eMedicine Specialties > Ophthalmology > Retina

Retinitis, CMV: Treatment & Medication

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): Matthew D Reed, MD, Fellow, Department of Ophthalmology and Visual Sciences, University of Wisconsin Clinical Science Center
Contributor Information and Disclosures

Updated: Apr 18, 2006

Treatment

Medical Care

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
    • This treatment regimen has altered the long-term management of CMV retinitis. Because the antiviral medications used to treat CMV are virustatic, it was necessary for patients to continue their use for the rest of their lives. The advent of HAART with consequent recovery of immune function allows individuals to discontinue their CMV therapy if the process has resolved adequately with initial antiviral treatment. As long as the CD4 count remains elevated, there is little risk of disease recurrence.
    • Intravenous or oral therapy can be discontinued, or a scheduled implant replacement can be delayed indefinitely.
    • Careful monitoring of both immune status and ophthalmic findings are necessary to prevent retinal damage from an asymptomatic recurrence.

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 or implantation.

  • Retinal detachment due to CMV retinitis
    • This condition occurs in 5-29% of eyes in various case series. High incidence of bilaterality exists.
    • Repair is most successful with vitrectomy, endolaser, scleral buckle, and silicone oil endotamponade.
    • A total reattachment rate of 76% exists; macular attachment occurs in 90%. Mean postoperative visual acuity is 6/18.
    • Prophylactic laser for the other eye with CMV did not prevent retinal detachment.
  • Intravitreal ganciclovir implant
    • 1 µg/h sustained release with life span of 8 months - 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.
    • Pros
      • 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.
    • Cons
      • Sixty-seven percent developed CMV in the fellow eye versus 0-15% rate in intravenous treatment group.
      • No systemic effect for CMV organ disease
  • Intravitreal ganciclovir injection
    • Delayed progression of disease
    • Topical anesthesia
    • Short half-life - Injection is required twice per week.
    • Increased risk of endophthalmitis, retinal detachment, and vitreous hemorrhage

Consultations

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

Medication

A number of different antiviral medications are available for the treatment of CMV retinitis. Routes of delivery and adverse effect profiles vary significantly, so treatment programs are tailored to individual patients and their response to treatment. Current therapies use an induction dose to halt active disease followed by a lower maintenance dose that must be continued indefinitely unless immune recovery occurs. In recent years, several developments have drastically improved the quality of life for patients with CMV retinitis.

HAART therapy, as previously mentioned, has allowed immune recovery that, in turn, allows discontinuation of anti-CMV medication. This often obviates the need for multiple implant procedures or the long-term dose related adverse effects of anti-CMV medications.

Valganciclovir, a prodrug of ganciclovir that possesses excellent oral bioavailability and antiviral activity, has been shown to be effective in both the induction phase and the maintenance phase of CMV retinitis treatment. It is available in convenient once daily or twice daily dosing. Valganciclovir has largely replaced other treatments since it avoids the need for frequent IV infusions and long-term IV access ports.

Neupogen (granulocyte colony stimulating factor) can be used in conjunction with valganciclovir in patients experiencing neutropenia. This has helped to lessen one of the most common treatment terminating adverse effects of a very convenient and useful medication.

Foscarnet and cidofovir are effective alternatives in the treatment of CMV retinitis. However, because of their adverse effect profiles and the lack of an orally bioavailable form, they have become second-line treatments. Intravitreal implants are used less frequently but are still needed in patients who have reactivation of retinitis despite systemic treatment or in those who cannot tolerate systemic treatment.

At this time, primary treatment generally consists of induction with either valganciclovir (900 mg PO bid for 2-3 wk) or ganciclovir (5 mg/kg IV bid for 2-3 wk) followed by maintenance with valganciclovir (900 mg PO qd) until the CD4 count is above 100 cells/mL.

Finally, IRU has added a new postscript to the treatment of CMV retinitis. Treatment options are varied, and close follow-up by an experienced ophthalmologist is needed to guard against vision-threatening complications.

Antivirals

Direct action is to inhibit the DNA polymerase of CMV, preventing viral replication.


Ganciclovir (Cytovene, Vitrasert)

Analog of guanosine, 10-100 times more potent than acyclovir versus CMV in vitro. Selectively inhibits DNA polymerase of CMV cells. Renal excretion.
Virostatic - Discontinuation of use leads to 100% relapse rate within 4 weeks.
Effective - 88% complete response, 9% partial.
Long-term IV access is necessary. Oral administration is possible, but the bioavailability of oral ganciclovir is limited to less than 10%. Although use of this medication for prophylaxis reduces the incidence of CMV end-organ disease by up to 50%, its use usually is not recommended because most patients would be using it unnecessarily and the incidence of side effects is high. A valine ester prodrug of ganciclovir, valganciclovir, has good bioavailability and can be used in place of intravenous ganciclovir for maintenance dosing and for the prevention of recurrences.
Oral ganciclovir - Two trials for maintenance treatment. A faster rate of progression was found in the first trial. With higher dosing (1 g tid), there was an equal rate of progression.A dose dependent increase in neutropenia exists.

Adult

IV induction: 5-7.5 mg/kg/d for 2-3 wk IV maintenance: 5 mg/kg/d 5 d/wk
Decrease dose for severe renal failure, neutropenia, or thrombocytopenia; reactivation of retinitis while on maintenance dose will require reinduction
PO maintenance: 1000 mg tid
Intravitreal implant is an effective longer term alternative

Pediatric

5 mg/kg IV qd

Synergistic effect with foscarnet; less neutropenia if GCSF coadministered; zidovudine, imipenem, didanosine, tacrolimus

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Myelosuppressive; neutropenia up to 40%, usually resolves with drug cessation; thrombocytopenia up to 18%; anemia; teratogenic; infertility; rash
Monitor CBC/platelets q2d during induction, then weekly; reactivation occurs in 50% by 4 mo, median of 47 d; then, repeat induction dose


Foscarnet (Foscavir)

Analog of pyrophosphate. Inhibits DNA polymerase of CMV and reverse transcriptase of HIV. Virostatic; renal excretion. As effective as ganciclovir. Median time to relapse on Rx is 53 d. Foscarnet/ganciclovir CMV retinitis trial: 234 newly diagnosed patients randomized. Same efficacy for controlling retinitis and preserving vision. Survival with foscarnet 12.6 mo versus 8.5 for ganciclovir group; mortality risk 1.79x. Controlling for antiretroviral use, still better survival with foscarnet. Foscarnet has anti-HIV activity but has more dose-limiting toxicity.

Adult

Prehydration (infusion pump): Long-term IV access Induction: 90 mg/kg q12h for 14-21 d
Maintenance: 90-120 mg/kg IV qd
Intravitreal injection: 2400 mcg/0.1 mL q72h
Decrease dose in renal failure

Pediatric

Administer as in adults

Synergistic effect with ganciclovir; compared ganciclovir and foscarnet at half dose versus daily alternation at regular dose 37% incidence of neutropenia, GCSF reversed the majority; dose-limiting nephrotoxicity in 4%; alternating regime preferred, as effective for limiting progression cidofovir, pentamidine

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Monitor CBC, creatinine, calcium, magnesium, and potassium q3d during induction, then weekly; adverse effects include nephrotoxic (up to 30% require cessation of use), hypocalcemia, confusion, seizures, arrhythmia, diabetes insipidus, hyperphosphatemia, genital ulcerations


Cidofovir (Vistide)

Nucleotide analog that selectively inhibits viral DNA production in CMV and other herpes viruses.

Adult

5 mg/kg IV every other wk, plus probenecid (2 g PO 3 h prior, 1 g 2 h after, and 1 g 8 h after cidofovir) Concomitant use of probenecid and prehydration reduces incidence of nephrotoxicity
Intravitreal injection dose: 20 mcg

Pediatric

Not established

Avoid use with foscarnet, which also can be nephrotoxic; amikacin, tobramycin, gentamicin

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Adverse effects include nephrotoxicity, proteinuria, neutropenia, ocular hypotony; monitor for changes in renal function (urine protein, serum creatinine)


Valganciclovir (Valcyte)

L-valyl ester prodrug of ganciclovir used to treat CMV retinitis in patients with AIDS. Ganciclovir is synthetic analogue of 2'-deoxyguanosine, which inhibits replication of human CMV in vitro and in vivo. Inhibits viral activity by inhibiting viral DNA synthesis. Has the advantage of qd or bid PO administration. Achieves levels comparable to those obtained with IV ganciclovir.

Adult

Induction (active CMV retinitis): 900 mg PO bid with food for 21 d
Maintenance: 900 mg PO qd with food

Pediatric

Not established

Interactions are similar to those reported with ganciclovir; coadministration with cytotoxic drugs, such as dapsone, vinblastine, adriamycin, pentamidine, flucytosine, vincristine, amphotericin B, trimethoprim/sulfamethoxazole combinations, or other nucleoside analogs may result in additive toxicity of rapidly dividing cell populations, including bone marrow, spermatogonia, germinal layers of skin, and GI mucosa (coadminister only if benefits outweigh risks); coadministration with imipenem-cilastatin may cause generalized seizures (use only if benefits outweigh risks); serum creatinine may increase following concurrent use of ganciclovir with either cyclosporine or amphotericin B; in presence of probenecid, ganciclovir renal clearance is reduced; bioavailability may increase when didanosine is administered either 2 h prior to or simultaneously with ganciclovir; bioavailability of ganciclovir may decrease in presence of zidovudine, while bioavailability of zidovudine is increased in presence of ganciclovir

Documented hypersensitivity; severe renal dysfunction or hemodialysis; pregnancy; breastfeeding; absolute neutrophil count is <500 cells/mm3, platelet count is <25,000/mm3, or hemoglobin is <8 g/dL

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Strict adherence to dosage guidelines essential to avoid overdose; valganciclovir tablets may not be substituted for ganciclovir capsules on one-to-one basis; adjust dose according to CrCl in impaired renal function; may cause granulocytopenia, anemia, and thrombocytopenia

Antisense medications

Inhibit viral replication by interfering with the regulation of viral gene expression.


Fomivirsen sodium (Vitravene)

A phosphorothioate oligonucleotide. The nucleotide sequence is complimentary to the CMV viral mRNA, which encodes proteins responsible for regulation of viral gene expression. Inhibition of viral protein synthesis is achieved when fomivirsen binds the target mRNA. Second-line management.

Adult

330 mcg (0.05 mL) intravitreal injection q2wk for 2 doses, then q4wk

Pediatric

Not established

Interaction with systemically administered drugs has not been studied

Documented hypersensitivity; cidofovir administration within preceding 2 weeks, potential worsening of uveitis

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Adverse effects include uveitis, ocular discomfort, blurred vision, increased intraocular pressure

Colony stimulating factors

Stimulation of stem cells to produce differentiation, proliferation, and increased functional activity of neutrophils, monocytes, eosinophils, and macrophages.


Filgrastim (Neupogen)

Up to 40% of ganciclovir users experience dose-limiting neutropenia, which may require discontinuation. GCSF has limited this effect markedly in some studies.

Adult

5-10 mcg/kg SC injection qd for 2-4 wk

Pediatric

5 mcg/kg SC injection qd for 2-4 wk

May develop greater than expected elevation in white blood cell count with lithium; peripheral neuropathy may develop with vincristine

Documented hypersensitivity to E coli -derived proteins

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

May possibly act as a growth factor for tumors

More on Retinitis, CMV

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Further Reading

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Keywords

cytomegalovirus retinitis, CMV retinitis

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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)

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

Medical Editor

Vytautas A Pakainis, MD, Chief of Ophthalmology, Dorn Veterans Administration Medical Center, Professor of Ophthalmology, Ophthalmology, University of South Carolina School of Medicine
Vytautas A Pakainis, MD 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
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

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.

 
 
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