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ORIGINAL ARTICLE
Ahead of print publication  

A modified surgical technique of fibrin glue-assisted double bipedicle conjunctival flaps for patients with ocular surface diseases


1 Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan
2 Department of Ophthalmology, National Taiwan University Hospital, Taipei; Department of Ophthalmology, National Taiwan University Biomedical Park Hospital, Hsinchu, Taiwan
3 Department of Ophthalmology, Shiley Eye Institute and Viterbi Family, University of California, San Diego, California, USA
4 Department of Ophthalmology, National Taiwan University Hospital, Taipei; Department of Ophthalmology, Fu-Jen Catholic University Hospital; School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
5 Department of Ophthalmology, National Taiwan University Hospital; Department of Ophthalmology, College of Medicine, National Taiwan University; Advanced Ocular Surface and Corneal Nerve Regeneration Center, National Taiwan University Hospital, Taipei, Taiwan

Date of Submission15-Nov-2021
Date of Acceptance01-Mar-2022
Date of Web Publication13-May-2022

Correspondence Address:
Wei-Li Chen,
Department of Ophthalmology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei
Taiwan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tjo.tjo_14_22

  Abstract 


PURPOSE: This study aimed to describe and investigate the surgical outcome and complications of fibrin glue-assisted double bipedicle conjunctival flaps (CFs) (F. A. D. C. O. F.), an alternative surgical technique that restores a stable ocular surface in patients with painful blinding ocular surface disease combined with a shortage of bulbar conjunctiva.
MATERIALS AND METHODS: Six eyes of six patients with painful blinding ocular surface disease were enrolled in this study. All patients had inadequate superior or inferior conjunctiva tissue to cover the whole corneal surface owing to previous surgeries or ocular surface diseases. These patients received F. A. D. C. O. F. between 2009 and 2019. The main outcome included surgical success rate, visual analog scale (VAS) pain score, ocular inflammation score, and postoperative complications. Surgical success was defined as resolution of initial ocular complaints and restoration of a stable ocular surface with no flap melting, retraction, or dehiscence resulting in re-exposure of the corneal surface.
RESULTS: All of the six eyes (100%) achieved surgical success. All patients reported significant improvement in subjective symptoms and complete resolution of ocular pain after the surgery (VAS pain score: 6.5 ± 0.5 preoperatively to 0.0 ± 0.0 at 1 month). Ocular inflammation score decreased significantly from a presurgical value of 1.83 ± 0.69 to 0.33 ± 0.47 1 month after the surgery. No postoperative complication was found during the long-term follow-up (range: 12–82 months).
CONCLUSION: F. A. D. C. O. F. is a reliable alternative for patients with painful blinding ocular surface diseases unsuitable for single total CF surgery. This surgical technique yields fast ocular surface stabilization, satisfactory recovery, and low complication rates.

Keywords: Conjunctiva, fibrin tissue adhesive, surgical flaps



How to cite this URL:
Liu JY, Huang WL, Hsieh YH, Wu JH, Huang CJ, Chen WL. A modified surgical technique of fibrin glue-assisted double bipedicle conjunctival flaps for patients with ocular surface diseases. Taiwan J Ophthalmol [Epub ahead of print] [cited 2022 Sep 28]. Available from: https://www.e-tjo.org/preprintarticle.asp?id=345183




  Introduction Top


Conjunctival flaps (CFs) have long been used to restore corneal surfaces in patients with painful blinding ocular surface diseases.[1],[2] Several types of CFs have been proposed in the past, including total CF described by Gundersen, bipedicle bridge flaps, single pedicle flaps, and advancement flaps for paralimbal lesions. Among all, total CF prevails in treating painful blinding ocular surface diseases since it covers the whole surface area and is most likely to restore a stable corneal surface.[3],[4] For all types of CF surgeries, robust suturing technique that secures the CFs onto the corneal surface and an adequate conjunctival tissue is crucial. However, suturing a total CF with a large surface area is not only time consuming but also prone to overtightening/loosening of the sutures, cutting through of the CF, and accidental creation of conjunctival buttonholes and corneal/scleral perforation.[5] Patients may experience ptosis if a large area of superior bulbar conjunctiva was sacrificed, and other postoperative complications include partial flap retraction and epithelial inclusion cysts.[4],[6] For patients suffering from a shortage of bulbar conjunctival tissue, reconstruction of a stable ocular surface with a single CF is even more challenging.

To prevent these suture-related complications and limitations, we presented a modified surgical technique named “fibrin glue-assisted double bipedicle conjunctival flaps (F. A. D. C. O. F.)”. In F. A. D. C. O. F., two hemi-bipedicle CFs, one from the superior and the other from the inferior bulbar conjunctiva, were attached to and fully covered the denuded corneal surface using fibrin glue, which was proven a beneficial alternative to suture for managing total CFs.[4],[5],[7],[8],[9] In this study, we evaluated the surgical success, pain relief, and long-term satisfactory result of F. A. D. C. O. F., as well as whether it is suitable for patients with painful blinding ocular surface problems, especially those with insufficient conjunctival reserve.


  Materials and Methods Top


We performed a retrospective case analysis of patients who received F. A. D. C. O. F. between 2009 and 2019 in the Department of Ophthalmology, National Taiwan University Hospital (NTUH), in accordance with the tenets of the Declaration of Helsinki. This study was approved by the NTUH Institutional Review Board (approval number: NCT00155402). All surgeries were performed by one experienced surgeon (W.L. C.) after obtaining informed consent from the patients.

Surgical technique

The F. A. D. C. O. F. technique was performed under local anesthesia. Two 6-0 silk traction sutures were first placed over the superior and inferior rectus muscles to aid in the manipulation of the eyeball [Figure 1]a. The epithelium, superficial calcium plaques, and the sterile infiltrates were debrided with No 64 blade (Bard-Parker 64 blade). After subconjunctival injection of anesthetics [Figure 1]b, a curved incision slightly wider than the corneal diameter was made on superior bulbar conjunctiva, approximately 5–6 mm apart from and parallel to the corneal limbus [Figure 1]c. The dimension of the incision was designed to provide an adequate surface area from both superior and inferior sides to cover the entire denuded corneal surface. Dissection of the CF from the underneath Tenon's capsule was then performed with meticulous care to avoid the formation of buttonholes [Figure 1]d. The above procedures were repeated over the inferior bulbar conjunctiva [Figure 1]e, [Figure 1]f, [Figure 1]g. A 360° peritomy was then performed to create two hemi-bipedicle CFs [Figure 1]h. The CFs were then mobilized and adhered to the entire corneal surface with fibrin glue (TISSUCOL DUO QUICK, Baxter, IL). The contents of fibrin glue including sealer protein and thrombin solution were placed in a double-chamber syringe and mixed during application by passing the joining piece to the application cannula. To achieve a sealing effect that is strong enough to hold the flap, we waited for 2 min until the next step based on the instructions [Figure 1]i. One to four stitches of 10–0 nylon were anchored to the junction of the two CFs in the central cornea, then four stitches of 10-0 nylon were sutured to anchor the two CFs to the episcleral area [Figure 1]j. The postoperative regimen consisted of the application of a therapeutic contact lens (PureVision, Bausch, and Lomb) immediately after the surgery. Topical levofloxacin 0.5% (Cravit, Santen, Osaka, Japan) and betamethasone 0.1% (Betame, Aseptic Innovative Medicine Co, Taoyuan, Taiwan) were applied and maintained for 3 months.
Figure 1: Schematic representation of the fibrin glue-assisted double bipedicle conjunctival flaps technique. (a) Place two 6-0 Silk traction sutures over recti muscles. (b) Inject anesthetics subconjunctivally. (c) Incise the superior bulbar conjunctiva 5–6 mm from the limbus. (d) Dissect the conjunctival flap from the underneath Tenon's capsule. (e-g) Repeat the above procedures over the inferior bulbar conjunctiva. (h) Perform 360° peritomy to free the two hemi-bipedicle conjunctival flap. (i) Mobilize and adhere the conjunctival flap to the entire corneal surface with fibrin glue. (j) Anchor the conjunctival flap to the episcleral area

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Evaluation of surgical outcome

Patient demographics, indications for surgery, and follow-up duration were collected from electronic medical records. Intraoperative and postoperative complications, including formation of buttonholes, corneal perforation, flap retraction, epithelial cysts formation, epithelial ingrowth, and ptosis were recorded. Postoperative outcomes including visual analog scale (VAS) pain scores and inflammation scores were documented preoperatively, at the 1-month postoperative visit, and at their last clinic visit. The pain score was rated as none (scale 0), mild (1–3), moderate (4–6), or severe (7–10) based on the subjective report by the patients. A similar scale was used to evaluate ocular inflammation by the surgeon during the same time periods. Data were analyzed using the appropriate statistical test with the aid of the SPSS version 25.0 (SPSS, Inc, Chicago, IL, USA). P < 0.05 was designated as statistically significant. Surgical success was defined as restoration of a stable ocular surface with no flap melting, retraction, or dehiscence resulting in re-exposure of the corneal surface and the resolution of ocular complaints.


  Results Top


A total of six eyes of six patients were enrolled and underwent F. A. D. C. O. F. surgery. The summary of patient demographics and surgical outcomes is provided in [Table 1]. The mean age of patients was 75.8 ± 12.8 years (range: 57–91 years). Two subjects (33.3%) were male. The mean duration of follow-up was 47.3 ± 31.1 months (range: 12–82 months). Preoperative visual acuity was less than hand movement in all cases, which remained unchanged postoperatively. The average VAS pain score decreased from 6.5 ± 0.5 (preoperative) to 0.0 ± 0.0 (Wilcoxon signed-rank test, P = 0.024) 1 month after the surgery. No recurrence of ocular pain was noted during the entire follow-up period. The average inflammation score also decreased from 1.83 ± 0.69 to 0.33 ± 0.47 (Wilcoxon signed-rank test, P = 0.041) within 1 month postoperatively.
Table 1: Patient demographics and treatment outcome

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No intraoperative complication was documented, and surgical success based on the aforementioned definition was achieved in all subjects. During the follow-up period, none showed flap retraction, flap melting, or conjunctival buttonholes. The thickness of CFs decreased gradually, while the surface area remained stable, leading to a progressive improvement of cosmesis [Figure 2]. Postoperative ptosis or limitation of eye movements was not encountered in any of the patients.
Figure 2: Case demonstration. (a) Severe corneal edema, recurrent corneal erosion, and conjunctival injection in an 82-year-old woman with pseudophakic bullous keratopathy after repeated vitreoretinal surgeries. (b) immediately after the surgery, two hemi-bipedicle conjunctival flaps were spread smoothly by fibrin glue and covered the whole corneal surface. Junction of the superior and inferior flaps (arrows) was strengthened by several anchoring sutures. (c) on postoperative day 1, anterior segment optical coherence tomography demonstrated smooth adherence of the conjunctival flap onto the corneal surface without dehiscence or fluid accumulation at the interface (arrows). (d) smooth corneal surface without inflammation was achieved and maintained 1 year after the operation. The superficial vessels across both conjunctival flaps indicate the complete adhesion of the two conjunctival flaps on the corneal surface


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  Discussion Top


The use of total CF is a simple and efficacious way to restore the ocular surface stability in cases with painful blinding ocular surface diseases involving the whole corneal surface.[6] This viable surgical technique has been underused owing to the prevalence of alternative therapeutic options stabilizing the ocular surface, inclusive of amniotic membrane transplantation (AMT), usage of bandage contact lens, and therapeutic penetrating keratoplasty.[4],[5],[10] AMT has already been playing a major role in the management of persistent or recurrent corneal epithelial defects, taking advantage of its anti-inflammatory, anti-scarring, anti-fibrotic, and antimicrobial actions.[6],[11],[12] However, there is no blood supply on the amnion membrane (AM), with anti-angiogenic factors of AM transplants further impeding vascularization. Combining with its thin thickness, AM transplants are more prone to melting and dissolving after transplantation.[11],[12],[13] CFs, on the other hand, may provide stronger support and longer durability due to its better vascular supply and less susceptibility to sloughing and dislocation. In addition, the fibrous layer of the propria lamina of those CFs could adhere firmly to the corneal stroma.[4],[5],[10],[14] Prior studies have also shown CF with a lower complication rate or better treatment outcome as compared to AMT in selective cases.[13],[14] Therefore, for patients with a concern of a less ideal healing condition due to insufficient vascular supply and significant scar tissue produced by prior surgeries, CF may be a superior choice. Furthermore, there are other concerns when using AMT, including the need of a tissue bank and the higher cost, which should also be considered when choosing between AMT and CF. Total CFs still possess its unique advantages of a simpler technique, lower complication rate, fewer surgical material requirements, longer durability, greater convenience for follow-up examination, and a lower medical cost.[4],[5],[9],[10]

The key to surgical success of total CF transplantation is the harvesting of a thin, adequate-sized conjunctiva with as little tenon remnant as possible. Usually, a single CF, mostly from the superior bulbar conjunctiva and sometimes from the inferior one, is anchored onto the corneal surface with many sutures.[15] Suturing the CFs onto the corneal surface is another challenging quest as tight sutures would create irregular conjunctival surfaces or buttonholes, while loose sutures may result in poor healing and early postoperative flap detachment[4],[5],[6], which leads to flap retraction. In previous case series adopting the traditional CF procedure, reported flap retraction rates ranged from 7% to 85%.[6],[10],[16],[17],[18] Similar difficulties and complications can be found in other conjunctival surgeries, such as in pterygium surgery. We have long noticed the establishment of fibrin glue use in pterygium surgery. Fibrin glue-assisted pterygium surgery has been found to be superior to sutures with conjunctival autografting as it reduces pterygium recurrence without increasing complication rates and is associated with a significantly faster surgical time coupled with a reduction in the intensity of postoperative pain, foreign-body sensation, and epiphora.[19] Chung et al. further demonstrated the use of fibrin glue for CFs attachment in a case series involving seven eyes of seven patients undergoing CFs surgery. No flap retraction was noted and the recovery process was promising.[5] These results implied that the use of fibrin glue in conjunctival surgery carries the benefit of less tissue manipulation, better tissue adherence, reduced surgical time, and reduced risk of flap retraction.[5],[9]

Another difficulty encountered in traditional total CF surgery is the lack of adequate conjunctival tissue for the creation of a single CF. Predisposing conditions that lead to a painful blinding ocular surface disease, such as end-stage glaucoma, cicatricial diseases, or chemical burn may result in shortened superior and/or inferior bulbar conjunctiva due to repeated glaucoma or vitroretinal surgeries. As a surgeon experience, every 1 in four patients requiring CFs may suffer from this problem. Single total CF transplantation may not be applicable in such cases since a large area of healthy conjunctiva is required to achieve a well-vascularized stable ocular surface and to provide anti-inflammatory cellular components or cytokines to control the inflammation process.[6] Shall a total CF surgery be performed in such circumstances, a higher chance of ptosis and eye movement limitation due to fornix shortage may diminish the postoperative satisfaction.

The modified surgical technique we presented here incorporates the strength of fibrin glue and can be performed on patients with shortened superior and inferior bulbar conjunctiva. With the aid of fibrin glue, we can simply attach the two hemi-bipedicle CFs to cover the whole corneal surface. To counteract the retraction-prone nature of the CFs, fibrin glue secured the adhesion between the CFs and the corneal surface, hence facilitating the CFs to spread evenly across larger surface areas beyond which could be achieved by sutures.

Our results showed a high surgical success rate and a low complication rate of F. A. D. C. O. F. We achieved a total surgical success, and our overall graft retraction rate compares favorably with that reported by Chung and Mehta,(0%)[5] Alino et al., (11.4%),[18] and Paton and Milauskas (85%),[16] of which fibrin glue usage or partial CFs were included. In patients with chronic ocular surface disorders, this new technique can rapidly relieve pain and decrease inflammation with an average period of resolution <1 month, which is noninferior to fibrin glue-assisted single CF surgeries.[5],[6]


  Conclusion Top


In cases with limited reserve of healthy bulbar conjunctiva, F. A. D. C. O. F. provides sufficient and stable coverage of the corneal surface by the adherence of two hemi-bipedicle CFs with the assistance of fibrin glue. Our case series with a long-term follow-up demonstrated that F. A. D. C. O. F. is a reliable technique to treat patients with painful blinding ocular surface diseases.

Acknowledgment

We thank Hsiao-Jung Liu for depicting the artwork in Figure 1.

Financial support and sponsorship

The work is partially supported by (1) the Department of Medical Research, NTUH, and (2) National Taiwan University Hospital Research Grant for Advanced Ocular Surface and Cornea Nerve Research Center (108-A144).

Conflicts of interest

The authors declare that there are no conflicts of interests of this article.



 
  References Top

1.
Gundersen T. Conjunctival flaps in the treatment of corneal disease with reference to a new technique of application. AMA Arch Ophthalmol 1958;60:880-8.  Back to cited text no. 1
    
2.
Gundersen T, Pearlson HR. Conjunctival flaps for corneal disease: Their usefulness and complications. Trans Am Ophthalmol Soc 1969;67:78-95.  Back to cited text no. 2
    
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Rootman DS, Ku JY, Yeung SN. 36 – Ocular surface disease: Surgical management. In: Holland EJ, Mannis MJ, Lee WB, editors. Ocular Surface Disease: Cornea, Conjunctiva and Tear Film. London, U.K: W.B. Saunders; 2013. p. 293-308.  Back to cited text no. 3
    
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Zemba M, Stamate AC, Tataru CP, Branisteanu DC, Balta F. Conjunctival flap surgery in the management of ocular surface disease (Review). Exp Ther Med 2020;20:3412-6.  Back to cited text no. 4
    
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7.
Ozdamar Y, Mutevelli S, Han U, Ileri D, Onal B, Ilhan O, et al. A comparative study of tissue glue and vicryl suture for closing limbal-conjunctival autografts and histologic evaluation after pterygium excision. Cornea 2008;27:552-8.  Back to cited text no. 7
    
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Karalezli A, Kucukerdonmez C, Akova YA, Altan-Yaycioglu R, Borazan M. Fibrin glue versus sutures for conjunctival autografting in pterygium surgery: A prospective comparative study. Br J Ophthalmol 2008;92:1206-10.  Back to cited text no. 8
    
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Lee GA, Holcombe DJ. Surgical revision of dysfunctional filtration blebs with bleb preservation, sliding conjunctival flap and fibrin glue. Eye (Lond) 2010;24:947-53.  Back to cited text no. 9
    
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Oostra TD, Mauger TF. Conjunctival flaps: A case series and review of the literature. Eye Contact Lens 2020;46:70-3.  Back to cited text no. 10
    
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Fernandes M, Sridhar MS, Sangwan VS, Rao GN. Amniotic membrane transplantation for ocular surface reconstruction. Cornea 2005;24:643-53.  Back to cited text no. 11
    
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Walkden A. Amniotic membrane transplantation in ophthalmology: An updated perspective. Clin Ophthalmol 2020;14:2057-72.  Back to cited text no. 12
    
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Budenz DL, Barton K, Tseng SC. Amniotic membrane transplantation for repair of leaking glaucoma filtering blebs. Am J Ophthalmol 2000;130:580-8.  Back to cited text no. 13
    
14.
Gao H, Jia Y, Li S, Wang T, Tan Y, Shi W. Conjunctival flap covering combined with antiviral and steroid therapy for severe herpes simplex virus necrotizing stromal keratitis. Sci World J 2015;2015:565964.  Back to cited text no. 14
    
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Bawazeer A, Maniyar A, Mintsioulis G, Al-Muammar A. The gundersen flap: A new modification. JKAU Med Sci 2009;16:21-27.  Back to cited text no. 15
    
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Paton D, Milauskas AT. Indications, surgical technique, and results of thin conjunctival flaps on the cornea: A review of 122 consecutive cases. Int Ophthalmol Clin 1970;10:329-45.  Back to cited text no. 16
    
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Brown DD, McCulley JP, Bowman RW, Halsted MA. The use of conjunctival flaps in the treatment of herpes keratouveitis. Cornea 1992;11:44-6.  Back to cited text no. 17
    
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Alino AM, Perry HD, Kanellopoulos AJ, Donnenfeld ED, Rahn EK. Conjunctival flaps. Ophthalmology 1998;105:1120-3.  Back to cited text no. 18
    
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Romano V, Cruciani M, Conti L, Fontana L. Fibrin glue versus sutures for conjunctival autografting in primary pterygium surgery. Cochrane Database Syst Rev 2016;12:CD011308.  Back to cited text no. 19
    


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