Seamless Conjunctiva and AM-UC Graft Integration Helps Minimize Tube Exposure

Study says amniotic membrane-umbilical cord (AM-UC) tissue offers an alternative to pericardium for safe and stable tube shunt coverage

By Mohamed S. Sayed, MD 

During the past 10 years, we have seen increasing utilization of glaucoma drainage devices (GDDs) by glaucoma surgeons in the management of uncontrolled glaucoma, thanks, in part, to the results of the Tube Versus Trabeculectomy (TVT) study.¹ The incorporation of tube shunt surgery earlier on in the surgical treatment paradigm has likely helped reduce the incidence of trabeculectomy-associated complications, such as hypotony and bleb-related complications. I see this first-hand in my practice, as I get numerous surgical referrals of glaucoma patients who need revisional surgery or a primary operation for uncontrolled glaucoma. Although the recent introduction of minimally invasive glaucoma surgery (MIGS) has rendered surgical treatment of glaucoma simpler, less time-consuming, and relatively safer for many patients, I still typically perform between 5 and 10 tube shunt surgeries per week for patients with advanced glaucoma.

Although tube shunt surgery is generally successful in preventing the progression to blindness that can occur in patients with glaucoma, it is still associated with significant complications that can’t be ignored, including motility disturbances, corneal endothelial cell loss, and tube exposure.² 

The TVT study demonstrated that the rate of tube erosion or exposure was 5% at 5 years.³ A retrospective review found that a history of concomitant ocular surgery, at the time of the tube’s placement, as well as a history of smoking, dry eye disease, or pseudoexfoliation, might also predispose a patient to tube exposure.⁴ A more recent study⁵ suggested that younger age and inflammation may be significant risk factors for tube exposure after drainage implant surgery, as well. 

Tube Exposure and Patch Grafts
Tube exposure is a serious postoperative complication that increases the risk of sight-threatening intraocular endophthalmitis.^6,7 I’m always on the lookout for new and better ways to perform tube shunt surgery to minimize this complication. 

Allogenic patch grafts made of sclera, pericardium, and cornea reduce the rate of tube exposure, but they are associated with progressive thinning and silent melt, which may be due to immune-related processes.^8-10 Amniotic membrane (AM) tissue, and buccal mucosal membrane,^11,12 are useful when primary conjunctival closure is precluded by significant scarring or melting.

Investigators suspected that graft thinning might be the result of poor host-tissue integration. Prior research demonstrated the short-term safety and efficacy of a 300- mm thick AM, harvested from the amniotic sac near the umbilical cord (UC).¹³  

In that study, tube exposure rate was 2.3%, and anterior segment OCT demonstrated a well-integrated conjunctiva-AM bilayer that maintained its thickness over time. Hence, we theorized that a thicker version of AM, with high tensile strength and low immunogenicity, might provide good tectonic support and avert immune-related graft thinning and melting.¹⁴

To ascertain whether our theories were valid, we initiated a randomized study to compare the long-term safety and efficacy of AM umbilical cord (AM-UC) tissue with pericardium patch grafts to reduce glaucoma shunt tube exposure.¹⁵ The study group received a single layer of AM-UC (Amnioguard; BioTissue, Miami, FL) and the control group received pericardium (Tutoplast; IOP, Costa Mesa, CA) patch graft. The thickness of both AM-UC and pericardium ranged from 400 mm to 500 mm. 

A total of 81 eyes of 81 patients (50 women, 31 men) with a mean age of 67 underwent GGD implantation using Baerveldt (72 patients) or Ahmed valve (9 patients). Tubes were covered with AM-UC (41 patients) or pericardium (40 patients), and follow-up time ranged from 13 to 40 months. Tube exposure occurred in 1 eye in the AM-UC group 3 months post-operatively, and in 2 eyes in the pericardium group at 2 and 6 months postoperatively. Sequential anterior segment OCT showed better host-tissue integration and significantly less graft thinning in the AM-UC group. Early graft thinning – at or before 3 months – occurred in 5 eyes in the AM-UC group, and in 17 eyes in the pericardium group. Late graft thinning occurred in 2 eyes in the AM-UC group and in 11 eyes in the pericardium group. No evidence of graft rejection or infection was associated with the patch grafts in either group.

The study results demonstrated the long-term safety and efficacy of AM-UC tissue in reducing tube exposure and graft thinning. The anterior segment OCT findings support our hypotheses that AM-UC tissue not only may provide strong tectonic support and avert the possible immune-related graft melting but also could promote improved host-tissue integration to prolong graft survival. 

Amniotic Membrane Advantages
Our research indicates that there could be several potential benefits associated with the use of AM-UC tissue grafts in tube shunt surgeries. First, it is at least equivalent in safety and efficacy to pericardium in preventing tube exposure. Second, it integrates better with the host conjunctiva. Third, it provides a better cosmetic appearance. 

Efficacy:  AM-UC was equivalent in safety and efficacy to pericardium in preventing tube exposure throughout the study period. The tube exposure rate was similar in the AM-UC group and pericardium group; and the incidence and timing of tube exposures were comparable with those reported in the literature.^{9,10,13,16,17} A meta-analysis of 38 studies demonstrated a tube exposure rate of 2.0% with an average follow-up of 26 months.¹⁸ In our study, which had follow-up of 29 months, tube exposure occurred within 2 to 6 months and was not preceded by progressive graft thinning in either group. 

Aesthetics: Glaucoma surgery is not a cosmetic procedure, but scleral pericardium appears like a white patch on the eye and patients are often dismayed by its appearance. For patients who prefer that people not know that they’ve had this procedure, a graft that is imperceptible is appropriate. In our study, the cosmetic appearance of the AM-UC tissue was superior to pericardium because of graft translucency, particularly when adequate covering by the eyelid is not possible such as in inferonasal tube placement. In everyday clinical practice, the translucency of the AM-UC graft, in addition to being more aesthetically appealing, allows direct visualization of the underlying tube. This permits easy laser suture lysis when needed to control elevated pressure before the ligature dissolves, when necessary. This is not possible when using opaque patch graft material such as pericardium or sclera. Cornea is also imperceptible and therefore more aesthetically appealing than pericardium.

Integration: Our results revealed better graft-host integration with the AM-UC tissue. This anterior segment OCT image (Figure 1) from our study, shows a cut section 90° perpendicular on the tube. The boundary between the overlying conjunctiva and the underlying AM-UC graft cannot be defined, which suggests excellent host tissue/AM-UC integration. Theoretically, the more integrated the graft material into the host conjunctiva the more stability and tensile strength the conjoined tissue will have, and the less chance of exposure. 

Poor graft-host tissue integration is shown in Figure 2. In this anterior segment OCT, we see a large space between the conjunctiva and the patch graft. In our study, we saw this repeatedly among the patients who received pericardium grafts. That poor integration may result in erosion or exposure. If patients were followed longer, it’s possible that we would ultimately see that this graft material, which did not integrate well with the conjunctiva, may get progressively thinner. This is, in part, supported by our findings, which showed that the pericardium patch grafts continue to become progressively thinner.

Graft Thinning: According to the literature, AM-UC tissue used for primary tube coverage represents a reasonably low rate of graft thinning as measured both clinically and with anterior segment OCT.10,18 In our study, the incidence of early graft thinning was significantly lower in the AM-UC group, at 12%, compared with the pericardium group, at 42.5%; and the incidence of late progressive graft thinning also was significantly lower in the AM-UC group, at 4.9%, compared with the pericardium group, at 27.5%. Furthermore, graft thinning was insignificant after 12 months in the AM-UC group without further incidence of tube exposure. From my perspective, thinning of the pericardium graft material was not the same as thinning of the AM-UC in our study because thinning of pericardium preceded tube exposure, whereas thinning of the AM-UC translated into better integration. 

In conclusion, AM-UC grafts are well tolerated and offer an alternative to pericardium for safe and stable tube shunt coverage. While we have not yet integrated AM-UC tissue grafts into our surgical armamentarium, I’m excited about the potential for this tissue because of all the theoretical benefits revealed in our study. I believe this is something that offers long-term benefits, particularly because of the excellent host tissue/patch graft integration. 

Mohamed S. Sayed, MD is a glaucoma surgeon with The Glaucoma Institute at New Vision Eye Center, Vero Beach, FL, and member of the Teaching Faculty, Florida State University College of Medicine, Fort Pierce Regional Campus.
Contact: [email protected]
Disclosure: Dr. Sayed has no financial disclosure to report.

References

1. Gedde SJ, Schiffman JC, Feuer WJ, et al. Tube versus Trabeculectomy Study Group. Treatment outcomes in the Tube Versus Trabeculectomy (TVT) study after five years of follow-up. Am J Ophthalmol.2012; 153(5):789-803. 
2. Gedde SJ, Parrish RK, Budenz DL. et al. Update on Aqueous Shunts. Experimental Eye Research. 2011;93: 284-290.
3. Gedde SJ, Herndon LW, Brandt JD, et al; Tube Versus Trabeculectomy Study Group. Postoperative complications in the Tube Versus Trabeculectomy (TVT) study during five years of follow-up. Am J Ophthalmol. 2012;153(5):804-814. 
4. Trubnik V, Zangalli C, Moster MR, et al. Evaluation of risk factors for glaucoma drainage device-related erosions: a retrospective case-control study. J Glaucoma. 2015 Sep;24(7):498-502.
5. Chaku M, Netland PA, Ishida K, et al. Risk factors for tube exposure as a late complication of glaucoma drainage implant surgery. Clin Ophthalmol.2016;10: 547-553.
6. Al-Torbak AA, Al-Shahwan S, Al-Jadaan I, et al. Endophthalmitis associated with the Ahmed Glaucoma Valve implant. Br J Ophthalmol. 2005;89:454–458. 
7. Gedde SJ, Scott IU, Tabandeh H, et al. Late endophthalmitis associated with glaucoma drainage implants. Ophthalmology. 2001;108:1323–1327.
8. Stewart WC, Kristoffersen CJ, Demos CM, et al. Incidence of conjunctival exposure following drainage device implantation in patients with glaucoma. Eur J Ophthalmol. 2010;20(1): 124-130.
9. Lama PJ, Fechtner RD. Tube erosion following insertion of a glaucoma drainage device with a pericardial patch graft. Arch Ophthalmol. 1999;117(9):1243-1244.
10. Smith MF, Doyle JW, Ticrney Jr JW. A comparison of glaucoma drainage implant tube coverage. J Glaucoma. 2002;11(2):143-147.
11. Rootman DB, Trope GE, Rootman DS. Glaucoma aqueous drainage device erosion repair with buccal mucous membrane grafts. J Glaucoma.2009;18(8):618-622.
12. Ainsworth G, Rotchford A, Dua HS, et al. A novel use of amniotic membrane in the management of tube exposure following glaucoma tube shunt surgery. Br J Ophthalmol. 2006;90(4):41741-41749.
13. Anand A, Sheha H, Teng CC, et al. Use of amniotic membrane graft in glaucoma shunt surgery. Ophthalmic Surg Lasers Imaging.2011;42(3):184-189.
14. Liu J, Sheha H, Fu Y, et al. Update on amniotic membrane transplantation. Expert Rev Ophthalmol. 2010;5(5):645-661.
15. Sheha H. Tello C, Al-Aswad AL. Outcomes of the Shunt Tube Exposure Prevention Study: A Randomized Clinical Trial. Ophthalmology Glaucoma.2019;2(6):392-401. 
16. Wigton E, Swanner JC, Joiner W, et al. Outcomes of shunt tube coverage with glycerol preserved cornea versus pericardium. J Glaucoma. 2014;23(4):258-261.
17. Ekici F, Moster MR, Cvintal V, et al. Tube shunt coverage with gamma-irradiated cornea allograft (VisionGraft). Clin Ophthalmol. 2015;9:751-755.
18. Raviv T, Greenfield DS, Liebmann JM, et al. Pericardial patch grafts in glaucoma implant surgery. J Glaucoma. 1998;7(1): 27-32.

Photo captions:

Figure 1: OCT reveals excellent graft-host integration with AM-UC graft. 

Figure 2:  OCT shows poor graft-host tissue integration with pericardium graft.

Figures 3 and 4: Bandage contact lens covering the exposed tube, and anterior segment OCT showing the contact lens over the exposed tube and with the erosion of the patch graft material and overlying conjunctiva.