Incidence of ocular manifestations in patients with graft versus host disease after allogeneic stem cell transplant in Riyadh, Saudi Arabia

AIM: To evaluate the incidence and severity of ocular graft versus host disease (oGVHD) in patients who underwent allogeneic stem cell transplant (SCT) in King Abdul-Aziz Medical City, Saudi Arabia. METHODS: This is a retrospective cohort study conducted in King Abdul Aziz Medical City on patients who underwent allogeneic hematopoietic cell transplant (allo-HCT) from 2010 to 2017. The ocular examination findings including visual acuity, meibomian gland dysfunction, corneal and conjunctival staining with severity, corneal scarring, tear film meniscus and breakup time, anterior and posterior segment examination findings, intraocular pressure, treatment given, punctual plugs used or not, and follow up response were collected. RESULTS: The five years cumulative incidence of oGVHD among post-transplant patients was 56.98% (95%CI 38.6%-71.7%). The potential risk factors assessed for developing ocular manifestation were age, gender, donor’s age, donor gender mismatch CD3 and CD34 infusion, while none of the correlates were identified as statistically significant risk factors of developing ocular manifestation. However, the incidence was statistically significantly different between patients diagnosed with acute myelocytic leukemia and acute lymphocytic leukemia (P=0.038). The mean latent period to develop ocular symptoms was 20.5mo. All patients had variable degree of dry eyes. None of the patients developed any posterior segment complication. CONCLUSION: The incidence of oGVHD is low in King Abdul-Aziz Medical City. This can be attributed to the preconditioning and immunosuppressive regime.     

Impact of ocular graft‐versus‐host disease on visual quality of life in patients after allogeneic stem cell transplantation: questionnaire study

Purpose: To determine the influence of ocular complications on quality of life (QoL) 3 years after allogeneic stem cell transplantation (allo‐SCT). Methods: All 54 adult patients that underwent and survived allo‐SCT in 2006/2007 in our centre received two questionnaires (VFQ‐25: visual function questionnaire‐25 and OSDI: ocular surface disease index). In addition, the following data were included: gender, age, underlying disease, presence of chronic and/or ocular graft‐versus‐host disease (GVHD), number of visits to an ophthalmologist, manifestations of dry eye disease, the duration of follow‐up and treatment for ocular GVHD. Results: Ocular GVHD developed in 26% (14 of 54) of patients and 71% (10 of 14) received treatment for ocular GVHD. The presence of ocular GVHD correlated with the severity of systemic GVHD (correlation coefficient: 0.52, p = 0.00). The Karnofsky scores were significantly lower in the patients with ocular GVHD compared to the patients with no ocular GVHD (p = 0.001). Karnofsky scores were weakly correlated with the severity of systemic GVHD (correlation coefficient: 0.25, p = 0.03. Three years after the all‐SCT, OSDI and VFQ‐25 scores were significantly impaired in patients with ocular GVHD [mean: 76.5; range (46.1–100) and mean: 31.1; range (0–72.9)] compared to patients with no ocular GVHD [mean: 89.4; range (45.2–100) and mean: 12.9; range (0–58.3); p = 0.02]. The scores of the VFQ‐25 were significantly lower in the domains of general health, ocular pain, social functioning and role difficulties. Conclusion: The long‐term vision‐related QoL measured by the OSDI and VFQ‐25 was impaired in patients with ocular GVHD.     

造血干细胞移植术后的眼部观察

目的 观察造血干细胞术后移植物抗宿主病(GVHD)及预处理措施对眼部的影响。方法 对35例行造血干细胞移植患者的眼科检查进行回顾性分析。结果 35例中慢性GVHD14例，占异基因造血干细胞移植的70％。其中8例合并有干眼，占GVHD患者的57．14％；6例睑板腺功能障碍并伴有干眼。眼部其他并发症有结膜瘢痕、睑球粘连、角膜溃疡、白内障、急性结膜炎、眼底出血或结膜出血。自体造血干细胞移植不出现移植物抗宿主病及干眼。结论 干眼是异基因造血干细胞移植术后的主要眼部并发症，仅见于发生GVHD的患者。异基因造血干细胞移植的眼部并发症明显高于自体干细胞移植。     

玻璃酸钠联合环孢素A治疗混合型干眼症的疗效观察

目的：观察0.3%玻璃酸钠滴眼液联合1%环孢素A滴眼液治疗混合型干眼症的临床效果。

方法：将2018-02/2019-02于本院被确诊为混合型干眼症患者60例120眼采用随机数字表法分为2组,每组30例60眼,两组患者均接受眼睑热敷清洁和睑板腺按摩等常规治疗,研究组采用0.3%玻璃酸钠滴眼液联合1%环孢素A滴眼液进行治疗,对照组单纯采用0.3%玻璃酸钠滴眼液进行对照治疗。分析两组患者治疗前,治疗1、3mo患者的主观感受评分、泪液分泌试验(SⅠt)、泪膜破裂时间(BUT)、角膜荧光素染色评分(CFS)的结果。

结果：治疗前,对照组的主观感受评分(13.52±2.15)分、SⅠt(5.22±2.23)mm/5min、BUT(5.02±1.58)s、CFS评分(2.82±0.81)分与研究组的主观感受(13.75±3.05)分、SⅠt(5.54±2.89)mm/5min、BUT(5.14±1.84)s、CFS评分(2.73±0.45)分比较无差异。治疗1mo后,对照组的主观感受评分(12.22±2.64)分、SⅠt(7.94±2.15)mm/5min、BUT(5.32±1.34)s、CFS评分(2.68±0.27)分与研究组的主观感受评分(11.42±2.06)分、SⅠt(8.63±2.78)mm/5min、BUT(5.46±1.45)s、CFS评分(2.58±0.69)分均较治疗前有好转。两组间主观感受评分、SⅠt有差异,但BUT和CFS评分无差异。治疗3mo后,对照组的主观感受评分(11.57±2.98)分、SⅠt(8.44±2.35)mm/5min、BUT(5.92±1.75)s、CFS评分(1.92±0.44)分,研究组的主观感受评分(9.23±2.34)分、SⅠt(10.45±2.65)mm/5min、BUT(8.69±1.78)s、CFS评分(1.59±0.79),组间比较均有差异(P<0.05)。

结论：0.3%玻璃酸钠滴眼液联合1%环孢素A滴眼液治疗混合型干眼症具有显著的疗效。     

Donor-recipient gender difference affects severity of dry eye after hematopoietic stem cell transplantation

Purpose

To determine whether the incidence rate and severity of dry eye after hematopoietic stem cell transplantation varies with donor vsrecipient gender.

Methods

We limited this study to patients received bone marrow transplantation (BMT). In all, 172 patients received BMT at Keio University School of Medicine between January 2000 and May 2007. Of them, 136 recipients who survived at least 70 days were studied prospectively. We classified the 136 patients according to the gender of the donor and the recipient (group I: female to female; group II: male to male; group III: male to female; group IV: female to male). The incidence and severity of chronic graft-vs-host disease-associated dry eye were determined for each group. The donor gender was masked when we assessed dry eye and calculate the incidence.

Results

The incidence of dry eye was 47.4% for group I, 37.5% for group II, 58.6% for group III, and 42.9% for group IV. The percentage of patients with severe dry eye was 44.4, 50.0, 35.3, and 77.8% respectively. There was a significant difference between the percent severe dry eye/total dry eye incidences in groups III and IV (P=0.0375) (odds ratio, 7.6; 95% confidence interval, 1.00–101.01).

Conclusions

Close attention must be paid to the development of dry eye in cases of female to male BMTs, because the ratio of severe/total dry eye is more common in cases of female to male BMTs than in other gender combination.     

Tear cytokine levels in the diagnosis and severity assessment of ocular chronic graft-versus-host disease(GVHD)

PurposeTo analyse the tear cytokine levels of patients diagnosed with ocular chronic graft-versus-host disease(GVHD)and examine the consistency of these levels with different ocular surface parameters.Methods23 ocular chronic GVHD patients were selected for the assessment of tear cytokine levels and ocular surface parameters (TBUT, CFS, OSDI, and Schirmer's test), and 16 dry eye disease(DED)patients without systemic immune disease were selected as the control group. The 23 cytokines were measured using microsphere-based immunoassay analysis and their consistency with different ocular surface parameters was studied.ResultsICAM-1, IL-1β, IL-6, and IL-8 showed elevated levels in the eyes of oGVHD patients compared to DED [P < 0.001]. IL-7 and EGF showed lower levels in the eyes of patients with oGVHD than in those of patients with DED [P < 0.0001]. Furthermore, the levels of IL-6 and IL-8 showed a stronger correlation with corneal fluorescein staining (CFS) (P < 0.05), and the levels of IL-6 and ICAM-1 were most consistent with fluorescein tear film break-up time (TBUT) (P < 0.05).ConclusionsOur study demonstrated certain tear cytokines, including ICAM-1, IL-1β, IL-6, IL-8 IL-7 and EGF, as promising new possible diagnostic markers of chronic oGVHD and criteria for chronic ocular GVHD severity. Because tear sampling is noninvasive and simple, this method is expected to be an overwhelming applicable for the screening and diagnosis of chronic GVHD.     

0.5g/L环孢素A滴眼液对中重度干眼患者眼部症状及体征评分的影响

目的：探讨0.5g/L环孢素A滴眼液对中重度干眼患者眼部症状及体征评分的影响。
　　方法：中重度干眼症患者80例160眼依据随机双盲试验原则将其分为两组：观察组40例80眼,采用10 g/L羧甲基纤维素钠和0.5g/L环孢素A滴眼液治疗,对照组40例80眼,采用10 g/L羧甲基纤维素钠滴眼液治疗,比较两组患者眼部症状和体征评分变化。
　　结果：观察组治疗总有效率95.0%,显著高于对照组(85.0%),差异有统计学意义(P<0.05);观察组和对照组患者未治疗时症状积分分别为36.1±4.4、36.4±4.5分,经治疗后,观察组1、3 lo 时症状积分下降至25.2±3.2、11.09±3.9分,对照组下降至29.4±4.1、22.05±3.1分,治疗前后差异具有统计学意义(P<0.05),但观察组治疗1、3 lo的症状积分显著低于对照组,差异有统计学意义(P<0.05);治疗前,两组患者泪膜破裂时间(BUT)、泪液分泌试验( Slt)、角膜荧光素染色( FL)和生活质量(OSDI)评分之间无统计学差异(P>0.05);经治疗后,观察组四项指标均显著下降(P<0.05),对照组仅 FL 和OSDI评分显著下降,差异有统计学意义( P<0.05);观察组治疗后四项指标均显著高于对照组,差异具有统计学意义(P<0.05);观察组在用药14~28d时3眼出现刺痛感,对照组2眼刺痛感,1眼结膜充血,继续用药时2 d后全部消失。
　　结论：0.5g/L环孢素A滴眼液能够有效缓解中重度干眼患者症状和体征,促进泪液分泌,改善患者眼表环境,治疗效果良好。     

Ocular manifestations and quality of life in patients after hematopoietic stem cell transplantation

AIM: To explore the relationship between ocular and systemic conditions and the impact of ocular complications on the quality of life (QOL) in patients after allogeneic hematopoietic stem cell transplantation (ALLO-HSCT). METHODS: Forty-four patients with severe hematopoietic disease were enrolled after ALLO-HSCT at our center from July 2018 to October 2020. They completed two questionnaires: the Ocular Surface Disease Index (OSDI) and the quality-of-life scale for Chinese patients with visual impairment (SQOL-DV1). Ocular conditions and systemic conditions were also assessed. RESULTS: Eye damage was correlated with total bilirubin (P=0.005), and gamma-glutamyl transferase (GGT) (P=0.021). There was no significant correlation between the overall QOL score and OSDI (P=0.8226) or SQOL-DV1 (P=0.9526) scores. The OSDI and the overall QOL score were not correlated with ocular conditions, including best-corrected visual acuity (BCVA), intraocular pressure, Schirmer tear test II, sodium fluorescein staining, tear film breakup time, and tear meniscus height. SQOL-DV1 was correlated with BCVA (P=0.0007), sodium fluorescein staining (P=0.007), and tear film breakup time (P=0.0146). CONCLUSION: In some patients, early ocular symptoms are not evident after ALLO-HSCT, while ocular surface complications can be observed after a comprehensive ophthalmological examination. Especially for those with elevated total bilirubin or GGT, regular ophthalmic follow-up visits are essential to diagnose and treat ocular graft versus host disease (oGVHD), especially for patients with elevated total bilirubin or GGT.     

Update on ocular graft-versus-host disease

Ocular graft-versus-host disease (oGVHD) occurs as a complication following hematopoietic stem cell transplantation and is associated with significant ocular morbidity resulting in a marked reduction in the quality of life. With no current consensus on treatment protocols, management becomes challenging as recurrent oGVHD often refractory to conventional treatment. Most authors now diagnose and grade the disease based on criteria provided by the National Institutes of Health Consensus Conference (NIH CC) or the International Chronic oGVHD (ICCGVHD) consensus group. This article will provide an insight into the diagnostic criteria of oGVHD, its classification, and clinical severity grading scales. The inflammatory process in oGVHD can involve the entire ocular surface including the eyelids, meibomian gland, corneal, conjunctiva, and lacrimal system. The varied clinical presentations and treatment strategies employed to manage them have been discussed in the present study. The recent advances in ocular surface imaging in oGVHD patients such as the use of meibography and in vivo confocal microscopy may help in early diagnosis and prognostication of the disease. Researching tear proteomics and identification of novel potential tear biomarkers in oGVHD patients is an exciting field as they may help in objectively diagnosing the disease and monitoring the response to treatment.     

Ocular chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation in an Italian referral center

Purpose

This study aimed to assess the prevalence and clinical manifestations of ocular graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

带角膜缘干细胞的自体结膜瓣移植术对翼状胬肉患者泪膜稳定性的影响

目的:探讨带角膜缘干细胞的自体结膜瓣移植术对翼状胬肉患者干眼及泪膜稳定性的分析。方法:选择114例138眼翼状胬肉患者,根据治疗方式不同分为传统组56例67眼,试验组58例71眼,观察两组术前、术后1、3mo的SⅠt值、BUT值、FL值以及术后两组患者眼球表面温度及干眼症评分。结果:传统组总有效率83.6%,试验组总有效率95.8%,两组有差异(χ2=5.207,P=0.022);两组术前SⅠt值无差异(P>0.05),试验组术后1、3mo SⅠt值较传统组升高更为显著(均P<0.05);传统组、试验组术前BUT值无差异(P>0.05),术后1、3mo试验组BUT值较传统组明显增加(均P<0.05);传统组、试验组术前FL分值无差异(P>0.05),试验组术后1、3mo FL值较传统组有所降低(均P<0.001);传统组、试验组眼球表面温度无差异(P>0.05),干眼症评分试验组明显低于传统组(P<0.05)。结论:采用带角膜缘干细胞的自体结膜瓣移植术疗效优于行翼状胬肉切除联合羊膜移植术,可促进翼状胬肉患者泪膜稳定性恢复,患者干眼症状有明显改善。     

环孢霉素A在治疗重症干眼中的作用

目的:研究环孢霉素A在治疗重症干眼中的作用。方法:52例(104眼)重症干眼患者随机分为加0.5g/L环孢霉素A点眼实验组26例(52眼)和单纯用人工泪液点眼对照组26例(52眼),治疗3mo后测其泪液分泌试验、泪膜破裂时间、泪河弯曲面的曲率半径、泪膜干涉成像级别,并作对比。结果:泪液分泌试验改善了3~5mm:实验组的有效率为80.8%,对照组为23.1%;泪膜破裂时间延长3~5s:实验组的有效率为76.9%,对照组为19.2%;泪河弯曲面的曲率半径>0.2mm:实验组的有效率为65.4%,对照组为11.5%;泪膜干涉成像级别>Ⅲ级:实验组有效率为57.7%,对照组为11.5%。实验组与对照组之间的差异具有统计学意义(P<0.01)。结论:环孢霉素A在治疗重症干眼中起着非常重要的作用,具有良好的治疗效果。     

环孢素A纳米粒滴眼液抑制大鼠高危角膜移植免疫排斥反应的实验研究

目的 探讨环孢素A纳米粒滴眼液对大鼠高危角膜移植术后排斥反应的抑制作用。设计 实验研究。研究对象 Lewis大鼠50只为受体,F344大鼠25只为供体。方法 50只Lewis大鼠右眼采用缝线法诱导角膜新生血管形成,第7天新生血管到达角膜中周部时,全部行穿透性角膜移植术。因术后滴眼液不同将大鼠随机分为5组（A到E组,每组10只大鼠）,A组为对照组,给予环孢素A纳米粒滴眼液的基质点药,B组为普通环孢素A滴眼液组,C组、D组、E组分别为0.5%、1%、2%环孢素A纳米粒滴眼液组。术后各组滴用相应的滴眼液,每日3次。拍摄大鼠角膜照片每日1次至14天,以后每2日拍摄角膜照片1次至28天。以角膜植片水肿、混浊、新生血管评分之和为角膜排斥反应指数（RI）,记录角膜存活时间（从角膜移植开始到RI=6的时间）,术后第14天每组取2只大鼠眼球,以光镜进行角膜病理学观察。主要指标 角膜植片存活时间、角膜排斥反应指数（RI）,角膜的病理学改变。结果 A到E组角膜存活时间分别为（7.20±2.93）天、（10.89±3.62）天、（10.50±3.40）天、（11.13±3.94）天和（12.80±4.07）天,各组间比较差异有统计学意义（F=3.20,P=0.022）。B、C、D、E组与A组相比,角膜存活时间明显延长,差异均有统计学意义（P=0.031、0.047、0.027、0.001）。B组与C、D、E组之间比较差异均无统计学意义（P=0.815、0.853、0.255）,C组与D、E组之间差异均无统计学意义（P=0.716、0.161）,D组与E组之间差异无统计学意义（P=0.333）。A到E组RI分别为7.80±1.48、5.67±1.80、6.10±1.66、5.25±1.75和4.80±1.23,组间比较差异具有统计学意义（F=5.202,P=0.002）。B、C、D、E组与A组相比,RI明显减小,差异有统计学意义（P=0.005、0.021、0.002、0.000）。B组与C、D、E组比较差异均无统计学意义（P=0.555、0.592、0.241）。C组与D、E组比较差异无统计学意义（P=0.265、0.074）。D组与E组之间差异无统计学意义（P=0.553）。A组角膜植片明显水肿、增厚,基质层可见大量细胞浸润,细胞排列紊乱。B~E组角膜基质层浸润程度较A组明显减轻。结论 普通环孢素滴眼液组及高、中、低浓度的环孢素A纳米粒滴眼液均能有效地抑制高危角膜移植术后的排斥反应。（眼科,2012, 21: 116-120）     

Clinical efficacy of 0.05% cyclosporine nano-emulsion in the treatment of dry eye syndrome associated with meibomian gland dysfunction

AIM: To evaluate the clinical efficacy of topical 0.05% cyclosporine nano-emulsion in the treatment of dry eye syndrome (DES) with meibomian gland dysfunction (MGD). METHODS: This prospective study included 64 patients with DES and MGD who were randomly assigned to three groups: Group 1 (n=24, conventional cyclosporine), Group 2 (n=21, nano-emulsion cyclosporine), and Group 3 (n=19, control). Lid margin telangiectasia (LMT), meibomian gland secretion (MGS), conjunctival injection (CI), corneal staining (CS), tear break-up time (TBUT), Schirmer test I (STI), Ocular Surface Disease Index (OSDI), and lipid layer thickness (LLT) was evaluated at 4, 8, and 12wk of treatment. RESULTS: In Group 3 (control), LMT, CS, and CI improved after 8wk, MGS, TBUT after 12wk of treatment. In Group 1 (conventional cyclosporine), LMT, MGS, and TBUT improved significantly after 4wk, whereas CS, CI, STI, and LLT improved significantly after 8wk, and OSDI at 12wk. In Group 2 (nano-cyclosporine), LMT, MGS, CS, CI, TBUT, and OSDI significantly improved after 4wk, and STI after 8wk. Especially, LLT was significantly higher than other groups after 4wk. CONCLUSION: Cyclosporine and nano-cyclosporine shows significant improvement in DES with MGD than the control group. In contrast, the nano-cyclosporine group shows more statistically improved CI and CS at 4wk, especially LLT at 4, 8, and 12wk compared to the conventional cyclosporine group.     

眼局部应用骨髓间充质干细胞（BMSC）治疗小鼠干眼的实验研究

目的　探讨局部应用骨髓间充质干细胞（ｂｏｎｅｍａｒｒｏｗｍｅｓｅｎｃｈｙｍａｌｓｔｅｍｃｅｌｌｓ,ＢＭＳＣ）对干眼小鼠的治疗作用及其机制,并比较ＢＭＳＣ滴眼与眼眶注射两种不同应用途径的疗效差异。方法　收集ＢＡＬＢ／ｃ小鼠双侧股骨、胫骨骨髓,采用贴壁培养法纯化ＢＡＬＢ／ｃ小鼠ＢＭＳＣ。利用随机数字表法将３５只健康６～８周龄ＢＡＬＢ／ｃ小鼠分为正常对照组、模型组、阳性对照组、ＢＭＳＣ滴眼组、ＢＭＳＣ眼眶注射组,每组７只,除正常对照组外的２８只小鼠使用２．５ｇ·Ｌ－１苯扎氯铵溶液滴双眼,连续滴２１ｄ,建立中重度干眼动物模型。造模结束后开始治疗,模型组给予磷酸盐缓冲液滴双眼;阳性对照组给予普拉洛芬眼液滴双眼;ＢＭＳＣ滴眼组给予含１×１０５ＢＭＳＣ的磷酸盐缓冲悬垂液滴双眼;ＢＭＳＣ眼眶注射组给予含１×１０５ＢＭＳＣ的磷酸盐缓冲悬垂液分别于治疗当天、第４天注射。治疗的第８天检测并比较各组小鼠眼表炎症指数、泪液分泌试验（ＳｃｈｉｒｍｅｒⅠｔｅｓｔ,ＳⅠｔ）、泪膜破裂时间（ｔｅａｒｆｉｌｍｂｒｅａｋ-ｕｐｔｉｍｅ,ＢＵＴ）、角膜荧光素染色（ｃｏｒｎｅａｌｆｌｕｏｒｅｓｃｅｉｎｓｔａｉｎｉｎｇ,ＦＬＳ）评分结果。第９天过量麻醉法处死３５只小鼠,每组随机选取５眼制备ＨＥ染色、ＰＡＳ染色切片,行眼表组织病理学观察,并进行杯状细胞计数;４眼用于制备冰冻切片,观察有无ＰＫ６７标记的异体ＢＭＳＣ在眼表组织迁移,５眼用于ＥＬＩＳＡ测定小鼠眼表组织中ＩＬ-１０、ＩＬ-１β蛋白含量。结果　模型组眼表炎症指数０．３１±０．０５、ＦＬＳ评分８．８０±１．２１分别高于正常对照组０．０１±０．０１、０．１４±０．１４,差异均有统计学意义（均为Ｐ＜０．０５）;而阳性对照组、ＢＭＳＣ滴眼组、ＢＭＳＣ眼眶注射组炎症指数分别为０．１５±０．０３、０．１８±０．０３、０．０６±０．０２,均明显低于模型组,差异均有统计学意义（均为Ｐ＜０．０５）,且ＢＭＳＣ眼眶注射组低于ＢＭＳＣ滴眼组,差异有统计学意义（Ｐ＜０．０５）;仅ＢＭ-ＳＣ眼眶注射组ＦＬＳ评分３．９３±０．７４明显低于模型组,差异有统计学意义（Ｐ＜０．０５）;模型组ＳＩｔ（４．００±０．３９）ｍｍ明显小于正常对照组（６．３６±０．４８）ｍｍ,差异有统计学意义（Ｐ＜０．０５）;而ＢＭＳＣ眼眶注射组ＳＩｔ（５．８６±０．５４）ｍｍ明显高于模型组、阳性对照组（３．９２±０．３８）ｍｍ、ＢＭＳＣ滴眼组（３．９０±０．３１）ｍｍ,差异均有统计学意义（均为Ｐ＜０．０５）;模型组ＢＵＴ（３．００±０．２１）ｓ较正常对照组（６．００±０．２１）ｓ明显缩短,差异有统计学意义（Ｐ＜０．０５）,而阳性对照组（４．２０±０．２９）ｓ、ＢＭＳＣ滴眼组（４．４０±０．２７）ｓ、ＢＭＳＣ眼眶注射组（４．７９±０．０２）ｓ均较模型组明显延长,差异均有统计学意义（均为Ｐ＜０．０５）。眼表组织ＨＥ染色:模型组角膜上皮细胞肿胀、大量炎性细胞浸润,基质层胶原纤维排列紊乱、肿胀;ＢＭＳＣ滴眼组、眼眶注射组角膜上皮表面平整,基质层胶原纤维排列紧密,形态接近正常小鼠,两组间差异不明显。ＰＡＳ染色杯状细胞数量ＢＭＳＣ眼眶注射组１３．８０±２．４８与阳性对照组１３．１７±２．０９相当,均多于模型组５．２０±１．０７,差异均有统计学意义（均为Ｐ＜０．０５）。冰冻切片:在ＢＭＳＣ滴眼组及ＢＭＳＣ眼眶注射组睑板、结膜下及角膜均未见带ＰＫＨ６７标记的ＢＭＳＣ。ＢＭＳＣ眼眶注射组ＩＬ-１０蛋白含量（５０９．８０±１９０．２１）μｇ·ｇ－１明显高于ＢＭＳＣ滴眼组（４３．６４±４３．６４）μｇ·ｇ－１,差异有统计学意义（Ｐ＜０．０５）;ＩＬ-１β蛋白含量各组间存在差异,但差异无统计学意义（Ｐ＞０．０５）。结论　眼局部应用ＢＭＳＣ能使眼表炎症减轻、ＢＵＴ延长、角膜上皮修复,从而有效缓解干眼的症状。ＢＭ-ＳＣ眼眶注射更能显著促进泪液分泌、增加杯状细胞数量,疗效优于ＢＭＳＣ滴眼。     

Midterm outcomes of penetrating keratoplasty following allogeneic cultivated limbal epithelial transplantation in patients with bilateral limbal stem cell deficiency

AIM: To evaluate the midterm outcomes of penetrating keratoplasty (PK) following allogeneic cultivated limbal epithelial transplantation (CLET) for bilateral total limbal stem cell deficiency (LSCD). METHODS: Ten patients (10 eyes) with bilateral LSCD were enrolled in this prospective noncomparative case series study. Each participant underwent PK approximately 6mo after a CLET. Topical tacrolimus, topical and systemic steroids, and oral ciclosporin were administered postoperatively. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), ocular surface grading scores (OSS), corneal graft epithelial rehabilitation, persistent epithelial defect (PED), immunological rejection, and graft survival rate were assessed. RESULTS: The time interval between PK and allogeneic CLET was 6.90±1.29 (6-10)mo. BCVA improved from 2.46±0.32 logMAR preoperatively to 0.77±0.55 logMAR post-PK (P<0.001). Kaplan-Meier analysis of mean graft survival revealed graft survival rates of 100% at 12 and 24mo and 80.0% at 36mo. PEDs appeared in 5 eyes at different periods post-PK, and graft rejection occurred in 4 eyes. The total OSS decreased from 12.4±4.4 before allogeneic CLET to 1.4±1.51 after PK. CONCLUSION: A sequential therapy design of PK following allogeneic CLET can maintain a stable ocular surface with improved BCVA despite the relatively high graft rejection rate.     

Effect of topical 0.05% cyclosporine A on corneal endothelium in patients with dry eye disease

AIM:To determine the effect of topical 0.05% cyclosporine A (CsA) on corneal endothelium in patients with dry eye disease.METHODS: Observational, prospective, case series study. Fifty-five eyes of 29 consecutive patients (9 males and 20 females; median age:66.8 years, interquartile range:61-73.2 years) with moderate-severe dry eye disease were evaluated. All patients were treated with topical 0.05% CsA ophthalmic emulsion twice a day in addition to lubricant eyedrops 5 times a day. The follow-up period was 12 months. Before treatment and at 3 and 12 months post-treatment central corneal specular microscopy was performed. The endothelial cell density (ECD), coefficient of variation of cell size (CoV), and percentage of hexagonal cells (Hex %) were analyzed.RESULTS: The median ECDs pre-treatment and at 3 and 12 months post-treatment were 2 352.5/mm² (interquartile range, 2 178-2 548.5), 2364/mm² (interquartile range, 2 174.25-2 657.5), and 2366 cells/mm² (interquartile range, 2 174.75-2 539.75), respectively (P=0.927, one way ANOVA). The median CoVs pre-treatment and at 3 and 12 months post-treatment were 34.5 (interquartile range, 30-37), 35 (interquartile range, 30-38), and 34 (interquartile range, 30.75-38.25), respectively (P=0.7193, one way ANOVA). The median Hex % values pre-treatment and at 3 and 12 months post-treatment were 53 (interquartile range, 47-58), 54 (interquartile range, 45.75-59), and 50.5 (interquartile range, 45.75-58), respectively (P=0.824, one way ANOVA).CONCLUSION: Treatment of patients with dry eye disease for 12 months with topical 0.05% CsA does not seem to cause substantial changes on corneal endothelium.