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REVIEW ARTICLE
Year : 1988  |  Volume : 36  |  Issue : 4  |  Page : 151-155

Diagnosis and management of ocular lesions in acquired immune deficiency syndrome


Doheny Eye Institute, 1355 San Pablo St., Los Angeles, California, 90033, India

Correspondence Address:
Narsing A Rao
Doheny Eye Institute, 1355 San Pablo St., Los Angeles, California, 90033
India
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Source of Support: None, Conflict of Interest: None


PMID: 2855324

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  Abstract 

The eye is one of the most commonly effected organs in Acquired Immune Deficiency Syndrome (AIDS), a new disease of this decade. An update of various ocular lesions along with their man­agement is described.

Keywords: AIDS = Acquired Immune Deficiency Syndrome CMV = Cytomegalo Virus CDC = Centres for Disease Control ARC = Acquired Immune Deficiency Syndrome Related Complex WHO = World Health Organization


How to cite this article:
Biswas J, Rao NA, Irvine R R. Diagnosis and management of ocular lesions in acquired immune deficiency syndrome. Indian J Ophthalmol 1988;36:151-5

How to cite this URL:
Biswas J, Rao NA, Irvine R R. Diagnosis and management of ocular lesions in acquired immune deficiency syndrome. Indian J Ophthalmol [serial online] 1988 [cited 2020 Feb 27];36:151-5. Available from: http://www.ijo.in/text.asp?1988/36/4/151/26125


  Introduction Top


The acquired immune deficiency syndrome (AIDS) is a new disease entity first recognized in June 1981 when 5 cases of Pneumocystis carinii pneumonia in young homosexual men were reported to the Centres for Disease Control (CDC) in the United States [1]. Since then, the disease has risen to epidemic propor­tions, and more than 70,000 cases have been reported to the WHO from 129 countries as of January 1988 [2]. The disease has become a major threat to world health in the present decade, requiring an international approach for its prevention and control.


  Definition Top


AIDS is currently defined by the CDC as a reliably diagnosed disease that is at least moderately indicative of an underlying cellular immunodeficiency in a person infected with human immunodeficiency virus (HIV) with no other known cause of underlying cellular immunodeficiency, resulting in the developement of multiple opportunistic infections and unusual neop­lasms. Those individuals who are infected with HIV but who have not developed opportunistic infection or Kaposi's sarcoma at the time of examinations are categorized as having acquired immune deficiency syndrome related complex (ARC). Patients with ARC commonly show signs of lymphadenopathy, fatigue and weight loss.


  Epidemiology Top


Since AIDS was first reported, the incidence of the disease has increased at a rapid and alarming rate, reaching epidemic proportions. According to WHO statistics, in the United States alone over 50,000 cases of AIDS (70% of the total) had been reported by the end of 1987; 18,000 cases have been reported from other countries, 8,000 cases each from Europe and Africa and less than 2,000 cases from Asia and the Pacific islands [2]. There is an ever increasing incidence of the disease, and it is believed that, at the current rate of increase, there will be 2,70,000 cumulative cases of AIDS by 1991 [4]. Fifty-eight percent of the diagnosed patients have already died of this fatal disease, 80% of whom were diagnosed before 1985 [5].

Certain population groups are at greater risk of developing this disease. These are homosexual and bisexual men with no history of intravenous drug abuse (65%), homosexual intravenous drug abusers (8%), heterosexual intravenous drug abusers (17%), heterosexual contacts without any history of drug abuse (4%), and blood tranfusion recipients (2%). In 3% of the diagnosed cases, no risk factor was found. Homosexual and bisexual men constitute the largest group (75%) of adult cases in the United States [6].


  Aetiology and Mode of Transmission Top


The aetiologic agent of this new synodrome has been identified and is currently referred to as the human immunodeficiency virus (HIV) [7],[8],[9]. This virus was earlier known as human T-lymphotrophic virus type III (HTLV III), lymphadenopathy associated virus (LAV), and AIDS related virus (ARV). It is a member of the retrovirus family. The mode of trans­mission is primarily through sexual contact, through parenteral exposure to infected blood and blood pro­ducts, and from infected mothers to foetuses in utero. The virus has been isolated from lymphocytes and macrophages of AIDS patients as well as from various viscera, central nervous system tissues and from the eye in the cornea [10], conjunctival epithelium [11], tears [12] and retina [l3]. Though there is no report of transmission of the virus from ocular examinations of AIDS patients, several precautionary measures have been recommended to prevent dissemination of the disease to other patients and to eye care personnel.


  Ocular Lesions of AIDS Top


From the ophthalmic point of view, AIDS is an - important disorder due to the fact that the eye is one of the most commonly affected organs. The incidence of ocualr involvement has been reported to be as high as 75% [14]. Ocular lesions are varied and affect almost all structures of the eye. Further, AIDS patients often present with ophthalmic complaints in the early phase of the disease, while they are in good general condition without any clinical evidence of systemic opportunistic infections. Early recognition of the ophthalmic manifestations of this disease is often the basis for the identification of primary HIV infection and its associated opportunistic infections. Ocular lesions associated with AIDS can be categorised in­to four major groups:­

1. Non-infectious retinopathy

2. Opportunitistic infections of the eye

3. Unusual neoplasms,
such as Kaposi's sarcoma

and Bur kitt's lymphoma 4. Neuro-ophthalmic lesions

Non-infectious retinal lesions Cotton-wool spots:­

Cotton-wool spots are the most common ocular lesions, occurring in approximately 50% of AIDS patients [15]. Clinically, they appear as discrete, fluffy opacities in the superficial retina, usually in the posterior pole adjacent to the major vascular arcades [Figure - 1]. Rarely, flame-shaped haemorrhages accompany the cotton-wool spots. These are of course, nonspecific findings and are seen in a variety of systemic disorders, including d i:abetes, hypertension, serve an and collagen vascular diseases. The precise cause of cotton-wool spots in AIDS patients remains unclear, but immune complex deposition in precapillary arterioles has been suggested [16]. In addition, several infectious agents have been thought to be associated with the cotton-wool spots in AIDS patients; these include Pneumocystis carinii [17],[18],Cryptococcus neoformans [16] and HIV perse [13].

Retinal haemorrhages and microvascular abnormalities:

Retinal haemorrhages, either flame-shaped or blot hemorrhages, are seen in 15 to 40% of patients with

AIDS [16],[19],[20].Three cases of retinal hemorrhages with white central areas were reported in one series; histologic examination showed acute inflammatory cells in the white central area of the retina [15]. Mic­roaneur'sms have been reported in 20% of AIDS patients [20]. Other microvascular changes observed are telangiectasia, focal areas of nonperfusion and capillary loss, changes that are similar to those observed in diabetic retinopathy [21].


  Opportunistic infections of the eye Top


The most serious ocular manufestations of AIDS result from opportunistic infections that frequently lead to visual loss. Various pathogenic organisms have been implicated, including viruses, fungi, bacteria, and pro­tozoa. These organisms rarely affect the external surface of the eye. Even though opportunistic infection of the eye occurs less commonly than in other parts of the body, it is important to note that these ocular infections are always associated with infection in other parts of the body and may he the initial manifestation of systemic infection. Therefore, when such an ocular infection is diagnosed, a thorough systemic workup for opportunistic infection is mandatory.

Viral infection:

Cytomegalovirus infection is the most common ocular opportunistic infection, and occurs in about 25% of the cases [15],[16],[19]. Clinically, the fundus lesions are similar to those seen in immunosuppressed individuals and in children with cytomegalovirus inclusion disease. The lesions are bilateral in 50% of the cases and are situated in the periphery, in the posterior pole, or at both of these sites; they are frequently seen along the vascular arcades. These retinal lesions are white and granular, with areas of infiltration and necrosis. Prominent retinal hemorrhages are often seen in the necrotic areas [Figure - 2].

Retinal necrosis is slowly progressive, with doubling or tripling of the size of lesion within a month. Lesions progressively coalesce, and can destroy the entire retina within 6 months. A thin gliotic membrane then replaces the retina after several months, especially when the patients are treated with an antiviral agent [Figure - 3]. Along with retinal infection, vitritis may be present in a mild and nonprogressive form, and anterior uveitis is seen occasionally [14],[15],[19],[20],[22].CMV retinitis concomitant with optic neuritis has been noted [23].

Histopathologically, CMV retinitis consists of necrotic retina containing cytomegalovirus inclusion bodies in all the layers of the retina including retinal pigment epithelium [16],[19],[20],[22],[23][Figure - 4]. Inclusion bodies are seen also in the optic nerve [24]. Electron microscopic study of the involved retina shows hexagonal capsomers characteristic of the her es family of viruses, of which CMV is member [16],[19],[20]. The destroyed retina contains viral DNA, as demonstrated by in situ DNA hybridi­zation. This virus has been isolated from both retina and vitreous of AIDS patients having retinitis [25]. Herpes zoster and Herpes simplex infections of ocular tissue have also been reported. Herpes zoster ophthalmicus leads to blephai-itis. conjunctivitis. keratitis and uveitis [26]. Herpes simplex in AIDS patients can involve both cornea and retina [27]; this virus has been observed in all layers of the retina, including the retinal pigment epithelium [28].

Bacterial infections:

Opportunistic bacterial infections within the eye are very rare in AIDS. Mvcohacterium avium intracellulare was identified in 6%, of autopsy eyes in one study [16]. In one reported case of AIDS-related complex necrotiz­ing retinitis with large white retinal lesions were ob­served in the periphery; this was believed to be from tryponema pallidum infection [29].

Fungal infection:

Opportunistic fungal infections of the retina in AIDS patients have been due to candida [23], cryptococcus [16],[19], histoplasma [30] and sporothrix schenckii [31]. The lesions are very similar to those observed in immunosuppressed hosts. Bilateral corneal ulcers caused by fungus have also been reported in AIDS patients [32],[33].

Protozoal infection

There have been several reports of toxoplasmic en­cephalitis in AIDS patients, but ocular involvement has only rarely been noted [23],[24]sub .We have observed toxoplasmic retinochoroiditis in conjunction with other opportunistic infections, such as CMV retinitis.


  Unusual Neoplasms Top


Kaposi's sarcoma is seen in about 30% of AIDS cases [35], and is characterized by erythematous or vio­laceous soft lesions involving the eyelid, conjunctiva or orbit. The lesions are usually multicentric, with involvement of the viscera and other mucocutaneous sites. Kaposi's sarcoma of the eyelids, which present as purple-red nodules, can produce secondary changes, such as edema of the eyelid, entropion, trichiasis and chronic blepharoconjunctivitis from ulceration and re­current hemorrhages. In contrast to the lid tumors, Kaposi's sarcoma of the conjunctiva appears as a bright red hemorrhagic mass [Figure - 5]. The flat lesions mimic subconjunctival hemorrhages, while elevated lesions simulate granuloma pyogenicum, cavernous hemangioma, foreign body granuloma, malignant melanoma and metastatic tumors. Kaposi's sarcoma, though common in the lid and conjunctiva, rarely occurs in the orbit [14]. Patients with AIDS are also at a higher risk of developing other malignant lesions, such as Burkitt's lymphoma. Orbital Burkitt's I%m­phoma has been reported in one case of AIDS [36].


  Neuro-ophthalmic changes Top


Intracranial inflammation in AIDS patients leads to multiple cranial nerve palsies [20]. Cranial nerves supply­ing extraocular muscles, and eyelids and sensory nerves to the eye can also be affected by meningeal inflam­mation, encephalitis, and intracranial masses.


  Management Top


Though AIDS, continues to be extensively well studied, treatment is still unsatisfactory and a vaccine against this virus is still not available. Various measures have been recommended to prevent transmission of this virus, and general awareness of the disease and its mode of transmission is essential, especially in endemic areas.

Prevention

Ophthalmologists and other health care professionals for AIDS patients should observe precautions recom­mended by the Centres for Disease Contro1 [37]. Although HIV has been detected in human tears, transmission through tears has not been reported. However, barrier precautions should be observed during clinical exami­nation of AIDS patients as well as during surgical and laboratory procedures. The use of gloves during ophthalmic examination is recommended. Ophthalmic instruments, such as tonometer tips should be wiped after direct contact with the ocular surface, then soaked in either a fresh solution of 3% hydrogen peroxide or a fresh solution of 0.525% sodium hypoch­lorite (1:10 dilution of household bleach) for 10 minutes. Contact lens trial sets should be disinfected after use by hydrogen peroxide solution or by heat disinfection (78°-80°c) for at least 10 minutes [38].

Treatment

Treatment for AIDS remains unsatisfactory. Although various drugs are under trial, an effective drug without serious complications is still unavailable to the clinician. Ziduvidine (3'-azido-3'-deoxythymidine), also known as Retrovir or AZT is a thymidine analog that inhibits HIV replication in vitro [39]. The drug has been found to decrease the frequency of opportunistic infections and mortality in a selected group of patients, at least over 8 to 24 weeks of observation [40]. This drug does have potential bone marrow toxicity, thus limiting its prolonged use.

Management of AIDS cases consists primarily of treatment of the opportunistic infections, malignancies, and other sequelae. The ideal drug for treatment of CMV infection is not available as yet. Of the various drugs that are used against it, ganciclovir, 9-(1 ,3-dihyd­roxy-2-propoxymethyl)-guanine, also known as DHPG and BW759U, has been found to be very promising. This drug is under clinical trial in a few centres and has been observed to produce dramatic reversal of the retinitis [41],[42]. It inhibits progression of retinitis and induces healing of the necrotic retina. It is usually given intravenously. Recently, intravitreal injection of DHPG has been tried. Initially, a loading dose of 5 mg/kg of body weight every 12 hours is given intraven­ously for 14 consecutive days, followed by a daily maintenance dose of 5 mg/kg of body weight. Initial responses are excellent with 100% success in suppres­sing the retinitis. Rhegmatogenous retinal detachments were observed in 23% of our cases treated with this antiviral agent. This was probably due to focal retinal necrosis leading to retinal detachment in these cases [43] Unfortunately, toxicity of this drug is quite high, which limits its repeated use. Bone marrow depression with secondary neutropenia occurs in 30% of patients, and it is also known to cause azospermia. Another problem is that discontinuation of treatment leads to reactivation of lesions in about 3 weeks.

Foscarnet is another promising drug in the treatment of AIDS. This is a DNA-polymerase inhibitor with anti-CMV activity. It is given as a continuous infusion, every 8 to 12 hours. While this drug does not have bone marrow toxicity, it is known to be nephrotoxic, although the nephrotoxicity is reversible on discon­tinuance of the drug. In a recent clinical trial, Foscarnet was found to be superior to DHPG in the treatment of CMV retinitis in that patients showed fewer recurr­ences [44]. Foscarnet and Ziduvidine are synergistic in action, and can be combined for enhanced therapeutic purposes and to reduce bone marrow toxicity.

Agents that are of limited effects in the treatment of AIDS are Acyclovir, Vidaribine, Alpha Interferon and Interleukin-2 and the immunoglobulins.

Research is currently under way to develop a vaccine against HIV. There is no specific treatment for Kaposi's sarcoma of the conjunctiva, eyelid and orbit. Treatment with Vincristine and alpha-2 interferon has led to

partial remission of this tumor [45],[46 ] In other cases, palliative radiotherapy has proven helpful. The lym­phomas in AIDS patients can be treated with chemotherapy or radiation.

In summary, AIDS is a serious infectious disease with high mortality and morbidity, for which there is presently no therapy. However, the lives of these individuals can be prolonged by various anti-viral agents. Vision threatening complications e.g. CMV retinitis can be successfully managed by the newer anti-viral drugs mentioned above. As the vast majority of patients with AIDS develop ocular symptoms at some point during the course of the disease, it is essential that ophthalmologists be aware of the various manifestations of the disease and its complications, as well as the precautionary measures that can prevent the spread of this deadly disease.

 
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    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]


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