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Background: Introduction of highly active antiretroviral therapy has altered the course of disease for persons infected with human immunodeficiency virus by elevating CD4+ T-lymphocyte levels. Changes in the spectrum of systemic diseases encountered in human immunodeficiency virus-positive individuals are reported in the general medical literature., Design: Retrospective case series., Participants: Sixty-one individuals infected with human immunodeficiency virus, who presented with uveitis when the peripheral CD4+ T-lymphocyte count was over 200 cells/μL., Methods: Standardized data collection at seven tertiary-referral inflammatory eye disease clinics., Main Outcome Measures: Standardization of Uveitis Nomenclature anatomic classification and descriptors, cause of uveitis, and visual acuity, Results: Peripheral CD4+ T cell counts varied between 207 and 1777 (median = 421) cells/μL at the time of diagnosis of uveitis. Uveitis was classified anatomically as anterior (47.5%), intermediate (6.6%), anterior/intermediate (16.4%), posterior (14.8%) and pan (14.8%). Specific causes of uveitis included infections (34.4%), with syphilis responsible for 16.4% of all cases, and defined immunological disorders (27.0%); no cause for the inflammation was identified in 34.4% of persons. Visual acuity was better than 6/15 in 66.7% and 6/60 or worse in 11.8% of 93 eyes at presentation, and better than 6/15 in 82.4% and 6/60 or worse in 8.8% of 34 eyes at 1 year of follow-up., Conclusions: Both infectious and non-infectious forms of uveitis occur in individuals who are infected with human immunodeficiency virus and have preserved or restored peripheral CD4+ T cell levels. Individuals who are human immunodeficiency virus-positive and present with uveitis should be evaluated in the same way all patients with uveitis are assessed., (© 2013 Royal Australian and New Zealand College of Ophthalmologists.)

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in low- and middle-income settings., Methods: We conducted a systematic review and meta-analysis of published and unpublished studies reporting prevalence of CMV retinitis in low- and middle-income countries.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

Background: On rare occasions, patients infected with human immunodeficiency virus (HIV) can develop a disorder similar to chronic progressive external ophthalmoplegia (CPEO) while undergoing long-term treatment with antiretroviral therapy. Orbital imaging may help explain the pathogenesis of this abnormality., Methods: In this case series, 5 adult patients who presented with a CPEO-like disorder after more than 10 years of antiretroviral therapy and who underwent T1-weighted high-resolution magnetic resonance imaging (MRI) of the orbits and brain were retrospectively identified. Patients also were screened for acetylcholine receptor antibody levels., Results: All patients had bilateral external ophthalmoplegia and blepharoptosis. Acetylcholine receptor antibody titers were not increased. Brain MRI was unremarkable. Orbital MRI showed patchy bright signal inside the extraocular muscles that had conserved volume., Conclusions: Patients with HIV under long-term antiretroviral therapy may develop functional abnormalities of extraocular muscles that are structurally normal in size, that is, changes are similar to those observed in the orbital MRIs of patients with CPEO. This constellation of signs and symptoms suggests a possible role of HIV disease or antiretroviral therapy in the CPEO-like syndrome observed in some HIV-infected individuals., (Copyright © 2012 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.)

Purpose: To investigate relationships between contrast sensitivity (CS), color vision, and retinal nerve fiber layer (RNFL) among people with human immunodeficiency virus (HIV) infection; to evaluate the effect of time since diagnosis of HIV infection on RNFL thickness., Design: Noninterventional cross-sectional study., Methods: We evaluated 102 eyes of 57 HIV-infected individuals without ocular opportunistic infections. Peripapillary RNFL thickness was determined with spectral-domain optical coherence tomography in 4 quadrants. CS was measured with the Pelli-Robson technique (expressed as logCS); color vision was measured with the Lanthony desaturated 15-hue technique (expressed as color confusion index [C-index], with higher scores indicating worse color vision). Correlations between values were assessed using Spearman correlation coefficients., Results: Median RNFL thickness (average of 4 quadrants) was 102.9 μm (range, 75.0-134.7 μm). Median logCS was 1.90 (range, 1.25-1.95). Median C-index was 1.58 (range, 0.96-4.07). Temporal RNFL thickness was correlated with logCS (r=0.295, P=.003) and C-index (r=-0.338, P=.0005). Time since diagnosis of HIV infection was shorter for those with thick average RNFL than for those with thin average RNFL (P=.18)., Conclusions: Both worse CS and worse color vision are correlated with thinning of the temporal RNFL, with possible threshold effects. Increased prevalences of abnormal CS and abnormal color vision in this population are therefore likely attributable to neuroretinal compromise. This pattern of structural and functional losses may reflect preferential damage to small-caliber axons in the maculopapillary bundle, possibly associated with mitochondrial dysfunction, providing a potential disease mechanism for HIV-associated "neuroretinal disorder.", (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the prevalence and risk factors for vision loss in patients with clinical or immunologic AIDS without infectious retinitis., Design: A prospective, multicenter cohort study of patients with AIDS., Methods: One thousand three hundred and fifty-one patients (2,671 eyes) at 19 clinical trials centers diagnosed with AIDS but without major ocular complications of HIV. Standardized measurements of visual acuity, automated perimetry, and contrast sensitivity were analyzed and correlated with measurements of patients' health and medical data relating to HIV infection. We evaluated correlations between vision function testing and HIV-related risk factors and medical testing., Results: There were significant (P<.05) associations between measures of decreasing vision function and indices of increasing disease severity, including Karnofsky score and hemoglobin. A significant relationship was seen between low-contrast sensitivity and decreasing levels of CD4+ T-cell count. Three percent of eyes had a visual acuity worse than 20/40 Snellen equivalents, which was significantly associated with a history of opportunistic infections and low Karnofsky score. When compared with external groups with normal vision, 39% of eyes had abnormal mean deviation on automated perimetry, 33% had abnormal pattern standard deviation, and 12% of eyes had low contrast sensitivity., Conclusions: This study confirms that visual dysfunction is common in patients with AIDS but without retinitis. The most prevalent visual dysfunction is loss of visual field; nearly 40% of patients have some abnormal visual field. There is an association between general disease severity and less access to care and vision loss. The pathophysiology of this vision loss is unknown but is consistent with retinovascular disease or optic nerve disease.

The eye is a common site for complications of human immunodeficiency virus (HIV) infection. Although cytomegalovirus retinitis remains the most prevalent of the blinding ocular disorders that can occur in individuals with the acquired immunodeficiency syndrome (AIDS), several important HIV-associated disorders may involve the anterior segment, ocular surface, and adnexae. Some of these entities, such as Kaposi sarcoma, were well described, but uncommon, before the HIV epidemic. Others, like microsporidial keratoconjunctivitis, have presentations that differ between affected individuals with HIV disease and those from the general population who are immunocompetent. The treatment of many of these diseases is challenging because of host immunodeficiency. Survival after the diagnosis of AIDS has increased among individuals with HIV disease because of more effective antiretroviral therapies and improved prophylaxis against, and treatment of, opportunistic infections. This longer survival may lead to an increased prevalence of anterior segment and external ocular disorders. In addition, the evaluation and management of disorders such as blepharitis and dry eye, which were previously overshadowed by more severe, blinding disorders, may demand increased attention, as the general health of this population improves. Not all individuals infected with HIV receive potent antiretroviral therapy, however, because of socioeconomic or other factors, and others will be intolerant of these drugs or experience drug failure. Ophthalmologists must, therefore, still be aware of the ocular findings that develop in the setting of severe immunosuppression. This article reviews the spectrum of HIV-associated anterior segment and external ocular disorders, with recommendations for their evaluation and management.

Purpose: To investigate possible alterations of erythrocyte aggregation and deformability, which are factors that can influence blood flow, in human immunodeficiency virus (HIV)-infected individuals and to determine whether these factors are related to the severity of immunodeficiency., Methods: Laboratory evaluations were performed on 46 HIV-infected individuals and 44 HIV-negative control subjects. Current and nadir (lowest previous) CD4+ T-lymphocyte counts were identified for each subject. Erythrocyte aggregation was measured using a fully automatic erythrocyte aggregometer. Factors related to erythrocyte aggregation were also determined: erythrocyte sedimentation rate (ESR), zeta sedimentation ratio (ZSR), and plasma fibrinogen levels. Erythrocyte deformability was observed at various fluid shear stress levels, with a laser diffraction ektacytometer. Correlations were sought between each of these measures and current or nadir CD4+ T-lymphocyte counts, and each measure was compared between three subgroups based on current and nadir CD4+ T-lymphocyte counts (severely immunosuppressed, immune reconstituted, never severely immunosuppressed)., Results: The following parameters were significantly different between HIV-infected subjects and controls: increased erythrocyte aggregation, at stasis (P < 0.001) and low shear stress (P < 0.001), increased ESR (P < 0.001), increased ZSR (P < 0.028), increased serum fibrinogen (P = 0.015), and decreased erythrocyte deformability (P < 0.001). Only erythrocyte aggregation at stasis correlated significantly with current CD4+ T-lymphocyte count (r = - 0.344, P = 0.022). None of the parameters was significantly different between HIV-infected subgroups., Conclusions: Increased aggregation and decreased deformability of erythrocytes are associated with HIV-infection regardless of the severity of immunodeficiency. HIV-infected individuals may be at risk for progressive retinal microvascular damage from persistent hemorheologic abnormalities, despite immune reconstitution associated with potent antiretroviral drug therapies.

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.

Purpose: To investigate the relationship between abnormal contrast sensitivity and abnormal color vision among human immunodeficiency virus (HIV)-infected individuals who have normal visual acuity and to seek host factors that predict these abnormalities., Design: Noninterventional, cross-sectional study., Methods: We evaluated 71 HIV-infected subjects with visual acuity of 20/25 or better, clear media, and no vision-threatening retinal lesions. Visual function was determined using the Pelli-Robson contrast sensitivity test and the Farnsworth-Munsell 100-Hue color test (FM-100). Results were compared with published values for normal populations and to measures of HIV disease severity. We evaluated two levels of impairment for each visual function. "Mild dysfunction" was defined as > or =1 standard deviation (SD), but <2 SD from normal means. "Abnormal" was defined as > or =2 SD from normal means., Results: The prevalences of abnormal contrast sensitivity and abnormal color vision were 7.0% and 9.9%, respectively. We did not identify relationships between impaired contrast sensitivity and impaired color vision. Impaired color vision was associated with increasing age (r = 0.36, P = .002). We could not identify significant correlations between either contrast sensitivity or color vision values and the following factors: current or nadir (lowest previous) CD4+ T-lymphocyte count, HIV blood level, and Karnofsky score., Conclusions: Abnormal contrast sensitivity and abnormal color vision can occur independently in HIV-infected individuals and can be present in the absence of severe immunosuppression.

Purpose: To describe a keratopathy in patients with the human immunodeficiency virus (HIV) infection., Methods: Retrospective review of ophthalmic and medical records, including laboratory evaluations, of seven patients with HIV infection and posterior intracorneal opacities., Results: Each patient had a bilateral peripheral keratopathy located at the level of the Descemet membrane that was unassociated with intraocular inflammation. All patients were receiving highly active antiretroviral therapy (HAART). All patients had elevations in their CD4+ T-lymphocyte counts due to HAART prior to presenting with the corneal opacities. Five of the seven patients had elevated serum cholesterol, triglycerides, or both. Best-corrected visual acuity was 20/25 or better in six of the seven patients at the time of diagnosis, and vision remained stable through the follow-up period in all patients (median follow-up: 25 months; range: 14-82 months). The corneal opacities remained unchanged in all seven over the follow-up period., Conclusion: These patients have a bilateral keratopathy that appears to be non-progressive and has no effect on visual acuity.

Purpose: To determine whether polymorphonuclear leukocytes (PMNs) remain rigid after immune reconstitution in human immunodeficiency virus (HIV)-infected individuals with a history of severe immunosuppression., Methods: PMN rigidity was measured in vitro in three groups: (1) HIV-infected individuals with a history of CD4+ T-lymphocyte counts of less than 50/microL, but with current counts of more than 200/microL attributable to potent antiretroviral therapy (group 1); (2) HIV-infected individuals whose CD4+ T-lymphocyte counts had always been more than 200/microL (group 2); and (3) HIV-negative control subjects. Rigidity was determined with a cell transit analyzer (containing a micropore filter with 30 identical, 8-microm diameter pores), representing a simple in vitro model of a capillary bed. A longer PMN pore transit time reflects increased PMN rigidity., Results: PMN transit time (median) in group 1 (n = 11) was 3.34 ms, in group 2 (n = 9) was 3.19 ms, and in control subjects (n = 15) was 2.66 ms. PMN rigidity was significantly greater in groups 1 (P = 0.014) and 2 (P = 0.046) than in control subjects (Wilcoxon rank-sum test). A significant difference was not identified between groups 1 and 2 (P = 0.518)., Conclusions: The increased PMN rigidity known to occur in severely immunosuppressed HIV-infected individuals persists after immune reconstitution. Furthermore, PMN rigidity is increased in those HIV-infected individuals who do not have a history of severe immunosuppression. Because PMN rigidity can alter microvascular blood flow, HIV-infected individuals may remain at risk for retinal vascular damage in the era of potent antiretroviral therapy.

Purpose: To determine whether human immunodeficiency virus (HIV)-infected individuals have decreased macular capillary blood flow in vivo., Design: Case control study., Methods: Macular leukocyte velocity and perceived leukocyte density were determined in 41 HIV-infected individuals without cytomegalovirus retinitis and 31 HIV-negative control subjects using the blue field simulation technique (BFS-2000, Oculix, Inc., Jenkintown, PA). Velocity and density measurements for HIV-infected individuals were compared to current and lowest previous CD4+ T-lymphocyte counts, HIV RNA blood levels, and blood leukocyte counts., Results: Mean macular leukocyte velocity was lower in HIV-infected individuals than in controls (P = 0.0006). No correlations were identified between velocity measurements and the following factors in HIV-infected individuals: current or lowest previous CD4+ T-lymphocyte count; or HIV RNA blood level. Mean perceived leukocyte density in HIV-infected individuals was lower than in controls (P = 0.003), but was not correlated with blood leukocyte count in HIV-infected individuals. No relationships were identified between macular leukocyte velocity and duration of medication use or duration of elevated CD4+ T-lymphocyte count in patients receiving potent antiretroviral therapy., Conclusions: Reduced macular leukocyte velocity may have important implications for understanding the retinal microvasculopathy of HIV disease, the pathogenesis of opportunistic retinal infections, and visual dysfunction in HIV-infected individuals who do not have opportunistic retinal infections. We found no evidence that macular leukocyte velocity increased with immune reconstitution.

Aim: Individuals with human immunodeficiency virus (HIV) infection were evaluated for evidence of abnormal polymorphonuclear leucocyte (PMN) rigidity, which can alter capillary blood flow., Methods: The transit time of individual PMN through 8 microm pores in a cell transit analyser was used as a measure of cell rigidity. PMN transit time was compared between HIV infected individuals (n=45) with and without CMV retinitis and HIV negative controls (n=17)., Results: Transit times were longer for PMN from HIV infected individuals than for PMN from controls (p<0.001). PMN from HIV infected individuals with CMV retinitis (n=13) had longer transit times than PMN from those without CMV retinitis (n=32, p<0.001). Transit times were longer in HIV infected individuals with lower CD4+ T lymphocyte counts (p<0.001). Regression analysis indicated that the relation between transit times and the presence of CMV retinitis could not be explained solely on the basis of low CD4+ T lymphocytes. In HIV infected individuals, mean transit time was not correlated with age, blood pressure, or serum creatinine, cholesterol, or triglycerides., Conclusions: HIV infected individuals appear to have increased PMN rigidity, a cellular change that might be involved in the pathogenesis of HIV related retinal microvasculopathy. PMN rigidity appears to be related to severity of immune dysfunction. PMN rigidity may remain high in patients with CMV retinitis after elevations of CD4+ T lymphocyte counts that result from potent antiretroviral therapy.

Purpose: To report uveitis associated with human immunodeficiency virus (HIV) infection and to suggest guidelines for treatment., Methods: Six HIV-seropositive patients (10 eyes) with anterior or posterior uveitis or both were evaluated. After ineffective prolonged treatment with systemic and topical corticosteroids, specific systemic antiretroviral therapy with zidovudine was initiated in all patients. Aqueous humor was cultured in three eyes of three patients, and vitreous humor was cultured in one eye of one patient., Results: In all 10 eyes of six patients, there was resolution of inflammation in 10 to 42 days after commencement of treatment with zidovudine (600 to 800 mg/day), despite no or minimal response to corticosteroids. Cultures of aqueous humor from three eyes of three patients and culture of vitreous humor from one eye of one patient were positive for HIV; no other organism was isolated. Systemic evaluation disclosed no other identifiable cause for the uveitis in any patient., Conclusions: Infection with HIV appears to be a cause of uveitis. A trial of zidovudine may be warranted in HIV-seropositive patients with uveitis that is poorly responsive to corticosteroid treatment when no other cause is identified. The efficacy of other retroviral agents was not determined.

Purpose: To describe the clinical features of a disorder characterized by chronic multifocal retinal infiltrates and uveitis in individuals with human immunodeficiency virus (HIV) disease., Methods: We reviewed the medical records of HIV-infected patients with multifocal retinal infiltrates of unknown cause seen by investigators at four institutions. The following data were collected: demographic characteristics, presenting signs and symptoms, laboratory test results, and course of disease., Results: We identified 26 HIV-infected patients (50 involved eyes) with this syndrome. Median CD4+ T-lymphocyte count at presentation was 272 per microl (range, 7 to 2,118 per microl). The most common presenting symptom was floaters. Median visual acuity of involved eyes at presentation was 20/20 (range, 20/15 to 20/100) and remained stable (median, 20/20; range, 20/15 to 20/70) after a median follow-up period of 9 months (range, 0 to 110 months). Typical retinal lesions were gray-white or yellow, irregular in shape, and less than 200 microm in greatest dimension. All were located in the midperiphery or anterior retina and enlarged slowly or remained static in size. Mild to moderate anterior chamber or vitreous humor inflammatory cells were present in 47 of 50 eyes (26 of 26 patients). Retinal lesions possibly responded to zidovudine but not to acyclovir or ganciclovir. Anterior chamber and vitreous humor inflammatory reactions responded to topical or periocular injections of corticosteroid., Conclusions: Uveitis with chronic multifocal retinal infiltrates is a distinct clinical entity of unknown cause that occurs in HIV-infected patients. Retinal lesions may respond to antiretroviral therapy. Visual prognosis is good.

Opportunistic ocular infections are a common and important complication of the acquired immunodeficiency syndrome. Cytomegalovirus retinitis is by far the most frequent infection, but other viral, bacterial, and parasitic infections of the posterior segment of the eye may be seen. Infections of the anterior segment are less common but may cause visual loss if not treated. Prompt recognition of these diseases is essential because ocular involvement may be an early sign of systemic dissemination.

The severity of conjunctival microvascular changes and the presence of cotton-wool spots were compared to factors that may affect blood flow (hematocrit level, red cell aggregation, fibrinogen level, plasma viscosity, circulating immune complexes, and quantitative immunoglobulin levels) in 22 human immunodeficiency virus-infected individuals. The severity of conjunctival disease was associated with increased zeta sedimentation ratios (a measure of red cell aggregation) and fibrinogen levels. The presence of cotton-wool spots was also associated with higher fibrinogen levels. Plasma viscosity and quantitative IgG levels were above normal levels in most patients, although a relationship to disease severity was not established. Altered blood flow may contribute to vascular damage and ocular ischemic lesions in patients with human immunodeficiency virus infection.