The following transcript has been edited for clarity:
Lisa Feulner, MD: Welcome to AAO 2025 Orlando. I'm Dr. Lisa Feulner, chief medical editor of Ophthalmology Management, and I have the honor and privilege of two guests with me today, Dr. Mark Milner and Dr. Brandon Ayres. And we're going to be talking about some really common issues that we see in our offices, specifically neurotrophic keratitis. Gentlemen, can we talk about why practices should be testing for neurotrophic keratitis?
Brandon Ayres, MD: Sure. So, for years and years we've been battling difficult-to-treat ocular surface disease, calling it dry eye, using the typical dry eye medications and sort of getting nowhere with our patients. And now that we have some really good treatments for NK, or neurotrophic keratitis, we've introduced testing in the office for NK and found out that so many of the patients who we had diagnosed with X, Y, or Z actually have a base problem of NK. And so by testing and finding those patients and using some really good effective treatments for the disease process, we can really get to the root source of the problem, treat the patients, get them better, and then they're not being seen so frequently with problems and breakdown and we can really heal them and really give them their life back.
Mark Milner, MD: NK is one of the most underdiagnosed diseases we see, and we obviously know that the DEWS changed their definition to include neurosensory abnormalities because we know that dry eye can cause NK and NK can cause dry eye. But one of the things that we should be doing is basically looking for this disease before even they walk into our office. So if you have a patient that comes in with diabetes, if they've had a history of herpes, if they've had shingles, if they've had certain surgeries around their orbit, we need to look for NK. If we think about it, we'll find that diagnosis.
Dr. Feulner: So how would you advise a general ophthalmology [practice], or another practice that isn't currently testing for neurotrophic keratitis, on the easiest way, most efficient and effective way [to do so] without spending a lot of money?
Dr. Milner: First and foremost is you have to retrain your staff that if a patient comes in with a dry eye evaluation or if they're coming in for a corneal evaluation, I don't want my staff putting any anesthetic in, because then you can't test for NK. So that's the first thing. Staff should not put any drops in; they should let you see the eye before anything goes in. Second is to use dental floss. You can use a cotton wisp. No one has a Cochet-Bonnet [aesthesiometer] unless you're doing studies. But we use unwaxed dental floss, and then I have a kind of subjective way that I do it. If you have no sensation at all, that's 0 out of 4. If you have a normal reflux where you pull back, that's a 4 out of 4. One means that you feel it, but you have absolutely no reflux, you're not blinking. And then 2 and 3 are somewhere in between. So I kind of try to gauge the NK so I can grade it and get a more quantitative reading.
Dr. Ayres: It doesn't take a lot to test. You just have to think about it. So when you're talking to your patients and they've got some of those key diagnoses–diabetes, multiple surgeries, laser refractive surgery, long history of dry eye–you've got to think there could be a base of neurotrophic keratitis here. And then we do the same thing. I actually carry a little spool of non-waxed, non-minted dental floss, take a couple inches off, and touch the cornea. And I think that you have to touch and test normal patients to get that grading system that you use. You have to know what a normal patient would do when you touch them with a piece of dental floss. And remember, you don't have to have an anesthetic cornea. It's just reduced sensation is neurotrophic keratitis. It's not an anesthetic cornea.
Dr. Milner: The history is critical because if a patient comes in and says, I feel fine, and you see their cornea and it looks so riddled with punctate staining and even persistent defects, you have to suspect NK anyway. The other little pearl that I always try to teach is if somebody comes in and they're in the healthcare field, you always want to make sure that they're not using topical anesthetic because that's something that often gets missed and is one of the types of NK that you don't realize unless if they're a physician.
Dr. Feulner: I think we also can't forget contact lens-wearing patients. So many patients are uncomfortable in their contact lenses, and those are patients we should be testing as well. We can treat their dry eye, but if they're neurotrophic, they're going to have an endless cycle where they're going to be uncomfortable, and many of these patients are neurotrophic. What is it that you guys are using in your offices to treat neurotrophic and when do you initiate this?
Dr. Ayres: So, my take on this is that we can do much more good for a patient the earlier we intervene, and we use lots of products. I mean, treating the ocular surface in some ways does treat NK, but the only approved product we have right now is recombinant nerve growth factor, trade name Oxervate (Dompe). And so if I really feel that the neurotrophic state of the cornea is impacting the cornea, the corneal disease, quality of life, quality of vision, then even in early-stage NK, we'll initiate Oxervate therapy. And once again, it gets to the source of the problem. I've seen patients “healed” from their dry eye, but it's not the dry eye, it's the NK. So I think starting early really gets people better. And we do better by our patients by treating early.
Dr. Milner: Treating early is critical. Brandon, I can't agree with you more, but it's important to understand the stages very quickly. Stage 1 is where you have punctate staining. Stage 2 is where you have a persistent defect with no thinning or ulceration. Stage 3 is an ulcerated cornea where you get thinning. And at that point the race is between re-epithelialization vs perforation. When treating early is critical and [you're] suspecting it, obviously it's easier to make the diagnosis when you have a defect or you have an ulcer. But if you have punctate staining, you don't always think about it. That's where the history comes into play. So for me, I do the same thing: treating the surface, treating the dry eye. Oxervate is a great treatment for those patients, especially the persistent stage 1, but obviously stage 2 and 3. In addition to Oxervate, we'll use amniotic membrane transplantation (AMT), because there have been studies showing that you're increasing nerve density and sensation.
Dr. Ayres: And even if we're not using an AMT, we're not waiting for this therapy to come. So we're still using tears. We use a lot of autologous serum. There are other things that you can do to bridge the gap, if you will from the time you make the diagnosis to the time you get the appropriate prescription therapy.
Dr. Milner: Like punctal plugs. And again, we want to make it easier in your office, make it easier for you to take care of these patients because the cost can go up as you have these patients coming in and being seen in multiple visits. Autologous serum is a great treatment. Serum works a lot like really good artificial tears. It'll help with that surface healing. And we use that with NK as well.
Dr. Ayres: There's lots of products coming too, Lisa. I mean, there's new things there. There's studies being done right now for new therapies for NK and persistent epithelial defects. So although right now we have one approved product, I think in the foreseeable future we'll have a couple more.
Dr. Feulner: So I look forward to next year at this time, coming back and hearing about those products. Hopefully they'll have hit the market and we can now introduce them and talk about them as well. So the bottom line here, I think you heard, is test early. Train your staff not to put anesthetic in and consider treating the neurotrophic disease early in your ocular surface evaluation.
Dr. Milner: And think about it when they come in. Have a suspicion. You're not going to make the diagnosis unless you suspect NK.
Dr. Feulner: Thank you so much for being with us and taking time out of your busy schedules today. We really appreciate it.
Dr. Milner: Thank you. Thanks for having us.