Honors celebrate research, future generation in retina

By Michelle Dalton, ELS; Reviewed by Rishi Singh, MD, and Charles Wykoff, MD, PhD

At the inaugural Ophthalmology Times Research Scholar Honoree Program, five leading retina experts weighed in on topics ranging from ellipsoid zone loss to using optical coherence tomography angiography to assess parafoveal retinal vessel density to the effects of anti-angiogenic drugs on expression patterns of epigenetic acetylation pathway genes.

Chairman Rishi P. Singh, MD, praising the event, said, “One of the huge plusses was to see the level of caliber that residents and fellows are performing.”

Observing that one of the presenters was still in medical school, Dr. Singh noted the obvious conclusion: it wasn’t necessarily the amount of experience that someone had, but rather commitment to the science and the experimental process.

Dr. Singh and fellow judges Richard F. Spaide, MD (New York); David M. Brown, MD (Houston); Judy E. Kim, MD (Milwaukee); and Charles C. Wykoff, MD, PhD (Houston), pre-selected 16 presenters from among all entrants.

Each presenter was allowed 7 minutes to discuss his or her results, including what role he or she played in the research, with a 3-minute allotment left for a question and answer by the judges.

IOP and anti-VEGFs

The overall leading research presentation was on the real-world effect of anti-vascular endothelial growth factor (VEGF) injections on IOP, presented by Elizabeth Atchinson, MD, a senior fellow at Rush University and Illinois Retina Associates. Dr. Atchinson used the American Academy of Ophthalmology (AAO) IRIS Registry to evaluate how anti-VEGF injections’ effect on IOP in the treated eye compared with the patient’s untreated fellow eye.

The primary outcome was the IOP change from baseline, and considered a clinically significant IOP rise as an increase of at least 6 mm Hg with an IOP >21 mm Hg among treatment-naïve eyes, or those previously diagnosed with age-related macular degeneration (AMD). Subjects could receive any of the commonly used anti-VEGFs (aflibercept, bevacizumab, or ranibizumab).

In 2016, there were 4,548 aflibercept injections, 13,349 bevacizumab injections, and 5,879 ranibizumab injections (60% of which were received by females) recorded in the IRIS Registry. The AMD eyes received about 8 to 9 injections, and treatment-naïve eyes received about 6 to 9 injections.

In the aflibercept and bevacizumab eyes, there was a statistically significant decrease in IOP between the treated and fellow eyes when evaluated by the anti-VEGF drug. There was a statistically significant increase in IOP between treated and untreated eyes when evaluated by disease state.

“These rates were lower than seen in clinical trials,” Dr. Atchinson said. “In our real-world dataset, there was a 2.6% increase in IOP over 1.8 years, compared with 8% in VIEW and 23% in MARINA and ANCHOR.”

More importantly, these real-world data increases were not clinically significant.

This year’s remaining top five finalists were: Xuejing (Jing) Chen, MD; Parisi Enami-Naeini, MD, PhD; Malvika Arya, BS; and Peter Tang, MD, PhD.

Idiopathic Epiretinal

Dr. Chen, vitreoretinal fellow, Tufts Medical Center, Boston, asked what the risk of progression to intolerable symptoms exists for patients who currently tolerated visual symptoms associated with epiretinal membrane (ERM).

“We looked at eyes with new diagnosis of idiopathic ERM referred to a single retina practice that had vision 20/40 or better without intolerable symptoms between the years 2009 and 2012,” Dr. Chen said. “This was a retrospective study and 5 retinal surgeons were involved in the care of patients.”

“All eligible eyes were then categorized by their baseline OCT morphology into normal foveal contour, mild loss or incomplete loss of foveal contour and loss of foveal contour,” Dr. Chen said.

Dr. Chen found 14% of ERMs referred to a retina practice with good vision became sufficiently symptomatic to consider surgery at 7 years. She stressed that the study was not designed to advocate for early or late surgery for ERMs with good vision, “but rather to produce statistics to help counsel patients and allow them to make an informed decision with their retina specialist.”

Retinopexy

Dr. Enami-Naeini, vitreoretinal fellow, University of California-Davis, Sacramento, conducted a multicenter study of pneumatic retinopexy (PR), which often involves less supervision of fellows compared to other surgical procedures. Experience and training of fellows “varies widely,” she said.

She evaluated the experience of vitreoretinal fellows performing PR and outcomes of patients at six academic centers between 2002 and 2016.

“Anatomic success of PR in the hands of fellows is comparable to rates reported from experienced surgeons,” she said, adding the data can be used to design more uniform curriculum and the creation of educational milestones in fellowship training.

OCT

Ms. Arya, OCT research fellow, New England Eye Center at Tufts University, Boston, assessed the variability in vessel density measurements across three OCTA devices (Optovue RTVue, Zeiss Cirrus, and Zeiss Plex Elite 9000) to identify a method that offers the least amount of variation in vessel density.  She found a statistically significant variability existed among the devices for a single normal imaged patient.

The vessel area density values varied less than vessel skeleton density (VSD) values.

“After registration of multiple repeats, mean VSD was significantly different than that of unregistered scans on each device,” she said. “However, numerically, the differences noted were small with mean VSD remaining within 1% of a single volumetric scan, for which clinical significance remains to be determined.”

Dendritic Cell Migration

Dr. Tang, vitreoretinal surgery fellow, Stanford University Byers Eye Institute, Palo Alto, CA, studied whether dendritic cells (early responders to ocular injury) are involved in cone death in LCA2. In a mouse model, Dr. Tang found dendritic cells are recruited to the outer retina, and cone death triggers dendritic cell recruitment.

“It may be the dendritic cells are cone protective,” he said. The clinical significance could affect how researchers treat white dot syndromes, S-cone syndromes, Stargardt disease, Leber congenital amaurosis, cone dystrophy, retinitis pigmentosa, and Behcet disease, among others.

Research Scholar Program

Supported by unrestricted grants from Regeneron Pharmaceuticals and Carl Zeiss Meditec, these top five finalists will be featured in a supplement to Ophthalmology Retina, and each received the Crystal Award. All the presenters will have their research highlighted throughout the year in Ophthalmology Times and online at OphthalmologyTimes.com.

The Research Scholar Honoree Program is dedicated to the education of retina fellows and residents by providing a unique opportunity for selected researchers to share their notable research and challenging cases with their peers and mentors.

Dr. Wykoff noted the event was a success, and particularly liked the dynamic discussion portions. He added that next year the sponsors could consider augmenting the discussion sections even further.

For those interested in submitting next year, Dr. Singh suggests researchers be passionate about their submission.

“Take on research that you find appealing, and then working on it and speaking about it will become easy,” he said. “Mentors can be key in pointing you in the right direction.”

Equating Research to … Dating?

Attendees also heard insights from keynote speaker Dr. Spaide, who compared writing research papers with dating.

As he joked with attendees, “Why would you want to write a paper? It takes work, you get no money, and there’s a significant chance of rejection,” he said. “But why try to date? It takes work, you get no money, and there’s a significant chance of rejection.”

Like dating and getting married, numerous naysayers will tell fellows not to bother with research, but that is analogous to “undergoing a sort of mental atrophy,” he said. “Conducting research and publishing, it lets you sharpen your mind, learn a lot of new information, and make a contribution to medicine.”

In his experience, there are two big determinants to becoming a good researcher: a mental picture of yourself after fellowship, and drive.

“Your mental picture of your future will determine your expectations,” he said. “Those expectations will determine your actions, and those actions determine your world and what you become.”

Drive entails having the energy and passion to see the research through.

Dr. Spaide reminded the presenters they are among the brightest of their generation.

He remarked, “You have a passion to study, but do you have a passion to be creative?”

Part of the creativity is determining what to research in the first place, he explained.

“Anything you want to look at is a potential research idea,” he said.

The secret to success as a researcher is to “be like a jazz musician,” communicating freely within your group about the research, collaborating with other groups, but pursuing solo projects when the time is right.

Be prepared that while some people will be receptive to a new idea, some will push back.

“Believe in yourself,” Dr. Spaide advised.  “Get out and show initiative, do work, never stop learning, be open to new ideas, think for yourself, and stick out your neck.”