Ocular Complications of Human Immunodeficiency Virus Infection in Eastern China




Purpose


To investigate ocular complications in patients with HIV/AIDS in eastern China during the time of highly active antiretroviral therapy (HAART).


Design


Prospective study.


Methods


This study was carried out from August 1, 2009 to July 31, 2010. Recruited HIV/AIDS patients underwent a series of surveys and ophthalmologic and laboratory examinations (including CD4 level) at enrollment.


Results


In this study, all 787 HIV/AIDS patients (1574 eyes) had a history of HAART. Of these patients, 28.72% (95% CI = 0.26–0.32) had a history of systemic disease and 26.30% (95% CI = 0.23–0.29) had ocular complications. Of these ocular complications, cytomegalovirus retinitis (CMVR) had the highest prevalence (10.6%, 83/787) and ocular microangiopathy had the second-highest prevalence (9.4%, 74/787). Among the patients with CMVR, 16.9% (14/83) suffered from immune recovery uveitis (IRU). Furthermore, 3.4% (27/787) of the recruited AIDS patients had neuro-ophthalmologic disorders. The mean logMAR visual acuity of the group with ocular complications was 0.47 ± 0.64, which was significantly different from the asymptomatic group (0.17 ± 0.39, P < .001). The median CD4 T-cell count of the group with ocular complications is 43 cells/μL, which was significantly different from the asymptomatic group (116.5 cells/μL, P < .001).


Conclusions


The study shows a high rate of treatable ocular complications among patients with HIV/AIDS in eastern China. HIV/AIDS treatment programs in China must be prepared to identify ocular complications and refer patients to the correct treatment facilities.


Human Immunodeficiency Virus (HIV)/acquired immune deficiency syndrome (AIDS) is considered to be one of the most terrible infectious diseases of the late 20th century. The first HIV infection was introduced to China in 1985. For the next 2 decades, HIV/AIDS made rapid inroads into China; cases became increasingly prevalent among the normally low-risk general population. China has a low prevalence proportion, with the HIV infection rate among China’s population being 0.05% (700 000 cases), but a high prevalence in terms of the absolute number of cases. For example, there were 60 081 new HIV infection cases in 2008. China’s huge population base and the rapidly growing numbers of HIV/AIDS patients can set the stage for serious social problems related to HIV/AIDS.


HIV/AIDS can affect multiple organs and, in the natural development of HIV/AIDS, 52% to 100% of patients will generate ocular complications. Ocular complications in HIV/AIDS patients are mainly attributable to various ocular opportunistic infections, which are directly or indirectly caused by immune deficiency. Cytomegalovirus retinitis (CMVR) is the most common complication caused by ocular opportunistic infection, and patients with HIV/AIDS have a 30% lifetime probability of developing CMVR. With the promotion of highly active antiretroviral therapy (HAART), the HIV/AIDS epidemic has undergone significant changes and there has been a substantial decline in the fatality rate among AIDS patients and in the incidence of opportunistic infections. The incidence rate of CMVR has dropped by about 80%.


China is a developing country with vast territory and a large population. The HIV/AIDS epidemic is spreading from high-risk groups to the general population with a wide range of risk factors associated with the HIV/AIDS epidemic. A high prevalence trend of HIV/AIDS has emerged in some areas such as Yunnan, Sichuan, Xinjiang, and Guangxi provinces; however, there are few reports on HIV/AIDS-related ocular complications in the Chinese population. Currently, there are no epidemiologic data on HIV/AIDS-related ocular complications for certain populations in China. In this study, we investigated the prevalence and types of ocular complications in patients with HIV/AIDS in Eastern China. Our aim is to obtain epidemiologic data on such cases during the time of HAART usage.


Methods


This prospective survey was carried out from August 1, 2009 to July 31, 2010. China initiated a comprehensive program to promote free HAART in 2003. The subjects of our study were HIV/AIDS patients diagnosed at the Shanghai Public Health Clinical Center at Fudan University, the HIV/AIDS diagnosis and treatment institution in eastern China, and offered free regular HAART treatment. Patients were diagnosed with HIV/AIDS according to the 1993 Centers for Disease Control and Prevention case surveillance definition of AIDS. We obtained detailed medical histories for all of the patients, including HIV/AIDS-related diseases and antiviral treatment history. We then performed a range of ophthalmologic examinations including best-corrected visual acuity (VA), ocular adnexal examination, anterior segment slit-lamp microscopy, examination of the posterior segment with an indirect ophthalmoscope, and slit-lamp examination with pupillary dilation and fundus photography. Some of the suspected cases were examined with fundus fluorescence angiography (FFA) and optical coherence tomography.


In this study, we were looking for all of the ocular complications of these HIV/AIDS patients. CMVR is clinically diagnosed by the characteristic appearance of a necrotizing retinitis with either edematous white borders or a granular white border with or without hemorrhage. HIV vasculopathy included HIV microangiopathy and large vessel disease. HIV microangiopathy is diagnosed when the patient presents with cotton-wool spots, microaneurysms, retinal hemorrhages, telangiectatic vessels, and ischemic maculopathy. HIV large-vessel disease included branch retinal artery occlusion and central and branch retinal vein occlusions. In patients whose CD4+ T-lymphocyte counts have increased after receiving HAART, immune recovery uveitis (IRU) was clinically diagnosed by a decrease in vision caused by moderate or severe vitritis, macular edema, epiretinal membranes, keratic precipitate, neovascularization of the optic disc or retina, posterior synechia, and cataract. The absence of other inflammatory conditions such as syphilis, herpetic retinitis, drug toxicity, trauma, and so on confirmed the diagnosis.


The diagnosis of acute retinal necrosis (ARN) followed the standard diagnostic criteria developed by the Executive Committee of the American Uveitis Society, including the triad of vitreous inflammation, peripheral retinitis, and retinal arteritis. Complicated cataract referred to the characteristic opacity of anterior and posterior lens capsules. Other ocular complications, such as retinal detachment (RD), optic neuropathy, disc edema, ptosis, keratitis, and Kaposi sarcoma, were diagnosed according to the Studies of Ocular Complications of AIDS by certified ophthalmologists using standardized descriptions and characteristic clinical features. Other complications of AIDS were diagnosed according to the AIDS Clinical Trials Group guidelines for evaluation and diagnosis of these disorders.


The HAART regime that the patients received included lamivudine (300 mg, twice daily), zidovudine (300 mg, twice daily), or stavudine (30 mg, twice daily); and nevirapine (200 mg, every night) or efavirenz (600 mg, every night).


In this study, the HIV/AIDS patients were assigned to 2 groups: 1 with ocular complications and the other without ocular complications. All data were statistically analyzed using SPSS version 17.0 (SPSS, Inc, Chicago, Illinois, USA). The categorical variables of sex, age, race/ethnicity, history of HIV exposure, educational degree, visual acuity, and CD4 levels were analyzed by χ 2 or Fisher exact tests and Student or nonparametric tests to obtain P values. P < .05 is considered significant.




Results


There were 1132 outpatients or inpatients enrolled at the Shanghai Public Health Clinical Center at Fudan University from January 2003 to July 2010 who were still eligible for our study. From that group, 69.5% (787/1132) of the patients agreed to be recruited and enrolled in the study. All of them had a history of HAART and 87.5% of these patients (689/787) were receiving HAART. Of the 787 participants, 226 (28.72%; 95% confidence interval [CI] = 0.26−0.32) had a systemic disease. The prevalence of ocular complications was 26.3% (95% CI = 0.23−0.29; 207/787). Patient sex, age, race/ethnicity, history of HIV exposure, and education level are listed in Table 1 . All 787 patients were Chinese and 83.5% of the participants (657/787) were male. There were no significant differences in the morbidity of the patients with ocular complications between sexes (χ 2 test, P > .05) and ages ( t test, P > .05). The patient group was mostly of Han ethnicity (779/787, 99.0%), with the remaining patients of other race/ethnicity (8/787, 1.0%). There is a significant difference in education level between the group with ocular complications and the group without ocular complications (χ 2 test, P < .05); the group with ocular complications had more individuals with an education level of high school or college (98/207, 47.3%) compared to the group without ocular complications (341/580, 58.8%). Of all the 787 enrolled HIV/AIDS patients, 73.58% (579/787) had sex contact history, which included homosexual (30.40%, 176/579), heterosexual (66.10%, 383/579), and homosexual and heterosexual (3.50%, 20/579). There was no significant difference in the history of HIV exposure between the group with ocular complications and the group without ocular complications (χ 2 test, P > .05).



TABLE 1

Baseline Characteristics of Patients With and Without Ocular Complications of Human Immunodeficiency Virus Infection in Eastern China






































































































































































Ocular Complication Without Ocular Complication Total P Value
Sex .966
Male 173 484 657
Female 34 96 130
Age (years ± SD) 43.09 ± 12.03 40.60 ± 12.08 41.26 ± 12.27 .413
Race .44
Han people 204 575 779
Minorities 3 5 8
Education level .029
Primary school 19 56 75
Junior high school 90 183 273
Senior high school 59 200 259
College graduate 39 141 180
HIV exposure category .14
Sex contact 138 441 579
Homosexual 33 143 176
Heterosexual 103 280 383
Homosexual & heterosexual 2 18 20
Injection drug 11 28 39
Hemophilia/blood product 19 37 56
Other/no risk reported 39 74 113
Systematic diseases .00
Cryptococcal pneumonitis 32 64 96
Oral fungal infection 24 42 66
Pneumocystis jiroveci pneumonia 6 24 30
Pulmonary tuberculosis 6 15 21
Cryptococcal encephalitis 10 11 21
Syphilis 6 14 20
Hematologic diseases 9 5 14
Kaposi sarcoma 3 1 4
Toxoplasmosis 1 1 2

SD = standard deviation.


The VA and ocular complications for all 787 patients (1574 eyes) are listed in Table 2 . The VA of the group with ocular complications was significantly poorer than that of the group without ocular complications ( t test, P < .01). CMVR is the most common ocular complication (10.5%, 83/787), with 44.5% of these patients (37/83) demonstrating binocular involvement and 10.8% of them (9/83) blind (RD, 5 patients; IRU, 4 patients). Among all 83 CMVR patients, only 28 (33.7%) were treated with ganciclovir (5 mg/kg is administered twice a day by intravenous injection for 2 to 3 weeks during the inductive phase and the same dose is given once a day intravenously or 1000 mg 3 times a day orally during the maintenance phase). Fourteen patients (22 eyes) who had received or were receiving HAART had the complication of IRU (16.9%, 14/83). Ocular drops of corticosteroids were used in all of the 14 IRU patients during the active and maintenance phase, and there was no history of sub-Tenon’s or systemic injections of repository corticosteroids and vitrectomy. Also, 5 of the IRU patients had a history of ganciclovir treatment. There were 9 patients (12 eyes) with RD, among which 9 eyes were secondary to atrophic hole with 4 eyes treated by pars plana vitrectomy. Of these 9 eyes, the 5 that were left untreated became blind. Three eyes with exudative RD secondary to CMVR were treated with intravenous ganciclovir and local or systemic steroid injection but vision remained poor. Microangiopathy (9.4%, 74/787) was the second most common complication, with 45.9% (34/74) demonstrating binocular involvement. Twenty-seven of the 787 HIV/AIDS patients (3.4%) suffered from neuro-ophthalmologic disorders, in which optic disc edema had the highest prevalence (63.0%, 17/27), followed by optic neuritis (29.6%, 8/27), abducent paralysis (3.7%, 1/27), and ptosis of herpes zoster ophthalmoplegia (3.7%, 1/27).



TABLE 2

Visual Acuity in Eyes of HIV/AIDS Patients With and Without Ocular Complications in Eastern China



























































































































Persons (n) Eyes VA (logMAR) (n) VA (logMAR) (95% CI) VA (Decimal) (Mean ± SD)
Total 787 1574 0.25 ± 0.49 0.219−0.28 0.82 ± 0.37
No ocular complications 580 1267 0.17 ± 0.39 0.14−0.20 0.88 ± 0.35
Ocular complications 207 a 307 0.47 ± 0.64 0.38−0.56 0.58 ± 0.36
CMV retinitis 83 120 0.51 ± 0.63 0.37−0.64 0.54 ± 0.37
IRU 14 22 1.35 ± 1.56 −0.11−2.52 0.48 ± 0.35
RD 9 12 1.80 ± 0.59 1.35−2.26 0.02 ± 0.36
ARN 3 4 0.74 ± 1.10 −1.98−3.45 0.53 ± 0.50
HIVM 74 108 0.27 ± 0.35 0.19−0.35 0.66 ± 0.32
CRVO 7 7 0.28 ± 0.41 −0.10−0.66 0.70 ± 0.42
TC 1 2 0.09 ± 0.00 0.80 ± 0.00
Optic neuropathy 25 37 0.52 ± 0.64 0.25−0.79 0.54 ± 0.36
Cataract 14 22 0.76 ± 0.98 0.19−1.32 0.50 ± 0.57
Keratitis 11 16 0.64 ± 0.85 0.07−1.21 0.46 ± 0.35
Conjunctivitis 2 4 1.61 ± 1.96 0.30 ± 0.42
Abducent paralysis 1 1 0.00 ± 0.00 1.00 ± 0.00
Ptosis 1 1 0.09 ± 0.00 0.80 ± 0.00

AIDS = acquired immune deficiency syndrome; ARN = acute retinal necrosis; CI = confidence interval; CMV retinitis = cytomegalovirus retinitis; CRVO = central retinal vein occlusion; HIV = human immunodeficiency virus; HIVM = human immunodeficiency virus microangiopathy; IRU = immune recovery uveitis; logMAR = logarithm of minimal angle of resolution; RD = retinal detachment; SD = standard deviation; TC = tubercular choroiditis; VA = visual acuity.

a Some persons had complications in more than 1 category.



Most of the patients with HIV/AIDS had a history of severe immunodeficiency. After the HAART, patient immune functions reformed and the CD4 T-cell counts were improved or maintained at a steady level. The levels of CD4 T cells were monitored every 2 to 3 months in all patients, so the patient’s CD4 T-cell count was known at the time of the ocular examination. For the patients with newly diagnosed or active stage of ocular complications, we selected the CD4 T-cell count at the time of diagnosis during several 1-year visits. Even with treatment of HAART, the median CD4 T-cell count of the group with ocular complications was 43 cells/μL, which is significantly lower (nonparametric test, P < .01) than that in the group without ocular complications (116.5 cells/μL). The median CD4 nadir of IRU was 21 cells/μL. Apart from those with IRU, more than half of the patients with main complications, such as CMVR and HIV microangiopathy, had a CD4 T-cell count of <100 cells/μL. CD4 T-cell count data for all 787 patients are listed in Table 3 .



TABLE 3

Number of HIV/AIDS Patients With or Without Ocular Complications in Eastern China, by CD4 T-Cell Level













































































































































CD4 T-Cell Level (Cells/μL) Total Median Mean ± SD 95% CI
<50 50-<100 100-<200 ≥200
Total patients 305 111 145 226 787 89 137.03 ± 134.35 127.63–146.44
No ocular complication 194 86 115 185 580 116.5 149.39 ± 135.28 138.36–160.43
Ocular complication 111 a 25 a 30 a 41 a 207 a 43 102.40 ± 125.69 85.18–119.62
CMVR 51 9 11 12 83 35 83.71 ± 117.47 58.06–109.36
IRU 2 2 5 5 14 170 222.78 ± 213.34 11.45–301.98
RD 4 1 3 1 9 86 223.33 ± 212.71 59.83–386.84
ARN 0 1 2 0 3 101 123.33 ± 40.43 22.91–223.76
HIVM 37 9 12 16 74 49 106.51 ± 117.84 79.21–133.82
CRVO 5 2 0 0 7 25 36.29 ± 34.05 4.79–67.78
Optic neuropathy 14 1 4 6 25 40 118.68 ± 153.24 55.43–118.93
Cataract 3 1 0 3 7 73.5 127.71 ± 179.63 26.00–233.43
Keratitis 4 1 2 4 11 130 135.36 ± 144.64 38.19–232.53

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Jan 12, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Ocular Complications of Human Immunodeficiency Virus Infection in Eastern China

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