma (POAG) recruited at a single institution (University of Pennsylvania [UPenn], Department of Ophthalmology, Scheie Eye Institute) to date. DESIGN: Population-based, cross-sectional, case-control study. PARTICIPANTS: A total of 2520 African American subjects aged 35 years or more who were recruited from the greater Philadelphia, Pennsylvania area. METHODS: Each subject underwent a detailed interview and eye examination. The interview assessed demographic, behavioral, medical, and ocular risk factors. Current ZIP codes surrounding UPenn were recorded and US census data were queried to infer socioeconomic status. The eye examination included measurement of visual acuity (VA) and intraocular pressure, and a detailed anterior and posterior segment examination, including gonioscopy, dilated fundus and optic disc examination, visual fields, stereo disc photography, optical coherence tomography, and measurement of central corneal thickness. MAIN OUTCOME MEASURES: The baseline characteristics of gender, age, and glaucoma diagnosis were collected. Body mass index (BMI), hypertension, diabetes, alcohol and tobacco use, ocular conditions (including blindness, cataract, nonproliferative diabetic retinopathy, and age-related macular degeneration), and use of ocular medication and surgery were examined. Median population density, income, education level, and other socioeconomic measures were determined for the study cohort. RESULTS: Of the 2520 African Americans recruited to the POAAGG study to date, 2067 (82.0%), including 807 controls and 1260 POAG cases, met all inclusion criteria and completed the detailed clinical ocular examination. Cases were more likely to have a lower BMI (P < 0.01) and report a history of blindness (VA of ≤20/200; P < 0.001), whereas controls were more likely to have diabetes (P < 0.001), have nonproliferative diabetic retinopathy (P = 0.02), and be female (P < 0.001). Study participants were drawn largely from predominantly African American neighborhoods of low income, high unemployment, and lower education surrounding UPenn. CONCLUSIONS: The POAAGG study has currently recruited more than 2000 African Americans eligible for a POAG genetics study. Blindness and low BMI were significantly associated with POAG. This population was predominantly recruited from neighborhoods whose population income exists at or near the federal poverty level.

Color vision deficiency in preschool children: the multi-ethnic pediatric eye disease study.

PURPOSE: To determine the sex- and ethnicity-specific prevalence of color vision deficiency (CVD) in black, Asian, Hispanic, and non-Hispanic white preschool children. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: The Multi-Ethnic Pediatric Eye Disease Study is a population-based evaluation of the prevalence of vision disorders in children in Southern California. A total of 5960 subjects 30 to 72 months of age were recruited for the study, of whom 4177 were able to complete color vision testing (1265 black, 812 Asian, 1280 Hispanic, and 820 non-Hispanic white). METHODS: Color vision testing was performed using Color Vision Testing Made Easy color plates (Home Vision Care, Gulf Breeze, FL), and diagnostic confirmatory testing was performed using the Waggoner HRR Diagnostic Test color plates (Home Vision Care). MAIN OUTCOME MEASURES: Testability of color vision in preschool children between 30 and 72 months of age and prevalence of CVD stratified by age, sex, and ethnicity. RESULTS: Testability was 17% in children younger than 37 months of age, increasing to 57% in children 37 to 48 months of age, 89% in children 49 to 60 months of age, and 98% in children 61 to 72 months of age. The prevalence of CVD among boys was 1.4% for black, 3.1% for Asian, 2.6% for Hispanic, and 5.6% for non-Hispanic white children; the prevalence in girls was 0.0% to 0.5% for all ethnicities. The ethnic difference in CVD was statistically significant between black and non-Hispanic white children (P = 0.0003) and between Hispanic and non-Hispanic white children (P = 0.02). In boys, most CVD cases were either deutan (51%) or protan (34%); 32% were classified as mild, 15% as moderate, and 41% as severe. CONCLUSIONS: Testability for CVD in preschool children is high by 4 years of age. The prevalence of CVD in preschool boys varies by ethnicity, with the highest prevalence in non-Hispanic white and lowest in black children.

Age-related prevalence and met need for correctable and uncorrectable near vision impairment in a multi-country study.

PURPOSE: To estimate the prevalence, potential determinants, and proportion of met need for near vision impairment (NVI) correctable with refraction approximately 2 years after initial examination of a multi-country cohort. DESIGN: Population-based, prospective cohort study. PARTICIPANTS: People aged ≥35 years examined at baseline in semi-rural (Shunyi) and urban (Guangzhou) sites in China; rural sites in Nepal (Kaski), India (Madurai), and Niger (Dosso); a semi-urban site (Durban) in South Africa; and an urban site (Los Angeles) in the United States. METHODS: Near visual acuity (NVA) with and without current near correction was measured at 40 cm using a logarithm of the minimum angle of resolution near vision tumbling E chart. Participants with uncorrected binocular NVA ≤20/40 were tested with plus sphere lenses to obtain best-corrected binocular NVA. MAIN OUTCOME MEASURES: Prevalence of total NVI (defined as uncorrected NVA ≤20/40) and NVI correctable and uncorrectable to >20/40, and current spectacle wearing among those with bilateral NVA ≤20/63 improving to >20/40 with near correction (met need). RESULTS: Among 13 671 baseline participants, 10 533 (77.2%) attended the follow-up examination. The prevalence of correctable NVI increased with age from 35 to 50-60 years and then decreased at all sites. Multiple logistic regression modeling suggested that correctable NVI was not associated with gender at any site, whereas more educated persons aged >54 years were associated with a higher prevalence of correctable NVI in Nepal and India. Although near vision spectacles were provided free at baseline, wear among those who could benefit was <40% at all but 2 centers (Guangzhou and Los Angeles). CONCLUSIONS: Prevalence of correctable NVI is greatest among persons of working age, and rates of correction are low in many settings, suggesting that strategies targeting the workplace may be needed.

Risk of cataract among subjects with acquired immune deficiency syndrome free of ocular opportunistic infections.

PURPOSE: To evaluate the risk of cataract in the setting of AIDS. DESIGN: Prospective cohort study. PARTICIPANTS: Subjects with AIDS free of ocular opportunistic infections throughout catamnesis. METHODS: From 1998 through 2008, subjects 13 years of age or older were enrolled. Demographic characteristics and clinical characteristics were documented at enrollment and semiannually. MAIN OUTCOME MEASURES: Cataract was defined as high-grade lens opacity observed by biomicroscopy judged to be the cause of a best-corrected visual acuity worse than 20/40. Eyes that underwent cataract surgery during follow-up were considered to have developed cataract before the first visit when pseudophakia or aphakia was observed. RESULTS: Among 1606 participants (3212 eyes) at enrollment, 1.9% (95% confidence interval [CI]: 1.3%-2.7%) were observed to have cataract or prior cataract surgery. Among the 2812 eyes initially free of cataract and followed longitudinally (median follow-up, 4.6 years), the incidence of cataract was 0.37%/eye-year (95% CI: 0.26%-0.53%). In addition to age, significant cataract risk factors included prior cataract in the contralateral eye (adjusted hazard ratio [aHR], 21.6; 95% CI: 10.4-44.8), anterior segment inflammation (aHR, 4.40; 95% CI: 1.64-11.9), prior retinal detachment (aHR, 4.94; 95% CI: 2.21-11.0), and vitreous inflammation (aHR, 7.12; 95% CI: 2.02-25.0), each studied as a time-updated characteristic. Detectable human immunodeficiency virus RNA in peripheral blood was associated with lower risk of cataract at enrollment (adjusted odds ratio, 0.32; 95% CI: 0.12-0.80) but not of incident cataract (aHR, 1.58; 95% CI: 0.90-2.76). After adjustment for other factors, neither the then-current absolute CD4+ T-cell count nor antiretroviral therapy status showed consistent association with cataract risk, nor did an additive diagnosis of other comorbidities. Compared with the available population-based studies that used similar definitions of cataract, the age-specific prevalence of cataract in our cohort was higher than in 1 of 2 such studies, and the age-specific incidence of cataract surgery was higher. CONCLUSIONS: Our results suggest cataract may occur earlier among patients with AIDS free of ocular opportunistic infections than in the general population. Cataract risk was associated most strongly with age and with other ocular morbidity in this population. With improved survival, the burden of cataract likely will increase for persons with the human immunodeficiency virus or AIDS.

Vision-related function after ranibizumab treatment for diabetic macular edema: results from RIDE and RISE.

OBJECTIVE: To examine the effects of intravitreal ranibizumab (Lucentis; Genentech, Inc., South San Francisco, CA) treatment on patient-reported vision-related function, as assessed by 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) scores, in patients with visual impairment secondary to center-involved diabetic macular edema (DME). DESIGN: Within 2 randomized, double-masked, phase 3 clinical trials (RIDE [A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema {ME} With Center Involvement Secondary to Diabetes Mellitus; NCT00473382] and RISE [A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema {ME} With Center Involvement Secondary to Diabetes Mellitus; NCT00473330]), the NEI VFQ-25 was administered at baseline and at the 6-, 12-, 18-, and 24-month follow-up visits. PARTICIPANTS: Three hundred eighty-two (100%) RIDE patients and 377 (100%) RISE patients. INTERVENTION: Patients were randomized 1:1:1 to monthly injections of intravitreal ranibizumab 0.3 or 0.5 mg or sham. Study participants could receive macular laser for DME from month 3 onward if specific criteria were met. MAIN OUTCOME MEASURES: Exploratory post hoc analysis of mean change from baseline in NEI VFQ-25 scores at 12 and 24 months. RESULTS: Across all treatment arms, 13% to 28% of enrolled eyes were the better-seeing eye. For all eyes in RIDE and RISE, the mean change in NEI VFQ-25 composite score improved more in ranibizumab-treated eyes at both the 12- and 24-month visits compared with sham treatment. For the better-seeing eyes at baseline, the mean change in composite score with 0.3 mg ranibizumab at the 24-month visit was 10.9 more (95% confidence interval [CI], 2.5-19.2) than sham for RIDE patients and 1.3 more (95% CI, -10.5 to 13.0) than sham for RISE patients. For the worse-seeing eyes at baseline, the mean change in composite score with 0.3 mg ranibizumab at the 24-month visit was 1.0 more (95% CI, -4.7 to 6.7) than sham for RIDE patients and 1.8 more (95% CI, -2.7 to 6.2) than sham for RISE patients. Similar results for most of these outcomes were seen with 0.5 mg ranibizumab. CONCLUSIONS: These phase 3 trials demonstrated that ranibizumab treatment for DME likely improves patient-reported vision-related function outcomes compared with sham, further supporting treatment of DME with ranibizumab.

Noninvasive assessment of retinal vascular oxygen content among normal and diabetic human subjects: a study using hyperspectral computed tomographic imaging spectroscopy.

PURPOSE: This pilot study was aimed to demonstrate the clinical feasibility of using hyperspectral computed tomographic spectroscopy to measure blood oxygen content in human retinal vessels. METHODS: All procedures were performed under a University of Southern California Institutional Review Board-approved protocol and after obtaining informed consent. Fifty-seven subjects with and without diabetic retinopathy were dilated for standard fundus photography. Fundus photographs and retinal vascular oxygen measurements (oximetry) were made using a custom-made hyperspectral computed tomographic imaging spectrometer coupled to a standard fundus camera. Oximetry measurements were made along arteries (Aox) and veins (Vox) within vessel segments that were 1 to 2 disk diameters from the optic disk. RESULTS: For all control subjects (n = 45), mean Aox and Vox were 93 ± 7% and 65 ± 5% (P = 0.001), respectively. For all diabetic subjects (n = 12), mean Aox and Vox were 90 ± 7% and 68 ± 5% (P = 0.001), respectively. In subjects with proliferative diabetic retinopathy, Aox was significantly lower, and Vox was significantly higher than other groups (85 ± 4% and 71 ± 4%, respectively; P = 0.04, analysis of variance). There was a highly significant difference in the arteriovenous difference between subjects with proliferative diabetic retinopathy and those in the control group (14 vs. 26%, P = 0.003). CONCLUSION: Hyperspectral computed tomographic spectroscopy is a clinically feasible method for measurement and analysis of vascular oxygen content in retinal health and disease. This study uses the techniques relevant to oximetry; however, the breadth of spectral data available through this method may be applicable to study other anatomical and functional features of the retina in health and disease.