A History of Keratorefractive Surgery

An interview with a pioneer in the field

Marguerite McDonald, MD, is a pioneer in the field of keratorefractive surgery, having been the first in the world to perform photorefractive keratoectomy (PRK), in 1987. Therefore, it was a no brainer to interview Dr. McDonald, who will be inducted into the ASCRS Hall of Fame at the 2023 meeting, May 5 to May 8, in San Diego, California.

What follows is a question-and-answer session between me, (ATR), and Dr. McDonald (MM):

ATR: How did you first become interested in refractive surgery?

MM: My extreme myopia sparked my interest.

ATR: What options were available to patients when you started in the field?

MM: When I started my fellowship, my professor, Dr. Herbert Kaufman, had just given the Jackson Memorial Lecture at the American Academy of Ophthalmology on epikeratophakia. This was extremely controversial, as he only had a handful of patients who were no more than 2 weeks postoperative. When I arrived, I joined him in perfecting epikeratophakia for myopia, hyperopia, aphakia, and tectonic applications, such as keratoconus. The “KME procedure” as it was called (Kaufman McDonald Epikeratophakia) was performed globally for several years; the freeze-dried lenticles were custom manufactured by Abbott Medical Optics (AMO). The results were quite good, but other technologies eventually replaced epikeratophakia, as the lenticles took an average of 6 weeks to clear in adults.

Dr. McDonald performing a retinoscopy on a monkey in the mid 1980s.

Radial keratotomy soon became available for myopia and — when paired with astigmatic keratotomies — myopic astigmatism. I was fortunate, at a very young age, to be selected as 1 of the 9 PERK surgeons (Prospective Evaluation of Radial Keratotomy, a National Institutes of Health grant–funded 10-year clinical trial).

ATR: How did you become involved in excimer laser technology?

MM: When I read Stephen Trokel’s landmark 1983 paper in the American Journal of Ophthalmology, I called him. He had helped me with my retinoblastoma research when I was a medical student at Columbia University. I told him I was now an assistant professor of ophthalmology at Louisiana State University (LSU), and that I had access to the many rabbits and monkeys that would eventually be needed. I knew that the vivarium at Columbia University was very tiny and would not be sufficient. Basically, I asked if I could join his research team. He had already contacted Charles Munnerlyn, the brilliant PhD physicist, so the 3 of us started working together.

ATR: What were the initial studies/trials like, and how were they performed?

MM: We fired the very primitive excimer laser at countless plastic discs, then countless cadaver pig, rabbit, and monkey eyes, then many human cadaver eyes. We then moved to living subjects: rabbits. We fired at the rabbits from a distance of 5 to 6 feet, and the laser had a diaphragm that closed—by hand crank!—in 5 steps. The ablations resulted in thick hyperplastic scars, but we didn’t know what was wrong.

Above: The infamous trailer where Dr. McDonald and team (inset) performed PRK. Note the name of the trailer.

In 1 memorable week, my cornea fellow and 2 research assistants quit the team, saying that the project was doomed, and they were too depressed to continue wasting their time on it. After trying various things, we made the intuitive leap that, perhaps, smoother ablations might be better. Charles made the diaphragm close automatically and in 40 steps.

The rabbits started to look much better. Eventually, we moved to monkeys, who were under general anesthesia for the ablations (PRK).

We did innumerable monkey treatments, and presented the outcomes data to the FDA. They always wanted more monkeys to be treated.

ATR: Can you tell us about the first patient to receive PRK?

MM: Her name was Alberta Cassady. She was a 61-year-old woman about to undergo exenteration for orbital cancer. She had a healthy eye with 20/20 uncorrected vision that she was about to lose. She was facing certain disfigurement and likely death, as the prognosis was poor. In the face of all of this, she asked whether anyone wanted to do an experiment on her eye, before it was removed. The oculoplastics service called me, reporting her amazing offer. We had no time to waste; we notified the FDA of her offer, and they allowed us to take her to the Delta Regional Primate Center, across Lake Pontchartrain, and perform the surgery. We rushed her past the monkey cages, and prepared to perform a 4.5 D myopic PRK. On that day, I had the honor of performing the first laser vision correction procedure, a PRK, on a living human subject. We made her hyperopic, of course, and followed her every day until her exenteration 11 days later. The refractive outcome was perfect. Her cornea was clear, and we obtained the specimen after her exenteration. We might still be doing monkey trials if it weren’t for Mrs. Cassady’s generosity. With these data, the FDA allowed us to start the blind eye trial, then the partially sighted trial, then the fully sighted trials for myopia, myopic astigmatism, hyperopia, and PTK for corneal opacities.

ATR: Can you tell us how excimer laser vision correction has changed from the early days to the present? Specifically, what have been the main innovations in technology?

MM: So many things. First, there are now trackers. We had no trackers in the beginning, so we used retrobulbar blocks. Even with the blocks, there was some eye movement, so we used fixation devices as well. The fixation devices that we tried could fill a wing of the Smithsonian. Some were so huge, that a lateral canthotomy was sometimes needed. Some had 4 carpenters’ levels on them.

Second, much smoother ablations were created with flying spots. For years, we only had broad-beam lasers that were fired as a diaphragm closed. Flying spots are vastly superior, giving much smoother ablations.

Third, wavefront-based and topography-based ablations. These provided improved outcomes over standard ablations based on the manifest refraction alone.

ATR: Can you tell us about the transformation of epikeratophakia procedures to anterior lamellar keratoplasty, LASIK and SMILE?

MM: Epikeratophakia was not the precursor to LASIK and SMILE; PRK was. Epikeratophakia was a lamellar technique that taught us so much about corneal physiology, corneal processing, and corneal optics.

ATR: You have shared so many amazing and hilarious stories about your own journey in ophthalmology. Can you share 1 or 2?

MM: Here are 2: (1): With the help of AMO, I trained over 700 surgeons worldwide, always with proctored lab sessions. As it was too expensive to let the doctors use real lyophilized human lissamine-stained corneas, we used stained pig corneas. Everyone knew that “epi” lenticles were green and shipped in vacuum-sealed contact lens bottles. For 1 course in Latin America with 75 students, we were horrified to discover—at the last minute—that the manufacturer had forgotten to dye the corneas. So, we dashed to the hotel bar, bought their supply of crème de menthe, and dyed the 75 lenticles.

(2) This story is about a trailer. After the FDA accepted Mrs. Cassady’s PRK data and allowed us to start treating living humans, we brought the laser back across the lake and installed it at the LSU Medical Center. The dean was afraid gas would leak and kill everyone, so we were relegated to a trailer next to a trash compactor. The trailer shook from the trash compactor. I tried to stop the compacting trash during treatment sessions, to no avail. Even the dean wouldn’t help me. I said I would provide proof that the shaking was hurting patient outcomes. To my surprise, patients ablated during compacting did best. The gentle shaking of our trailer was clearly making the ablations smoother; more proof that smoother is better! This led us to automate the diaphragm to close in 120 steps instead of 40 steps. CP