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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 18  |  Issue : 3  |  Page : 138-142

Combined sutureless gluefree conjunctival autograft with subconjunctival bevacizumab for treatment of primary pterygium


Department of Ophthalmology, Faculty of Medicine (For Girls), Al-Azhar University, Cairo, Egypt

Date of Submission05-Apr-2017
Date of Acceptance19-Jun-2017
Date of Web Publication17-Oct-2017

Correspondence Address:
Mona M Aly
Department of Ophthalmology, Faculty of Medicine, Al-Azhar University, Nasr City 11754, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/DJO.DJO_29_17

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  Abstract 

Purpose The aim of this study was to assess the efficacy of subconjunctival bevacizumab injection as adjuvant therapy in the prevention of recurrence following excision of pterygium and application of sutureless gluefree conjunctival autograft (SL/GF CAG).
Patients and methods A prospective randomized comparative study was performed on 20 eyes of 20 patients with primary pterygium. They were divided into two groups: group A (10 eyes) had pterygium excision with SL/GF CAG and received subconjunctival 2.5 mg/0.1 ml of bevacizumab at the end of the surgery and group B (10 eyes) had pterygium excision with SL/GF CAG only followed by eye pressure patching for 24 h in both groups.
Results SL/GF CAG was successful in all cases except in one (10%) eye in group B that developed conjunctival graft retraction on the first postoperative day necessitating resurgery. Adjuvant subconjunctival bevacizumab injection used in group A was well tolerated with no systemic or local side effects but in the term of recurrence, no statistically significant difference was reported between the two groups in the postoperative 6 months follow-up period.
Conclusion SL/GF CAG is a novel technique for the treatment of primary pterygium. Augmentation of this technique with a single injection of bevacizumab by the end of surgery aiming at reducing the recurrence rate did not seem to provide any statistically significant difference than SL/GF CAG alone, although bevacizumab injection was well tolerated as an adjuvant therapy.

Keywords: bevacizumab, pterygium, sutureless gluefree conjunctival autograft


How to cite this article:
Aly MM, Mahmoud DA, Abd Al Rahman HM. Combined sutureless gluefree conjunctival autograft with subconjunctival bevacizumab for treatment of primary pterygium. Delta J Ophthalmol 2017;18:138-42

How to cite this URL:
Aly MM, Mahmoud DA, Abd Al Rahman HM. Combined sutureless gluefree conjunctival autograft with subconjunctival bevacizumab for treatment of primary pterygium. Delta J Ophthalmol [serial online] 2017 [cited 2022 Jan 26];18:138-42. Available from: http://www.djo.eg.net/text.asp?2017/18/3/138/216924


  Introduction Top


Pterygium is characterized by high vascularization, proliferation, invasive ocular surface lesions, and aberrant extracellular matrix remodeling. Surgical excision is the standard treatment for a pterygium [1]. Excision of the pterygium with conjunctival autograft is considered to be the procedure of choice in terms of efficacy and long-term safety [2] as the conjunctiva is the best replacement for conjunctiva [3]. The available techniques to secure conjunctival autograft are sutures, fibrin glue, and the sutureless gluefree technique [4]. The presence of sutures is believed to initiate inflammatory response and this is believed to be the cause of recurrence [5]. Although fibrin glue is considered safe and has the advantage of patients comfort, cost remains a major barrier for its universal use; moreover, it has a risk of transmission of infectious agents [4]. Sutureless and gluefree conjunctival autograft (SL/GF CAG) technique using the patient’s own blood as a bioadhesive was reported to be simple, easy, safe, effective, and less time consuming than sutured autograft technique with less postoperative discomfort and adverse events encountered with the use of suture material [6],[7].

Pterygia exhibit significantly higher levels of vascular endothelial growth factor (VEGF) than those in normal cornea and conjunctiva. Blocking VEGF may halt the vascularity and therefore growth of the pterygium. Anti-VEGF also reduces inflammation and thus may reduce symptoms such as redness and irritation [8]. Hosseini et al. [9] were the first to consider bevacizumab in the treatment of pterygium. It was hypothesized that local application of bevacizumab may inhibit neovascularization and thus may stop the progression or prevent the recurrence of pterygia.

The current study was conducted to evaluate the effect of anti-VEGF agent bevacizumab as a surgical adjuvant to SL/GF CAG in the prevention of recurrence after primary pterygium excision.


  Patients and methods Top


A prospective randomized interventional comparative study was performed. Twenty eyes of 20 patients with primary pterygia extending more than 2 mm onto the cornea were enrolled in the study.

Inclusion criteria

  1. Patients with grade II or III primary pterygium (according to Tan et al. [10] grading of pterygium) with the pterygium extending more than 2 mm onto the cornea.

    This involved classification of the appearance of pterygia at the slit lamp which included three grades based on the relative translucency of pterygium tissue, with the premise that loss of transparency was related to increased fleshiness or thickness of the fibrovascular component of the pterygium.
    1. Grade T1 (atrophic) denoted a pterygium in which episcleral vessels underlying the body of the pterygium were unobscured and clearly distinguished:
    2. Grade T2 (intermediate) denoted a pterygium in which episcleral vessel details were indistinctly seen or partially obscured.
    3. Grade T3 (fleshy) denoted a thick pterygium in which episcleral vessels underlying the body of the pterygium were totally obscured [10].
  2. Primary pterygium producing significant astigmatism, ocular irritation, or unaccepted cosmetic appearance.


Exclusion criteria

  1. Grade T1 pterygium.
  2. Recurrent pterygia.
  3. Patients with glaucoma.
  4. Patients with ocular surface diseases.
  5. History of previous ocular surgery.
  6. History of previous ocular trauma.
  7. Patients with hypertension, diabetes, autoimmune diseases, and cardiovascular diseases.
  8. Patients on anticoagulants.


Informed written consent was obtained from all patients after explanation of the procedure and the study was approved by the Local Ethics Committee. All patients had complete ophthalmological examination including best-corrected visual acuity, slit/lamp examination, intraocular pressure (IOP) measurement using Goldmann’s applanation tonometery, and fundus examination. The corneal astigmatism was measured using an autorefractor and the K-readings were obtained utilizing an autokeratometer. Patients were randomly subdivided into two groups: 10 patients each. Group A had SL/GF CAG with a single dose of subconjunctival bevacizumab (2.5 mg/0.1 ml) injection administered at the end of surgery and group B who had only SL/GF CAG.

Surgical technique

The pterygium excision was performed under topical, peribulbar, and subconjunctival anesthesia to the area of pterygium and the conjunctival graft area. The bare sclera technique was used for excision of the pterygia in all patients. Superotemporal bulbar conjunctival autograft was harvested with dimensions exceeding the future bed by 2 mm and was placed over the scleral defect after bare sclera excision of the pterygium was performed. No limbal tissue was included in the graft. Neither cautery nor saline irrigation was used at the excised pterygium bed and the excised graft tissue was placed on the bare sclera and left there without suturing for the natural patient’s autologous fibrin to glue the conjunctival autograft in place. At the end of surgery in group A patients, subconjunctival bevacizumab (2.5 mg/0.1 ml) (Avastin; Genentech Inc., San Francisco, California, USA) was injected; half the dose (1.25 mg/0.05 ml) was applied to the inferonasal quadrant, and the other half (1.25 mg/0.05 ml) was applied to the superonasal quadrant within the healthy conjunctiva adjacent to the location of the excised pterygium. Topical antibiotic and corticosteroid eye drops were instilled and followed by eye pressure patching for 24 h.

Patients were instructed to avoid eye rubbing. Combined antibiotic and corticosteroid eye drops were used four times a day for 1 week followed by tapering the dose till it was stopped after 4 weeks. The patients were followed up on the next day to evaluate the state of the graft regarding its adherence and the occurrence of complications, then the follow-up was scheduled on the first week, second week, first month, third month, and sixth month postoperatively.

The demographic data of the included patients were collected. The postoperative slit lamp examination data, refraction with detection of postoperative astigmatism with autorefractor, and the mean K-readings (K) were evaluated in both groups during the follow-up period. The state of the conjunctival autograft regarding the presence of retraction, detachment, ischemia, or necrosis was recorded and recurrence of pterygium was reported. The intact conjunctiva where bevacizumab was injected was evaluated for the occurrence of postinjection ischemia or hemorrhage.

Statistical analysis

Statistical analyses were performed using the statistical package for the social sciences, version 15.0 (SPSS Inc., Chicago, Illinois, USA). The demographic variables were analyzed using descriptive statistics. Preoperative and postoperative 1, 3, and 6 months measurements of the two 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 Top


This prospective randomized interventional comparative study included 20 eyes of 20 patients (15 men and five women) with primary pterygia. All pterygia were located nasally. The mean age at presentation was 44.9±4.9 years for group A and 45.0±5.5 years for group B. The demographic and preoperative ophthalmic data (including preoperative mean K-readings, corneal astigmatism, and IOP) for all included patients in the two groups are summarized in [Table 1]. There were no statistically significant differences between the two groups in terms of demographic data with regard to age and sex, preoperative mean keratometric readings, corneal astigmatism, or IOP (P>0.05).
Table 1 Demographic and ocular characteristics of the included patients

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All patients had uneventful surgeries. SL/GF CAG was successful in all cases except in one (10%) eye in group B that developed conjunctival graft retraction on the first postoperative day necessitating resurgery. All patients were followed for 6 months. Subconjunctival hemorrhage on the first postoperative day was reported in two (20%) eyes in group A and four (40%) eyes in group B ([Figure 1]). 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 months follow-up and only one (10%) eye in group A and one (10%) eye in group B had recurrence by the end of the follow-up period. The changes in keratometry, corneal astigmatism, and the recurrence of pterygium showed no statistically significant differences between the two groups in the postoperative follow-up period ([Table 2]). Adjuvant subconjunctival bevacizumab injection used in group A was well tolerated. No irritation, burning, or any systemic side effects of bevacizumab were reported during the follow-up period.
Figure 1 (a) Colored photography of a group A patient before the surgery. (b) The same patient immediately after surgery and bevacizumab injection with occurrence of subconjunctival hemorrhage.

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Table 2 Recurrence of pterygium and changes in keratomery and corneal astigmatism over the postoperative course in groups A and B

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  Discussion Top


Pterygium is characterized by the encroachment of a fleshy fibrovascular tissue from the bulbar conjunctiva onto the cornea [11]. The current treatments for pterygium focus on surgical excision and prevention of recurrence [12]. Methods to reduce recurrences in pterygium surgery include conjunctival autograft, amniotic membrane, mitomycin C, and other adjuvant therapies [13].

Recently, the role of inflammation and fibrovascular proliferation has been particularly highlighted as important factors in the pathogenesis of pterygia. VEGF had been shown to be increased in the pathogenesis of pterygia. Bevacizumab is a recombinant, humanized anti-VEGF antibody that binds all VEGF isoforms and exerts a neutralizing effect by inhibiting the VEGF–receptor interaction [14].

In the present study, we compared the efficacy of adding a single intraoperative subconjunctival bevacizumab injection as a surgical adjuvant to SL/GF CAG for the prevention of recurrence after primary pterygium excision versus SL/GF CAG alone. Twenty eyes of 20 patients with primary nasal pterygia were included in the study and were divided evenly between the two groups. The SL/GF CAG surgeries were uneventful in all eyes with no graft-related complications postoperatively apart from graft retraction in only one eye in group B on the first postoperative day necessitating resurgery. There were no side effects related to bevacizumab injection whether systemically or locally during the follow-up period.

In their study, Razeghinejad et al. [15] 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. In the current study, no difference in recurrence rate was observed between the SL/GF CAG group receiving single subconjunctival bevacizumab injection and the SL/GF CAG alone group by the end of the scheduled follow-up period. In their study, Shenasi et al. [11] have stated that subconjunctival injection of bevacizumab immediately after surgical excision of primary pterygium did not significantly prevent the recurrence of this condition.

In the present study, the authors used a single intraoperative injection of bevacizumab in a dose of 2.5 mg/0.1 ml divided in half (1.25 mg/0.05 ml each) between superonasal and inferonasal intact conjunctiva. This dose did not seem to be effective enough to stop pterygium recurrence. Teng et al. [16] have reported that 1.25 mg/0.05 ml bevacizumab caused rapid regression of neovascularization in primary inflamed pterygium, but the extent of this effect decreased over the course of their study and concluded that this transient effect was likely related to the limited bioavailability of the drug in a situation of continued VEGF expression. Park et al.’s [17] study has shown a dose-dependent inhibitory effect of bevacizumab in both primary and recurrent pterygium human Tenon’s fibroblasts. A significant increase in the antifibrotic effect, changes in the morphology, and reduction in the collagenase activity, occurred at a bevacizumab concentration of greater than 7.5 mg/ml.

The current study showed that a single subconjunctival bevacizumab injection after primary pterygium surgery as adjuvant therapy to SL/GF CAG technique although well tolerated had similar recurrence rate to SL/GF CAG technique alone. The limitations of the study were the small sample size and the short follow-up period; so, further studies with larger sample size and longer follow-up period with different doses and/or more number of injections is recommended to evaluate the efficacy of bevacizumab injection as an adjuvant therapy to SL/GF CAG in the prevention of pterygium recurrence and to evaluate properly the side effects related to it.


  Conclusion Top


SL/GF CAG is a novel technique for the treatment of primary pterygium. Augmentation of this technique with a single injection of bevacizumab by the end of surgery aiming at reducing the recurrence rate did not seem to provide any statistically significant difference than SL/GF CAG alone although bevacizumab injection was well tolerated as an adjuvant therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Kim YH, Jung JC, Gum SI, Park SB, Ma JY, Kim YI et al. Inhibition of pterygium fibroblast migration and outgrowth by bevacizumab and cyclosporine a involves down-regulation of matrix metalloproteinases-3 and −13. PLoS One 2017; 12:e0169675.  Back to cited text no. 1
    
2.
Ang LP, Chua JL, Tan DT. Current concepts and techniques in pterygium treatment. Curr Opin Ophthalmol 2007; 18:308–313.  Back to cited text no. 2
    
3.
Kenyon KR, Wagoner MD, Hettinger ME. Conjunctival autograft transplantation for advanced and recurrent pterygium. Ophthalmology 1985; 92:1461–1470.  Back to cited text no. 3
    
4.
Yadav AR, Bhattad KR, Sen PA, Jain EB, Sen A, Jain BK. Outcome of different techniques of pterygium excision with conjunctival autografting in pediatric population: our experience in central India. Indian J Ophthalmol 2015; 63:491–495.  Back to cited text no. 4
    
5.
Koranyi G, Seregard S, Kopp ED. The cut-and-paste method for primary pterygium surgery: long-term follow-up. Acta Ophthalmol Scand 2005; 83:298–301.  Back to cited text no. 5
    
6.
Singh PK, Singh S, Vyas C, Singh M. Conjunctival autografting without fibrin glue or sutures for pterygium surgery. Cornea 2013; 32:104–107.  Back to cited text no. 6
    
7.
Sharma A, Raj H, Gupta A, Raina AV. Suture-less and glue-free versus sutures for limbal conjunctival autografting in primary pterygium surgery: a prospective comparative study. J Clin Diagn Res 2015; 9:NC06–NC09.  Back to cited text no. 7
    
8.
Mak RK, Chan TC, Marcet MM, Choy BN, Shum JW, Shih KC et al. Use of anti-vascular endothelial growth factor in the management of pterygium. Acta Ophthalmol 2017; 95:20–27.  Back to cited text no. 8
    
9.
Hosseini H, Nejabat M, Khalili MR. Bevacizumab (Avastin) as a potential novel adjunct in the management of pterygia. Med Hypotheses 2007; 69:925–927.  Back to cited text no. 9
    
10.
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.  Back to cited text no. 10
    
11.
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.  Back to cited text no. 11
    
12.
Stival LR, Lago AM, Figueiredo MN, Bittar RH, Machado ML, Nassaralla Junior JJ. Efficacy and safety of subconjunctival bevacizumab for recurrent pterygium. Arq Bras Oftalmol 2014; 77:4–7.  Back to cited text no. 12
    
13.
Janson BJ, Sikder S. Surgical management of pterygium. Ocul Surf 2014; 12:112–119.  Back to cited text no. 13
    
14.
Hu Q, Qiao Y, Nie X, Cheng X, Ma Y. Bevacizumab in the treatment of pterygium: a meta-analysis. Cornea 2014; 33:154–160.  Back to cited text no. 14
    
15.
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.  Back to cited text no. 15
    
16.
Teng CC, Patel NN, Jacobson L. Effect of subconjunctival bevacizumab on primary pterygium. Cornea 2009; 28:468–470.  Back to cited text no. 16
    
17.
Park YM, Kim CD, Lee JS. Effect of bevacizumab on human tenon’s fibroblasts cultured from primary and recurrent pterygium. Korean J Physiol Pharmacol 2015; 19:357–363.  Back to cited text no. 17
    


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