Visual prognosis, clinical features, and predisposing factors in non-HIV patients with cytomegalovirus retinitis.

PURPOSE: To study the characteristics and visual outcome of cytomegalovirus retinitis in patients of a tertiary referral ophthalmology center. METHODS: This retrospective cross-sectional study included 16 patients who presented with CMV retinitis between February 2014 and January 2017. Demographics, clinical signs, course of treatment, and visual and anatomical results were analyzed. RESULTS: Twenty five eyes of 16 patients were included. Eleven (68.8%) were females. The mean age was 29.37 ± 17.12 (range 11-73) years. Involvement was bilateral in 9 (56.2%) cases. HIV serology was negative in all patients. Best-corrected visual acuity was 0.57 ± 0.55 logarithm of the minimal angle of resolution (LogMAR) at the time of presentation and decreased to 0.69 ± 0.55 LogMAR on final visit (P = 0.332). None of the patients participating in this study was HIV-positive. CONCLUSION: CMV retinitis is a devastating complication in immunosuppressed. The visual acuity usually decreases despite aggressive appropriate treatment. This observation supports the increasing incidence of CMV infection in non-HIV patients.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN MACULA-INVOLVING CYTOMEGALOVIRUS RETINITIS.

PURPOSE: To evaluate the microstructural features of cytomegalovirus (CMV) retinitis by spectral domain optical coherence tomography (OCT). METHODS: Subjects were patients with macula-involving CMV retinitis with OCT imaging. The leading edge of retinitis in the macula was identified based on fundus imaging, and OCT findings were longitudinally evaluated in three areas: within the area of active retinitis, at the leading edge of retinitis, and just beyond the leading edge of retinitis. RESULTS: Optical coherence tomography imaging of macular CMV retinitis identified vitreous cells in 10 eyes (100%), posterior vitreous detachment in four eyes (40%), broad-based vitreomacular traction in one eye (10%), epiretinal membrane in eight eyes (80%), and lamellar hole-associated epiretinal proliferation associated with an atrophic hole in one eye (10%). Retinal architectural disruption, disruption of inner retinal layers, disruption of the external limiting membrane, and ellipsoid zone abnormalities were noted within the area of retinitis in all eyes and decreased in frequency and severity at and beyond the leading edge of retinitis, although all 10 eyes (100%) exhibited one of these abnormalities, especially outer retinal microabnormalities, beyond the leading edge of retinitis. CONCLUSION: Microstructural abnormalities were frequently noted on OCT of CMV retinitis, including within the retina beyond the leading edge of retinitis identified by corresponding fundus imaging. Outer retinal abnormalities were noted more frequently than inner retinal abnormalities beyond the leading edge of retinitis. These findings provide insight into the effects of CMV retinitis on retinal microstructure and potentially on vision and highlight the potential utility of OCT for monitoring microprogression of macula-involving CMV retinitis.

COMPARISON OF VISUAL PROGNOSIS AND CLINICAL FEATURES OF CYTOMEGALOVIRUS RETINITIS IN HIV AND NON-HIV PATIENTS.

PURPOSE: To compare the visual prognosis and clinical features of cytomegalovirus (CMV) retinitis between HIV and non-HIV patients. METHODS: Retrospective cross-sectional study on patients diagnosed with CMV retinitis. Depending on the presence of HIV infection, best-corrected visual acuity (VA) and clinical feature of CMV retinitis were analyzed. The clinical characteristics associated with poor visual prognosis after antiviral treatment were also identified. RESULTS: A total of 78 eyes (58 patients) with CMV retinitis were included in this study: 21 eyes and 57 eyes in HIV and non-HIV patients, respectively. Best-corrected VA was not significantly different between HIV and non-HIV patients. The rate of foveal involvement, retinal detachment, involved zone, and mortality did not significantly differ between the two groups. Visual acuity after antiviral treatment was significantly worse (pretreatment logarithm of the minimal angle of resolution best-corrected VA, 0.54 ± 0.67 [Snellen VA, 20/63]; posttreatment logarithm of the minimal angle of resolution best-corrected VA, 0.77 ± 0.94 [Snellen VA, 20/125]; P = 0.014). Poor visual prognosis was significantly associated with Zone 1 involvement, retinal detachment, and a poor general condition. CONCLUSION: The overall visual prognosis and the clinical features of CMV retinitis do not differ between HIV and non-HIV patients. The visual prognosis of CMV retinitis still remains quite poor despite advancements in antiviral treatment. This poor prognosis after antiviral treatment is associated with retinal detachment during follow-up, Zone 1 involvement, and the poor general condition of the patient.

Outcome of cytomegalovirus retinitis in immunocompromised patients without Human Immunodeficiency Virus treated with intravitreal ganciclovir injection.

PURPOSE: To study the outcomes of treatment with intravitreal ganciclovir injection for cytomegalovirus (CMV) retinitis in patients without Human Immunodeficiency Virus (HIV) infection. METHODS: In this retrospective cohort study, demographic and clinical characteristics of patients with CMV retinitis without HIV were noted. Patients received intravitreal ganciclovir injection (2 mg/0.1 ml) alone until quiescence. The outcome measures were time taken for the lesions to heal, number of injections, change in best-corrected visual acuity (BCVA), recurrence of retinitis, occurrence of immune recovery uveitis (IRU) or injection-related complications and retinal detachment (RD). RESULTS: 18 eyes of ten patients (six males) with mean age of 33.7 years from June 2004 to March 2013 were included. Thirteen eyes with active lesions (mean BCVA of 0.51 ± 0.41) received 5.54 ± 3.36 intravitreal ganciclovir injections with complete healing within 1.81 ± 1.25 months. The final BCVA was 0.43 ± 0.52. IRU was observed in six eyes (33.33%) and RD developed in one eye. One eye had recurrence 1 month after stopping ganciclovir injections. The rest of the patients had recurrence-free follow-up at 9.46 ± 12.42 months. CONCLUSIONS: Non-HIV patients with CMV retinitis can be successfully treated with intravitreal ganciclovir injection alone, avoiding the systemic side effects of systemic anti-CMV therapy.

[Retinal detachment in HIV-infected patients with cytomegalovirus retinitis].

The authors present their own clinical experience in three HIV-infected patients with cytomegalovirus retinitis aged from 8 to 36 years. Detailed analysis of the results of physical and laboratory examinations is provided. Given short life expectancy for these patients, the authors pose a deontological question as to whether or not active treatment of retinal detachment in patients with AIDS and CMV retinitis is reasonable.

Comparison of treatment regimens for cytomegalovirus retinitis in patients with AIDS in the era of highly active antiretroviral therapy.

PURPOSE: To describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART). DESIGN: Prospective cohort study, the Longitudinal Study of the Ocular Complications of AIDS. PARTICIPANTS: A total of 250 patients with CMV retinitis and a CD4+ T-cell count <100 cells/µl (n = 221) at enrollment or incident retinitis (n = 29) during cohort follow-up. METHODS: The effects of systemic therapy (vs. intraocular therapy only) on systemic outcomes and the effect of intraocular therapies (ganciclovir implants, intravitreal injections) on ocular outcomes were evaluated. MAIN OUTCOME MEASURES: Mortality, CMV dissemination, retinitis progression, and treatment side effects. RESULTS: Regimens containing systemic anti-CMV therapy were associated with a 50% reduction in mortality (adjusted hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3-0.7; P = 0.006), a 90% reduction in new visceral CMV disease (adjusted HR, 0.1; 95% CI, 0.04-0.4; P = 0.004), and among those with unilateral CMV retinitis at presentation, an 80% reduction in second eye disease (adjusted HR, 0.2; 95% CI, 0.1-0.5; P = 0.0005) when compared with those using only intraocular therapy (implants or injections). Compared with systemic treatment only, regimens containing intravitreal injections had greater rates of retinitis progression (adjusted HR, 3.4; P = 0.004) and greater visual field loss (for loss of one half of the normal field, adjusted HR, 5.5; P < 0.01). Intravitreal implants were not significantly better than systemic therapy (adjusted HR for progression, 0.5; P = 0.26; adjusted HR for loss of one half of the visual field, 0.5; P = 0.45), but the sample size was small. Hematologic and renal side effect rates were similar between those groups with and without systemic anti-CMV therapy. The rate of endophthalmitis was 0.017 per eye-year (EY) (95% CI, 0.006-0.05) among those treated with intravitreal injections and 0.01 per EY (95% CI, 0.002-0.04) among those treated with an implant. CONCLUSIONS: In the HAART era, systemic anti-CMV therapy, while there is immune compromise, seems to provide benefits in terms of longer survival and decreased CMV dissemination. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Multiple intravitreal injections of ganciclovir for cytomegalovirus retinitis after stem-cell transplantation.

BACKGROUND: Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). Although much effort has been put into dealing with CMV retinitis secondary to acquired immunodeficiency syndrome (AIDS), the few reports which have been published have mainly focused on treatment of CMVR after HSCT. METHODS: This clinical interventional retrospective study included 14 patients (eight men; mean age 23.89 ± 12.09; 23 eyes) who suffered from CMV retinitis after stem-cell transplantation, in order to evaluate the efficacy and safety of multiple intravitreal injections of ganciclovir (IVG) for patients with CMV retinitis. All patients received 4 injections of IVG of 1 mg at 1 week intervals, and were followed up weekly for at least 2 months with measurement of best-corrected visual acuity (BCVA) and CMV levels in anterior aqueous humor with real-time polymerase chain reaction. Anterior aqueous humor was obtained before each injection. RESULTS: The levels of CMV in anterior aqueous humor showed significant decrease from (6.34 ± 15.78) × 10(5) copies/ml at baseline to (5.22 ± 12.15) × 10(3) copies/ml at 1 month (P < 0.001, Mann-Whitney U test). CMV couldn't be detected in 11 eyes (47.8 %) after two injections, and this rose to 18 eyes (78.3 %) at 1 month. The mean logMAR BCVA was 0.659 ± 0.572 at baseline and 0.680 ± 0.527 at 2 months, which suggested no significant improvement (P = 0.736, Mann-Whitney U test) during the procedure. All patients experienced improved vitreous opacity and diminished area of the lesion under funduscopy after 4 injections of IVG. No severe complications developed. CONCLUSIONS: Multiple IVG seemed to be beneficial for patients with CMV retinitis after stem-cell transplantation, in reducing CMV levels in aqueous humor. Further study to optimize the dose of ganciclovir is needed in order to achieve better treatment outcomes.

[Severe case of cytomegalovirus-associated immune reconstitution syndrome in AIDS].

BACKGROUND: Immune reconstitution syndrome (IRS) is a complication caused by reactivation of the immune system that can occur after starting highly active antiretroviral therapy (HAART) in patients with acquired immunodeficiency syndrome (AIDS). Severe IRS associated with cytomegalovirus (CMV) in both eyes who had lost his left vision is reported. CASE: A 37-year-old man with AIDS who had started HAART discontinued his medication. Two weeks after the re-induction of HAART, he suffered CMV retinitis OU. Vitreous opacity OU appeared 3 days later, and optic neuritis OS appeared 6 days after the onset; and visual acuity OS decreased to 0.06. As the number of CD 4 positive T lymphocytes (CD 4) increased from 39 to 118/microl in both the pre- and- post HAART, we diagnosed IRS and started anti- CMV and systemic steroid therapy and discontinued the HAART. The focus of CMV retinitis was improved; however, visual acuity OS did not improve. CONCLUSION: Severe IRS with visual loss induced by CMV retinitis after HAART needs to be considered in low CD 4 level patients during the induction phase.

Human immunodeficiency virus-associated cytomegalovirus infection with multiple small vessel cerebral infarcts in the setting of early immune reconstitution.

Cytomegalovirus (CMV) infection is an important cause of neurologic disease in the context of advanced human immunodeficiency virus (HIV) infection and is recognized as a cause of immune reconstitution inflammatory syndrome (IRIS) after initiation of highly active antiretroviral therapy (HAART). Central nervous system vasculitis secondary to CMV has only rarely been described in the context of HIV, despite the established ability of CMV to infect microvascular endothelial cells in the brain. However, we report a case that demonstrates the association between CMV and multiple small vessel cerebral infarct lesions after initiation of HAART.

Delayed presentation of cytomegalovirus retinitis in an infant with severe congenital cytomegalovirus infection.

PURPOSE: The purpose was to study the congenital cytomegalovirus (CMV), which is the most common cause for congenital infection in the United States, affecting nearly 40,000 infants per year. There is no widely accepted treatment protocol for congenital CMV infection despite recent clinical trials with antiviral medications ganciclovir and valganciclovir. METHODS: We present a case report of an infant with severe congenital CMV infection with presentation of chorioretinitis in both eyes at 5 months of age. RESULTS: The child did not receive treatment with ganciclovir during hospitalization after birth despite severe manifestations of CMV infection. Treatment was again withheld after diagnosis of retinitis because of immunocompetent status, potential side effects of ganciclovir treatment, and location of retinitis in the retinal periphery of both eyes. The retinitis resolved during a period of 3 months. CONCLUSION: This case shows that CMV retinitis in infants with congenital CMV infection can be delayed in presentation and can resolve without treatment. It shows the need for more consistent monitoring for chorioretinitis in infants with congenital CMV infection.

Juxtapapillary cytomegalovirus retinitis with optic neuritis.

A 49-year-old man with AIDS developed acute monocular visual loss and an ipsilateral swollen optic disc with a large right relative afferent pupillary defect, a nerve fiber bundle visual field defect, and a peripapillary retinal infiltrate. Lumbar puncture disclosed cytomegalovirus (CMV) DNA on polymerase chain reaction (PCR). Treatment with oral valganciclovir produced complete resolution of the visual deficits and the fundus abnormality. This case differs from previously reported cases of CMV optic neuritis in which visual function has been irreversibly lost.

Visual acuity outcomes in cytomegalovirus retinitis: early versus late diagnosis.

AIMS: To determine if early dilated fundus examination for cytomegalovirus (CMV) retinitis leads to better visual outcomes in areas with limited HIV care, where patients may have long-standing retinitis before they are diagnosed with HIV. METHODS: Twenty-four eyes of 17 patients with CMV retinitis who were seen at an urban HIV clinic in Chiang Mai, Thailand, were included in this retrospective cohort study. Participants were divided into two groups based on the amount of time from the first documented CD4 count below 100 cells/mm3 to the first eye examination for CMV retinitis. Average visual acuity in each group was calculated at the time CMV retinitis was first detected, and then at 3, 6 and 12 months after diagnosis. RESULTS: The group of patients who received an eye examination within approximately 4 months of the initial low CD4 count measurement had better baseline visual acuity (median 20/30,IQR 20/20 to 20/60) compared with patients who presented later (median 20/80, 20/60 to hand motion); p=0.03). Visual acuity did not change significantly during the 12-month study period in either the early group (p=0.69) or late group (p=0.17). CONCLUSION: In this study, patients who were examined sooner after a low CD4 count had better vision than patients who were examined later. Routine early screening of patients with CD4 counts under below 100 cells/mm3 may detect earlier disease and prevent vision loss.

[Cytomegalovirus infection--selected aspects of clinical pathology]. / Zakazenie wirusem cytomegalii--wybrane aspekty patologii klinicznej.

In this review short biological characteristics of human cytomegalovirus (CMV), the sources and its modes of transmission to human organisms, are presented. The authors described clinical pathology mainly of ocular organ and central nervous system in children with congenital cytomegalovirus infection and in acquired form of cytomegaly in adults with immunosupression (especially with HIV infection and AIDS). In review there are included contemporary diagnostic laboratory methods used in detection of CMV infection and in evaluation of clinical pathology.

Analysis and Outcomes of Cataract Surgery in Patients with Acquired Immunodeficiency Syndrome.

PURPOSE: To investigate the surgical outcomes, complications and postoperative progression in HIV patients undergoing cataract surgery in a teaching hospital. METHODS: A retrospective cohort study of patients with HIV/AIDS who had cataract surgery from January 2000 until December 2011 at a tertiary referral multidisciplinary hospital in Singapore. RESULTS: We identified 44 eyes from 29 patients. Preoperatively, 41.3% had no ophthalmic manifestations of HIV/AIDS, while 16 eyes had quiescent cytomegalovirus retinitis (CMVR). Postoperatively, 1 eye developed new CMVR, while 1 eye had reactivation of previous CMVR. Of eyes with new or previous CMVR, 1 eye developed rhegmatogenous retinal detachment (RD) postoperatively. Only 3 eyes had prolonged postoperative inflammation. There were no cases of endophthalmitis or cystoid macular edema. Postoperative improvement of at least two Snellen lines was achieved in 86.6% of eyes. CONCLUSIONS: Cataract surgery in HIV patients is generally safe, regardless of CD4 count, but their general and ocular health should be optimized preoperatively.

Hemorheologic abnormalities associated with HIV infection: in vivo assessment of retinal microvascular blood flow.

PURPOSE: To evaluate retinal microvascular blood flow in human immunodeficiency virus (HIV)-infected individuals using scanning laser Doppler flowmetry (SLDF) and to seek correlations between flow and various laboratory measures that may predict alterations in flow. METHODS: The Heidelberg Retina Flowmeter and SLDF software were used to acquire in vivo retinal blood flow data from 24 HIV-infected individuals and 16 HIV-negative control subjects. In each subject, separate scans were performed in each of six retinal regions: nasal parapapillary retina; macula; and the superior, nasal, inferior, and temporal periphery. Erythrocyte aggregation (assessed in vitro by a fully automatic erythrocyte aggregometer and by zeta sedimentation ratio [ZSR, a hematocrit-independent sedimentation rate]), serum fibrinogen level, plasma viscosity, and leukocyte rigidity (assessed in vitro with a cell transit analyzer) were compared with flow in selected regions. RESULTS: Flow was significantly higher in the periphery (superior, nasal, inferior, temporal) than in the posterior retina (nasal parapapillary retina, macula). Flow was highest in the temporal periphery for both HIV-infected subjects and control subjects. Flow in the posterior retina was significantly lower in HIV-infected subjects than in control subjects (P < 0.0001). Among HIV-infected individuals, flow in the macula correlated negatively with ZSR (r = -0.397, P = 0.0547) and leukocyte rigidity (r = -0.505, P = 0.0119). CONCLUSIONS: Microvascular blood flow in the posterior retina is reduced in HIV-infected individuals. Both increased erythrocyte aggregation and increased leukocyte rigidity contribute to this hemorheologic abnormality.

Diagnostic Utility of Ocular Symptoms and Vision for Cytomegalovirus Retinitis.

PURPOSE: Cytomegalovirus (CMV) retinitis remains a leading cause of blindness in countries with a high burden of AIDS. Although dilated fundus examinations are recommended for those with CD4 counts below 100 cells/µL, in practice only those with poor vision and/or symptoms are routinely referred for screening. Therefore, the predictive value of this common practice should be assessed. METHODS: This is a prospective cross-sectional study. Patients with known HIV and a CD4 count of less than 100 cells/µL attending an HIV clinic in Chiang Mai, Thailand completed a standardized questionnaire about visual symptoms and underwent visual acuity testing and dilated fundus examination. Participants without CMV retinitis were invited for repeated examinations every 3 months until their CD4 count exceeded 100 cells/µL. Patient-level statistical analyses were conducted to calculate diagnostic test characteristics, with bootstrapping to account for correlated data. RESULTS: Of 103 study participants, 16 had CMV retinitis diagnosed at some point during the study. Participants with CMV retinitis were more likely to complain of visual symptoms compared to those without CMV retinitis (p = 0.01), including scotoma (p = 0.0002), itchy or watery eyes (p < 0.0001), and eye pain (p = 0.003); they were also more likely to have visual acuity worse than Counting Fingers (p = 0.0003). However, the absence of eye symptoms and the absence of poor vision did not strongly affect the probability that a patient did not have disease (negative likelihood ratio 0.56 and 0.76, respectively). CONCLUSIONS: Ocular symptoms and poor visual acuity were poor diagnostic indicators for the presence of CMV retinitis. Systematic screening of HIV patients with CD4 counts below 100 cells/µl should be carried out to detect disease at an early stage, when blindness can still be prevented.

Long-term Follow-up of Cytomegalovirus Retinitis in Non-HIV Immunocompromised Patients: Clinical Features and Visual Prognosis.

PURPOSE: To evaluate clinical features and long-term visual outcome of cytomegalovirus (CMV) retinitis in patients without human immunodeficiency virus (HIV) infection, and to determine factors that predict visual outcome. DESIGN: Retrospective cohort study. METHODS: Consecutive patients with CMV retinitis without HIV infection were reviewed. Main outcome measures included clinical features, proportion of eyes with 6-month and final visual acuity (VA) <20/70 and <20/400, and odds ratios of factors associated with poor visual outcome. RESULTS: A total of 20 eyes from 13 patients were included with a median follow-up time of 17 months. All had at least 6 months of follow-up except 1 patient who died from sepsis at 1 month. At presentation, 50% of eyes had VA <20/70 and 25% had VA <20/400. Zone 1 involvement occurred in 55% and vitreous haze ≥grade 2+ occurred in 25%. Recurrence occurred in 33.3% at a mean time of 6.4 ± 3.3 weeks after discontinuation of anti-CMV therapy. The retinal detachment rate was 21.7% per eye-year and mortality rate was 11.7% per person-year. At final visit, 60% had VA <20/70 and 35% had VA <20/400. Macular involvement was significantly associated with poor final VA <20/400 (odds ratio = 25.00, P = .016). CONCLUSIONS: CMV retinitis without HIV infection was often aggressive at presentation. Significant intraocular inflammation was not uncommon. The long-term visual outcome was poor, especially in those with macular involvement.

Clinician versus reading center assessment of cytomegalovirus retinitis lesion size.

PURPOSE: To compare clinician and fundus photograph reading center assessments of the cytomegalovirus (CMV) retinitis area and change in the CMV retinitis area over time, and to investigate how these assessments correlate with the visual field (VF) of eyes with CMV retinitis. DESIGN: Analysis of pooled data from 2 multicenter randomized clinical trials and 1 prospective multicenter epidemiologic study. PARTICIPANTS: Ninety-five eyes of 79 patients. At baseline, each eye had CMV retinitis restricted to zone 1 and/or zone 2 (approximately the photographable postequatorial retina), as assessed by the evaluating clinician. METHODS: Comparison of CMV retinitis area, change in area over time as assessed by clinicians and a fundus photograph reading center, and correlation of these assessments with VF measurement. MAIN OUTCOME MEASURES: Cytomegalovirus retinitis area, change in CMV retinitis area over time, and VF score. RESULTS: Baseline assessments of the mean retinitis area were, by clinicians, 12.8% of the total retinal area and, by the reading center, 6.3% of the total retinal area (P<0.001). There was a positive correlation between clinician and reading center assessments of retinitis area at baseline (rho = 0.77 and P<0.0001 by Pearson correlation and rho = 0.54 and P<0.001 by concordance). Both clinician and reading center size measures correlated negatively with VF (Spearman correlation rhos = -0.38 and -0.52, respectively; P<0.001 each). Mean changes in area over a 3-month interval were, by clinicians, +1.2% and, by the reading center, +1.1% (P = 0.68). Regression analysis showed a positive concordance (rho = 0.42, P<0.001). Change in VF over a 3-month interval did not correlate with change in retinitis area as assessed by clinicians or the reading center. CONCLUSIONS: Awareness of the similarities and differences between clinician and reading center assessments of CMV retinitis area should permit clinicians to apply research data to clinical practice more effectively. Clinician assessment of retinitis area correlates negatively with VF, a clinically meaningful visual outcome in patients with CMV retinitis.

Incidence of cytomegalovirus (CMV) retinitis in second eyes of patients with the acquired immune deficiency syndrome and unilateral CMV retinitis.

PURPOSE: To evaluate the risk and risk factors for developing cytomegalovirus (CMV) retinitis in previously uninvolved second eyes among patients with unilateral CMV retinitis. DESIGN: Cohort study. SETTINGS: Single-center academic AIDS ophthalmology practice. PATIENT POPULATION: Three hundred seventy-six consecutive patients with AIDS and unilateral CMV retinitis were followed from the time of CMV retinitis diagnosis for the development of second-eye retinitis. EXPERIMENTAL PROCEDURES: Demographic and clinical characteristics were noted at baseline. Use of highly active antiretroviral therapy (HAART) and immune recovery in response to HAART were noted prospectively. MAIN OUTCOME MEASURE: Development of CMV retinitis in a previously uninvolved eye. RESULTS: Ninety-one percent of subjects received systemic anti-CMV treatment. Second-eye retinitis occurred in 26.1%/person-year (19.6% within the first 6 months), less than half the rate previously reported in untreated groups. Initial CD4+ T cell count >12 cells/microl, use of HAART, and initial posterior pole involvement were associated with 64%, 46%, and 41% reductions in incidence vis-à-vis comparison groups. Benefit from HAART was limited to that subset who developed immune recovery of a degree expected to restore innate control of CMV (a rise in the CD4+ T cell count by >50 cells/microl to a level >100 cells/microl). CONCLUSIONS: The risk of second-eye retinitis is substantial in patients with unilateral CMV retinitis but appears to be reduced by anti-CMV therapy and by HAART-induced immune recovery. Patients are at highest risk when CD4+ T cell counts are very low and in the months immediately after CMV retinitis diagnosis.