About MEAJO | Editorial board | Search | Ahead of print | Current Issue | Archives | Instructions to authors | Online submission | Subscribe | Advertise | Contact | Login 
Middle East African Journal of Ophthalmology Middle East African Journal of Ophthalmology
Users Online: 1880   Home Print this page Email this page Small font sizeDefault font sizeIncrease font size

  Table of Contents 
Year : 2019  |  Volume : 26  |  Issue : 3  |  Page : 148-152  

Glaucoma patch graft surgery utilizing corneas augmented with collagen cross-linking

1 Department of Research, ReWilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA; Department of Research, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia
2 Department of Research, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; Glaucoma Consultants of Washington, Virginia; Department of Ophthalmology and Visual Sciences, University of Maryland, Baltimore, Maryland, USA
3 Department of Research, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia

Date of Submission24-Mar-2018
Date of Decision14-Jul-2019
Date of Acceptance28-Aug-2019
Date of Web Publication30-Sep-2019

Correspondence Address:
Dr. Ohoud A Owaidhah
King Khaled Eye Specialist Hospital, P.O. Box 7191, Riyadh 11462
Saudi Arabia
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/meajo.MEAJO_78_18

Rights and Permissions

PURPOSE: Glaucoma drainage device surgery (GDDS) has gained popularity, with outcomes equivalent to trabeculectomy. Erosion of the tube through the overlying conjunctiva may occur in 5%–10% of eyes. Donor corneal tissue has been used as a patch graft for GDDS.
MATERIALS AND METHODS: This was a prospective proof of concept study in 10 patients undergoing GDDS. From patients undergoing endothelial keratoplasty, the donor tissue (approximately 300 μ in thickness) was placed epithelial side down in a well and was allowed to soak in riboflavin solution (VibeX, Avedro, Waltham, MA, USA) for 15 min. This anterior corneal lenticule received 8 mW/cm2 ultraviolet (UV) irradiation applied for 15 min (total energy of 7.2 J/cm2). Each lenticule was then bisected and utilized for the two study participants. The tissue was sutured over the tube during the GDDS and then was covered with recipient conjunctiva as per the usual technique. Representative graft tissues were fixed and examined to determine the depth of cross-linking effect. The patients were followed for 1 year.
RESULTS: Histology revealed no apparent demarcation line in the cross-linked grafts; this supported a full-thickness cross-linking treatment effect. There were no intra- or postoperative complications attributed to the graft tissue. No patient developed erosion or exposure of the tube during the 1-year follow-up.
CONCLUSIONS: UV-riboflavin cross-linking of the corneal tissue patch graft material appears to be a safe modification when used in GDDS and warrants ongoing study. This method of patch graft can replace other costy methods used with GDD.

Keywords: Cornea, cross-linking, glaucoma drainage device, patch graft

How to cite this article:
Stone DU, Craven ER, Ahmad SI, AlBeshri A, Owaidhah OA. Glaucoma patch graft surgery utilizing corneas augmented with collagen cross-linking. Middle East Afr J Ophthalmol 2019;26:148-52

How to cite this URL:
Stone DU, Craven ER, Ahmad SI, AlBeshri A, Owaidhah OA. Glaucoma patch graft surgery utilizing corneas augmented with collagen cross-linking. Middle East Afr J Ophthalmol [serial online] 2019 [cited 2021 Jan 23];26:148-52. Available from: http://www.meajo.org/text.asp?2019/26/3/148/268253

   Introduction Top

Glaucoma continues to be a major cause of visual impairment and blindness worldwide, in particular, Saudi Arabia.[1],[2],[3] With an increasing absolute number of patients with glaucoma,[4],[5] as well as increasing access to modern medical and surgical care for glaucoma, it can be predicted that the number of patients undergoing glaucoma surgery will only increase. As part of a comprehensive approach to glaucoma, which should include community screening, appropriate follow-up, medical intervention, and referral for surgical intervention when indicated, measures are needed to improve the outcomes for surgical intervention and decrease the need for reoperation.

Glaucoma drainage device surgery (GDDS) has gained popularity, with outcomes equivalent to trabeculectomy in a primarily North American population.[6],[7] However, erosion of the tube through the overlying conjunctiva may occur in 5%–10% of patients.[8],[9] The risk factors for this complication have not been well elucidated but may include a history of multiple prior intraocular surgeries,[10] aphakia, uveitic glaucoma, and long postoperative use of topical steroids.[11] Surgical repair of the erosion with rotational conjunctival or buccal mucosa grafts can be effective [12] but result in increased surgical complexity and morbidity; a recent attempt at developing an improved bioengineered patch graft material was not successful.[13] Another study suggested graft-free Ahmed valve implantation through a scleral tunnel as an alternative method to reduce the risk of conjunctival erosions.[11]

Given the likely increasing volume of surgical intervention for patients with glaucoma, measures to decrease the need for repeat operations will become increasingly important. Donor corneal tissue has been utilized as a patch graft for GDDS, with positive short-term results.[14] Variations on this technique have included utilizing glycerol-preserved or gamma-irradiated corneas.[15],[16] A series of keratoprosthesis patients received donor corneas that were treated with riboflavin-ultraviolet (UV) cross-linking, with no complications attributed to the cross-linking therapy.[17] Cross-linking appears to render the corneal tissue more resistant to collagenolysis.[18],[19]In vivo corneal collagen cross-linking has over 10 years of widespread use in patients with ectatic corneal disorders, with no long-term sequelae attributed to the therapy.[20],[21]

The purpose of this study was to assess the safety and efficacy of GDDS utilizing cross-linked donor corneal tissue. This pilot study was proposed to gain insight into the logistical and technical aspects of preparing and implementing the use of cross-linked donor corneal tissue, as well as gather outcomes data in anticipation of a future masked, randomized controlled treatment trial for comparison to other currently utilized techniques.

   Materials and Methods Top

This was a prospective interventional uncontrolled pilot study, with comparison to historical controls and descriptive analysis of adverse effects or complications.

Inclusion criteria

Ten adult patients who have glaucoma are recommended to undergo GDDS with patch graft.

Exclusion criteria

Patients who are monocular or have vision <20/200 in the fellow eye are under the age of 18 years, have an active cicatrizing disease of the conjunctiva or a history of scleritis, are unable to return for the 1-year follow-up visit, are unable to provide informed consent to participate in the study, are pregnant or anticipate becoming pregnant during the perioperative period, are deemed by the treating physician to be a poor candidate for the study for any reason, or would be expected to have a better outcome with a procedure other than GDDS.

Patients who elected to participate and provided informed consent underwent the surgery according to their treating physician's usual technique, with the exception of the tissue to be used as the patch graft over the tube during GDDS.

Technique for ultraviolet-riboflavin cross-linking

Donor corneas for endothelial keratoplasty were prepared by the corneal surgeon utilizing an artificial chamber and Moria keratome, with a goal posterior lamellar thickness of 100–150 μ (resulting in an anterior lenticule of approximately 300 μ after epithelial removal). The anterior lenticule was replaced in the transport media (Optisol GS, Bausch and Lomb, Bridgewater, NJ, USA) and was refrigerated at 4°C; the donor rim was sent for routine bacterial and fungal cultures. Within 36 h of lamellar graft cutting, the corneal graft for study use was treated with UV cross-linking. Sterile technique was utilized, and the UV-riboflavin cross-linking was performed by a single corneal surgeon Donald U. Stone (DUS). The tissue was placed in a Brightbill ceramic block and was soaked in a solution of 0.1% riboflavin (VibeX, Avedro, Waltham, MA, USA) for 15 min or until full-thickness saturation of the tissue was noted and then was treated with 15 min of pulsed 8 mW/cm 2 UV light at 370 nm utilizing the Avedro KXL device [Figure 1]. The treated tissue was then bisected into two semicircle sections for use in two recipients and returned to the transport media in new sterile containers; the tissue was refrigerated at 4°C until utilization. Approximately 1 h before the surgery, the tissue was taken to the operating theater and was allowed to reach room temperature. Two of the hemisections were mounted in optimum temperature cutting compound and were frozen for sectioning (to avoid distortion associated with formalin fixation) and then were evaluated with histopathology for evidence of the depth of cross-linking effect or demarcation line.
Figure 1: Corneal graft receiving ultraviolet irradiation after riboflavin soaking

Click here to view

The GDDS was performed per the surgeon's standard technique with the insertion of the tube into the anterior chamber just posterior to the limbus. The “half-moon” or semicircular graft was positioned over the tube and was secured with sutures to the sclera and direct conjunctival closure over the tube and tissue graft. Postoperative antibiotics, corticosteroids, and ocular antihypertensives were also used at the surgeon's discretion.

Follow-up and data acquisition

Patients were evaluated at 1 day and again within 1 week postoperatively. The study visits were scheduled at 3, 6, 12, 24, and 36 months postsurgery, with a ± 1 month window for each visit. Interim visits were at the surgeon's discretion. The primary endpoint was exposure of the glaucoma tube. Other data collected included any surgical complications, delays in wound healing or unexpected inflammation, intraocular pressure, anterior chamber cell, and flare as per the systematic uveitis nomenclature,[22] and other ocular findings that are worsening from the preoperative state or deemed by the treating surgeon to be unexpected in a typical postoperative patient. Any systemic adverse effects in the perioperative and postoperative period were also documented. Slit-lamp photography was obtained from the surgical site at each postoperative visit.

   Results Top

All tissues exhibited visible full-thickness riboflavin saturation after 15 min of soaking. Masson trichrome staining [Figure 2] and hematoxylin and eosin staining (data not shown) revealed no demarcation line in either specimen, consistent with full-thickness treatment effect.
Figure 2: Cornea graft after accelerated cross-linking; no demarcation line is noted (Masson trichrome, ×10)

Click here to view

Each of the 10 participants completed 1 year of follow-up; there were no episodes of tube erosion or wound dehiscence noted. [Table 1] details the diagnosis and postoperative findings of each patient. One patient in which the graft was not sutured to the sclera developed a partial dislocation of the graft, but the tube remained covered. One patient later developed microbial keratitis that was deemed unrelated to the glaucoma surgery or graft implant. No local or systemic adverse effects attributed to the corneal graft were noted. The typical appearance of the graft at 1 day, 3 months, and 1 year after implantation is demonstrated in [Figure 3] and [Figure 4].
Table 1: Demographic and clinical information for the study participants

Click here to view
Figure 3: One day postoperative appearance

Click here to view
Figure 4: (a) Three-month postoperative appearance. (b) One-year postoperative appearance

Click here to view

   Discussion Top

The ideal graft for preventing erosion or exposure after GDDS remains to be determined. This study evaluated a protocol that utilized the anterior corneal lenticule from Descemet's stripping automated endothelial keratoplasty surgery, augmented it with UV-riboflavin cross-linking, and provided two patch grafts from each donor tissue (in addition to the primary use for endothelial keratoplasty). No difficulties were noted by the treating surgeons, and no patients developed a postoperative infection or other complications related to the patch graft.

The protocol for tissue preparation was extrapolated from the current knowledge of in vivo studies. Full-thickness saturation of a patient's cornea is typically confirmed by the presence of riboflavin flare in the anterior chamber; the corneal tissue in this study rapidly demonstrated full-thickness saturation (demonstrated by visible yellow riboflavin) well before the 15 min predetermined time point. We propose that the 300-μ thickness of the grafts, as well as exposure of the corneal stroma to riboflavin on the anterior, lateral, and posterior surfaces contributed to rapid saturation; it is unlikely that additional time for riboflavin loading is required, and future studies could delineate the minimum time necessary. Accelerated UV irradiation has also been studied in ectatic corneal diseases; it appears that very brief treatment times (such as 2 min,[18] 3 min 40 s,[23] or 5 min [24]) may result in a less robust cross-linking effect. However, increased fluences with more brief treatment times of 5[25],[26] and 10 min [27],[28] have demonstrated similar clinical effects to the typical 30 min exposure time of the Dresden protocol.[29] These studies collectively suggest that a 10-min accelerated treatment interval would be adequate; therefore, we adopted a 15-min treatment time to ensure that adequate cross-linking was achieved.

Tube erosion or exposure after GDDS often presents long after the primary implantation; any study that evaluates this endpoint should be adequately powered and allow for an appropriate length of observation. This pilot study aimed to evaluate the protocol for tissue preparation and observe any unanticipated adverse effects, with encouraging results, but care should be taken before extrapolating these findings to predict long-term erosion rates or relative risks of erosion when compared to alternative graft techniques. The subjects of this study will continue to be observed for the development of tube exposure.

   Conclusions Top

In summary, this technique of UV-riboflavin cross-linking appears to effectively and safely augment corneal tissue, providing two patch grafts from each donor cornea. The lack of technical difficulties or surgical complications suggests that this technique should be compared to the current standard therapies; a prospective, randomized comparative treatment trial is needed to determine if this method of graft augmentation results in a meaningful reduction in GDD erosion rates.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Khairallah M, Kahloun R, Flaxman SR, Jonas JB, Keeffe J, Leasher J, et al. Prevalence and causes of vision loss in North Africa and the Middle East: 1990-2010. Br J Ophthalmol 2014;98:605-11.  Back to cited text no. 1
Tabbara KF, Ross-Degnan D. Blindness in Saudi Arabia. JAMA 1986;255:3378-84.  Back to cited text no. 2
Al-Shaaln FF, Bakrman MA, Ibrahim AM, Aljoudi AS. Prevalence and causes of visual impairment among Saudi adults attending primary health care centers in Northern Saudi Arabia. Ann Saudi Med 2011;31:473-80.  Back to cited text no. 3
[PUBMED]  [Full text]  
Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY, et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis. Ophthalmology 2014;121:2081-90.  Back to cited text no. 4
Kapetanakis VV, Chan MP, Foster PJ, Cook DG, Owen CG, Rudnicka AR, et al. Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): A systematic review and meta-analysis. Br J Ophthalmol 2016;100:86-93.  Back to cited text no. 5
Gedde SJ. Results from the tube versus trabeculectomy study. Middle East Afr J Ophthalmol 2009;16:107-11.  Back to cited text no. 6
[PUBMED]  [Full text]  
Gedde SJ, Schiffman JC, Feuer WJ, Herndon LW, Brandt JD, Budenz DL, et al. Three-year follow-up of the tube versus trabeculectomy study. Am J Ophthalmol 2009;148:670-84.  Back to cited text no. 7
Zalta AH. Long-term experience of patch graft failure after ahmed glaucoma valve® surgery using donor dura and sclera allografts. Ophthalmic Surg Lasers Imaging 2012;43:408-15.  Back to cited text no. 8
Lind JT, Shute TS, Sheybani A. Patch graft materials for glaucoma tube implants. Curr Opin Ophthalmol 2017;28:194-8.  Back to cited text no. 9
Trubnik V, Zangalli C, Moster MR, Chia T, Ali M, Martinez P, et al. Evaluation of risk factors for glaucoma drainage device-related erosions: A retrospective case-control study. J Glaucoma 2015;24:498-502.  Back to cited text no. 10
Zhou D, Zhou XY, Mas-Ramirez AM, Kim C, Juzych MS, Nassiri N, et al. Factors associated with conjunctival erosions after ahmed glaucoma valve implantation. J Ophthalmic Vis Res 2018;13:411-8.  Back to cited text no. 11
[PUBMED]  [Full text]  
Low SA, Rootman DB, Rootman DS, Trope GE. Repair of eroded glaucoma drainage devices: Mid-term outcomes. J Glaucoma 2012;21:619-22.  Back to cited text no. 12
Nagi KS, Cumba RJ, Bell NP, Blieden LS, Chuang AZ, Mankiewicz KA, et al. Short-term outcomes of KeraSys patch graft for glaucoma drainage devices: A case series. J Ophthalmol 2013;2013:784709.  Back to cited text no. 13
Spierer O, Waisbourd M, Golan Y, Newman H, Rachmiel R. Partial thickness corneal tissue as a patch graft material for prevention of glaucoma drainage device exposure. BMC Ophthalmol 2016;16:20.  Back to cited text no. 14
Daoud YJ, Smith R, Smith T, Akpek EK, Ward DE, Stark WJ, et al. The intraoperative impression and postoperative outcomes of gamma-irradiated corneas in corneal and glaucoma patch surgery. Cornea 2011;30:1387-91.  Back to cited text no. 15
Wigton E, C Swanner J, Joiner W, Feldman A, McGwin G Jr., Huisingh C, et al. Outcomes of shunt tube coverage with glycerol preserved cornea versus pericardium. J Glaucoma 2014;23:258-61.  Back to cited text no. 16
Kanellopoulos AJ, Asimellis G. Long-term safety and efficacy of high-fluence collagen crosslinking of the vehicle cornea in Bnoston keratoprosthesis type 1. Cornea 2014;33:914-8.  Back to cited text no. 17
Kanellopoulos AJ, Loukas YL, Asimellis G. Cross-linking biomechanical effect in human corneas by same energy, different UV-A fluence: An enzymatic digestion comparative evaluation. Cornea 2016;35:557-61.  Back to cited text no. 18
Arafat SN, Robert MC, Shukla AN, Dohlman CH, Chodosh J, Ciolino JB, et al. UV cross-linking of donor corneas confers resistance to keratolysis. Cornea 2014;33:955-9.  Back to cited text no. 19
Spoerl E, Mrochen M, Sliney D, Trokel S, Seiler T. Safety of UVA-riboflavin cross-linking of the cornea. Cornea 2007;26:385-9.  Back to cited text no. 20
Raiskup F, Spoerl E. Corneal crosslinking with riboflavin and ultraviolet A. Part II. Clinical indications and results. Ocul Surf 2013;11:93-108.  Back to cited text no. 21
Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop. Am J Ophthalmol 2005;140:509-16.  Back to cited text no. 22
Choi M, Kim J, Kim EK, Seo KY, Kim TI. Comparison of the conventional dresden protocol and accelerated protocol with higher ultraviolet intensity in corneal collagen cross-linking for keratoconus. Cornea 2017;36:523-9.  Back to cited text no. 23
Ng AL, Chan TC, Cheng AC. Conventional versus accelerated corneal collagen cross-linking in the treatment of keratoconus. Clin Exp Ophthalmol 2016;44:8-14.  Back to cited text no. 24
Razmjoo H, Peyman A, Rahimi A, Modrek HJ. Cornea collagen cross-linking for keratoconus: A comparison between accelerated and conventional methods. Adv Biomed Res 2017;6:10.  Back to cited text no. 25
Hashemi H, Fotouhi A, Miraftab M, Bahrmandy H, Seyedian MA, Amanzadeh K, et al. Short-term comparison of accelerated and standard methods of corneal collagen crosslinking. J Cataract Refract Surg 2015;41:533-40.  Back to cited text no. 26
Sadoughi MM, Einollahi B, Baradaran-Rafii A, Roshandel D, Hasani H, Nazeri M, et al. Accelerated versus conventional corneal collagen cross-linking in patients with keratoconus: An intrapatient comparative study. Int Ophthalmol 2018;38:67-74.  Back to cited text no. 27
Cummings AB, McQuaid R, Naughton S, Brennan E, Mrochen M. Optimizing corneal cross-linking in the treatment of keratoconus: A comparison of outcomes after standard – And high-intensity protocols. Cornea 2016;35:814-22.  Back to cited text no. 28
Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 2003;135:620-7.  Back to cited text no. 29


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
    Materials and Me...
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded44    
    Comments [Add]    

Recommend this journal