Cytomegalovirus retinitis after cardiac transplantation

Our results suggest that aggressive acute retinal necrosis treatment during pregnancy is both possible and necessary. Primer





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appearing at the necrotic retina. A milky fluid, probably debris from the necrotic retina, was noted in the subhyaloid space. DNA analysis of the vitreous aspirate by polymerase chain reaction identified herpes simplex virus as the causative virus (Table). Acyclovir (4,000 mg/day) was then administered orally in five separate doses over 2 weeks and thereafter 1,000 mg per day until delivery because of the immunocompromised state associated with pregnancy. Within 3 weeks of surgery, the entire necrotic retina became gliotic. The patient finally regained a visual acuity of LE, 20/40. The patient delivered a healthy baby (3,195 grams; Apgar score, 9 at 1 and 5 minutes) 39 weeks and 6 days into the gestational period. The postnatal development of the baby was unremarkable up to 1 year. Systemic administration of acyclovir has been indicated in maternal life-threatening conditions. However, the use of acyclovir during the first trimester of pregnancy has not been shown to increase the risk of birth defects or to increase any specific pattern of birth defects.’ Furthermore, acyclovir use during the second and third trimesters does not appear to present undue risk to the fetus. Therefore, acyclovir appears to be a reasonable therapy for pregnant patients with acute retinal necrosis. Interferon alpha or beta has been recommended as a synergistic adjunctive therapy to acyclovir for the treatment of acute retinal necrosis, in particular acute retinal necrosis by herpes zoster virus.3 A study has shown that interferon does not enter the fetus in humans.4 Furthermore, systemic interferon alpha in pregnant women has been used for treatment of Hodgkin disease and myeloproliferative disorders without adversely affecting the fetus.5 Based on these findings, interferon therapy was initiated in our patient during the twenty-sixth week of gestation. 104



REFERENCES 1. Saiki RK, Gelfand DH, Stoffel S, et al. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 1988;239:487-491. 2. Pregnancy outcomes following systemic prenatal acyclovir exposure: June 1, 1984-June 30, 1993. MMWR Morb Mortal Wkly Rep 1993;42:806-809. efficacy of antiherpes 3. Sakai J, Rai T, Usui M. Comparative drugs in acute necrosis [in Japanese]. Ganka Rinsyo Ihou 1991;85:876-881. 4. Pons JC, Lebon P, Frydman R, Delfraissy JF. Pharmacokinetits of interferon alpha in pregnant women and fetoplacental passage. Fetal Diagn Ther 1995;10:7-10. 5. Shpilberg 0, Shimon I, Dolitski M, Ben-Bassat I. Transient normal platelet counts and decreased requirement for interferon during pregnancy in essential thrombocythaemia. Br J Haematol 1996;92:491-493.

Cytomegalovirus Retinitis After Cardiac Transplantation Barron Albert0

C. Fishburne, MD, A. Mitrani, MD, and Janet L. Davis,


PURPOSE: To determine the prevalence of cytomegalovirus retinitis after cardiac transplantation. METHODS: Records of patients who had cardiac transplantation at Jackson Memorial Hospital between November 1986 and November 1994 were reviewed. Patients who had not previously had ophthalmic evaluation after transplantation were invited for retinal examination. RESULTS: Eighty-two patients had cardiac transplantation during the study period. One to 68 months (mean, 24.5 months) after transplantation, ophthalmoscopic examination was performed in 41 patients. Six ( 14.6%) of 41 patients had healed scars consistent with cytomegalovirus retinitis or active cytomegalovirus retinitis. CONCLUSIONS: Cytomegalovirus retinitis lesions were found in six (14.6%) of 41 patients. If remaining patients were unaffected and no patient developed cytomegalovirus retinitis after ophthalmoscopic examination, the prevalence would be 7.3% (6/82). W e recommend ophthalmic screening of all patients 3 to 4 months after cardiac OF OPHTHALMOLOGY


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transplantation with repeat examinations as ocular symptoms occur.





yearly or



plication of immunosuppression after organ transplantation. A multicenter review of cardiac transplantation yielded a 13% incidence of systemic cytomegalovirus infection by pathologic or clinical diagnosis with laboratory confirmation.’ Cytomegalovirus retinitis is well described in immunosuppressed patients. 2,3 Although initial reports were associated with transplantation, the association with the acquired immunodeficiency syndrome (AIDS) has overshadowed other causes. We screened cardiac transplant patients from Jackson Memorial Hospital for evidence of cytomegalovirus retinitis to determine the prevalence in this population. A retrospective review of cardiac transplant patients at Jackson Memorial Hospital was performed. Following Institutional Review Board approval, all surviving patients who had no post-transplantation ophthalmic examination were invited for retinal evaluation. From November 1986 until November 1994, the Cardiac Transplant Team at Jackson Memorial Hospital performed cardiac transplantation in 82 patients. A summary of the experience has been reported previously.4 All patients received an initial standard regimen of cyclosporine, 5 to 10 mg/kg daily; azathioprine, 2 mg/kg daily; and prednisone, 50 mg orally two times daily, after 3 days of intravenous methylprednisolone. MuromonabCD3, an anti-Tlymphocyte monoclonal antibody, was used in cases of severe rejection. Patients without evidence of rejection on endocardial biopsy were gradually tapered to 5 mg of prednisone daily by 1 year; azathioprine dose was adjusted until the white blood cell count fell to about 5,000 cells/mm3; and therapeutic blood levels of cyclosporine were maintained. Thirteen patients did not survive 3 months; one of these had ophthalmoscopic examination after cardiac transplantation. Nineteen (23.2%) of 82 had a histo-

Accepted for publication August 8, 1997. Carolina Retina Center, PA (B.C.F.); Departments of Internal Medicine (A.A.M.) and Ophthalmology, Bascom Palmer Eye Institute (J.L.D.), University of Miami School of Medicine. Inquiries to Janet Davis, MD, P.O. Box 016880, Miami, FL 331016880.





FIGURE 1. Active cytomegalovirus retinitis asymptomatic immunosuppressed patient after transplantation.

in an cardiac

ry of treatment for systemic cytomegalovirus. Two patients had active cytomegalovirus infection diag nosed at the eye examination. No patient developed systemic cytomegalovirus infection after his or her eye evaluation. Forty-one patients had ophthalmoscopic examinations performed 1 to 68 (mean, 24.5) months after cardiac transplantation. Twenty-eight (68%) of the examinations were by a single observer (J.L.D.). Eight of 41 patients complained of photopsias, floaters, or scotomata. Of the eight symptomatic patients, two had no abnormalities. Two had acute posterior vitreous separations. One had a nonspecific peripheral pigmentary degeneration. One had a history of multiple ocular surgeriesbut no new pathology. Two of the eight symptomatic patients had evidence of cytomegalovirus retinitis. Six (14.6%) of 41 patients had evidence of cytoc megalovirus retinitis. One patient with a history of systemic cytomegalovirus had a symptomatic retinal detachment at the border of scarred retina that required a scleral buckling procedure. Two patients had asymptomatic active cytomegalovirus retinitis (Figure 1). One patient had lesions that suggested healed cytomegalovirus retinitis and symptomatic cystoid macular edema that resolved without treatment. Two asymptomatic patients had retinal scarring consistent with cytomegalovirus (Figure 2).



prednisone.4 We recommend screening patients 3 to 4 months after cardiac transplantation for cytomegalovirus retinitis or its sequelae. Repeat examination should probably be performed yearly or more frequently if symptoms occur. REFERENCES

FIGURE 2. Chorioretinal scarring consistent with inactive cytomegalovirus retinitis found at screening in an asymptomatic immunosuppressed patient after cardiac transplantation.

We found lesions suggestive or diagnostic of cytomegalovirus retinitis in six (14.6%) of 41 patients who were examined 1 to 68 months after cardiac transplantation. Although we did not examine the entire cohort, we examined 41 (60%) of 69 patients surviving more than 3 months. If all unexamined patients did not have cytomegalovirus retinitis and no new cases developed after ophthalmoscopic examination, the prevalence would still be high at 7.3% (6/82). All patients retained good visual function, and most were diagnosed after the infection had healed with characteristic scars. Of the two patients with active cytomegalovirus retinitis, one was treated successfully with intravenous ganciclovir for 8 weeks, and one healed after reduction of immunosuppression. Occult cytomegalovirus retinitis in transplant patients appears to be more common than recognized. Seven of 14 patients were asymptomatic in the series by Egbert and associates. 3 In our series, four of six patients were asymptomatic despite cytomegalovirus lesions. Systemic cytomegalovirus by clinical or serologic criteria is most likely within 4 months after transplantation. It is during this period that immunosuppression is generally greatest because of the high doses of




1. Kirklin JK, Naftel DC, Levine TB, et al. Cytomegalovirus after heart transplantation: risk factors for infection and death: a multiinstitutional study. J Heart Lung Transplant 1994;13: 394-404. 2. Pollard RB, Egbert PR, Gallagher JG, Merigan TC. Cytomegalovirus retinitis in immunosuppressed hosts, I: natural history and effects of treatment with adenine arabinoside. Ann Intern Med 1980;93:655-664. 3. Egbert PR, Pollard RB, Gallagher JG, Merigan TC. Cytomegalovirus retinitis in an immunosuppressed host, II: ocular manifestations. Ann Intern Med 1980;93:664-670. D, de Marchena E, Mitrani A, Bolooki H, Cardiac 4. Norberg Transplant Team, University of Miami, Jackson Memorial Medical Center. Cardiac transplantation: University of Miami/Jackson Memorial Hospital experience. J Fl Med Assoc 1994;81:414-417. 5. Andersson R, Sandberg T, Berglin E, Jeansson S. Cytomegalovirus infections and toxoplasmosis in heart transplant recipients in Sweden. Stand J Infect Dis 1992;24:411-417.

Reduction of Cyclosporine Dosage with Ketoconazole in a Patient With Birdshot Retinochoroidopathy Bruce

E. Silverstein,


and Ira G. Wong, MD

PURPOSE: To report the successful reduction of cyclosporine dosage with adjunctive ketoconazole in a patient with birdshot retinochoriodopathy. METHOD: Case report. RESULTS: A 55year-old woman treated with cyclosporine for birdshot retinochoroidopathy had ketoconazole (200 mg/day) added to her medical regimen. Her cyclosporine dosage was reduced to 40 mg per day from 200 mg per day, an 80% reduction. No toxic effect was observed during 12 months of follow-up nor was there progression of the birdshot retinochoroidopathy. CONCLUSIONS: Cyclosporine dosage may be reduced considerably in patients with uveitis who use adjunctive ketoconazole. The regimen appears to be safe and efficacious. OF OPHTHALMOLOGY


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