Immunologic Research

, 11:141 | Cite as

Ocular tissue involvement in HIV infection: Immunological and pathological aspects

  • Kenneth E. Ugen
  • Daniel E. McCallus
  • Joan M. Von Feldt
  • William V. Williams
  • Mark I. Greene
  • David B. Weiner
Ocular HIV Infection


The CNS afflictions in AIDS are myriad and suggest a tropism of HIV to neural tissue. Ocular involvement is a frequent manifestation of the HIV infection, resulting in a high incidence of blindness within this patient population. Ocular lesions include cotton wool spots, presumably from HIV-induced microvasculopathy, retinal hemorrhage in cytomegalovirus retinitis and conjunctival Kaposi's sarcoma. These manifestations have been noted in up to 71% of AIDS patients. In fact, ocular disease is often the presenting symptom in an HIV-infected individual. Despite the high incidence of ocular involvement in AIDS patients, the etiology and pathogenesis of these manifestations are not well understood. The immunosuppressive action of HIV is the most likely primary cause for the development of ocular complications in AIDS. Here we review some of the important immunological and pathological features of AIDS affliction in the eye.

Key Words

AIDS Conjunctivitis Cotton wool spots Cytomegalovirus retinopathy Herpes zoster ophthalmicus HIV HHV-6 Kaposi's sarcoma Toxoplasmosis Zidovudine 


  1. 1.
    Gallo RC, Salahuddin SZ, Popovic M: Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 1984;224:497–500.PubMedCrossRefGoogle Scholar
  2. 2.
    Groopman JE, Salahuddin SZ, Sarngadharan MG: HTLV-III in saliva of people with AID-related complex and healthy homosexual men at risk for AIDS. Science 1984; 226:447–449.PubMedCrossRefGoogle Scholar
  3. 3.
    Lane HC, Depper JM, Green WC: Qualitative analysis of immune function in patients with the acquired immune deficiency syndrome: Evidence for a selective defect in soluble antigen recognition. N Engl J Med 1985;313:79–84.PubMedGoogle Scholar
  4. 4.
    Ammann AJ, Abrams D, Conant M: Acquired immune dysfunction in homoxesual men: Immunologic profile. Clin Immunol Immunopathol 1983;27:315–325.PubMedCrossRefGoogle Scholar
  5. 5.
    CDC: Revision of the case definition of acquired immune deficiency syndrome for national reporting—United States. MMWR CDC Surveill Summ 1985;34:373–375.Google Scholar
  6. 6.
    Palestine AG, Rodriques MM, Macher AM, Chan CC, Lane HC, Fauci AS, Masur H, Longo D, Reichert CM, Steis R, Rook AH, Nussenblatt RB: Ophthalmic involvement in acquired immune deficiency syndrome. Ophthalmology 1984;91:1092–1099.PubMedGoogle Scholar
  7. 7.
    Pepose JS, Holland GN, Nestor MS, Cochran AJ, Foos RY: Acquired immune deficiency syndrome: Pathogenic mechanism of ocular disease. Ophthalmology 1985;92:472–484.PubMedGoogle Scholar
  8. 8.
    Mines JA, Kaplan HJ: Acquired immunodeficiency syndrome (AIDS): The disease and its ocular manifestations. Int Ophthalmol Clin 1986; 26:73–115.PubMedCrossRefGoogle Scholar
  9. 9.
    Newsome DA: Noninfectious ocular complications of AIDS. Int Ophthalmol Clin 1989;29:95–97.PubMedCrossRefGoogle Scholar
  10. 10.
    Dalgleish A, Beverley P, Clapham P, Crawford D, Greaves M, Weiss R: The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 1984;312: 763–773.PubMedCrossRefGoogle Scholar
  11. 11.
    Klatzmann D, Champagne E, Chamoret S, Cruest J, Guetard D, Hercend T, Gluckman JC, Montagnier L: T-lymphocyte T4 molecule behaves as receptor for human retroviruses LAV. Nature 1984;312:767–768.PubMedCrossRefGoogle Scholar
  12. 12.
    Sattentau QJ, Weiss RA: The CD4 antigen: Physiological ligand and HIV receptor. Cell 1988;52:631–633.PubMedCrossRefGoogle Scholar
  13. 13.
    Maddon P, Dalgleish A, McDougal J, Chapham P, Weiss R, Axel R: The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell 1986;47:333–348.PubMedCrossRefGoogle Scholar
  14. 14.
    Peterlin BM, Luciw PA: Molecular biology of HIV AIDS 2;1988:S29-S40.PubMedCrossRefGoogle Scholar
  15. 15.
    Muesing M, Smith D, Cabradilla C Benton C, Lasky L, Capon D: Nucleic acid structure and expression of the human AIDS retrovirus. Nature 1985;313:450–458.PubMedCrossRefGoogle Scholar
  16. 16.
    Ratner L, Haseltine WA, Patarca R, Livak J, Starach B, Josephs SF, Doran ER, Rarlaski JA, Whitehorn EA, Baumeister K, Ivanoff L, Petteway SR, Jr, Pearson ML, Lautenberger JA, Papas TS, Ghrayeb J, Chang NT, Gallo RC, Wong-Stall F: Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature 1985;313:277–284.PubMedCrossRefGoogle Scholar
  17. 17.
    Sanchez-Pescador R, Power MD, Barr PJ, Steimer KS, Stempien MM, Brown-Shimer SL, Gee WW, Renard A, Randolph A, Levy J, Dina D, Luciw PA: Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). Science 1985; 227:484–492.PubMedCrossRefGoogle Scholar
  18. 18.
    Carlson JR, Bryant MI, Hinrichs SH: AIDS serology testing in low and high risk groups. JAMA 1985; 253:3405–3408.PubMedCrossRefGoogle Scholar
  19. 19.
    Zagany D, Bernard J, Leibowitch J: HTLV-III in cells cultured from semen of two patients with AIDS. Science 1984;226:449–451.CrossRefGoogle Scholar
  20. 20.
    Ho DD, Schooley RT, Rota TR: HTLV III in the semen and blood of a healthy homosexual man. Science 226:1984;451–453.PubMedCrossRefGoogle Scholar
  21. 21.
    Salahuddin SZ, Markham PD, Popovic M: Isolation of infectious human T cell leukemia/lymphotrophic virus type III (HTLV-III) from patiens with acquired immune deficiency syndrome (AIDS) or AIDS related complex (ARC) and from healthy carriers. A study of risk groups and tissue sources. Proc Natl Acad Sci (USA) 1985;82:5530–5534.CrossRefGoogle Scholar
  22. 22.
    Levy J, Kaminsky L, Morrow W, Steimer K, Luciw P, Dina D, Hoxie J, Oshiro L: Infection by the retrovirus associated with acquired immune deficiency syndrome. Ann Intern Med 1985;103:694–699.PubMedGoogle Scholar
  23. 23.
    Levy J, Shimabrikaro J, Hollander H, Mills J, Kaminsky L: Isolation of AIDS-associated retroviruses (ARV) from cerebrospinal fluid and brain from patients with neurological findings. Lancet 1985;i:586–588.Google Scholar
  24. 24.
    Wofsky C, Cohen J, Hauer L, Padier N, Michaelis B, Evans L, Levy J: Isolation of the AIDS-associated retroviruses from vaginal and cervical secretions from women with antibodies to the virus. Lancet 1986;i: 527–529.CrossRefGoogle Scholar
  25. 25.
    Fujikawa LS, Salahuddin SZ, Ablashi D: HTLV-III in the tears of AIDS patients. Ophthalmology 1986;93:1479–1481.PubMedGoogle Scholar
  26. 26.
    Fujikawa LS, Salahuddin SZ, Ablashi D: Human T cell leukemia/lymphotrophic virus type III in the conjunctival epithelium of a patient with AIDS. Am J Ophthalmol 1985; 100:507–509.PubMedGoogle Scholar
  27. 27.
    Snider WD, Simpson DM, Nielsen SL, Gold JWM, Metroka CE, Posner JB: Neurological complications of acquired immune deficiency syndrome: Analysis of 50 patients. Ann Neurol 1983;14:403–418.PubMedCrossRefGoogle Scholar
  28. 28.
    Koenig S, Gendelman HE, Orenstein JM, Dal Canto MC, Pezeshkpour GH, Yungbluth M, Janotta F, Aksamit A, Martin MA, Fauci AS: Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 1986;233:1089–1093.PubMedCrossRefGoogle Scholar
  29. 29.
    Wiley CA, Schier RD, Nelson JA, Lampert PN, Oldstone MBA: Cellular localization of human immunodeficiency virus infection within the brain of acquired immune deficiency syndrome patients. Proc Natl Acad Sci (USA) 1986;83:7089–7093.CrossRefGoogle Scholar
  30. 30.
    Bowen DL, Lane HC, Fauci AS: Immunopathogenesis of the acquired immunodeficiency syndrome. Ann Intern Med 1985;103:704–709.PubMedGoogle Scholar
  31. 31.
    Stobo JD, Levitt D, Copper MD: Lymphocytes: T cells, B cells; in Stites DP, Stobo JD, Wells JV (eds): Basic and Clinical Immunology. East Norwalk, Appleton and Lange, 1987, pp 65–81.Google Scholar
  32. 32.
    Goedert JJ, Biggar RJ, Melbye M, Mann DL, Wilson S, Gail MH, Grossman RJ, Digioria RA, Sanchez WC, Weissz SH, Blattner WA: Effect of T4 count and cofactors on the incidence of AIDS in homosexual men infected with human immunodeficiency virus. JAMA 1987; 257:331–335.PubMedCrossRefGoogle Scholar
  33. 33.
    Freeman WR, Chen A, Henderly DE, Levine AM, Luttrull JK, Urrea PT, Arthur J, Rasheed S, Cohen JL, Neuberg D, Leung RJ: Prevalence and significance of acquired immunodeficiency syndrome—Related retinal microvasculopathy. Am J Ophthalmol 1989;107:229–235.PubMedGoogle Scholar
  34. 34.
    Lare HC, Pepper JM, Greene WC: Qualitative analysis of immune function in patients with the acquired immune deficiency syndrome. N Engl J Med 1986;313:79–84.Google Scholar
  35. 35.
    McClellan BS, Whitney CR, Newman LP, Allansmith MR: Immunoglobulins in tears. Am J Ophthalmol 1973;76:89–101.PubMedGoogle Scholar
  36. 36.
    Culbertson WW: Infections of the retina in AIDS. Int Ophthalmol Clin 1989;29:108–118.PubMedCrossRefGoogle Scholar
  37. 37.
    Shuler JD, Engstrom RE, Holland GN: External ocular disease and anterior segment disorders associated with AIDS. Int Ophthalmol Clin 1989;29:98–104.PubMedCrossRefGoogle Scholar
  38. 38.
    Brown HH, Glasgow BJ, Holland GN, Foos RY: Cytomegalovirus infection of the conjunctiva in AIDS. Am J Ophthalmol 1988;106:102–104.PubMedGoogle Scholar
  39. 39.
    Newsome DA, Green WR, Miller ED, Kiessling LA, Morgan B, Jabs DA, Polk BF: Microvascular aspects of acquired immune deficiency syndrome retinopathy. Am J Ophthalmol 1984;98:590–601.PubMedGoogle Scholar
  40. 40.
    Holland GN, Engstrom RE, Glasgow BJ, Bergen BB, Daniels SA, Sidkano Y, Harman JA, Fischer DH, Boyer DS, Roo NA, Fagle RE, Krueger AE, Foos RY: Ocular toxoplasmosis in patients with the acquired immune deficiency syndrome. Am J Ophthalmol 1988;10: 653–667.Google Scholar
  41. 41.
    Jabs DA, Green WR, Fox R, Polk BF, Bartlett JG: Ocular manifestations of acquired immune deficiency syndrome. Ophthalmology 1989;96:1092–1099.PubMedGoogle Scholar
  42. 42.
    Qavi HB, Green MT, Segall GK, Font RL: Demonstration of HIV-1 and HHV-6 in AIDS associated retinitis. Curr Eye Res 1989;8:379–387.PubMedCrossRefGoogle Scholar
  43. 43.
    Davis JL, Nussenblatt RB, Bachman DM, Chan CC, Palestine AG: Endogenous bacterial retinitis in AIDS. Am J Ophthalmol 1989;107: 613–623.PubMedGoogle Scholar
  44. 44.
    Holland GN, Pepose JS, Pettit TH: Acquired immune deficiency syndrome. Ocular Manifestations. Ophthalmology 1983;90:859–873.PubMedGoogle Scholar
  45. 45.
    Rosenberg PR, Uliss AI, Friedland GH: Acquired immunodeficiency syndrome. Ophthalmic manifestations in ambulatory patients. Ophthalmology 1983;90:874–878.PubMedGoogle Scholar
  46. 46.
    Pomerantz RJ, Kuritzkis DR, DeLaMonte SM, Rota TR, Baker AS, Albert D, Bor DH, Feldman EL, Schooley RT, Horsch MS: Infections of the retina by human immunodeficiency virus type I. N Engl J Med 1987;317:1643–1647.PubMedGoogle Scholar
  47. 47.
    Safar B, Good RA: Kaposi's sarcoma: A review and recent developments. Cancer 1981;31:2–12.Google Scholar
  48. 48.
    Farell PL, Henemann MH, Roberts CW, Polsky B, Gold JWM, Mamelok A: Response of human immunodeficiency virus-associated uveitis to zidovudine. Am J Ophthalmol 1988;106:7–10.Google Scholar
  49. 49.
    Salahuddin SZ, Palestine AG, Heck E: Isolation of human T-cell leukemia/lymphotropic virus type III from the cornea. Am J Ophthalmol 1986;101:149–152.PubMedGoogle Scholar
  50. 50.
    Cantrill HL, Henry K, Jackson B, Erice A, Ussery FM, Balfour HH: Recovery of human immunodeficiency virus from ocular tissue in patients with acquired immune deficiency syndrome. Ophthalmology 1988;95:1458–1462.PubMedGoogle Scholar
  51. 51.
    Kennedy PGE, Newsome DA, Hess J: Cytomegalovirus but not human T lymphotropic virus type III/lymphadenopathy associated virus detected by in situ hybridization in retinal lesions in patients with acquired immune deficiency syndrome. BMJ 1986;293:162–164.PubMedCrossRefGoogle Scholar
  52. 52.
    Schuman JS, Orellana J, Friedman AH, Teich SA: Acquired immunodeficiency syndrome (AIDS). Surv Ophthalmol 1987;31:384–410.PubMedCrossRefGoogle Scholar
  53. 53.
    Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis CB, Erlich HA: Primer directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 1988;239:487–491.PubMedCrossRefGoogle Scholar
  54. 54.
    Loche M, Mach B: Identification of HIV-infected seronegative individuals by a direct diagnostic test based on hybridization to amplified DNA. Lancet 1988;ii:418–421.CrossRefGoogle Scholar
  55. 55.
    Passo MS, Rosenbaum JT: Ocular syphilis in patients with human immunodeficiency virus infection. Am J Ophthalmol 1988;106:1–6.PubMedGoogle Scholar
  56. 56.
    Schuman JS, Friedman AH: Retinal manifestations of the acquired immunodeficiency syndrome (AIDS): Cytomegalovirus,Candida albicans, Cryptococcus, toxoplasmosis andPneumocystis corinis. Trans Ophthalmol Soc UK 1983;103:177–190.PubMedGoogle Scholar
  57. 57.
    Kwok S, O'Donnell JJ, Wood IS: Retinal cotton-wool spots in a patient withPneumocystis carinii infection. N Engl J Med 1982;307: 184–185.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 1992

Authors and Affiliations

  • Kenneth E. Ugen
    • 1
    • 2
  • Daniel E. McCallus
    • 1
    • 2
  • Joan M. Von Feldt
    • 2
  • William V. Williams
    • 2
  • Mark I. Greene
    • 3
  • David B. Weiner
    • 1
    • 2
  1. 1.Wistar Institute of Anatomy and BiologyPhiladelphiaUSA
  2. 2.Department of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of PathologyUniversity of PennsylvaniaPhiladelphiaUSA

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