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   Table of Contents      
CME ARTICLES
Year : 1994  |  Volume : 42  |  Issue : 2  |  Page : 51-63

Acquired immunodeficiency syndrome and its ocular complications


Doheny Eye Institute and the Departments of Ophthalmology and Pathology, University of Southern California, USA

Correspondence Address:
Narsing A Rao
Doheny Eye Institute, Los Angeles, California 90033
USA
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Source of Support: None, Conflict of Interest: None


PMID: 7927632

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  Abstract 

Human immunodeficiency virus infection is the first major pandemic of the 20th century. At present, almost 10 million people are known to be infected with this virus, and it is estimated that by the year 2000, approximately 40 million people will be infected. Transmission of this deadly infection is predominantly by sexual contact. Individuals infected with this virus pass through several predictable stages with progressive decrease in circulating CD4+ T cells. During the advanced stage, these patients develop various opportunistic infections or malignancies, or both. It is this advanced stage that was first recognized as AIDS, which has a 100% mortality rate. The opportunistic organisms that can involve the eye in patients with AIDS include cytomegalovirus, herpes zoster, Toxoplasma gondii, Mycobacterium tuberculosis, Cryptococcus neoformans, Mycobacterium avium-intracellulare, Pneumocystis carinii, Histoplasma capsulatum, Candida, and others. Intraocular lesions from these agents often represent disseminated infections. Visual morbidity occurs secondary to retinitis due to cytomegalovirus, herpes zoster, or Toxoplasma gondii. Anti-viral agents such as ganciclovir or foscarnet are effective against cytomegalovirus infection. The role of the ophthalmologist in the diagnosis and management of AIDS is becoming increasingly important. Not only does the eye reflect systemic disease, but ocular involvement may often precede systemic manifestations. In the AIDS patient, the ophthalmologist thus has an opportunity to make not only a slight-saving, but also life-saving diagnosis of disseminated opportunistic infections.

Keywords: Human immunodeficiency virus Acquired immunodeficiency syndrome Ocular complications - Cytomegalovirus - Pneumocystis carinii - Tuberculosis


How to cite this article:
Rao NA. Acquired immunodeficiency syndrome and its ocular complications. Indian J Ophthalmol 1994;42:51-63

How to cite this URL:
Rao NA. Acquired immunodeficiency syndrome and its ocular complications. Indian J Ophthalmol [serial online] 1994 [cited 2019 Oct 16];42:51-63. Available from: http://www.ijo.in/text.asp?1994/42/2/51/25582



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Acquired immunodeficiency syndrome (AIDS) is an infectious disease caused by a retrovirus, the human immunodeficiency virus (HIV). This syndrome is characterized by a gradual decrease in circulating CD4+ T-lymphocytes and subsequent development of various opportunistic infections and neoplasia, such as Kaposi's sarcoma. AIDS is looked upon as a modem plague, and is the first major pandemic of the 20th century. AIDS was first described in 1981 in Los Angeles, and is believed to be a new infection of humans that began in Central Africa, perhaps in the 1950s. From there it probably spread to the Caribbean and then to the United States, Europe and other parts of the world. Although the aetiology of this deadly disease was discovered within three years after the initial clinical reports, it is remarkable that medical treatment has not yet been able to reduce the 100% mortality rate.

Although recognized initially in the United States, the AIDS epidemic entered its second decade with new cases being reported around the world. Moreover, spread of this infection continues to increase at an alarming rate, particularly in developing countries. At present, almost 10 million people are known to be infected with HIV, and it is estimated that by the year 2000, approximately 40 million people will be infected. [1] Most of this increase will be in developing countries, particularly in those countries with high rates of sexually transmitted diseases, which are known to be important cofactors in the transmission of HIV. Because of the 100% mortality rate, the worldwide distribution, and the enormous social stigma attached to its diagnosis, AIDS, unlike any other past epidemic, requires mobilization of national resources, the support of community leaders and education of the populace to modify sexual behaviour, training of health-care personnel and help from industry in developing vaccines and new anti­viral agents.

During the first decade of the AIDS epidemic it became clear that mass education could reduce the transmission of HIV. This education had a positive influence on changing high-risk sexual behaviour in the United States and other parts of the western world. HIV-infected individuals now live significantly longer, and the quality of their life has also improved, due to the introduction of various anti-viral agents and drugs that reduce morbidity and mortality from the myriad opportunistic infections that occur so often in the late stages of HIV infection. However, a cure for this deadly disease is nowhere near, and an effective vaccine for its prevention is still in the early developmental stage. But although AIDS is not yet curable, it is now recognized to be a manageable, albeit chronic and severe, medical condition. Moreover, if HIV infection is detected prior to the development of symptoms, prophylactic administration of the newer anti-HIV agents can have a significant beneficial effect on the overall course of the disease. [1]


  I. HUMAN IMMUNODEFICIENCY VIRUS Top


HIV is a retrovirus that is a member of the Lentivirinae subfamily. Two lentiviruses are currently known to infect humans: HIV-1 is more prevalent and is seen worldwide; HIV-2 is identified primarily in Western Africa. [2] HIV-2 virus shares roughly 40% homology in nucleotide sequences with HIV-1, and about 75% homology with simian immunodeficiency virus. HIV-1 and HIV-2 are each approximately 100 nm in diameter and have a single-stranded RNA genome. The virion has a cylindrical nucleocapsid [Figure - 1] that contains the single-stranded RNA and viral enzymes, including proteinase, integrase, and reverse transcriptase 3 Surrounding the capsid is a lipid envelope that is derived from the infected host cell and that contains virus-encoded glycoproteins. The viral genome contains three structural genes: gag, pol, and env. HIV-1 and HIV-2 are genetically similar in the gag and pol regions; the env regions, however, are different. This variation results in differences in the envelope glycoproteins of these viruses. Such heterogeneity leads to specific immune responses to these viruses, which necessitates different immune assays or Western blot procedures for serologic diagnosis of HIV-1 and HIV-2. In addition to the three structural genes, HIV contains six additional regulatory genes, tat, rev, nef, vif, vpr, and vpu, two of which (tat and rev) are essential for virus replication.

HIV isolates show marked heterogeneity in the env and the nef genes, which results in differing tissue and cell tropisms, variations in pathogenesis, disparate responses to therapy, and potential challenges to develop a broadly cross-reactive protective vaccine. This viral heterogeneity exists on multiple levels: continent to continent, infected individual to individual, and even within the same infected host. Some of this heterogeneity is from spontaneous mutation of the virus, is related to the frequent error rate of the reverse transcriptase enzyme, and/or is related possibly to anti-viral therapy. [1],[3]

a. Pathogenesis

Initial events in HIV infection include attachment of the virus to a distinct group of T-cells and monocytes/macrophages that display a membrane antigen complex known as CD4. However, other molecules on these cells may also play a minor role in the attachment of HIV to these cells. After attachment, the lipid membrane of the virus fuses with the target cell, thereby allowing entry of the viral core into the host cell cytoplasm. [4],[5] This viral core is subsequently uncoated and transcribed by reverse transcriptase enzyme, which results in a complementary strand of DNA. This DNA then becomes double-stranded by the action of cellular enzymes, and subsequently becomes circular and enters into the cell nucleus. Once inside the nucleus, the proviral DNA integrates into the host cellular genome by means of a viral endonuclease. This host cell can be either latently or actively infected. If latently infected, no viral RNA is produced, and a productive infection may not develop. If actively infected, however, the cell may produce mature virions by transcription of proviral DNA. This transcription also generates messenger RNA, which, in the cytoplasm is translated into HIV-specific structural proteins that are integrated with the viral core particles. These assembled virus particles then migrate to the plasma membrane of the infected cell. Final maturation of the virus occurs by a process of reverse endocytosis (budding) at the plasma membrane. Subsequent dissemination of the virus occurs either via free infectious particles that are released by the budding process or, more likely, by cell-to-cell transfer.

The initial target cells of HIV, namely CD4+ T­helper cells and macrophages, show different cytopathic effects. The T-cells gradually decrease in number from the virus replication. Because helper T-­cells play a pivotal role in immunologic response, their decrease in number leads to immune deficiency and subsequent secondary opportunistic infections. In contrast, the infected macrophages rarely undergo lysis or decrease in number. These cells harbour the virus, and it is believed that such circulating infected cells may disseminate the HIV virus throughout the body. Although the infected monocytes/macrophages may not undergo lysis, HIV does alter the immune-related functions of these cells. These alterations include decreased migration response to chemoattractants, defective intracellular killing of various microorganisms such as Toxoplasma gondii and Candida, reduced expression of class II molecules, which impairs the processing and presentation of antigen to T-helper cells, and excessive production of tumour necrosis factor alpha (by the macrophages), which leads to dementia, wasting syndrome and unexplained fever. [1]

b. Natural History

The illness that results from HIV infection varies from one individual to another. However, there are several predictable stages that lead invariably to death. In general, infected individuals initially experience an acute primary infection, followed by a relatively asymptomatic infection that can include generalized lymphadenopathy. This progresses to symptomatic disease associated with progressive decline in T-helper cells, and eventually to advanced HIV disease with the development of opportunistic infections or malignancies, or both. It is this advanced stage that was first recognized as AIDS.

The acute HIV infection lasts usually for about one to two weeks and is characterized by symptoms typical of a non-specific viral illness. Patients then invariably enter an asymptomatic phase that can last for two to more than ten years. During this phase the CD4+ lymphocyte count varies from about 750 to 200 cells per cubic millimeter (in immunocompetent adults the CD4+ lymphocyte count varies from 600 to 1400 cells per cubic millimeter). The asymptomatic phase is followed ultimately by advanced HIV disease, which may last for upto three years; during this stage the CD4+ cells decrease to less than 200 per cubic millimeter.

c. Transmission

Transmission of HIV is predominantly by sexual contact, by parenteral (intravenous drug use) or mucous membrane exposure to contaminated blood or blood products, and perinatally. Although HIV has been isolated from blood, semen, saliva, cerebrospinal fluid, tears, breast milk, amniotic fluid, vaginal secretions, cervical cells and bronchoalveolar lavage fluid, transmission by sexual intercourse accounts for 70 to 80% of all cases [1] ; intravenous drug use accounts for 5 to 10%; blood transfusion for 3 to 5%, and perinatal transmission for about 5 to 10% of the cases. However, efficiency of transmission by a single exposure through these events varies tremendously, as summarized in [Table - 1]. There are rare cases in which transmission of HIV has been attributed to transplantation of organs such as heart, liver, kidney, bone and pancreas.

d. Diagnosis

Laboratory investigations are essential to establish the diagnosis of HIV infection, which depends on demonstration of virus specific antibodies by enzyme-­linked immunosorbent assay (ELISA) and Western blot, virus antigen by enzyme immunoassay (EIA), direct isolation of HIV from the blood by culture, or detection of HIV nucleic acid by polymerase chain reaction (PCR) technology. ELISA is the most widely used method for screening individuals for antibodies to HIV or for direct detection of HIV antigen; Western blot analysis is used primarily to confirm the results of ELISA. The other investigations, such as PCR, are employed usually in circumstances where the immunoassays do not provide clearly positive results or in seronegative high-risk individuals.

e. Therapy

As the number of HIV infected individuals around the world increases, particularly in developing countries, it is important that physicians of these countries be aware of the means of preventing the complications associated with this deadly disease and of the management of this viral infection. The prevention of complications involves not only anti­retroviral therapy and prophylactic anti-microbials, but also immunization (e.g., hepatitis B, influenza and other vaccines) and early disease detection. With progression of the infection, protective immune function deteriorates and symptoms such as fatigue, night sweats, malaise, fever and weight loss will develop. Although thorough clinical examination provides some clues as to the stage of HIV infection, measurement of T-lymphocyte subsets, particularly absolute CD4 counts, has become a fundamental part of staging HIV infection. It has been shown that CD4 counts between 250 and 500 cells per cubic millimeter are associated with oral candidiasis and disseminated tuberculosis; counts between 150 and 200 cells per cubic millimeter are associated with Kaposi's sarcoma, lymphoma, and cryptosporidiosis; counts between 75 and 125 cells per cubic millimeter are associated with Pneumocytis carinii, disseminated Mycobacterium avium complex, ulcerated herpes simplex, cryptococcosis, toxoplasmosis and eosophageal candidiasis; and counts less than 50 cells per cubic millimeter are associated with cytomegalovirus retinitis. [6]

Currently, U.S. Food and Drug Administration approved anti-HIV agents include zidovudine, didanosine, and dideoxycytidine, all of which work through inhibition of the reverse transcriptase enzyme. Zidovudine is the only agent that has been shown to have a clinical effect on HIV. Zidovudine is instituted generally when the CD4 count falls below 500 cells per cubic millimeter, and such early intervention with this agent has been shown to delay progression of AIDS. Didanosine is currently indicated for treatment of advanced HIV disease or for those patients who are intolerant to or fail to respond to zidovudine therapy. [1] Treatment with all of these anti­-HIV agents is associated with toxic side effects, including severe bone marrow suppression. Patients with a CD4 count less than 200 cells per cubic millimeter require prophylaxis against pneumocystis pneumonia. During this stage it is important to rule out tuberculosis, as this also is a common complication of HIV infection; tuberculosis is 500 times more common in HIV infected individuals than in the general population. HIV patients with positive purified protein derivative (PPD) skin test require prophylaxis with INH for at least 12 months. The PPD skin test is notoriously unreliable in HIV patients because of altered cellular immune function. Because the skin test reaction is decreased in HIV patients, a skin test that measures greater than 2 mm may be considered a positive result in some patients. HIV infected individuals considered to be at high risk for tuberculosis may also be candidates for INH prophylaxis if they develop a positive PPD skin test that measures more than 2 mm. In addition, HIV patients with low CD4 counts require prophylaxis against recurrent opportunistic infections such as cerebral toxoplasmosis, cryptococcosis, Mycobacterium avium complex, oroesophageal or vulvovaginal candidiasis, and histoplasmosis. [7]


  II. OPHTHALMIC COMPLICATIONS Top


The role of the ophthalmologist in the diagnosis and management of AIDS is becoming increasingly important. Not only does the eye reflect systemic disease, but ocular involvement may often precede systemic manifestations. In the AIDS patient, the ophthalmologist truly has an opportunity to make not only a sight-saving, but also a life-saving diagnosis. Therefore, it is the responsibility of the ophthalmologist to provide not only a thorough and accurate ophthalmologic examination, but also a careful and pertinent systemic evaluation, timely referrals, and periodic follow-up care.

Ocular manifestations have been reported in upto 70% of individuals infected with HIV, and it is becoming increasingly apparent that the ocular manifestations almost invariably reflect systemic disease, and, in fact, may be the first sign of disseminated infection.

HIV retinopathy is the most common ocular finding in patients with AIDS, occurring in about 50 to 70% of cases. It is characterized by cotton-wool spots [Figure - 2], retinal haemorrhages, and microaneurysms. [8] The cotton-wool spots are oriented usually along vascular arcades, and represent focal areas of ischemia in the nerve fiber layer. HIV has been isolated from human retina and its antigen has been detected in retinal endothelial cells by immunohistochemistry. It is believed that such HIV endothelial infection may play a role in the development of cotton-wool spots and other vascular alterations. The microaneurysms and haemorrhages that characterize HIV retinopathy are distributed along the nerve fibre layer and in the inner retinal layers. Cotton-wool spots, retinal haemorrhages, and microaneurysms are probably the result of both an underlying microvasculopathy and haematologic abnormalities such as anaemia and functional abnormalities of haemostasis.

Other infectious agents that can involve the eye in patients with AIDS include cytomegalovirus (CMV), herpes zoster, Toxoplasma gondii, Mycobacterium tuberculosis, Cryptococcus neoformans, Mycobacterium avium-intracellulare, Pneumocystis carinii, Histoplasma capsulatum, and Candida 9 These agents can infect the ocular adnexa, anterior segment, or posterior segment. Visual morbidity, however, occurs primarily when there is posterior segment involvement, particularly retinitis caused by CMV, herpes zoster, or Toxoplasma gondii.

a. Cytomegalovirus Retinitis

CMV retinitis is the most commonly seen opportunistic ocular infection in patients with AIDS, occurring in 15 to 40% of AIDS patients. The median elapsed time between diagnosis of AIDS and the development of CMV retinitis is about nine months; however, more recent studies have shown that this infection can occur as long as 3 to 5 years after the diagnosis of AIDS, and usually develops when the CD4+ cell counts are below 50 cells per cubic millimeter. Occasionally, however, CMV retinitis can be the initial manifestation of AIDS. [10]

The modes of transmission for CMV are not completely understood, although epidemiologic and virologic studies implicate close or intimate contact with infected individuals shedding virus in their urine, saliva, or other excretions. CMV infection in otherwise healthy adults and children is usually asymptomatic, but can occasionally be associated with a mononucleosis-like syndrome. In contrast to the generally benign course of CMV infection in healthy individuals, CMV is a major cause of morbidity and mortality in patients who are immunocompromised. The high incidence of anti-CMV antibodies in the general population is evidence for widespread exposure to this virus. It is possible that CMV retinitis represents a reactivation of CMV that was present in a latent form.

Well established CMV retinitis is easily recognized as a full-thickness retinal opacification associated with hard exudates and haemorrhages. The infection typically spreads along one of the major vascular arcades [Figure - 3], but may begin anywhere in the retina, including the far periphery. Due to the severe immunosuppression of these patients, there is a minimal amount of overlying vitreous inflammation [11][12][13] Very early CMV retinitis lesions may resemble cotton-wool spots. CMV infection in the peripheral retina appears as granular white opacification of the retina with minimal or no retinal haemorrhage [Figure - 4]. Infections that involve the posterior pole generally demonstrate the more typical picture of full-thickness retinitis with hard exudates and haemorrhages. The diagnosis of CMV retinitis is based on its characteristic clinical appearance. Serologic investigation and viral cultures are of limited value because a large proportion of individuals show evidence of previous exposure to CMV on serologic testing. In addition, the serologic diagnosis of CMV in patients with AIDS can be equivocal; because of the profound immunosuppression of these patients, serologic tests may be inaccurate. Although culture­confirmed presence of CMV in the throat, urine, and blood may be more reliable, immunosuppressed patients, including those with AIDS, are often chronic carriers of this virus, so the mere presence of CMV does not necessarily indicate significant infection. Because of these confounding factors, the ophthalmic examination has assumed great importance, as the diagnosis of CMV infection involving the retina can be made easily and reliably by routine ophthalmic examination.

In the United States, there are only two currently approved medications for treatment of CMV retinitis: ganciclovir and foscarnet. [14] Both ganciclovir and foscarnet have an initial response rate of 80 to 100%. Moreover, treatment of CMV retinitis may prolong the survival of AIDS patients. The median survival time following the diagnosis of CMV retinitis is increased from 6 weeks in patients who receive no treatment to 10 months in patients who respond completely to ganciclovir treatment, and to 3.1 months for those who respond partially. An early clinical trial showed that the median survival was 8.5 months in patients who received ganciclovir, compared with 12.6 months for patients who received foscarnet. [14] Recent studies show longer survival as a result of more intensive treatment of AIDS and related complications; unfortunately, such treatment requires the use of an indwelling venous catheter.

The only form of ganciclovir currently approved for clinical use is intravenous. The initial, two week, high dosage induction therapy (5 mg/kg twice daily for two weeks) is aimed at controlling the infection, and is followed by long-term maintenance therapy (5 mg/kg once daily 7 days a week, or 6 mg/kg once daily 5 days a week). The primary side effect of ganciclovir is myelosuppression. Concomitant use of granulocyte colony stimulating factor can reduce the neutropenia, the most serious component of myelosuppression, and may allow continuation of ganciclovir therapy. Neutropenia is usually reversible but may necessitate interruption of the drug therapy. Thrombocytopenia has been reported to occur in 5 to 10% of patients treated with ganciclovir. At the time of diagnosis of CMV retinitis, most patients are already on zidovudine for treatment of HIV infection. Because zidovudine also has toxic effect on the bone marrow, the dose is usually decreased when used concomitantly with ganciclovir.

Foscarnet is also administered intravenously and, like ganciclovir, requires an initial two week, high dose induction therapy (60 mg/kg every 8 hours for two or three weeks) followed by long-term maintenance therapy (90 to 120 mg/kg daily 5 days a week). Although foscarnet does not have a toxic effect on the bone marrow and can be used concurrently with full-dose zidovudine therapy, it is toxic to the kidneys. Renal dysfunction and metabolic abnormalities of calcium and magnesium have been reported in upto 30% of patients receiving foscarnet. Seizures have been reported in approximately 10% of patients receiving foscarnet.

When assessing the response to treatment, the most important clinical parameter is the size of the lesion [Figure - 5]. Careful attention to the border of the lesion, not the central area, is essential. Through careful comparison of the clinical appearance to earlier clinical photographs, enlargement or stabilization of the size of the lesion can be assessed. The second most important clinical parameter is the degree of activity of the lesion, which is determined by the presence of retinal whitening and haemorrhages at the border of the lesion. In recurrent disease, lesions usually demonstrate fluffy white areas of active retinitis at the border of the original CMV lesion. In some cases of recurrence, lesions may enlarge despite minimal signs of retinal whitening or haemorrhage. As with the primary disease, it is the border of the lesion that reflects disease activity. In chronic stages of the disease, large atrophic holes may develop that can lead to retinal detachment.

Despite the impressive initial response to treatment, active retinitis recurs in 18 to 50% of patients while on maintenance therapy [Figure - 6], and occurs in virtually all patients if anti-CMV therapy is discontinued. Most investigators believe that, if given enough time, all patients will eventually suffer a relapse, although they generally respond to a second course of induction (reinduction) therapy. If a patient has a recurrence while receiving one of the two therapies, consideration must be given to either reinduction with the current medication or new induction using the second medication.

In patients who cannot tolerate systemic anti-CMV drugs, ganciclovir can be administered by intravitreal injection . [15],[16 ] Intravitreal ganciclovir or foscarnet can also be considered for patients who have shown retinitis progression despite high-dose ganciclovir, foscarnet, or combination therapy with both ganciclovir and foscarnet. [15][16][17] Using topical anaesthesia, an injection of 200 micrograms is given twice a week for two to three weeks for induction therapy, followed by once a week injections for maintenance therapy. Initial success rates are very high, with almost all patients showing early resolution of retinitis. As with intravenous forms of therapy, relapse occurs in a substantial proportion of patients. Risks associated with repeated intravitreal injections include vitreous haemorrhage, retinal detachment, and bacterial endophthalmitis. Perhaps the most serious drawback to the intravitreal route of administration is the lack of benefits for the fellow eye and for extraocular sites from systemic anti-CMV medications.

A second promising route of administration of ganciclovir is via an intravitreal device, which is currently under investigation but has not yet been approved for use by the U.S. Food and Drug Administration. This device is surgically implanted and delivers the drug in effective concentrations over 4 to 6 months. The intravitreal device would also be a useful alternative for those patients who cannot tolerate intravenous therapy. [18] Other anti-CMV therapies are currently under investigation, including alternate intravenous agents such as 1-(S)-(3-hydroxy­2-phosphonylmethoxypropyl) cytosine dihydrate and oral agents such as valaciclovir.

An additional complication of CMV retinitis is that upto 29% of patients develop retinal detachment. This can occur when retinitis is active or during successful treatment, when the retinitis is quiescent. In almost all patients with retinal detachment, the CMV lesions extend anteriorly to the pars plana, and the retinitis generally involves more than 50% of the retina. Myopia is an additional risk factor for the development of retinal detachment in patients with CMV retinitis. [19],[20]

Retinal detachment in patients with CMV retinitis are among the most difficult to repair because of extensive retinal necrosis and multiple, often posterior, hole formation. Most investigators agree that these detachments are not amenable to repair by scleral buckling alone; the procedure of choice appears to be pars plana vitrectomy with long-term silicone oil tamponade. [19] Anatomic reattachment can be achieved in 90% of such patients. The functional success, however, depends on the condition of the macula and the extent of affected retina.

A current topic of intense research is the possibility of identifying patients at risk for CMV retinitis. Recent studies have indicated that CMV retinitis does not develop unless the CD4+ lymphocyte count is less than 50 cells per cubic millimeter; thus severe immunosuppression may be a prerequisite for CMV retinitis and disseminated CMV infection.

b. Progressive Outer Retinal Necrosis (PORN)

A rare infection in AIDS patients is the progressive outer retinal necrosis syndrome, which may be caused by the herpes zoster virus or other viruses in the herpes family. [21] This can occur in the absence of, at the same time as, or subsequent to a cutaneous zoster infection. It is possible that PORN represents a distinct form of acute retinal necrosis, occurring in an immunocompromised host.

In its early stages, PORN may be difficult to differentiate from peripheral CMV retinitis. However, its rapid progression in a circumferential fashion, and sparing of the retinal vasculature [Figure - 7], allow this entity to be distinguished from the acute retinal necrosis syndrome (ARN) and cytomegalovirus infection. Although no adequate therapy presently exists, ganciclovir or foscarnet in combination with acyclovir may be more effective than acyclovir alone in stabilizing the infection.

c. Toxoplasma Retinochoroiditis

A number of recent reports of toxoplasmosis in AIDS patients have revealed important clinical differences from this disease in immunocompetent individuals. [22] In general, the size of the retinochoroiditic lesions is larger in patients with AIDS, with upto one-third of lesions greater than five disc diameters in size [Figure - 8]. Bilateral disease is seen in 18 to 38% of cases. Solitary, multifocal, and military patterns of retinitis have been observed. A vitreous inflammatory reaction is usually present overlying the area of active retinochoroiditis, but the degree of vitreous reaction is less than that observed in immunocompetent patients.

The diagnosis of ocular toxoplasmosis may be more difficult in patients with AIDS. Although the diagnosis of active ocular toxoplasmosis in immunocompetent patients is aided often by the presence of old retinochoroiditis scars, patients with AIDS rarely demonstrate preexisting scars; preexisting scars are present in only 4 to 6% of AIDS patients with ocular toxoplasmosis. Because the clinical manifestations on this population are so varied, and may be more severe than in immunocompetent individuals, ocular toxoplasmosis in AIDS patients may be difficult to distinguish from acute retinal necrosis syndrome and from variants of cytomegalovirus, herpes simplex, herpes zoster, and syphilitic retinitis.

The histologic features of ocular specimens from AIDS patients reflect the immunologic abnormalities of the host. In general, the inflammatory reaction in the choroid, retina, and vitreous is less than that in the patients with an intact immune system, and trophozoites and cysts can be observed in greater numbers within areas of retinitis. In contrast to immunologically normal individuals, T. gondii organisms can occasionally be observed invading the choroid. [22]

Ocular toxoplasmosis in immunocompetent individuals is usually the result of reactivation of a congenital infection. In contrast, many AIDS patients with ocular toxoplasmosis probably have newly acquired infection or dissemination from a non-ocular site of infection. These conclusions are drawn from the observation that preexisting retinochoroiditic scars are rarely present, and that Toxoplasma specific 1gM titres are present in only 6 to 12% of patients.

The prompt diagnosis of ocular toxoplasmosis is especially important in patients with immunosuppression because it inevitably progresses if left untreated, in contrast to the self-limited disease of immunocompetent individuals. [22] In addition, ocular toxoplasmosis in immunocompromised patients may be associated with cerebral or disseminated toxoplasmosis, an important cause of morbidity and mortality in AIDS patients. Antitoxoplasmic therapy with various combinations of pyrimethamine, sulfadiazine, and clindamycin is required. Corticosteroids should not be used because of the risk of further immunosuppression, and because the inflammatory reaction in this population is relatively mild. In selecting the therapeutic regimen, consideration must be given to the possibility of coexistent cerebral or disseminated toxoplasmosis and the toxic effects of pyrimethamine and sulfadiazine on the bone marrow. Once the active retinitis has resolved, it is necessary to continue antitoxoplasmic therapy throughout the life of the patient in order to prevent recurrence.

d. Syphilitic Chorioretinitis

The clinical presentations of syphilitic chorioretinitis include uveitis, optic neuritis, and retinitis. [23] Patients with syphilitic chorioretinitis may also have evidence of dermatologic and central nervous system manifestations. AIDS patients with syphilitic chorioretinitis present with vitritis associated with bilateral, large, solitary, placoid, pale-yellowish subretinal lesions, most of which show evidence of central fading, and a pattern of stippled hyperpigmentation of the retinal pigment epithelium (syphilitic posterior placoid chorioretinitis). [24] Syphilis may pursue a more aggressive course in AIDS patients. These patients require treatment with 12 to 24 million units daily of intravenous penicillin G administered for at least 10 days, followed by 2.4 million units of intramuscular benzathine penicillin C administered for three weeks.

e. Pneumocystis carinii Choroiditis

More than 80% of patients with AIDS develop Pneumocystis carinii pneumonia, which is commonly the initial opportunistic infection in these individuals. Although Pneumocystis carinii pneumonia is extremely common, P.carinii choroiditis is rare. In all reported patients with Pneumocystis choroiditis, systemic dissemination was found. [25]

Although the initial pulmonary infection can usually be treated successfully, more than 60% of the patients have a recurrence within one year unless they receive appropriate prophylaxis. Aerosolized pentamidine is one such prophylactic therapy, and prevents recurrence in approximately 80% of patients for upto one year. Drug deposition, however, is limited tq the lung, and there have been an increasing number of reports of extrapulmonary Pneumocystis carinii infection. Presumably, extrapulmonary dissemination occurred during a previous episode of Pneumocystis carinii pneumonia, and activation occurs at these sites following prophylaxis with aerosolized pentamidine. The choroid may be one such site of activation.

Fundus changes characteristic of Pneumocystis carinii choroiditis consists of slightly elevated, plaque­like, yellow-white lesions located in the choroid [Figure - 9], with minimal accompanying vitritis. [25] On fluorescein angiography, these lesions tend to be hypofluorescent in the early phase and hyperfluorescent in the later phases. If disseminated Pneumocystis carinii is suspected, an extensive examination is required and may include chest radiography, arterial blood gas analysis, liver function testing, and abdominal computed tomography. Treatment of P.carinii choroiditis requires hospitalization for a three-week combination of intravenous trimethoprim (20 mg/kg of body weight per day) and sulfamethoxazole (100 mg/kg of body weight per day) or pentamidine (4 mg/kg of body weight per day). Within three to 12 weeks, most of the yellow-white lesions disappear, leaving mild overlying pigmentary changes . [26]

f. Cryptococcus neoformans Choroiditis

In patients with AIDS, dissemination of Cryptococcus neoformans may result in a multifocal choroiditis similar to that seen in Pneumocystis carinii choroiditis. Ocular manifestations of C.neoformans infection may presage specific systemic manifestations such as central nervous system diseases, thereby leading to an early diagnosis of disseminated cryptococcosis [27]

g. Multifocal Choroiditis and Systemic Dissemination

Multifocal choroidal lesions from a variety of infectious agents are seen in 5 to 10% of AIDS patients. [9] Most of these lesions are caused by Cryptococcus neoformans, Pneumocystis carinii, Mycobacterium tuberculosis or atypical mycobacteria [Figure - 10]. Although multifocal choroiditis caused by any one of these infectious organisms is seen in many patients with AIDS, there are occasional cases in which two or more of these opportunistic organisms cause the choroiditis [Figure - 11].

Because it is so often the site of opportunistic disseminated infections, the choroid is a critical structure that needs to be carefully examined in AIDS patients. Multifocal choroiditis is alarming, although nonspecific, and should prompt an exhaustive work­up for disseminated infection. Because multifocal choroiditis frequently represents disseminated infection, the ophthalmologist may have life-saving role in the diagnosis and management of these patients.

h. External Eye Manifestations

Other ophthalmic manifestations of AIDS include Kaposi's sarcoma, Molluscum contagiosum, herpes zoster ophthalmicus, keratitis due to various viruses and protozoa, conjunctival infections and microvascular abnormalities. All of these conditions affect mainly the anterior segment of the globe and the ocular adnexa.

(i) Ocular Adnexal Kaposi's Sarcoma : Since the initial description of Kaposi's sarcoma in 1872, two more aggressive variants of this tumour have been described. In 1959, an endemic variety was described in Africa; this is especially prevalent in Kenya and Nigeria, where it accounts for nearly 20% of all malignancies. The second variant, epidemic Kaposi's sarcoma, was first noted in renal transplant patients, and currently occurs in 30% of all patients with AIDS.

AIDS-associated Kaposi's sarcoma is particularly aggressive, disseminating to visceral organs (gastrointestinal tract, lung, and liver) in 20 to 50% of patients. Prior to 1981, fewer than 25 patients with ocular adnexal Kaposi's sarcoma had been reported, but this now occurs in approximately 20% of patients with AIDS-associated systemic Kaposi's sarcoma.

Recent evidence suggests that AIDS-related Kaposi's sarcoma may have an infectious origin, and that HIV has a role in the pathogenesis of Kaposi's sarcoma is evident from studies of transgenic mice that bear the HIV-1 transactivator (tat) gene under the control of the virus regulatory region (HIV-LTR). The HIV tat protein has been shown to be a potent mitogen for human Kaposi's sarcoma derived cell lines. As in humans, these lesions in mice occur predominantly in males, which suggests that their development may be hormonally controlled.

Three stages of ocular adnexal Kaposi's sarcoma have been described. [28] Clinically, stage I and stage II tumours are patchy, flat (less than 3 mm in height), and of less than four months' duration. Stage III tumours are nodular, elevated (greater than 3 mm in height), and of greater than four months' duration [Figure - 12]. The treatment of Kaposi's sarcoma is based on the clinical stage of the tumour, its location, and the presence or absence of disseminated lesions. When the lesion is confined to the ocular adnexa, local treatment is appropriate. If the tumour is confined to the bulbar conjunctiva and is stage I or stage II, an excisional biopsy with 1 to 2 mm tumour-free margins should be considered only if the lesion is symptomatic. Stage III Kaposi's sarcoma of the bulbar conjunctiva should be surgically excised, preferably after delineation by fluorescein angiography. Stage I and stage II Kaposi's sarcoma involving the eyelid may be treated with cryotherapy. Stage III Kaposi's sarcoma of the eyelid may be treated with either radiation or cryotherapy. Radiation treatment is preferred because of a lower recurrence rate. In order to avoid radiation-related complications, however, lesions may be treated with cryotherapy if the patient is aware that recurrence is more likely and may necessitate retreatment. When evaluating an AIDS patient with ocular adnexal Kaposi's sarcoma, a full systemic examination for tumour dissemination must be done. If chemotherapy is administered for systemic Kaposi's sarcoma, the ophthalmologist should wait at least four to six weeks to observe the response to treatment before deciding whether further therapy is warranted. [28]

(ii)Molluscum Contagiosum : Molluscum contagiosum is a DNA virus of the pox virus family. The characteristic skin lesions show a small elevation with central umbilication. In healthy individuals, Molluscum lesions are few in number, unilateral and involve the eyelids. In AIDS patients, however, these lesions may be numerous and bilateral [29] If Molluscum lesions in AIDS patients are symptomatic or cause conjunctivitis, surgical excision may be necessary.

(iii) Herpes Zoster: Apparently healthy young people who present with herpes zoster lesions of the face or eyelids should be suspected of having AIDS and should be tested for HIV. Corneal involvement can cause a persistent chronic keratitis, and treatment consists of intravenous and topical acyclovir. Although the progressive outer retinal necrosis syndrome is extremely rare, these patients should be followed periodically with retinal examinations.

i.Other Infections

AIDS does not appear to predispose to bacterial keratitis but, in AIDS patients who do develop bacterial ulcers, these infections are severe and more likely to cause perforation than in immunocompetent patients. Fungal keratitis can occur in patients with AIDS who have no apparent predisposing factors such as trauma of topical steroid use. Herpes simplex keratitis does not appear to occur with higher incidence in patients with AIDS, but may have a more prolonged course and involve the limbus in these patients. Recently, microsporidia have been shown to cause a coarse, superficial punctate keratitis with a minimal conjunctival reaction in AIDS patients [30]sub Electron microscopy of the epithelial scrapings revealed the organism to be an obligate, intracellular, protozoan parasite. [31]

Solitary granulomatous conjunctivitis from cryptococcal infection, tuberculosis, or other mycotic infections can occur in HIV infected individuals. As with all other infections in AIDS, the possibility of dissemination must be entertained and aggressively sought. In recent years, orbital lymphomas and intraocular, lymphomas, mostly large B-cell lymphomas, have beeh described in patients with AIDS.


  III. PRECAUTIONS IN THE HEALTH-CARE SETTING Top


Specific precautionary measures against HIV infection have been advocated by the U.S. Centers for Disease Control and other governmental agencies, including the Occupational Safety and Health Administration. These agencies insist upon adoption of blood-borne pathogen standards, commonly referred to as "universal precautions." These precautions include steps in preventing accidental needle stick injury, routine wearing of gloves when collecting and handling specimens, and disposal of contaminated sharp objects in puncture-resistant containers; proper shielding of eyes and mouth must be incorporated into the routine of laboratory workers. Physical examination equipment that comes in contact with mucosal surfaces must be thoroughly disinfected after each use. All blood spills in the examining room or waiting area must be promptly cleaned by a gloved person using 10% bleach solution. Hepatitis B vaccine must be offered to all personnel who come in contact with patient blood. Whether or not a patient is known to be HIV positive, the universal precautions should be followed.

Precautions for Ophthalmic Health-Care Personnel

The American Academy of Ophthalmology has advocated the following precautionary measures against HIV infection in ophthalmic practice. These measures are meant to provide protection to patients, ancillary health-care personnel, and ophthalmologists. It appears that there is a lower level of risk in ophthalmology than in some other specialities. Even though there are no published reports of HIV transmission in ophthalmic health-care settings, hand­-washing with soap and water and thorough drying with fresh or disposable towels between various tests on a given patient and between patients are recommended. If an open wound or weeping lesion is present, disposable gloves should be worn. Tonometers and diagnostic contact lenses should be wiped with an alcohol sponge. Similarly, the Schiotz tonometer can be cleaned with an alcohol sponge after disassembling the instrument. However, the Centers for Disease Control recommend household bleach (1:10 dilution) to clean such instruments. Contact lens trial sets need to be disinfected between patients. For hard contact lenses and rigid gas permeable contact lenses, hydrogen peroxide disinfection or a chlorhexidine-containing disinfectant system should be employed. For soft contact lenses, hydrogen peroxide or a heat disinfection system should be used. Corneal and scleral tissue used for transplantations should be screened for HIV and hepatitis-B virus, in accordance with the guidelines provided by the Eye Bank Association of America. Barrier precautions, such as disposable gloves, should be used during diagnostic procedures such as injection of the dye for fluorescein angiographic studies. During surgical procedures, particularly where contact with blood or blood contaminated fluids is likely, disposable gloves, masks and protective eye wear should be worn by all personnel in attendance.


  IV. FUTURE PROSPECTS FOR HIV INFECTION Top


Although several anti-retrovirals, such as zidovudine (AZT), dideoxyinosine (DDI), and dideoxycytidine, have been used in the treatment of HIV infection, many patients fail to respond to such therapy. In part, such treatment failures are considered to be from the emergence of drug resistant viruses, and such resistance appears to be more common in later stages of the disease. There are now troublesome reports of possible transmission of AZT-resistant phenotypes. Determining the extent and significance of such transmission has become a public health priority. Currently, AZT-resistant HIV infections are treated by DDI therapy.

There are several new anti-retroviral drugs under development. These agents are designed to inhibit: (a) reverse transcriptase; (b) protease that cleaves polyprotein precursors into mature structural proteins and enzymes during particle assembly and maturation; (c) tat protein that is required for HIV replication; and (d) viral entry utilizing soluble forms of CD4 receptors. In addition, nucleic acid-based therapies such as antisense oligonucleotides or ribozymes that recognize and cleave specific viral sequences are under development. Furthermore, therapeutic approaches to reconstitute immunity are being investigated. These therapies include modulation of cytokines, CD8+ cells, syngeneic bone marrow transplantation and adoptive transfer of peripheral blood lymphocytes in combination with anti-retroviral agents.

In conclusion, it is likely that new drugs to combat HIV infection, and other agents to suppress the opportunistic infections that accompany HIV, will become available soon. In the future, an anti-HIV vaccine may be introduced. However, at present, every effort must be made to prevent HIV transmission. It is critical that the public be educated on "safe sexual practices," that government agencies continue to support basic and clinical research, and that the pharmaceutical industry continue its search for therapeutic and preventive agents to halt this deadly modern plague, the HIV pandemic.


  Acknowledgement Top


This work was supported in part by Research to Prevent Blindness, Inc., New York, New York, U.S.A., and by grant EY03040 from the National Eye Institute, Bethesda, Maryland, U.S.A.

 
  References Top

1.
Kessler HA, Bick JA, Pottage JC Jr, et al. AIDS: Part 1. Dis Mon. 38:633-690, 1992.  Back to cited text no. 1
    
2.
Clavel F, Guetard D, Brun-Vezinet F, et al. Isolation of a new retrovirus from West African patients with AIDS. Science. 233:343-346, 1986.  Back to cited text no. 2
    
3.
Haseltine WA, Wong-Staal F. The molecular biology of the AIDS virus. Sci Am. 259(4):52-63, 1988.  Back to cited text no. 3
    
4.
Levy JA. Human immunodeficiency viruses and the pathogenesis of AIDS. JAMA 261:2997-3006, 1989.  Back to cited text no. 4
    
5.
Weiss RA. How does HIV cause AIDS? Science. 260:1273-1279, 1993.  Back to cited text no. 5
    
6.
Crowe SM, Carlin JB, Stewart KI, et al. Predective value of CD4 lymphocyte numbers for the development of opportunistic infections and malignancies in HIV - infected persons. J Acquir Immune Defic Syndr. 4:770­776, 1991.  Back to cited text no. 6
    
7.
Kessler HA, Bick JA, Pottage JC Jr, et al. AIDS: Part II. Dis Mon. 38:691-764, 1992.  Back to cited text no. 7
    
8.
Holland GN, Pepose JS, Pettit TH, et al. Acquired immune deficiency syndrome: ocular manifestations. Ophthalmology. 90:859-873, 1983.  Back to cited text no. 8
    
9.
Morinelli EN, Dugel PU, Riffenburgh R, et al. Infectious multifocal choroiditis in patients with acquired immune deficiency syndrome. Ophthalmology. 100:1014-1021, 1993.  Back to cited text no. 9
    
10.
Henderly DE, Freeman WR, Smith RE, et al. Cytomegalovirus retinitis as the initial manifestation of the acquired immune deficiency syndrome. Am J Ophthalmol. 103:316-320,.1987.  Back to cited text no. 10
    
11.
Dugel PU, Rao NA. Ocular infections in the acquired immunodeficiency syndrome. Int Ophthalmol Clin.33(1):103-127, 1993.  Back to cited text no. 11
    
12.
Jabs DA, Enger C, Bartlett JG. Cytomegalovirus retinitis and acquired immunodeficiency syndrome. Arch Ophthalmol. 107:75-80, 1989.  Back to cited text no. 12
    
13.
Holland GN, Sison RF, Jatulis DE, et al. Survival of patients with the acquired immune deficiency syndrome after development of cytomegalovirus retinopathy. Ophthalmology. 97:204-211, 1990.  Back to cited text no. 13
    
14.
Studies of Ocular Complications of AIDS Research Group, in collaboration with the AIDS Clinical Trails Group. Mortality on patients with the acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. N Engl J Med. 326:213-220, 1992.  Back to cited text no. 14
    
15.
Cochereau-Massin I, Lehoang P, Lautier-Frau M, et al. Efficacy and tolerance of intravitreal ganciclovir in cytomegalovirus retinitis in acquired immune deficiency syndrome. Ophthalmology. 98:1348-1355, 1991.  Back to cited text no. 15
    
16.
Ussery FM III, Gibson SR, Conklin RH, et al. Intravitreal ganciclovir in the treatment of AIDS­associated cytomegalovirus retinitis. Ophthalmology. 95:640-648, 1988.  Back to cited text no. 16
    
17.
Diaz-Llopis M, Chipont E, Sanchez S, et al. Intravitreal foscarnet for cytomegalovirus retinits in a patient with acquired immunodificiency syndrome. Am J Ophthalmol. 114:742-747, 1992.  Back to cited text no. 17
    
18.
Anand R, Nightingle SD, Fish RH, et al. Control of cytomegalovirus retinitis using sustained release of intraocular ganciclovir. Arch Ophthalmol. 111: 223-227, 1993.  Back to cited text no. 18
    
19.
Dugel PU, Liggett PE, Lee MB, et al. Repair of retinal detachment caused by cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. Am J Ophthalmol. 112:235-242, 1991.  Back to cited text no. 19
    
20.
Irvine AR. Treatment of retinal detachment due to cytomegalovirus retinitis in patients with AIDS. Trans Am Ophthalmol Soc. 89:349-367, 1991.  Back to cited text no. 20
    
21.
Forster DJ, Dugel PU, Frangieh GT, et al. Rapidly progressive outer retinal necrosis in the acquired immunodeficiency syndrome. Am J Ophthalmol 110:341-348, 1990.  Back to cited text no. 21
    
22.
Moorthy RS, Smith RE, Rao NA. Progressive ocular toxoplasmosis in patients with acquired immunodeficiency syndrome. Am J Ophthalmol. 115:742-747, 1993.  Back to cited text no. 22
    
23.
Tamesis RR, Foster CS. Ocular syphilis. Ophthalmology. 97:1281-1287, 1990.  Back to cited text no. 23
    
24.
Gass JDM, Braunstein RA, Chenoweth RG. Acute syphilitic posterior placoid chorioretinitis. Ophthalmology. 97:1288-1297, 1990.  Back to cited text no. 24
    
25.
Rao. NA, Zimmerman PL, Boyer D, et al. A clinical histopathologic, and electron microscopic study of Pneumocystis carinii choroiditis. Am. J Ophthalmol. 107:218-228, 1989.  Back to cited text no. 25
    
26.
Dugel PU, Rao NA, Forster DJ, et al. Pneumocystis carinii choroiditis after long-term aerosolized pentamidine therapy. Am J Ophthalmol. 110:113-117, 1990.  Back to cited text no. 26
    
27.
Frangieh GT, Dugel PU, Rao NA. Ocular manifestations of acquired immunodeficiency syndrome. Curr Opin Ophthalmol. 3:228-235, 1992.  Back to cited text no. 27
    
28.
Dugel PU, Gill PS, Frangieh GT, Rao NA. Ocular adnexal Kaposi's sarcoma in acquired immunodeficiency syndrome. Am J Ophthalmol. 110:500-5Q3, 1990.  Back to cited text no. 28
    
29.
Robinson MR, Udell' IJ, Garber PF, et al. Molluscum contagiosum of the patients with acquired immune deficiency syndrome. Ophthalmology.99:1745­1747, 1992.  Back to cited text no. 29
    
30.
Schwartz DA, Visvesvara GS, Diesenhouse MC, et al. Pathologic features and immunofluorescent antibody demonstration of ocular microsporidiosis (Encephatitozoon hellein) in seven patients with acquired immunodeficiency syndrome. Am J Ophthalmol. 115:285-292, 1993.  Back to cited text no. 30
    
31.
Lowder CY, Meisler DM, McMahon JT, et al. Microsporidia infection of the cornea in a man seropositive for human immunodeficiency virus. Am J Ophthalmol. 109:242-244, 1990.  Back to cited text no. 31
    


    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9], [Figure - 10], [Figure - 11], [Figure - 12]
 
 
    Tables

  [Table - 1]


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