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Retina  |   July 2014
The Prevalence and Incidence of Epiretinal Membranes in Eyes With Inactive Extramacular CMV Retinitis
Author Affiliations & Notes
  • Igor Kozak
    King Khaled Eye Specialist Hospital, Vitreoretinal Division, Riyadh, Kingdom of Saudi Arabia
    University of California-San Diego, Jacobs Retina Center, La Jolla, California, United States
  • Vijay Vaidya
    Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Mark L. Van Natta
    Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Jeong W. Pak
    Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • K. Patrick May
    Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Jennifer E. Thorne
    Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
    Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Correspondence: Igor Kozak, King Khaled Eye Specialist Hospital, Vitreoretinal Division, PO Box 7191, Riyadh 11462, Kingdom of Saudi Arabia; ikozak@kkesh.med.sa
Investigative Ophthalmology & Visual Science July 2014, Vol.55, 4304-4312. doi:10.1167/iovs.14-14479
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      Igor Kozak, Vijay Vaidya, Mark L. Van Natta, Jeong W. Pak, K. Patrick May, Jennifer E. Thorne, ; The Prevalence and Incidence of Epiretinal Membranes in Eyes With Inactive Extramacular CMV Retinitis. Invest. Ophthalmol. Vis. Sci. 2014;55(7):4304-4312. doi: 10.1167/iovs.14-14479.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose.: To determine the prevalence and incidence of epiretinal membranes (ERM) in eyes with inactive extramacular cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS).

Methods.: A case–control report from a longitudinal multicenter observational study by the Studies of the Ocular Complications of AIDS (SOCA) Research Group. A total of 357 eyes of 270 patients with inactive CMV retinitis and 1084 eyes of 552 patients with no ocular opportunistic infection (OOI) were studied. Stereoscopic views of the posterior pole from fundus photographs were assessed at baseline and year 5 visits for the presence of macular ERM. Generalized estimating equations (GEE) logistic regression was used to compare the prevalence and 5-year incidence of ERM in eyes with and without CMV retinitis at enrollment. Crude and adjusted logistic regression was performed adjusting for possible confounders. Main outcome measures included the prevalence, incidence, estimated prevalence, and incidence odds ratios.

Results.: The prevalence of ERM at enrollment was 14.8% (53/357) in eyes with CMV retinitis versus 1.8% (19/1084) in eyes with no OOI. The incidence of ERM at 5 years was 18.6% (16/86) in eyes with CMV retinitis versus 2.4% (6/253) in eyes with no OOI. The crude odds ratio (OR) (95% confidence interval, CI) for prevalence was 9.8 (5.5–17.5) (P < 0.01). The crude OR (95% CI) for incidence was 9.4 (3.2–27.9) (P < 0.01).

Conclusions.: A history of extramacular CMV retinitis is associated with increased prevalence and incidence of ERM formation compared to what is seen in eyes without ocular opportunistic infections in AIDS patients.

Introduction
Cytomegalovirus (CMV) retinitis is a common ocular opportunistic infection (OOI) resulting in visual loss among patients with the acquired immune deficiency syndrome (AIDS). 1 Although the use of combination antiretroviral therapy has reduced the incidence of CMV retinitis by approximately 80%, 24 the risk of vision loss among patients with CMV retinitis, including those with inactive CMV retinitis, remains substantial when compared to patients without CMV retinitis. 5,6  
Vision loss attributed to CMV retinitis has been well documented and occurs most commonly as a result of direct macular tissue destruction (e.g., full-thickness retinal necrosis) and/or secondarily as part of rhegmatogenous retinal detachment. 79 A cause of visual impairment observed in patients who have undergone immune recovery and have inactive extramacular CMV retinitis is immune recovery uveitis (IRU), which may cause visual impairment from active intraocular inflammation (i.e., vitritis) or its attendant structural ocular complications such as cataract, macular edema, proliferative retinopathy, and epiretinal membrane (ERM) formation. 4,1017 Retinal imaging studies have demonstrated vitreoretinal abnormalities in inactive CMV retinitis. In a recent pilot study, retina adjacent to inactive CMV retinitis scars appeared to show a higher frequency of vitreoretinal traction and ERM formation. 18  
The purpose of this study is to report the prevalence and incidence of ERM in eyes with inactive extramacular CMV retinitis in patients with AIDS enrolled in the Longitudinal Studies of Ocular Complications of AIDS (LSOCA). We hypothesized that eyes with a history of CMV retinitis were more likely to develop ERM compared to eyes without OOI and that ERM may be present in the retinal areas free of CMV retinitis scar. 
Methods
Study Subjects
LSOCA is a prospective observational study of patients with AIDS conducted entirely within the era of highly active antiretroviral therapy (HAART). Patients with diagnosis of AIDS aged 13 years or older were enrolled, regardless of immunologic or CMV retinitis status. Acquired immune deficiency syndrome diagnosis was according to the 1993 Centers for Disease Control and Prevention Revised Surveillance Case Definition. This study was approved by the Institutional Review Board at each participating center and the three resource centers. The study was conducted in compliance with the Declaration of Helsinki. All patients gave written informed consent prior to participating in the study. 
Patients were enrolled with or without CMV retinitis; data were collected on medication use and comorbidities, and detailed ophthalmologic evaluations, including fundus photography, were performed. Film and digital equipment and photographers at the participating clinical centers were certified, based on submission of a set of sample images, by a centralized Fundus Photograph Reading Center (FPRC) at the Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison. Specific imaging protocol included one central stereoscopic (posterior pole) and eight peripheral monoscopic 50° or 60° views, extending nearly to the equator. These retinal photographs are sent to the reading center for evaluation of ocular complications of AIDS, especially CMV retinitis, by trained and certified graders (Studies of the Ocular Complications of AIDS Research Group, SOCA cytomegalovirus retinitis grading protocol, 1997; available from the National Technical Information Services, US Department of Commerce, 5285 Port Royal Road, Springfield, VA, USA; NTIS Accession no. PB97-192082). 
Topography and Definition of Vitreoretinal Abnormalities
The location and extent of CMV retinitis is assessed using standard grid templates. The LSOCA grid demarcates the retinal regions into three contiguous zones. Zone 1 corresponds to an area of 2 disc diameters (DD) (3600 μm) from the center of macula and 1 DD (1800 μm) from the margins of the optic disc. Zone 2 extends from zone 1 to the vortex veins, and zone 3 extends from zone 2 to the ora serrata. 19 Zone 2 is further divided into eight peripheral sectors (corresponding to the eight peripheral photographic fields). The proportionate areas represented by zone 1 and zone 2 are 22 disc areas (DA) and 279 DA of the posterior pole, respectively, out of a total 394 DA of a known total human retinal area (Fig. 1). 
Figure 1
 
The LSOCA fundus photography grid outlining the retinal regions into three zones. Zone 1 corresponds to an area of 2 disc diameters (DD) (3600 μm) from the center of macula (green macular circle) and 1 DD (1800 μm) from the margins of the optic disc (green optic disc circle). Zone 2 extends from zone 1 to the vortex veins, and zone 3 extends from zone 2 to the ora serrata.
Figure 1
 
The LSOCA fundus photography grid outlining the retinal regions into three zones. Zone 1 corresponds to an area of 2 disc diameters (DD) (3600 μm) from the center of macula (green macular circle) and 1 DD (1800 μm) from the margins of the optic disc (green optic disc circle). Zone 2 extends from zone 1 to the vortex veins, and zone 3 extends from zone 2 to the ora serrata.
In this report, we focus on the ERM in zone 1 in eyes with extramacular CMV retinitis using stereoscopic views of the posterior pole (Fig. 2). A total 1441 eyes were assessed at baseline for the presence of structural changes of the macular area including cellophane reflex, subtle ERM, obvious ERM, tension line, vessel distortion, dragged macula, and retinal detachment. All represent a spectrum of ERM. All LSOCA subjects enrolled since 2005 were included in this study as the ERM evaluation was implemented in that year. Additionally, all eyes with CMV retinitis diagnosis at enrollment prior to 2005 were included for the ERM evaluation to meet a statistically robust sample size. Cellophane reflex is fine glistening patches of variable size and number overlying the macula. Appearance is somewhat similar to that of “wet” retina. An ERM shows some substance that is consistent over an area of the retina. Subtle visible membrane appears as a thin gray or opaque area through which the retinal details and RPE are seen. Obvious membrane is thickened, whitish tissue that obscures the underlying retinal details and RPE. Dragged macula is macula being displaced from its anatomic position by traction. 
Figure 2
 
A mosaic image with the LSOCA grid showing an inactive cytomegalovirus (CMV) retinitis lesion in periphery, and epiretinal membrane and tension lines in macular zone 1 area (inset).
Figure 2
 
A mosaic image with the LSOCA grid showing an inactive cytomegalovirus (CMV) retinitis lesion in periphery, and epiretinal membrane and tension lines in macular zone 1 area (inset).
Statistical Analysis
Eyes were classified as either CMV retinitis or no opportunistic ocular infection (No-OOI) on the basis of assessment at enrollment. Eyes at enrollment with CMV retinitis in zone 1 or diagnosed with herpetic retinitis, toxoplasmic retinitis, or choroiditis were excluded. Due to correlation of eyes in the same patient, generalized estimating equations (GEE) logistic regression was used to compare the prevalence and 5-year incidence of ERM in eyes with and without CMV retinitis at enrollment. 
Eyes diagnosed with ERM at enrollment were excluded from the calculation of 5-year incidence. Patients in the No-OOI group who were diagnosed with CMV retinitis within the 5 years of follow-up also were excluded. Crude and adjusted logistic regression was performed adjusting for age, Karnofsky score, HIV viral load, CD4+ T-cell count, and nadir CD4+ T-cell count. 
Patient- and eye-specific risk factors for time-to-event analysis of incident ERM were evaluated in the CMV retinitis group. Person-time was calculated from enrollment to the first reported event of ERM during follow-up or last follow-up date for the patients who were not diagnosed with ERM. The following risk factors were evaluated: newly diagnosed CMV retinitis cases (diagnosed within the 45 days of enrollment) versus longstanding cases, eyes affected with one zone (zone 2 or 3 versus both the zones), presence of an active CMV retinitis border, number of lesions in the affected eye, CD4+ T-cell count, HIV viral load, and age. Cox regression with staggered entries 20 was used to estimate the hazard ratios and 95% confidence intervals (CIs). SAS version 9.3 (SAS Institute, Inc., Cary, NC, USA) and STATA version 12.1 (STATA Corp., College Station, TX, USA) were used for the analyses. 
Results
The comparison of patient characteristics at enrollment between 357 eyes from 270 patients with zone(s) 2/3 CMV retinitis (e.g., extramacular CMV retinitis) versus 1084 eyes from 552 patients with no OOI is shown in Table 1. The overall mean (range) age of the 822 patients was 44 years (38–51), with 80.7% male, 42.7% white, and 60.6% with higher than high school education. As compared to patients with no OOI, patients with CMV retinitis were significantly younger but were similar with respect to sex, race, and education. In addition, patients with CMV retinitis had significantly lower Karnofsky score, CD4+ T-cell count, and nadir CD4+ T-cell count and higher HIV viral load but were similar with respect to employment and prevalence of self-reported tuberculosis, syphilis, and hepatitis as compared to patients with no OOI. 
Table 1
 
Baseline Patient-Level Characteristics of All the Participants Who Had ERM Data for CMV and No-OOI Participants
Table 1
 
Baseline Patient-Level Characteristics of All the Participants Who Had ERM Data for CMV and No-OOI Participants
Total N = 822 CMV N = 270 No-OOI N = 552 P Value
Age, y, median (q1, q3) 44.0 (38, 51) 41.0 (35, 46) 46 (40, 52) 0.005
Sex, n (%) 0.17
 Male 663 (80.7) 225 (83.3) 438 (79.3)
 Female 159 (19.3) 45 (16.7) 114 (20.7)
Race, n (%) <0.01
 White, non-Hispanic 351 (42.7) 143 (53.0) 208 (37.7)
 Black, non-Hispanic 335 (40.8) 74 (27.4) 261 (47.3)
 Other 136 (16.5) 53 (19.6) 83 (15.0)
Education, n (%) 0.001
 High school or below 324 (39.4) 80 (29.6) 244 (44.2)
 Above high school 498 (60.6) 190 (70.4) 308 (55.8)
Karnofsky score*, median (q1, q3) 8.0 (8, 9) 8.0 (8, 9) 8.0 (8, 9) 0.002
CD4 count, cells/μL, median (q1, q3) 210 (76, 407) 103 (21, 306) 258 (116, 427) <0.01
CD4 nadir, cells/μL, median (q1, q3) 29 (8, 91) 10 (4, 26) 47 (15, 123) <0.01
HIV viral load, copies/mL, log10, median (q1, q3) 2.6 (2, 4) 3.3 (2, 5) 2.3 (2, 3) <0.01
Employment, n (%) 0.60
 Disabled 476 (57.9) 160 (59.3) 316 (57.2)
 Other 345 (42.0) 110 (40.7) 235 (42.6)
Tuberculosis, n (%) 0.71
 Yes 57 (6.9) 20 (7.4) 37 (6.7)
Syphilis, n (%) <0.01
 Yes 194 (23.6) 39 (14.4) 155 (28.1)
Hepatitis, n (%) <0.01
 Yes 324 (39.4) 81 (30.0) 243 (44.0)
Smoker, n (%) 0.12
 Missing 399 (48.5) 224 (83.0) 175 (31.7)
 Yes 144 (17.5) 11 (4.1) 133 (24.1)
The prevalence of ERM at enrollment was 14.8% (53/357) in eyes with CMV retinitis versus 1.8% (19/1084) in eyes with no OOI. The crude odds ratio (OR) (95% CI) was 9.8 (5.5–17.5) (P < 0.01). The OR (95% CI) adjusting for age, Karnofsky score, HIV viral load, and current and nadir CD4+ T-cell count was 11.1 (5.6–22.3) (P < 0.01) (Table 2). 
Table 2
 
Estimated Prevalence Odds Ratios for ERM in CMV Retinitis (CMV-R) Versus No-OOI Group*
Table 2
 
Estimated Prevalence Odds Ratios for ERM in CMV Retinitis (CMV-R) Versus No-OOI Group*
Odds Ratio Lower CI Upper CI P Value
CMV-R vs. no OOI after adjusting for baseline covariates† 9.77 5.45 17.53 <0.01
CMV-R vs. no OOI 11.12 5.55 22.31 <0.01
Age, y 0.83 0.60 1.16 0.28
Karnofsky score 1.21 0.94 1.56 0.14
Viral load, copies/mL, log 10 0.99 0.79 1.25 0.97
CD4 count, cells/μL 1.08 0.95 1.24 0.23
CD4 nadir, cells/μL 1.04 0.82 1.31 0.75
Among eyes without ERM at enrollment, there were 86 eyes from 80 patients with CMV retinitis and 253 eyes from 131 patients with no OOI graded for ERM at 5 years. The incidence of ERM at 5 years was 18.6% (16/86) in eyes with CMV retinitis versus 2.4% (6/253) in eyes with no OOI. The crude OR (95% CI) was 9.4 (3.2–27.9) (P < 0.01). The OR (95% CI) adjusted for age, Karnofsky score, HIV viral load, and current and nadir CD4+ T-cell count was 9.6 (3.4–27.9) (P < 0.01) (Table 3). 
Table 3
 
Estimated Incidence Odds Ratios for ERM in CMV-R Versus No-OOI Group*
Table 3
 
Estimated Incidence Odds Ratios for ERM in CMV-R Versus No-OOI Group*
Odds Ratio Lower CI Upper CI P Value
CMV-R vs. no OOI after adjusting for baseline covariates† 9.41 3.18 27.86 <0.01
CMV-R vs. no OOI 9.65 3.35 27.86 <0.01
Age, y 1.54 0.79 3.02 0.21
Karnofsky score 0.74 0.48 1.12 0.16
Viral load, copies/mL, log 10 0.91 0.63 1.34 0.64
CD4 count, cells/μL 1.17 0.91 1.50 0.23
CD4 nadir, cells/μL 0.55 0.17 1.80 0.32
Within the subgroup of eyes with CMV retinitis, the incidence of ERM at 5 years was compared among CMV retinitis-specific risk factors, including time since diagnosis, activity, zone, bilaterality, and number of lesions, as well as patient-specific risk factors including CD4+ T-cell count, HIV viral load, and age (Table 4). The relative rate (95% CI) of incidence of ERM at 5 years comparing eyes with newly diagnosed versus longstanding CMV retinitis was 2.6 (1.2–5.5) (P = 0.01). There were no other significant risk factors among eyes with CMV retinitis for incidence of ERM. 
Table 4
 
Estimated Incidence Rate Ratios* (Outcome = Incidence Rate)
Table 4
 
Estimated Incidence Rate Ratios* (Outcome = Incidence Rate)
IRR Lower CI Upper CI P Value
New OOI in last 45 days 2.62 1.24 5.52 0.01
CD4 count, cells/μL 0.99 0.99 1.001 0.47
Active border 1.79 0.77 4.18 0.18
Both eyes zones vs. zone 2 or 3 1.23 0.66 2.38 0.50
Bilateral eyes vs. unilateral eyes 0.72 0.43 1.18 0.19
Number of visible discrete lesions 0.92 0.72 1.18 0.52
Viral load, copies/mL, log 10 0.92 0.72 1.18 0.52
Age† 1.38 0.96 1.99 0.08
Four LSOCA participants were eligible for cataract surgery out of the 201 participants who were at risk for ERM at 5 years (3/131 patients [253 eyes] in the No-OOI group and 1/70 participants [86 eyes] in the OOI group) (P = 0.39). Retinal detachment (RD) surgery was necessary in 9 eyes in the No-OOI group and in 27 eyes in the OOI group (P < 0.001). Laser barrier was not performed in the No-OOI group and was done in 1 eye in the OOI group (P = 0.25 Fisher exact test for all). The OR for OOI status adjusting for RD surgery is similar to OR when not adjusting for RD (10.8 vs. 11.4, P = 0.29). 
Discussion
Epiretinal membrane is a vitreoretinal interface abnormality resulting in a disturbance of macular vision. 21 This study demonstrates increased prevalence and incidence of ERM in eyes with inactive extramacular CMV retinitis compared to eyes with no OOI in patients with AIDS. Epiretinal membranes comprise the spectrum of severity from cellophane macular reflex without retinal folds to preretinal macular fibrosis with retinal folds. This may have implication for correlation with visual function, and therefore some studies look at different degrees of ERM separately. 22 However, because our outcome measure was not visual function, we did not differentiate between different degrees of ERM, and all degrees were classified as presence of ERM. 
The prevalence of ERM in eyes without ocular disease (idiopathic ERM) has been reported to vary with age and among different ethnic groups, with a range of 0.5% to 1.02% in patients younger than 60 years of age and 9.3% in persons 80 years of age and older. 2224 This is consistent with the frequency of ERM at enrollment in our patients without OOI for those given age ranges. Both unadjusted and adjusted prevalence ratios in our group show significantly increased prevalence of ERM in eyes with extramacular CMV retinitis compared to eyes with no OOI. Patient's age and immune and health status do not seem to contribute to this finding. All eyes with active retinitis had both zones 2 and 3 affected, and the eyes had activity in less than 25% of total retinal area. Therefore, we did not look into correlation of extent of inactive retinitis and the presence of ERM. In one-third of cases the retinitis had active border at baseline, and almost half of the patients had bilateral disease. We have not studied association of CMV retinitis treatments and the presence of ERM, as the HAART regimens were constantly evolving over the years. 
A previous study using spectral-domain optical coherence tomography investigated vitreoretinal interface abnormalities at the site of inactive extrafoveal CMV retinitis and adjacent areas. It demonstrated the presence of ERM, vitreoretinal gliosis, and traction in those areas. 18 Our study utilized color fundus photographs and showed that ERM may be present even in the macular area of eyes without an adjacent CMV scar. This expands our knowledge of the distribution of vitreoretinal interface abnormalities in eyes with a history of CMV retinitis. We acknowledge that advanced imaging technology such as optical coherence tomography yields more accurate information on the presence of ERM compared to human evaluation, but this technology has not been a part of LSOCA study. We thus acknowledge that the numbers presented in this report may be slight underestimations of the true prevalence. Another limitation of our study is a survivor bias. Survivor bias in the context of this study means that we cannot evaluate the rate of change in AIDS patients who have died during study follow-up. Even though this is not a population-based study, the strength of our cohort lies in the presence of its own internal control group of HIV-positive patients without OOI, robust sample size from the largest cohort of ocular complications of AIDS in the United States, and protocol-driven data collection at the 5-year interval. 
Similar to our prevalence data, the incidence of ERM in eyes with inactive CMV retinitis was statistically significantly higher than in eyes with no OOI as well as higher than reported incidence rates in the literature. In the Blue Mountains Eye Study, the incidence of ERM was reported as 4.4% over 5 years. 22 Cataract surgery has been reported to increase the incidence of ERM. 25 In our study, only four patients underwent cataract surgery during the follow-up period, three of whom were in the No-OOI group. More eyes underwent RD surgery in the OOI group than in the No-OOI group. However, given the nonsignificant difference in ORs for OOI status, the effect of OOI status on prevalence of ERM is not confounded by RD surgery. 
Our data suggest that ERM develop more frequently in eyes with peripheral CMV retinitis. Although CMV retinitis is the most common OOI in AIDS patients, other infectious causes can be numerous. Several other (chorio-)retinitides have been associated with ERM, including Candida chorioretinitis, 26 ocular toxoplasma, 27 syphilis, 28 diffuse unilateral subacute neuroretinitis, 29 and Eales disease, 30 among others. The eye-specific characteristics for incidence of ERM in our patients correlate with the prevalence of ERM data except that retinitis had active border in one-fourth of incident cases. Patient's age, immune status, laterality, location and number of lesions, and activity of the border do not seem to be risk factors for development of ERM. The only risk factor found to be significant was new OOI in the last 45 days. This indicates that proximity of ocular infection can trigger formation of ERM. 
There is evidence that certain inflammatory cytokines such as tumor necrosis factor (TNF)-α are expressed within the ocular compartment during AIDS-related CMV retinitis. 31 Several reports describe the presence of TNF-α in ERM in proliferative vitreoretinopathy 32,33 and diabetic retinopathy. 33 It is therefore plausible that active infectious retinitis produces cytokines capable of contributing to ERM formation. Similarly, it has been documented that patients with longstanding CMV retinitis who have experienced immune recovery and subsequent uveitis (so-called immune recovery uveitis or IRU) are at increased risk of development of cataract, CME, and ERM. 12 Along with immune-mediated tissue inflammation after recovery of T-lymphocyte counts, there may be additional mechanism(s) causing structural changes in the macula and at the vitreoretinal interface. These may include vitreous changes (liquefaction and clouding) and vitreoretinal traction as previously described. 18 It is also plausible that most, if not all, eyes with healed CMV retinitis develop IRU at some point, which may be of various severity, subclinical, or not diagnosed during exam. This then predisposes eyes to formation of ERM. Human immunodeficiency virus–associated inflammatory cytokines have been detected also in retinal tissue in noninfectious HIV retinopathy. 34 The exact cellular mechanism underlying the above findings, however, remains largely unknown at this time. 
In summary, history of extramacular CMV retinitis is associated with increased prevalence and incidence of ERM formation compared to what is seen in eyes without OOI. Recent onset of OOI is most significant risk factor for the presence of ERM. Epiretinal membranes can be a cause of visual disturbance and ocular morbidity. It would be insightful to extend these observations to other causes of infectious retinitis and to immunocompetent populations. 
Acknowledgments
Supported by Grants EY08052 to the Icahn School of Medicine at Mount Sinai, New York, New York, United States; EY08057 to the Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States; and EY08067 to the University of Wisconsin-Madison, Madison, Wisconsin, United States (Ronald Danis) from the National Eye Institute, the National Institutes of Health, Bethesda, Maryland, United States. 
Disclosure: I. Kozak, None; V. Vaidya, None; M.L. Van Natta, None; J.W. Pak, None; K.P. May, None; J.E. Thorne, None 
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Footnotes
 See the appendix for the members of the Studies of the Ocular Complications of AIDS Research Group.
APPENDIX
Longitudinal Study of Ocular Complications of AIDS Clinical Centers—Credit Roster (as of November 21, 2013)
Key Personnel (LSOCA Certified) 1997–2013.
Baylor College of Medicine, Cullen Eye Institute, Houston, TX, USA: Richard Alan Lewis, MD, MS (Director); Robert E. Coffee III, MD; Valerie Gudell, DMA; Joseph F. Morales, CRA; Silvia Orengo-Nania, MD; Steven S. Spencer, BA, COMT, CCRP; Mitchell P. Weikert, MD. Former Members: Richard C. Allen, MD; John Michael Bourg; Victor Fainstein, MD; Pamela Frady, COMT; Ronald Gross, MD; Zbigniew Krason, CRA; Tobias C. Samo, MD; Allison Schmidt, CRA; Laura Shawver, COT/CCRP; James Shigley, CRA (deceased); Benita Slight, COT; Rachel Sotuyo, COT; Kay R. Stephenson, COT, BA, CCRP; Stephen Travers, CRA. 
Emory University Eye Center, Atlanta, GA, USA: Steven Yeh, MD (Director); Deborah Gibbs, COMT, CCRC, CCRP; Debora Jordan, CRA; Janna Rutter, CRA. Former Members: Antonio Capone Jr., MD; David Furukuwa, PA; Allison Gibbs, BS; Baker Hubbard, MD; Steven Kim, MD; Daniel F. Martin, MD; Bob Myles, CRA; Bryan Schwent, MD; Sunil K. Srivastava, MD. 
Johns Hopkins University School of Medicine, Baltimore, MD, USA: J.P. Dunn, MD (Director); Kristen Brotherson, BS; Bryn Burkholder, MD; Nicholas Butler, MD; Dennis Cain; David Emmert; Theresa Gan Leung, MD; Charles Mark Herring; Ahmadreza Moradi, MD; Antonia Nwankwo-Marshall; Jennifer E. Thorne, MD, PhD. Former Members: Ellen Arnold, BS; Patricia Barditch-Crovo, MD; Patricia Barnabie, BS; Marie-Lyne Bélair, MD; Stephen G. Bolton, CRNP; Joseph B. Brodine; Diane M. Brown, RN; Lisa M. Brune, RN, BSN; Anat Galor, MD; Douglas A. Jabs, MD, MBA; Adam Jacobowitz, MD; Meera Kapoor; Sanjay R. Kedhar, MD; John H. Kempen, MD, PhD; Stephen J. Kim, MD; Henry A. Leder, MD; Alison G. Livingston, RN, BSN; Yavette Morton; Kisten D. Nolan, RN, BSN, MPH; Armando L. Oliver, MD; George B. Peters III, MD; Richard D. Semba, MD, MPH; Priscilla Soto; Ricardo Stevenson, MD; Michelle Tarver-Carr, MD, PhD; Lynnet Tirabassi, RN, BSN; Susan Wittenberg, MD; Michelle Yue Wang, MD. 
Louisiana State University Health Sciences Center, New Orleans, LA, USA: Donald Bergsma, MD (Director); Rebecca Clark, MD; Robin Cooper, COMT; Christine Jarrott, RN, ACRN; P. Sean O'Sullivan, MD; Maria Reinoso, MD; Christine Romero, COT, ROUB. Former Members: Bruce Barron, MD; Robin Bye, RN; Mandi Conway, MD; Larry Dillon, COT/CRA; Jasmine Elison, MD; Butler Fuller, MD; Audrey Lombard, RN; Lynn Otillio, COT; Gholman Peyman, MD. 
Memorial Sloan Kettering Center, New York, NY, USA: Murk-Hein Heinemann, MD (Director); Susana Coleman; Sara Daniel; Roberta Janis, RN, BSN; Andrzej Kozbial; Kent Sepkowitz, MD. Former Members: Kenneth Boyd; Robinson V.P. Chan, MD; Cynthia Chiu, MD; Minhee Cho, MD; Charles Cole, MD; Charles Doering, MD; Jasmine Elison, MD; Aziz Khanifar, MD; Fang Lu; Joseph Murphy; Sophia Pachydaki, MD; Christiana Peroni, MD; Firas M. Rahhal, MD; Ashok Reddy, MD. 
New York University Medical Center, New York, NY, USA: Dorothy N. Friedberg, MD, PhD (Director); Adrienne Addessi, MA, RN; Douglas Dieterich, MD; Monica Lorenzo-Latkany, MD; Maria Pei, COA. Former Member: Alex McMeeking, MD. 
Northwestern University, Chicago, IL, USA: Alice T. Lyon, MD (Director); Lori Ackatz, RN, MPH; Manjot Gill, MD; Lori Kaminski, RN, MS; Rukshana Mirza, MD; Robert Murphy, MD; Frank Palella, MD; Carmen Ramirez; Zuzanna Rozenbajgier, MA; Dawn Ryan, CRA; Evica Simjanoski, BFA, CRA; Former Members: Alexander Habib; Jill Koecher; Jeevan Mathura, MD; Annmarie Muñana, RN; Jonathan Shankle; David V. Weinberg, MD; James Yuhr. 
University of California, Los Angeles, CA, USA: Gary N. Holland, MD (Director); Robert D. Almanzor, COA; Margrit E. Carlson, MD; Jose T. Castellanos, COT; Serina Gonzales; Ann K. Johiro, MN, RN, BC, FNP-C, AACRN, AAHIVS; Susan S. Ransome, MD. Former Members: Suzette A. Chafey, RN, NP; Alexander C. Charonis, MD; Jeffrey A. Craddock, COT; Partho S. Kalyani, MD; Michael A. Kapamajian, MD; Peter J. Kappel, MD; David L. LeBeck (deceased); Kristin M. Lipka; Ardis A. Moe, MD; Germán Piñón; Angela Sanderson; Kayur H. Shah, MD; Robert Stalling, COA; Dennis Thayer, CRA; Jean D. Vaudaux, MD. 
University of California, San Diego, CA, USA: Cheryl A. Arcinue, MD (Director); Payam Amini, MD; Janne Chuang; Isaac Ezon, MD; William R. Freeman, MD; Leonard Holmes; Azadeh Khatibi, MD; Veronica Mendoza. Former Members: Sunan Chaidhawanqual, MD; Lingyun Cheng, MD; Tom Clark; Mark Cleveland; Denise Cochran; Randall L. Gannon; Claudio Garcia, MD; Daniel Goldberg, MD; Joshua Hedaya, MD; Marietta Karavellas, MD; Tiara Kemper; Brian Kosobucki; Igor Kozak, MD (Director); Megan Loughran; Luzandra Magana; Alona Mask; Victoria Morrison, MD; Vivian Nguyen; Stephen Oster, MD; Nicole Reagan, MD; Mi-Kyoung Song, MD; Francesca Torriani, MD; Dorothy Wong; Karen Yesensky; Tekeena Young. 
University of California, San Francisco, CA, USA: Jacque Duncan, MD (Director); Robert Bhisitkul, MD, PhD; David Clay; Michael Deiner; Donald Eubank; Mark Jacobson, MD; Mary Lew, COT; Todd Margolis, MD, PhD; Arshia Mian. Former Members: Judith Aberg, MD; Fermin Ballesteros Jr.; Debra Brown; Jacqueline Hoffman; Alexander Irvine, MD; James Larson; Jody Lawrence, MD; Michael Narahara; Monique Trinidad. 
University of North Carolina, Chapel Hill, NC, USA: Travis A. Meredith, MD (Director); Sandy Barnhart, MPH; Debra Cantrell; Seema Garg, MD, PhD; Odette Houghton, MD; Megha Karmalkar; Maurice B. Landers, MD; Sarah Moyer; David Wohl, MD. Former Members: Cynthia Aurrichio, OD; Stephanie Betran; Kelly DeBoer; Elizabeth DuBose, MPH; David Eifrig, MD; John Foley, MD; Elizabeth Hartnett, MD; Angela Jeffries; Harpreet Kaur; Jan Kylstra, MD; Barbara Longmire; Sharon Myers; Fatima N'Dure, COA; Kean T. Oh, MD; Jeremy Pantell; Susan Pedersen, RN; Cadmus Rich, MD; Cecilia A. Sotelo, RN; Charles van der Horst, MD; Samir Wadhvania. 
University of Pennsylvania Medical Center, Philadelphia, PA, USA: Charles W. Nichols, MD (Director); Mark Bardsley, BSN; John Beaver, RN; Cheryl C. Devine; Jay Kostman, MD; Albert Maguire, MD; William Nyberg. Former Members: Chris Helker, RN; RobRoy MacGregor, MD; Karen McGibney, RN; Keith Mickelberg, RN; Leslie Smith, RN. 
University of South Florida, Tampa, FL, USA: Peter Reed Pavan, MD (Director); Ken Albritton; Linda Clark; JoAnn Leto, COT; Brian Madow, MD; Lori Mayor; Richard Oehler, MD; Wyatt Saxon. Former Members: Linda Bergen-Losee; Andrew Burrows, MD; Steve Carlton; Burton Goldstein, MD; Sandra Gompf, MD; Bonnie Hernandez, COT; Mohan Iyer, MD; Patrick Kelty, MD; Amy Kramer, COT; Julie Larkin, MD; Sharon Millard, RN, COT; Jeffrey Nadler, MD; Robert Nelson, MD; Nandesh Patel, MD; Scott E. Paulter, MD; James Powers, MD; Susan Sherouse, COT; Jennifer Tordilla-Wadia, MD; Nancy Walker, COA. 
Chairman's Office, Mount Sinai School of Medicine, New York, NY, USA: Douglas A. Jabs, MD, MBA (Study Chairman); Amanda Allen; Karen Pascual, MBA; Jill Slutsky-Sanon, MPA. Former Members: Amy Cooperstein, MPH; Yasmin Hilal, MHS; Melissa Nieves, BA; Judith C. Southall; Maria Stevens, CM. 
Coordinating Center, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA: Curtis L. Meinert, PhD (Director); Alka Ahuja, MS; Debra A. Amend-Libercci; Karen L. Collins; Betty J. Collison; John Dodge; Michele Donithan, MHS; Lea T. Drye, MS, PhD; Cathleen Ewing; Janet T. Holbrook, MS, MPH, PhD; Milana R. Isaacson, BS; Rosetta M. Jackson; Patrick May, MS; Girlie Reyes; Lee Sensinger, MA; Efe Sezgin, PhD; Jacki Smith, AA; Michael Smith, BS; Elizabeth Sugar, PhD; Jennifer E. Thorne, MD, PhD; James A. Tonascia, PhD; Vijay Vaidya, MS, MPH; Mark L. Van Natta, MHS; Annette Wagoner. Former Members: Carley Benham; Laura Coleson-Schreur, RN; Ryan Colvin, MPH; Kathryn Connor, BA; Gregory Foster, MS; Kevin Frick, PhD; Judith Harle; Adele M. Kaplan Gilpin, JD, PhD; John H. Kempen, MD, PhD; Hope Livingston; Barbara K. Martin, PhD; Nancy Min, MPH, PhD; Laurel Murrow, MS; Maria J. Oziemkowska, MS, MPH; Bonnie Piantadosi, MS; Milo Puhan, MD, PhD; Wai Ping Ng, BS; Shoshana Reshef, PhD, MPH; Pamela E. Scott, MA; Erica Smothers; Emily West, PhD; Claudine Woo, MPH; Albert Wu, MD, MPH; Alice Zong. 
Fundus Photograph Reading Center, University of Wisconsin, Madison, WI, USA: Ronald Danis, MD (Director); Charles Chandler; Gregory Guilfoil; Jeffrey Joyce; Nancy Robinson; Dennis Thayer; Jeong Won Pak, PhD; Grace Zhang. Former Members: Michael Altaweel, MD; Jane Armstrong; Matthew D. Davis, MD; Sapna Gangaputra, MD, MPH; Sheri Glaeser; Larry Hubbard, MAT; Katrina Hughes; Dolores Hurlburt; Linda Kastorff; Michael Neider, BA; Thomas Pauli; Therese Traut; Marilyn Vanderhoof-Young; Hugh Wabers. 
National Eye Institute, Bethesda, MD, USA: Natalie Kurinij, PhD; Steven Oversby, PsyD. Former Project Officer: Richard Mowery, PhD. 
Officers of the Study: Douglas A. Jabs, MD, MBA (Chair); Ronald Danis, MD; Natalie Kurinij, PhD; Curtis L. Meinert, PhD; Steven Oversby, PsyD; Jennifer E. Thorne, MD, PhD. Former Members: Matthew D. Davis, MD; Janet T. Holbrook, MS, MPH, PhD. 
Steering Committee: Douglas A. Jabs, MD, MBA (Chair); Lori Ackatz, RN, MPH; Ronald Danis, MD; Dorothy Friedberg, MD; Gary N. Holland, MD; Milana R. Isaccson, BS; Mark Jacobson, MD; Ann Johiro, MN, RN, BC, FNP-C, AACRN; Natalie Kurinij, PhD; Alice Lyon, MD; Curtis L. Meinert, PhD; Christine Romero, COT; Steven Oversby, PsyD; Jennifer E. Thorne, MD, PhD. Former Members: Adrienne Addessi, MA, RN; Lisa Brune, RN, BSN; Rebecca Clark, MD; Tom Clark, CRA; Janet Davis, MD; Matthew D. Davis, MD; James P. Dunn, MD; William R. Freeman, MD; Dorothy Friedberg, MD; James Gilman; Janet T. Holbrook, MS, MPH, PhD; John Horna; Larry Hubbard, MAT; Mark Jacobson, MD; Richard Lewis, MD, MS; Daniel F. Martin, MD; Travis A. Meredith, MD; Annmarie Muñana, RN; Robert Murphy, MD; Kisten D. Nolan, RN, BSN, MPH; William Nyberg; Frank Palella, MD; P. Reed Pavan, MD; Steven Spencer, BA, COMT; Tim Steffens, CRA; Dennis Thayer; Charles van der Horst, MD; Fran Wallach. 
Policy and Data Monitoring Board: John P. Phair, MD (Chair); Brian P. Conway, MD; Ronald Danis, MD; Barry R. Davis, MD, PhD; Douglas A. Jabs, MD, MBA; Natalie Kurinij, PhD; Curtis L. Meinert, PhD; David Musch, PhD; Robert B. Nussenblatt, MD; Steven Oversby, PsyD; Jennifer E. Thorne, MD, PhD; Richard Whitley, MD; Leslie Wolf, JD, MPH. Former Members: Beverly Alston, MD; B. William Brown Jr., PhD; Matthew D. Davis, MD; James Grizzle, PhD; Argye Hillis, PhD; Janet T. Holbrook, MS, MPH, PhD; Harmon Smith, PhD; James A. Tonascia, PhD. 
Visual Function Quality Assurance Committee: Steven Spencer, BA, COMT, CCRP (Chair); Robert D. Almanzor, COT; Deborah Gibbs, COMT; Milana Isaacson, BS; Mary Lew, COT; Richard Alan Lewis, MD, MS (Advisor). Former Members: Ferman Ballesteros; Jeff Grijalva, COT; Karen Lopez; Laura G. Neisser, COT; Rosa Paez-Boham, COST. 
Former Clinics
Indiana University, Indianapolis, IN, USA [Active from October 1997 to July 2008]: Former Members: Mitchell Goldman, MD (Director); Janice Brown; Thomas Ciulla, MD; Jean Craft, RN, CS; Ronald Danis, MD; Paul Fry; Hua Gao, MD; Samir Gupta, MD; Janet Hernandez, RN; Debra Poe; Linda Pratt, RN; James D. Richardson, MD; Tim Steffens, CRA; L. Joseph Wheat, MD; Beth Zwickl, RN, CS, MSN. 
New Jersey Medical School, Newark, NJ, USA [Active from April 1995 to January 2009]: Former Members: Ronald Rescigno, MD (Director); Neelakshi Bhagat, MD; Rosa Paez-Boham, COMT; Marta Paez-Quinde. 
Rush University, Chicago, IL, USA [Active from June 2001 to January 2009]: Former Members: Mathew W. MacCumber, MD, PhD (Director); Bruce Gaynes, OD, PharmD; Christina Giannoulis; Pamela Hulvey; Harold Kessler, MD; Heena S. Khan; Andrea Kopp; Pauline Merrill, MD; Frank Morini; Nada Smith; Allen Tenorio, MD; Denise Voskuil-Marre; Kisung Woo. 
University of California, Irvine, CA, USA [Active from April 1998 to January 2009]: Former Members: Baruch D. Kuppermann, MD, PhD (Director); Bogdan Alexandiescu, MD; Donald N. Forthal, MD; Jeff Grijalva, COT; Faisal Jehan, MD; Karen Lopez; Rosie Magallon, BA; Nader Moinfar, MD; Bret Trump; Melody Vega, COA; Randy Williams. 
University of Southern California, Los Angeles, CA, USA [Active from April 1998 to July 2008]: Former Members: Jennifer I. Lim, MD (Director); Rizwan Bhatti, MD; John Canzano, MD; Thomas S. Chang, MD; Alexander Charonis, MD; Lawrence Chong, MD; Robert Equi, MD; Amani Fawzi, MD; Christina Flaxel, MD; Jesus Garcia; Todd Klesert, MD; Francoise Kramer, MD; Lori Levin, MPH; Tracy Nichols, COA, CRA; Christopher Pelzek, MD; Margaret Podilla, BS; Len Richine; Danny Romo, COA; Srinivas Sadda, MD; Richard Scartozzi, MD; Robert See, MD; Kevin Shiramizu, MD; Mark Thomas; A. Frances Walonker, CO, MPH; Alexander Walsh, MD; Ziquiang Wu, MD. 
University of Texas Medical Branch, Galveston, TX, USA [Active from July 1997 to January 2009]: Former Members: Garvin Davis, MD (Director); Robert Blem, MD; J. Mike Bourg, BA; Gibran Khurshid, MD; John Horna, BS; Craig Kelso; Vivian Keys; Zbigniew Krason, BS; Helen K. Li, MD; Lan-Chi Nguyen, COMT; Rhonda Nolen, BS, CRC; Michelle Onarato, MD; David Paar, MD; Steven Rivas; Vicky Seitz, COT; Happy Spillar; Sami Uwaydat, MD. 
LSOCA Grant Support.
Supported by cooperative agreements from the National Eye Institute to Mount Sinai School of Medicine (U10 EY 08052), The Johns Hopkins University Bloomberg School of Public Health (U10 EY 08057), and the University of Wisconsin, Madison School of Medicine (U10 EY 08067). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Eye Institute or the National Institutes of Health. 
Additional support provided by National Center for Research Resources through General Clinical Research Center Grants: 
5M01 RR 00350 (Baylor College of Medicine) 
5M01 RR00039 (Emory University) 
5M01 RR 05096 (LSU/Tulane/Charity Hospital) 
5M01 RR00096 (New York University Medical Center, New York) 
5M01 RR 00865 (University of California, Los Angeles) 
5M01 RR00046 (University of North Carolina) 
5M01 RR00043 (University of Southern California) 
ULI RR024996 (Weill Medical College of Cornell University) 
Support also provided through cooperative agreements: 
U01 AI 27674 (Louisiana State University/Tulane) 
U01 AI 27660 (University of California, Los Angeles) 
U01 AI 27670 (University of California, San Diego) 
U01 AI 27663 (University of California, San Francisco) 
U01 AI25868 (University of North Carolina) 
U01 AI32783 (University of Pennsylvania) 
Figure 1
 
The LSOCA fundus photography grid outlining the retinal regions into three zones. Zone 1 corresponds to an area of 2 disc diameters (DD) (3600 μm) from the center of macula (green macular circle) and 1 DD (1800 μm) from the margins of the optic disc (green optic disc circle). Zone 2 extends from zone 1 to the vortex veins, and zone 3 extends from zone 2 to the ora serrata.
Figure 1
 
The LSOCA fundus photography grid outlining the retinal regions into three zones. Zone 1 corresponds to an area of 2 disc diameters (DD) (3600 μm) from the center of macula (green macular circle) and 1 DD (1800 μm) from the margins of the optic disc (green optic disc circle). Zone 2 extends from zone 1 to the vortex veins, and zone 3 extends from zone 2 to the ora serrata.
Figure 2
 
A mosaic image with the LSOCA grid showing an inactive cytomegalovirus (CMV) retinitis lesion in periphery, and epiretinal membrane and tension lines in macular zone 1 area (inset).
Figure 2
 
A mosaic image with the LSOCA grid showing an inactive cytomegalovirus (CMV) retinitis lesion in periphery, and epiretinal membrane and tension lines in macular zone 1 area (inset).
Table 1
 
Baseline Patient-Level Characteristics of All the Participants Who Had ERM Data for CMV and No-OOI Participants
Table 1
 
Baseline Patient-Level Characteristics of All the Participants Who Had ERM Data for CMV and No-OOI Participants
Total N = 822 CMV N = 270 No-OOI N = 552 P Value
Age, y, median (q1, q3) 44.0 (38, 51) 41.0 (35, 46) 46 (40, 52) 0.005
Sex, n (%) 0.17
 Male 663 (80.7) 225 (83.3) 438 (79.3)
 Female 159 (19.3) 45 (16.7) 114 (20.7)
Race, n (%) <0.01
 White, non-Hispanic 351 (42.7) 143 (53.0) 208 (37.7)
 Black, non-Hispanic 335 (40.8) 74 (27.4) 261 (47.3)
 Other 136 (16.5) 53 (19.6) 83 (15.0)
Education, n (%) 0.001
 High school or below 324 (39.4) 80 (29.6) 244 (44.2)
 Above high school 498 (60.6) 190 (70.4) 308 (55.8)
Karnofsky score*, median (q1, q3) 8.0 (8, 9) 8.0 (8, 9) 8.0 (8, 9) 0.002
CD4 count, cells/μL, median (q1, q3) 210 (76, 407) 103 (21, 306) 258 (116, 427) <0.01
CD4 nadir, cells/μL, median (q1, q3) 29 (8, 91) 10 (4, 26) 47 (15, 123) <0.01
HIV viral load, copies/mL, log10, median (q1, q3) 2.6 (2, 4) 3.3 (2, 5) 2.3 (2, 3) <0.01
Employment, n (%) 0.60
 Disabled 476 (57.9) 160 (59.3) 316 (57.2)
 Other 345 (42.0) 110 (40.7) 235 (42.6)
Tuberculosis, n (%) 0.71
 Yes 57 (6.9) 20 (7.4) 37 (6.7)
Syphilis, n (%) <0.01
 Yes 194 (23.6) 39 (14.4) 155 (28.1)
Hepatitis, n (%) <0.01
 Yes 324 (39.4) 81 (30.0) 243 (44.0)
Smoker, n (%) 0.12
 Missing 399 (48.5) 224 (83.0) 175 (31.7)
 Yes 144 (17.5) 11 (4.1) 133 (24.1)
Table 2
 
Estimated Prevalence Odds Ratios for ERM in CMV Retinitis (CMV-R) Versus No-OOI Group*
Table 2
 
Estimated Prevalence Odds Ratios for ERM in CMV Retinitis (CMV-R) Versus No-OOI Group*
Odds Ratio Lower CI Upper CI P Value
CMV-R vs. no OOI after adjusting for baseline covariates† 9.77 5.45 17.53 <0.01
CMV-R vs. no OOI 11.12 5.55 22.31 <0.01
Age, y 0.83 0.60 1.16 0.28
Karnofsky score 1.21 0.94 1.56 0.14
Viral load, copies/mL, log 10 0.99 0.79 1.25 0.97
CD4 count, cells/μL 1.08 0.95 1.24 0.23
CD4 nadir, cells/μL 1.04 0.82 1.31 0.75
Table 3
 
Estimated Incidence Odds Ratios for ERM in CMV-R Versus No-OOI Group*
Table 3
 
Estimated Incidence Odds Ratios for ERM in CMV-R Versus No-OOI Group*
Odds Ratio Lower CI Upper CI P Value
CMV-R vs. no OOI after adjusting for baseline covariates† 9.41 3.18 27.86 <0.01
CMV-R vs. no OOI 9.65 3.35 27.86 <0.01
Age, y 1.54 0.79 3.02 0.21
Karnofsky score 0.74 0.48 1.12 0.16
Viral load, copies/mL, log 10 0.91 0.63 1.34 0.64
CD4 count, cells/μL 1.17 0.91 1.50 0.23
CD4 nadir, cells/μL 0.55 0.17 1.80 0.32
Table 4
 
Estimated Incidence Rate Ratios* (Outcome = Incidence Rate)
Table 4
 
Estimated Incidence Rate Ratios* (Outcome = Incidence Rate)
IRR Lower CI Upper CI P Value
New OOI in last 45 days 2.62 1.24 5.52 0.01
CD4 count, cells/μL 0.99 0.99 1.001 0.47
Active border 1.79 0.77 4.18 0.18
Both eyes zones vs. zone 2 or 3 1.23 0.66 2.38 0.50
Bilateral eyes vs. unilateral eyes 0.72 0.43 1.18 0.19
Number of visible discrete lesions 0.92 0.72 1.18 0.52
Viral load, copies/mL, log 10 0.92 0.72 1.18 0.52
Age† 1.38 0.96 1.99 0.08
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