Glaucoma filtering surgery with 5-fluorouracil

A life-table analysis of surgical outcomes was performed on the first eye of 155 patients who were enrolled in a pilot study of glaucoma filtering surgery with postoperative subconjunctival 5-fluorouracil (5-FU) injections. The success rates at 1-, 2-, and 3-year intervals were 68, 63, and 63%, respectively, for 88 patients with non-neovascular glaucoma in aphakia; 82, 75, and 75% for 39 patients with non-neovascular glaucoma after unsuccessful filtering surgery; and 68% at each yearly interval for 28 patients with neovascular glaucoma. Complications which resulted from filtering surgery and the 5-FU injections included corneal epithelial defects (55.5%), conjunctival wound leaks (36.8%), suprachoroidal hemorrhage (5.8%), rhegmatogenous retinal detachment (2.6%), endophthalmitis and phthisis (1.9% each), and corneal scarring, late bleb leak, malignant glaucoma, and traction retinal detachment (1.3% each). A Cox Model regression analysis failed to demonstrate a correlation between surgical success and age, race, type of filtering procedure, or total dose of 5-FU received. Postoperative subconjunctival 5-FU may increase the operative success rate for selected patients with a high risk for failure after glaucoma filtering surgery.     

Analysis of bleb morphology after trabeculectomy with Visante anterior segment optical coherence tomography

BACKGROUND: To describe the use of anterior segment optical coherence tomography (OCT) in imaging intrableb morphology after trabeculectomy. METHODS: 14 post-trabeculectomy eyes from 11 primary open angle glaucoma and 3 primary angle closure glaucoma subjects were studied. The blebs were classified with reference to slit lamp morphology and bleb function. They included diffuse filtering (n = 7), cystic (n = 2), encapsulated (n = 2) and flattened (n = 3) bleb types. One eye in each patient was imaged with the Visante anterior segment OCT. A vertical scan line of 10 mm consisting of 512 A-scans was positioned at the centre of the bleb. The images were then analysed by built-in software. Intrableb morphologies and structures, including bleb wall thickness, subconjunctival fluid collections, suprascleral fluid space, scleral flap thickness, intrableb intensity (low, medium or high) and the route under the scleral flap were characterised and measured. RESULTS: Diffuse filtering blebs were found by subconjunctival fluid collections. Suprascleral fluid space and the route under the scleral flap were identified in four of the seven cases. Cystic blebs were composed of a large hyporeflective space with multiloculated fluid collections covered by a thin layer of conjunctiva. Encapsulated blebs had a thick bleb wall with high reflectivity and an enclosed fluid filled space. Flattened blebs demonstrated high scleral reflectivity and no bleb elevation. CONCLUSIONS: Visante anterior segment OCT can be used for bleb imaging. The different patterns of intrableb morphology identified by OCT were related to slit lamp appearance and bleb function. This information may be useful to study the different surgical outcomes and the process of wound healing in trabeculectomised eyes.     

Classification of filtering blebs in trabeculectomy: biomicroscopy and functionality

The long-term success of filtering surgery is not dependent on surgical technique alone. The development of the filtering bleb in the postoperative period, in particular with regard to wound healing and subconjunctival scarring, is equally important. Morphologic changes of the developing filtering bleb after trabeculectomy can predict early failure even if the intraocular pressure is still normal. A basic understanding of wound healing processes and histologic changes of the developing filtering bleb are mandatory to interpret correctly the morphologic appearance of the developing filtering bleb. In clinical practice, follow-up of the filtering bleb according to a standardized morphologic classification may help to predict outcome and provide clues for the necessity and timing of further treatment.     

Needle revision of failed filtering blebs using 5-Fluorouracil and a combined ab-externo and ab-interno approach

PURPOSE: To evaluate a surgical technique to revise a failed filtering bleb using subconjunctival 5-Fluorouracil with a combined ab-externo and ab-interno approach. PATIENTS AND METHODS: This study is a retrospective review of the outcome of 77 consecutive bleb revisions, with greater than 6-month follow-up, performed by a single glaucoma surgeon (MW). All eyes had previously functioning filtering blebs with currently inadequately controlled intraocular pressures (IOP) prior to the bleb revisions. All surgery was performed in the operating room, using a retrobulbar injection and a microscope. Visco-elastic was injected into the anterior chamber. 5-Fluorouracil (0.1 mL; 50 mg/ml) was infiltrated around the bleb. A 30-gauge needle was used to lyse subconjunctival fibrosis and episcleral scar tissue binding down the scleral flap, and elevate the scleral flap. Through an inferior paracentesis, a cyclodialysis spatula was used to confirm and enlarge the communication with the subconjunctival space. The main outcome measurements were IOP and number of glaucoma medications. A successful outcome was defined as a 20% reduction from baseline IOP and a maximum IOP of 18 mm Hg, with or without medications, and a minimal follow-up of 6 months. RESULTS: 52% of patients achieved success after one revision with an average follow-up of 29.6 +/- 14.4 months. In successful cases, the mean IOP decreased from 22.7 +/- 4.5 mm Hg to 11.3 +/- 3.5 mm Hg and medications were reduced from an average of 2.2 +/- 1.1 to 0.4 +/- 0.7. Kaplan-Meier survival analysis calculated a success of 77% at 1 year, 68% at 2 years, and 58% at 3 years. CONCLUSIONS: In failed filtering blebs, needle revision with 5-Fluorouracil and a combined ab-externo and ab-interno approach results in high success and low complication rates. The outcome of this procedure compares favorably with previously reported revision techniques.     

反复针刺分离联合结膜下注射5-FU治疗青光眼术后滤过泡功能不良

目的:评估以反复针刺分离联合结膜下注射5-FU的方法处理青光眼术后功能不良滤过泡的效果。方法:回顾性分析2009-03/2013-02在我院以反复针刺分离联合结膜下注射5-FU的方法处理因青光眼术后滤过泡功能不良而眼压升高的连续病例34例34眼。分析治疗后眼压、滤过泡形态的变化及眼部并发症。结果:治疗后平均眼压从35.51mmHg降至14.43mmHg(P<0.05),成功率达91%。常见并发症包括角膜上皮损伤、结膜撕裂和脉络膜脱离等。结论:反复针刺分离联合结膜下注射5-FU的方法处理青光眼术后滤过泡功能不良安全有效。     

针刺分离联合5-FU治疗青光眼术后早期滤过泡功能不良

目的探讨对于青光眼术后早期功能不良的滤过泡采用针刺分离联合结膜下注射5-FU的治疗效果。方法青光眼滤过术后3月内25眼功能不良的滤过泡采用针刺分离滤过泡周围纤维瘢痕,联合结膜下注射5-FU 5mg/次,隔日1次,最多5次,分析治疗后眼压和滤过泡形态的变化及治疗后的眼部并发症。结果 25眼中,21眼眼压控制在21mmHg以下,其中18眼在15mmHg以下;滤过泡形态：有19眼表现为功能性滤过泡;并发症：常见并发症有结膜下出血、角膜上皮损伤、滤过泡损伤等。结论对于青光眼术后早期功能不良的滤过泡采用针刺分离联合结膜下注射5-FU是安全、有效的。     

The surgical management of leaking filtering blebs.

Leaking blebs may be encountered in the early postoperative period, or months to years after filtering surgery. Early postoperative bleb leaks are most often related to surgical trauma to the conjunctiva and can be avoided by careful surgical technique. Spontaneous late bleb leaks occur more frequently in glaucoma filtering surgery following adjunctive use of antimetabolites and full-thickness procedures. As we endeavor to achieve better long-term success with filtering surgery, antimetabolites have gained increasing popularity. With this change in clinical practice, a higher rate of bleb leaks is being recognized. These leaks may be uncomplicated or may be associated with sight-threatening complications such as endophthalmitis. The plethora of treatment options for bleb leaks described in the literature reflects the widespread nature of this problem. It also reflects the failure of any one particular approach not only to resolve bleb leaks but also to prevent their recurrence. This paper reviews the contemporary surgical management of leaking blebs and formulates a practical approach to their management.     

A modified model of glaucoma filtering surgery in Sprague-Dawley rats

Animal models are useful in glaucoma research to study tissue response to wound healing. Smaller animals such as rats offer additional advantages in terms of availability of detection antibodies and microarrays with cheaper maintenance costs. In this study, we describe a glaucoma filtering surgery (GFS) model in adult Sprague–Dawley rats by performing a sclerostomy using a 26-G needle and additionally placing a silicone tube (27 G) connecting the anterior chamber to the subconjunctival space to maintain a patent fistula for the flow of aqueous humor, thus providing a more definitive bleb. This technique will be useful in identifying and modifying newer targets in the wound healing process in order to improve surgical outcomes following GFS.     

喜树碱抑制滤过泡瘢痕化的临床研究

用抗代谢药物喜树碱作青光眼滤过性手术中抗瘢痕形成的辅助药物，并设立５－氟尿嘧啶对照组与未注药对照组。结果近期疗效三组均无显著性差异，但喜树碱较５－Ｆｕ局部反应轻，术后并发症少。     

Selected abstracts of the Joint Meeting of the Belgian Ophthalmological Society,The Dutch Ophthalmological Society,and the Netherlands Ophthalmic Research Institute,Antwerp, 21 January 1995

After glaucoma filtering surgery subconjunctival injection of human recombinant tissue plasminogen activator may promote the function of glaucoma filter bleb and increase outflow facility. It can also increase postoperativae complications, such as corneal damage. The aim of our research was to determine corneal endothelial permeability (Pac) in subjects with glaucoma filter bleb protected by a plasminogen activator (Actilyse, Boehringer) when haemorrhagic clots obstructing a glaucoma filtering site had occurred. Two weeks, three months and six months after goniotrephining with scleral cover, in groups with and without subconjunctival injection of 25 mg human tissue plasminogen activator, Pac was calculated. In both groups, no significant differences in the level of Pac measured by fluorophotometry were found.     

The changing conceptual basis of trabeculectomy: a review of past and current surgical techniques

The original intent of glaucoma surgery was to allow aqueous humor to exit more easily either through the sclera or into the suprachoroidal space. The former came to be called, generically, a glaucoma filtering procedure. As this surgery evolved, some explored the concept of lowering pressure without producing a hole in the sclera, with its resultant "filtering bleb." For example, Cairns hoped that cutting open the edges of Schlemm's canal would allow aqueous to leave without producing a filtering bleb; however, it became apparent that Cairns's "trabeculectomy" only worked when a filtering bleb developed. The goal of today's trabeculectomy is the creation of a longlasting transscleral fistula. In fact, trabeculectomy is a misnomer as excision of trabecular meshwork is unimportant. Frequently, the tissue excised to create a trans-scleral fistula is sclera, cornea, or both. The current trabeculectomy is really a guarded sclerokeratectomy. Newer techniques hope to increase aqueous outflow through Schlemm's canal to avoid complications associated with subconjunctival filtering blebs. Non-penetrating glaucoma surgeries (deep sclerectomy, viscocanalostomy) and ab interno trabecular surgery attempt to lower intraocular pressure with bleb-less procedures. We describe the recent evolution of glaucoma surgery, particularly the idea that intraocular pressure may be lowered satisfactorily without creating a filtering bleb.     

难治性青光眼早期功能不良滤过泡处理的临床观察

目的：观察难治性青光眼小梁切除术后早期功能不良滤过泡的处理方法、治疗效果,探讨有效、安全的早期功能不良滤过泡处理方法。

方法：收集我院2006-01/2012-01诊断为难治性青光眼且行小梁切除术后出现早期功能不良滤过泡(或倾向)者20例20眼于小梁切除术后3～8d进行治疗,治疗方法包括：眼球按摩、断(或拆除)巩膜缝线后再行眼球按摩、钝针头针拨分离滤过泡或联合结膜下注射5-氟尿嘧啶(5-FU)。所有患者术中曾用过抗代谢药丝裂霉素C(MMC, 0.3g/L)。随访6mo。

结果：经眼球按摩后有9眼获得功能滤过泡,联合钝针头针拨分离滤过泡治疗后有5眼为功能滤过泡,4眼经联合5-FU结膜下注射后为功能滤过泡,其综合成功率达90%。治疗前平均眼压24.61±5.4mmHg(1mmHg=0.133kPa),随访6mo结束时平均眼压为15.20±4.8mmHg,治疗前后眼压差异有显著统计学意义(P<0.01)。操作中和操作后未见任何并发症。

结论：难治性青光眼病情复杂,小梁切除术后极易出现早期功能不良滤过泡(或倾向),我们提倡尽早处理,综合眼球按摩、断(或拆除)巩膜缝线、钝针头针拨分离滤过泡或联合结膜下注射5-FU更安全有效,可很大程度上挽救早期濒临失败的滤过泡,提高手术成功率。     

针刺分离联合结膜下注射5-FU治疗青光眼术后早期滤过泡功能不良

目的:探讨对于青光眼术后早期功能不良的滤过泡采用针刺分离联合结膜下注射5-FU的治疗效果。方法:青光眼滤过术后3mo内25眼功能不良的滤过泡采用针刺分离滤过泡周围纤维瘢痕,然后结膜下注射5-FU5～10mg,隔日1次共5次,分析治疗后眼压和滤过泡形态的变化及治疗后的眼部并发症。结果:25眼中,21眼眼压控制在21mmHg以下,其中18眼在15mmHg以下;滤过泡形态:有19眼表现为功能性滤过泡;并发症:常见并发症有角膜上皮损伤、结膜下出血、滤过泡损伤等。结论:对于青光眼术后早期功能不良的滤过泡采用针刺分离联合结膜下注射5-FU是安全、有效的。     

The critical role of the conjunctiva in glaucoma filtration surgery

This review considers the critical role of the conjunctiva in determining the success or failure of glaucoma filtration surgery. Glaucoma filtration surgery can be defined as an attempt to lower intraocular pressure (IOP) by the surgical formation of an artificial drainage pathway from the anterior chamber to the subconjunctival space. Many types of glaucoma filtration surgery have been developed since the first attempts almost 180 years ago. The wide range of new techniques and devices currently under investigation is testament to the limitations of current techniques and the need for improved therapeutic outcomes. Whilst great attention has been paid to surgical techniques and devices to create the drainage pathway, relatively little attention has been given to address the question of why drainage from such artificial pathways is often problematic. This is in contrast to normal drainage pathways which last a lifetime. Furthermore, the consequences of potential changes in aqueous humour properties induced by glaucoma filtration surgery have not been sufficiently addressed. The mechanisms by which aqueous fluid is drained from the subconjunctival space after filtration surgery have also received relatively little attention. We propose that factors such as the degree of tissue damage during surgery, the surrounding tissue reaction to any surgical implant, and the degree of disruption of normal aqueous properties, are all factors which influence the successful formation of long term drainage channels from the conjunctiva, and that these channels are the key to successful filtration surgery. In recent years it has been suggested that the rate of fluid drainage from the subconjunctival space is actually the determining factor in the resultant IOP reduction. Improved knowledge of aqueous humour induced changes in such drainage pathways has the potential to significantly improve the surgical management of glaucoma.We describe for the first time a novel type of drainage surgery which attempts to minimise surgical trauma to the overlying conjunctiva. The rationale is that a healthy conjunctiva allows drainage channels to form and less opportunity for inflammation and scar tissue formation which are a frequent cause of failure in glaucoma filtration surgery. Successful drainage over extended periods of time has been demonstrated in monkey and rabbit eyes. Long lasting drainage pathways were clearly associated with the presence of lymphatic drainage pathways. A new philosophy in glaucoma drainage surgery is proposed in which minimisation of surgical trauma to the conjunctiva and the encouragement of the development of conjunctival drainage pathways, particularly lymphatic pathways, are central pillars to a successful outcome in glaucoma filtration surgery.     

Complications and Management of the Filtration Bleb

Filtration surgery is the commonest operation performed for closed angle or open angle glaucoma when medical treatment or laser trabeculoplasty has failed to control the intraocular pressure. It is characterized by the formation of an artificial drainage fistula between the anterior chamber and subconjunctival space. The successful operation is evidenced by the appearance of a subconjunctival filtration bleb which in turn depends on the patency of this pathway. Despite numerous modification, the procedure trabeculectomy first described by Sugar in 1961 and later on popularized by Watson and Cairns in 1968 is the most popular filtration surgery performed nowadays. It is a safe, relatively easy operation which carries a success rate of around 76% to 84% with a small complication rate. Repeat filtration surgery, however, is often less successful, making a successful initial surgery critically important. A successful outcome of filtration surgery can be enhanced by pre-operative preparation, meticulous technique with modification for individual case, and early identification and prompt treatment of the complications arisen.     

Evaluation of anti-TGF-beta2 antibody as a new postoperative anti-scarring agent in glaucoma surgery

PURPOSE: Postoperative subconjunctival wound healing remains the commonest cause of late bleb failure after glaucoma filtration surgery. This study was undertaken to investigate whether the human monoclonal antibody that neutralizes transforming growth factor-beta2 (CAT-152; lerdelimumab) could be used as a postoperative agent to prevent scarring after glaucoma surgery and compared it with 5-fluorouracil (5-FU), to benchmark its potential clinical benefit. METHODS: In a randomized, controlled, masked-observer study, after modified glaucoma surgery, 48 rabbits were randomly allocated to receive a postoperative course of seven subconjunctival injections of CAT-152 (1 mg/mL), 5-FU (50 mg/mL), or no treatment. Bleb characteristics, the presence of subconjunctival drainage, and local reaction to treatment were assessed. Animals were killed on days 10, 21, and 30. Immunohistochemistry, histologic staining and electron microscopy were performed to demonstrate the mechanism of CAT-152-mediated effects on the extracellular matrix. RESULTS: CAT-152 significantly improved surgical outcome (log rank test, P < 0.001) and reduced subconjunctival collagen deposition (P < 0.01) compared with 5-FU and control. Median bleb survival was increased in the CAT-152 group (23.5 days) compared with the 5-FU (20 days) and control (16 days) treatment groups. CAT-152 treatment improved bleb morphology (P < 0.05) and was well tolerated. 5-FU prolonged the duration of corneal epitheliopathy (P < 0.01). CONCLUSIONS: Postoperative administration of CAT-152 significantly improved surgical outcome, reduced subconjunctival scarring, and minimized the risk of corneal side effects compared with the anti-scarring agent 5-FU. These findings suggest that CAT-152 may offer therapeutic benefit as a postoperative agent to prevent subconjunctival scarring after glaucoma filtration surgery.     

Long-term results of 5-fluorouracil trabeculectomy for primary open-angle glaucoma

The effect of 5-fluorouracil (5-FU) subconjunctival injection on the bleb formation and intraocular pressure (IOP) following trabeculectomy was studied in 27 primary open-angle glaucoma patients (33 eyes) who had never been operated upon (25 eyes) or had undergone single trabeculectomy that failed to reduce IOP (8 eyes). The results were analyzed by means of life table analysis and compared with those of 65 primary open-angle glaucoma eyes that had undergone trabeculectomy without postoperative administration of 5-FU as the first or the second filtering surgery. The surgical techniques and postoperative care were virtually identical between the eyes treated with 5-FU and the eyes that had undergone trabeculectomy without 5-FU. At the end of 28-month follow-up, the success probability was 74.8% without any postoperative antiglaucoma medication, and 100% with antiglaucoma medication. Whereas, the success probability with postoperative antiglaucoma medication was as low as 60.8% for the first, and 51.5% for the second trabeculectomy without 5-FU at the 24-month follow-up. Postoperative, subconjunctival injection of 5-FU appears to improve the prognosis following trabeculectomy in primary open-angle glaucoma patients.     

眼球按摩在难治性青光眼滤过手术后的应用观察

目的 观察抗青光眼滤过术后应用眼球按摩的临床效果.方法 对37例难治性青光眼42眼行复合小梁切除术后行眼球按摩患眼,在术后第一天起进行眼球按摩.经测量眼压,观察前房,滤过泡（Seidel试验）,等进行临床分析.结果 37例滤过手术42眼,患者眼压均正常,滤过泡功能良好,前房良好.结论 难治性青光眼滤过术后早期及时发现滤过功能减退的征象及时准确进行眼球按摩,是提高难治性青光眼手术成功率的简单有效的治疗方法.     

Use of 5-fluorouracil in the surgery of glaucoma

63 eyes (46 patients) with different types of glaucoma have been operated by filtering surgery with subconjunctival 5 fluoro-uracil (5-FU) injections. The mean follow up is 7 months. Two groups of patients have been studied: In the 33 eyes with previous unsuccessful glaucoma surgery, the result was very good: 73% of complete success (IOP less than or = 20 mmHg without additional therapy) 18% of qualified success (IOP less than or = 20 mmHg with additional therapy) 8% of failure. The other group included 30 eyes without previous glaucoma surgery, but with a bad surgical prognosis. In all the cases, the result was good, only one eye required additional therapy. The corneal complications are the most frequent, but do not last long. The other complications depend upon the indications, there are many in the aphakic patients. The durable flat anterior chamber must also be quoted.     

青光眼滤过泡的活体形态观察

滤过手术是目前临床上常用的抗青光眼手术方式之一,而术后滤过道的瘢痕化是导致滤过手术失败的重要原因.因此,临床医师对于滤过道状态的判断,尤其对那些术后早期眼压处于正常范围内的患者,观察并分析其滤过泡的形态和功能就显得更为重要.对于出现瘢痕化趋势的滤过道应进行早期干预,如应用抗代谢药物、按摩眼球等方法,均有利于维持滤过道的通畅,提高手术成功率.因此,临床医师应重视对青光眼术后患者活体滤过泡形态和功能的观察与评价.