Patient Population

LSOCA is an NIH-sponsored prospective epidemiologic study of people with AIDS, which began in September 1998. A description of its design and methods and a summary of data for participants at study enrollment (baseline) have been published previously. Data were collected from study participants every 6 months per protocol. The current study includes data collected through December 31, 2008 for participants without ocular opportunistic infections at baseline.

Data Collection

We collected baseline demographic, medical, and laboratory information as described in a companion article dealing with the same cohort. AIDS-related information at baseline included time since AIDS diagnosis, lymphopenia as AIDS-defining illness, CD4+ T lymphocyte count (baseline and nadir), CD8+ T lymphocyte count, human immunodeficiency virus (HIV) RNA blood level (baseline and peak), history of HAART (on HAART at baseline; ever on HAART), and Karnofsky score. We collected data on the following visual function measures at baseline: BCVA, as per LSOCA protocol; CS; and various visual field variables, as described below. CS was determined using the method of Pelli-Robson and analyzed using protocols described in a previous LSOCA publication. Goldmann perimetry used a modified Diabetic Retinopathy Study protocol, in which a score is computed by summing the degrees of visual field along 12 meridians spaced 30 degrees apart, as described previously. Using this technique, the mean score for people with AIDS is approximately 700 ± 100 degrees of visual field. Automated perimetry was performed using the Humphrey Field Analyzer Model 600 or 700 (Carl Zeiss Meditec, Dublin, California, USA) and the 24-2 full-threshold program, as described in a previous LSOCA publication. As recommended by the manufacturer, automated perimetry test results were excluded from analyses as being unreliable if fixation losses were ≥20% or false-positive errors were ≥33% or false-negative errors were ≥33%. We also identified those participants who had cataract on examination at baseline.

The following vessel caliber indices were determined in a semi-automated manner by certified graders at the University of Wisconsin Fundus Photograph Reading Center (IVAN software; Department of Ophthalmology and Visual Science, University of Wisconsin, Madison, Wisconsin, USA) using a standardized protocol: central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR). An explanation of these indices, and procedures for their determination, are described in the companion article dealing with this cohort.

Definitions

For purposes of this study, HAART was defined as the concurrent use of 3 or more antiretroviral drugs. Abnormal CS was defined as logCS <1.5, which corresponds to the lower 2.5 percentile for a normal control population described by Myers and associates. With regard to automated VF testing, abnormal mean deviation (MD) was defined as <−2.63 dB. Abnormal VF pattern standard deviation (PSD) was defined as >2.57 dB. The rationale for use of these thresholds is discussed in previous LSOCA publications.

Data Analysis and Statistical Techniques

Unless otherwise noted, the unit of analysis was the eye, and 1 eye per study participant was evaluated. Wong and associates have demonstrated a strong correlation between the eyes of an individual, for both CRAE and CRVE, and concluded that measurements from 1 eye accurately reflect a person’s systemic vascular status. If vessel caliber indices could be determined for both eyes, the eye with better photographic quality was selected as the study eye. Values for each vessel caliber index were grouped by quartiles and modeled ordinally. With regard to CRAE and CRVE, the first quartile contained narrower arterioles and venules, respectively, while the fourth quartile contained wider arterioles and venules. With regard to AVR, the first quartile included relatively narrower arterioles vs venules, while the fourth quartile included relatively wider arterioles vs venules.

Demographic, medical, and laboratory factors that were statistically related to vessel caliber indices in the companion study of this cohort were chosen as covariates in the adjusted models for each index in the cross-sectional portion of the study. The following baseline covariates were used in all adjusted models for the longitudinal portion of the study: current use of HAART, CD4+ T lymphocyte count, HIV RNA blood level, age, black race, mean corpuscular volume, hematocrit, and time since diagnosis of AIDS. Vessel caliber indices were used as predictors in: 1) cross-sectional analyses using linear regression of visual function variables at baseline; and 2) longitudinal analyses using Cox regression of incident events in visual function variables during follow-up.

Because diabetes mellitus can cause vascular disease similar to that seen in people with AIDS, we performed subgroup analyses, looking for significant ( P < .01) interactions between diabetes mellitus and relationships that involve vessel caliber. Similar subgroup analyses were performed to look for significant ( P < .01) interactions with hypertension. Because vessel caliber indices have been related to glaucomatous optic disc changes, subgroup analyses were also performed to look for significant ( P < .01) interactions with diagnoses of glaucoma or elevated intraocular pressure (>21 mm Hg) at baseline for those comparisons that involved visual field variables. Similar subgroup analyses were performed to look for significant ( P < .01) interactions between cataract and relationships that involve vessel caliber.

P values were 2-sided and were not adjusted for multiple comparisons. Statistical analyses were performed using SAS (SAS/STAT User’s Guide, Version 9.2, 2010; SAS Institute, Cary, North Carolina, USA) and Stata (Stata Statistical Software: Release 11, 2009; StataCorp LP, College Station, Texas, USA) statistical packages.