环孢素滴眼液联合抗感染治疗中重度化脓性角膜炎的临床疗效

目的 探讨应用环孢素滴眼液联合抗感染治疗中重度化脓性角膜炎的效果。 设计 回顾性病例系列。 研究对象 2018年10月至2019年11月在北京同仁眼科中心就诊的连续中重度化脓性角膜炎患者20例（20眼）。 方法 对20例中重度化脓性角膜炎患者应用环孢素滴眼液联合抗感染治疗,治疗方法：患眼用1%环孢素滴眼液点眼,每日4次;同时根据角膜炎类型先进行经验性抗感染治疗,待微生物培养及药敏结果回报后再调整用药;出现前房炎性反应（如角膜后沉着物,大量浮游细胞,前房积脓）可加用硫酸阿托品眼用凝胶。所有患者随访至停药后6个月,记录患者的一般情况、病因、外院诊疗情况、角膜感染程度分级、角膜炎类型、视力、眼压、药物不良反应,停药后复发情况等资料,并根据患者首诊、治疗1周、1、2、3个月后的眼前节照相进行结膜充血、角膜水肿分级,并测量角膜溃疡面积,前房积脓高度。疗效判断标准：有效：疼痛症状减轻或消失,角膜溃疡部分或全部愈合,荧光素染色（±）,后弹力层皱褶及水肿明显减轻或消失,前房积脓减少或消失,视力无变化或有提高;无效：各种症状改善不明显,病灶无变化或扩大,前房积脓无消失或有并发症发生。主要指标 视力、眼压、结膜充血、角膜水肿分级,角膜溃疡面积,前房积脓高度,药物不良反应,停药后复发情况等。 结果 20例患眼首诊时结膜充血评分[中位数（M）,25%分位数（Q25）~75%分位数（Q75）]为2.50,2.00～3.00;治疗1周、1、2、3个月后结膜充血评分分别为2.00,2.00~3.00;1.50,1.00~2.00;1.00,0~1.00;0,0~1.00;治疗后各时间点与首诊时的差异均有统计学意义（P均<0.05）。首诊时角膜水肿评分为2.00,2.00～3.00;治疗1周、1、2、3个月后角膜水肿评分分别为1.50,1.00～2.75;1.00,0～1.75;0,0～0;0,0～0;治疗后各时间点与首诊时的差异均有统计学意义（P均<0.05）。首诊时角膜溃疡面积为7.63 mm2,6.00～29.81 mm2;治疗1周、1、2、3个月后角膜溃疡面积分别为4.50 mm2,3.00～21.88 mm2;0 mm2,0～4.88 mm2;0 mm2,0～0 mm2;0 mm2,0～0 mm2;治疗后各时间点与首诊时的差异均有统计学意义（P均<0.05）。首诊时前房积脓高度为0.25 mm,0～1.88 mm;治疗1周、1、2、3个月后前房积脓高度分别为0 mm,0～0.95 mm;0 mm,0～0 mm;0 mm,0～0 mm;0 mm,0～0 mm;治疗后各时间点与首诊时的差异均有统计学意义（P均<0.05）。12例患眼的首诊视力＜0.05,6例患眼视力在0.05～0.3之间,2例患眼视力＞0.3;治疗后,6例患眼的愈后视力＜0.05,8例患眼视力在0.05～0.3之间,6例患眼视力＞0.3,治疗后所有患眼视力均有不同程度的提高,但愈后视力与首诊视力比较,差异无统计学意义（χ2=4.286,P=0.134）。仅1例患眼治疗过程中出现眼压升高。所有患者均治疗有效,且未出现药物刺激症状及不良反应,停药后6个月内均无复发。 结论 眼局部应用环孢素滴眼液联合抗感染治疗中重度化脓性角膜炎安全、有效。

Efficacy of cyclosporine eyedrops combined with anti-infectious drugs for moderate/severe suppurative keratitis

Objective To evaluate the efficacy of cyclosporine eyedrops combined with anti-infectious drugs for moderate/severe suppurative keratitis. Design Retrospective cases series. Participants 20 patients (20 eyes) who were diagnosed as moderate/severe suppurative keratitis from October 2018 to November 2019 in Beijing Tongren Eye Center. Methods All patients received topical application of cyclosporine eyedrops and anti-infectious drugs. Therapeutic method: 1% cyclosporin eyedrops 4 times a day; at the same time, an empirical anti-infection treatment was performed according to the type of keratitis. Then the drug can be adjusted according to the microbial culture results or drug sensitivity results. If anterior chamber inflammation appears (e.g. keratic precipitate, lots of anterior chamber cells, hypopyon), atropine sulfate eye gel will be applied. Follow-up time ≥6 months after drug withdrawal. Patient's general condition, etiology, medical history, degree of corneal infection, type of keratitis, visual acuity, intraocular pressure, adverse drug reactions, and recurrence after drug withdrawal were recorded. Conjunctival congestion and corneal edema were graded according to the anterior segment photographs at the first visit, 1 week, 1, 2, and 3 months after treatment. Corneal ulcer area and hypopyon height were measured at the same time. Criteria for evaluation of efficacy: Effective: relief or disappearance of pain, partial or complete healing of corneal ulcer, fluorescein staining (±), significant reduction or disappearance of Descemet's membrane striae and edema, reduction or disappearance of hypopyon, no change or improvement of visual acuity; Noneffective: no obvious improvement of symptoms, no change or expansion of lesions, no disappearance of hypopyon or complications occurred. Main Outcome Measures Visual acuity, intraocular pressure, grading of conjunctival congestion and corneal edema, corneal ulcer area, hypopyon height, adverse drug reactions, and recurrence after drug withdrawal. Results Conjunctival congestion score（M,Q25~Q75) was 2.50, 2.00~3.00 at the first visit; and 2.00, 2.00~3.00; 1.50, 1.00~2.00; 1.00, 0~1.00; 0, 0~1.00 at 1 week, 1, 2 and 3 months after treatment respectively (all P<0.05). Corneal edema score was 2.00, 2.00~3.00 at the first visit; and 1.50, 1.00~2.75; 1.00, 0~1.75; 0, 0~0; 0, 0~0 at 1 week, 1, 2 and 3 months after treatment respectively (all P<0.05). Corneal ulcer area was 7.63 mm2, 6.00～29.81 mm2 at the first visit; 4.50 mm2, 3.00~21.88 mm2; 0 mm2, 0~4.88 mm2; 0 mm2, 0~0 mm2; 0 mm2, 0~0 mm2 at 1 week, 1, 2 and 3 months after treatment respectively (all P<0.05). Hypopyon height was 0.25mm, 0～1.88 mm at the first visit; 0 mm, 0～0.95 mm; 0 mm, 0～0 mm; 0 mm, 0～0 mm; 0 mm, 0～0 mm at 1 week, 1, 2 and 3 months after treatment respectively (all P<0.05). At the first visit, visual acuity of 12 cases was < 0.05, 6 cases was between 0.05 and 0.3, and 2 cases was > 0.3. After treatment, the visual acuity of 6 cases was < 0.05, 8 cases was between 0.05 and 0.3, and 6 cases was > 0.3. Visual acuity improved in all cases after treatment, but the difference was not statistically significant (χ2=4.286,P=0.134). Only one case had elevated intraocular pressure during the treatment. All the cases were effectively treated, and no drug irritation symptoms or adverse reactions occurred. No recurrence occurred within 6 months after drug withdrawal. Conclusion Topical application of cyclosporine eyedrops combined with anti-infectious drugs is an effective and safe modality for treatment of moderate/severe suppurative keratitis.