Part 4 • Infectious Uveitic Conditions

Chapter 11 Acquired Immunodeficiency Syndrome

Figure 11-6.  Dense vitritis in a patient with immune-recovery uveitis in the eye with inactive CMV retinitis.

Figure 11-7.  Cystoid macular edema in a patient with immune recovery uveitis and inactive CMV retinitis.

vitritis;74 however, because the inflammation is characterized not only by a profound vitritis (Fig. 11-6) but also by anterior uveitis, cataract, macular edema (Fig. 11-7), epiretinal membranes, and optic disc edema, we referred to these findings as immune recovery uveitis (IRU).39,75,76 In a prospective clinical trial in which specific anti-CMV therapy was discontinued in 14 patients with stable CMV retinitis and HIV infection during HAART, 12 (89.7%) of the 14 patients had IRU before they stopped their CMV therapy.39 Three of these 12 patients had a profound increase in IRU during the course of the trial. Other investigators have reported high rates of IRU in patients with stable CMV retinitis receiving HAART;77 however, there is large variability in the prevalence of this finding. High rates of IRU may be related to better immune responses in these patients due to strict compliance with aggressive HAART. The median CD4+ count at baseline in the study detailed above was >300 cells/ L. The amount of CMV antigen in the eye may also affect the development of IRU. The incidence of IRU may be lower in patients with CMV retinitis who have not received HAART before the control of retinal disease with anti-CMV therapy.78

Interestingly, in our prospective study of patients with CMV retinitis receiving HAART, no new retinal detachments occurred during the study.39 This is surprising because the risk of retinal detachment in a similar population before the

use of HAART was 19% at 6 months.79 Intraocular inflammation and hypertrophy of the retinal pigment epithelium may lead to increased adherence of the retina and a reduced risk of retinal detachment.

Immune recovery uveitis may require treatment. Although the best therapy is unknown, we have treated anterior uveitis with topical prednisolone acetate. In addition, we have used periocular injections of triamcinolone or short courses of prednisone to treat vitritis and macular edema associated with decreased visual acuity. More recently, intravitreal triamcinolone has been used to treat macular edema associated with IRU.80 The exact mechanism of immune recovery uveitis has not been elucidated. It does not occur in eyes without CMV retinitis; therefore, the inflammation appears to be related to the infection, but it is unclear whether IRU is related partly to subclinical viral replication in the eye. If this were true, therapy with specific anti-CMV therapy might limit the uveitis, but this has yet to be demonstrated. In any event, the severity of IRU appears to be related to the amount of infected retina. In our experience, eyes without IRU had very small areas of retinitis. This could be related either to the amount of CMV antigen in the eye or to the degree of the breakdown in the blood–retinal barrier as a result of the retinal necrosis. Finally, the type of anti-CMV therapy could also affect the amount of retinal involvement and CMV antigen in the eye. More effective treatment may reduce CMV involvement of the retina and limit the development of IRU.

Other inflammatory diseases have developed after immune recovery in patients receiving HAART. Patients with subclinical Mycobacterium avium complex infection develop fever, leukocytosis, and lymphadenitis after the initiation of HAART.81 Meningitis has been reported in patients with latent cryptococcal central nervous system infection after initiation of HAART.82 In developing countries tuberculosis is commonly noted after starting HAART, and is one of the major opportunistic infections seen in many parts of the world.

Herpes zoster

Herpes zoster ophthalmicus occurs more frequently in HIVpositive patients and may often be the presenting sign of the disease. Cutaneous zoster occurring in a severely immunosuppressed patient with AIDS is more likely to disseminate and may be more difficult to treat with aciclovir compared to its effectiveness in the immunocompetent patient. Intravenously administered aciclovir sometimes is required for cutaneous dermatomal zoster, and is certainly needed for disseminated zoster.

Varicella-zoster virus (VZV) retinitis in the HIV-positive patient has a somewhat more varied clinical spectrum than that seen in immunocompetent patients. Although the clinical picture in some patients is identical to that of acute retinal necrosis, other clinical appearances have been described. In one study 17% of HIV-positive patients with herpes zoster ophthalmicus subsequently developed acute retinal necrosis.83 A form of retinitis termed progressive outer retinal necrosis (PORN) appears as multifocal areas of retinitis with good preservation of the inner retina and retinal vasculature in the early clinical stages84 (discussed in detail in Chapter 12). The areas of necrosis occasionally

appear similar to those in acute retinal necrosis. In progressive outer retinal necrosis the lesions are small, often multifocal, and consist of multiple punctate white retinal dots located in the outer retina (see Fig. 12-6). Still other patients may initially manifest multiple retinal vascular occlusions with areas of retinitis (see Fig. 12-5).

The response to systemic aciclovir in these immunosuppressed patients is inconsistent. Approximately half have a good response to intravenous aciclovir followed by oral aciclovir, with resultant quieting of the retinitis. Some of these patients can be weaned from the oral drug, but others have recurrences without maintenance therapy.85 In contrast, other patients have progressive retinitis despite treatment with intravenous aciclovir. Also, because of the rapid progression of PORN and the difficulty of making a definitive diagnosis, many clinicians start therapy with aciclovir and foscarnet to cover CMV retinitis and provide ‘double coverage’ for the PORN. A combination of intravitreal and intravenous antiviral therapy has also been used to treat the disease.86 Despite therapy the disease can be relentlessly progressive, and severe visual disability can result. The risk of retinal detachment appears similar for immunosuppressed and immunocompetent patients with VZV retinitis, and repair techniques are similar. With HAART, once the CD4+ T cell counts rise, antiviral therapy for zoster may be discontinued in some patients.

The major differential diagnosis in the HIV-positive patient is between CMV and VZV retinitis. This differentiation is important because aciclovir is considerably less toxic than either ganciclovir or foscarnet. CMV retinitis is at least 20 times more common than VZV retinitis, and the differential diagnosis is based primarily on clinical criteria, taking into account the rate of progression and the multifocality.

Pneumocystis jirovecii choroiditis

Pneumocystis carinii choroiditis was first reported by Macher et al.87 Since that time it has been renamed Pneumocystis jirovecii and classified as a fungus. The choroiditis is characterized by multifocal white plaques in the choroid with little evidence of intraocular inflammation (Fig. 11-8).88 It is an extrapulmonary form of pneumocystic disease usually seen in patients using a prophylactic inhalant for this condition, which prevents pulmonary involvement but does not provide systemic prophylaxis. This has become a less common problem as the use of aerosolized pentamidine has decreased. Histopathologic examination in these patients shows numerous cysts in the choroid (Fig. 11-9).

The lesions rarely cause visual loss because they are located beneath the retinal pigment epithelium (RPE) and have no associated inflammation. Trimethoprimsulfamethoxazole is usually the first choice for therapy. Alternative therapy includes dapsone, aerosolized pentamidine, and atovaquone. Histologic examination has demonstrated large numbers of cysts with no host response. It is important to identify this disease so that the internist can be aware of the potential for extrapulmonary pneumocystic involvement. The ocular disease is associated with prophylactic aerosolized pentamidine and appears to be less common as aerosolized pentamidine use has decreased.

Other diseases

Figure 11-8.  Fundus photograph of patient with AIDS and Pneumocystis carinii pneumonia shows multiple yellow deep choroidal lesions. Histopathologic examination revealed not only P. carinii cysts but also cytomegalovirus (see Fig. 11-9) and Mycobacterium avium-intracellulare (see Fig. 11-10). (From Whitcup SM, Fenton RM, Pluda JM, et al. Pneumocystis carinii and Mycobacterium avium-intracellulare infection of the choroid. Retina 1992; 12: 331–5.)

Figure 11-9.  Photomicrograph of choroidal lesion in the right eye showing numerous Pneumocystis carinii cysts (white arrowheads) and cytomegalovirus cells in choroidal blood vessel (arrows). (Gomori’s methenamine silver stain; ×400.) (From Whitcup SM, Fenton RM, Pluda JM, et al.

Pneumocystis carinii and Mycobacterium avium-intracellulare infection of the choroid. Retina 1992; 12: 331–5.)

Mycobacterium avium-intracellulare choroiditis

M. avium-intracellulare manifests as infiltrates, usually 50– 100 m in size and scattered throughout the fundus.89,90 It usually causes no visual symptoms, but, as in the case of pneumocystic disease, is evidence of disseminated systemic infection. M. avium-intracellulare is a common pathogen in patients with AIDS which often involves the bone marrow and leads to marrow failure.

Other diseases

Multiple infections in a single eye may be present in patients with AIDS. Choroidal lesions such as those caused by Pneumocystis can be seen concurrently with infections from other organisms such as CMV and M. avium-intracellulare

171

Figure 11-10.  Photomicrograph of choroid adjacent to area infiltrated with Pneumocystis carinii shows cluster of acid-fast bacilli (arrow). (Ziehl-Neelsen stain; ×100.) (From Whitcup SM, Fenton RM, Pluda JM, et al. Pneumocystis carinii and Mycobacterium avium-intracellulare infection of the choroid. Retina 1992; 12: 331–5.)

Figure 11-11.  Photographic montage of patient with didanosine-related retinal lesions. Atrophic areas of RPE hypopigmentation and hyperpigmentation are seen in the midperiphery of the fundus.

(Figs 11-9 and 11-10), but the greatest concern is a CMV infection combined with herpes zoster or herpes simplex. In this situation the retinitis response can be atypical, and if the zoster infection is treated with aciclovir the CMV infection will continue to progress. Toxoplasmosis, which is discussed in Chapter 14, is also seen as a retinal infection with a vitritis and should be managed with an antitoxoplasmosis regimen.90 In addition, B-cell lymphoma can occur in AIDS, manifesting as choroidal, retinal, or vitreous lesions.91 A posterior ocular process that fails to respond to the therapy chosen on the basis of the clinical presentation may require a biopsy to ascertain the presence of lymphoma. Finally, syphilis is becoming increasingly common in HIV-infected patients and is discussed in detail in Chapter 10.92

Drug-related ocular inflammation

Several reports have identified both anterior and posterior uveitis in patients treated with rifabutin.93 These inflammatory findings can occur months after the initiation of therapy. Rifabutin is used to treat M. avium-intracellulare infection. A severe uveitis that is often bilateral can result. The uveitis associated with rifabutin is most commonly seen in persons also receiving fluconazole or a macrolide drug, which raises serum levels of rifabutin. The inflammation responds to appropriate steroid therapy or to a reduction in the rifabutin dosage. The mechanism of this inflammation is unclear and may be either direct drug hypersensitivity or a response to mycobacterial death, with a subsequent inflammatory response. In addition, we have described retinal lesions in patients treated with the antiretroviral agent didanosine that appear to predominantly involve the RPE (Fig. 11-11).94 Uveitis has been reported in about one of four patients treated with fomivirsen. This uveitis appears to respond to topical corticosteroids. RPE changes have also been reported with fomivirsen.

Remarkable progress has been made in the treatment of HIV infection and the associated opportunistic infections, but of course we have far to go before we can claim victory over this disease. Nevertheless, there has been a dramatic change in the presentation and course of many of the

ophthalmic manifestations of HIV infection, particularly CMV retinitis. Case 11-1 describes a typical case of CMV retinitis before HAART. Case 11-2 demonstrates the differences in the course of the disease after HAART.

Case 11-1

A 42-year-old man with a diagnosis of AIDS reported a 2-week history of reduced vision in the right eye. He had no light perception in this eye and 20/20 visual acuity in the left eye. The right eye contained 1+ vitreous cells and had a significant area of necrotic retinitis involving the optic disc. Blood cultures were positive for cytomegalovirus. The left eye had a small white infiltrate with an associated hemorrhage near the superior vascular arcade.

Over the next few weeks the area of involvement in the left eye increased in size. Treatment with ganciclovir was begun, with a marked improvement of the retinitis in both eyes.

Vision did not return in the right eye. Ganciclovir therapy was discontinued after 3 weeks, and the vision in the left eye remained 20/20 for 2 weeks. It then decreased to 20/300 because of macular edema. The area of necrotic retinitis was larger. A second course of ganciclovir was begun, and the retinitis again resolved and the vision returned to 20/25. Maintenance therapy was begun, but because of neutropenia the patient could not tolerate a dose of 5 mg/kg 5 days/ week. He lost all vision in the left eye approximately 2 months later and died several weeks after that.

Case 11-2

AIDS was diagnosed in a 37-year-old man who had a CD4+ cell count of 5/ L. A routine ophthalmologic examination revealed active CMV retinitis in both eyes. Highly active antiretroviral therapy was begun. The CMV

retinitis was initially treated with intravenous ganciclovir, but the therapy was changed to intravenous foscarnet because of leukopenia.

The HIV load decreased to an undetectable level and the CMV retinitis remained quiescent with foscarnet therapy. On examination, visual acuity was 20/25 in the right eye and 20/40 in the left. Slit-lamp biomicroscopy revealed anterior chamber cells and flare and moderate vitritis in both eyes. Retinal examination revealed stable CMV retinitis involving the midperipheral retina bilaterally. Slight macular edema was noted, which was worse in the left eye. The CD4+ cell

References

count increased and anti-CMV therapy was stopped. The CMV retinitis remained inactive when anticytomegalovirus therapy was stopped; however, over the next year vitritis and macular edema in both eyes worsened, with visual acuity dropping to 20/40 in the right eye and 20/63 in the left. The patient was offered treatment with periocular or systemic corticosteroids, but refused antiinflammatory drug therapy.

1.Achega JB, Hislop M, Dowdy DW, et al. Adherence to nonnucleoside reverse transcriptase inhibitor-based HIV therapy and virologic outcomes.

Ann Intern Med 2007; 146: 564–573.

2.Gallo R. The AIDS virus. Sci Am 1987;

256:46–56.

3.The global HIV and AIDS epidemic, 2001. MMWR Morb Mortal Wkly Rep 2001; 50: 434–439.

4.Hall HI, Song R, Rhodes P, et al. Estimation of HIV incidence in the United States. JAMA 2008; 300: 520–529.

5.Curran JW, Morgan WM, Hardy AM, et al. The epidemiology of AIDS: current status and future prospects. Science 1985; 229: 1352–1357.

6.Layon J, Warzynski M, Idus R. Acquired immunodeficiency syndrome in the United States – a selective review. Crit Care Med 1986; 14: 819–827.

7.Salahuddin SZ, Palestine AG, Heck E, et al. Isolation of the human T-cell leukemia/lymphotropic virus type III from the cornea. Am J Ophthalmol 1986; 101: 149–152.

8.Pomerantz RJ, Kuritzkes DR, de la Monte SM, et al. Infection of the retina by human immunodeficiency virus type I. N Engl J Med 1987; 317: 1643–1647.

9.Mellors JW, Munoz A, Giorgi JV, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 1997;

126:946–954.

10.Hanna GJ, Hirsch MS. Antiretroviral therapy of human immunodeficiency virus infection. In Mandell GL, Bennett JE, Dolin R, editors: Principles and Practice of Infectious Diseases,

ed 6, Philadelphia, 2005, Elsevier, pp 1655–1678.

11.Palestine AG, Rodrigues MM, Macher AM, et al. Ophthalmic involvement in the acquired immune deficiency syndrome. Ophthalmology 1984; 91: 1092–1099.

12.Freeman WR, Lerner CW, Mines JA, et al. A prospective study of the ophthalmologic findings in the

acquired immune deficiency syndrome. Am J Ophthalmol 1984; 97: 133–142.

13.Newsome DA, Green WR, Miller ED, et al. Microvascular aspects of acquired immune deficiency syndrome retinopathy, Am J Ophthalmol 1984;

98:590–601.

14.Kestelyn P, Van de Perre P, Rouvroy D, et al. A prospective study of the ophthalmologic findings in the acquired immune deficiency syndrome in Africa. Am J Ophthalmol 1985; 100: 230–238.

15.Pepose JS, Holland GN, Nestor MS, et al. Acquired immune deficiency syndrome: pathogenic mechanisms of ocular disease. Ophthalmology 1985;

92:474–484.

16.Meillet D, Hoang PL, Unanue F, et al. Filtration and local synthesis of lacrimal proteins in acquired immunodeficiency syndrome. Eur J Clin Chem Clin Biochem 1992; 30: 319–323.

17.Belfort R Jr, de Smet M, Whitcup SM, et al. Ocular complications of Stevens–Johnson syndrome and toxic epidermal necrolysis in patients with AIDS. Cornea 1991; 10: 536–538.

18.Freeman WR, Van Natta ML, Jabs D, et al. Vision function in HIV-infected individuals without retinitis: report of

the Studies of Ocular Complications of AIDS Research Group. Am J Ophthalmol 2008; 145: 453–462.

19.Schuman JS, Friedman AH. Retinal manifestations of the acquired immune deficiency syndrome. Trans Ophthalmol Soc UK 1983; 103: 177– 189.

20.Weiss A, Margo CE, Ledford DK, et al. Toxoplasmic retinochoroiditis as an initial manifestation of the acquired immune deficiency syndrome. Am J Ophthalmol 1986; 101: 248–249.

21.Stoumbos VD, Klein ML. Syphilitic retinitis in a patient with acquired immunodeficiency syndrome-related complex. Am J Ophthalmol 1987; 103: 103–104.

22.Croxatto JO, Mestre C, Puente S, et al. Nonreactive tuberculosis in a patient with acquired immune deficiency syndrome. Am J Ophthalmol 1986;

102:659–660.

23.Macher A, Rodrigue MM, Kaplan W, et al. Disseminated bilateral chorioretinitis due to Histoplasma capsulatum in a patient with the acquired immunodeficiency syndrome. Ophthalmology 1985; 92: 1159–1164.

24.Sandor EV, Millman A, Croxson TS, et al. Herpes zoster ophthalmicus in patients at risk for the acquired immune deficiency syndrome (AIDS). Am J Ophthalmol 1986; 101: 153– 155.

25.Egbert PR, Pollard RB, Gallagher JG, et al. Cytomegalovirus retinitis in immunosuppressed hosts. II. Ocular manifestations. Ann Intern Med 1980;

93:664–670.

26.Kupperman BD, Petty JG, Richman DD, et al. Correlation between CD4+ counts and the prevalence of cytomegalovirus retinitis and human immunodeficiency virus-related noninfectious retinal vasculopathy in patients with acquired immunodeficiency syndrome. Am J Ophthalmol 1993; 115: 575–582.

27.Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group. Mortality in patients with the acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. N Engl J Med 1992; 326: 213–220.

28.Jacobson MA, O’Donnell JJ, Porteous D, et al. Retinal and gastrointestinal disease due to cytomegalovirus in patients with the acquired immune deficiency syndrome: prevalence, natural history, and response to ganciclovir therapy. QJ Med 1988; 67: 473–486.

29.Lalezari JP, Stagg RJ, Kuppermann BD, et al. Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS: a randomized, controlled trial. Ann Intern Med 1997;

126:257–263.

30.Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group. Parenteral cidofovir for cytomegalovirus retinitis in patients with AIDS: the HPMPC peripheral cytomegalovirus retinitis trial: a randomized, controlled trial. Ann Intern Med 1997; 126: 264–274.

31.Martin DF, Parks DJ, Mellow SD, et al. Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant. A randomized controlled clinical trial. Arch Ophthalmol 1994; 112: 1531–1539.

32.Cavert W, Notermans DW, Staskus K, et al. Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1 infection. Science 1997; 276: 960–963.

33.Perelson AS, Essunger P, Cao Y, et al. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature 1997; 387: 188–191.

immunodeficiency syndrome. Am J Ophthalmol 1995; 119: 466–476.

59.Kirsch L, Arevalo JF, Chavez de la Pax E, et al. Intravitreal cidofovir (HPMPC) treatment of cytomegalovirus retinitis in patients with acquired immune deficiency syndrome. Ophthalmology 1995; 102: 533–543.

60.Paya C, Humar A, Dominguez E, et al. Valganciclovir Solid Organ Transplant Study Group. Efficacy and safety of valganciclovir vs. oral ganciclovir

for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 2004; 4: 611–620.

61.Martin DF, Sierra-Madero J, Walmsley S, et al. A controlled trial of valganciclovir as induction therapy for cytomegalovirus retinitis. N Engl J Med 2002; 346: 1119–1126.

62.Jabs DA. AIDS and Ophthalmology, 2008. Arch Ophthalmol 2008; 126: 113–1146.

63.Feinberg MB, Carpenter C, Fauci AS,

et al. Report of the NIH panel to define principles of therapy of HIV infection. Ann Intern Med 1998; 128: 1057– 1078.

64.Centers for Disease Control and Prevention. 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. MMWR Morb Mortal Wkly Rep 1999; 48: 1–66.

65.Drew WL, Ives D, Lalezari JP, et al. Oral ganciclovir as maintenance treatment for cytomegalovirus retinitis in patients with AIDS, N Engl J Med 1995; 333: 615–620.

66.Martin DF, Sierra-Madero J, Walmsley S, et al. A controlled trial of valganciclovir as induction therapy for cytomegalovirus retinitis. N Engl J Med 2002; 346: 1119–1126.

67.Freeman WR, Friedberg DN, Berry C, et al. Risk factors for the development of rhegmatogenous retinal detachment in patients with cytomegalovirus retinitis. Am J Ophthalmol 1993; 116: 713–720.

68.Thorne JE, Jabs DA, Kempen JH, et al. Incidence of and risk factors for visual acuity loss among patients with AIDS and cytomegalovirus retinitis in the era of highly active antiretrovial therapy. Ophthlamology 2006; 113: 1001– 1008.

69.Palestine AG, Rodrigues MM, Macher AM, et al. Ophthalmic involvement in acquired immunodeficiency syndrome. Ophthalmology 1984; 91: 1092–1099.

70.Jabs DA, Bartlett JG. AIDS and ophthalmology: a period of transition. Am J Ophthalmol 1997; 124: 227– 233.

71.Zegans ME, Walton RC, Holland GN, et al. Transient vitreous inflammatory reactions associated with combination antiretroviral therapy in patients with AIDS and cytomegalovirus retinitis. Am J Ophthalmol 1998; 125: 292–300.

72.Karavellas MP, Lowder CY, Macdonald JC, et al. Immune recovery vitritis

associated with inactive cytomegalovirus retinitis: a new syndrome. Arch Ophthalmol 1998;

116:169–175.

73.Weinberg DV, Moorthy RS. Cystoid macular edema due to cytomegalovirus in a patient with acquired immunodeficiency virus. Retina 1996;

16:1443–1445.

74.Zegans ME, Walton RC, Holland GN, et al. Transient vitreous inflammatory reactions associated with combination antiretroviral therapy in patients with AIDS and cytomegalovirus retinitis. Am J Ophthalmol 1998; 125: 292–300.

75.Whitcup SM. Cytomegalovirus retinitis in the era of highly active antiretroviral therapy. JAMA 2000; 283: 653–657.

76.Robinson MR, Reed G, Csaky KG, et al. Immune-recovery uveitis in patients with cytomegalovirus retinitis taking highly active antiretroviral therapy. Am J Ophthalmol 2000; 130: 49–56.

77.Karavellas MP, Plummer DJ, Macdonald JC, et al. Incidence of immune recovery vitritis in cytomegalovirus retinitis in patients following institution of successful highly active antiretroviral therapy. J Infect Dis 1999; 179: 697–700.

78.Ortega-Larrocea G, Espinosa E, Reyes-Teran G. Lower incidence and severity of cytomegalovirus-associated immune recovery uveitis in HIVinfected patients with delayed highly active antiretroviral therapy. Ophthalmology 2006; 19: 735–738.

79.The Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group. Rhegmatogenous retinal detachment in patients with cytomegalovirus retinitis: the FoscarnetGanciclovir Cytomegalovirus Retinitis

Trial. Am J Ophthalmol 1997; 121: 61–70.

80.Morrison VL, Kozak I, LaBree LD, et al. Intravitreal triamcinolone acetonide for the treatment of immune recovery uveitis macular edema. Ophthamology 2007; 114: 334–339.

81.Race EM, Adelson-Mitty J, Kriegel GR, et al. Focal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease. Lancet 1998; 351: 252–255.

82.Woods ML, MacGinley R, Eisen DP,

et al. HIV combination therapy: partial immune restitution unmasking latent cryptococcal infection. AIDS 1998; 12: 1491–1494.

83.Sellitti TP, Huang AJ, Schiffman J, et al. Association of herpes zoster ophthalmicus with the acquired immunodeficiency syndrome and acute retinal necrosis. Am J Ophthalmol 1992; 116: 297–301.

84.Forster DJ, Dugel PU, Frangieh GT, et al. Rapidly progressive outer retinal necrosis in the acquired immunodeficiency syndrome. Am J Ophthalmol 1990; 110: 341–348.

85.Johnston WH, Holland GN, Engstrom RE, et al. Recurrence of presumed varicella zoster virus retinopathy in patients with the acquired immunodeficiency syndrome. Am J Ophthalmol 1993; 116: 42–50.

86.Yin PD, Kurup SK, Fischer SH, et al. Progressive outer retinal necrosis in the era of highly active antiretroviral therapy: successful management with intravitreal injections and monitoring with quantitative PCR. J Clin Virol 2007; 38: 254–259.

87.Macher AM, Bardenstein DS, Zimmerman LE, et al. Pneumocystis

References

carinii choroiditis in a male homosexual with AIDS and disseminated pulmonary and extrapulmonary P. carinii infection. N Engl J Med 1987; 316: 1092.

88.Sha BE, Benson CA, Deutsch T, et al.

Pneumocystis carinii choroiditis in patients with AIDS: clinical features, response to therapy and outcome.

J AIDS 1992; 5: 1051–1058.

89.Whitcup SM, Fenton RM, Pluda JM, et al. Pneumocystis carinii and Mycobacterium avium-intracellulare infection of the choroid. Retina 1992;

12:331–335.

90.Morinelli EN, Dugel PU, Riffenburgh R, et al. Infectious multifocal choroiditis in patients with acquired immune deficiency syndrome. Ophthalmology 1993; 100: 1014–1021.

91.Stanton CA, Sloan B III, Slusher MM, et al. Acquired immunodeficiency syndrome-related primary intraocular lymphoma. Arch Ophthalmol 1992;

110:1614–1617.

92.Johns DR, Tierney M, Felsenstein D. Alteration in the natural history of neurosyphilis by concurrent infection with the human immunodeficiency virus. N Engl J Med 1987; 316: 1569–1572.

93.Shafran SD, Deschenes J, Miller M, et al. Uveitis and pseudojaundice during a regimen of clarithromycin, rifabutin and ethambutol. N Engl J Med 1994; 330: 438–439.

94.Whitcup SM, Butler KM, Caruso R, et al. Retinal toxicity in human immunodeficiency virus-infected

children treated with 2´,3´-dideoxyinosine. Am J Ophthalmol 1992; 113: 1–7.