|Year : 1999 | Volume
| Issue : 2 | Page : 79-85
Ocular manifestations of HIV infection/AIDS in South Indian patients
Dinesh K Sahu, P Namperumalsamy, Prasad Walimbe, Chitra Rajalakshmi
Retina-Vitreous Services, Aravind Eye Hospital & Postgraduate Institute of Ophthalmology, Madurai, India. Dr. Sahu is currently with Department of Ophthalmology, Manipal Hospital, Bangalore, India,
Dinesh K Sahu
Vitreo-Retinal Surgeon, Manipal Hospital, 98 Rustom Bagh Airport Road, Bangalore - 560 017
Purpose: To evaluate the nature and prevalence of ocular manifestations in a group of patients with Human Immunodeficiency Virus (HIV) infection/Acquired Immunodeficiency Syndrome (AIDS) from South India, and to elaborate the impact of the disease on existing health agencies. Methods: We examined 19 consecutive patients with AIDS (Group-A) who presented to our centre. After counselling, HIV screening tests were also performed on 8 individuals related to the patients and those who were seropositive (Group-B) were examined for ophthalmic lesions. Results:In Group-A, HIV retinopathy was present in 34%, CMV retinitis in 39%, Herpes Simplex-related Acute Retinal Necrosis (ARN) and retinitis in 11%, tubercular choroiditis in 11%, while Herpes Zoster retinitis and presumed P. carinii choroidopathy each were observed in 2.5% of the eyes. Results of screening tests in Group-B revealed HIV-seropositive asymptomatic status in 6 (75%) of them with no ocular manifestations. Conclusion: HIV retinopathy and opportuninstic ocular infections were common in AIDS patients. Heterosexuality was the most common mode of transmission. Since no effective management is readily available, prevention through proper counselling appears to be the only defence against AIDS in India.
Keywords: AIDS, HIV, South Indian patients, ocular manifestation
|How to cite this article:|
Sahu DK, Namperumalsamy P, Walimbe P, Rajalakshmi C. Ocular manifestations of HIV infection/AIDS in South Indian patients. Indian J Ophthalmol 1999;47:79-85
|How to cite this URL:|
Sahu DK, Namperumalsamy P, Walimbe P, Rajalakshmi C. Ocular manifestations of HIV infection/AIDS in South Indian patients. Indian J Ophthalmol [serial online] 1999 [cited 2014 Sep 16];47:79-85. Available from: http://www.ijo.in/text.asp?1999/47/2/79/22797
Since its discovery in 1981, Acquired Immunodeficiency Syndrome (AIDS) has emerged as a global health problem of extraordinary proportions and unprecedented emergency. According to a World Health Organisation (WHO) report, it is estimated that currently around 20 million people including 1.5 million children have been infected with the Human Immunodeficiency Virus (HIV) worldwide. Of the total cases, 58% are thought to be in sub-Saharan Africa and Asia, 15% in America and 4% in Western Europe. In India, more than 1 million people (by 1992) are estimated to be infected with HIV and it is presumed that India will harbour the highest number of cases by the turn of this century.
HIV causes a wide spectrum of diseases, including an acute mononucleosis-like syndrome, an asymptomatic carrier state, persistent generalised lymphadenopathy, AIDS-related complex, and AIDS itself
Ocular involvement in AIDS is very common and includes various clinical presentations. These ocular manifestations can be the presenting signs of a systemic infection in an otherwise asymptomatic HIV-positive patient. The severity of ophthalmic sequelae of HIV infection increases as immunocompetency decreases. While the presumed HIV-related asymptomatic ocular lesions occur in the earlier stage, the relentless, destructive and blinding infections, especially opportunistic ones, occur in the late stage of AIDS.
There is a large body of literature now which describes ocular manifestations of HIV infection/AIDS in developed countries and tremendous strides have been made to understand the disease process and its serious complications. However, this pattern of ocular morbidity associated with HIV infection/AIDS in developed countries may not be representative of the epidemiology of the disease in the developing countries because of the real paucity of reports from these areas. There have been very few reports from India, which further indicates that the epidemiology of ocular manifestations of HIV infection/AIDS in India is not well understood.
In order to analyse the nature and prevalence of ocular involvement in HIV infected/AIDS patients from South India, we evaluated 19 consecutive patients at our center over an 18-month period (Group-A). In addition, 6 individuals related to these patients were found to be HIV seropositive on screening tests. They were also examined for ocular lesions (Group-B). Our findings indicate that the potential impact of the imminent AIDS epidemic on existing health services must be stressed and the importance of counselling emphasized.
| Materials and Methods|| |
The study was undertaken at Aravind Eye Hospital, Madurai, from January 1995 to July 1996. Nineteen cases of suspected HIV infection/AIDS (Group-A) were evaluated for their ophthalmic findings. Suspicion was based on history and characteristic findings. Subsequently, all these patients underwent screening followed by confirmatory tests using commercial kits to establish the diagnosis of the disease, based on the criteria formulated by WHO/CDC., All the patients underwent a complete ophthalmic examination including a detailed history, best corrected visual acuity, slitlamp examination, indirect ophthalmoscopy and fundus contact lens or +90D biomicroscopy. Additionally, standard 45° fundus photographs were taken and fluorescein angiography was performed following universal precautions.
Routine blood tests including total and differential leucocyte counts, haemoglobin levels, erythrocyte sedimentation rate, and erythrocyte and platelet counts were done. Serologic tests (ELISA for IgM Abs) for Herpes Simplex Virus (HSV), Herpes Zoster Virus (HZV), Cytomegalovirus (CMV), and Toxoplasma were carried out using commercially available kits. For all patients, purified protein derivative skin test, VDRL/ TPHA, and chest X-ray were performed.
For the laboratory diagnosis of HIV, serum samples were considered positive only if they were found to be repeatedly reactive by the rapid enzyme immunoassays (Serocard and Tridot screening tests). Diagnosis was then confirmed by Enzyme-linked immunosorbent assay (ELISA). In a few equivocal cases, the Western Blot test was done for further confirmation. CD4+ cell count was not done since the facility was unavailable.
A thorough medical examination was carried out by an internist to rule out any underlying systemic disease. Since most of the patients had underlying systemic diseases related to HIV infection/AIDS, they were referred to an AIDS referral centre (YRG AIDS Care Centre, Chennai; AIDS division, Christian Medical College, Vellore; AIDS division, Institute of Virology, Pune) for further management. Oral acyclovir was given for Herpes infections in 3 patients while 1 patient was treated with trimethoprim for presumed P. carinii infection.
In married patients, their spouses and children were screened for evidence of HIV (Group-B) after obtaining informed consent. A counselling session was then conducted concerning the disease, modes of transmission, consequences of the disease, rehabilitation and referral centres dealing with HIV infection/AIDS cases in India.
A majority of the patients did not come in for follow up. Only 4 patients could be followed for up to 8-12 weeks after which they were referred to an AIDS referral centre for their systemic problems.
| Results|| |
The mean age of the patients was 34 years (range 25-43 years); 17 (90%) were males and 2 (10%) were females. Of 19 patients, 14 (73.6%) were married and gave history of extramarital sexual contact with multiple partners. Most of these patients were from a low socio-economic community. Seventeen patients were seropositive for antibodies against HIV (HIV 1-10 pts, HIV 1 & 2-7 pts). In two equivocal cases which were seropositive in the initial screening tests but seronegative in ELISA, the Western Blot test was performed at the Department of Virology, CMC, Vellore, Tamil Nadu and they were reported to be positive for HIV 1 and 2.
All the patients in Group A had AIDS according to the criteria formulated by CDC/ WHO.,, They gave a history of prolonged low-grade fever, recurrent respiratory tract infections, gastro-intestinal disturbances and unexplained weight loss. Many of these patients (>85%) were referred by local ophthalmologists as cases of tuberculosis-related uveitis and retinochoroiditis, presumed sarcoidosis, syphilitic uveitis, optic neuritis, toxoplasmic uveitis or Eales' disease. Apart from AIDS-related opportunistic infections, systemic mycobacterial infection was found in 4 patients (21%), syphilis in 3 patients (15.5%), and P. carinii pneumonia in one patient (5%).
| Ocular manifestations in Group A|| |
In Group-A, all 19 patients showed posterior segment involvement primarily. None of them had conjunctival malignancies or corneal involvement. The prevalence of the various ocular manifestations in this group of AIDS patients is shown in [Table - 1] and some of these are listed below.
| HIV retinopathy|| |
HIV microangiopathies were found in 13 eyes (34%) in the form of multiple cottonwool spots (CWS) and /or intraretinal haemorrhages without any evidence of retinitis or vasculitis. The number of CWS varied from 2 to 12; they were present posterior to the equator. On fundus fluorescein angiography (FFA), focal discrete areas of capillary non-perfusion (CNP) and/or microaneurysms could be demonstrated in these eyes. Four patients had HIV retinopathy in both the eyes. It was unilateral in 5 patients whose other eye showed CMV retinitis (3 eyes), varicella zoster related retinitis (1 eye), and presumed P. carinii choroiditis (1 eye).
| Opportunistic ocular infections|| |
Cytomegalovirus Retinitis (CMV retinitis) was the most common ocular lesion encountered in our patients and was found in 15 eyes (39.5%). The disease was bilateral in 6 patients (12 eyes) while in the remaining 3 patients (unilateral), the fellow eye showed evidence of HIV retinopathy. Of the 15 eyes with CMV retinitis, 14 (94%) had haemorrhagic retinitis with characteristic pizza-sauce appearance [Figure - 1], perivascular cuffing and obliterative vasculitis, while the remaining one eye (6%) showed optic disc involvement and haemorrhagic retinitis patches in the peripapillary area. Most of these patients were severely ill, with systemic manifestations of AIDS/HIV infection.
Other opportunistic ocular infections were considerably less common. Herpes zoster retinitis occurred in one patient. This patient had extensive retinitis with vasculitis and disc pallor simulating Acute Retinal Necrosis (ARN) in the same eye [Figure - 2] while the fellow eye showed HIV retinopathy. The interval between the appearance of dermatological manifestations and that of retinal lesions was 4 weeks.
Herpes simplex retinitis was found in one patient while another patient had a clinical appearance of the fundus similar to that seen in ARN syndrome. The latter patient was positive for the IgM antibodies against Herpes Simplex virus. All the patients with Herpes zoster or Herpes simplex retinitis responded well to oral acyclovir [Figure - 3]-[Figure - 4].
Presumed P. carinii choroiditis was present in one eye (2.6%) of a patient [Figure - 5] while the fellow eye had HIV retinopathy. This patient had severe recurrent respiratory tract infection with parenchymal infiltration and fibrosis on chest X-ray and a positive sputum examination for P. carinii cysts. He was treated with trimethoprim and subsequently referred to an AIDS referral centre for his systemic problems.
Tubercular choroiditis was seen in 2 patients (4 eyes, 10.5%). Both these patients had pulmonary tuberculosis, on chemotherapy. Ophthalmoscopically, discrete yellow choroidal lesions were seen mainly in the posterior pole [Figure - 6]. A minimal degree of vitritis was observed in these eyes. They were also referred to an AIDS referral centre for further management.
| Findings in Group B|| |
Despite proper counselling, many of our patients were reluctant to agree to HIV screening of their spouses/ children/sex partners because of the social stigma attached. Consent could be obtained from only 8 married patients and 6 individuals (spouses only) were found positive for HIV. None of these individuals had any evidence of systemic or ocular manifestations of HIV/ AIDS. They were informed about their HIV status, given proper counselling and advised a further check up at the AIDS referral centre.
| Discussion|| |
HIV infection has become one of the world's greatest public health problems in recent years. Ocular manifestations are among the most common clinical features in HIV infection/AIDS patients., These include: i) a non-infectious retinal microangiopathy (HIV retinopathy) consisting of CWS with or without intraretinal haemorrhages and other microvascular changes such as microaneurysms and telangiectasiae; ii) opportunistic ocular infections, primarily CMV retinitis; iii) conjunctival, lid and orbital involvement by neoplasms like Kaposi's sarcoma and lymphoma; and iv) neuro-ophthalmic signs. These ocular manifestations occur throughout the illness with increasing HIV virulence and progressive loss of CD4+ T-cell numbers. The frequency of these ocular lesions is higher in AIDS patients than HIV-seropositive asymptomatic cases. Similarly, in our series, none of the cases in Group-B had any evidence of ocular involvement whereas all the patients in Group-A had ocular lesions.
A comparison of the nature and prevalence of ophthalmic lesions in AIDS patients of our series (Group-A) with those reported elsewhere is shown in [Table - 2].
HIV microangiopathy is the most common ocular manifestation of HIV/ AIDS patients described in Western literature., The frequency of the CWS varied from 28-92% but approximately half of all AIDS patients have been described as having CWS. These CWS may occur in isolation or may be associated with other microvascular abnormalities. The prevalence of HIV retinopathy was 34.2% in Group-A of our series, a figure slightly lower than that reported in Western literature. Likely reasons for the variability in the prevalence of HIV retinopathy are the asymptomatic nature of the disease, different patient population studied, sample size, the referral pattern, and lack of awareness of these ocular findings amongst the ophthalmologists. We observed that the number of CWS was greater and was associated with intraretinal haemorrhages in unilateral cases than those in bilateral cases. This reflects that the prevalence and severity of HIV retinopathy is related to the increasing immunnological dysfunction seen in AIDS patients, a finding similar to those described by other investigators.
In contrast to the asymptomatic nature of HIV retinopathy, opportunistic ocular infections (especially CMV retinitis) are the major causes of blindness in patients with AIDS. Prior to the AIDS epidemic, CMV retinitis was a rare disease but with the rapid spread of this disease it has become the most common intraocular infection in patients with HIV infection/ AIDS in the western world, where a 10-40% occurrence rate has been reported. However, a few of the cases with AIDS/ HIV infection reported from Africa had CMV retinitis. In previously reported cases of AIDS in India, only two cases were found to have CMV retinitis.,  In this series, its prevalence was found to be 39.5%. CMV retinitis is a relatively late-stage infection in patients with AIDS and is associated with CD4+T cell count of fewer than 100 cells per millimeter. Although some authors have advocated screening these patients for low CD4+T cell counts, the cost-effectiveness of such an approach has never been documented. Its merit has been debated and it appears to have more prognostic rather than diagnostic value., Because CMV retinitis causes irreversible retinal destruction, early detection to prevent retinal damage is very important. Due to nonavailability of treatment at our institute, we referred our patients to the AIDS Care Centre.
Other opportunistic ocular infections are considerably less common. Presumed P. carinii choroidopathy and Herpes zoster retinitis were found in one case each whereas Herpes simplex infection and tubercular choroiditis occurred in two cases each, including a patient with ARN in association with Herpes simplex virus. Except tubercular choroiditis, other infections are frequently described in Western literature.[7-13, 18, 19, 31-35] A high prevalence of tubercular choroiditis in our series may be related to the higher prevalence of tuberculosis in the general population.
The frequency of ocular manifestations in asymptomatic HIV patients is reported to be 0-2%., In our series, none of the cases in Group-B showed any evidence of ocular involvement. These patients did not come for the follow-up and hence any further ocular involvement could not be recorded.
There are many contagious bacterial and viral diseases in India which when coupled with HIV can lead to atypical disease presentations and may thus present a confusing and complex picture. One of the major problems in these situations is the lack of specific investigations that can provide rapid and reliable confirmation of a clinical diagnosis. The diagnosis of the most common forms of posterior uveitis in patients with HIV infection still rests on the clinical acumen of the ophthalmologist. Hence awareness of the ocular manifestations of AIDS is important for the early recognition and management or early referral to AIDS care centres.
A careful observation of our patients with HIV infection/ AIDS and the comparison between these patients and their Caucasian counterparts showed differences in some important aspects such as sexual habits, microbiologic environment and lifestyles. Reports from Africa[21-23] on AIDS/ HIV infection also disclosed some of these differences.
To combat the evolving HIV/ AIDS epidemic in India, NACO, the National AIDS Control Organisation, was set up by Government of India in 1992. Underutilization of funds at various state and district levels, compounded with cultural taboos surrounding sexual behaviour in India have made AIDS a disease to reckon with. Only with a planned strategy, involving trained medical and paramedical staff, and NGOs which addresses the socioeconomic dimensions of the disease, can there be an early and adequate management and psycho-social care of AIDS/ HIV patients in Indian settings.
| References|| |
|1.||Centers for Disease Control (CDC). Pneumocystis Pneumonia-Los Angeles. Morb. Mortal. Wkly. Rep 1981;30:250. |
|2.||Gottlieb MS, Schroff R, Schanker HM, Weisman JD, Fan PT, Wolf AR, et al. Penumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: Evidence of a new acquired cellular immunodeficiency. N Eng J Med 1981;305:1425-31. |
|3.||Masur H, Michelis MA, Greene HB, Onorato I, Vande Stouwe RH, Holzman RS, et al. An outbreak of community-aquired Pneumocystis carinii pneumonia: Initial manifestation of cellular immune dysfunction. N Engl J Med 1981;305:1431-1438. |
|4.||World Health Organisation. WHO global programme on AIDS: The current global situation of the HIV infection/ AIDS pandemic.Geneva: WHO/GPA/NP/EVA/94.1.1993;l-10. |
|5.||Asthana S. AIDS related policies, legislation and programme implementation in India. Health Policy and Planning 1996;11:184-197. [PUBMED] |
|6.||Centers for Disease Control Revision of the CDC surveillance case definition for the acquired immunodeficiency syndrome. Morb. Mortal. Wkly. Rep 1987;36(suppl.l):lS-15S. |
|7.||Fauci AS, Macher AM, Longo DL, Lane HC, Rook AH, Masur H, et al. Acquired immunodeficiency syndrome: Epidemiologic, clinical, immunologic and theraupetic considerations. Ann Intern Med 1984;100:92-106. [PUBMED] |
|8.||Schuman JS, Orellana J, Friedman AH, Teich S A. Acquired immunodeficiency syndrome. Surv Ophthalmol 1987;31:384-10. |
|9.||Holland GN, Pepose JS, Pettit TH, Gottlieb MS, Yee RD, Foos RY. Acquired immune deficiency syndrome: Ocular manifestations. Ophthalmology 1993;90:859-73. |
|10.||Freeman WR, Lerner CW, Mines JA, Lash RS, Nadel AJ, Starr MB, et al. A prospective study of the ophthalmologic findings in the acquired immune deficiency syndrome. Am J Ophthalmol 1984;97:133-42. [PUBMED] |
|11.||Jabs DA, Green WR, Fox R, Polk BF, Bartlett JG. Ocular manifestations of acquired immune deficiency syndrome. Ophthalmology 1989;96:1092-99. [PUBMED] |
|12.||Pepose JS, Holland GN, Nestor Ms, Cochran AJ, Foos RY. Acquired immune deficiency syndrome: Pathogenic mechanisms of ocular disease. Ophthalmology 1985;92:472-84. [PUBMED] |
|13.||Khadem M, Kalish SB, Goldsmith JA, Fetkenhour C, O'Grady RB, Phair JP, et al. Ophthalmologic findings in acquired immune deficiency syndrome (AIDS). Arch Ophthalmol 1984;102:201-6. |
|14.||Lehl SS, Bambrey P, Avasthi A, Dogra MR, Deodhar SD. CMV retinitis and dementia in an Indian with AIDS. J Assoc Phy India 1995;43:136-37. |
|15.||Biswas J, Madhavan HN, Badrinath SS. Ouclar lesions in AIDS: A report of first two cases in India. Indian J Ophthalmol 1995;43:69-72. |
|16.||Jalali S, Rao VRK, Laxmi V. Acute retinal necrosis in HIV positive case: The first case reported from India. Ind J Ophthalmol 1996;44:95-97. |
|17.||WHO: Provisional clinical case definition for AIDS. Week Epidemiol Rec. 1986;61:72-73. |
|18.||Margolis TP, Lowder CY, Holland GN, Spaide RF, Logan AG, Weisman SS, et al. Varicella-zoster virus retinitis in patients with AIDS. Am J Ophthalmol 1991;112:119-31. |
|19.||Bloom P, Graham E, Migdal C. Ophthalmic manifestations of HIV disease and the acquired immune deficiency syndrome. In Jay B, Kirkness CM, editors. Recent Advances in Ophthalmology. Vol IX. New York:Livingstone, 1995:pp25-58. |
|20.||Newsome DA, Green WR, Miller ED, Kiessling LN, Morgan B, Jabs DA, et al. Microvascular aspects of acquired immune deficiency syndrome retinopathy. Am J Ophthalmol 1984;98:590-601. |
|21.||Kestelyn P, Van de Perre P, Rouvroy D, Lepage P, Bogaerts J, Nzaramba D, et al. A prospective study of the ophthalmologic findings in the acquired immune deficiency syndrome in Africa. Am J Ophthalmol 1985;100:230-38. |
|22.||Lawallen S, Kumwenda J, Maher D, Harries A. Retinal findings in Malawian patients with AIDS. Br J Ophthalmol 1994;78:757-59. |
|23.||Kestelyn P, Tadman H, Bogaerts J, Kagame A, Aziz MA, Batungwanayaj, et al. Ophthalmic manifestations of infections with cryptococcus neoformans in patients with the acquired immunodeficiency syndrome. Am J Ophthalmol 1993;116:721-27. |
|24.||Kupperman BD, Petty JG, Richman DD, Mathews WC, Fullerton SC, Rickman LS, et al. Correlation between CD4+counts and prevalence of cytomegalovirus retinitis and human immunodeficiency virus related noninfectious retinal vasculopathy in patients with acquired immunodeficiency syndrome. Am J Ophthalmol 1993;115:575-82. |
|25.||Baldassano V, Dunn JP, Feinberg, Jabs D A. CMV retinitis and low CD4+ T-lymphocyte counts. N Engl J Med 1995;333:670. |
|26.||Peutherer JF. Retroviruses. In:Greenwood D, Slack BB, Peutherer JF, editors. Medical Microbiology. A Guide to Microbial Infections:Pathogenesis, Immunity, Laboratory Diagnosis and Control. 14th edition. New York, USA:Livingstone, 1992. p 627-38. |
|27.||Mukadi Y, Perriens JH, St.Louis ME, Brown C, Prignot J, Williame JC, et al. Spectrum of immunodeficiency in HIV-1 infected patients with pulmonary tuberculosis in Zaire. Lancet 1993;342:143-46. |
|28.||Spector SA, Weinngeist T, Pollard RB, Freeman WR, Kellerman L, De Armond B, et al. A randomized, controlled study of intravenous gancyclovir therapy for CMV peripheral retinitis in patients with AIDS. J Infect Dis 1993;168:557-63. |
|29.||Martin DF, Parks DJ, Mellaw SD, Ferris FL, Walton RC, Remaley NA, et al. Treatment of CMV retinitis with an intraocular sustained-release gancyclovir implant:A randomized controlled clinical trial. Arch Ophthalmol 1994;112:1531-39. |
|30.||The studies of ocular complications of AIDS research group in collaboration with the AIDS (SOCA) clinical trials group. Foscarnet-gancyclovir CME retinitis trial, 4:visual outcomes. Ophthalmology 1994;101:1250-61. |
|31.||Rao NA, Zimmermann PL, Boyer D, Biswas J, Causey D, Beniz J, et al. A clinical, histologic and electron microscopic study of Pneumocystis carinii choroiditis. Am J Ophthalmol 1989;107:218-28. |
|32.||Shami MJ, Freeman WR, Friedberg D, Siderides E, Listhaus A, Ai E. A multicenter study of Pneumocystis choroidopathy. Am J Ophthalmol 1991;112:15-22. |
|33.||Cunningham ET, Short GA, Irvine AR, Duker JS, Margolis TP. AIDS-associated herpes simplex virus retinitis:Clinical description and use of polymerase chain reaction based assay as a diagnostic tool. Arch Ophthalmol 1996;114:834-40. |
|34.||Chess J, Maran DM. Zoster-related bilateral acute retinal necrosis syndrome. Ann Ophthalmol 1988;20:431-35. |
|35.||Friberg TR, Jost BE Acute retinal necrosis in immuno-compromised patients. Am J Ophthalmol 1984;98:1555-56. |
|36.||Mishra MP, Mukherjee S. Infection. In:Saini G, editor. API Textbook of Medicine. V ed. Bombay, India: API;1992. p 16-82. |
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6]
[Table - 1], [Table - 2]