February 2019


Facing complicated glaucoma cases
Glaucoma surgery and managing the corneal endothelium

by Stefanie Petrou Binder, MD, EyeWorld Contributing Writer

Figures 1 and 2. A 2.4-millimeter keratome is used to create a wound angle for the stent followed by lidocaine and viscoelastic.

Figure 3. On gonioscopy you can see several rings of the stent are visible and it is near the cornea.

Figure 4. Additional viscoelastic is used to create space above and below the stent and to protect the cornea during removal.

Figure 5. Large MST scissors are then used to trim the stent. The angle of approach is very important in order to avoid trauma to the cornea and iris and to avoid moving the stent to the side and creating a cyclodialysis cleft. In this case the wound needed to be enlarged slightly to provide an optimal angle.

Figure 6. MST graspers are then used to remove the stent.

Figure 7. On gonio you can see the stent is flush with the angle and away from the cornea.
Source (all): John Berdahl, MD

Glaucoma patients will frequently have a reduced endothelial cell count due to various changes that come along with the disease. Glaucoma surgery, which is performed to reduce IOP in these individuals, will likely compound the problem by causing further endothelial cell loss. The ensuing corneal decompensation adversely affects vision and is best addressed by Descemet’s membrane endothelial keratoplasty (DMEK) or Descemet’s stripping endothelial keratoplasty (DSEK), procedures that replace the endothelium using donor corneal endothelium. Patients will often require both, however, combining glaucoma surgery with DMEK/DSEK warrants a great deal of caution.
EyeWorld spoke to glaucoma specialists Ramesh Ayyala, MD, FRCS, University of South Florida, Tampa, Florida, and John Berdahl, MD, Vance Thompson Vision, Sioux Falls, South Dakota, about what they have learned with respect to managing glaucoma in the setting of a damaged corneal endothelium in patients with glaucoma.

The endothelium

The corneal endothelium is a single layer of squamous cells lining the posterior surface of the cornea that plays a unique role in the regulation of hydration through a system of active ion transport. When this regulation becomes impaired through damage to the endothelium, corneal cells can become edematous and indurated, leading to a loss in transparency and compromising clear vision. As endothelial cells do not regenerate, it is paramount to protect this fragile layer of cells.
Normal corneas lose 0.6% of endothelial cells (2,500–3,000 cells per square millimeter in adults) per year. In conditions that predispose to endothelial cell damage, such as glaucoma, endothelial cell loss is enhanced. Glaucoma—and its management—can have deleterious effects on the corneal endothelium. Increased IOP, mechanical forces, and the aqueous environment have been implicated in endothelial cell loss, as have glaucoma surgery or a history of glaucoma surgery, which present a particularly significant risk for endothelial cell health and cornea transplant graft survival.1

Endothelial cell damage

“Corneal issues in glaucoma patients mostly have to do with endothelial decomposition, with resulting corneal edema,” Dr. Ayyala told EyeWorld. “Corneal diseases and glaucoma are seen together in almost 50% of glaucoma patients.”
Precisely how the endothelium is damaged in glaucomatous eyes is incompletely understood. In a published study he conducted on penetrating keratoplasty and glaucoma, Dr. Ayyala observed that glaucoma issues in corneal patients were multifactorial in origin, usually due to angle closure, steroid response, and inflammation.2
In his experience, endothelial cell damage can result from glaucoma surgery, as well as from bouts of acute or sustained elevated intraocular pressures. “Acute angle closure glaucoma is an outstanding example of increased IOP that can cause damage to endothelial cells,” Dr. Ayyala explained. “Some glaucoma surgeries increase the risk of corneal decompensation more than others. For instance, glaucoma drainage devices (GDD) are associated with a 20–30% risk of corneal decompensation. The exact reason is unknown. Direct contact of the silicone tube of a GDD with the corneal endothelium can cause endothelial cell death and sequential endothelial decompensation. In the majority of the cases, the tube is kept away from corneal endothelium, but it still develops corneal decompensation. We think that this is due to a nutritional deficiency as the aqueous humor circulation in the anterior chamber is disrupted. Rabbit studies we conducted suggested significant hypoxia and nutritional deficiency in the GDD eye compared to the unoperated eye.”3
The corneal endothelium is critical in maintaining a healthy and clear cornea. Corneal endothelial cells have a significant reserve function but preservation of these cells is paramount due to their limited regenerative capacity. Understanding how glaucoma and glaucoma surgery impact the endothelium is important for protecting corneal clarity in affected patients. “Most devices that we put into the anterior chamber are glaucoma devices, however, sometimes phakic IOLs are placed there, too,” Dr. Berdahl explained in his interview with
EyeWorld. “If these devices come into contact with the corneal endothelium, it will lead to a decreased endothelial cell count. We also know that low intraocular pressures alone, hypotony, can cause a loss of endothelial cells. I think we have to be extra diligent in making sure devices are not in contact, or in too close proximity, to the corneal endothelium. We also need to ensure that the surgeries that we are doing are at a very low likelihood of creating hypotony.”

Combining surgeries

Ophthalmic surgeons always need to take the altered endothelium into account in patients with glaucoma or with a history of glaucoma surgery. Often individuals will require both glaucoma surgery and partial or full thickness keratoplasty. According to Dr. Berdahl, the biggest challenge in these eyes is how the anterior chamber will behave during surgery. “The anterior chamber is the challenge. You have to retain the air bubble long enough to ensure attaching the graft,” he said. “I generally put some viscoelastic in the lumen of the tube shunt or the ostium of the trabeculectomy in an effort to keep air in the anterior chamber and not going into the bleb. This is only modestly successful, so I do think that endothelial transplants are more challenging in these eyes. Some surgeons advocate for DSEK only, although there is literature to support that DMEK does just as well in these scenarios. I generally make a judgment call on how the eye is going to behave, and if I think it is going to be more difficult, then I do a DSEK,” Dr. Berdahl said.
In Dr. Ayyala’s extensive experience with penetrating keratoplasty and glaucoma over many years that includes a number of publications, what a successful surgery comes down to is eye pressure and the donor corneal graft. “I had the opportunity to operate on a lot of penetrating keratoplasty glaucoma (PKPG) cases over the past 20 years. There are two main things to consider in these cases; the first is IOP control and the second is saving the graft. One at the exclusion of the other is not good for the patient,”4 he said.
According to Dr. Ayyala, most glaucoma surgeries are going to be detrimental to the survival of the corneal graft. “GDD controls IOP but increases the risk of graft rejection by 30–50%. Cyclo-destructive procedures have unpredictable IOP results with an increased risk of graft rejection. This applies also to micropulse, which in our experience in these complex cases has been less than POAG patients with regard to IOP control.5 MIGS might work, but once you enter the anterior chamber, graft rejection is a risk. Trab or trab-like procedures are good for graft survival and IOP control but contraindicated (relative) in the presence of contact lens use secondary to the risk of infection. Finally, canaloplasty ab externo with 10.0 Prolene is for me the best procedure both for IOP control and graft survival, with no concerns for contact lens related issues, as there is no bleb. I have a series of patients in this category over the years with long-term success, and it is my preferred method in patients with PKPG,” Dr. Ayyala said.
When it comes to combining these surgeries, experience counts. Dr. Berdahl thinks that endothelial/corneal replacement procedures and glaucoma surgery can be combined, however, with caution. “I have done a number of iStents [Glaukos, San Clemente, California] at the same time as DMEK. However, you need to realize that there can be reflux and heme, and that can make doing a DMEK very difficult,” he explained. “The more conservative play is a DSEK. We have presented our data showing that it can be done successfully.6 One of the things I like about the combined approach is that I am less worried about steroid-induced IOP spikes when there is a trabecular bypass stent. I would suggest using the procedure that is least likely to induce hyphema. If you’re doing it in combination with a cataract surgery, I would suggest doing the glaucoma procedure prior to removing the cataract so that the heme can be washed away and bleeding likely stopped by the time the endothelial transplant occurs.”
The study, for which he was a co-investigator, involved combining DMEK or DSEK with a trabecular micro-bypass stent replacement, along with cataract surgery in 15 patients with Fuchs’ endothelial dystrophy, open angle glaucoma, and visually significant cataract. His results showed a visual improvement to 20/40 and by at least two lines in 13 of the study patients, a decrease in medications from 0.9 to 0.7 (p=.8), and an average IOP decrease of 1.7 mm Hg. Only one eye required a graft exchange and another required a glaucoma valve to better control IOP.6
Each surgeon will have an individual approach to highly complicated surgical scenarios. Dr. Ayyala does not advise combining DSEK and glaucoma surgery due to the difficulties in maintaining the air bubble in the anterior chamber needed to float the graft, particularly when the glaucoma surgery in question is a trabeculectomy or GDD. On the other hand, canal based procedures such as the iStent and Kahook Dual Blade (New World Medical, Rancho Cucamonga, California) may be combined with DSEK, although it is not always advisable since these procedures are associated with reflex blood into the anterior chamber, which will complicate DSEK surgery. Dr. Ayyala follows his patients via good clinical evaluation, and he recommends serial endothelial cell counts.

How to monitor

“We monitor surgical glaucoma patients clinically and visually and on their regular glaucoma follow-up visits,” Dr. Berdahl said. “We will do an occasional pachymetry and endothelial cell count if the vision is suboptimal, which can be helpful, but I don’t think that there is an algorithmic approach to monitoring the corneal endothelium. The best thing to protect the corneal endothelium is good surgical technique, avoiding hypotony, and ensuring that any devices in the anterior chamber are far away from the corneal endothelium,” he said.


1. Janson BJ, et al. Glaucoma-associated corneal endothelial cell damage: a review. Surv Ophthalmol. 2017;63:500–506.
2. Ayyala RS. Penetrating keratoplasty and glaucoma. Surv Ophthalmol. 2000;45:91–105.
3. Williamson BK, et al. The effects of glaucoma drainage devices on oxygen tension, glycolytic metabolites, and metabolomics profile of aqueous humor in the rabbit. Transl Vis Sci Technol. 2018;7:14.
4. Ayyala RS, et al. Comparison of mitomycin C trabeculectomy, glaucoma drainage device implantation, and laser neodymium:YAG cyclophotocoagulation in the management of intractable glaucoma after penetrating keratoplasty. Ophthalmology. 1998;105:1550–6.
5. Yelenskiy A, et al. Patient outcomes following micropulse transscleral cyclophotocoagulation: intermediate-term results. J Glaucoma. 2018;27:920–925.
6. Stunkel M, et al. Outcomes of partial-thickness corneal transplantation combined with trabecular bypass stent implantation and cataract surgery. Presented at the 2017 ASCRS•ASOA Symposium & Congress.

Editors’ note: Dr. Berdahl has financial interests with Alcon (Fort Worth, Texas), Glaukos, New World Medical, and CorneaGen (Seattle). Dr. Ayyala has no financial interests related to his comments.

Contact information

: rayyala@health.usf.edu
Berdahl: johnberdahl@gmail.com

Glaucoma surgery and managing the corneal endothelium Glaucoma surgery and managing the corneal endothelium
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