Fornix-based versus limbal-based conjunctival trabeculectomy flaps for glaucoma

Review question
We reviewed the evidence for the effectiveness and complications of different approaches (fornix-based versus limbal-based incisions) of drainage surgery (trabeculectomy) in adults with glaucoma.

Background
Glaucoma is one of the leading largely-preventable causes of blindness in the world. Surgical treatment aims at opening the drainage system and lowering the pressure in the eye when other medical treatments with eyedrops fail. Trabeculectomy is one surgical technique that creates a fistula, allowing drainage of fluid from inside the eye to lower the eye pressure. There are two incision types in this surgery: fornix-based (between the cornea and conjunctiva) and limbal-based (further away under the eyelid). This review aims to look at whether there are any differences in the surgical outcomes (eye pressure control and complications) between these two different surgical approaches (fornix- and limbal-based techniques).

Study characteristics
Six randomised controlled trials (RCTs) were reviewed with a total of 361 participants consisting of adults with any type of glaucoma and follow-up of at least 24 months. We last searched the databases on 23 October 2015.

Key results
Failure rate at 24 months was not reported in any included studies, and one study reported "late complications" but did not specify a time period, which favoured the fornix-based treatment. No difference was noted with respect to lowering eye pressure after 24 months (two trials) and after 12 months (four trials). The number of medications needed to control eye pressure after surgery was also similar. Moreover, most of the studies reported that the complication rates after the operation were similar except in one complication which was narrowing in the anterior part of the eye after the procedure (more common in the limbal surgery group), but this did not affect the final outcome of the surgery.

Quality of evidence
Although all six trials were reported to be randomised, the procedures followed for randomisation were mostly unclear (four of the six studies). Masking of the outcomes was not clear or not addressed in all six trials. Missing information was encountered in only one trial which also suffered from bias in reporting its outcomes. All other trials had an unclear risk of reporting bias as there was no access to original data.

Authors' conclusions: 

The main result of this review was that there was uncertainty as to the difference between fornix- and limbal-based trabeculectomy surgeries due to the small number of events and confidence intervals that cross the null. This also applied to postoperative complications, but without any impact on long-term failure rate between the two surgical techniques.

Read the full abstract...
Background: 

Glaucoma is one of the leading largely preventable causes of blindness in the world. It usually is addressed first medically with topical intraocular pressure-lowering drops or by laser trabeculoplasty. In cases where such treatment fails, glaucoma-filtering surgery is considered, most commonly trabeculectomy surgery with variations in technique, for example, the type of conjunctival flap (fornix- or limbal-based). In a fornix-based flap, the surgical wound is performed at the corneal limbus; while in a limbal-based flap, the incision is further away. Many studies in the literature compare fornix- and limbal-based trabeculectomy with respect to outcomes and complications.

Objectives: 

To assess the comparative effectiveness of fornix- versus limbal-based conjunctival flaps in trabeculectomy for adult glaucoma, with a specific focus on intraocular pressure (IOP) control and complications (adverse effects).

Search strategy: 

We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2015), EMBASE (January 1980 to October 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 23 October 2015.

We reviewed the bibliographic references of identified randomised controlled trials (RCTs) in order to find trials not identified by the electronic searches. We contacted researchers and practitioners active in the field of glaucoma to identify other published and unpublished trials.

Selection criteria: 

We included RCTs comparing the benefits and complications of fornix- versus limbal-based trabeculectomy for glaucoma, irrespective of glaucoma type, publication status, and language. We excluded studies on children less than 18 years of age, since wound healing is different in this age group and the rate of bleb scarring postoperatively is high.

Data collection and analysis: 

Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional information.

The primary outcome was the proportion of failed trabeculectomies at 24 months. Failure was defined as the need for repeat surgery or uncontrolled IOP (more than 22 mmHg), despite additional topical/systemic medications. Needling and 5-fluorouracil (5-FU) injections were allowed only during the first six months postoperatively; additional needling or 5-FU injections were considered as failure. Mean post-operative IOP at 12 and 24 months also was recorded.

Main results: 

The review included six trials with a total of 361 participants. Two studies were conducted in America and one each in Germany, Greece, India, and Saudi Arabia. The participants of four trials had open-angle glaucoma; one study included participants with primary open-angle or primary closed-angle glaucoma, and one study did not specify the type of glaucoma. Three studies used a combined procedure (phacotrabeculectomy). Trabeculectomy with mitomycin C (MMC) was performed in four studies, and trabeculectomy with 5-fluorouracil (5-FU) was performed in only one study.

None of the included trials reported trabeculectomy failure at 24 months. Only one trial reported the failure rate of trabeculectomy as a late complication. Failure was higher among participants randomised to the limbal-based surgery: 1/50 eyes failed trabeculectomy in the fornix group compared with 3/50 in the limbal group (risk ratio (RR) 0.33, 95% confidence interval (95% CI) 0.04 to 3.10); therefore we are very uncertain as to the relative effect of the two procedures on failure rate.

Four studies including 252 participants provided measures of mean IOP at 12 months. In the fornix-based surgeries, mean IOP ranged from 12.5 to 15.5 mmHg and similar results were noted in limbal-based surgeries with mean IOP ranging from 11.7 to 15.1 mmHg without significant difference. Mean difference was 0.44 mmHg (95% CI −0.45 to 1.33) and 0.86 mmHg, (95% CI −0.52 to 2.24) at 12 and 24 months of follow-up, respectively. Neither of these pooled analyses showed a statistically significant difference in IOP between groups (moderate quality of evidence).

One trial reported number of anti-glaucoma medications at 24 months of follow-up with no difference noted between surgical groups. However, three trials reported the mean number of anti-glaucoma medications at 12 months of follow-up without significant difference in the mean number of postoperative IOP-lowering medications between the two surgical techniques. Mean difference was 0.02, (95% CI −0.15 to 0.19) at 12 months of follow-up (high quality of evidence).

Because of the small numbers of events and total participants, the risk of many reported adverse events were uncertain and those that were found to be statistically significant may have been due to chance.

For risk of bias assessment: although all six trials were randomised selection bias was mostly unclear, with unclear random sequence generation in four of the six studies and unclear allocation concealment in five of the six studies. Attrition bias was encountered in only one trial which also suffered from reporting bias. All other trials had an unclear risk of reporting bias as there was no access to study protocols. All included trials were judged to have high risk of detection bias due to lack of masking of the outcomes. Trabeculectomy is quite a standard procedure and unlikely to induce bias due to surgeon 'performance', hence performance bias was not evaluated.

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