CYTOMEGALOVIRUS RETINITIS AFTER INTRAVITREOUS TRIAMCINOLONE TREATMENT OF A VITRECTOMIZED EYE IN AN IMMUNOCOMPETENT PATIENT Mariko Furukawa, MD,* Kazuyuki Kumagai, MD,† Nobuchika Ogino, MD,† Satoshi Okinami, MD,‡ Akinori Uemura, MD,§ Eric Larson, PHD¶
Purpose: To report a case of cytomegalovirus (CMV) retinitis after intravitreous injection of triamcinolone for a vitrectomized eye in an immunocompetent patient. Design: Observational case report. Methods: Review of medical records. Results: A 54-year-old woman with well-controlled type 2 diabetes developed anterior uveitis, papillitis, retinal vasculitis, and retinal exudates 3 months after intravitreous triamcinolone for the treatment of recurred macular edema. The intravitreal white mass of triamcinolone was ophthalmoscopically observed on the inferior peripheral retina. Polymerase chain reaction of the vitreous was positive for CMV DNA. There was no sign of systemic CMV infection. Laboratory examination revealed that the patient was a human T cell lymphotropic virus type 1 carrier and HIV negative. The retinitis responded well to systemic ganciclovir and intravitreous foscarnet, but the treatment of anterior uveitis and vitreous opacity needed repeated vitreous surgery. Conclusion: CMV retinitis can occur after intravitreous triamcinolone for a vitrectomized eye in an immunocompetent patient. RETINAL CASES & BRIEF REPORTS 1:205–207, 2007
From the *Department of Ophthalmology, Kamiiida First General Hospital, Nagoya, Japan; †Shinjo Ophthalmologic Institute, Miyazaki, Japan; the ‡Department of Ophthalmology, Saga University, Saga, Japan; the §Department of Ophthalmology, Kagoshima City Hospital, Kagoshima, Japan; and the ¶Department of English, Miyazaki Prefectural Nursing University, Miyazaki, Japan.
triamcinolone acetonide (TA) treatment of a vitrectomized eye in a human immunodeficiency virus–negative woman without other evidence of immune system dysfunctions and systemic symptoms. Case Report In June 2004, a 54-year-old woman with well controlled type 2 diabetes mellitus presented to our clinic for decreased vision in the left eye. At examination, visual acuity was 0.5, and cystoid macular edema, due to central retinal vein occlusion with panretinal photocoagulation, was noted and treated with vitrectomy combined with cataract surgery on June 17, 2004. Cystoid macular edema resolved, and visual acuity improved to 1.0. In October 2004, cystoid macular edema recurred with visual acuity decreasing to 0.5. After extensive discussion and obtained informed consent, the recurred cystoid macular edema was treated with intravitreous TA (10 mg) on November 11, 2004. Cystoid macular edema resolved, and visual acuity improved to 1.2. However, the patient returned on
C
ytomegalovirus (CMV) retinitis commonly develops in patients with systemic immunodeficiency. There have been few reports of CMV retinitis without immune deficiency and systemic symptoms.1– 4 We describe a case of CMV retinitis after intravitreous Proprietary interest for this report is credited to Kazuyuki Kumagai. Reprint requests: Kazuyuki Kumagai, MD, 889 Mego, Shimokitakata-cho, Miyazaki 880-0035 Japan.
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Fig. 1. Fundus photograph of the left eye 3 months after intravitreal triamcinolone acetonide treatment of recurrent macular edema. Note papillitis, retinal vasculitis, and retinal exudates.
February 10, 2005, complaining of blurred vision in the left eye. Examination of the left eye revealed visual acuity of 1.0, intraocular pressure of 32 mmHg, small granulomatous keratic precipitates, 1⫹ aqueous cell and flare, and 1⫹ vitreous inflammatory cell. Funduscopic examination disclosed papillitis, retinal vasculitis, and retinal exudates (Fig. 1). The intravitreal white mass (4 ⫻ 2 disk diameter) of TA was ophthalmoscopically observed on the inferior peripheral retina. There were no signs of systemic CMV infection. Laboratory examination revealed that the patient was a carrier of human T-cell lymphotropic virus type 1 and negative for human immunodeficiency virus (CD4 cell count of 499/mm3). Serum titers of IgM and IgG antibodies to herpes simplex virus, varicella-zoster virus, and Toxoplasma were negative. Serum titers of IgG, but not IgM, antibody to CMV were positive. Intravenous panipenem treatment was administered for 5 days, but papillitis and retinitis continued to progress. Wash out of the vitreous cavity with vancomycin and panipenem removed the TA mass on February 21, 2005 (Fig. 2). Bacterial cultures of vitreous were negative. Polymerase chain reaction (PCR) analysis of vitreous was positive for CMV DNA (1.2 ⫻ 106 copies/mL) and negative for herpes simplex virus and varicella-zoster virus DNA. Intravenous injections of ganciclovir (500 mg) were repeated daily
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Fig. 3. Fundus photograph of the left eye during intravenous ganciclovir and intravitreous foscarnet treatment. Although papillitis and retinitis were resolved, anterior uveitis and vitreous opacity gradually progressed.
between February 25, 2005, and March 11, 2005. Intravitreous injections of foscarnet (2,400 g [total of 8 injections]) were repeated between February 28, 2005, and March 22, 2005. Although papillitis and retinitis resolved, vitreous opacity and pigmentation of the intraocular lens surface increased (Fig. 3). Wash out of the vitreous cavity with foscarnet fluid (2,400 g/4 mL) was performed on March 25, 2005. Intraoperative findings included yellowish vitreous liquid and resolution of papillitis and retinitis. After surgery, vitreous opacity progressed, and iris neovascularization occurred as well. Wash out of the vitreous cavity with foscarnet fluid (2,400 g/4 mL) was done again on March 30, 2005. During the following surgery, the intraocular lens was removed, and additional retinal photocoagulation and silicone oil tamponade were performed. PCR assay of vitreous was positive for CMV DNA (1.6 ⫻ 104 copies/mL). Two months later, iris neovascularization resolved with visual acuity improving to 0.5, and PCR analysis of aqueous humor was positive for CMV DNA (1.0 ⫻ 103 copies/mL). Silicone oil removal was performed on June 22, 2005. PCR assay of vitreous was negative for CMV DNA (⬍1.0 ⫻ 102 copies/mL) (Fig. 4). Two weeks later, iris neovascularization and inferior peripheral retinal detachment occurred. Vitrectomy and silicone oil tamponade were performed again on July 12, 2005. PCR analysis of vitreous was negative for CMV DNA (⬍1.0 ⫻ 102 copies/mL). Thereafter, retinitis did not occur. Final vision was 0.5 on April 3, 2006.
Discussion
Fig. 2. Fundus photograph of the left eye after systemic panipenem treatment. Note progression of papillitis and retinitis.
There have been four cases in which PCR analysis was positive for CMV DNA for patients with CMV retinitis who did not have systemic immune deficiency and systemic symptoms.1– 4 Saidel et al4 described a 75-year-old man with diabetic macular edema who developed arcuate retinal whitening after intravitreous TA treatment. To our knowledge, our case is the second report of CMV retinitis after intravitreal TA treatment in an immunocompetent patient. The local
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Fig. 4. Fundus photograph of the left eye on July 1, 2005. Papillitis and retinitis were resolved with visual acuity of 0.5.
use of TA for treatment of ocular disease may be related to local ocular immunosuppression. Dalessandro and Bottaro5 described a human immunodeficiency virus– infected patient who developed reactivation of CMV retinitis after posterior sub–Tenon space injection of TA for the treatment of immune recovery uveitis. In the report by Saidel et al,4 the nonvitrectomized eye developed CMV retinitis 4 months after intravitreous TA (4 mg) treatment without observation of intravitreous TA. Our patient developed CMV retinitis 3 months after intravitreous TA (10 mg) treatment. The intravitreal white mass of TA was ophthalmoscopically observed on the inferior peripheral retina. We believe that development of CMV retinitis in our patient was related to local ocular immunosuppression by the residual TA mass. CMV ocular infection in patients with systemic immune dysfunction generally presents in the form of CMV retinitis, resulting in necrosis of the retina with hemorrhages and mild inflammation of the anterior chamber and vitreous. On the other hand, CMV retinitis in individuals without systemic immune dysfunction is associated with various degrees of anterior uveitis.1– 4 Saidel et al4 reported that the patient responded well to intravitreal ganciclovir and oral valganciclovir treatment, but when therapy was discontinued, anterior uveitis and retinitis recurred. They suspected immune recovery vitritis, which was then treated with topical corticosteroid therapy. Although the inflammation improved rapidly, retinitis recurred, and CMV DNA was again detected in vitreous. In our patient, anterior uveitis progressed during antiviral therapy, but papillitis and retinitis resolved. We performed vitrectomy during combined therapy with gan-
ciclovir and foscarnet. Final vision was 0.5, and at the time of this writing, the patient was free of retinitis. Immune recovery vitritis was not described in the previous reports without TA usage.1–3 These findings may be related to local ocular immunosuppression by TA. Our patient was a human T-cell lymphotropic virus type 1 carrier with type 2 diabetes mellitus. Human T-cell lymphotropic virus type 1 carriers may have latent immune deficiency. Although two of the previously described four patients1– 4 had diabetes mellitus, the relationships between diabetes mellitus and occurrence of CMV retinitis remain unclear. We had no cytologic or histologic results showing CMV infection in the eye, although we detected CMV DNA by PCR assay on several occasions. The fundus photograph of the initial presentation showed what appeared to be multifocal retinal vasculitis and papillitis; the lesions were certainly not typical for CMV retinitis. Specifically, there was no large confluent area of retinitis with hemorrhaging. We did not perform culture or PCR analysis of blood for CMV. It is possible that there was systemic CMV in the patient that migrated into the eye due to a blood–retinal barrier breakdown. However, we believe that this is a case of CMV retinitis after intravitreous TA treatment without other evidence of immune system dysfunctions and systemic symptoms. CMV retinitis can occur after intravitreous TA treatment of a vitrectomized eye in an immunocompetent patient. Papillitis and retinitis respond well to systemic ganciclovir and intravitreous foscarnet treatment. However, vitrectomy may be necessary for treatment of anterior uveitis and vitreous opacity. Key words: cytomegalovirus retinitis, human T-cell lymphotropic virus type 1, triamcinolone acetonide. Acknowledgment The authors acknowledge Professor Manabu Mochizuki (Tokyo Medical and Dental University) for the case discussion.
References 1. 2.
3.
4.
5.
Takahashi K, Fujii K, Inoue A, Ikeda T. Cytomegalovirus retinitis in a healthy person. Jpn J Clin Ophthalmol 1998;52:615–617. Matsunaga M, Abe T, Satoh N, Sakuragi S. A case of cytomegalovirus retinitis with diabetes mellitus. Journal of the Eye 1998;15:1021–1024. Kita Y, Fujino Y, Ishida M, Takeuchi S. A case of cytomegalovirus retinitis with severe ocular hypertension and anterior chamber inflammation which occurred in a healthy individual. Journal of the Eye 2005;22:845–849. 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.
Purpose: To report a case of cytomegalovirus (CMV) retinitis after intravitreous injection of triamcinolone for a vitrectomized eye in an immunocompetent patient. Design: Observational case report. Methods: Review of medical records. Results: A 54-year-old woman with well-controlled type 2 diabetes developed anterior uveitis, papillitis, retinal vasculitis, and retinal exudates 3 months after intravitreous triamcinolone for the treatment of recurred macular edema. The intravitreal white mass of triamcinolone was ophthalmoscopically observed on the inferior peripheral retina. Polymerase chain reaction of the vitreous was positive for CMV DNA. There was no sign of systemic CMV infection. Laboratory examination revealed that the patient was a human T cell lymphotropic virus type 1 carrier and HIV negative. The retinitis responded well to systemic ganciclovir and intravitreous foscarnet, but the treatment of anterior uveitis and vitreous opacity needed repeated vitreous surgery. Conclusion: CMV retinitis can occur after intravitreous triamcinolone for a vitrectomized eye in an immunocompetent patient. RETINAL CASES & BRIEF REPORTS 1:205–207, 2007
From the *Department of Ophthalmology, Kamiiida First General Hospital, Nagoya, Japan; †Shinjo Ophthalmologic Institute, Miyazaki, Japan; the ‡Department of Ophthalmology, Saga University, Saga, Japan; the §Department of Ophthalmology, Kagoshima City Hospital, Kagoshima, Japan; and the ¶Department of English, Miyazaki Prefectural Nursing University, Miyazaki, Japan.
triamcinolone acetonide (TA) treatment of a vitrectomized eye in a human immunodeficiency virus–negative woman without other evidence of immune system dysfunctions and systemic symptoms. Case Report In June 2004, a 54-year-old woman with well controlled type 2 diabetes mellitus presented to our clinic for decreased vision in the left eye. At examination, visual acuity was 0.5, and cystoid macular edema, due to central retinal vein occlusion with panretinal photocoagulation, was noted and treated with vitrectomy combined with cataract surgery on June 17, 2004. Cystoid macular edema resolved, and visual acuity improved to 1.0. In October 2004, cystoid macular edema recurred with visual acuity decreasing to 0.5. After extensive discussion and obtained informed consent, the recurred cystoid macular edema was treated with intravitreous TA (10 mg) on November 11, 2004. Cystoid macular edema resolved, and visual acuity improved to 1.2. However, the patient returned on
C
ytomegalovirus (CMV) retinitis commonly develops in patients with systemic immunodeficiency. There have been few reports of CMV retinitis without immune deficiency and systemic symptoms.1– 4 We describe a case of CMV retinitis after intravitreous Proprietary interest for this report is credited to Kazuyuki Kumagai. Reprint requests: Kazuyuki Kumagai, MD, 889 Mego, Shimokitakata-cho, Miyazaki 880-0035 Japan.
205
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RETINAL CASES & BRIEF REPORTSℜ
Fig. 1. Fundus photograph of the left eye 3 months after intravitreal triamcinolone acetonide treatment of recurrent macular edema. Note papillitis, retinal vasculitis, and retinal exudates.
February 10, 2005, complaining of blurred vision in the left eye. Examination of the left eye revealed visual acuity of 1.0, intraocular pressure of 32 mmHg, small granulomatous keratic precipitates, 1⫹ aqueous cell and flare, and 1⫹ vitreous inflammatory cell. Funduscopic examination disclosed papillitis, retinal vasculitis, and retinal exudates (Fig. 1). The intravitreal white mass (4 ⫻ 2 disk diameter) of TA was ophthalmoscopically observed on the inferior peripheral retina. There were no signs of systemic CMV infection. Laboratory examination revealed that the patient was a carrier of human T-cell lymphotropic virus type 1 and negative for human immunodeficiency virus (CD4 cell count of 499/mm3). Serum titers of IgM and IgG antibodies to herpes simplex virus, varicella-zoster virus, and Toxoplasma were negative. Serum titers of IgG, but not IgM, antibody to CMV were positive. Intravenous panipenem treatment was administered for 5 days, but papillitis and retinitis continued to progress. Wash out of the vitreous cavity with vancomycin and panipenem removed the TA mass on February 21, 2005 (Fig. 2). Bacterial cultures of vitreous were negative. Polymerase chain reaction (PCR) analysis of vitreous was positive for CMV DNA (1.2 ⫻ 106 copies/mL) and negative for herpes simplex virus and varicella-zoster virus DNA. Intravenous injections of ganciclovir (500 mg) were repeated daily
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Fig. 3. Fundus photograph of the left eye during intravenous ganciclovir and intravitreous foscarnet treatment. Although papillitis and retinitis were resolved, anterior uveitis and vitreous opacity gradually progressed.
between February 25, 2005, and March 11, 2005. Intravitreous injections of foscarnet (2,400 g [total of 8 injections]) were repeated between February 28, 2005, and March 22, 2005. Although papillitis and retinitis resolved, vitreous opacity and pigmentation of the intraocular lens surface increased (Fig. 3). Wash out of the vitreous cavity with foscarnet fluid (2,400 g/4 mL) was performed on March 25, 2005. Intraoperative findings included yellowish vitreous liquid and resolution of papillitis and retinitis. After surgery, vitreous opacity progressed, and iris neovascularization occurred as well. Wash out of the vitreous cavity with foscarnet fluid (2,400 g/4 mL) was done again on March 30, 2005. During the following surgery, the intraocular lens was removed, and additional retinal photocoagulation and silicone oil tamponade were performed. PCR assay of vitreous was positive for CMV DNA (1.6 ⫻ 104 copies/mL). Two months later, iris neovascularization resolved with visual acuity improving to 0.5, and PCR analysis of aqueous humor was positive for CMV DNA (1.0 ⫻ 103 copies/mL). Silicone oil removal was performed on June 22, 2005. PCR assay of vitreous was negative for CMV DNA (⬍1.0 ⫻ 102 copies/mL) (Fig. 4). Two weeks later, iris neovascularization and inferior peripheral retinal detachment occurred. Vitrectomy and silicone oil tamponade were performed again on July 12, 2005. PCR analysis of vitreous was negative for CMV DNA (⬍1.0 ⫻ 102 copies/mL). Thereafter, retinitis did not occur. Final vision was 0.5 on April 3, 2006.
Discussion
Fig. 2. Fundus photograph of the left eye after systemic panipenem treatment. Note progression of papillitis and retinitis.
There have been four cases in which PCR analysis was positive for CMV DNA for patients with CMV retinitis who did not have systemic immune deficiency and systemic symptoms.1– 4 Saidel et al4 described a 75-year-old man with diabetic macular edema who developed arcuate retinal whitening after intravitreous TA treatment. To our knowledge, our case is the second report of CMV retinitis after intravitreal TA treatment in an immunocompetent patient. The local
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CMV RETINITIS AND INTRAVITREOUS TA
Fig. 4. Fundus photograph of the left eye on July 1, 2005. Papillitis and retinitis were resolved with visual acuity of 0.5.
use of TA for treatment of ocular disease may be related to local ocular immunosuppression. Dalessandro and Bottaro5 described a human immunodeficiency virus– infected patient who developed reactivation of CMV retinitis after posterior sub–Tenon space injection of TA for the treatment of immune recovery uveitis. In the report by Saidel et al,4 the nonvitrectomized eye developed CMV retinitis 4 months after intravitreous TA (4 mg) treatment without observation of intravitreous TA. Our patient developed CMV retinitis 3 months after intravitreous TA (10 mg) treatment. The intravitreal white mass of TA was ophthalmoscopically observed on the inferior peripheral retina. We believe that development of CMV retinitis in our patient was related to local ocular immunosuppression by the residual TA mass. CMV ocular infection in patients with systemic immune dysfunction generally presents in the form of CMV retinitis, resulting in necrosis of the retina with hemorrhages and mild inflammation of the anterior chamber and vitreous. On the other hand, CMV retinitis in individuals without systemic immune dysfunction is associated with various degrees of anterior uveitis.1– 4 Saidel et al4 reported that the patient responded well to intravitreal ganciclovir and oral valganciclovir treatment, but when therapy was discontinued, anterior uveitis and retinitis recurred. They suspected immune recovery vitritis, which was then treated with topical corticosteroid therapy. Although the inflammation improved rapidly, retinitis recurred, and CMV DNA was again detected in vitreous. In our patient, anterior uveitis progressed during antiviral therapy, but papillitis and retinitis resolved. We performed vitrectomy during combined therapy with gan-
ciclovir and foscarnet. Final vision was 0.5, and at the time of this writing, the patient was free of retinitis. Immune recovery vitritis was not described in the previous reports without TA usage.1–3 These findings may be related to local ocular immunosuppression by TA. Our patient was a human T-cell lymphotropic virus type 1 carrier with type 2 diabetes mellitus. Human T-cell lymphotropic virus type 1 carriers may have latent immune deficiency. Although two of the previously described four patients1– 4 had diabetes mellitus, the relationships between diabetes mellitus and occurrence of CMV retinitis remain unclear. We had no cytologic or histologic results showing CMV infection in the eye, although we detected CMV DNA by PCR assay on several occasions. The fundus photograph of the initial presentation showed what appeared to be multifocal retinal vasculitis and papillitis; the lesions were certainly not typical for CMV retinitis. Specifically, there was no large confluent area of retinitis with hemorrhaging. We did not perform culture or PCR analysis of blood for CMV. It is possible that there was systemic CMV in the patient that migrated into the eye due to a blood–retinal barrier breakdown. However, we believe that this is a case of CMV retinitis after intravitreous TA treatment without other evidence of immune system dysfunctions and systemic symptoms. CMV retinitis can occur after intravitreous TA treatment of a vitrectomized eye in an immunocompetent patient. Papillitis and retinitis respond well to systemic ganciclovir and intravitreous foscarnet treatment. However, vitrectomy may be necessary for treatment of anterior uveitis and vitreous opacity. Key words: cytomegalovirus retinitis, human T-cell lymphotropic virus type 1, triamcinolone acetonide. Acknowledgment The authors acknowledge Professor Manabu Mochizuki (Tokyo Medical and Dental University) for the case discussion.
References 1. 2.
3.
4.
5.
Takahashi K, Fujii K, Inoue A, Ikeda T. Cytomegalovirus retinitis in a healthy person. Jpn J Clin Ophthalmol 1998;52:615–617. Matsunaga M, Abe T, Satoh N, Sakuragi S. A case of cytomegalovirus retinitis with diabetes mellitus. Journal of the Eye 1998;15:1021–1024. Kita Y, Fujino Y, Ishida M, Takeuchi S. A case of cytomegalovirus retinitis with severe ocular hypertension and anterior chamber inflammation which occurred in a healthy individual. Journal of the Eye 2005;22:845–849. 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.
