Mrinali P Gupta1, Lisa R Koenig2, Ekaterina Doubrovina3, Aisha Hasan3, Parastoo B Dahi3, Richard J O'Reilly3, Guenther Koehne4, Anton Orlin2, Robison V Paul Chan5, Donald J D'Amico2, Susanna S Park6, Bryn M Burkholder7, Szilárd Kiss8. 1. Department of Ophthalmology, Weill Cornell Medical College, New York, New York; Retina Associates of Orange County, Laguna Hills, California. 2. Department of Ophthalmology, Weill Cornell Medical College, New York, New York. 3. Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York; Allogeneic Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center, New York, New York. 4. Miami Cancer Institute, Miami, Florida. 5. Department of Ophthalmology, Illinois Eye & Ear Infirmary, University of Illinois-Chicago, Chicago, Illinois. 6. Department of Ophthalmology & Vision Science, University of California Davis Eye Center, Sacramento, California. 7. Department of Ophthalmology, Wilmer Eye Institute of Johns Hopkins University, Baltimore, Maryland. 8. Department of Ophthalmology, Weill Cornell Medical College, New York, New York. Electronic address: szk7001@med.cornell.edu.
Abstract
PURPOSE: To describe ocular outcomes in eyes with cytomegalovirus (CMV) retinitis treated with adoptive immunotherapy using systemic administration of CMV-specific cytotoxic Tlymphocytes (CMV-specific CTLs). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with active CMV retinitis evaluated at a tertiary care academic center. METHODS: Treatment of CMV retinitis with standard-of-care therapy (systemic or intravitreal antivirals) or CMV-specific CTLs (with or without concurrent standard-of-care therapies). MAIN OUTCOME MEASURES: The electronic medical record was reviewed to determine baseline characteristics, treatment course, and ocular outcomes, including best-corrected visual acuity (BCVA), treatments administered (CMV-specific CTLs, systemic antivirals, intravitreal antivirals), resolution of CMV retinitis, any occurrence of immune recovery uveitis, cystoid macular edema, retinal detachment, or a combination thereof. RESULTS: Seven patients (3 of whom had bilateral disease [n = 10 eyes]) were treated with CMV-specific CTLs, whereas 20 patients (6 of whom had bilateral disease [n = 26 eyes]) received standard-of-care treatment. Indications for CMV-specific CTL therapy included persistent or progressive CMV retinitis (71.4% of patients); CMV UL54 or UL97 antiviral resistance mutations (42.9%); side effects or toxicity from antiviral agents (57.1%); patient intolerance to longstanding, frequent antiviral therapy for persistent retinitis (28.6%); or a combination thereof. Two patients (28.6%; 4 eyes [40%]) received CMV-specific CTL therapy without concurrent systemic or intravitreal antiviral therapy for active CMV retinitis, whereas 5 patients (71.4%; 6 eyes [60%]) continued to receive concurrent antiviral therapies. Resolution of CMV retinitis was achieved in 9 eyes (90%) treated with CMV-specific CTLs, with BCVA stabilizing (4 eyes [40%]) or improving (4 eyes [40%]) in 80% of eyes over an average follow-up of 33.4 months. Rates of immune recovery uveitis, new-onset cystoid macular edema, and retinal detachment were 0%, 10% (1 eye), and 20% (2 eyes), respectively. These outcomes compared favorably with a nonrandomized cohort of eyes treated with standard-of-care therapy alone, despite potentially worse baseline characteristics. CONCLUSIONS: CMV-specific CTL therapy may represent a novel monotherapy or adjunctive therapy, or both, for CMV retinitis, especially in eyes that are resistant, refractory, or intolerant of standard-of-care antiviral therapies. More generally, adoptive cell transfer and adoptive immunotherapy may have a role in refractory CMV retinitis. Larger prospective, randomized trials are necessary.
PURPOSE: To describe ocular outcomes in eyes with cytomegalovirus (CMV) retinitis treated with adoptive immunotherapy using systemic administration of CMV-specific cytotoxic Tlymphocytes (CMV-specific CTLs). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with active CMV retinitis evaluated at a tertiary care academic center. METHODS: Treatment of CMV retinitis with standard-of-care therapy (systemic or intravitreal antivirals) or CMV-specific CTLs (with or without concurrent standard-of-care therapies). MAIN OUTCOME MEASURES: The electronic medical record was reviewed to determine baseline characteristics, treatment course, and ocular outcomes, including best-corrected visual acuity (BCVA), treatments administered (CMV-specific CTLs, systemic antivirals, intravitreal antivirals), resolution of CMV retinitis, any occurrence of immune recovery uveitis, cystoid macular edema, retinal detachment, or a combination thereof. RESULTS: Seven patients (3 of whom had bilateral disease [n = 10 eyes]) were treated with CMV-specific CTLs, whereas 20 patients (6 of whom had bilateral disease [n = 26 eyes]) received standard-of-care treatment. Indications for CMV-specific CTL therapy included persistent or progressive CMV retinitis (71.4% of patients); CMV UL54 or UL97 antiviral resistance mutations (42.9%); side effects or toxicity from antiviral agents (57.1%); patient intolerance to longstanding, frequent antiviral therapy for persistent retinitis (28.6%); or a combination thereof. Two patients (28.6%; 4 eyes [40%]) received CMV-specific CTL therapy without concurrent systemic or intravitreal antiviral therapy for active CMV retinitis, whereas 5 patients (71.4%; 6 eyes [60%]) continued to receive concurrent antiviral therapies. Resolution of CMV retinitis was achieved in 9 eyes (90%) treated with CMV-specific CTLs, with BCVA stabilizing (4 eyes [40%]) or improving (4 eyes [40%]) in 80% of eyes over an average follow-up of 33.4 months. Rates of immune recovery uveitis, new-onset cystoid macular edema, and retinal detachment were 0%, 10% (1 eye), and 20% (2 eyes), respectively. These outcomes compared favorably with a nonrandomized cohort of eyes treated with standard-of-care therapy alone, despite potentially worse baseline characteristics. CONCLUSIONS: CMV-specific CTL therapy may represent a novel monotherapy or adjunctive therapy, or both, for CMV retinitis, especially in eyes that are resistant, refractory, or intolerant of standard-of-care antiviral therapies. More generally, adoptive cell transfer and adoptive immunotherapy may have a role in refractory CMV retinitis. Larger prospective, randomized trials are necessary.
Authors: Elizabeth A Sugar; Douglas A Jabs; Alka Ahuja; Jennifer E Thorne; Ronald P Danis; Curtis L Meinert Journal: Am J Ophthalmol Date: 2012-02-04 Impact factor: 5.258
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Authors: Douglas A Jabs; Alka Ahuja; Mark L Van Natta; Alice T Lyon; Steven Yeh; Ronald Danis Journal: Ophthalmology Date: 2015-04-17 Impact factor: 12.079
Authors: Mrinali Patel Gupta; Peter Coombs; Susan E Prockop; Aisha A Hasan; Ekatarina Doubrovina; Richard J O'Reilly; Stuart H Cohen; Susanna S Park; Szilárd Kiss Journal: Ophthalmic Surg Lasers Imaging Retina Date: 2015-01 Impact factor: 1.300