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Ophthalmic Manifestations of HIV Infection

Digital Journal of Ophthalmology 2004

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Breno Rocha Lima, M.D. | University of Miami School of Medicine - William J. Harrington Medical Training Programs

ABSTRACT INTRODUCTION DISCUSSION ACKNOWLEDGEMENTS REFERENCES CLINICAL PICTURES

Abstract

ObjectiveThis review is intended to describe the most common ophthalmic manifestations of HIV infection. It is estimated that more than 70% of adult AIDS patients will experience an ocular complication at some point of the disease. Orbital and adnexal manifestations include tumors of the periocular tissues and external infections. Anterior segment findings consist of keratitis, keratoconjunctivitis sicca, iridocyclitis, and other complications. Posterior segment findings include a HIV associated retinopathy and a number of opportunistic infections of the retina and choroid. HIV has also been related to neuro-ophthalmic manifestations such as visual field defects and papilledema.

MethodsThe author performed a search of Medline, using PubMed. Search words included HIV, cytomegalovirus retinitis, retinal microvasculopathy, herpes zoster ophthalmicus, Kaposi`s sarcoma, immune recovery uveitis, orbital lymphoma, toxoplasmosis, herpes simplex virus, pneumocystis carinii, microsporidia, syphilis, molluscum contagiosum, ganciclovir and keratoconjunctivitis sicca. Articles were selected based on clinical importance. Additional references of key articles were also included. Articles were excluded if they had non-English abstracts.

KeywordsHIV, Cytomegalovirus (CMV) retinitis, Retinal microvasculopathy, Herpes Zoster Ophthalmicus, Kaposi`s Sarcoma, Immune Recovery Uveitis, Toxoplasmic Retinochoroiditis

topIntroduction

The human immunodeficiency virus (HIV) infection has spread worldwide, with various adverse health and economic implications, particularly in the developing world.(1) A global summary of the HIV/AIDS epidemic from December 2003 by the Joint United Nations Programee on HIV/AIDS (UNAIDS) and World Health Organization (WHO) estimates that there are 40 million people worldwide living with HIV/AIDS. Approximately 5 million people were infected with HIV and there were about 3 million AIDS deaths in 2003.(2) At present, around 90% of HIV-infected persons live in developing countries, particularly those in sub-Saharan Africa and Southeast Asia.(2, 3) Unless a cure is found or life prolonging therapy can be made more widely available, the majority of people will remain suffering the profound impacts the disease has on their quality of life.(4) Numerous ophthalmic manifestations of HIV infection may involve the anterior or posterior segment of the eye. Since the first report of the ocular manifestations of AIDS by Holland et al. in 1982,(5, 6) subsequent studies have described several AIDS related conditions in the eye and orbit. 7080% of adult AIDS patients will experience an ocular complication at some point of their illness.(5, 7) Orbital and adnexal findings include tumors of the periocular tissues and external infections. Anterior segment manifestations consist of keratitis, keratoconjunctivitis sicca, iridocyclitis, and other complications. Posterior segment findings include a HIV associated retinopathy and a number of opportunistic infections (OI) of the retina and choroid. HIV has also been related to neuro-ophthalmic manifestations, such as visual field defects, papilledema, and diplopia. The occurrence of ophthalmic complications associated with HIV infection is significantly lower in the pediatric age group. All patients with HIV disease should undergo routine ophthalmologic examinations, since proper diagnosis and treatment may help to maintain vision and prolong life. Some retinal OI may have a rapid and devastating course.CD4+ T Lymphocyte proved to be a reliable predictor of ocular complications of HIV infection.(7, 8) The use of highly active antiretroviral therapy (HAART), which consists of a combination of nucleoside reverse transcriptase inhibitors, HIV protease inhibitors and non nucleoside reverse transcriptase inhibitors, has decreased plasma levels of HIV RNA and increased CD4+ T lymphocytes counts, improving the immune function of patients with HIV infection.(9, 10, 11) The clinical presentation of HIV related diseases may be modified by HAART, which has dramatically improved the prognosis of HIV infection. Before the introduction of HAART, patients with cytomegalovirus retinitis commonly had CD4+ counts less than 50 cells/l with minimal ocular inflammation.(9) There are some reports of spontaneous resolution of cytomegalovirus retinitis in patients with increased CD4+ counts related to such therapy, although the recovery in T lymphocytes may take many months.(12, 13, 14) Nevertheless, substantial intraocular inflammation in patients with healed cytomegalovirus retinitis receiving HAART has been reported, which is known as immune recovery uveitis.(9,105)

topDiscussion

II Orbital Manifestations

Orbital manifestations of HIV infection are not seen very often. However, some cases of orbital cellulitis and orbital lymphoma have been reported. The cases of orbital cellulitis were related to Aspergillus infection most times, being treated with systemic antimicrobial drugs. Other organisms reported in the literature that caused orbital infections in patients with HIV include Rhizopus arrhizus, Toxoplasma gondii, and Pneumocystis carinii. Children may present with recurrent episodes of orbital/peri-orbital cellulitis.(15, 16) Primary non-Hodgkin`s lymphoma (NHL) of the orbit and ocular adnexa is a rare disease. It accounts for only 1% of all NHL. In general, the risk of developing NHL is higher in HIV infected patients. The reported cases of lymphoma responded well to radiotherapy. However, high doses may be correlated to late ocular complications.(17, 18)

III Adnexal Manifestations

The most common adnexal manifestations in patients who have HIV infection are Kaposi`s sarcoma, herpes zoster ophthalmicus, moluscum contagiosum and conjunctival microvasculopathy.(19) Conjunctival squamous-cell carcinoma is a rare finding.

Kaposi`s Sarcoma

Kaposi`s sarcoma was a rare tumor. After the spread of HIV, the incidence markedly increased. It is a highly vascularized, painless mesenchymal tumor that affects the skin and mucous membranes and occurs in up to 25% of HIV infected patients. Around 20% of these patients have asymptomatic Kaposi`s sarcoma of the eyelids, conjunctiva and rarely the orbit.(7, 20)However, a study by Biswas et al., who followed 100 HIV positive individuals in India, did not observe a single case of Kaposi`s sarcoma of the eye. The low prevalence of this tumor in India may be attributed to the lower proportion of cases associated with homosexual behavior in that country. DNA sequences of human herpes virus 8 have been detected in patients with Kaposi`s sarcoma either with or without HIV infection. The low incidence of human herpes virus 8 in India may also contribute to the low occurrence of this tumor in that country.(3, 21)Kaposi`s sarcoma may present as purple papules in the eyelids, which may be either flat or slightly raised. Sometimes, these lesions are part of a multifocal presentation, which may include visceral involvement.(5, 22)Conjunctival Kaposi`s sarcoma may occur in up to 1% of patients with HIV infection. The classic presentation is a reddish plaque that may mimic a subconjunctival hemorrhage or chalazion. This lesion is often located in the cul de sac. Even small lesions can cause important cosmetic and functional discomfort, which may be related to mass effect or secondary corneal changes.(5, 23)Kaposi`s sarcoma does not invade the eye. Most lesions are slowly progressive and respond to systemic drug therapy (106). Radiation therapy may be effective when functional discomfort is reported. Nevertheless, it is expensive and can cause skin irritation and conjunctivitis. Doses of 20 Gy may be sufficient to produce shrinkage of the tumor. Excision and intralesional chemotherapy with vinblastine are other treatment options. If there is systemic involvement, systemic chemotherapy may be indicated.(7, 23)There are some reports of regression in patients treated with HAART containing a protease-inhibitor. Saquinavir, indinavir, ritonavir and nelfinavir may affect angiogenesis, cell survival, tumor growth and invasion.(24)

Herpes Zoster Ophthalmicus

Reactivation of latent varicella zoster virus in the ophthalmic division of the trigeminal nerve causes herpes zoster ophthalmicus. The ophthalmic division branches into the lacrimal, nasociliary and frontal nerves. Involvement of the frontal nerve is common. When the nasociliary nerve is affected, the patients may present with vesicles at the tip of the nose, known as Hutchinson`s sign. Studies have shown ophthalmic involvement in 99% of patients with this sign.(25) Herpes zoster occurs in patients with HIV infection as well as other patients with depressed cellular immunity such as lymphoma patients and patients receiving immunosuppressive therapy. Characteristic prodromal symptoms include headache, generalized malaise and fever.(26)In younger individuals, it may be the initial manifestation of HIV infection.(27) Any patient younger than 50 years of age who presents with herpes zoster ophthalmicus is suspect of having HIV infection or any other immunosuppressive condition.(5, 28) A study by Hodge et al. showed a relative incidence risk ratio of 6.6/1 in HIV positive patients compared to HIV negative patients.(29) Reports suggest that it affects 515% of HIV positive patients and may have a high rate of painful and sight threatening complications.(7, 27) Forty one percent of the patients studied by Lewallen in Malawi developed corneal perforation and seventeen percent of the patients stu