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      Drugs & Diseases > Ophthalmology

      Cytomegalovirus (CMV) Retinitis Treatment & Management

      Updated: Feb 11, 2019
      • Author: Michael Altaweel, MD, FRCSC; Chief Editor: Andrew A Dahl, MD, FACS  more...
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      Treatment

      Medical Care

      After diagnosis, the first step in treatment is to administer systemic medications either in the form of intravenous infusion or oral administration. The most common choice is oral valganciclovir given its ease of use and excellent pharmacokinetics. This is the recommended regimen given CMV's broad presence, both in the eyes and other organs. Local/regional ocular therapy is largely reserved for cases in which systemic therapy is contraindicated or not well tolerated. The most common reason for cessation of systemic therapy is myelosuppression, following by kidney injury. [89] An internist or infectious disease specialist coordinates medical care. Ophthalmic assessment is required on a regular basis, with frequency dependent on existence of CMV retinitis and on CD4 count. The immunosuppressed individual requires evaluation for other opportunistic infections and surveillance for side effects of prescribed medications.

      Highly active antiretroviral therapy (HAART)   [90]

      This treatment regimen has altered the long-term management of CMV retinitis. [91, 92] Because the antiviral medications used to treat CMV are virustatic, patients needed to continue their use for the rest of their lives. The advent of HAART, with consequent recovery of immune function (2 consecutive CD4+ T-cell counts of ≥ 100 cells/μL at least 6 months apart) allows individuals to discontinue their CMV therapy if the retinitis has resolved adequately with antiviral treatment. [13] As long as the CD4 count remains elevated, disease recurrence is unlikely. [93]

      Intravenous or oral therapy can be discontinued, or a scheduled implant replacement can be delayed indefinitely. [94, 95] Careful monitoring of both immune status and ophthalmic findings are necessary to prevent retinal damage from an asymptomatic recurrence.

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      Surgical Care

      Individuals with CMV retinitis commonly require surgical intervention, whether for repair of a retinal detachment or for intravitreal instillation of ganciclovir by injection. Ganciclovir-eluting implants are no longer used in the United States.

      Retinal detachment due to CMV retinitis

      This condition occurs in 5-29% of eyes in various case series. High incidence of bilaterality exists. [96] Repair is most successful with vitrectomy, endolaser, and silicone oil endotamponade. [97, 98]

      Intravitreal ganciclovir implant   [99, 100]

      This is not currently available in the United States. Dosing is 1 µg/h sustained release with life span of 8 months. [101] Study of immediate versus deferred therapy:

      • Deferred - 15 days to progression
      • Immediate - 226 days to progression, only 5 of 14 progressed
      • Retinal detachment rate 11% (13-26% in IV treatment group)
      • Within 6 months, 50% develop CMV retinitis in fellow eye.

      Advantages include the following:

      • Less systemic toxicity
      • Better effect versus CMV in implanted eye
      • Can use AZT concomitantly
      • No indwelling catheter
      • Implant is useful if intolerant of systemic ganciclovir or if progression continues despite intravenous treatment. [102]

      Disadvantages include the following:

      • Sixty-seven percent developed CMV in the fellow eye versus 0-15% rate in intravenous treatment group.
      • No systemic effect for CMV organ disease
      • Risk of retinal detachment and vitreous hemorrhage: [103] Retinal detachment may occur despite the implant rather than as a consequence of surgery. The risk of detachment is reduced if immune recovery occurs in the period after the ganciclovir implant. [72]

      Intravitreal ganciclovir injection   [104]

      Details are as follows:

      • Delayed progression of disease
      • Topical anesthesia
      • Short half-life - Injection is required twice per week.
      • Increased risk of endophthalmitis, retinal detachment, and vitreous hemorrhage
      • Can be successful as sole treatment for CMV retinitis associated with immunosuppression without AIDS; in a case series of 13 eyes with active lesions, 5.54 ± 3.36 intravitreal ganciclovir injections were required, allowing resolution in 1.81 ± 1.25 months, with one late recurrence [105]

      Intravitreal foscarnet   [79] or cidofovir   [80] injection

      High-dose injection (2.4 mg) of foscarnet once to twice per week as an alternative to ganciclovir in patients who are intolerant. Cidofovir is given every 5-6 weeks. Potential side effects include iritis (18% with prophylactic oral probenecid) and/or visually significant hypotony (1%).

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      Consultations

      See the list below:

      • Infectious disease specialist
      • Evaluation of general medical condition - Assessment for other end-organ sequelae of CMV infection (pneumonitis, gastroenteritis); evaluation for other opportunistic infections
      • Evaluation for criteria sufficient to meet the diagnosis of AIDS
      • Assessment of confirmatory lab tests
      • Institution of systemic therapy (for CMV retinitis and for AIDS)
      • General internist, hematologist, and/or oncologist referral if CMV retinitis is associated with immunosuppression for non–HIV-related reasons
      • Transplantation specialist for transplant-related CMV retinitis
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      Complications

      Drug resistance

      Resistance to ganciclovir, [106]  foscarnet, [107, 108]  or cidofovir may occur since these drugs are administered long term; however, no in vitro studies or tissue sample studies have evaluated this theory definitively. Resistance is claimed based on an aberrant response to otherwise effective therapy. The chance of this occurring may increase with time. In a study of 76 newly diagnosed patients treated for CMV retinitis with intravenous ganciclovir, likely resistant isolates were obtained from blood or urine samples in 5.4% of patients at 3 months, 11.4% of patients at 6 months, and 27.5% of patients at 9 months.

      Management of drug resistance leading to reactivation of CMV retinitis or occurrence in the other eye involves combination therapy. [109, 110, 111, 112]  Ganciclovir and foscarnet are synergistic and may be combined in intravenous or intravitreal therapy.

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      Prevention

      CMV retinitis occurs in immunocompromised individuals. Treatment of underlying disorders can prevent the development of retinitis. Prevention practices to reduce the transmission of HIV would concomitantly reduce the incidence of CMV retinitis.

      In patients with HIV infection, CMV retinitis and other end-organ disease is best prevented using HAART to maintain the CD4 count above 100 cells/µL. Before HAART was widely available, several randomized trials evaluated the use of oral prophylactic therapy such as ganciclovir and valganciclovir. [113, 114] While ganciclovir is not available in this formulation in the United States, both did not show and preventative benefit both for patients receiving and not receiving HAART. [113, 114]

      The primary method for preventing severe CMV disease is recognizing the early manifestations of the disease and instituting proper therapy. Patients should be made aware of the implications of increased floaters in the eye and should establish care with a local ophthalmologist should symptoms arise. In the pre-modern HAART era, some specialists recommended ophthalmologic examinations every 3-4 months for patients with CD4 cells of less than 50 cells/µL, as up to half of early CMV retinitis cases were asymptomatic. [115] However, with the decline in CMV incidence in the modern HAART era, the value of this recommendation is unknown.

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      Long-Term Monitoring

      Ophthalmic follow-up care depends on stage of disease (ie, active vs atrophic retinitis), and CD4 count.

      Transplant-related CMV retinitis may occur late after transplantation. In a large series of pediatric allogeneic hematopoietic stem cell transplantation, CMV retinitis developed at a median of 199 days after transplantation. In addition, this occurred with a higher CD4 T-cell count (≥200/μL) and a lower CMV load than is generally associated with AIDS or with other organ system involvement following transplantation. This indicates the need for dilated examination, particularly if viremic. [5]

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