Department of Ophthalmology, Weill Cornell Medical College, New York, New York; Retina Associates of Orange County, Laguna Hills, California.
Department of Ophthalmology, Weill Cornell Medical College, New York, New York.
Ophthalmol Retina. 2021 Sep;5(9):838-849. doi: 10.1016/j.oret.2021.04.009. Epub 2021 Apr 20.
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).
Retrospective cohort study.
Patients with active CMV retinitis evaluated at a tertiary care academic center.
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).
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.
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.
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.
描述采用全身性给予巨细胞病毒（CMV）特异性细胞毒性 T 淋巴细胞（CMV 特异性 CTL）进行过继免疫治疗的 CMV 视网膜炎患者的眼部结局。
回顾性队列研究。
在一家三级保健学术中心接受评估的活动性 CMV 视网膜炎患者。
采用标准护理疗法（全身或玻璃体内抗病毒药物）或 CMV 特异性 CTL（有或无同时进行的标准护理疗法）治疗 CMV 视网膜炎。
回顾电子病历以确定基线特征、治疗经过和眼部结局，包括最佳矫正视力（BCVA）、给予的治疗（CMV 特异性 CTL、全身抗病毒药物、玻璃体内抗病毒药物）、CMV 视网膜炎的消退、是否发生免疫恢复性葡萄膜炎、囊样黄斑水肿、视网膜脱离或上述情况的组合。
7 名患者（3 名患者患有双侧疾病[10 只眼]）接受了 CMV 特异性 CTL 治疗，而 20 名患者（6 名患者患有双侧疾病[26 只眼]）接受了标准护理治疗。CMV 特异性 CTL 治疗的适应证包括持续性或进行性 CMV 视网膜炎（71.4%的患者）；CMV UL54 或 UL97 抗病毒耐药突变（42.9%）；抗病毒药物的副作用或毒性（57.1%）；患者无法耐受长期频繁使用抗病毒药物治疗持续性视网膜炎（28.6%）；或以上情况的组合。2 名患者（28.6%；4 只眼[40%]）因活动性 CMV 视网膜炎接受了无全身或玻璃体内抗病毒治疗的 CMV 特异性 CTL 治疗，而 5 名患者（71.4%；6 只眼[60%]）继续接受联合抗病毒治疗。接受 CMV 特异性 CTL 治疗的 9 只眼（90%）CMV 视网膜炎消退，80%的眼在平均 33.4 个月的随访中 BCVA 稳定（4 只眼[40%]）或改善（4 只眼[40%]）。免疫恢复性葡萄膜炎、新发囊样黄斑水肿和视网膜脱离的发生率分别为 0%（1 只眼）、10%（1 只眼）和 20%（2 只眼）。与单独接受标准护理治疗的非随机队列相比，尽管基线特征可能更差，但这些结果均表明 CMV 特异性 CTL 治疗可能是 CMV 视网膜炎的新型单一疗法或辅助疗法，或两者兼而有之。更普遍地说，过继性细胞转移和过继免疫疗法可能在难治性 CMV 视网膜炎中发挥作用。需要更大规模的前瞻性、随机试验。
