Role of Bevacizumab in Reducing Recurrence of Pterygium after Excision & Conjunctival Autograft

Objective: The purpose of this study is to evaluate the effect of subconjunctival injection of Bevacizumab following pterygium excision and conjunctival autograft in reducing recurrence. It was a Quasi experimental study

Method: This study was carried out at Khalid Eye Clinic, Karachi from July 2018 to June 2019. It included sixty patients of both genders between the ages of 20 to 40 years and divided into two groups, Group A and Group B, with thirty patients in each group. All the patients underwent pterygium excision followed by conjunctival autograft.

Material and Method. Patients of Group A received sub conjunctival injection of Bevacizumab, (5mg/0.2 ml), superior and inferior to the graft at the level of limbus, whereas, Group B patients did not receive Bevacizumab injection. All the patients of both groups were followed up for a period of six months for recurrence, which was defined as crossing of conjunctival tissue over the limbus 1mm onto the cornea. All patients were briefed about the study dynamics and study approval was obtained from the ethical review committee.

Results: This study included sixty patients and observed recurrence of pterygium in one (3%) patient of group A (Bevacizumab) as compared to three (10%) patients of group B.

Conclusion: Anti VEGF Bevacizumab is an effective drug in reducing recurrence after Pterygium excision followed by conjunctival autograft, but this study found no significant difference in the outcome of both the groups.

Keywords: Bevacizumab, Pterygium, conjunctival autograft

Received: July’2020                        Accepted: Sep’2020

INTRODUCTION

First described by AC Susruta,1 Pterygium is a benign degenerative ocular lesion, which may be active over months to years, or dormant and linger steady for decades as a triangular growth comprising of fibrovascular tissue, beginning from the bulbar conjunctiva, moving across the limbus and coming onto the cornea. It can crop up on whichever side of the cornea but the nasal limbus frequently involved.2 Chronic exposure to the sun, outdoors and dry climate increases the risk of developing pterygium to 1.5-fold with advanced cases disturbing the vision since it disrupts the cornea and leads to astigmatism and corneal scarring.3

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Anti VEGF Bevacizumab is an effective drug in
reducing recurrence after Pterygium excision followed
by conjunctival autograft, but this study
found no significant difference in the outcome of
both the groups.

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Traditionally, pterygium is managed via conservative treatment as long as it is not succeeding onto the pupillary region and resulting in astigmatism and decreased vision. If progressive, surgical excision of the pterygium is the customary treatment leaving exposed sclera, surgical excision with primary closure, conjunctival autograft, limbal autograft and transplantation of limbal stem cells.4 Even though it is a benign condition, there are reported rates of recurrence after simple excision of the primary pterygium with subsequent unrelenting distress; visual alteration and constrained ocular motility.5,6 The noteworthy post operative recurrence rate is due to the insufficiency of corneal limbal stem cells, age of the patient, duration, environmental factors, the pterygium morphology and the fleshiness of pterygium.7 Conjunctival autograft fixation technique is traditionally done via sutures by attaching it to the bare sclera underneath. It has been suggested in recent times, that there is an alteration in the p53 gene on chromosome 17 as the reason of creation of pterygium ensuing in variable expression of various growth factors, such as vascular endothelial growth factor A (VEGF-A).8 Bevacizumab, a recombinant humanized monoclonal antibody, anti VEGF has been used as an anti cancer agent 9 whereas, off label utilization of Bevacizumab has been carried out for certain neo-vascular ocular disorders with promising outcomes.10,11 The sub conjunctival use of Bevacizumab injection has been used reportedly used for the management primary and recurrent pterygia with minimal adverse effects.12 This study was conducted to observe the superiority of using Bevacizumab as an adjunct with pterygium excision and conjunctival autograft in reducing the recurrence rate.

MATERIAL AND METHOD

This study was carried out at Khalid Eye Clinic, Karachi from July 2018 to June 2019. It included sixty patients of both genders divided into two groups, Group A and Group B. A thorough ocular and systemic history was taken and complete eye exam was done prior to the operation. Eyes having primary pterygium (Tan et al., 1997, Grade 1: Up to ¼ the corneal diameter, Grade 2: ¼- ½ the corneal diameter 3-6mm, Grade 3: Extending beyond the visual axis >6mm) were incorporated in this study whereas patients having ocular surface disorders, pseudo-pterygium, history of allergy to blood components, presence of systemic autoimmune and viruses along with long term use of topical medications were not included in this study. Every recruited patient was randomly categorized into the two groups, with thirty patients in each group. All the patients underwent pterygium excision followed by conjunctival autograft done by a single oculoplastic surgeon. After all aseptic measures and peri-bulbar anesthesia, 2% xylocaine was injected at the location of the pterygium to raise it up to its adherence to the cornea. A Crescent blade was used to shave off pterygium from the cornea. The pterygium attached with the conjunctiva was divided and excised from the scleral surface with tenotomy scissor leaving a bare sclera. Free conjunctival autograft was obtained from the superior limbal region 1 mm bigger than the recipient site. Graft was then shifted to the recipient area and stitched with 10-0 Vicryl sutures. Patients of Group A received sub conjunctival injection of Bevacizumab, (5mg/0.2 ml), superior and inferior to the conjunctival autograft at the level of limbus, whereas, Group B patients did not receive Bevacizumab injection following pterygium excision followed by conjunctival autograft. All the patients of both groups were followed up for a period of six months for recurrence, which was defined as crossing of conjunctival tissue over the limbus 1mm onto the cornea. All patients were briefed about the study dynamics and study approval was obtained from the ethical review committee.

RESULTS

This study included sixty patients divided in to two groups with thirty patients in each group. Mean age was 31.3± 4.6 years. There were forty two (70%) males and eighteen (30%) females. Involvement of the right eye was present in thirty six (60%) patients whereas left eye was involved in twenty four (40%) patients. At the conclusion of the six months follow up period, recurrence of Pterygium was observed in only one (3%) patient of group A (Bevacizumab) whereas, three (10%) patients of group B reported recurrence of pterygium. No complications such as infection, granuloma formation or graft loss reported in either group. Mean follow up period was 186± 6.3 days.

DISCUSSION

Due to an increased rate of recurrence post surgery, management of pterygium poses a challenge. The aim of this study is to use Bevacizumab as an adjunct to pterygium excision with conjunctival autograft in further reducing the recurrence of pterygium formation. Vascular endothelial growth factor (VEGF) has a pivotal role in the formation of vessels, promoting migration of the endothelial cells, inflammation resulting in recurrence of pterygium after pterygium excision surgery.13 Keeping this in mind, anti-VEGF therapy cause the degeneration and inhibition of new blood vessels, hence reducing the extent of pterygium formation and play an important role in the prevention of recurrence. One such anti VEGF agent, Bevacizumab, helps in the decrease of size and vascularization of pterygium and reduces the recurrence rate. Lee et al reported the first ever role of increased VEGF in the development of pterygium in 200114 thereby, explaining that by giving anti- VEGF such as, Bevacizumab, may lessen the proliferation of fibroblast and limit pterygium recurrence. In this study patients of group A received sub conjunctival injection of Bevacizumab, (5mg/0.2 ml) superior and inferior to the conjunctival autograft at the level of limbus, after pterygium excision and conjunctival autograft placement and followed for a period of six months. By the end of the follow up period recurrence of pterygium was observed in only one (3%) patient of group A (Bevacizumab) whereas, three (10%) patients of group B (no Bevaciumab injection) reported recurrence of pterygium. Another study injected Bevacizumab at a concentration of 1.25 mg/0.05 ml and followed up the patients for a period of three months and observed a recurrence rate of 8.3%.15 In accordance with this, comparable results were reported by studies done by Fallah Tafti et al and Besharati et al with a reduction in pterygium size three months after repeated Bevacizumab injections.16,17 Oguz et al showed a recurrence rate of 9.52% after pterygium excision with conjunctival autograft,18 which was similar to group B in this study with a recurrence of 10%. Other studies also demonstrated recurrence rates of 13.3%, 14% and 12% pterygium excision with conjunctival autograft without Bevacizumab injection.19,20,21 These observations inferred that bevacizumab has potential to cause contraction and regression in the vascular caliber of pterygium blood vessels. Singh et al and Teng et al also showed significant diminishing in the symptoms after Bevacizumab injection such as pain, photophobia, redness, itching, watering, and irritation.15,22 This was in contrast with a study done previously which showed development of graft edema with subconjunctival hemorrhage along with conjunctival cysts formation and recurrence after Bevacizumab injection.15 Another study by Kim et al reported a 60% rate of unprompted loss of epithelial integrity after using topical bevacizumab at a concentration of 1.25% twice daily for 3 months.23 This study used a single sub conjunctival injection of Bevacizumab at a dose of 5mg/0.2 ml and followed for a period of six months and observed no per operative or post operative complications such as infection, granuloma formation or graft loss were reported in either group. This study was done on patients belonging to both genders between the ages of 20 to 40 years. Studies have reported that majority of the recurrences occur below the age of 50 years.15,24,25 This study also documented a greater prevalence of pterygium in the male gender (70%) as compared to the females (30%), which in our setting reflects the fact the males are normally the providers for the family and more exposed to the outside environment. Apart from vascular endothelial growth factor, several other factors inclduing anti-apoptotic mechanisms, pro-inflammatory cytokines, growth factors, extracellular matrix remodeling, immunological mechanisms, viral infections and the genetics are responsible for the formation of pterygium and since Bevacizumab is an anti VEGF, it is not directed against other growth factors found in pterygium.

CONCLUSION

This study conclded that anti VEGF Bevacizumab is an effective drug in reducing recurrence after Pterygium excision followed by conjunctival autograft with almost negligible side effects, but this study found no significant difference in the outcome of both the groups.

Conflict of Interest – None.
Financial disclosure – None.

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