eMedicine Specialties > Ophthalmology > Retina

Retinitis, CMV

Author: Michael Altaweel, MD, FRCS(C), Associate Professor, Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health
Coauthor(s): Peter N Youssef, MD,, Clinical Instructor, Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison; Matthew D Reed, MD, Fellow, Department of Ophthalmology and Visual Sciences, University of Wisconsin Clinical Science Center
Contributor Information and Disclosures

Updated: Jan 28, 2010

Introduction

Background

Cytomegalovirus (CMV) is a ubiquitous DNA virus that infects the majority of the adult population. In the immunocompetent host, infection is generally asymptomatic or limited to a mononucleosis-like syndrome. Like many other herpesviruses, CMV remains latent in the host and may reactivate if host immunity is compromised.

In immunocompromised individuals, primary infection or reactivation of latent virus can lead to opportunistic infection of multiple organ systems. In the eye, CMV most commonly presents as a viral necrotizing retinitis with a characteristic ophthalmoscopic appearance (see image below).1 Untreated CMV retinitis inexorably progresses to visual loss and blindness.2

Retinitis typically starts in the midperiphery an...

Retinitis typically starts in the midperiphery and can progress in a "brush fire" pattern.

Retinitis typically starts in the midperiphery an...

Retinitis typically starts in the midperiphery and can progress in a "brush fire" pattern.


Although postnatally acquired CMV retinitis is seen most commonly in patients with acquired immunodeficiency syndrome (AIDS), transplant patients3 or other patients receiving immunosuppressive medications are also at risk.

Multiple antiviral agents, delivered locally, systemically, or in combination, are currently in use to delay or arrest the progress of the disease.4 In addition, highly active antiretroviral therapy (HAART) for HIV infection has revolutionized the treatment of CMV retinitis by allowing immune reconstitution in many individuals.5,6

Over a period of 3 years, the incidence of opportunistic infections has reduced, and newly diagnosed cases of CMV retinitis have decreased by up to 83%.

Pathophysiology

Transmission of CMV occurs through placental transfer, breast milk, saliva, sexually transmitted fluids, blood transfusions, and organ or bone marrow transplants. In the immunocompetent pediatric or adult host, infection is generally asymptomatic or limited to a mononucleosis-like syndrome with signs and symptoms including fever, myalgia, cervical lymphadenopathy, and mild hepatitis.

CMV generally dwells as a latent intracellular virus in immunocompetent children and adults. CMV may reactivate if host immunity is compromised. In immunocompromised individuals, primary infection or reactivation of latent virus can lead to opportunistic infection of multiple organ systems, including the skin (eg, rashes, ulcers, pustules), lungs (eg, interstitial pneumonitis), gastrointestinal tract (eg, colitis, esophagitis), peripheral nerves (eg, radiculopathy, myelopathy), brain (eg, meningoencephalitis), and eye (eg, retinitis, optic neuritis).7

In the eye, CMV commonly presents as a viral necrotizing retinitis with vitreitis and may result in retinal detachment. Untreated CMV retinitis inexorably progresses to visual loss and blindness.

Frequency

United States

CMV is ubiquitous, infecting 50-80% of the adult population. Clinically evident disease is found almost exclusively in immunosuppressed individuals. Prior to HAART, CMV occurred in 25-40% of all AIDS patients and was the most common opportunistic infection in AIDS patients with a CD4 count below 50 cells/mL. While HAART has decreased the incidence of CMV retinitis by 55-83%, the decline in AIDS-related mortality has led to an increase in the number of patients with CMV disease.

CMV retinitis remains a leading cause of visual loss in patients with AIDS and is increasing in organ transplant recipients as the number of those procedures performed each year increases.

International

The frequency of CMV retinitis in other developed countries is equivalent to that of the United States. The prevalence of CMV retinitis in HIV-infected individuals in developing countries is generally lower than in North America and Western Europe. The lower reported prevalence of CMV retinitis in developing countries, particularly those on the African continent, may be attributed the fact that many HIV-infected individuals die before their immune function deteriorates to the level at which CMV retinitis typically occurs.8 In general, the incidence of CMV in developing countries reflects the spread of the HIV virus and the availability of antiretroviral medications.9,10

Mortality/Morbidity

CMV retinitis frequently results in considerable loss of visual acuity, and, without treatment, it almost universally leads to blindness.11,12 Severe visual loss primarily occurs from the direct spread of retinitis into the posterior pole, affecting central vision, or from retinal detachment (RD) secondary to multiple retinal breaks in the peripheral, necrotic retina.13,14

Early and aggressive treatment with antiviral medication for both CMV and HIV, combined with improved surgical techniques for RD repair, has helped to improve the visual outcomes in these patients.

  • Untreated CMV leads to progressive visual loss and eventual blindness.
  • Retinal detachment occurs in up to 29%.15
  • CMV retinitis causes full thickness necrosis of the retina.
  • Retinitis permanently destroys the retina; lesions change appearance with treatment but do not become smaller.
  • If the CD4 count is less than 100 cells/mL, CMV retinitis will develop in 20-30% of patients over a year, although retinitis typically develops if the CD4 count is reduced below 50 cells/mL. Of these patients, 5-10% develop other systemic infections (eg, pneumonitis, colitis, esophagitis).
  • With the advent of HAART and immune reconstitution, some patients suffer from a relatively new condition known as immune recovery uveitis (IRU).16,17,18 IRU occurs when the poor immune response of an immunocompromised individual is suddenly increased as the patients restored immune system recognizes and reacts to viral antigens in the retina. This reaction can lead to several complications, including uveitis, leading to hypotony, cataract, and glaucoma; epiretinal membrane (ERM); and cystoid macular edema (CME).19,20

Sex

Although the incidence of CMV retinitis is the same among men and women, the prevalence is higher in men than in women because of the higher prevalence of AIDS in men. The prevalence of CMV retinitis in the heterosexual community has been steadily increasing.

Age

The age of most individuals developing CMV retinitis is 20-50 years.

Clinical

History

Presenting symptoms vary depending on the location of retinal involvement. Posterior lesions present with diminished visual acuity. More peripheral lesions initially can be asymptomatic. Floaters often are noted if significant vitreitis is present. The eye usually is white and quiet.

  • Active CMV retinitis usually is found in conjunction with immunosuppression, whether from AIDS, leukemia, or use of chemotherapy. These points are important in evaluating the patient history. Rarely, CMV retinitis is the first presenting manifestation of AIDS.
  • Natural history
    • CMV retinitis is a slowly progressive disease, requiring weeks to months to involve the entire retina.21,22 Vision is lost with involvement of the posterior pole (macula or optic nerve) or retinal detachment.23
    • Initial reports described CMV retinitis as an end-stage disease, which indicated a life expectancy of 6 weeks. With the use of antiviral medications, the average survival after diagnosis ranged from 5.5-8 months. The advent of HAART has prolonged survival to years in some instances, and it has allowed discontinuation of medications targeted against CMV retinitis if clinical resolution occurs and the immune status recovers (reflected by a CD4 count of >100 cells/mL).
  • After initiation of therapy, some advance of the leading edge of retinitis may be noted. This usually is not a treatment failure but rather the revealing of an area of subclinical infection that was not previously evident.

Physical

Patients with suspected CMV retinitis should have a complete ocular examination of both eyes. A careful examination should include the following:

  • Carefully check and record the patient's best corrected visual acuity as a baseline. Check for visual field defects that could represent optic nerve damage, retinal detachment (RD), or CNS disease from AIDS-related brain diseases (eg, encephalitis, stroke, CNS lymphoma).24,25 Ocular motility should be assessed as part of a cranial nerve examination. Pupils should be checked for a relative afferent pupillary defect indicating optic nerve involvement.
  • External examination of the lids and adnexa should be performed for other AIDS-associated findings, such as Kaposi sarcoma or lymphoma.
  • A thorough slit lamp examination should show a white and quiet conjunctiva. A red hot eye in an immunocompromised patient should alert the clinician to another possible diagnosis. Fine, stellate keratitic precipitates (KP) characteristic of CMV may be seen on the corneal endothelium.26 Uveitis may be present in the anterior chamber and, if severe, may require treatment. The level of vitreitis can be assessed in the anterior vitreous and may be important for monitoring response to treatment or the occurrence of IRU.
  • A dilated fundus examination with indirect ophthalmoscopy is essential for assessing the location and extent of retinal involvement as well as for evaluating for retinal breaks or detachment. Retinal lesions have several characteristics,27,28 as follows:
    • Initial examination typically reveals 1 or 2 foci of disease. Multifocal disease at time of presentation is uncommon.
    • Most early lesions occur in a perivascular distribution, likely reflecting the hematogenous spread of the virus.
    • Lesions that present posteriorly appear along retinal vessels as large areas of thick white infiltrate accompanied by retinal hemorrhage described as "pizza pie" or "cheese pizza" in appearance.
    • The peripheral type of lesion demonstrates a more granular appearance with satellite lesions and less hemorrhage. Behind the advancing border is necrotic retina with mottled pigmentation from hyperplasia of the retinal pigment epithelium (RPE).
    • Lesions usually begin peripherally and spread posteriorly in a contiguous fashion (see image below). However, multiple unconnected lesions are frequent, and involvement of the posterior pole with minimal peripheral disease is possible (5-10%).

      • Retinitis typically starts in the midperiphery an...

        Retinitis typically starts in the midperiphery and can progress in a "brush fire" pattern.

        Retinitis typically starts in the midperiphery an...

        Retinitis typically starts in the midperiphery and can progress in a "brush fire" pattern.

    • Retinitis follows the nerve fiber layer.
    • Retinitis produces wide areas of necrosis, scarring, and atrophy (see image below).

      • Early necrosis at periphery.

        Early necrosis at periphery.

        Early necrosis at periphery.

        Early necrosis at periphery.

    • Even severe retinitis is usually accompanied by minimal vitreitis in the immunocompromised patient. If HAART is instituted and immune reconstitution occurs, then IRU with severe anterior and posterior uveitis may occur.
    • Extensive vascular sheathing, often described as frosted branch angiitis, is a known but uncommon appearance (see image below).29,30

      • Frosted branch angiitis.

        Frosted branch angiitis.

        Frosted branch angiitis.

        Frosted branch angiitis.

    • Retinal vascular occlusion/nonperfusion can be seen on fluorescein angiogram.31
  • Peripheral holes and tears frequently occur in areas of necrosis (see image below).

    • Retinal detachment due to peripheral tear in area...

      Retinal detachment due to peripheral tear in area of necrosis.

      Retinal detachment due to peripheral tear in area...

      Retinal detachment due to peripheral tear in area of necrosis.

  • Rate of progression of untreated retinitis is 250-350 µm per week. Skip lesions can occur.
  • Serial examinations may be necessary at early stages to distinguish CMV retinitis from HIV retinopathy with multiple cotton-wool spots.
  • Optic neuritis can develop without apparent retinitis.32
  • Most patients with CMV retinitis will initially present with unilateral disease. Untreated, the immunocompromised patient has a 50% risk of developing disease in the contralateral eye within 6 months.33,34 This is reduced to 20% with antiviral treatment and further reduced with HAART.

Causes

Any immunosuppression due to disease or medication may allow clinical CMV infection to develop.

  • Acquired immune deficiency syndrome35
  • Leukemia, lymphoma, and aplastic anemia36
  • Use of immunosuppressive chemotherapy
  • Organ transplant recipients

Congenital CMV retinitis is acquired from vertical transmission during pregnancy. When primary maternal infection occurs during pregnancy, the risk of transmission to the fetus ranges between 30% and 40%. Transmission during the first half of pregnancy generally causes more severe disease.

More on Retinitis, CMV

Overview: Retinitis, CMV
Differential Diagnoses & Workup: Retinitis, CMV
Treatment & Medication: Retinitis, CMV
Follow-up: Retinitis, CMV
Multimedia: Retinitis, CMV
References

References

  1. Murray HW, Knox DL, Green WR, Susel RM. Cytomegalovirus retinitis in adults. A manifestation of disseminated viral infection. Am J Med. Oct 1977;63(4):574-84. [Medline].

  2. Egbert PR, Pollard RB, Gallagher JG, Merigan TC. Cytomegalovirus retinitis in immunosuppressed hosts. II. Ocular manifestations. Ann Intern Med. Nov 1980;93(5):664-70. [Medline].

  3. McAuliffe PF, Hall MJ, Castro-Malaspina H, Heinemann MH. Use of the ganciclovir implant for treating cytomegalovirus retinitis secondary to immunosuppression after bone marrow transplantation. Am J Ophthalmol. May 1997;123(5):702-3. [Medline].

  4. Whitcup SM. Cytomegalovirus Retinitis in the Era of Highly Active Antiretroviral Therapy. JAMA. 2000;283 No. 5:653-657.

  5. Mitchell SM, Membrey WL, Youle MS, et al. Cytomegalovirus retinitis after the initiation of highly active antiretroviral therapy: a 2 year prospective study. Br J Ophthalmol. Jun 1999;83(6):652-5. [Medline].

  6. Zegans M, Marsh B, Walton RC. Cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Int Ophthalmol Clin. Spring 2000;40(2):127-35. [Medline].

  7. Baumal CR, Levin AV, Read SE. Cytomegalovirus retinitis in immunosuppressed children. Am J Ophthalmol. May 1999;127(5):550-8. [Medline].

  8. Knox CM, Chandler D, Short GA, Margolis TP. Polymerase chain reaction-based assays of vitreous samples for the diagnosis of viral retinitis. Use in diagnostic dilemmas. Ophthalmology. Jan 1998;105(1):37-44; discussion 44-5. [Medline].

  9. Grant AD, Djomand G, De Cock KM. Natural history and spectrum of disease in adults with HIV/AIDS in Africa. AIDS. 1997;11 Suppl B:S43-54. [Medline].

  10. Kestelyn P. The epidemiology of CMV retinitis in Africa. Ocul Immunol Inflamm. Dec 1999;7(3-4):173-7. [Medline].

  11. Studies of Ocular Complications of AIDS (SOCA) Research Group. Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial. 4. Visual outcomes. Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group. Ophthalmology. Jul 1994;101(7):1250-61. [Medline].

  12. Thorne JE, Holbrook JT, Jabs DA, Kempen JH, Nichols C, Meinert CL. Effect of cytomegalovirus retinitis on the risk of visual acuity loss among patients with AIDS. Ophthalmology. Mar 2007;114(3):591-8. [Medline].

  13. Holbrook JT, Jabs DA, Weinberg DV. Visual loss in patients with cytomegalovirus retinitis and acquired immunodeficiency syndrome before widespread availability of highly active antiretroviral therapy. Arch Ophthalmol. Jan 2003;121(1):99-107. [Medline].

  14. Studies of Ocular Complications of AIDS (SOCA) Research Group. Rhegmatogenous retinal detachment in patients with cytomegalovirus retinitis: the Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial. The Studies of Ocular Complications of AIDS (SOCA) Research Group in Collaboration with the AIDS Clinical Trials G. Am J Ophthalmol. Jul 1997;124(1):61-70. [Medline].

  15. Sandy CJ, Bloom PA, Graham EM, et al. Retinal detachment in AIDS-related cytomegalovirus retinitis. Eye. 1995;9 ( Pt 3):277-81. [Medline].

  16. Boyraz-Ikiz HD, Witmer JP, Frissen PH. Cytomegalovirus (re)activation plays no role in the ocular vitritis observed after initiation of highly active antiretroviral therapy. AIDS. May 7 1999;13(7):867. [Medline].

  17. Holland GN. New issues in the management of patients with AIDS-related cytomegalovirus retinitis. Arch Ophthalmol. May 2000;118(5):704-6. [Medline].

  18. Kempen JH, Min YI, Freeman WR, Holland GN, Friedberg DN, Dieterich DT, et al. Risk of immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis. Ophthalmology. Apr 2006;113(4):684-94. [Medline].

  19. Karavellas MP, Plummer DJ, Macdonald JC, et al. Incidence of immune recovery vitritis in cytomegalovirus retinitis patients following institution of successful highly active antiretroviral therapy. J Infect Dis. Mar 1999;179(3):697-700. [Medline].

  20. Nguyen QD, Kempen JH, Bolton SG, et al. Immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis after highly active antiretroviral therapy. Am J Ophthalmol. May 2000;129(5):634-9. [Medline].

  21. Bowen EF, Griffiths PD, Davey CC, et al. Lessons from the natural history of cytomegalovirus. AIDS. Nov 1996;10 Suppl 1:S37-41. [Medline].

  22. Bowen EF, Wilson P, Atkins M, et al. Natural history of untreated cytomegalovirus retinitis. Lancet. Dec 23-30 1995;346(8991-8992):1671-3. [Medline].

  23. Bloom PA, Sandy CJ, Migdal CS, et al. Visual prognosis of AIDS patients with cytomegalovirus retinitis. Eye. 1995;9 ( Pt 6):697-702. [Medline].

  24. McCutchan JA. Clinical impact of cytomegalovirus infections of the nervous system in patients with AIDS. Clin Infect Dis. Oct 1995;21 Suppl 2:S196-201. [Medline].

  25. McCutchan JA. Cytomegalovirus infections of the nervous system in patients with AIDS. Clin Infect Dis. Apr 1995;20(4):747-54. [Medline].

  26. Brody JM, Butrus SI, Laby DM, et al. Anterior segment findings in AIDS patients with cytomegalovirus retinitis. Graefes Arch Clin Exp Ophthalmol. Jun 1995;233(6):374-6. [Medline].

  27. Biswas J, Madhavan HN, George AE, et al. Ocular lesions associated with HIV infection in India: a series of 100 consecutive patients evaluated at a referral center. Am J Ophthalmol. Jan 2000;129(1):9-15. [Medline].

  28. Studies of Ocular Complications of AIDS (SOCA) Research Group. Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial: 5. Clinical features of cytomegalovirus retinitis at diagnosis. Studies of ocular complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group. Am J Ophthalmol. Aug 1997;124(2):141-57. [Medline].

  29. Biswas J, Raizada S, Gopal L, et al. Bilateral frosted branch angiitis and cytomegalovirus retinitis in acquired immunodeficiency syndrome. Indian J Ophthalmol. Sep 1999;47(3):195-7. [Medline].

  30. Mansour AM, Li HK. Frosted retinal periphlebitis in the acquired immunodeficiency syndrome. Ophthalmologica. 1993;207(4):182-6. [Medline].

  31. Saran BR, Pomilla PV. Retinal vascular nonperfusion and retinal neovascularization as a consequence of cytomegalovirus retinitis and cryptococcal choroiditis. Retina. 1996;16(6):510-2. [Medline].

  32. Mansor AM, Li HK. Cytomegalovirus optic neuritis: characteristics, therapy and survival. Ophthalmologica. 1995;209(5):260-6. [Medline].

  33. Kempen JH, Jabs DA, Wilson LA. Risk of vision loss in patients with cytomegalovirus retinitis and the acquired immunodeficiency syndrome. Arch Ophthalmol. Apr 2003;121(4):466-76. [Medline].

  34. Kempen JH, Jabs DA, Wilson LA. Incidence of cytomegalovirus (CMV) retinitis in second eyes of patients with the acquired immune deficiency syndrome and unilateral CMV retinitis. Am J Ophthalmol. Jun 2005;139(6):1028-34. [Medline].

  35. Pertel P, Hirschtick R, Phair J, et al. Risk of developing cytomegalovirus retinitis in persons infected with the human immunodeficiency virus. J Acquir Immune Defic Syndr. 1992;5(11):1069-74. [Medline].

  36. Nasir MA, Jaffe GJ. Cytomegalovirus retinitis associated with Hodgkin''s disease. Retina. 1996;16(4):324-7. [Medline].

  37. Elkins BS, Holland GN, Opremcak EM, et al. Ocular toxoplasmosis misdiagnosed as cytomegalovirus retinopathy in immunocompromised patients. Ophthalmology. Mar 1994;101(3):499-507. [Medline].

  38. Davis JL. Differential diagnosis of CMV retinitis. Ocul Immunol Inflamm. Dec 1999;7(3-4):159-66. [Medline].

  39. Phillips AN, Lazzarin A, Gonzales-Lahoz J, et al. Factors associated with the CD4+ lymphocyte count at diagnosis of acquired immunodeficiency syndrome. The AIDS IN EUROPE Study Group. J Clin Epidemiol. Nov 1996;49(11):1253-8. [Medline].

  40. Baldassano V, Dunn JP, Feinberg J, Jabs DA. Cytomegalovirus retinitis and low CD4+ T-lymphocyte counts. N Engl J Med. Sep 7 1995;333(10):670. [Medline].

  41. Sandy CJ, Ferris JD, Bloom PA, et al. Screening for cytomegalovirus retinitis in HIV-positive and AIDS patients. QJM. Dec 1995;88(12):899-903. [Medline].

  42. Holbrook JT, Davis MD, Hubbard LD, et al. Risk factors for advancement of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. Studies of Ocular Complications of AIDS Research Group. Arch Ophthalmol. Sep 2000;118(9):1196-204. [Medline].

  43. Chernoff DN, Miner RC, Hoo BS, et al. Quantification of cytomegalovirus DNA in peripheral blood leukocytes by a branched-DNA signal amplification assay. J Clin Microbiol. Nov 1997;35(11):2740-4. [Medline].

  44. Rasmussen L, Morris S, Zipeto D, et al. Quantitation of human cytomegalovirus DNA from peripheral blood cells of human immunodeficiency virus-infected patients could predict cytomegalovirus retinitis. J Infect Dis. Jan 1995;171(1):177-82. [Medline].

  45. Tufail A, Moe AA, Miller MJ, et al. Quantitative cytomegalovirus DNA level in the blood and its relationship to cytomegalovirus retinitis in patients with acquired immune deficiency syndrome. Ophthalmology. Jan 1999;106(1):133-41. [Medline].

  46. Wattanamano P, Clayton JL, Kopicko JJ, et al. Comparison of three assays for cytomegalovirus detection in AIDS patients at risk for retinitis. J Clin Microbiol. Feb 2000;38(2):727-32. [Medline].

  47. Liu JH, Hsu WM, Wong WW, et al. Using conjunctival swab with polymerase chain reaction to aid diagnosis of cytomegalovirus retinitis in AIDS patients. Ophthalmologica. 2000;214(2):126-30. [Medline].

  48. Sugita S, Shimizu N, Watanabe K, Mizukami M, Morio T, Sugamoto Y, et al. Use of multiplex PCR and real-time PCR to detect human herpes virus genome in ocular fluids of patients with uveitis. Br J Ophthalmol. Jul 2008;92(7):928-32. [Medline].

  49. Fuchs AV, Wolf E, Scheider A, Jager H, Kampik A. [Cytomegalovirus (CMV) retinitis in AIDS. Gancilovir implantation in comparison with systemic therapy]. Ophthalmologe. Jan 1999;96(1):11-5. [Medline].

  50. Musch DC, Martin DF, Gordon JF, et al. Treatment of cytomegalovirus retinitis with a sustained-release ganciclovir implant. The Ganciclovir Implant Study Group. N Engl J Med. Jul 10 1997;337(2):83-90. [Medline].

  51. Guembel HO, Krieglsteiner S, Rosenkranz C, et al. Complications after implantation of intraocular devices in patients with cytomegalovirus retinitis. Graefes Arch Clin Exp Ophthalmol. Oct 1999;237(10):824-9. [Medline].

  52. Boyer DS, Posalski J. Potential complication associated with removal of ganciclovir implants. Am J Ophthalmol. Mar 1999;127(3):349-50. [Medline].

  53. Freeman WR, Friedberg DN, Berry C, et al. Risk factors for development of rhegmatogenous retinal detachment in patients with cytomegalovirus retinitis. Am J Ophthalmol. Dec 15 1993;116(6):713-20. [Medline].

  54. Baumal CR, Reichel E. Management of cytomegalovirus-related rhegmatogenous retinal detachments. Ophthalmic Surg Lasers. Nov 1998;29(11):916-25. [Medline].

  55. Davis JL, Serfass MS, Lai MY, et al. Silicone oil in repair of retinal detachments caused by necrotizing retinitis in HIV infection. Arch Ophthalmol. Nov 1995;113(11):1401-9. [Medline].

  56. Freeman WR. Retinal detachment in cytomegalovirus retinitis: should our approach be changed?. Retina. 1999;19(4):271-3. [Medline].

  57. Ross WH, Bryan JS, Barloon AS. Management of retinal detachments secondary to cytomegalovirus retinitis. Can J Ophthalmol. Jun 1994;29(3):129-33. [Medline].

  58. Erice A, Jordan MC, Chace BA, et al. Ganciclovir treatment of cytomegalovirus disease in transplant recipients and other immunocompromised hosts. JAMA. Jun 12 1987;257(22):3082-7. [Medline].

  59. Jensen OA, Gerstoft J, Thomsen HK, Marner K. Cytomegalovirus retinitis in the acquired immunodeficiency syndrome (AIDS). Light-microscopical, ultrastructural and immunohistochemical examination of a case. Acta Ophthalmol (Copenh). Feb 1984;62(1):1-9. [Medline].

  60. Pecorella I, Ciardi A, Credendino A, et al. Ocular, cerebral and systemic interrelationships of cytomegalovirus infection in a post-mortem study of AIDS patients. Eye. Dec 1999;13 ( Pt 6):781-5. [Medline].

  61. Jabs DA, Van Natta ML, Holbrook JT, Kempen JH, Meinert CL, Davis MD. Longitudinal study of the ocular complications of AIDS: 2. Ocular examination results at enrollment. Ophthalmology. Apr 2007;114(4):787-93. [Medline].

  62. Jabs DA, Van Natta ML, Thorne JE, et al. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: 1. Retinitis progression. Ophthalmology. Dec 2004;111(12):2224-31. [Medline].

  63. Jabs DA, Van Natta ML, Thorne JE, et al. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: 2. Second eye involvement and retinal detachment. Ophthalmology. Dec 2004;111(12):2232-9. [Medline].

  64. D'Aquila R, Walker B. Exploring the benefits and limits of highly active antiretroviral therapy. JAMA. Nov 3 1999;282(17):1668-9. [Medline].

  65. Doan S, Cochereau I, Guvenisik N, et al. Cytomegalovirus retinitis in HIV-infected patients with and without highly active antiretroviral therapy. Am J Ophthalmol. Aug 1999;128(2):250-1. [Medline].

  66. Kedhar SR, Jabs DA. Cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Herpes. Dec 2007;14(3):66-71. [Medline].

  67. Macdonald JC, Torriani FJ, Morse LS, et al. Lack of reactivation of cytomegalovirus (CMV) retinitis after stopping CMV maintenance therapy in AIDS patients with sustained elevations in CD4 T cells in response to highly active antiretroviral therapy. J Infect Dis. May 1998;177(5):1182-7. [Medline].

  68. Margolis TP. Discontinuation of anticytomegalovirus therapy in patients with HIV infection and cytomegalovirus retinitis. Surv Ophthalmol. Mar-Apr 2000;44(5):455. [Medline].

  69. Soriano V, Dona C, Rodriguez-Rosado R, et al. Discontinuation of secondary prophylaxis for opportunistic infections in HIV-infected patients receiving highly active antiretroviral therapy. AIDS. Mar 10 2000;14(4):383-6. [Medline].

  70. Nasemann JE, Mutsch A, Wiltfang R, Klauss V. Early pars plana vitrectomy without buckling procedure in cytomegalovirus retinitis-induced retinal detachment. Retina. 1995;15(2):111-6. [Medline].

  71. Azen SP, Scott IU, Flynn HW Jr, et al. Silicone oil in the repair of complex retinal detachments. A prospective observational multicenter study. Ophthalmology. Sep 1998;105(9):1587-97. [Medline].

  72. Althaus C, Loeffler KU, Schimkat M, et al. Prophylactic argon laser coagulation for rhegmatogenous retinal detachment in AIDS patients with cytomegalovirus retinitis. Graefes Arch Clin Exp Ophthalmol. May 1998;236(5):359-64. [Medline].

  73. Meffert SA, Ai E. Laser photocoagulation prophylaxis for CMV retinal detachments. Ophthalmology. Aug 1998;105(8):1353-5. [Medline].

  74. Martin DF, Dunn JP, Davis JL, et al. Use of the ganciclovir implant for the treatment of cytomegalovirus retinitis in the era of potent antiretroviral therapy: recommendations of the International AIDS Society-USA panel. Am J Ophthalmol. Mar 1999;127(3):329-39. [Medline].

  75. Sanborn GE, Anand R, Torti RE, et al. Sustained-release ganciclovir therapy for treatment of cytomegalovirus retinitis. Use of an intravitreal device. Arch Ophthalmol. Feb 1992;110(2):188-95. [Medline].

  76. Martin DF, Ferris FL, Parks DJ, et al. Ganciclovir implant exchange. Timing, surgical procedure, and complications. Arch Ophthalmol. Nov 1997;115(11):1389-94. [Medline].

  77. Roth DB, Feuer WJ, Blenke AJ, Davis JL. Treatment of recurrent cytomegalovirus retinitis with the ganciclovir implant. Am J Ophthalmol. Mar 1999;127(3):276-82. [Medline].

  78. Lim JI, Wolitz RA, Dowling AH, et al. Visual and anatomic outcomes associated with posterior segment complications after ganciclovir implant procedures in patients with AIDS and cytomegalovirus retinitis. Am J Ophthalmol. Mar 1999;127(3):288-93. [Medline].

  79. Desatnik HR, Foster RE, Lowder CY. Treatment of clinically resistant cytomegalovirus retinitis with combined intravitreal injections of ganciclovir and foscarnet. Am J Ophthalmol. Jul 1996;122(1):121-3. [Medline].

  80. Akerele T, Lightman S. Current and novel agents for the treatment of cytomegalovirus retinitis. Drugs R D. Nov 1999;2(5):289-97. [Medline].

  81. Holland GN. Treatment options for cytomegalovirus retinitis: a time for reassessment. Arch Ophthalmol. Nov 1999;117(11):1549-50. [Medline].

  82. Whitley RJ, Jacobson MA, Friedberg DN, et al. Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA. Arch Intern Med. May 11 1998;158(9):957-69. [Medline].

  83. Marwick C. First "antisense" drug will treat CMV retinitis. JAMA. Sep 9 1998;280(10):871. [Medline].

  84. Studies of Ocular Complications of AIDS (SOCA) Research Group. Cytomegalovirus (CMV) culture results, drug resistance, and clinical outcome in patients with AIDS and CMV retinitis treated with foscarnet or ganciclovir. Studies of Ocular Complications of AIDS (SOCA) in collaboration with the AIDS Clinical Trial Gr. J Infect Dis. Jul 1997;176(1):50-8. [Medline].

  85. Drew WL, Ives D, Lalezari JP, et al. Oral ganciclovir as maintenance treatment for cytomegalovirus retinitis in patients with AIDS. Syntex Cooperative Oral Ganciclovir Study Group. N Engl J Med. Sep 7 1995;333(10):615-20. [Medline].

  86. Holland GN, Buhles WC Jr, Mastre B, Kaplan HJ. A controlled retrospective study of ganciclovir treatment for cytomegalovirus retinopathy. Use of a standardized system for the assessment of disease outcome. UCLA CMV Retinopathy. Study Group. Arch Ophthalmol. Dec 1989;107(12):1759-66. [Medline].

  87. Kuppermann BD, Quiceno JI, Flores-Aguilar M, et al. Intravitreal ganciclovir concentration after intravenous administration in AIDS patients with cytomegalovirus retinitis: implications for therapy. J Infect Dis. Dec 1993;168(6):1506-9. [Medline].

  88. Goldberg DE, Wang H, Azen SP. Long term visual outcome of patients with cytomegalovirus retinitis treated with highly active antiretroviral therapy. Br J Ophthalmol. Jul 2003;87(7):853-5. [Medline].

  89. Whitcup SM. Cytomegalovirus retinitis in the era of highly active antiretroviral therapy. JAMA. Feb 2 2000;283(5):653-7. [Medline].

  90. Whitcup, SM, Fortin, E, Linblad, AS. Discontinuation of Anticytomegalovirus Therapy in Patients With HIV Infection and Cytomegalovirus Retinits. JAMA. 1999;282:1633-1637.

  91. Martin DF, Sierra-Madero J, Walmsley S. A controlled trial of valganciclovir as induction therapy for cytomegalovirus retinitis. N Engl J Med. Apr 11 2002;346(15):1119-26. [Medline].

  92. Brown F, Banken L, Saywell K, Arum I. Pharmacokinetics of valganciclovir and ganciclovir following multiple oral dosages of valganciclovir in HIV- and CMV-seropositive volunteers. Clin Pharmacokinet. Aug 1999;37(2):167-76. [Medline].

  93. Stalder N, Sudre P, Olmari M, et al. Cytomegalovirus retinitis: decreased risk of bilaterality with increased use of systemic treatment. Swiss HIV Cohort Study Group. Clin Infect Dis. Apr 1997;24(4):620-4. [Medline].

  94. Spector SA, Busch DF, Follansbee S, et al. Pharmacokinetic, safety, and antiviral profiles of oral ganciclovir in persons infected with human immunodeficiency virus: a phase I/II study. AIDS Clinical Trials Group, and Cytomegalovirus Cooperative Study Group. J Infect Dis. Jun 1995;171(6):1431-7. [Medline].

  95. Spector SA, McKinley GF, Lalezari JP, et al. Oral ganciclovir for the prevention of cytomegalovirus disease in persons with AIDS. Roche Cooperative Oral Ganciclovir Study Group. N Engl J Med. Jun 6 1996;334(23):1491-7. [Medline].

  96. Squires KE. Oral ganciclovir for cytomegalovirus retinitis in patients with AIDS: results of two randomized studies. AIDS. Dec 1996;10 Suppl 4:S13-8. [Medline].

  97. Cvetkovic RS, Wellington K. Valganciclovir: a review of its use in the management of CMV infection and disease in immunocompromised patients. Drugs. 2005;65(6):859-78. [Medline].

  98. Danner SA, Matheron S. Cytomegalovirus retinitis in AIDS patients: a comparative study of intravenous and oral ganciclovir as maintenance therapy. AIDS. Dec 1996;10 Suppl 4:S7-11. [Medline].

  99. Gilbert C, Handfield J, Toma E, et al. Emergence and prevalence of cytomegalovirus UL97 mutations associated with ganciclovir resistance in AIDS patients. AIDS. Jan 22 1998;12(2):125-9. [Medline].

  100. Spector SA, Weingeist T, Pollard RB, et al. A randomized, controlled study of intravenous ganciclovir therapy for cytomegalovirus peripheral retinitis in patients with AIDS. AIDS Clinical Trials Group and Cytomegalovirus Cooperative Study Group. J Infect Dis. Sep 1993;168(3):557-63. [Medline].

  101. Lietman PS. Clinical pharmacology: foscarnet. Am J Med. Feb 14 1992;92(2A):8S-11S. [Medline].

  102. Lalezari JP. Cidofovir: a new therapy for cytomegalovirus retinitis. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;14 Suppl 1:S22-6. [Medline].

  103. Lalezari JP, Holland GN, Kramer F, et al. Randomized, controlled study of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS. J Acquir Immune Defic Syndr Hum Retrovirol. Apr 1 1998;17(4):339-44. [Medline].

  104. Plosker GL, Noble S. Cidofovir: a review of its use in cytomegalovirus retinitis in patients with AIDS. Drugs. Aug 1999;58(2):325-45. [Medline].

  105. Rahhal FM, Arevalo JF, Munguia D, et al. Intravitreal cidofovir for the maintenance treatment of cytomegalovirus retinitis. Ophthalmology. Jul 1996;103(7):1078-83. [Medline].

  106. Studies of Ocular Complications of AIDS (SOCA) Research Group. Parenteral cidofovir for cytomegalovirus retinitis in patients with AIDS: the HPMPC peripheral cytomegalovirus retinitis trial. A randomized, controlled trial. Studies of Ocular complications of AIDS Research Group in Collaboration with the AIDS Clini. Ann Intern Med. Feb 15 1997;126(4):264-74. [Medline].

  107. Drusano GL, Aweeka F, Gambertoglio J, et al. Relationship between foscarnet exposure, baseline cytomegalovirus (CMV) blood culture and the time to progression of CMV retinitis in HIV- positive patients. AIDS. Sep 1996;10(10):1113-9. [Medline].

  108. Harb GE, Bacchetti P, Jacobson MA. Survival of patients with AIDS and cytomegalovirus disease treated with ganciclovir or foscarnet. AIDS. Aug 1991;5(8):959-65. [Medline].

  109. Jabs DA. Controversies in the treatment of cytomegalovirus retinitis: foscarnet versus ganciclovir. Infect Agents Dis. Sep 1995;4(3):131-42. [Medline].

  110. Ambati J, Wynne KB, Angerame MC, Robinson MR. Anterior uveitis associated with intravenous cidofovir use in patients with cytomegalovirus retinitis. Br J Ophthalmol. Oct 1999;83(10):1153-8. [Medline].

  111. Cochereau I, Doan S, Diraison MC, et al. Uveitis in patients treated with intravenous cidofovir. Ocul Immunol Inflamm. Dec 1999;7(3-4):223-9. [Medline].

  112. Studies of Ocular Complications of AIDS (SOCA) Research Group. Morbidity and toxic effects associated with ganciclovir or foscarnet therapy in a randomized cytomegalovirus retinitis trial. Studies of ocular complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials Group. Arch Intern Med. Jan 9 1995;155(1):65-74. [Medline].

  113. Tseng AL, Mortimer CB, Salit IE. Iritis associated with intravenous cidofovir. Ann Pharmacother. Feb 1999;33(2):167-71. [Medline].

  114. Studies of Ocular Complications of AIDS (SOCA) Research Group. Combination foscarnet and ganciclovir therapy vs monotherapy for the treatment of relapsed cytomegalovirus retinitis in patients with AIDS. The Cytomegalovirus Retreatment Trial. The Studies of Ocular Complications of AIDS Research Group in Collaborat. Arch Ophthalmol. Jan 1996;114(1):23-33. [Medline].

  115. Studies of Ocular Complications of AIDS (SOCA) Research Group. MSL-109 adjuvant therapy for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome: the Monoclonal Antibody Cytomegalovirus Retinitis Trial. The Studies of Ocular Complications of AIDS Research Group. AIDS Clinical Trials Group. Arch Ophthalmol. Dec 1997;115(12):1528-36. [Medline].

  116. Walsh JC, Jones CD, Barnes EA, et al. Increasing survival in AIDS patients with cytomegalovirus retinitis treated with combination antiretroviral therapy including HIV protease inhibitors. AIDS. Apr 16 1998;12(6):613-8. [Medline].

  117. Martin DF, Kuppermann BD, Wolitz RA, et al. Oral ganciclovir for patients with cytomegalovirus retinitis treated with a ganciclovir implant. Roche Ganciclovir Study Group. N Engl J Med. Apr 8 1999;340(14):1063-70. [Medline].

  118. Holland GN, Vaudaux JD, Jeng SM, Yu F, Goldenberg DT, Folz IC, et al. Characteristics of untreated AIDS-related cytomegalovirus retinitis. I. Findings before the era of highly active antiretroviral therapy (1988 to 1994). Am J Ophthalmol. Jan 2008;145(1):5-11. [Medline].

  119. Holland GN, Vaudaux JD, Shiramizu KM, Yu F, Goldenberg DT, Gupta A, et al. Characteristics of untreated AIDS-related cytomegalovirus retinitis. II. Findings in the era of highly active antiretroviral therapy (1997 to 2000). Am J Ophthalmol. Jan 2008;145(1):12-22. [Medline].

  120. Jabs DA, Enger C, Dunn JP, et al. Cytomegalovirus retinitis and viral resistance: 3. Culture results. CMV Retinitis and Viral Resistance Study Group. Am J Ophthalmol. Oct 1998;126(4):543-9. [Medline].

  121. Jabs DA, Enger C, Forman M, et al. Incidence of foscarnet resistance and cidofovir resistance in patients treated for cytomegalovirus retinitis. The Cytomegalovirus Retinitis and Viral Resistance Study Group. Antimicrob Agents Chemother. Sep 1998;42(9):2240-4. [Medline].

  122. Hardy WD. Combined ganciclovir and recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. J Acquir Immune Defic Syndr. 1991;4 Suppl 1:S22-8. [Medline].

  123. Hardy WD. Management strategies for patients with cytomegalovirus retinitis. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;14 Suppl 1:S7-12. [Medline].

  124. Jacobson MA, Wilson S, Stanley H, et al. Phase I study of combination therapy with intravenous cidofovir and oral ganciclovir for cytomegalovirus retinitis in patients with AIDS. Clin Infect Dis. Mar 1999;28(3):528-33. [Medline].

  125. Jabs DA. Design of clinical trials for drug combinations: cytomegalovirus retinitis--foscarnet and ganciclovir. The CMV retinitis retreatment trial. Antiviral Res. Jan 1996;29(1):69-71. [Medline].

  126. Davis JL, Hummer J, Feuer WJ. Laser photocoagulation for retinal detachments and retinal tears in cytomegalovirus retinitis. Ophthalmology. Dec 1997;104(12):2053-60; discussion 2060-1. [Medline].

  127. Gross JG, Bozzette SA, Mathews WC, et al. Longitudinal study of cytomegalovirus retinitis in acquired immune deficiency syndrome. Ophthalmology. May 1990;97(5):681-6. [Medline].

  128. Lim JI, Enger C, Haller JA, et al. Improved visual results after surgical repair of cytomegalovirus- related retinal detachments. Ophthalmology. Feb 1994;101(2):264-9. [Medline].

Further Reading

Keywords

cytomegalovirus retinitis, CMV retinitis

Contributor Information and Disclosures

Author

Michael Altaweel, MD, FRCS(C), Associate Professor, Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health
Michael Altaweel, MD, FRCS(C) is a member of the following medical societies: American Academy of Ophthalmology and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Coauthor(s)

Peter N Youssef, MD,, Clinical Instructor, Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison
Disclosure: Nothing to disclose.

Matthew D Reed, MD, Fellow, Department of Ophthalmology and Visual Sciences, University of Wisconsin Clinical Science Center
Disclosure: Nothing to disclose.

Medical Editor

V Al Pakalnis, MD, PhD, Professor of Ophthalmology, University of South Carolina School of Medicine; Chief of Ophthalmology, Dorn Veterans Affairs Medical Center
V Al Pakalnis, MD, PhD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and South Carolina Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Managing Editor

Steve Charles, MD, Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine; Adjunct Professor of Ophthalmology, Columbia College of Physicians & Surgeons; Clinical Professor Ophthalmology, Chinese University of Hong Kong
Steve Charles, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Club Jules Gonin, Macula Society, and Retina Society
Disclosure: Alcon Laboratories Consulting fee Consulting; OptiMedica Ownership interest Consulting

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.