SPARC Deficiency Results in Improved Surgical Survival in a Novel Mouse Model of Glaucoma Filtration Surgery

Glaucoma is a disease frequently associated with elevated intraocular pressure that can be alleviated by filtration surgery. However, the post-operative subconjunctival scarring response which blocks filtration efficiency is a major hurdle to the achievement of long-term surgical success. Current application of anti-proliferatives to modulate the scarring response is not ideal as these often give rise to sight-threatening complications. SPARC (secreted protein, acidic and rich in cysteine) is a matricellular protein involved in extracellular matrix (ECM) production and organization. In this study, we investigated post-operative surgical wound survival in an experimental glaucoma filtration model in SPARC-null mice. Loss of SPARC resulted in a marked (87.5%) surgical wound survival rate compared to 0% in wild-type (WT) counterparts. The larger SPARC-null wounds implied that aqueous filtration through the subconjunctival space was more efficient in comparison to WT wounds. The pronounced increase in both surgical survival and filtration efficiency was associated with a less collagenous ECM, smaller collagen fibril diameter, and a loosely-organized subconjunctival matrix in the SPARC-null wounds. In contrast, WT wounds exhibited a densely packed collagenous ECM with no evidence of filtration capacity. Immunolocalization assays confirmed the accumulation of ECM proteins in the WT but not in the SPARC-null wounds. The observations in vivo were corroborated by complementary data performed on WT and SPARC-null conjunctival fibroblasts in vitro. These findings indicate that depletion of SPARC bestows an inherent change in post-operative ECM remodeling to favor wound maintenance. The evidence presented in this report is strongly supportive for the targeting of SPARC to increase the success of glaucoma filtration surgery.     

Trabeculectomy with mitomycin C in glaucoma associated with uveitis

The patients with uveitic glaucoma are at high risk for failure following drainage surgery because of young age of these patients, preoperative long-term control of inflammation and postoperative complications. Twenty-two trabeculectomies performed in 22 patients with uveitic glaucoma were retrospectively evaluated to analyze the effect of intraoperative application of mitomycin C (MMC). Success rates, postoperative levels of intraocular pressure (IOP) and postoperative complications were studied. After a mean follow-up of 10.6 months (range, 5-28 months), 15 patients (68.2%) achieved IOP of 21mmHg or less without antiglaucoma medications. There were statistically significant reduction in IOP postoperatively during the period studied (p < 0.001). Early postoperative complications included chorioidal detachment (9.1%), shallow anterior chamber (9.1%), hyphema (13.6%), macular edema (4.5%) and raised IOP (27.3%). Late postoperative complications included exacerbation of uveitis (4.5%), macular edema (4.5%), cataract (22.7%) and raised IOP (31.8%). The eyes with raised IOP needed additional antiglaucoma medication. The results of this retrospective and uncontrolled study suggest that intraoperative application of MMC may be a good option for enhancement of short-term trabeculectomy success rates in patients with uveitic glaucoma.     

24 例眼外伤继发性青光眼的临床分析

目的:分析眼外伤继发青光眼的临床特点、病因及治疗方法,为临床治疗提供参考。方法:回顾性分析24例(24只眼)眼外伤继发青光眼患者的临床资料,分析诱发青光眼的原因、临床分型,根据具体情况选择治疗方法。结果:眼外伤诱发青光眼的原因为眼内积血11例,晶状体损伤7例,前房角挫伤4例,外伤性虹睫炎2例;单纯药物治疗4例,前房穿刺或冲洗4例,小梁切除联合丝裂霉素术10例,玻璃体切除术2例,滤过手术1例,激光周边虹膜切除术5例。治疗后随访6~12个月,眼压恢复正常率87.50%;视力下降或丧失8.33%;术中1例眼出血,1例术后晶体状浑浊加重,1例视网膜脱离。结论:眼外伤继发青光眼的临床表现复杂,治疗难度大,临床应根据患者的具体情况选择治疗措施。     

Inhibition of placental growth factor improves surgical outcome of glaucoma surgery

Excessive post‐operative wound healing with subsequent scarring frequently leads to surgical failure of glaucoma filtration surgery (trabeculectomy). We investigated the hypothesis that placental growth factor (PlGF) plays a role in post‐operative scar formation, and that it therefore may be a target for improvement of filtration surgery outcome. ELISA experiments showed that PlGF levels were significantly increased in aqueous humour of glaucoma patients and after VEGF treatment, which may indicate an important contribution of this growth factor to wound healing after trabeculectomy. Using a mouse model of glaucoma filtration surgery, we were able to show that intracameral injection of a previously characterized anti‐PlGF antibody (ThromboGenics NV) significantly improved surgical outcome by increasing bleb survival and bleb area. This was associated with a significant reduction in post‐operative proliferation, inflammation and angiogenesis during the first post‐operative days after surgery, and with a decrease in collagen deposition at later stages. Furthermore, inhibition of PlGF seemed to be more effective than anti‐VEGF‐R2 treatment in improving surgical outcome, possibly via its additional effect on inflammation. These results render PlGF an appealing target for ocular wound healing and point to potential therapeutic benefits of PlGF inhibition for the prevention of surgical failure.     

Application of 5-Fluorouracil-Polycaprolactone Sustained-Release Film in Ahmed Glaucoma Valve Implantation Inhibits Postoperative Bleb Scarring in Rabbit Eyes

This study was designed to investigate whether 5-fluorouracil (5-Fu)-polycaprolactone sustained-release film in Ahmed glaucoma valve implantation inhibits postoperative bleb scarring in rabbit eyes. Eighteen New Zealand white rabbits were randomly divided into three groups (A, B and C; n = 6 per group). Group A received combined 5-Fu-polycaprolactone sustained-release film application and Ahmed glaucoma valve implantation, group B received local infiltration of 5-Fu and Ahmed glaucoma valve implantation, and group C received Ahmed glaucoma valve implantation. Postoperative observations were made of the anterior segment, intraocular pressure, central anterior chamber depth, blebs, drainage tube, and accompanying ciliary body detachment. The pathology of the blebs and surrounding tissues were observed at month 3 postoperatively. We revealed that the 5-Fu-polycaprolactone sustained-release film maintained a release concentration range of 13.7 ± 0.12 to 37.41 ± 0.47 μg/ml over three months in vitro. Postoperatively, diffuse blebs with ridges were found in all eyes in group A, two blebs were observed in group B, and no bleb formation was present in group C. The postoperative central anterior chamber depth in group A was significantly less than that of the other two groups. The postoperative intraocular pressure of group A stabilized at 6.33–8.67 mmHg, whereas that of group C gradually remained at 7.55–10.02 mmHg. The histopathology showed that the fibrous tissue thickness of the blebs in group A was significantly thinner than that of the other groups. We conclude that the 5-Fu-polycaprolactone sustained-release film had a sustained drug release effect, which promoted the inhibition of bleb scarring after Ahmed glaucoma valve implantation.     

Postoperative outcomes after implantation of intraocular lenses in eyes with cataract and uveitis

Despite advances in surgical technique and implant materials, cataract surgery in patients with uveitis is still a challenging procedure. We retrospectively evaluated postoperative outcomes of cataract surgery in 35 eyes of 29 patients with uveitis. Phacoemulsification with posterior chamber intraocular lens implantation was performed in all eyes. Postoperative evaluations were performed at day 2, and then at 7 days, 1, 3, and 6 months respectively. There were 16 males, and 13 females, aged 31 to 68 years. Follow-up ranged from 4 to 35 months. At final follow-up 33 eyes (94%) had an improvement in visual acuity compared with preoperative levels (p < 0,05). Giant cells were observed in the intraocular lens optic in 7 eyes (20%). Posterior capsule opacification occurred in 10 eyes (29%). Clinical cystoid macular edema was observed in 4 eyes, and 2 eyes required trabeculectomy with mitomycin C due to secondary glaucoma. Cataract surgery in patients with uveitis leads to successful visual results after correct surgical timing, and adequate anti-inflammatory therapy. There were no significant differences in the degree of inflammation after implantation of various types of intraocular lenses.     

青光眼术后抗滤过泡瘢痕化药物进展

青光眼是全世界排名第二位的导致视力下降或丧失的眼病,对视力的损害严重且不可逆,使青光眼的早期诊断和治疗显得尤为重要。目前,青光眼滤过性手术仍是降低患者眼内压最有效的治疗方法,但经滤过减压术后,青光眼患者滤过泡成纤维细胞的增殖和胶原的沉积,会导致滤过泡功能不同程度的减退,减少了滤过性手术的成功率。为减轻这种不必要的瘢痕愈合,一些抗瘢痕形成药物被越来越多应用于青光眼滤过手术的实验与临床研究中。本文对目前这些主要的青光眼滤过性手术后抗滤过泡瘢痕的药物的作用机制及临床治疗效果进行综述。     

Lithium chloride inhibits TGF-β1-induced myofibroblast transdifferentiation via PI3K/Akt pathway in cultured fibroblasts from Tenon’s capsule of the human eye

Excess scarring of the conjunctiva after glaucoma filtration surgery is a major cause of failure. Transforming growth factor (TGF)-β is critically involved in post-operative scarring. Lithium inhibits TGF-β-induced gene protein expression in corneal fibroblasts and inhibits TGF-β-induced epithelial mesenchymal transition. Here, we investigated the effects of LiCl on TGF-β1-mediated signaling pathways and on myofibroblast transdifferentiation of human Tenon’s capsule fibroblasts (HTFs). LiCl treatment reduced expression of TGF-β1-induced α-SMA expression in HTFs. LiCl also decreased Akt phosphorylation induced by TGF-β1. TGF-β1-induced α-SMA expression was significantly decreased by LY294002 and Akt siRNA indicating that these changes are mediated by the PI3K/Akt pathway. Thus, LiCl induces the suppression of transdifferentiation stimulated by TGF-β1 by the regulation of PI3K/Akt signaling in HTFs.     

Prevention of ocular scarring post glaucoma filtration surgery using the inflammatory cell and platelet binding modulator saratin in a rabbit model

Clinical Relevance

Late complications can occur with use of current antimetabolites to prevent scarring following glaucoma filtration surgery (GFS). Safer, more targeted, anti-fibrosis agents are sought.

Objectives

The protein saratin has been shown to exhibit anti-fibrotic and anti-thrombotic properties in response to injury, but had not been used for glaucoma surgery. The goal of this study was to compare the efficacy of saratin with that of the widely accepted mitomycin-C (MMC) in prolonging bleb survival following GFS in the rabbit model. Two saratin delivery routes were compared; a single intraoperative topical application versus a combination of intraoperative topical application with two additional postoperative injections.

Methods

Twenty-four New Zealand White rabbits underwent GFS and received either intraoperative topical saratin, intraoperative topical saratin plus two injections on post-operative days 4 and 8, balanced saline solution (BSS), or MMC. The bleb tissues and their elevation durations were compared based on clinical and histological findings.

Results

Rabbits receiving topical+injections of saratin had a mean bleb survival of 33.6±8.5 days, significantly higher than the negative BSS controls, which averaged 17.4±6.0 days (p = 0.018). No improvement over BSS was seen for rabbits receiving topical saratin only (15.5±4.8 days, p = 0.749). Rabbits receiving saratin did not develop bleb avascularity and thinning associated with MMC treatment and there were no apparent clinical signs of toxicity.

Conclusions

Treatment with a single intraoperative topical application plus two additional postoperative injections significantly prolonged bleb elevation comparable to MMC, but without toxicity; however, topical application alone was ineffective.     

Development of diagnostic and treatment strategies for glaucoma through understanding and modification of scleral and lamina cribrosa connective tissue

Considerable evidence indicates that the state of ocular connective tissues and their response in glaucomatous disease affect the degree of glaucoma damage. Both experimental and clinical data suggest that improved diagnostic and prognostic information can be derived from the assessment of the mechanical responsiveness of the sclera and lamina cribrosa to intraocular pressure (IOP). Controlled mutagenesis of the sclera has produced a mouse strain that is relatively resistant to increased IOP. Alteration of the baseline scleral state can be accomplished through either increased cross-linking of fibrillar components or their reduction. The sclera is a dynamic structure, altering its structure and behavior in response to IOP change. The biochemical pathways that control these responses are fertile areas for new glaucoma treatments.     

不同术式治疗新生血管性青光眼的疗效比较

目的：比较不同手术方法治疗新生血管性青光眼（neovascular glaucoma,NVG）的疗效。方法：对接受不同术式治疗的57例57只眼NVG的临床资料进行回顾性分析,其中行单纯睫状体冷凝术20例（A组）,改良小梁切除术15例（B组）,引流阀植入术联合全视网膜光凝术22例（c组）。比较各组患者手术前后主观眼痛症状、眼压及视力变化情况,并随访3～6个月。结果：A组患者出院时的平均眼压为（28．13＋4．83）mmHg,B组为（19．24±5．48）mmHg,C组为（21．22±4．76）mmHg。随访期间,术后A组9例眼压正常,手术成功率45％;B组11例眼压正常,手术成功率73．3％;C组13例眼压正常,手术成功率57．1％。B组手术成功率最高,A组最低。结论：三种手术方法均可不同程度降低新生血管性青光眼的眼压。单纯睫状体冷凝术后眼压控制效果欠佳,有视力眼不宜采用此种手术方式;改良小梁切除术是治疗新生血管性青光眼安全、有效、经济的手术方式;引流阀植入术联合全视网膜光凝术费用较高。     

A One-Piece Ocular Drainage Implant for Glaucoma Surgery: A Preliminary Report

A one-piece silicone filtration implant for glaucoma surgery was evaluated in 18 normotensive rabbits. During the follow-up period of 60 days the function of the implant and the effect of the implant on intraocular pressure (IOP) and local reaction in operated eyes were examined. Mean IOP in operated eyes during the whole follow-up period stayed in a level that was statistically significantly (p<0.001) lower than the preoperative starting value. Despite of a slight inflammatory reaction in the immediate postoperative period the implants were well tolerated. No marked foreign body reaction were noted around the implants in histological sections. In 3 eyes the implants had to be removed due to complications caused by surgical technique.     

Clinical Outcomes of FP-7/8 Ahmed Glaucoma Valves in the Management of Refractory Glaucoma in the Mainland Chinese Population

BackgroundTo evaluate the efficacy and safety of the Ahmed glaucoma valve (AGV) and the risk factors associated with AGV implantation failure in a population of Chinese patients with refractory glaucoma.MethodIn total, 79 eyes with refractory glaucoma from 79 patients treated in our institution from November 2007 to November 2010 were enrolled in this retrospective study. The demographic data, preoperative and postoperative intraocular pressures (IOPs), best corrected visual acuity (BCVA), number of anti-glaucoma medications used, completed and qualified surgery success rates and postoperative complications were recorded to evaluate the outcomes of AGV implantation. Factors that were associated with implant failure were determined using Cox proportional hazard regression model analysis and multiple linear regression analysis.ConclusionAGV implantation was safe and effective for the management of refractory glaucoma. Patients with a greater number of previous surgeries were more likely to experience surgical failure, and patients with previous trabeculectomy were more likely to use multiple anti-glaucoma drugs to control postoperative IOP.     

Long-Term Outcomes and Complications of Trabeculectomy for Secondary Glaucoma in Patients with Familial Amyloidotic Polyneuropathy

Objective

Secondary glaucoma is a serious complication in patients with transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP). We assessed the long-term outcomes and complications of trabeculectomy with mitomycin C (MMC) for secondary glaucoma associated with FAP.

Methods

Medical case records of Kumamoto University Hospital were retrospectively reviewed. Twenty-one eyes of 13 patients (10 with FAP ATTR Val30Met; 3 with FAP ATTR Tyr114Cys) underwent trabeculectomy with MMC and follow-up of at least 2 years. The primary outcome measure was Kaplan-Meier survival, with failure of this treatment being defined as an intraocular pressure (IOP) of ≤5 mm Hg or ≥22 mm Hg on two consecutive visits or as additional operations needed to reduce IOP. Secondary outcome measures included complications, bleb characteristics, and additional postoperative interventions required.

Results

The mean postoperative follow-up period was 5.7 years (range, 2.2–12.7 years). Kaplan-Meier analysis indicated probabilities of success of 0.76, 0.67, and 0.53 at 1, 2, and 3 years after operation, respectively. Significant complications included ocular decompression retinopathy in 7 eyes (33%) and bleb encapsulation in 10 eyes (48%). Twelve eyes (57%) needed additional surgery, such as bleb revision or trabeculectomy with MMC, to reduce IOP.

Conclusions

Trabeculectomy with MMC may not be optimal for patients with FAP-related glaucoma and may have several significant complications.     

羊膜移植联合低浓度丝裂霉素治疗原发性青光眼的临床疗效

目的:探究羊膜移植联合低浓度丝裂霉素在治疗原发性青光眼的临床疗效。方法:选取2013年6月~2014年1月我院收治的原发性青光眼患者58例(80眼),按照随机数字表法分为观察组(30例,40眼)和对照组(28例,40眼),观察组行小梁切除、羊膜移植联合低浓度丝裂霉素治疗,对照组行小梁切除治疗,比较两组的手术效果及术后并发症情况。结果:观察组术后优良率为97%(38/40),显著优于对照组的75%(28/40),差异有统计学意义(x2=9.764,P=0.008);两组术后1、6个月眼压较术前均明显降低(P0.05),且观察组较对照组更低(P0.05);观察组功能性滤泡明显多于对照组(x2=4.943,P=0.026),术后并发症明显低于对照组(x2=4.501,P=0.034),复发情况明显低于对照组(x2=3.914,P=0.047)。结论:羊膜移植联合低浓度丝裂霉素治疗原发性青光眼能够有效控制眼压,减缓患者视力的丧失,术后并发症及复发率均较低,值得临床推广。     

Glaucoma triple procedure: a one-site vs. a two-site approach

The purpose of this study is to describe and evaluate the success rate of combined glaucoma and small cataract surgery by means of a one-site versus two-site approach. Fifty-eight eyes of fifty-five patients undergoing combined surgery were operated: thirty-one eyes underwent two-site approach and twenty-seven eyes underwent one-site approach. Short term and long term mean intraocular pressure (IOP) was similar in both groups. There was no significant difference in postoperative inflammation and complication rates between two groups. There is no significant difference in the postoperative results in those two different approaches to perform combined operations of cataract and glaucoma.     

两种手术方式治疗原发性闭角型青光眼疗效比较

目的:探讨治疗原发性闭角型青光眼二种手术方式的适应症和初步临床疗效观察。方法:拟订手术适应症,对临床收治的42例48眼原发性闭角型青光眼进行手术处理:单纯抗青光眼手术--小梁切除术(Trabeculectomy,Trab)、青白联合手术--超声乳化白内障吸除联合小梁切除+人工晶体植入术(Phacotrabeculectomy+IOL,PhacoTrab+IOL)。比较不同适应症下二种手术方式初步的临床疗效。包括术前术后眼压情况、前房深度、眼轴长度的变化。随访时间平均1个月。结果均经统计学处理。结果:原发性闭角型青光眼患者术后眼压有显著改变,有统计学差异,Trab组手术后平均(10.92±1.74)mmHg,Phaco Trab+IOL组手术后平均(10.86±1.73)mmHg。术后眼压明显降低(t检验,P值<0.001),Trab组和Phaco Trab+IOL组两组间术后眼压无显著差异(t检验,P值>0.05)。Trab组手术前后前房深度无统计学差异(t检验,P值>0.05),Phaco Trab+IOL组手术前后前房深度有统计学差异(t检验,P值均<0.001)。术前分别为(1.74±0.16)mm、(1.72±0.16)mm,术后分别为(1.74±0.17)mm、(2.06±0.14)mm。Trab组及Phaco Trab+IOL组手术前后眼轴长度无统计学差异(t检验,P值>0.05)。结论:青-白联合手术可以改善前房深度,明显降低眼压,不同手术方式适合不同的病人情况,但要注意适应症的选择。利用A超检查可快速、有效、准确地观察眼前节结构,有助于早期进行手术。     

超声乳化手术治疗慢性闭角型青光眼合并白内障的临床疗效分析

目的:探讨超声乳化手术治疗慢性闭角型青光眼合并白内障的临床效果。方法:慢性闭角型青光眼合并白内障64例(64眼)根据治疗方法的不同分为治疗组与对照组各32例,对照组采用传统小梁切除手术,治疗组采用超声乳化手术。结果:(1)两组术前视力对比无明显差异,治疗后视力情况都明显改善,同时组间对比有明显差异(P0.05)。(2)两组术前眼压比较无显著性差异,术后两组组间与组内对比都有明显差异(P0.05)。(3)两组术前前房深度比较无显著性差异,治疗后都有明显上升(P0.05),同时组间对比差异明显(P0.05)。(4)两组患者术中与术后都无严重并发症发生。结论:对于慢性闭角型青光眼合并白内障患者行超声乳化手术具备加深前房、控制眼压、提高视力的作用,同时安全性好,可作为标准治疗选择。