|Year : 2019 | Volume
| Issue : 4 | Page : 139-143
Subconjunctival bevacizumab injection versus mitomycin C application after primary pterygium surgery
Hani A Albialy, Haitham Y Al-Nashar
Ophthalmology Department, Zagazig University, Zagazig, Egypt
|Date of Submission||29-Apr-2019|
|Date of Acceptance||08-Sep-2019|
|Date of Web Publication||17-Dec-2019|
MD Hani A Albialy
Ophthalmology Department, Zagazig University, Zagazig 44519
Source of Support: None, Conflict of Interest: None
Purpose The aim of this study was to compare subconjunctival bevacizumab injection and mitomycin C (MMC) application after primary pterygium surgery in terms of recurrence rates and complications.
Patients and methods This prospective comparative clinical study included 90 eyes of 90 patients with primary pterygium who underwent excision with bare sclera technique. Patients were randomized into three groups: group A (30 eyes), in which MMC 0.02% was applied to the bare scleral area for 3 min; group B (30 eyes), which received 2.5 mg/0.1 ml subconjunctival bevacizumab injection at the end of surgery; and group C (30 eyes), which was used as a control group and did not receive any adjuvant medications after pterygium excision. Patients were followed up for 6 months, and the recurrence rates of pterygium and any complications were reported.
Results At 6 months after surgery, the recurrence rates in the three groups were as follows: two (6.7%) eyes in the MMC group A, two (6.7%) eyes in the bevacizumab group B, and 11 (36.7%) eyes in the control group C, with a significant difference among groups (P=0.01). No serious complications, except subconjunctival hemorrhage, were observed in all groups.
Conclusion Groups receiving topical 0.02% MMC and 2.5 mg/0.1 ml subconjunctival bevacizumab injections after surgery showed lower recurrence rates than the control group. However, no difference in the recurrence rate was observed between both groups.
Keywords: bevacizumab, mitomycin C, primary pterygium, recurrence
|How to cite this article:|
Albialy HA, Al-Nashar HY. Subconjunctival bevacizumab injection versus mitomycin C application after primary pterygium surgery. Delta J Ophthalmol 2019;20:139-43
|How to cite this URL:|
Albialy HA, Al-Nashar HY. Subconjunctival bevacizumab injection versus mitomycin C application after primary pterygium surgery. Delta J Ophthalmol [serial online] 2019 [cited 2020 Feb 27];20:139-43. Available from: http://www.djo.eg.net/text.asp?2019/20/4/139/273321
| Introduction|| |
Pterygium is a common ocular disorder characterized by abnormal fibrovascular tissue overgrowth from the conjunctiva toward the cornea . The exact etiology of pterygium formation is still unclear. It is thought to be caused by increased exposure to sunlight, ultraviolet rays, dust, wind, heat, dryness, trauma, or inflammation .
In addition to the cosmetic element, pterygium may impair visual function, restrict ocular motility, and cause redness or irritation. Surgical removal may be required to resolve one or more of these problems ,.
Recurrence after pterygium surgery is common and is a major challenge, as the recurrent pterygium is more aggressive than the primary one, with extensive proliferation that may adversely affect visual acuity. Furthermore, there is a greater possibility of additional recurrences with shorter intervals between each .
The recurrence is mainly owing to accelerated fibroblastic proliferation produced by the surgical trauma . The abundant expression of the vascular endothelial growth factor (VEGF) in pterygia may also explain the cause of recurrence and suggest that anti-VEGF therapy may have a role in regression of the vascular element in pterygium or in preventing its recurrence after excision .
Although it is the classic and most basic approach for pterygium excision, the bare sclera technique has a great recurrence rate, which forced surgeons to use more efficient surgical techniques and adjuvant therapies. Many postoperative adjuvant therapies such as mitomycin C (MMC), cyclosporine, β-irradiation, and bevacizumab were used to decrease the postoperative recurrence rate ,,,.
MMC is an alkylating agent with cytotoxic effects, which inhibits DNA synthesis and is widely used as an adjuvant therapy in glaucoma and pterygium surgery, but it is used with caution owing to severe adverse effects such as scleral thinning, ischemia, and necrosis . Bevacizumab is a recombinant monoclonal immunoglobulin that inhibits the VEGF-A isoform which is considered the main stimulant of angiogenesis .
The aim of this study was to compare the recurrence rates and complications after surgical excision of primary pterygium with MMC application compared with bevacizumab injection.
| Patients and methods|| |
This prospective comparative clinical study included 90 eyes of 90 patients with primary pterygium who underwent excision with bare sclera technique. Before surgery, pterygium was classified according to Tan et al. classification  into the following: T1 (atrophic) in which the episcleral blood vessels were clearly visible below the body of the pterygium, T2 (intermediate) when the episcleral blood vessels were partially seen below the pterygium body, and T3 (fleshy) when the episcleral blood vessels were completely obscured by the pterygium body.
The study included patients more than 40 years of age, with grade 1, 2, or 3 primary pterygium with its apex extending 2 mm or more beyond the limbus, who were able to participate in the study and comply with the follow-up visits.
Patients with recurrent pterygium, ocular surface disease or infection, autoimmune disorders, and previous ocular surgery were excluded from the study. Patients with uncontrollable systemic diseases such as hypertension, diabetes, or cardiovascular diseases were also excluded.
A written informed consent was obtained from all patients before participation in the study with full explanation of the treatment process, possible complications, and available alternatives. The study was carried out in accordance with the tenets of the Declaration of Helsinki and was approved by the Ethical Committee of a Private Center (AlFath Eye Hospital).
Visual acuity measurement and full ophthalmological examination with anterior segment slit lamp examination were done for all patients before and after surgery. The mean keratometric (K) reading was measured using Oculus pentacam (OCULUS Optikgerate GmbH, Wetzlar, Germany), and preoperative intraocular pressure (IOP) was measured using applanation tonometer.
Pterygium excision with bare sclera technique was performed after peribulbar anesthesia using 2% xylocaine. Xylocaine was also injected at the site of the pterygium to raise it up to its attachment to the cornea. Using a crescent blade, the pterygium was shaved off the cornea starting 0.5 mm in front of its head. The pterygium attached with the conjunctiva was separated from the scleral surface with scissors and excised leaving ∼3–4-mm area of bare sclera.
Patients were randomized into three groups. Group A included 30 eyes, in which MMC (0.02%) was applied to the bare sclera and the undersurface of the surrounding residual conjunctiva for 3 min, taking care not to spill any excess MMC onto the cornea and the limbus. The site of the application was then irrigated carefully with a balanced salt solution. The residual conjunctival edges were sutured 2–3 mm from the limbus with 8–0 vicryl ([Figure 1]). Group B included 30 eyes that received 2.5 mg/0.1 ml subconjunctival bevacizumab injection at the nasal quadrant (Avastin; Genentech Inc., South San Francisco, California, USA) ([Figure 2]). Group C included 30 eyes as a control group and did not receive any adjuvant measures after pterygium excision.
|Figure 1 Pterygium excision with mitomycin C. (a) Preoperative appearance. (b) Application of mitomycin C. (c) Postoperative appearance.|
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|Figure 2 Pterygium excision with bevacizumab. (a) Preoperative appearance. (b) Injection of bevacizumab. (c) Postoperative appearance.|
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All cases were given dexamethasone and moxifloxacin eye drops postoperatively four times daily for 2 weeks and a pressure patch was applied for 1 day.
Patients were followed up for 6 months to assess recurrence of pterygium among the three groups. Follow-up visits were scheduled at 1 day, 1 week, and 1, 3, and 6 months, postoperatively. Recurrence was determined according to the classification done by Prabhasawat et al.  with grade 0: normal appearance, grade I: fine episcleral vessels without corneal extension, grade II: episcleral vessels and fibrovascular tissue without corneal extension, and grade III: fibrovascular tissue extending past the limbus. Recurrence was recorded in patients with grade II or III.
All statistical analyses were carried out using SPSS program version 18.0 (SPSS Inc., Chicago, Illinois, USA). Preoperative and postoperative 1, 3, and 6 months measurements of the three groups for all variables were tested by paired sample t-test. All values were expressed as mean±SD. A P value of less than 0.05 was considered statistically significant.
| Results|| |
A total of 90 eyes of 90 (55 males and 35 females) patients were included in this study. All eyes had primary pterygium. They were divided into three groups: group A (30 eyes), with a mean age of 56.4±6.7 years (range: 49–65 years); group B (30 eyes), with a mean age of 61.6±5.2 years (range: 51–62 years); and group C (30 eyes), with a mean age of 59.2±3.1 years (range: 45–63 years). No significant difference in age among the three groups was noticed (P=0.53).
The preoperative mean K-reading, corneal astigmatism, and IOP were recorded for all eyes included in the study, with no significant difference among the three groups (P=0.42, 0.32 and 0.21, respectively; [Table 1]).
Subconjunctival hemorrhage on the first postoperative day was reported in three (10%) eyes in group A, five (16.6%) eyes in group, B and six (20%) eyes in group C (P=0.24). In MMC group, no other significant complications were reported such as scleral thinning or necrosis throughout the follow-up period. In addition, the normal nasal conjunctiva in the region where bevacizumab was injected did not show any ischemic changes or necrosis during the follow-up period.
Recurrence of pterygium was recorded during the 6-month follow-up period, where two (6.7%) eyes in group A, two (6.7%) eyes in group B, and 11 (36.7%) eyes in group C had recurrence by the end of the follow-up period, with a statistically significant difference (P=0.01).
Adjuvant subconjunctival bevacizumab injection used in group A was well tolerated. No irritation, burning, or any systemic adverse effects of bevacizumab were reported during the follow-up period.
The changes in keratometry and corneal astigmatism showed no statistically significant differences between the two groups of MMC and avastin injection; however, there was a significant difference with group C of bare scleral technique (P=0.001). Postoperative data are summarized in [Table 2].
| Discussion|| |
Pterygium is an encroachment of a fibrovascular conjunctival tissue onto the cornea. There are many lines of treatment for pterygium including surgical excision with the aim of prevention of recurrence . Methods to reduce recurrence in pterygium surgery include conjunctival autograft, amniotic membrane graft, MMC application, and other adjuvant therapies such as subconjuctival bevacizumab injection .
Recurrence rates after surgical treatment for pterygium ranged from 19.4 to 75.0%. It depends on the surgical treatment method and the postoperative adjuvant therapy .
MMC is an antibiotic and anticarcinogenic compound extracted from Streptomyces caespitosus that suppresses the proliferation of fibroblasts by inhibiting DNA synthesis . MMC also acts on normal tissues; however, complications such as scleral necrosis, corneal perforation, corneal edema, secondary glaucoma, corneal calcification, and cataracts are possible. It thus must be used with caution .
Bevacizumab, a recombinant human monoclonal antibody, is an inhibitor that binds to all biologically active forms of VEGF. In 2004, the US Food and Drug Administration approved the drug for the treatment of metastatic colorectal cancer. In addition, bevacizumab showed promising results in ophthalmology for the treatment of many diseases related to angiogenesis, such as age-related macular choroidal neovascularization, proliferative diabetic retinopathy, and retinal vein occlusion .
In their study, Razeghinejad et al.  reported that a single intraoperative subconjunctival bevacizumab injection has no effect on early postoperative conjunctival erythema, lacrimation, photophobia, or healing of corneal epithelial defects after primary pterygium excision.
Turan-Vural et al.  divided 36 eyes (34 patients) with primary pterygium into two groups and reported that the rate of recurrence was 44.4% in the group that received pterygium surgery using the bare sclera method alone but was 22.2% in the group that received postoperative instillation of 0.05% cyclosporine.
In this study, we investigated whether topical MMC or bevacizumab was effective as an adjuvant therapy in reducing recurrence rates after pterygium surgery, compared with a control group using bare sclera technique only. There was no difference in recurrence rate between the group of MMC and that of subconjunctival bevacizumab injection.
Similar to previous studies, the results of this study indicated that the use of bevacizumab to treat pterygium does not cause severe complications, with no particular complications other than subconjunctival hemorrhage. Thus, bevacizumab appears to be relatively safe to use.
The comparative study done by Hwang and Choi  using topical MMC, cyclosporine, and bevacizumab after primary pterygium excision concluded that the groups that received topical 0.02% MMC and 0.05% cyclosporine after surgery showed lower recurrence rates than the control group; however, no difference in recurrence rate was observed between the control group and the group receiving topical 2.5% bevacizumab after surgery.Razeghinejad and Banifatemi  in their study found that bevacizumab had no significant effect on the recurrence rate of pterygium. Although the frequency of fibrovascular tissue crossing the limbus in the bevacizumab group was half that of the balanced salt solution group, the difference failed to reach a statistically significant level.
Nuzzi and Tridico  in their study applied a subconjunctival injection of 2.5 mg/0.1 ml bevacizumab before and after surgical pterygium excision, and they concluded that these injections may be useful in preventing lesion recurrence after bare scleral procedures. Furthermore, bevacizumab subconjunctival administration was well tolerated and may represent a safer alternative when compared with other surgical techniques and adjunctive drugs. Singh et al.  injected a single dose of subconjunctival bevacizumab 1 week before the pterygium excision with conjunctival autograft, and they found a decrease in the newly formed blood vessels with subsequently decrease in recurrence rate.
| Conclusion|| |
The use of both topical 0.02% MMC and subconjunctival bevacizumab with pterygium excision is safe and was associated with lower recurrence rates compared with bare sclera technique alone.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Liu L, Wu J, Geng J, Yuan Z, Huang D. Geographical prevalence and risk factors for pterygium: a systematic review and meta-analysis. BMJ Open 2013; 3:e003787.
Kunimoto D, Kanitkar K, Makar M. The Wills Eye Manual: Office and Emergency Room Diagnosis and Treatment of Eye Disease. 4th edition. Philadelphia, PA: Lippincott Williams & Wilkins. 2004. pp. 50-51.
Han SB, Jeon HS, Kim M, Lee SJ, Yang HK, Hwang JM et al.
Quantification of astigmatism induced by pterygium using automated image analysis. Cornea 2016; 35:370–376.
Twelker JD, Bailey IL, Mannis MJ, Satariano WA. Evaluating pterygium severity: a survey of corneal specialists. Cornea 2000; 19:292–296.
Hirst LW, Sebban A, Chant D. Pterygium recurrence time. Ophthalmology 1994; 101:755–758.
Cameron ME. Histology of pterygium: an electron microscopic study. Br J Ophthalmol 1983; 67:604–608.
Marcovich AL, Morad Y, Sandbank J, Huszar M, Rosner M, Pollack A et al.
Angiogenesis in pterygium: morphometric and immunohistochemical study. Curr Eye Res 2002; 25:17–22.
Chung DS, Cho BJ, Moon NJ. Mitomycin C single soaking during surgery for primary pterygium. J Korean Ophthalmol Soc 1996; 37:927–933.
Turan-Vural E, Torun-Acar B, Kivanc SA, Acar S. The effect of topical 0.05% cyclosporine on recurrence following pterygium surgery. Clin Ophthalmol 2011; 5:881–885.
Bahrassa F, Datta R. Postoperative beta radiation treatment of pterygium. Int J Radiat Oncol Biol Phys 1983; 9:679–684.
Shenasi A, Mousavi F, Shoa-Ahari S, Rahimi-Ardabili B, Fouladi RF. Subconjunctival bevacizumab immediately after excision of primary pterygium: the first clinical trial. Cornea 2011; 30:1219–1222.
Katırcıoglu YA, Altiparmak U, EngurGoktas S, Cakir B, Singar E, Ornek F. Comparison of two techniques for the treatment of recurrent pterygium: amniotic membrane vs conjunctival autograft combined with mitomycin C. Semin Ophthalmol 2015; 30:321–327.
Razeghinejad M, Banifatemi V. Subconjunctival bevacizumab for primary pterygium excision; a randomized clinical trial. J Ophthalmic Vis Res 2014; 9:22–30.
Tan DT, 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.
Prabhasawat P, Barton K, Burkett G, Tseng SC. Comparison of conjunctivalautografts, amniotic membrane grafts, and primary closure for pterygium excision. Ophthalmology 1997; 104:974–985.
Mootha VV, Pingree M, Jaramillo J. Pterygia with deep corneal changes. Cornea 2004; 23:635–638.
Dushku N, Jhon MK, Schultz GS, Reid TW. Pterygia pathogenesis: corneal invasion by matrix metalloproteinase expressing altered limbal epithelial basal cells. Arch Ophthalmol 2001; 119:695–706.
Buratto L, Phillips RL, Carito G. Epidemiology, etiology, histology. In: Buratto L, Phillips RL, Carito G, editors. Pterygium surgery. Thorofare, NJ: Slack Inc; 2007. pp. 7–16.
Wan Norliza WM, Raihan IS, Azwa JA, Ibrahim M. Scleral melting 16 years after pterygium excision with topical mitomycin C adjuvant therapy. Cont Lens Anterior Eye 2006; 29:165–167.
Martins TGDS, de Costa ALF, Alves MR, Chammas R, Schor P. Mitomycin C in pterygium treatment. Int J Ophthalmol 2016; 9:465–468.
Hu Q, Qiao Y, Nie X, Cheng X, Ma Y. Bevacizumab in the treatment of pterygium: a meta-analysis. Cornea 2014; 33:154–160.
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.
Hwang S, Choi S. A comparative study of topical mitomycin C, cyclosporine, and bevacizumab after primary pterygium surgery. Korean J Ophthalmol 2015; 29:375–381.
Nuzzi R, Tridico F. Efficacy of subconjunctival bevacizumab injections before and after surgical excision in preventing pterygium recurrence. J Ophthalmol 2017; 2017:6824670.
Singh P, Sarkar L, Sethi HS, Gupta VS. Randomized controlled prospective study to assess the role of subconjunctival bevacizumab in primary pterygium surgery in Indian patients. Indian J Ophthalmol 2015; 63:779–784.
[Figure 1], [Figure 2]
[Table 1], [Table 2]