|Year : 2015 | Volume
| Issue : 4 | Page : 897-901
Injection of bevacizumab in the subpterygial tissue at the time of surgical removal against 2 weeks before surgery
Sameh S Mandour, Ahmad M Shannah, Hoda M El Sobky
Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||13-Nov-2014|
|Date of Acceptance||01-Feb-2015|
|Date of Web Publication||12-Jan-2016|
Hoda M El Sobky
Department of Ophthalmology, Faculty of Medicine, Menoufia University, 32511
Source of Support: None, Conflict of Interest: None
The aim of this study was to evaluate the postoperative outcome and the recurrence rate after primary pterygium excision using preoperative subpterygial bevacizumab injection at the time of surgical removal as against 2 weeks before surgery.
Recurrence after pterygium excision represents a challenge for ophthalmologists and is considered to be the most common postoperative complication. Several techniques have evolved in a trial to overcome the high rate of postoperative recurrence. However, none proved to be totally effective.
Patients and methods
Forty eyes with primary pterygium were divided into two groups. Group A eyes (included 20 eyes) were operated upon with pterygium excision after subpterygial injection of bevacizumab. Group B eyes (included 20 eyes) were operated upon with pterygium excision 2 weeks after subpterygial injection of bevacizumab. Pterygium regrowth over the cornea for 1 mm or more was considered as a recurrence.
The follow-up period was 6 months. In group A, recurrence was reported in two (10%) eyes, whereas in group B, recurrence was reported in one (5%) eye. No serious postoperative complications were reported. There was no statistically significant difference between the two groups regarding the recurrence rate and the complication rate.
Both techniques used in the current study proved to be effective in reducing the recurrence rate after excision of the primary nasal pterygium with minimal postoperative complications. Injection of bevacizumab 2 weeks before had a better effect on decreasing the pterygium vascularity, which minimized bleeding during operation in addition to decreasing the recurrence rate, according to this study.
Keywords: avastin, bevacizumab, excision, primary pterygium, recurrence
|How to cite this article:|
Mandour SS, Shannah AM, El Sobky HM. Injection of bevacizumab in the subpterygial tissue at the time of surgical removal against 2 weeks before surgery. Menoufia Med J 2015;28:897-901
|How to cite this URL:|
Mandour SS, Shannah AM, El Sobky HM. Injection of bevacizumab in the subpterygial tissue at the time of surgical removal against 2 weeks before surgery. Menoufia Med J [serial online] 2015 [cited 2020 Sep 27];28:897-901. Available from: http://www.mmj.eg.net/text.asp?2015/28/4/897/173610
| Introduction|| |
Pterygium is a common ocular surface disorder in Egypt. Recurrence after pterygium excision represents a challenge for ophthalmologists and is considered to be the most common postoperative complication  .
Several techniques have evolved in a trial to overcome the high rate of postoperative recurrence. However, none proved to be totally effective. Among these modalities are postoperative B-irradiation  , conjunctival autografting  , intraoperative , or postoperative adjuvant mitomycin C , , amniotic membrane transplantation  , and antivascular endothelial growth factor (anti-VEGF)  .
We represent our experience for the control of postoperative pterygium recurrence using two different techniques on two groups of patients with primary nasal pterygia. Then, we compared the postoperative outcome in both participating groups in reducing the pterygium recurrence rate in our country.
The first group had undergone bare scleral excision of the primary nasal pterygium after subconjunctival injection of bevacizumab 1.25 mg/0.05 ml. The second group had undergone bare scleral excision of the primary nasal pterygium after 2 weeks of subconjunctival injection of bevacizumab 1.25 mg/0.05 ml to give the patient a satisfactory period between the injection of bevacizumab and pterygium excision.
| Patients and methods|| |
This was a prospective randomized study conducted on 40 eyes of 40 patients with primary nasal pterygium who attended the health service in Menoufia University Hospitals in Shebin El Kom and Kafr El-Sheikh eye hospital during the period from October 2013 to October 2014.
Patients were enrolled randomly into two groups. The first group had undergone bare scleral excision of the primary nasal pterygium after subconjunctival injection of bevacizumab 1.25 mg/0.05 ml. The second group had undergone bare scleral excision of the primary nasal pterygium after 2 weeks of subconjunctival injection of bevacizumab 1.25 mg/0.05 ml. All surgeries were performed by the same surgeon. The effect of bevacizumab occurs intraoperatively by the regression of feeding blood vessels and the easy removal of the pterygium. Unfortunately, histopathological examination of the excised tissue is not applicable.
All patients of the study had a primary nasal pterygium encroached on the surface of the cornea with no other ocular pathology. A comprehensive ophthalmic examination, including best-corrected visual acuity testing, slit-lamp examination, Goldmann applanation tonometry, fundus examination, and examination of ocular motility, was carried out for all patients. Consents were taken from all patients, and the research was approved by the institutional review board. All measures were in accordance with the tenets of the Declaration of Helsinki.
The Surgical technique
Group A: The technique of bevacizumab injection was as follows: topical anesthesia (benoxinate hydrochloride 0.4%) was first applied in the involved eye, followed by subconjunctival injection of 1.25 mg/0.05 ml bevacizumab into the pterygium at the limbus using a 27-G needle on an insulin syringe. A cotton-tipped applicator was applied at the site of injection on withdrawal of the needle to prevent reflux of the injected drug. Thorough rinsing of the ocular surface with saline was performed to remove any residuals of bevacizumab.
After injection, the patient underwent bare scleral excision of the pterygium. Bare scleral excision of the pterygium was performed as follows: topical anesthesia was instilled, followed by the placement of a self-retaining eyelid speculum. Subconjunctival lidocaine 2% with adrenaline was injected beneath the body of the pterygium using a 27-G needle.
A Bard Barker knife no. 15 or a crescent knife was used to dissect the head of the pterygium starting 0.5 mm temporal to the advancing edge till the limbus. Blunt Wesscot scissors were used to undermine the planned conjunctival resection and to dissect the pterygium 5 mm from the limbus, leaving the peripheral base to avoid medial rectus tendon damage. Excision of the pterygium did not extend to or involve the plica semilunaris. When there was a large bare sclera, the conjunctiva was sutured to the episcleral 3 mm from the limbus using an interrupted 8/0 vicryl suture.
Group B: After injection of bevacizumab, the patient received topical-combined antibiotic-steroid eye drops four times daily and dexamethasone 0.1% ointment at bedtime for 1 week. The patient was seen at 1 day and 1 week after subconjunctival injection of bevacizumab. A complete ophthalmic examination was performed at each visit. Two weeks after the injection, the patient underwent bare scleral excision of the pterygium.
The process and the detection of early postoperative complications: Patients were reexamined at 1, 2, 3, and 6 months postoperatively. During each visit, a complete ophthalmic examination was performed. It was judged that the lesion has recurred if there was fibrovascular growth over the cornea for 1 mm or more. Statistical presentation and analysis of the present study were conducted using the mean, the SD, the χ2 -test, and the t-test, with a level of significance at 95% by SPSS V.18 software (SPSS Inc., Chicago, Illinois, USA)  .
| Results|| |
Forty eyes of 40 patients were enrolled in the study, including 20 eyes in group A and 20 eyes in group B. There were 10 (50%) male and 10 (50%) female patients in groups A and 12 (60%) male and eight (40%) female patients in group B. The patient age ranged from 32 to 65 years, with a mean age of 47.15 ± 9.874 years in group A, and from 23 to 65 years, with a mean age of 43.57 ± 14.821 years, in group B. The mean of extension of the pterygia onto the cornea was 3.04 ± 1.08 mm in group A and 3.44 ± 1.21 mm in group B.
The mean width of the pterygium on the limbus was 4.46 ± 1.44 mm in group A and 5.06 ± 1.39 mm in group B.
The pterygia were less vascular and less inflamed at the 2-week follow-up visit at the time of pterygium excision in group B eyes. The follow-up period in groups A and B for 6 months were at 2 weeks and 1, 3, and 6 months.
The visual acuity in group A was improved by 1-2 lines in 11 (55%) eyes, whereas in group B, an improvement in visual acuity by 1-3 lines was recorded in 14 (70%) eyes. Other cases in both groups showed no improvement.
In group A, reported recurrence was found in two (10%) eyes. The time interval from the surgery to the recurrence was 2 months in one case and 4 months in the other one. However, in group B, recurrence was reported in one (5%) eye. The time interval from the surgery to the recurrence was 4 months. There was no statistically significant difference between the two groups regarding the recurrence rate (P = 0.0964).
Regarding postoperative complications, in group A, photophobia and lacrimation occurred in six (35%) cases. Conjunctival vascularization was reported in two (10%) cases, but it was away from the limbus and was not considered as a recurrence. No patients developed a persistent epithelial defect, dellen, or signs of scleral melting at any time during the postoperative follow-up. In group B, photophobia and lacrimation occurred in three (15%) cases. No serious postoperative complications were reported. There was no statistically significant difference between the two groups regarding the complication rate (P = 0.386).
| Discussion|| |
Because of the high recurrence rates of 30-80% after pterygium excision using the bare sclera technique, a variety of other treatment modalities have been proposed  . Epithelial dysplasia, epithelial and stromal inflammation, vascular proliferation, fibrosis, and solar elastosis were identified in the pterygium  . Vascular growth factors, such as the VEGF, have been detected in the pterygium. There is marked elevation of VEGF in the pterygium compared with normal conjunctival samples. It has been postulated that the development of pterygium depends on a changed angiogenic stimulator-to-inhibitor ratio  . Adjunctive treatment with bevacizumab before bare sclera excision plays a role in reducing the recurrence rate. Bevacizumab (avastin) is a full-length, humanized, monoclonal antibody against all types of VEGF. It binds to and neutralizes the biologic activity of all types of human VEGF, thus preventing its interaction with its receptors on the surface of endothelial cells. Hence, it may inhibit neovascularization, and thus stop the progression or prevent the recurrence of pterygium  .
In this study, we compared subpterygial injection of bevacizumab (avastin) before surgical removal of the pterygium (group A) with subpterygial injection of bevacizumab (avastin) 2 weeks before surgical removal of the pterygium (group B). The study included 40 eyes of 40 patients. In this study, we found that the age of the patients in group A ranged from 32 to 65 years, with a mean age of 47.15 ± 9.874 years, and in group B, it ranged from 23 to 65, years, with a mean age of 43.57 ± 14.821 years.
This finding was in agreement with Solomon et al.  , who studied 21 eyes, with the highest incidence of pterygia in the age group of 27-79 years, with a mean age of 41.8 + 9.33 years, and Prabhasawat et al.  , who studied eight eyes and found a high incidence of pterygia in the age group of 59-34 years, with a mean age of 42.6 + 5.38 years.
In the present study, it was noticed that pterygia were more common in men than in women (women 45% and men 55%). Tan et al.  found that men were at a much higher risk than women, but when we consider only indoor workers, the difference between the two sexes was negligible.
Diaz et al.  found that male sex was statistically related in a significant manner to pterygium incidence. Karukonda and Thompson  found that the majority of the affected patients had outdoor occupations and it is more common in farmers than in city dwellers, and Khoo et al.  found a high rate of pterygium in farmers, miners, and gas and electric workers.
Ozkurt et al.  mentioned that a pterygium is strongly correlated to ultraviolet light exposure, dryness, exposure to wind, dust, heat, and viruses. However, Teng et al.  mentioned that a pterygium is thought to be caused by immunologic and genetic factors.
Hence, all of the above showed the relation between pterygium and outdoor workers with high exposure to UV rays, which was considered as an important etiological factor in pterygium development.
Many studies have been conducted to show the effect of bevacizumab on the pterygium.
Teng and colleagues found that 1 week after the injection of a single dose of bevacizumab (0.05 ml), the irritation and hyperemia showed near-total regression. At week 2, the pterygium maintained this appearance. By week 7, the degree of vascularity and symptoms of irritation had returned to their preinjection state  .
Omar et al. found that subconjunctival bevacizumab injection was useful in the management of patients with primary pterygium without local or systemic adverse effects. There was a significant difference in the mean surface area of the pterygium and the size of the pterygium was reduced  .
Besharati et al. studied the clinical effect of subconjunctival administration of bevacizumab in patients with primary and recurrent pterygium. The study involved 22 patients with primary and recurrent pterygium. They received subconjunctival bevacizumab (0.2 ml). The pterygium vascularity and thickness were graded. The size of the pterygium (measured by the surface area in cm 2 ) was recorded from baseline to 12 weeks after injection. Treatment-related complications and adverse events were reported. The main outcome of measurements was a decrease in the size, the vascularity, the thickness, and the color intensity; hence, subconjunctival bevacizumab injection is useful in the management of patients with primary and recurrent pterygium without significant local or systemic adverse effects  .
Mandalos and colleagues studied the effect of ranibizumab injection on the clinical and the histological picture of primary pterygium: patients with primary pterygia received a single subconjunctival injection of ranibizumab (0.3 mg). Treated pterygia were removed surgically 3 days, 1 week, 2 weeks, 1 month, and 2 months after the injection, and by histological examination, there was no effect on the extent of vascularization of the pterygium, regardless of the interval between the injection and the operation  .
Razeghineja and colleagues evaluated the efficacy of subconjunctival bevacizumab as an adjunctive therapy for primary pterygium surgery. They studied 30 eyes of 30 patients. After pterygium excision and accomplishment of a rotational conjunctival flap, patients received 1.25 ml bevacizumab. The recurrence rate was 13.4% during the follow-up period of 8 months; hence, a single intraoperative subconjunctival bevacizumab injection had no effect on the pterygium recurrence rate  .
Another study was performed to evaluate the effect of a preoperative subconjunctival injection of bevacizumab in pterygium surgery. The case group received subconjunctival bevacizumab injection 1 to 2 weeks preoperatively and were followed up for 3 months. Recurrence of the pterygium did not occur in any case. This was attributed to the short period of follow-up  . However, in our study, the follow-up period was long enough for recurrence to occur.
Galor and colleagues evaluated subconjunctival ranibizumab in patients with primary pterygium undergoing pterygium surgery; 10 patients with primary pterygium received subconjunctival ranibizumab (0.5 mg/0.05 ml) administered at the limbus, adjacent to the pterygium, 3 days before surgery. Then, pterygium excision and conjunctival autograft were placed. Patients were followed for 6 months prospectively. At the end of the follow-up, Galor et al.  mentioned that all 10 patients tolerated the injection well, there was dehiscence of the autograft in one patient, and there were three cases of recurrence (30%).
Our study showed that all patients in group A tolerated the injection well, and there were no complications during and after the injection of bevacizumab (avastin). There were two cases of recurrence after 1 month in group A and only one case in group B.
In our study, no intraoperative complications occurred in any case in both groups. Regarding postoperative complications, there was no statistically significant difference between both groups ([Figure 1], [Figure 2], [Figure 3] and [Table 1]).
| Conclusion|| |
Both techniques used in the current study proved to be effective in reducing the recurrence rate after excision of the primary nasal pterygium with minimal postoperative complications. Injection of bevacizumab 2 weeks before had a better effect on decreasing the pterygium vascularity, which minimized the bleeding during operation in addition to decreasing the recurrence rate according to our study.
| Acknowledgements|| |
Conflicts of interest
| References|| |
Hirst LW, Sebban A, Chant D. Pterygium recurrence time. Ophthalmology 1994; 101
Fukushima S, Inoue T, Inoue T, Ozeki S. Postoperative irradiation of pterygium with 90Sr eye applicator. Int J Radiat Oncol Biol Phys 1999; 43
Figueiredo RS, Cohen EJ, Gomes JA, Rapuano CJ, Laibson PR. Conjunctival autograft for pterygium surgery: how well does it prevent recurrence? Ophthalmic Surg Lasers 1997; 28
Pery JF, Siganos CS, Ilsar M. Intraoperative application of topical mitomycin C for pterygium surgery. Ophthalmology 1996; 103
Manning CA, Kloess PM, Diaz MD,Yee RW. Intraoperative mitomycin in primary pterygium excision. A prospective, randomized trial. Ophthalmology 1997; 104
Singh, G, Wilson MR, Foster CS. Mitomycin eye drops as treatment for pterygium. Ophthalmology 1988; 95
Caliskan S, Orhan M, Irkec M. Intraoperative and postoperative use of mitomycin-C in the treatment of primary pterygium. Ophthalmic Surg Lasers 1996; 27
Tananuvat N, Martin T. The results of amniotic membrane transplantation for primary pterygium compared with conjunctival autograft. Cornea 2004; 23
Kim SW, Ha BJ, Kim EK, Tchah H, Kim TI. The effect of topical bevacizumab on corneal neovascularization. Ophthalmology 2008; 115
Gnandesikan R. Methods for statistical data analysis of multivariate observations
. New York: John Wiley and Sons; 1977. 1-82.
Oguz H, Basar E, Gurler B. Intraoperative application versus postoperative mitomycin C eye drops in pterygium surgery. Acta Ophthalmol Scand 1999; 77
Nassar MK, El-Sebaey AR, Abdel-Rahman MH, El-Ghonemy K, Shebl AM. Clinical, pathological, and molecular aspects of recurrent versus primary pterygium. Menoufia Med J 2014; 27
Jin J, Guan M, Sima J, Gao G, Zhang M, Liu Z, et al.
Decreased pigment epithelium-derived factor and increased vascular endothelial growth factor levels in pterygia. Cornea 2003; 22
Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al.
Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J 2004; 350
Solomon A, Pires RT, Tseng SC. Amniotic membrane transplantation after extensive removal of primary and recurrent pterygia. Ophthalmology 2001; 108
Prabhasawat P, Barton K, Burkett G, Tseng SC. Comparison conjunctival auto graft, amniotic membrane grafts and primary closure for pterygium excision. Ophthalmology 1997; 104
Tan CS, Lim TH, Koh WP, Liew GC, Hoh ST, Tan CC, Au Eong KG. Epidemiology of pterygium on a tropical island in the Riau Archipelago. Eye (Lond) 2006; 20
Diaz L, Villegas VM, Emanuelli A, Izquierdo NJ. Efficacy and safety of intraoperative mitomycin C as adjunct therapy for pterygium surgery. Cornea 2008; 27
Karukonda RK, Thompson WH. Cell cycle kinetics in pterygium at three attitudes. Br J Ophthalmology 1995; 79
Khoo J, Saw SM, Banerjee K, Chia SE, Tan D. Outdoor work and the risk of pterygia: a case-control study. Int Ophthalmol 1998; 22
Ozkurt YB, Kocamis O, Comez AT, Uslu B, Dogan OK. Treatment of primary pterygium. Optom Vis Sci 2009; 86
Teng CC, Patel NN, Jacobson L. Effect of subconjunctival bevacizumab on primary pterygium. Cornea 2009; 28
Omar R, Rimsha S, Waseem R, Arshad R, Shahzada BS, Assif S. Role of subconjunctival bevacizumab in treatment of pterygium. Pak J Ophthalmol 2012; 28
Besharati MR, Manaviat MR, Souzani A. Subconjunctival bevacizumab injection in treatment of pterygium. Acta Med Iran 2011; 49
Mandalos A, Tsakpinis D, Karayannopoulou G, Tsinopoulos I, Karkavelas G, Chalvatzis N, Dimitrakos S. The effect of subconjunctival ranibizumab on primary pterygium: a pilot study. Cornea 2010; 29
Razeghinejad MR, Hosseini H, Ahmadi F, Rahat F, Eghbal H. Preliminary results of subconjunctival bevacizumab in primary pterygium excision. Ophthalmic Res 2010; 43
Park YJ, Lee JW,Lee KW. Effect of preoperative subconjunctival injection of bevacizumab in pterygium surgery. J Krean Ophthalmol Soc 2008; 49
Galor A, Yoo SH, Piccoli FV, Schmitt AJ, Chang V, Perez VL. Phase I study of subconjunctival ranibizumab in patients with primary pterygium undergoing pterygium surgery. Am J Ophthalmol 2010; 149
[Figure 1], [Figure 2], [Figure 3]