|Year : 2014 | Volume
| Issue : 2 | Page : 113-116
The outcome of preoperative subconjunctival bevacizumab injection in pterygium surgery
Ahmed M.K. El Shafie, Ahmed S Mohamed, Mohamed F Sayed
Department of Ophthalmology, El Minia Faculty of Medicine, El Minia University, El Minia, Egypt
|Date of Submission||13-Feb-2013|
|Date of Acceptance||12-Feb-2014|
|Date of Web Publication||12-Sep-2014|
Ahmed S Mohamed
MD, El minia Samalot Elbiha Nasser Ebada Street, El Minia 23244
Source of Support: None, Conflict of Interest: None
The aim of this study was to evaluate the safety and the efficacy of subconjunctival injection of bevacizumab (Avastin) for the management of primary and recurrent pterygia and to estimate the recurrent rate of pterygia after surgery.
Patients and methods
The study included 60 eyes of 60 patients (45 male and 15 female), with a mean age of 41 ± 4.8 years. Forty patients (66.6%) had primary pterygia and the remaining 20 patients had recurrent pterygia after a previous surgery. A preoperative injection of bevacizumab was given at a dose of 1.25 mg (0.05 ml) 1 week before pterygium surgery was performed using the conjunctival flap technique. Twenty patients were enrolled as a control group and they were operated upon without preoperative bevacizumab injection. Mitomycin C (0.1 mg/ml) was used intraoperatively in recurrent cases. All patients were followed up for 3-6 months.
Most of the patients (48.3%) had grade 2 pterygium. The average time for each procedure was 30 ± 15 min. No patient lost vision after the procedure. Recurrence was noted in five patients (8.3%), and all of them had primary pterygia. Conjunctival graft rejection occurred in three patients (5%); this graft rejection occurred in recurrent pterygia. Postoperative conjunctival vascularization occurred in four patients (6.7%), and this vascularization occurred in the recurrent cases. A significant improvement of visual acuity and corneal clearance was noticed in all patients.
Preoperative subconjunctival injection of bevacizumab reduces the recurrence rate of pterygium surgery as it reduces the vascular element of the pterygium. Intraoperative application of mitomycin C in addition to preoperative subconjunctival injection of bevacizumab reduces recurrence in recurrent pterygium cases. Further long-term, large-scale studies are recommended.
Keywords: bevacizumab, graft, mitomycin C, pterygium, subconjunctival injection
|How to cite this article:|
El Shafie AM, Mohamed AS, Sayed MF. The outcome of preoperative subconjunctival bevacizumab injection in pterygium surgery. J Egypt Ophthalmol Soc 2014;107:113-6
|How to cite this URL:|
El Shafie AM, Mohamed AS, Sayed MF. The outcome of preoperative subconjunctival bevacizumab injection in pterygium surgery. J Egypt Ophthalmol Soc [serial online] 2014 [cited 2017 Oct 23];107:113-6. Available from: http://www.jeos.eg.net/text.asp?2014/107/2/113/140643
| Introduction|| |
A pterygium is a very common conjunctival degenerative condition. It has been well established that there are different factors that are interrelated and involved in the growth of pterygia . As pterygia are composed of proliferating fibrovascular tissue and the pterygium formation and progression require neovascularization, many molecules that positively regulate angiogenesis have been identified, suggesting that the vascular endothelial growth factor (VEGF) may be involved directly or indirectly in the pathogenesis of pterygia [2,3].
A recombinant humanized monoclonal antibody directed against VEGF is available (bevacizumab, Avastin; Genentech) for cancer therapy . Off-label use of this drug in some neovascular disorders of the eye has been associated with promising short-term results [5,6].
Recent studies showed that subconjunctival bevacizumab injection is useful in the management of patients with primary and recurrent pterygium without significant local or systemic adverse effects [7-10]. The present study evaluated the clinical efficacy and the safety of preoperative subconjunctival injection of bevacizumab for primary or recurrent pterygium.
| Patients and methods|| |
This study was conducted on patients with a diagnosis of primary or recurrent pterygium at the Department of Ophthalmology, El Minya University Hospital, from October 2008 to June 2011. The study group consisted of 60 eyes of 60 patients (45 male and 15 female), with an age range of 35-49 years (mean 41 ± 4.8 years). Forty patients (66.6%) had primary pterygia and the remaining 20 patients had recurrent pterygia after a previous surgery. Exclusion criteria included any form of ocular surgery except pterygium removal, an evidence of other ocular diseases except refraction errors, a history of any autoimmune disease and any condition for which bevacizumab is contraindicated (allergy to bevacizumab, hypertension, proteinuria, bleeding tendencies, previous myocardial infarction or stroke, and pregnant and lactating women). Informed written consent was obtained from all study patients.
Pterygium was graded into three levels of severity, according to a clinical classification system . The three grades, based on the relative transparency of the pterygium tissue, were grade 1 (transparent), grade 2 (intermediate), and grade 3 (opaque). In grade 1 pterygium, the episcleral vessels underlying the body of the pterygium were clearly visible. In grade 3 pterygium, the episcleral vessels were totally obscured. All other pterygia not classified as grade 1 or 3 were classified as grade 2 .
Twenty patients of primary pterygia were operated upon without avastin injection and they were included as a control group.
A preoperative injection of bevacizumab was given at a dose of 1.25 mg (0.05 ml) 1 week before surgery, using a 30-G needle. The site of the needle entrance was at least 8 mm away from the site of injection to prevent any leakage. The pterygium surgery was performed using the conjunctival flap technique. The pterygium was grasped at the limbus and avulsed from the corneal surface with a muscle hook. Westcott scissors were used to remove the pterygium body, and the corneal and sclera surfaces were polished with a no. 15 Bard-Parker blade. Minimal cautery was performed to control bleeding. In recurrent cases, mitomycin C (MMC) (0.1 mg/ml) was applied to the bared scleral bed for 2 min, followed by copious irrigation of the ocular surface with at least 30 ml balanced salt solution. After releasing the superior conjunctiva, a conjunctival flap was rotated and fixed over the bare sclera using 8-0 vicryl stitches to cover the resection site, except a 2 mm zone adjacent to the limbus. Topical ointments of erythromycin and hydrocortisone were applied and the eye was pressure patched.
After surgery, a therapeutic contact lens was applied until corneal re-epithelialization was completed. All patients were treated with ciprofloxacin eye drops, and 0.1% betamethasone eye drops were given four times daily for 2 weeks. Follow-up visits were scheduled at 1, 3, and 6 months after surgery. All patients completed the follow-up period. A complete set of ophthalmic examinations was repeated with special focus on probable complications and the recurrence rate. Recurrence of the pterygium was defined as a corneal recurrence that is evidenced by growth of fibrovascular tissue across the limbus onto the cornea .
All statistical analyses were performed with SPSS version 15 (SPSS Inc., Chicago, Illinois, USA). Both descriptive and analytic approaches were used in data analyses. Data were expressed as the number and percent or the mean and SD as appropriate. A two-tailed test was used, and the statistical significance level was set at P-value less than 0.05.
| Results|| |
Demographic and preoperative data including age, sex, operated eye, risk factors, and the grade of pterygium are shown in [Table 1]. There were 22 patients (36.7%) in grade 1, 29 patients (48.3%) in grade 2, and nine patients (15%) in grade 3. The average time for each procedure was 30 ± 15 min.
No patient lost vision after the procedure, with visual acuity being maintained or improved in all [Table 2]. Early pterygium recurrence was noted in five patients (8.3%) at the 6-month visit (all of them had primary pterygia). Four recurrences occurred in the control group, at a percentage of 20% of this group. Only one case occurred in the patients of primary pterygia who received preoperative avastin at a percentage of 5% in this group.
|Table 2: A comparison of the preoperative and the postoperative visual acuity of the 40 eyes studied|
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There was no recurrence in group of patients with recurrent pterygium who received antimetabolites (MMC). Conjunctival graft rejection occurred in three patients (5%). Postoperative conjunctival vascularization occurred in four patients (6.6%) [Figure 1] and [Table 3].
|Figure 1: Grade 2 primary pterygium in a 43-year-old male patient. (a) The preoperative view. (b) Three months after pterygium surgery with preoperative subconjunctival injection of bevacizumab .|
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| Discussion|| |
Pterygium is a proliferative disease with hyperplastic growth of the corneo-conjunctival fibrovascular tissue onto the cornea . Surgical therapy can be used to manage pterygia successfully; however, recurrence remains a problem . Given the fact that VEGF is upregulated in pterygial tissue, it is not surprising that direct inhibition of this molecule could help in controlling angiogenesis in the pterygia, and these data support the hypothesis that local administration of bevacizumab could induce regression or prevent recurrence after surgical excision .
Recently, there have been several studies conducted to evaluate the effect of local therapy of bevacizumab in both primary and recurrent pterygium [7-10, 16, 17]. In the present study, we chose to use subconjunctival instead of topical administration because subconjunctival injection seemed to provide better compliance, it was more economical for patients, and it has been reported to be more effective than the topical route in treating corneal neovascularization .
In the present study, subconjunctival bevacizumab injection before pterygium surgery was safe and effective in primary or recurrent cases. Short-term results of the study by Bahar et al.  suggest that subconjunctival bevacizumab is well tolerated but does not cause regression of corneal vessels in recurrent pterygium. Teng et al.  concluded that the treatment of primary pterygium with subconjunctival bevacizumab results in a short-term decrease in vascularization and irritation.
The study by Besharati et al.  found that subconjunctival bevacizumab injection was useful in the management of patients with primary and recurrent pterygium without significant local or systemic adverse effects. There was a significant reduction in the mean pterygium size and color intensity in both eyes.
A recent study by Lekhanont et al.  concluded that a single subconjunctival bevacizumab injection seems to only partially and transiently decrease conjunctival vascularization in impending recurrent pterygium in a dose-dependent manner. This treatment does not cause regression or reduce the recurrent rate of impending recurrent pterygium. Thus, these authors recommended that a combination of other drugs with subconjunctival bevacizumab may offer greater benefits for the treatment of impending recurrent pterygium.
The present study showed that preoperative subconjunctival injection of bevacizumab reduces the recurrence rate of pterygium surgery (8.3%), with a low rate of postoperative conjunctival vascularization (6.6%) and few cases with graft rejection (5%). In case of simple excision with conjunctival autograft with sutures as performed in our study, the recurrence rates in the literature ranged from 1.9 to 39% [19-22]. Our data of 12.5% are constant with these findings.
In the present study, the recurrence rate was 0% after intraoperative administration of antimetabolite (MMC, 0.1 mg/ml) in patients with recurrent pterygium using a subconjunctival injection of bevacizumab. MMC is a naturally occurring antibiotic-antineoplastic compound that inhibits the proliferation of fibroblasts and suppresses vascular ingrowths . The literature reveals 0-13.3% recurrence rates after using intraoperative MMC adjunctively with surgical excision [23-25]. The optimum concentration and the exposure time for MMC are not well known and vary between 0.1-0.5 mg/ml and 1-5 min, respectively. A low or intermediate risk of recurrence indicates the use of a low concentration (0.1 mg/ml), whereas high risk implies the need for a higher concentration (0.4-0.5 mg/ml). Higher concentrations and extended exposure times are associated with an increased risk of complications [26,27].
| Conclusion|| |
Subconjunctival injection of bevacizumab at a dose of 1.25 mg (0.05 ml) 1 week before surgery of pterygium is safe and effective in terms of recurrence and the complication rate for primary or recurrent pterygium treatment. The use of MMC reduces recurrence in recurrent pterygium cases. Studies with a larger sample size, a longer follow-up period, and a more diverse patient population should be designed for the evaluation of long-term success and potential complications in a more comprehensive clinical situation.
| Acknowledgements|| |
| References|| |
|1.||Mauro J, Foster CS. Pterygia: pathogenesis and the role of subconjunctival bevacizumab in treatment. Semin Ophthalmol 2009; 24 :130-134. |
|2.|| Hill JC, Maske R. Pathogenesis of pterygium. Eye 1989; 3 :218-226. |
|3.|| Di GN, Coroneo MT, Wakefield D. Active matrilysin (MMP-7) in human pterygia: potential role in angiogenesis. Invest Ophthalmol Vis Sci 2001; 42 :1963-1968. |
|4.|| Ferrara N, Hillan KJ, Gerber HP, Novotny W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 2004; 3 :391-400. |
|5.|| Iliev ME, Domig D, Wolf-Schnurrbursch U, Wolf S, Sarra GM. Intravitreal bevacizumab (Avastin) in the treatment of neovascular glaucoma. Am J Ophthalmol 2006; 142 :1054-1056. |
|6.|| Jorge R, Costa RA, Calucci D, Cintra LP, Scott IU. Intravitreal bevacizumab (Avastin) for persistent new vessels in diabetic retinopathy (IBEPE study). Retina 2006; 26 :1006-1013. |
|7.|| Teng CC, Patel NN, Jacobson L. Effect of subconjunctival bevacizumab on primary pterygium. Cornea 2009; 28 :468-470. |
|8.|| Razeghinejad MR, Hosseini H, Ahmadi F, Rahat F, Eghbal H. Preliminary results of subconjunctival bevacizumab in primary pterygium excision. Ophthalmic Res 2010; 43 :134-138. |
|9.|| Besharati MR, Manaviat MR, Souzani A. Subconjunctival bevacizumab injection in treatment of pterygium. Acta Med Iran 2011; 49 :179-183. |
|10.||Lekhanont K, Patarakittam T, Thongphiew P, Suwan-apichon O, Hanutsaha P. Randomized controlled trial of subconjunctival bevacizumab injection in impending recurrent pterygium: a pilot study. Cornea 2012; 31 :155-161. |
|11.||Tan DTH, Chee SP, Dear KB, Lim AS. Effect of pterygium morphology on pterygium recurrence in a controlled trial comparing conjunctival autografting with bare sclera excision. Arch Ophthalmol 1997; 115 : 1235-1240. |
|12.||Wong TY, Foster PJ, Johnson GJ, Seaha SKL, Tan DTH. The prevalence and risk factors for pterygium in an adult Chinese population in Singapore: the Tanjong Pagar survey. Am J Ophthalmol 2001; 131 :176-183. |
|13.||Chowers I, Pèer J, Zamir E, Livni N, Ilsar M, Frucht-Pery J. Proliferative activity and p53 expression in primary and recurrent pterygia. Ophthalmology 2001; 108 :985-988. |
|14.||Chui J, Coroneo MT, Tat LT, Crouch R, Wakefield D, di Girolamo N. Ophthalmic pterygium: a stem cell disorder with premalignant features. Am J Pathol 2011; 178 :817-827. |
|15.||Mutlu FM, Sobaci G, Tatar T, Yildirim E. A comparative study of recurrent pterygium surgery: limbal conjunctival autograft transplantation versus mitomycin C with conjunctival flap . Ophthalmology 1999; 106 :817-821. |
|16.||Hosseini H, Nejabat M, Khalili MR. Bevacizumab (Avastin) as a potential novel adjunct in the management of pterygia. Med Hypotheses 2007; 69 :925-927. |
|17.||Bahar I, Kaiserman I, McAllum P, Rootman D, Slomovic A. Subconjunctival bevacizumab injection for corneal neovascularization in recurrent pterygium. Curr Eye Res 2008; 33 :23-28. |
|18.||Dastjerdi MH, Saban DR, Okanobo A, Nallasamy N, Sadrai Z, Chauhan SK, et al. Effects of topical and subconjunctival bevacizumab in high-risk corneal transplant survival. Invest Ophthalmol Vis Sci 2010; 51 : 2411-2417. |
|19.||Sanchez-Thorin JC, Rocha G, Yelin JB. Meta-analysis on the recurrence rates after bare sclera resection with and without mitomycin C use and conjunctival autograft placement in surgery for primary pterygium. Br J Ophthalmol 1998; 82 :661-665. |
|20.||Young AL, Leung GY, Wong AK, et al. A randomised trial comparing 0.02% mitomycin C and limbal conjunctival autograft after excision of primary pterygium. Br J Ophthalmol 2004; 88 :995-997. |
|21.||Jiang J, Yang Y, Zhang M. Comparison of fibrin sealant and sutures for conjunctival autograft fixation in pterygium surgery: one-year follow-up. Ophthalmologica 2008; 222 :105-111. |
|22.||Chen PP, Ariyasu RG, Kaza V. A randomized trial comparing mitomycin C and conjunctival autograft after excision of primary pterygium. Am J Ophthalmol 1995; 120 :151-160. |
|23.||Sutphin JE. Basic and clinical science course: external disease and cornea. Vol 8. San Francisco: American Academy of Ophthalmology; 2008: 394 . 429-432 |
|24.||Wong VA, Law FC. Use of MMC with conjunctival auto graft in pterygium surgery in Asian-Canadians. Ophthalmology 1999; 106 :1512-1515. |
|25.||Altiparmak UE, Katircioðlu YA, Yaðci R, Yalniz Z, Duman S. Mitomycin C and conjunctival autograft for recurrent pterygium. Int Ophthalmol 2007; 27 :339-343. |
|26.||Kanski JJ. The conjunctiva. In: Kanski JJ. editor.Clinical ophthalmology: a systematic approach. 7th ed. Oxford: Butterworth-Heinemann; 2011. |
|27.||Menghini M, Watson SL, Bosch MM. Corneal melting two weeks after pterygium excision with topical mitomycin C: successfully treated with lamellar keratoplasty and amnion membrane transplantation. Case Rep Ophthalmol 2012; 3 :24-29. |
[Table 1], [Table 2], [Table 3]