Expert panel tackles challenging cornea cases

Roundtable Participants

Arun C. Gulani, MD: It is important to determine the visual impact of the epithelial ingrowth besides looking for progression, which can be determined by my retroillumination technique that I had described in 1996. The epithelial ingrowth may stay stationary in the periphery, and it is best left alone if nonprogressive unless there is the obvious break in the LASIK flap edge creating a space for epithelium to grow continuously. Once determined that the epithelial ingrowth is either progressive or visually impactful, it needs to be addressed from all three layers: the LASIK flap itself, the stromal bed and the underside of the flap. Closure of the peripheral edge if detected is important and can be done with glue, and in some aggressive cases referred to me, I have tacked down the LASIK flap edge with radial sutures diametrically opposite to the hinge to avoid inducing astigmatism.

McDonald: Believe it or not, this patient is easygoing and OK with her vision. What is upsetting her is that she has been taken to the operating room so many times to try to get rid of this.

I always had a rule that if the epithelial ingrowth extended more than 2 mm in any direction, then the aqueous could not make its way around that obstruction. In other words, because the cornea breathes air and eats aqueous, the aqueous would come up from the anterior chamber, hit the obstruction and not be able to swim around a 2-mm obstruction. If it were smaller than that, it always seemed to work out. But this patient’s flaps showed no sign of stress. She has no superficial punctate keratitis (SPK), and she does not have boggy epithelium. She is making me rethink my 2-mm rule because these are the healthiest flaps I have ever seen. And because she is OK with 20/40-2 in the right eye and 20/40+ 2 in the left eye, I am watching her every few months. If I see the flaps breaking down, I will lift the flap — I find that most of the ingrowth is stuck to the underbelly of the flap — to get rid of the ingrowth and then carefully make sure none of it drips onto the bed. I would use dilute alcohol and then, as Dr. Trattler mentioned, suture this down tightly. Most ingrowth, in my opinion, comes from pinching. The surgeon pinches the flap to move it. That area stays compressed or pinched for hours after the surgery, and that is where the epithelium goes in. So, I have never touched a flap. I flip it with closed forceps, but I have never actually grabbed the edge of the flap. I will update you next year, but so far, I have told the surgeon, “Let’s do nothing.”

I have tried to shoot at epithelial ingrowth with an Nd:YAG laser. Has anybody here ever tried shooting an ingrowth with the YAG?

Brandon D. Ayres, MD: I don’t think it helped all that much. Maybe it helps for just those small islands, but that is about it.

Jai G. Parekh, MD, MBA: I think staining the patient on the exam is good as well because if the ingrowth stains and pools, it means it is an active condition. If it is not staining, looks pretty quiet, if she is asymptomatic, has no striae and no secondary astigmatism that is causing vision worse than 20/40, leaving it alone is a good option too. We tend to always feel like we have to intervene, but reassurance through waiting and watching is the beauty of our specialty because we see exactly what a patient has.

Neurotrophic keratitis and recombinant human nerve growth factor

Alice T. Epitropoulos, MD, FACS: A 62-year-old woman was referred to me by her optometrist. Her medical history included LASIK elsewhere, and she had a history of Sjögren’s disease and hypothyroidism. She presented with 20/20 vision in both eyes with severe diffuse staining in the cornea bilaterally, 1 second of tear breakup time and nicely healed LASIK flaps. She had a history of Sjögren’s syndrome with low Schirmer test scores. Despite her history and findings, she had no visual or ocular complaints. She stated what bothered her most was repeatedly being told by her eye care practitioners that she had diffuse keratitis.

Her ocular surface disease had been treated with serum tears, amniotic membrane, immunomodulators, omega-3s and thermal pulsation.

She had reduced corneal sensation on exam in both eyes. When patients come in with staining and they are not complaining, we should always think about the possibility of neurotrophic keratitis. We treated the patient with an 8-week course of Oxervate (cenegermin ophthalmic solution 0.002%, Dompé) six times a day.

After the course, she remained 20/20 in both eyes. During the treatment with cenegermin, she felt like her eyes were a little tender and achy. At baseline, her NEI scores were 15 in the right eye and 13 in the left eye. Then, after 6 months and 9 months, her keratitis was pretty much resolved.

The subjective gain for patients like this is minimal because they are not having any complaints visually or symptomatically. Would anybody treat this patient differently?

Ayres: I think it is the right thing to do because that surface disease is going to break down and become a problem. And once you have confirmed that the sensation is reduced, I think your best option is to use recombinant human nerve growth factor. You are preventing a disaster down the road, and the patient did not even realize they were heading in a bad direction. You avoided the problem.

Jennifer Loh, MD: Would you have thought about doing an amniotic membrane in the patient before treating them with cenegermin?

Epitropoulos: We did. We treated the patient with serum tears, we had her on immunomodulators, and we used a cryopreserved amniotic membrane.

McDonald: In a case like this, I will do the same thing. I will put on the amniotic membrane while waiting for the cenegermin. It will be a few days until you get the patient on cenegermin, and an amniotic membrane helps.

Trattler: What about punctal occlusion?

Epitropoulos: Before coming to my office, she had had the lower ducts cauterized.

Trattler: Did you consider closing the upper ducts? Closing the upper ducts can help create a higher tear film.

Epitropoulos: Great point. Closing the upper puncta would have been a good option for this patient, especially with her history of Sjögren’s disease.

Neurotrophic keratitis is a corneal degenerative disease characterized by reduction or absence of corneal sensitivity due to damage to the trigeminal nerve. This is a progressive disease, and it is divided into three stages. Stage 1 is characterized by punctate epithelial staining, stage 2 by a persistent epithelial defect, and stage 3 usually has stromal involvement and may include corneal ulceration or perforation. Neurotrophic keratitis is a chronic progressive disease that can lead to permanent vision loss, so early diagnosis and treatment are imperative.

Unilateral keratitis after trigeminal nerve surgery

Loh: A 69-year-old woman was referred by a local eye doctor for an emergency visit. The concern was for herpes zoster virus keratitis, and she had been started on oral valacyclovir. She had also seen another eye doctor for a recent corneal abrasion. Her main complaint was blurred vision, and she denied pain or eye irritation.

Her right eye vision was decreased to 20/70, and she also had elevated pressures in both eyes. She had been placed on latanoprost drops for elevated IOP in the past, but she had stopped them recently due to her current eye issues. She also mentioned that she had a recent surgery on her trigeminal nerve to help reduce her chronic trigeminal neuralgia. She was quoted as saying, “Since the surgery, I haven’t been able to feel the right side of my face.” What would be the next step?

I tested corneal sensation with a cotton wisp, and my techs used the iCare device to check pressure. She had not received any prior topical anesthesia. Interestingly, she had no corneal sensation on the right eye but did have a normal corneal sensation on the left.

She did have staining (Figure 2). There was no corneal melting or ulcer, but she had diffuse SPK. Her corneal appearance had concerned the outside optometrist that maybe she had a dendrite, and that is why she was placed on oral valacyclovir. Her conjunctiva and sclera were white, interestingly enough. She did have retinal nerve fiber layer thinning, which is indicative of possible early glaucoma.

I restarted her on latanoprost because her pressures were pretty high, and I wanted to treat her for what I believed to be stage 1 neurotrophic keratitis. I believe it was from her trigeminal nerve surgery because it was purely unilateral, and she had some classic history symptoms. I placed upper and lower plugs in the office. I started her on preservative-free artificial tears every hour and told her not to use her contact lenses. I did not place an amniotic membrane although, in retrospect, that could have also been a good option initially, but I decided to start the patient on cenegermin. Do you think that cenegermin could be helpful in patients following a trigeminal nerve surgery in which you believe the trigeminal nerve has been possibly severed?

Ayres: Cenegermin, or nerve growth factor, is one of the neuropeptides, and so we often think of it as the nerve grower. But there is actually a trophic effect with cenegermin on the corneal epithelium. It is like adding autologous serum, so it works in more than one way.

In a patient who has a transection of the trigeminal nerve where you don’t think there is going to be regrowth, there is still some benefit in putting nerve growth factor on the ocular surface because it will do better. The question here would be if we can get somebody on cenegermin once or twice a day for good to act as a trophic support for the corneal epithelium, which is off label but may be of benefit.

Loh: We did start her on cenegermin six times a day for 8 weeks. She finished her course, and her vision improved to 20/20. Of course, she has never had pain. These are her photos before and after cenegermin (Figure 3). She looks much better, and she is still able to tolerate latanoprost.

She did quite well for 6 to 8 months, and then her SPK started to look worse. She never had an abrasion or ulcer, but I did proceed with another round of cenegermin. We were able to get it approved, and I thought, “Why not do it?” She has had a severe situation with her trigeminal nerve, and it is probably not going to regrow. She still has zero sensation on the right side of her face, and it has been over a year, so I think the likelihood of her regaining sensation is low. I am curious if the panel would also have proceeded with a second round of cenegermin?

Henry D. Perry, MD: I was wondering if you were able to try any other methods, and how did you justify the cost of this medication to the patient?

Loh: Good question. I had already placed upper and lower plugs to increase the tear lake. The one thing I did not do that I could have, in retrospect, was an amniotic graft because there had been some evidence of improvement; however, amniotic membrane alone would not have likely been enough in this situation. I told her that this is a sight- and eye-threatening condition if she ended up developing a corneal melt or a perforation, and through much of my office staff’s work, we were able to get the cost of the medication approved. So, she did not pay anything. But it was a lot of discussion, and there was behind the scenes work my staff had to do; however, the company that produces cenegermin was helpful and supportive for the patient and my team. As you know, you have to prepare the drop and place it every several hours. The patient was concerned about the actual process of using and storing the drops as they have to be refrigerated, but eventually she was on board with it and happy that we had done it.

Ayres: These are the patients who I would work so hard to keep healthy because once the cornea breaks down, it is a world of hurt to get them turned around again. So, is a round of recombinant nerve growth factor worth it once or twice a year vs. developing an epithelial defect?

In these patients, I think it is well worth avoiding the hassle because we can see what is down the road. Patients don’t get that. So, I think it is a good use of nerve growth factor.

McDonald: And I think selective laser trabeculoplasty to reduce the need for glaucoma drops is a great idea.

Epitropoulos: Consider getting the patient off the preserved latanoprost and maybe putting her on a preservative-free glaucoma drop or even bimatoprost intracamerally.

• For more information:
• Brandon D. Ayres, MD, of Wills Eye Hospital in Philadelphia, can be reached at bayres@willseye.org.
• Alice T. Epitropoulos, MD, FACS, of Central Ohio Eye and Plastic Surgery, The Eye Center of Columbus, can be reached at eyesmd33@gmail.com.
• Arun C. Gulani, MD, of Gulani Vision Institute in Jacksonville, Florida, can be reached at gulanivision@gulani.com.
• Jennifer Loh, MD, of Loh Ophthalmology Associates in Miami, can be reached at jenniferlohmd@gmail.com.
• Marguerite B. McDonald, MD, FACS, of OCLI Vision in New York, can be reached at margueritemcdmd@aol.com.
• Jai G. Parekh, MD, MBA, of EyeCare Consultants of NJ, can be reached at kerajai@gmail.com.
• Henry Perry, MD, of OCLI Vision in New York, can be reached at hankcornea@gmail.com.
• William B. Trattler, MD, of the Center for Excellence in Eye Care in Miami, can be reached at wtrattler@gmail.com.