CYTOMEGALOVIRUS RETINITIS AFTER TREATMENT WITH INTRAVITREAL TRIAMCINOLONE ACETONIDE IN AN IMMUNOCOMPETENT PATIENT Jason Hsu, MD, Eric Chen, MD, James F. Vander, MD
Purpose: To describe a case of cytomegalovirus (CMV) retinitis following intravitreal triamcinolone acetonide (IVTA) in an immunocompetent patient. Methods: A 77-year-old man with a history of diabetes mellitus developed retinal whitening with a vasculitis 6 weeks after receiving IVTA in the left eye. A vitreous biopsy was performed. Results: Polymerase chain reaction was positive for CMV (419,000 copies/mL). A complete medical evaluation, including a negative test for human immunodeficiency virus, showed no systemic evidence of immunosuppression except for a highly elevated hemoglobin A1C level. Conclusion: CMV retinitis may be a rare complication of IVTA, possibly due to local ocular immunosuppression from the steroid medication. Poorly controlled diabetes mellitus may have contributed to this development. RETINAL CASES & BRIEF REPORTS 1:208 –210, 2007
From the Retina Service, Wills Eye Institute, Philadelphia, Pennsylvania.
after complicated cataract surgery in the left eye. Two days later, pars plana vitrectomy, lensectomy, and IVTA treatment (4 mg) were performed. Two weeks after surgery, visual acuity was 3/200 in the left eye. Fundus examination revealed cystoid macular edema and residual IVTA inferiorly but was otherwise unremarkable. At his 6-week postoperative visit, examination revealed visual acuity of 3/200 in the left eye, trace anterior chamber cell, and retinal whitening with small satellite lesions associated with vasculitis along the inferotemporal arcade (Fig. 1). Viral retinitis was suspected, and vitreous biopsy was performed. One week later, the area of retinal whitening had increased with a new area in the superotemporal periphery (Fig. 2). Results of vitreous biopsy were positive for CMV (419,000 copies/mL) and negative for herpes simplex virus as well as varicella-zoster virus by polymerase chain reaction analysis. Blood studies revealed an elevated titer of IgG antibody to CMV with no IgM antibody detected, suggesting previous exposure to CMV rather than acute infection. Therapy with valganciclovir (900 mg twice daily for 3 weeks then once daily) was started. Complete medical evaluation showed no systemic evidence of immunosuppression. White blood cell and differential cell counts were normal. Mild anemia was noted with a hemoglobin concentration of 10.3 g/dL. Results of testing for human immunodeficiency virus were negative. The hemoglobin A1c level was 11.1%, indicating poor glycemic control. One month later, visual acuity was 20/400 in the left eye. Examination revealed a decrease in retinal whitening with atrophic areas (Fig. 3). He was instructed to continue therapy with valgan-
C
ytomegalovirus (CMV) retinitis has been well described in immunocompromised patients, including those receiving systemic immunosuppressant therapy after bone marrow or organ transplantation,1 those with acquired immunodeficiency syndrome,2 and those with congenital infection.3 We describe a case of CMV retinitis after treatment with intravitreal triamcinolone acetonide (IVTA) in a human immunodeficiency virus–negative patient with poorly controlled diabetes mellitus but no evidence of immunosuppression otherwise. Case Report A 77-year-old man with a history of type 2 diabetes mellitus presented with retained lens material and cystoid macular edema Supported by the Retina Service of Wills Eye Institute (Philadelphia, PA). The authors have no relevant financial interest in this report. Correspondence to: James F. Vander, MD, Retina Service, Wills Eye Hospital, 840 Walnut Street, Suite 1020, Philadelphia, PA 19107; e-mail: [email protected]
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CMV RETINITIS AFTER IVTA TREATMENT
Fig. 1. Color fundus photograph of the left eye taken 6 weeks after intravitreal injection of triamcinolone acetonide for cystoid macular edema after complicated cataract surgery. An area of retinal whitening with satellite lesions and vasculitis is seen along the inferotemporal arcade.
ciclovir (900 mg once daily) and follow-up with his internist for improved glycemic control.
Discussion To our knowledge, only one other case of CMV retinitis after IVTA treatment in an immunocompetent patient has been reported.4 This patient developed the disease 4 months after IVTA therapy for diabetic
Fig. 2. Color fundus photograph of the left eye taken 1 week after initial presentation of retinal whitening. Vitreous fluid was positive for cytomegalovirus by polymerase chain reaction analysis. Note the increase in the area of retinal whitening along the inferotemporal arcade.
209
Fig. 3. Color fundus photograph of the left eye taken 5 weeks after initial presentation of retinal whitening and after 4 weeks of valganciclovir therapy for cytomegalovirus retinitis. Decreased retinal whitening with vascular attenuation and retinal atrophy is now seen. A new hemorrhage with a cotton-wool spot is seen in the macula superotemporal to the foveola.
macular edema. The researchers postulated that their patient developed CMV retinitis after local ocular immunosuppression from IVTA treatment despite a normal systemic immune system. A report of reactivation of CMV retinitis in a human immunodeficiency virus–positive patient after posterior sub–Tenon space injection of triamcinolone supports this theory.5 The temporal course in our patient strongly implicates triamcinolone acetonide as the inciting factor because he developed CMV retinitis 6 weeks after IVTA treatment. Comparing the patients, both were elderly men with type 2 diabetes mellitus, although the previous patient was described as having “wellcontrolled” diabetes, while our patient had poorly controlled diabetes. The hyperglycemia associated with diabetes mellitus is believed to cause abnormalities in cell-mediated immunity and phagocyte function leading to the development of more severe and unusual infections.6 Perhaps the combination of diabetes with targeted ocular immunosuppression from IVTA treatment may have predisposed these patients to developing CMV retinitis. Alternatively, the presence of diabetes in both patients may be coincidental because IVTA treatment is used relatively frequently for these patients. Nonetheless, this occurrence must be exceedingly rare because so few cases have been reported despite the large number of IVTA injections performed on diabetic patients over the past several years.
RETINAL CASES & BRIEF REPORTSℜ
210
Key words: cytomegalovirus, retinitis, triamcinolone acetonide, immunocompetent. References 1.
2.
Egbert PR, Pollard RB, Gallagher JG, et al. Cytomegalovirus retinitis in immunosuppressed hosts. II. Ocular manifestations. Ann Intern Med 1980;93:664–670. Hoover DR, Peng Y, Saah A, et al. Occurrence of cytomegalovirus retinitis after human immunodeficiency virus immunosuppression. Arch Ophthalmol 1996;114:821–827.
3. 4.
5.
6.
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2007
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NUMBER 4
Stagno S, Reynolds DW, Huang ES, et al. Congenital cytomegalovirus infections. N Engl J Med 1977;296:1254–1258. Saidel MA, Berreen J, Margolis TP. Cytomegalovirus retinitis after intravitreous triamcinolone in an immunocompetent patient. Am J Ophthalmol 2005;140:1141–1143. Dalessandro L, Bottaro E. Reactivation of CMV retinitis after treatment with subtenon corticosteroids for immune recovery uveitis in a patient with AIDS. Scand J Infect Dis 2002;34: 780–782. Joshi N, Caputo GM, Weitekamp MR, Karchmer AW. Infections in patients with diabetes mellitus. N Engl J Med 1999; 341:1906–1912.
Purpose: To describe a case of cytomegalovirus (CMV) retinitis following intravitreal triamcinolone acetonide (IVTA) in an immunocompetent patient. Methods: A 77-year-old man with a history of diabetes mellitus developed retinal whitening with a vasculitis 6 weeks after receiving IVTA in the left eye. A vitreous biopsy was performed. Results: Polymerase chain reaction was positive for CMV (419,000 copies/mL). A complete medical evaluation, including a negative test for human immunodeficiency virus, showed no systemic evidence of immunosuppression except for a highly elevated hemoglobin A1C level. Conclusion: CMV retinitis may be a rare complication of IVTA, possibly due to local ocular immunosuppression from the steroid medication. Poorly controlled diabetes mellitus may have contributed to this development. RETINAL CASES & BRIEF REPORTS 1:208 –210, 2007
From the Retina Service, Wills Eye Institute, Philadelphia, Pennsylvania.
after complicated cataract surgery in the left eye. Two days later, pars plana vitrectomy, lensectomy, and IVTA treatment (4 mg) were performed. Two weeks after surgery, visual acuity was 3/200 in the left eye. Fundus examination revealed cystoid macular edema and residual IVTA inferiorly but was otherwise unremarkable. At his 6-week postoperative visit, examination revealed visual acuity of 3/200 in the left eye, trace anterior chamber cell, and retinal whitening with small satellite lesions associated with vasculitis along the inferotemporal arcade (Fig. 1). Viral retinitis was suspected, and vitreous biopsy was performed. One week later, the area of retinal whitening had increased with a new area in the superotemporal periphery (Fig. 2). Results of vitreous biopsy were positive for CMV (419,000 copies/mL) and negative for herpes simplex virus as well as varicella-zoster virus by polymerase chain reaction analysis. Blood studies revealed an elevated titer of IgG antibody to CMV with no IgM antibody detected, suggesting previous exposure to CMV rather than acute infection. Therapy with valganciclovir (900 mg twice daily for 3 weeks then once daily) was started. Complete medical evaluation showed no systemic evidence of immunosuppression. White blood cell and differential cell counts were normal. Mild anemia was noted with a hemoglobin concentration of 10.3 g/dL. Results of testing for human immunodeficiency virus were negative. The hemoglobin A1c level was 11.1%, indicating poor glycemic control. One month later, visual acuity was 20/400 in the left eye. Examination revealed a decrease in retinal whitening with atrophic areas (Fig. 3). He was instructed to continue therapy with valgan-
C
ytomegalovirus (CMV) retinitis has been well described in immunocompromised patients, including those receiving systemic immunosuppressant therapy after bone marrow or organ transplantation,1 those with acquired immunodeficiency syndrome,2 and those with congenital infection.3 We describe a case of CMV retinitis after treatment with intravitreal triamcinolone acetonide (IVTA) in a human immunodeficiency virus–negative patient with poorly controlled diabetes mellitus but no evidence of immunosuppression otherwise. Case Report A 77-year-old man with a history of type 2 diabetes mellitus presented with retained lens material and cystoid macular edema Supported by the Retina Service of Wills Eye Institute (Philadelphia, PA). The authors have no relevant financial interest in this report. Correspondence to: James F. Vander, MD, Retina Service, Wills Eye Hospital, 840 Walnut Street, Suite 1020, Philadelphia, PA 19107; e-mail: [email protected]
208
CMV RETINITIS AFTER IVTA TREATMENT
Fig. 1. Color fundus photograph of the left eye taken 6 weeks after intravitreal injection of triamcinolone acetonide for cystoid macular edema after complicated cataract surgery. An area of retinal whitening with satellite lesions and vasculitis is seen along the inferotemporal arcade.
ciclovir (900 mg once daily) and follow-up with his internist for improved glycemic control.
Discussion To our knowledge, only one other case of CMV retinitis after IVTA treatment in an immunocompetent patient has been reported.4 This patient developed the disease 4 months after IVTA therapy for diabetic
Fig. 2. Color fundus photograph of the left eye taken 1 week after initial presentation of retinal whitening. Vitreous fluid was positive for cytomegalovirus by polymerase chain reaction analysis. Note the increase in the area of retinal whitening along the inferotemporal arcade.
209
Fig. 3. Color fundus photograph of the left eye taken 5 weeks after initial presentation of retinal whitening and after 4 weeks of valganciclovir therapy for cytomegalovirus retinitis. Decreased retinal whitening with vascular attenuation and retinal atrophy is now seen. A new hemorrhage with a cotton-wool spot is seen in the macula superotemporal to the foveola.
macular edema. The researchers postulated that their patient developed CMV retinitis after local ocular immunosuppression from IVTA treatment despite a normal systemic immune system. A report of reactivation of CMV retinitis in a human immunodeficiency virus–positive patient after posterior sub–Tenon space injection of triamcinolone supports this theory.5 The temporal course in our patient strongly implicates triamcinolone acetonide as the inciting factor because he developed CMV retinitis 6 weeks after IVTA treatment. Comparing the patients, both were elderly men with type 2 diabetes mellitus, although the previous patient was described as having “wellcontrolled” diabetes, while our patient had poorly controlled diabetes. The hyperglycemia associated with diabetes mellitus is believed to cause abnormalities in cell-mediated immunity and phagocyte function leading to the development of more severe and unusual infections.6 Perhaps the combination of diabetes with targeted ocular immunosuppression from IVTA treatment may have predisposed these patients to developing CMV retinitis. Alternatively, the presence of diabetes in both patients may be coincidental because IVTA treatment is used relatively frequently for these patients. Nonetheless, this occurrence must be exceedingly rare because so few cases have been reported despite the large number of IVTA injections performed on diabetic patients over the past several years.
RETINAL CASES & BRIEF REPORTSℜ
210
Key words: cytomegalovirus, retinitis, triamcinolone acetonide, immunocompetent. References 1.
2.
Egbert PR, Pollard RB, Gallagher JG, et al. Cytomegalovirus retinitis in immunosuppressed hosts. II. Ocular manifestations. Ann Intern Med 1980;93:664–670. Hoover DR, Peng Y, Saah A, et al. Occurrence of cytomegalovirus retinitis after human immunodeficiency virus immunosuppression. Arch Ophthalmol 1996;114:821–827.
3. 4.
5.
6.
●
2007
●
VOLUME 1
●
NUMBER 4
Stagno S, Reynolds DW, Huang ES, et al. Congenital cytomegalovirus infections. N Engl J Med 1977;296:1254–1258. Saidel MA, Berreen J, Margolis TP. Cytomegalovirus retinitis after intravitreous triamcinolone in an immunocompetent patient. Am J Ophthalmol 2005;140:1141–1143. Dalessandro L, Bottaro E. Reactivation of CMV retinitis after treatment with subtenon corticosteroids for immune recovery uveitis in a patient with AIDS. Scand J Infect Dis 2002;34: 780–782. Joshi N, Caputo GM, Weitekamp MR, Karchmer AW. Infections in patients with diabetes mellitus. N Engl J Med 1999; 341:1906–1912.
