Biological Tissue Adhesive versus Standard Suture in Conjuctival Autograft for the Surgical Treatment of Pterygium

PICHON RIVIERE, A.; AUGUSTOVSKI, F. A.; GARCIA MARTI, S.; GLUJOVSKY, D.; ALCARAZ, A.; LOPEZ, A.; BARDACH, A.; CIAPPONI, A

Documento de Evaluación de Tecnologías Sanitarias

IECS

Año: 2012 p. 1 - 30

1668-2793

Pterygium is the anomalous and benign fibrovascular proliferation of the bulbar conjunctiva that begins in the limbus and progresses to the cornea. It is more common in tropical regions with an approximate prevalence of 4-11%, and may reach 20-25%. It is associated with UV radiation exposure and to chronic microtrauma and inflammation. When active, pterygium often grows for months or years thus the area where it grows becomes redenned and thickened. Its more common symptoms are local irritation, consultations because of aesthetic reasons or because it obstructs vision. One of the alterations that pterygium may result in is astigmatism, but it may also grow centrally thus resulting in opacity and decreased visual acuity. Symptomatic treatment is intended to relieve discomforts, but does not stop or revert pterygium. Surgical treatment is proposed when pterygium results in astigmatism, when it decreases visual acuity or when there is suspicion that soon any of the two above mentioned symptoms will take place. Surgery is ambulatory, simply resecting pterygium. Given the high recurrence reported (30-50%), measures have been assessed to reduce it. Among them, beta radiation, C-mitomycin, human amniotic membrane graft and conjunctival autograft may be mentioned. Some studies have been published showing that both the use of C-mitomycin and conjunctival autograft significantly reduce the recurrence rate. Conjunctival autograft is conventionally carried out by adhering the conjunctival graft to the sclera by means of a suture that usually delays the surgical procedure. To reduce surgical times and due to the use of threads that would result in inflammation and post-surgical discomfort, the alternative of using a biological glue that allows adhering the conjunctiva without these adverse effects is being assessed. TechnologyFibrin glue consists of two components: a) a concentrated fibrinogen and Factor XIII solution and b) a thrombin and calcium solution. Once both solutions are combined, a fibrin clot is formed in seconds, simulating the final stage of the coagulation cascade. In this clinical setting, after resecting the pterygium, a drop of fibrinogen is poured on the naked sclera and then the thrombin solution is added to activate the sealant. Then the graft is placed on the sclera, in the proper direction. Although the use of fibrin glue has been approved for other uses more than a decade ago in Europe (EMA, European Medicines Agency) and also by the US Food and Drug Administration (FDA), its use in ophthalmology is not included in the indicated therapeutic options. Purpose To assess the available evidence on the efficacy, safety and issues related with coverage policies for the biological tissue adhesive in conjunctival autograft for the surgical treatment of pterygium. Methods A bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of systematic reviews; controlled, randomized clinical trials (RCTs); health technology assessments and economic evaluations; clinical practice guidelines and coverage policies of other health systems. Results One systematic review published in 2011 was found. Two RCTs published after this systematic review were also found. No clinical practice guidelines on conjunctival autografts in patients with pterygium were found and the health sponsors surveyed do not include this intervention. In 2011, one systematic review comparing the use of fibrin glue with conventional suture was published. Finally, 7 studies with 342 subjects (and 366 eyes) were included. The studies included 22 to 137 patients each, with a 2 to 12-month follow up. Surgical times were significantly lower in the fibrin glue group (-17.6 minutes, 95% CI -26.0 to -9.2, p<0.01). Also, the recurrence rate was lower in the fibrin group ranging from 0 to 10% versus the suture group which ranged from 0 to 18% (Peto OR 0.33, 95% CI 0.15?0.71, p<0.01). No significant differences were found in the rate of complications (Peto OR 1.82, 95% CI 0.63?5.27, p=NS). In 2011, one RCT compared the use of fibrin glue with conventional suture in 47 eyes with pterygium with conjunctival autograft. Surgical times were significantly lower in the fibrin glue group (19.1 ± 6.1 minutes versus 48.5 ± 7.1, p<0.01). According to the visual analog scale, less discomfort was observed in the fibrin glue group 24 hours after surgery (3.9 vs. 4.9; p<0.01), as well as after 7 (2.4 vs. 4.1; p<0.01) and 21 days (1.6 vs. 3.4; p<0.01). There were no differences as to complications. Follow up was carried out in only 66% of patients at 6 months, showing one relapse in the fibrin glue group and two relapses in the conventional suture group. In 2010, in an open-label RCT, 50 patients (50 eyes) with recurrent pterygium were randomized to fibrin glue or conventional suture in conjunctival autograft. Patients had an average 3.1 and 4.4 previous surgeries for pterygium in the fibrin glue and conventional suture groups, respectively (p=NS). No statistically significant differences were found in recurrence in both groups (1 eye after 5 months in the glue group vs. 3 eyes after 7-8 months in the suture group), after a mean follow up of 9 and 13 months, respectively. The fibrin glue group had a significantly lower surgical time (18.2 ± 2.2 minutes vs. 26.6 ± 1.9 minutes; p<0.01). Post-surgical discomfort was also significantly lower in the fibrin glue group (0.44 ± 0.6 vs. 3.3 ± 0.8; p<0.01), assessed by the Wong-Bakers FACES Pain Rating Scale. No clinical practice guidelines on conjunctival autograft in patients operated for pterygium were found and no health sponsors covering this type of surgeries were found either; therefore this technology is not mentioned in their coverage policies. The cost of the surgery using fibrin glue (including medical fees) is approximately $5,600 (Argentine pesos, November 2011; 1,300 United States dollars), and the cost of surgery with conventional suture is approximately $740 (Argentine pesos, November 2011; 172 United States dollars). Hospitalization costs are not included and are similar in both cases. ConclusionsGood quality evidence was found on the benefits of the use of fibrin glue versus conventional suture in patients with pterygium who undergo conjunctival autograft. However, this benefit was limited to reducing surgical times in fewer minutes and to a lower level of discomfort in the post-surgical period. No differences were found as regards complications or recurrence rate. Most studies were conducted on patients with primary pterygium, although one study was conducted in patients with recurrent pterygium and showed similar results. No clinical practice guidelines on conjunctival autograft in patients operated for pterygium were found and no health sponsors covering this type of surgeries were found either; therefore this technology is not mentioned in their coverage policies. Based on the evidence found, the use of fibrin glue in conjunctival autograft would benefit patients being operated for pterygium. However, due to the difference in costs between both techniques, a cost-effectiveness analysis should be carried out in order to make a proper decision as regards covering this technology.