Autologous serum eye drops for the treatment of dry eye diseases

Conventional treatment of dry eye mainly consists of the use of preservative-free artificial eye drops and punctal occlusion. None of the commercially available artificial tear preparations include essential tear components such as epidermal growth factor, hepatocyte growth factor, fibronectin, neurotrophic growth factor, and vitamin A-all of which have been shown to play important roles in the maintenance of a healthy ocular surface epithelial milieu. We reported previously that autologous serum (AS) eye drops contain these essential factors and that AS eye drops are beneficial in the treatment of ocular surface diseases such as persistent epithelial defects, superior limbic keratoconjunctivitis, keratoconjunctivitis sicca, and neurotrophic keratopathy. However, there is some controversy regarding the efficacy of AS treatment. We demonstrated that this modality is more effective than artificial tears in a randomized control study. In in vivo and in vitro experiments, AS eye drops showed marked suppression of apoptosis in the conjunctival and corneal epithelium. Albumin, the major protein in serum, improved ocular surface damage in vivo and rescued apoptosis after serum deprivation in vitro. The biological background of AS eye drops and previous clinical studies of these medications for the treatment of dry eye are discussed.     

Autologous serum eye drops for ocular surface disorders

Tears have antimicrobial, nourishing, mechanical, and optical properties. They contain components such as growth factors, fibronectin, and vitamins to support proliferation, migration, and differentiation of the corneal and conjunctival epithelium. A lack of these epitheliotrophic factors--for example, in dry eye, can result in severe ocular surface disorders such as persistent epithelial defects. Recently, the use of autologous serum in the form of eye drops has been reported as a new treatment for severe ocular surface disorders. Serum eye drops may be produced as an unpreserved blood preparation. They are by nature non-allergenic and their biomechanical and biochemical properties are similar to normal tears. In vitro cell culture experiments showed that corneal epithelial cell morphology and function are better maintained by serum than by pharmaceutical tear substitutes. Clinical cohort studies have reported its successful use for severe dry eyes and persistent epithelial defects. However, the protocols to prepare and use autologous serum eye drops varied considerably between the studies. As this can result in different biochemical properties protocol variations may also influence the epitheliotrophic effect of the product. Before the definitive role of serum eye drops in the management of severe ocular surface disease can be established in a large randomised controlled trial this has to be evaluated in more detail. In view of legislative restrictions and based upon the literature reviewed here a preliminary standard operating procedure for the manufacture of serum eye drops is proposed.     

玻璃酸钠及碱性成纤维细胞生长因子滴眼液用于单纯干眼和LASIK术后患者的临床疗效

目的 观察0.1%玻璃酸钠滴眼液（SH）、碱性成纤维细胞生长因子（bFGF）滴眼液在单纯干眼和准分子激光原位角膜磨镶术（LASIK） 后应用的有效性和安全性。设计 随机对照研究。研究对象  2012年1月至2012年8月于北京协和医院就诊的单纯干眼患者70例（组Ⅰ）和接受LASIK手术后的患者40例（组II）。方法 采用随机、平行对照试验方法,组Ⅰ和组II各分为两个亚组,采用随机数字法分别使用0.1% SH滴眼液（A组）和bFGF滴眼液（B组）,每日4次,组Ⅰ局部连续使用14天,组II连续使用30天。在不同时间点（组I用药前、用药7天和14天,组II手术前、手术后1天、3天、10天和30天）观察患者症状和体征。问卷调查患者用药前后不同时间段的干眼症状,包括易疲劳、异物感、干涩感、烧灼感、眼胀感、眼痛、畏光和眼红,根据患者症状严重程度评为0～9分。主要指标 干眼症状评分,泪膜破裂时间（BUT）、Schirmer Ⅰ试验和角膜结膜荧光素染色（FL）,症状评分。结果  单纯干眼组（组I）治疗后干眼症状均明显改善,治疗后14天易疲劳（P=0.006）和眼痛（P=0.040）的改善ⅠA组优于ⅠB组,差异有统计学意义。症状明显改善的患者在ⅠA、ⅠB中分别为94.3%、78.6%。BUT（P=0.055）、Schirmer Ⅰ试验（P=0.573）改善ⅠA高于ⅠB, FL（P=0.375）减少ⅠB优于ⅠA,差异无统计学意义。LASIK术后组（组II）,患者术后1、3天较术前出现不适症状,术后30天所有症状有明显改善,其中异物感（P=0.004）、烧灼感（P<0.001）、眼胀（P=0.005）、眼红（P=0.007）改善分数IIA组优于IIB组。术后10天,BUT、Schirmer Ⅰ试验均较术前减少,FL较术前增加,术后30天各项体征较术后10天改善（IIA组BUT： P=0.142,Schirmer Ⅰ试验：P=0.053,FL：P=0.005;IIB组BUT： P=0.006,Schirmer Ⅰ试验：P=0.010,FL：P=0.079）,IIA组与IIB组各项体征改善比较无统计学意义（BUT：P=0.251,Schirmer Ⅰ试验：P=0.369,FL：P=0.060）。所有患者用药后未见副作用。结论 SH和bFGF滴眼液均能促进单纯干眼和LASIK术后角膜上皮修复,维持泪膜稳定性,减轻症状。SH滴眼液在改善某些（如易疲劳、异物感、烧灼感、眼胀、眼红、眼痛等）症状方面优于bFGF滴眼液。（眼科,2014, 23： 274-279）     

LASIK术后角膜知觉的变化及干眼的发生

目的：探讨准分子激光原位角膜磨镶术（LASIK）后角膜知觉的变化及其对干眼的影响与切削深度的关系。 方法：观察上方蒂做瓣的LASIK手术30例（60眼），观察指标包括患者术中切削深度及术前，术后1wk，lmo，3mo的角膜中央知觉、基础泪液分泌量、泪膜破裂时间（BUT）、角膜荧光素钠染色评分、干眼主觉症状评分。 结果：术后1wk，1mo角膜知觉敏感度与术前相比差异均非常显著（P〈0．01），术后3mo平与术前相比差异无统计学意义（P〉0．05）；术后1wk患者的主觉症状与术前相比无显著差异（P=0．079〉0．05），术后mo时差异显著（P=0．025〈0．05），术后3mo时差异极其显著（P=0．001〈0．01）；患者术后泪流量在术后1wk：1mo时明显低于术前（P〈0．01），直至术后3mo仍未恢复至术前水平（P〈0．01）；术后1wk，1mo，3mo泪膜破裂时间缩短，术后3mo时与术前相比差异显著（P〈0．01）；角膜荧光素钠染色评分方面，术后1mo时角膜上皮损伤最明显，术后3㈤时与术前仍有显著差异（P〈0．01）直线回归与相关分析结果，说明在两者之间存在直线相关的关系r=0．798，P〈0．01。 结论：LASIK术后角膜中央知觉明显下降并随时间延续而逐渐恢复，3mo时与术前无统计学差异；但是干眼的相关指标并未随之恢复至术前水平；术后角膜知觉的下降与术中切削深度间存在正相关。     

Comparison of autologous serum and umbilical cord serum eye drops for dry eye syndrome

PURPOSE: To compare the therapeutic effect between autologous serum and umbilical cord serum eye drops in the treatment of severe dry eye syndrome. DESIGN: Prospective case-control study. METHODS: Ninety-two eyes of 48 patients with severe dry eye syndrome (34 eyes of 17 patients with Sj?gren syndrome and 58 eyes of 31 patients with non-Sj?gren syndrome) were treated with either 20% autologous serum (41 eyes of 21 patients) or umbilical cord serum eye drops (51 eyes of 27 patients). Symptom scoring, corneal sensitivity test, tear film break-up time (BUT), Schirmer test, tear clearance rate (TCR), corneal fluorescein staining, and conjunctival impression cytologic analysis were performed before and one month and two months after treatment. RESULTS: Both autologous serum and umbilical serum treatments led to improvement in the symptom score, tear film BUT, keratoepitheliopathy score, and impression cytologic findings. Symptom and keratoepitheliopathy scores were lower at one month (P = .03 and P = .12) and two months (P = .04 and .02) for those treated with umbilical cord serum compared with those treated with autologous serum. In Sj?gren syndrome patients, goblet cell density was higher at two months of umbilical cord serum treatment compared with autologous serum treatment (P = .04). CONCLUSIONS: Umbilical cord serum eye drops were more effective in decreasing symptoms and keratoepitheliopathy in severe dry eye syndrome and increasing goblet cell density in Sj?gren syndrome compared with autologous serum eye drops.     

LASIK and dry eye

Dry eye is one of the most common complications after laser-assisted in situ keratomileusis (LASIK). The clinical signs of post-LASIK dry eye include positive vital staining of ocular surface, decreased tear film breakup time and Schirmer test, reduced corneal sensitivity, and decreased functional visual acuity. The symptoms and signs last at least 1 month after LASIK. Although the mechanisms for developing post-LASIK dry eye are not completely understood, loss of corneal innervation by flap-making may affect the reflex loops of the corneal-lacrimal gland, corneal-blinking, and blinking-meibomian gland, and blinking-meibomian gland, resulting in decreased aqueous and lipid tear secretion and mucin expression. As LASIK enhancement by flap-lifting induces less dry eye symptoms and signs than first surgery, it is suggested that other factors rather than loss of neurotrophic effect may be involved in the mechanisms of post-LASIK dry eye. The treatments of dry eye include artificial tears, topical cyclosporine, hot compress, punctal plugs, and autologous serum eye drops. For patients with severe preoperative dry eye, a combination of punctal plugs and serum eye drops is required to be used before surgery.     

准分子激光角膜原位磨镶术术后干眼症的研究进展

准分子激光角膜原位磨镶术（LASIK）是目前矫正屈光不正最常用的方法之一,具有良好的安全性、可预测性和有效性。如术中支配角膜的神经受到损伤,则引起角膜知觉的减退及干眼症的发生。就LASIK术后干眼症的临床表现、发病机制、预防和治疗等进行系统分析,对临床上手术方式的选择、设备的更新、技术的改进及术后用药具有一定的指导意义。     

双氯芬酸钠联合玻璃酸钠治疗眼科术后干眼症的临床分析

目的:观察双氯芬酸钠联合玻璃酸钠治疗眼科术后干眼症的临床疗效.方法:选择我院眼科术后不同程度干眼症患者94例94眼,并将其随机分为研究组和对照组各47例47眼,对照组患者在常规治疗的基础上联合玻璃酸钠滴眼液治疗,研究组患者在对照组的基础上配合双氯芬酸钠滴眼液治疗.比较两组患者治疗效果、干眼症状调查问卷评分、检测角膜荧光染色(corneal fluorescein staining,CFS)、泪膜破裂时间 (tear film break-up time,BUT)及泪液分泌(Schirmer Ⅰ test,SⅠt)情况.结果:治疗后两组患者干眼症临床症状调查得分、CFS得分均明显低于治疗前,差异具有统计学意义(P<0.05),BUT及SⅠt情况比治疗前增加,差异具有统计学意义(P<0.05);研究组患者在治疗后干眼症临床症状调查得分、CFS得分、BUT及SⅠt结果均优于对照组患者,两组之间差异具有统计学意义(P<0.05).研究组患者的治疗总有效率(98%)明显优于对照组(74%),差异具有统计学意义(P<0.05).结论:对眼科手术后干眼症患者在常规治疗基础上给予双氯芬酸钠眼液联合玻璃酸钠眼液治疗可以有效缓解患者干眼的临床症状,减少角膜荧光染色情况,增加泪膜破裂时间及泪液分泌量.     

Autologous serum eye drops used to treat an ulcerated dermis-fat graft

A 49-year-old woman with a contracted and keratinized anophthalmic socket underwent a dermis-fat graft for orbital augmentation. She presented with an early ulcer on the surface of the dermis, with inhibited conjunctival growth. There was no improvement after 1 month of conservative treatment. The authors applied autologous serum eye drops to accelerate epithelial repair, with resolution of the ulcer and reduction of surface keratin within 3 weeks. This is the first report of dermis-fat graft ulcer treated with autologous serum.     

噻吗洛尔滴眼液对LASIK术后屈光回退的应用

目的探讨噻吗洛尔滴眼液对准分于激光原位角膜磨馕术（LASIK）术后屈光回退的治疗效果。方法2007年8章至2008年8月在我院屈光手术中心接受LASIK手术治疗的近视821例（1621眼）,随访1年余。发生屈光回退者有54例（88眼）。随机分为2组：一组使用0．25％马来酸噻吗洛尔滴眼液进行治疗,另一组（即埘照组）使用0．1％普拉洛芬滴眼液治疗。治疗时间均为3个月,治疗结束后将两组的各项指标（视力提高行数、眼压变化程度）进行分析比较：结果视力提高行数：噻吗洛尔组视力提高1～4行,平均（3．17±1．16）行;对照组提高-2～2行,平均（-0．12±0．93）行,两组差异有统计学意义（t=5．46,P〈0．01）。眼压变化：噻吗洛尔组眼压下降2～6mmHg,平均（4．084-0．34）mmHg,对照组眼压下降-1～1mmHg,平均（0．23±0．38）mmHg;两组差异何统计学意义（t=11．16,P〈0．01）．结论0．25％马来酸噻吗洛尔滴眼液对LASIK术后的屈光回退具有明显的治疗效果,是一种简单、易行、有效的治疗厅法。     

LASIK术后糖皮质激素应用方案比较

目的　评价LASIK术后糖皮质激素的合理应用时间。方法　采用前瞻性研究 (双盲 ) ,观察行LASIK治疗的 10 0例 (2 0 0眼 )患者 ,根据术后用药不同随机分为试验组、对照组 ,各10 0眼。其中试验组LASIK术后使用典必殊滴眼液一周 ,对照组使用 0 1%氟美童滴眼液一月及托百士滴眼液一周 ,两组患者除术后糖皮质激素应用不同外 ,术前准备、手术方法及术后其他用药均相同 ;为不掩盖症状 ,术后均不使用人工泪液。观察指标包括术前、术后一日、术后三日、术后一周、术后二周、术后一月、术后三月的眼部症状 (包括疼痛、眼干、异物感 )及体症 ,包括裸眼视力、最佳矫正视力及有效球镜、弥漫性角膜基质炎 (DLK)、荧光素染色 (FL)、眼压。等级资料采用非参数独立样本U检验 (Mann -WhitneyTest) ,计量资料采用计量资料统计学方法。结果　术后二周时试验组和对照组DLK存在统计学差异 (P <0 0 5 ) ;角膜荧光素染色 ,试验组二周时恢复术前水平 ,对照组三月时尚未恢复术前水平 ;其他观察指标各时间段差异均无显著意义 (P >0 0 5 )。结论　LASIK术后短期应用强效激素 (一周 )即可获得预期临床效果 ,更有效预防DLK ,以避免长时间使用激素的副作用 ,同时方便患者使用提高治疗依从性     

Autologous serum in the management of recalcitrant dry eye syndrome

Purpose: To evaluate the efficacy and safety of long‐term application of autologous serum eye drops treating recalcitrant dry eye syndrome. Methods: A retrospective chart review was conducted of patients who had serum eye drops between May 2001 and March 2006. The clinical data collected included sex, age, indications for serum eye drops, frequency of lubricant eye drops use before and after serum eye drop treatment, Schirmer tear function test with anaesthesia, fluorescein staining at baseline and at follow up and changes in subjective symptoms. Results: There were 46 eyes of 23 patients (19 female and 4 male) in the study group. The average follow‐up period was 17.3 months (range 6–55 months). Corneal fluorescein staining of 34 eyes (73.9%) showed improvement at follow up. Sixteen patients (32 eyes, 69.6%) reported a decreased frequency of lubricant use including eight patients (16 eyes, 34.8%) who used only serum eye drops for dry eye treatment. Eighteen patients (35 eyes, 76.1%) reported subjective improvement after using serum eye drops. No significant complications were reported in this study. Conclusion: Serum eye drops can be effective in treating recalcitrant dry eye syndrome and should be available as a management option when other treatments have failed. Meticulous attention must be paid to the possible contamination of the bottle to minimize the risk of infection.     

The incidence and risk factors for developing dry eye after myopic LASIK

PURPOSE: To determine the incidence of dry eye and its risk factors after myopic laser-assisted in situ keratomileusis (LASIK). DESIGN: Single-center, prospective randomized clinical trial of 35 adult patients, aged 24 to 54 years, with myopia undergoing LASIK. METHODS: setting and study population: Participants were randomized to undergo LASIK with a superior or a nasal hinge flap. They were evaluated at 1 week and 1, 3, and 6 months after surgery. intervention: Bilateral LASIK with either a superior-hinge Hansatome microkeratome (n = 17) or a nasal-hinge Amadeus microkeratome (n = 18). main outcome measures: The criterion for dry eye was a total corneal fluorescein staining score > or =3. Visual acuity, ocular surface parameters, and corneal sensitivity were also analyzed. Cox proportional-hazard regression was used to assess rate ratios (RRs) with 95% confidence intervals. RESULTS: The incidence of dry eye in the nasal- and superior-hinge group was eight (47.06%) of 17 and nine (52.94%) of 17 at 1 week, seven (38.89%) of 18 and seven (41.18%) of 17 at 1 month, four (25%) of 16 and three (17.65%) of 17 at 3 months, and two (12.50%) of 16 and six (35.29%) of 17 at 6 months, respectively. Dry eye was associated with level of preoperative myopia (RR 0.88/each diopter, P = .04), laser-calculated ablation depth (RR 1.01/microm, P = 0.01), and combined ablation depth and flap thickness (RR 1.01/microm, P = 0.01). CONCLUSIONS: Dry eye occurs commonly after LASIK surgery in patients with no history of dry eye. The risk of developing dry eye is correlated with the degree of preoperative myopia and the depth of laser treatment.     

不同浓度人血清滴眼液治疗重症干眼大鼠的实验研究

目的 探讨不同浓度人血清滴眼液在重症干眼大鼠中的治疗效果.设计实验研究.研究对象 Sprague-Dawley （SD）大鼠28只.方法 28只健康成年雄性SD大鼠,随机分为正常对照组（n=4）,重症干眼组（n=24）,使用0.2%苯扎氯铵溶液点眼1周制作重症干眼模型.然后将重症干眼大鼠随机分为阴性对照组（n=6）,20%血清组（n=6）,50%血清组（n=6）,100%血清组（n=6）,使用相应浓度的血清滴眼液治疗28天,观察各组大鼠在制模后第0、7、14、21、28天的泪液分泌情况和眼表的改变.主要指标应用Schirmer试验、角膜荧光素染色、结膜印迹细胞学检查干眼程度.结果 重症干眼组与正常组大鼠各观察指标的差异有统计学意义,其中Schirmer试验（2.12±1.50 mm vs 8.67±2.36 mm,P=0.000）,角膜荧光素染色分级（4.0 vs 0.33±0.58,P=0.008）.结膜印迹细胞学分级（1.76±0.52 vs 0.33±0.58,P=0.000）.20%血清组大鼠较阴性对照组在第7、21天泪液分泌增ta（P=0.003,0.035）;第7、14、21、28天角膜荧光素染色减轻（P=0.001,0.006,0.021,0.001）;第14、21、28天印迹细胞学分级减轻（P=0.015,0.002,0.01）. 50%血清组较阴性对照组在第7、14、28天角膜荧光素染色减轻（P=0.025,0.023,0.004）;第14天印迹细胞学分级减轻（P=0.046）. 100%血清组较阴性对照组在第28天角膜荧光素染色减轻（P=0.021）,余差异无统计学意义（P〉0.05）.结论 不同浓度人血清滴眼液均有助于重症干眼大鼠角膜上皮的修复,其中20%的人血清滴眼液效果最理想,可以增加泪液分泌,减轻结膜和角膜上皮的损害.     

重视对LASIK围手术期干眼的认识和处理

干眼是LASIK术后最常见的并发症,加强对术前干眼的筛查,避免术中过度操作和术后滥用药等多种危险因素对术后干眼的影响,合理进行围手术期的干预治疗是减少术后发生干眼的重要措施。(眼科,2006,15:154-155)