RETINA REFLECTIONS

Michael T. Trese, MD, FASRS

Michael T. Trese, MD, FASRS, is widely considered the father of modern pediatric vitreoretinal surgery. In a career spanning more than 40 years, he has been credited with significant breakthroughs and has taught many of today’s leading pediatric retina specialists.

In the 1980s, he revolutionized pediatric vitreoretinal surgery with his concept of lens-sparing vitrectomy for the treatment of complex pediatric retinal detachment due to advanced retinopathy of prematurity (ROP). His techniques have also been applied to diseases such as familial exudative vitreoretinopathy, juvenile X-linked retinoschisis and Coats disease. He led the way to the first FDA-approved drug for pharmacologic vitreolysis.

Early on, Dr. Trese recognized the critical importance of timely screening of babies for ROP and the need to educate ophthalmologists about the disease. He developed photographic screening protocols with telemedicine and an educational program called FocusROP that is now used throughout the world.

Dr. Trese (center) with Judy and Trex Topping, MD, and George Williams, MD. Photo Credit Kevin Caldwell Photography

Over the years, Dr. Trese  shared his extraordinary knowledge, insight and skills with innumerable colleagues and fellows and his innovative techniques have had a profound impact on the lives of grateful patients and families around the world.    

His research interests included extensive exploration of concepts related to regenerative medicine involving cellular signaling pathways in the retina. This work holds enormous promise for the preservation and restoration of sight.

He served on the executive committee of the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) Study, and the committee for the International Classification of the Late Stages of Retinopathy of Prematurity. He was a Founder and Chairman of the Pediatric Retinal Research Foundation and a founding editor of Pediatric Retina—the definitive textbook on pediatric retinal diseases and surgery.

Dr. Trese received many of the field’s most prestigious awards, including the AAO’s 2021 Laureate Award, which has been awarded only 21 times in the Academy’s history. He also received the J. Donald Gass Award from The Retina Society in 2013. Dr. Trese was a past president of both The Retina Society and the Club Jules Gonin. 

Please share an impactful moment that shaped your career? Was there a time that you felt that you were witnessing history in the making?

When I was in residency training, I got the impression that if you were operating on an eye, and you touched the retina, that it was very likely that the patient's head would explode. And so, we didn't touch the retina. Later, it became quite clear that you could manipulate the retina and the layers of the retina. I found that to be rather fascinating, because it went against everything that I had learned before.

I was very lucky because retina was evolving as I was evolving which made it exciting. I had several people who made a huge impression on me during my training and there were a lot of things going on that were new, things that people thought were impossible before but were now possible. Things like treatment of retinal detachment with vitrectomy, as opposed to scleral buckling. In fact, buckling itself changed from the Boston School to a Miami school to Duke. It was an interesting adventure.

What career accomplishment provides you with the greatest sense of satisfaction?

The lens-sparing vitrectomy is probably the thing that's made the biggest difference in people's lives. I have patients, who had detachments for ROP and for other pediatric retinal diseases, that are now sending me emails thanking me for 25 years of vision. I think that is the most rewarding.

As I’ve always said, if you're lucky and you're doing things properly, you are probably going to put yourself out of business. And I didn't exactly put myself out of business, but I did end up having to do harder and harder cases.

When we first started doing the lens-sparing vitrectomy, a lot of people didn't believe our results and so we had a lot of visitors come to observe. And fellows started to realize that it was a big draw because nobody knew how to do it and it became a draw for fellows in terms of job placement. That was nice to see.

I had a patient who went back to his doctor in Texas and the doctor looked inside his eye and said, “I didn't believe anybody could fix that.” That was not an uncommon reaction. I had one doctor call me and explain that he told a mother that her child was going to be blind, but suggested she visit us in Detroit to be sure nothing more could be done. The kid ended up not being blind.

I think ophthalmologists are very much success oriented. And they don't like to deal with bad stuff, but that is when you really need a doctor. When things are bad it’s good to have someone that can guide you through it, maybe get you better. It can be very rewarding.

At the time when you were so immersed in these very intense surgeries, could you imagine what the pediatric ROP retinal detachment field would look like in the future? Did you think there was going to be a slowing down of the number of ROP detachments with the advancement of technology? Could you see how this trajectory was going to change?

We could not only see it, but we worked to make it happen. We’ve trained a lot of people. You really can't make a break when you're doing pediatric dissection. And so, if people interested in doing peds, we would have them do some pediatric surgeries during the last two or three months of their fellowships and then also support them as they went through their careers. We've had some really stellar fellows.

Back when I started, if you got to detachment, you were blind. We couldn’t do anything about it. When I was a resident, I was given the job of screening the NICU babies without an attending. I saw one case I thought didn't look bad and I told the parents to come back to the clinic in a month. By then, the child had bilateral detachments. I ran like crazy to get the retina attending who came down and proceeded to tell the mother that the child was going to be blind and there was nothing we can do about it. And I said to myself, I don't believe that, that can't be right! It was a very powerful moment that focused my attention on ROP.

The next ROP case I worked on was with Robert Machemer, MD. We made five or six observations that Robert thought were brand new. But 25 minutes after leaving the OR, I was in the main library in the eye center at Duke reading what Dr. Terry had written about ROP and discovered that he had previously cited every single thing we had noticed. Years later, I’m seeing a baby with bilateral detachments in Detroit and I called Robert to say that I thought I should send the patient his way. He said, “Well, let's think about this for a minute. How many of these cases have you been involved in?” I said, “I’ve done that one that we did when I was a fellow.” Robert asked, “And how many have I done?” I said, “I have no idea,” and he said, “I’ve done 2, so your experience is half of mine. You keep him.” And that was how I ended up doing my first stage five was that patient. There was an epidemic of ROP in Grand Rapids and I did 20 bilateral babies in 18 months. They seemed to be following all the guidelines that were present at the time. It gave me a lot of experience right off the bat.

During the years that followed, did you ever get the feeling that ROP would just stop being an issue? For example, when you were working on plasmin and other treatment options?

No, I knew it would continue because it is set up to continue physiologically – unless you can alter the biochemistry and anatomy.

As time went on, we gained a better understanding of the disease. I remember when we referred to VEGF as Factor X, which was Michelson’s designation of that factor. In fact, I wrote a thesis for a very prestigious family group that suggested that Factor X drove ROP. And in feedback I was told that I was wrong, that there was no way that Factor X could in any way be related to ROP. They've since apologized. It’s a lot of fun to unfurl things that seem very cloaked in secrecy or the unknown.

I love ocular pathology and we did a lot of histo-pathologic correlation studies, in terms of looking at scar tissue and looking at the materials that were detaching the retina and discovered that they were part of the hyaloid system that was changed to fibrotic-producing tissue. It was a very interesting time.

I find pediatric retinal diseases fascinating, in terms of understanding their inheritance patterns, how they change, particularly things like FEVR, which paralleled ROP, and other vitro retinal dystrophies. Sometimes a vitro retinal dystrophy is not characteristic of an already described thing and you have to realize what constitutes an unnamed vitreo retinal dystrophy. And those are things that have like an empty vitreous cavity, have unusual collagen, have retina that stretched larger than the retinal pigment epithelium. All of those things contribute to a vitreo retinal dystrophy. Even myopia to a certain extent can be vitreo retinal dystrophy in more pathologicmyopia status. So, I consider myself very fortunate to have been able to work with these little kids and their families. You can't forget the families, the families are struggling through this, just like any other major disease.

What do you feel is the most significant development or change in the practice of retina?

I think cell-based therapies are going to be playing a role. We are working on drug development for a regenerative ocular therapeutic, retinal therapeutic, that recreates the environment that your cells had when you were an infant. In some cases, it gets turned off and we have found a way to turn it back on. In animals, it shows normal neuronal and vascular growth in the oxygen-induced retinopathy (OIR) model, which has become the standard test agent for many things.

I think there will be a role for gene therapy, but there also may be a role for introducing cells that have adapted or been nonfunctional in the person's eye to be reintroduced. The work that Mark Humayun, MD, PhD, and Amir Kashani, MD, PhD, have done showed promise. The problem is that, just like with retinal rotation where the area to which the macula is rotated RPE degrade, the same thing may be true that the introduced RPE may degrade over time. Amir's answer was that the patient will die before the cells die, and that is not a good answer. But Amir is a very smart guy and I know he'll work to try and improve it. It’s going to be very interesting.

I think gene therapy and retinoschisis are a good mix. Even though nothing positive has happened to them, I think that the gene has been delivered to the wrong area in the eye. It needs to be delivered either under the retina or within the schisis cavity, if the schisis is scattered, the inner wall is intact. And those things I think, are going to become more routine for the retina surgeon as we get used to doing subretinal injections. Tamer Mahmoud, MD, who works with us, has a very nice system for introducing material in the subretinal space. And there are other approaches that have been used to reach the supra retinal space. If you look back, PVR came somewhat under control as people learned to use the indirect better. But as that was going on, macular hole surgery, epiretinal membranes and such were increasing. There is always some newer type of surgical procedures that will capture people's attention.

How do you imagine the practice of retina will change by2040?

I have great hope for the regenerative medicine projects we are working on. I think that you're going to be able to introduce, by a variety of techniques, material, whether its cell-based, protein-based or small-molecule-based, to maintain or maybe even regrow retina.

Just like everything else, you have to have an open mind when you deal with these things, because they're not possible now. But you know, once upon a time vitrectomy wasn't possible. When I was a fellow, I wrote three papers on macular pucker with Robert Machemer, MD, and David Chandler who was the histologist. At that time, people didn't believe you could actually peel membranes off the retina. And so, we had a paper that had 40 patients and 75% did pretty well. Even the 25% who didn’t said they would go through the surgery again. And I remember asking Robert why people would believe that we could get improved vision when we remove the epiretinal tissue, and he said, “Because I've never lied to them before.” And I think that's true. You have to realize that some things may not be possible. But unless you try, it's going to remain impossible. And so, you have to look at what the newer technology is bringing and see how it might fit into a regenerative process.

Can you share any advice for future generations of retina specialists?

I think it’s important to keep your mind open to what may be useful. If you're dealing with a pediatric population, you really need to be sensitive to the family, and the family's interaction with the child. And be very honest with them. If you're being honest with the family, the family wants the best for their child and that’s what the doctor wants, then I think you've got a real team effort to try and do the best thing for those children. And it's also true when you're dealing with adult patients. Adults want the best they can get and if you're honest with them, and you explain the pros and cons of what you're doing, that helps in dealing with whatever the outcome may be. It gives you a frame of reference to go back to when you're talking with them after surgery.

We're very fortunate to be in retina because it is a very innovative part of medicine. And there are so many people in retina, like Mark Blumenkranz, MD, and Kirk Packo, MD, to name a couple, who have innovated and moved us forward and have been very generous with their innovation. They've really helped people in retina move forward. And I think that's critical. We go forward or backward together.

Our sincere thanks to Dr. Trese for sharing his retina reflections.

Click to hear more reflections from Dr. Trese in his Leaders & Legends interview

(Retina Reflection published 2022)

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