|Year : 1999 | Volume
| Issue : 2 | Page : 87-93
Ophthalmic manifestations of human immunodeficiency virus (HIV) infection in India
Jyotirmay Biswas1, Amala Joseph1, Seemant Raizada1, N Kumamsamy2, Suniti Solomon2
1 Medical and Vision Research Foundation, Chennai, India
2 YRG Care Centre, Chennai, India
Medical and Vision Research Foundation, 18, College Road, Chennai - 600 006
Source of Support: None, Conflict of Interest: None
Purpose: To describe ophthalmic and systemic findings in 70 patients with Human Immunodeficiency Virus (HIV) infection examined at a referral eye centre in India.Methods: A complete ophthalmological examination was performed on each patient. Relevant investigations were carried out on selected patients.Results: Thirty two (45.7%) had ocular lesions, the most common being cytomegalovirus (CMV) retinitis (21.4%). Other lesions included cotton-wool spots (12.8%), chorioretinitis (5.7%), endogenous endophthalmitis (8.5%), anterior uveitis (4.2%), and molluscum contagiosum (1.4%). The most common systemic infection was pulmonary tuberculosis (50%). The others were oral candidiasis (41.4%), Pneumocystitis carinii pneumonia (11.4%), HIV enteropathy (12.8%) and toxoplasmosis (4.2%). Systemic and intravitreal ganciclovir treatment were given in selected cases and the outcome was documented.
Conclusion: Our study indicates that ocular lesions in HIV patients in India are less common than in USA and Africa. Unlike HIV patients in USA, the most common ocular lesion among HIV patients in India is CMV retinitis and not the cottonwool spots.
Keywords: Acquired immunodeficiency syndrome, human immunodeficiency virus, cytomegalovirus retinitis, cottonwool spots, molluscum contagiosum, ganciclovir
|How to cite this article:|
Biswas J, Joseph A, Raizada S, Kumamsamy N, Solomon S. Ophthalmic manifestations of human immunodeficiency virus (HIV) infection in India. Indian J Ophthalmol 1999;47:87-93
|How to cite this URL:|
Biswas J, Joseph A, Raizada S, Kumamsamy N, Solomon S. Ophthalmic manifestations of human immunodeficiency virus (HIV) infection in India. Indian J Ophthalmol [serial online] 1999 [cited 2019 May 22];47:87-93. Available from: http://www.ijo.in/text.asp?1999/47/2/87/22798
Acquired immunodeficiency syndrome (AIDS) is a potentially lethal multisystem disorder caused by a retrovirus, the Human Immunodeficiency Virus (HIV). The virus infects the T-lymphocytes, resulting in profound immunodeficiency leading to opportunistic infections and neoplasms such as Kaposi's sarcoma. Since the original description of ocular involvement in patients with AIDS by Holland and coworkers in 1982, a number of clinic-based surveys have been reported from different parts of the world. Ocular lesions occur in as many as 70% of patients infected with HIV, can involve almost all parts of the eyeball, and can be the initial manifestation., First described in 1981 in Los Angeles, USA, HIV was detected in India in 1986 The first two cases of ocular lesions in AIDS patients in India were reported by Biswas et al in 1995. The present study was conducted to evaluate ocular lesions in HIV-infected individuals in India, to compare the findings with those in other parts of the world and gather baseline data for further clinical and basic research on ophthalmic lesions in HIV infection in India. To the best of our knowledge (Medline search) this is the largest series of ocular lesions in patients with HIV infection in India.
| Materials and Methods|| |
All HIV-infected patients who presented or were referred to our hospital between December 1993 and October 1997 were included in the study. The ophthalmic examination included: (i) visual acuity, (ii) external eye examination, (iii) ocular motility, (iv) pupillary reflexes, (v) anterior segment examination by slitlamp biomicroscopy, and (vi) dilated fundus examination by indirect ophthalmoscopy.
HIV seropositivity was established by enzyme-linked immunosorbent assay (ELISA; MERIND Diagnostics, Belgium) for HIV-1 and HIV-2 and confirmed by Western Blot methods (Biotechnology Kit, Singapore) in all cases. A positive Western Blot was defined as the presence of at least one band corresponding to gag, env, and pol gene translates of HIV-1. The systemic evaluation of these patients was done in an AIDS care and research centre in the city (NK, SS). External, slitlamp and fundus photographs of all cases with abnormal findings were documented. Relevant laboratory and radiological investigations were carried out on all the patients and the information was recorded in a precoded proforma. CD4 and CD8 lymphocyte subsets were analyzed in four cases of cytomegalovirus (CMV) retinitis. Since these tests were expensive, routine testing was not done in all cases. Viral load was performed in one case of frosted branch angiitis with CMV retinitis.
Ten patients received induction therapy of ganciclovir in our series, 6 were followed up for periods ranging from one month to one year. Five patients were treated with induction dose of intravenous ganciclovir at 5 mg/ kg of body weight every 12 hours for 2 weeks. Due to resource constraints, maintenance dose of ganciclovir (5 mg/kg of body weight, 7 days a week) could not be continued for more than one week for any of the patients. Two of them were given intravitreal injection of ganciclovir (400 µg) in addition to intravenous therapy.
| Results|| |
Seventy HIV- positive patients were examined for ocular lesions. All of them were found to have HIV-1 antibody (by ELISA) except one who tested positive for both HIV-1 and HIV-2 antibody. In all cases Western Blot tests confirmed HIV positivity. But for one who hailed from the Sultanate of Oman, all the patients (52 males, 15 females) were Indians. Their ages ranged from 9 months to 61 years with the mean age at 26 years. The majority (74.6%) were in the 20-40 years age group [Figure - 1]. The number of patients with ocular lesions at the time of initial examination was 32 (26 men and 4 women) and comprised 45.7% of the total cases. The most common risk factor was heterosexual exposure, recorded in 42 cases (60%). Thirteen patients (18.5%) received blood transfusions and 5 were intravenous drug abusers (7.1%) [Figure - 2]. Five children (7.1%) contracted the disease via perinatal transmission.
The most frequently associated systemic illnesses were pulmonary tuberculosis (50%, 35 cases) [Figure - 3] and oropharyngeal candidiasis (41.4%, 29 cases) [Figure - 4]. The other commonly associated illnesses were Pneumocystis carini pneumonia (11.4%, 8 cases), HIV-enteropathy (12.8%, 9 cases), toxoplasmosis (4.2%, 3 cases), and anogenital lesions (8.5%, 6 cases). Central nervous system (CNS) involvement in the form of HIV dementia (one case), multiple cerebral abscesses (one case) and CNS glioma (one case) was also observed. Generalized molluscum contagiosum, eosinophilic folliculitis, tineasis, herpetic lesions, and extrapulmonary tuberculosis were also noticed. Most of the patients with ocular involvement had multiple HIV-associated systemic lesions, (34.0%). Seven patients with ocular involvement had no evidence of systemic lesions at the time of presentation [Table - 1].
CMV retinitis (21.4%, 15 cases) [Figure - 5] and cotton-wool spots (12.8%, 9 cases) [Figure - 6] were the most frequently encountered ocular lesions. Others were focal chorioretinitis (5.7%, 4 cases), endophthalmitis (8.5%, 6 cases), isolated anterior uveitis (4.2%, 3 cases), optic atrophy (2.8%, 2 cases), lid ulceration (2.8%, 2 cases) molluscum contagiosum (1.4%, 1 case), and Herpes zoster ophthalmicus (1.4%, 1 case). Seven patients subsequently developed retinal detachment due to CMV retinitis [Figure - 7] [Table - 2]. One patient with CMV retinitis had frosted branch angiitis. He was found to have low CD4+ cell count (69/cu.ml), CD8 cell count (564/cu ml) CD4+/CD5 ratio (0.12) with a viral load (HIV RNA level) of 223,000 copies per cubic microlitre. One patient who subsequently died of central nervous system glioma had restriction of superior gaze. Lymphocyte subsets were analysed in 4 cases of CMV retinitis. In two cases the CD4+ cell count was 50-100 cells/cu ml and in the other two it was less than 50 cells/ cu ml. External lesions were less compared to posterior segment lesions. There was a patient with an ulcerated lid lesion and another with extensive blepharitis (earlier reported). In both cases, the organism identified was Staphylococcus aureus. Another patient had extensive molluscum contagiosum lesions over both eyelids as well as multiple molluscum lesions over his face and right leg. All the three patients subsequently developed multiple opportunistic systemic infections. Two of these patients died within a year of developing ocular lesions. The majority of the patients who reported for follow-up had ocular lesions. One patient had cotton-wool spots on the first visit. Five months later, he developed frosted branch angiitis with CMV retinitis. Another patient who had lid ulcer and normal fundus in both eyes developed cotton wool spots in left eye 22 days later and developed CMV retinitis in the right eye after 29 days. The majority of the patients could not be followed up by us as they were from different parts of the country.
Of two patients who received intravitreal Gancyclovir, one died of CNS tumour. The other patient was followed up for nearly a year. The CMV retinitis gradually progressed in both the eyes till total retinal detachment occurred. The Gancyclovir therapy appeared to have slowed the progress of the disease but did not alter the final outcome. One patient on intravenous Gancyclovir therapy showed eventual regression of CMV retinitis. Six months later, the patient died of AIDS-related systemic lesions. Two other patients are currently being followed up. One patient showed evidence of frosted branch angiitis in addition to CMV retinitis. In this case there was complete regression of retinal perivasculitis on induction of Gancyclovir therapy but later the patient developed rhegmatogenous retinal detachment. He underwent pars plana vitrectomy, fluid gas exchange and silicon oil injection at our centre.
| Discussion|| |
Since it was first reported in 1981, AIDS has spread rapidly across the continents. Worldwide, an estimated 27 million adults and 3 million children are infected with HIV. HIV infection is the leading cause of death among men aged 25-44 years and the third leading cause among women of the same range of age in the United States. An estimated 2-5 million AIDS patients live in India. Of the 3 million people screened in India so far the seropositivity rate has been found to be 18.6 per thousand. According to the National AIDS Control Organisation (NACO, New Delhi), the number of HIV-positive patients in India is 67,067 and the total number of reported AIDS cases is 3,183. According to UNAIDS (United Nations AIDS Control Program) about 50,000 to 1,00,000 cases of AIDS might have already occurred in the country. The gross discrepancy between the official and estimated figures could be due to inadequate statistical records and under-diagnosis. Contributing factors may be lack of awareness among physicians and inadequate diagnostic facilities in the country. As 70% of AIDS patients eventually develop ocular complications, the role of the ophthalmologist in the management of a HIV-positive patient is becoming increasingly important., The epidemic in Asia is in its early phase, and the ocular lesions here are not well described. The first ophthalmic report about patients with ocular diseases attributed to AIDS in India was published in 1995. Ocular lesions in the two cases reported there included CMV retinitis with cottonwool spots in one and endogenous endophthalmitis in the other. Both patients had systemic tuberculosis. One patient had systemic nocardiosis in addition. The statistical analysis in this paper includes the above two cases reported by the author.
In our study, the majority of patients were men, in the 20-40 years age group. This is also reflected in the national statistics. Heterosexual exposure to commercial sex workers was the most common risk factor (60%) for HIV infection. National figures rate this as the risk factor in 45.7% of cases.
Pulmonary tuberculosis (50%) followed by oropharyngeal candidiasis (41.4%) was the most commonly associated systemic infection. In a series of 100 AIDS patients reported by Kumarasamy and coworkers the most common systemic opportunistic infection was tuberculosis (61%). The most common form of tuberculosis was pulmonary (46%). This is due to the high prevalence of systemic tuberculosis in India. In addition, tuberculosis can increase HIV replication either in local tissue sites or at a systemic level, thereby accelerating the progression of HIV disease. Vigorous prophylactic measures against tuberculosis are needed to prevent not only the spread of the bacterial disease but also the increased replication of HIV associated with tuberculosis. Epidemiological studies have shown that as compared to those not infected, HIV-infected individuals have a higher susceptibility to developing active tuberculosis after exposure, 113 times higher in HIV-infected individuals and 170 times higher in AIDS patients. Whalen and co-workers have found that AIDS patients with co-infection with Mycobacterium tuberculosis have a lower survival rate than matched controls. HIV enteropathy, Pneumocystis carinii pneumonia, and toxoplasmosis were the other common associations in our patients.
Ocular manifestations of HIV infection in any geographic area depends on the overall availability of health-care facilities and the prevalence of disease patterns. In a country where the majority of people are of lower socio-economic status, many patients may die in the relatively early phase of infection, even before development of opportunistic infections. They also run the risk of contracting diseases like tuberculosis which are prevalent in the country. Likewise it has been noted that a large number of cases of ocular toxoplasmosis in AIDS patients in Brazil reflects the high seroprevalence of ocular toxoplasmosis in the country.
Adequate health-care facilities combined with awareness among the general physicians of HIV infection can lead to early detection, and prompt and adequate treatment. It has been noted in developing countries that inadequate treatment of tuberculosis, syphilis, toxoplasmosis, cryptococcosis and even ordinary bacterial infection can lead to more ocular complications in HIV- infected patients.
Poor hygiene can also lead to skin infection as was the case in two of our patients who developed extensive Staphylococcal blepharitis and one patient had a lid ulcer. Such lid infections in AIDS patients have been reported only rarely.
The most common ophthalmic opportunistic infection seen in our study was CMV retinitis (21.4%). This is also the most common opportunistic ocular infection in HIV-infected patients in studies conducted in other parts of the world.[2-5] Clinically CMV retinitis presents as full-thickness granular retinal opacification with hard exudates and haemorrhage with minimal vitritis and anterior chamber reaction. The infection usually spreads along one of the major retinal vascular arcades. In our cases, diagnosis of CMV retinitis was based on clinical features alone. The CD4 cell count was less than 100 cells /cu.ml, in two cases. The association of low CD4 cell counts with CMV retinitis has been reported earlier.
The second most common ocular manifestation of HIV infection in our series, was cottonwool spots caused by HIV-related microvasculopathy. These are transient white superficial lesions found around the vascular arcades in the posterior pole. Nine patients (12.8%) in this series had cottonwool spots. Two patients showed no change in the cottonwool spots during the follow-up period. In one patient the spots disappeared and optic atrophy was noted after 3 months. In one patient, there was subsequent development of CMV retinitis.
Four patients in our study had evidence of multifocal choroidal infiltrates. The cause was presumed to be syphilis in one case and toxoplasmosis in the other. No diagnosis could be established in two patients. Four patients had endogenous endophthalmitis with extensive areas of retinal necrosis, haemorrhage, vitritis, and anterior uveitis. In all these cases anterior chamber aspirate was done but the culture of the aspirate failed to reveal a definitive pathogen. Isolated anterior uveitis was seen in 2 patients. Mild nongranulomatous anterior uveitis was associated with some cases of cytomegalovirus retinitis.
Another patient in our series had molluscum contagiosum. He presented with multiple nodular pearly white lesions of the right eyelid, right half of the forehead, cheek and legs, suggestive of molluscum contagiosum. Multiple abscesses were seen associated with the lesions. Severe molloscum contagiosum of the eyelid has been reported in AIDS patients. They are usually multiple, bilateral, confluent and tend to recur within 6-8 weeks after removal. In addition to multiple molluscum lesion, our patient had associated bacterial infection.
Neurophthalmic manifestations occur in 10-15% of HIV-infected patients. These include optic nerve edema either due to papilloedema or optic neuritis, nonspecific optic atrophy, cranial nerve palsies, gaze palsies, intranuclear ophthalmoparesis and skew deviations., Two of our patients developed optic atrophy. Another patient had superior gaze palsy. Subsequently she died of a glioma of the central nervous system.
Studies of ocular involvement in the developing countries of Sub-Saharan Africa and Southern Asia have been of considerable interest due to different sexual behaviour (less homosexuality), prevalence of different systemic infection like tuberculosis, poor hygiene, availability of health-care facilities including awareness of early signs and symptoms of HIV infection. Our study has shown less ocular involvement in HIV infection (45.7%) compared to similar USA (63%) and African (55%) reports [Table - 3]. In our series the majority of cases were referred due to complaints of visual impairment. As cotton-wool spots alone do not cause visual impairment, they probably remain undetected. Unlike the US, studies, we did not observe Kaposi's sarcoma of the eye. Kaposi's sarcoma was also not reported in a series of 100 patients of AIDS reported by Kumarasamy et al, To the best of our knowledge only two cases of Kaposi's sarcoma, one in a 19-year-old male AIDS patient from Madras and another in a 35-year-old female from Bombay have been reported.
The important issue in the management of HIV-positive cases in developing countries is the cost of therapy. It is therefore important to identify practical strategies to manage such cases. As has been done in other developing countries, this requires the support of the government and non-governmental organisations.
HIV-positive patients may cause transmission of the virus during ocular examination particularly during procedures like applanation tonometry, fluorescein angiography, etc. We would like to reiterate that if proper precautions are taken, AIDS patients like others can be provided the entire range of treatment including surgery. We used routine barrier precautions for ophthalmic examination. Applanation tonometer tip was cleaned with 70% alcohol sponge. Fundus fluorescein angiography and laboratory investigations were done by health-care personnel after taking adequate precautions. Two patients, one with retinal detachment and the other with senile cataract, were operated using updated guidelines of the American Academy of Ophthalmology and Centres for Disease Control (CDC)., Based on the guidelines, ophthalmologists can improve the quality of life of these patients by taking adequate care of ocular lesions.
The progress of CMV retinitis is relentless unless interrupted by certain drugs. The treatment options currently available include intravenous or intravitreal injections of three drugs approved by the FDA (Food and Drug Administration, USA), Gancyclovir, Foscarnet, and Cidofovir. Combination therapy of intravenous ganciclovir and Foscarnet is recommended in cases resistant to either drug used alone. Intravitreal injection of ganciclovir or Foscarnet or intraocular sustained-release ganciclovir implant can also successfully control CMV retinitis without controlling systemic CMV infection.
The prohibitive cost and lack of availability of ganciclovir are the limiting factors for our recourse to this mode of therapy in all cases of CMV retinitis. Currently, induction therapy of Gancyclovir in an adult costs Rs. 22,400 (approximately US$ 575) for one week. In addition, Ziduvudine (AZT) therapy for HIV infection costs Rs. 5000 a month. Combination therapy with three antiretroviral drugs costs Rs. 30,000 a month approximately. We have not been able to start induction therapy of anti-CMV drug in 5 cases needing such treatment. Of the 10 patients who were given induction therapy, none could be kept on maintenance therapy due to lack of financial support. Intravitreal ganciclovir (400 µg) injection has been given to some of these patients. Although such treatment is less expensive, it was beyond the reach of many of our patients.
India is on the verge of an AIDS epidemic; the focus has now shifted from the United States and European countries to Asia. The epidemic will pose a challenge to all practitioners of medicine including ophthalmologists. Ten patients (14%) in our series were in an advanced stage of the disease with ocular manifestations. This delay in diagnosis reflects the general lack of awareness about the disease in the population as well as among physicians. Ophthalmologists need to recognize ocular lesions in HIV infection as it may help in earlier diagnosis and prompt management of the disease. Recent reports indicated newer modalities of treatment, e.g., combination therapy of protease inhibitors and other anti-retroviral drugs, which can delay the disease progression and considerably reduce the mortality and morbidity.
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[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7]
[Table - 1], [Table - 2], [Table - 3]