Middle East African Journal of Ophthalmology

: 2019  |  Volume : 26  |  Issue : 3  |  Page : 148--152

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

Donald U Stone1, Earl Randy Craven1, Sameer I Ahmad2, Ali AlBeshri3, Ohoud A Owaidhah3,  
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

Correspondence Address:
Dr. Ohoud A Owaidhah
King Khaled Eye Specialist Hospital, P.O. Box 7191, Riyadh 11462
Saudi Arabia


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.

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;26:148-152

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 2020 Jan 25 ];26:148-152
Available from: http://www.meajo.org/text.asp?2019/26/3/148/268253

Full Text


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

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}

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.


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}

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}{Figure 3}{Figure 4}


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.


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.


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