Published in Retina

Finding Your Focus in Clinical Research

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12 min read

In the inaugural episode of Retina Mentor Moments, John Kitchens, MD, sits down with Chirag Jhaveri, MD, to discuss how to find your focus in clinical research.

Welcome to Retina Mentor Moments! This curated series features discussions between seasoned and up-and-coming retina specialists on mentorship in ophthalmology, compelling research, and novel disease treatments.
Hosted by John W. Kitchens, MD, a retina specialist and practice partner at Retina Associates of Kentucky, each episode offers insights from experts—providing tangible advice, personal anecdotes, and clinical pearls tailored for the next generation of retina specialists.
In the inaugural episode of Retinal Mentor Moments, Dr. Kitchens sits down with Chirag Jhaveri, MD, to discuss actionable steps ophthalmologists, residents, and fellows can take to begin their journey into retina research.

The journey from fellowship to practice ownership and clinical research

Dr. Jhaveri began by explaining that he was able to develop his research skills more seriously under the mentorship of Lee M. Jampol, MD, at Northwestern University during his vitreoretinal diseases and surgery fellowship.
After completing his fellowship, Dr. Jhaveri joined a solo practice in Austin, Texas with an active clinical trial center. There, he gained practical experience running a clinical trial site, recruiting well for clinical trials, and building on his healthcare experience to lead clinical research and co-manage a group practice.

Getting involved in retina research at your ophthalmology practice

Around the same time that Dr. Jhaveri joined this practice, his mentor Dr. Jampol became chair of the Diabetic Retinopathy Clinical Research (DRCR) Retina Network.
Formed in 2002 as DRCR, the organization expanded its scope to include other retinal disorders in 2018, and the name was changed to DRCR Retina Network in 2019. The DRCR Retina Network aids in the identification, design, and implementation of multicenter clinical research initiatives focused on retinal disorders. It oversees 160 participating sites with over 500 physicians throughout the US and Canada.1
Fortunately, the clinical trial center at Dr. Jhaveri’s practice was a registered site at the DRCR Retina Network, so he joined them and developed relationships with colleagues at the physician- and investigator-led network. He appreciated that the DRCR Retina Network creates a space where researchers can investigate questions and hypotheses that are not specifically driven by a pharmaceutical company or a sponsor with a specific motivation.
Joining the DRCR Retina Network allowed Dr. Jhaveri to wade into retina research while still early in his ophthalmology career. With time, he became a vice chairman and eventually became a protocol chair and sat on a steering committee—all of which began with him enrolling in the network because he was motivated to learn more about clinical trials for retinal diseases.

Dr. Kitchens highlighted that the Retina Consultants of Austin website has a page dedicated to ongoing clinical trials that he found very useful for both patients and doctors. He strongly recommended that other practices integrate this into their websites, as it allows patients to see which clinical trials the practice is involved in.

Recruiting new doctors: The transition from mentor to mentee

Dr. Jhaveri noted that starting a practice or working in a practice where you are actively involved in management has a steep learning curve. Much of the knowledge required for practice management and leading clinical research is not taught during medical school, meaning it needs to be developed through hands-on experience or with the guidance of a mentor.
Fast forward to now, Dr. Jhaveri is an integral member of the practice family at Retina Consultants of Austin, with years of experience guiding the process of recruiting new doctors to the practice. He explained that learning the ins and outs of leading clinical research and practice management goes so fast that when recruiting new partners, it may be easy to forget that not everyone has developed these skills.
Consequently, when recruiting a new co-owner, the first step is to seek out motivated retina specialists with a go-getter attitude. The second step is to determine their comfort with clinical research and practice management, and the third is to familiarize them with the management protocols specific to the practice.
Understanding processes such as revenue cycle management, inventory management, and required unemployment benefits is critical to contributing to the success of the practice because they are integral to running a business. As such, it is beneficial to include doctors with an interest in the business side of the practice in management meetings or take an active role in informing them about the ongoing discussions outside of clinical care to maintain the practice.
With time, eventually, this work can be distributed or managed together, but it is crucial to first educate doctors new to this skill set because this information was not in the books that they read in medical school, reiterated Dr. Jhaveri.

How the DRCR Retina Network advances care for diabetic eye disease

The DRCR Retina Network conducts high-impact “Protocol” studies that aim to elucidate and define the standard of care for diabetic retinopathy and other retinal pathologies.2 In the United States, many surgeons have to navigate step therapy requirements—meaning they are required to initiate treatment with specific medications—and often bevacizumab is required as a first step.3
Protocol T compared the 2-year outcomes of aflibercept (Eylea, Regeneron), bevacizumab (Avastin, Genentech/Roche), and ranibizumab (Lucentis, Genentech/Roche) in the treatment of visual impairment caused by center-involving diabetic macular edema (DME).4
Investigators found that the mean change in visual acuity (VA) from baseline was similar for eyes with better baseline VA (20/32 to 20/40). However for patients with baseline VA between 20/50 and 20/320, aflibercept was superior to bevacizumab and ranibizumab at 1 year and to bevacizumab at 2 years.4
The results from Protocol T inspired Dr. Jhaveri’s research team to compare whether initiating treatment for DME with aflibercept, bevacizumab, or switching the two during the treatment course caused differences in visual and treatment outcomes.

Protocol AC comparing aflibercept and bevacizumab

In the Protocol AC study, the research team included 312 eyes (270 adults) from 54 clinical sites and assigned either 2.0mg of intravitreous aflibercept or 1.25mg of intravitreous bevacizumab to eyes in adults who had center-involved DME and VA 20/320 to 20/50.5 Beginning at 12 weeks, eyes in the bevacizumab-first group were switched to aflibercept therapy if protocol-specified criteria were met.
In total, 158 eyes were assigned to receive aflibercept monotherapy, and 154 received bevacizumab first. Over the 2-year period, 70% of the eyes in the bevacizumab-first group were switched to aflibercept therapy. At 2 years, the mean changes in visual acuity and retinal central subfield thickness (CST) were similar in the two groups.5
These findings indicated no evidence of a significant difference in visual outcomes over a 2-year period between aflibercept monotherapy and treatment with bevacizumab first with a switch to aflibercept in the case of suboptimal response to treat moderate vision loss due to DME.
To summarize, it demonstrated that patients who switch from aflibercept to bevacizumab could have similar treatment outcomes to those who started with aflibercept, and the reduction of intravitreal injections was roughly seven injections over a 2-year period, though 70% eventually switched to aflibercept.5

The geographic atrophy treatment landscape

Dr. Jhaveri noted that being involved in retina research has been an interesting experience, as geographic atrophy (GA) is a frontier where great strides have been made to develop a treatment.
The novel anti-complement treatments are exciting for GA patients and have opened the door for a new set of long conversations with patients about the efficacy, safety, and burden of anti-complement therapies.
While having a viable intervention is critical to improving patient care, Dr. Jhaveri remarked that he is still keeping his eyes trained on treatments for GA with better reduction in lesion growth and a lower treatment burden.
Dr. Kitchens noted that the tandem increased attention to GA that followed the development of these therapies, he has seen a dramatic increase in the number of patients with GA and was shocked at how quickly it can progress once it has been detected. Dr. Jhaveri agreed, noting that, on average, 67% of patients will lose the ability to drive comfortably between 1.5 to 2 years after GA diagnosis.6

Retina Mentor Moments: Scleral buckling for retinal detachment

The pair then transitioned to discussing how Dr. Kitchens was an early virtual mentor for Dr. Jhaveri due to an instructional video he made on scleral buckling for retinal detachment.
The video spawned from Dr. Kitchens learning “old school” techniques from his practice partner, Thomas Stone, MD, FASRS. Dr. Stone showed him how to release subretinal fluid with needle drainage and performed modified external drainage, which was key to placing a primary buckle on the eye.
After this training, Dr. Kitchens realized that most people his age didn’t know how to buckle, instead they knew how to do primary vitrectomies and buckle vitrectomies. As a result, Dr. Kitchens translated what he learned for other doctors to benefit in an accessible video format. Dr. Kitchens now has a YouTube channel with surgical videos and 3D surgical videos as he follows his passion for ingenuity.

Ultimately, if you are a buckler, being able to do a lasting primary buckle will make you better at performing vit buckles, emphasized Dr. Kitchens.

What’s on the horizon for retina specialists?

A new frontier for retina specialists will likely be gene therapy, predicted Dr. Jhaveri, particularly if and how gene therapies could change the treatment landscape for many retinal diseases and other long-term drug delivery devices. Additional areas of interest are continuous drug delivery of anti-vascular endothelial growth factor (VEGF) via self-production or daily delivery of anti-VEGF with an implant system.
He was curious if daily suppression of a continuous amount results in better disease modification than the peaks and troughs in current anti-VEGF injections. Dr. Jhaveri compared anti-VEGF treatments to watering plants, explaining that it is better for plants to have a drip-line system that consistently provides moisture versus dousing the plants in water once a week to ensure the plants grow more efficiently.
Finally, Dr. Jhaveri was also interested in medical-related challenges that surgeons face in the near future, such as the changing landscape of the healthcare system—specifically how ophthalmologists will manage a growing aging population with a declining workforce.7

Conclusion

From developing the necessary skill set to manage a practice and lead clinical trials to primary scleral buckling for retinal detachment, there are endless opportunities to learn from mentors in ophthalmology.
Retina Mentor Moments seeks to highlight these moments and provide guidance to new retina specialists with the wisdom and clinical experiences of more seasoned surgeons.
  1. DRCR Retina Network. General Information about the DRCR Retina Network. DRCR Retina Network. Accessed May 6, 2024. https://public.jaeb.org/drcrnet/view/General_Info.
  2. Mott M, Schocket LS, Sternberg P, Thompson JT. Step therapy: Clinicians’ concerns and challenges. EyeNet Magazine. Published April 2022. Accessed May 6, 2024. https://www.aao.org/eyenet/article/step-therapy-clinicians-concerns-and-challenges.
  3. Kherani S, Kim JE. A DRCR Retina Network Update A to Z. Retina Today. Published September 2022. Accessed May 6, 2024. https://retinatoday.com/articles/2022-sept/a-drcr-retina-network-update-a-to-z.
  4. Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial. Ophthalmology. 2016;123(6):1351-1365. doi:https://doi.org/10.1016/j.ophtha.2016.02.022
  5. Jhaveri CD, Glassman AR, Ferris FL 3rd, et al. Aflibercept Monotherapy or Bevacizumab First for Diabetic Macular Edema. N Engl J Med. 2022;387(8):692-703. doi:10.1056/NEJMoa2204225
  6. Chakravarthy U, Bailey CC, Johnston, et al. Characterizing Disease Burden and Progression of Geographic Atrophy Secondary to Age-Related Macular Degeneration. Ophthalmology. 2018;125(6):842-849. doi:https://doi.org/10.1016/j.ophtha.2017.11.036
  7. Berkowitz ST, Finn AP, Parikh R, Kuriyan AE, Patel S. Ophthalmology Workforce Projections in the United States, 2020 to 2035. Ophthalmology. 2024;131(2):133-139. doi:https://doi.org/10.1016/j.ophtha.2023.09.018
John W. Kitchens, MD
About John W. Kitchens, MD

John W. Kitchens, MD, received his undergraduate degree from the University of Evansville, and his Doctor of Medicine degree from Indiana University School of Medicine. He served his ophthalmology residency at the University of Iowa Hospital. Dr. Kitchens completed his fellowship and was the chief resident at Bascom Palmer Eye Institute in Miami.

Dr. Kitchens enjoys speaking both nationally and internationally about new treatments for age-related macular degeneration (AMD), diabetes, and vascular disease. Dr. Kitchens has developed several innovative surgical techniques and has been awarded the American Society Retina Specialists “Rhett Buckler” Award on three different occasions.

John W. Kitchens, MD
Chirag Jhaveri, MD
About Chirag Jhaveri, MD

Chirag Jhaveri, MD, is a board-certified ophthalmologist at Retina Consultants of Austin. He completed his undergraduate education at the University of Texas at Austin, where he was a part of an accelerated honors program. After graduating, he returned to his hometown in Houston and attended the Baylor College of Medicine.

He later received internship training at the Emory University School of Medicine as well as residency training at Louisiana State University Health Sciences Center and the Ochsner Medical Center, where served as a chief resident during his senior year.

Dr. Jhaveri then completed an intense fellowship in vitreo-retinal diseases and surgery at Northwestern University in Chicago gaining invaluable experiences in rare retinal diseases. He holds a special interest in complex vitreoretinal diseases as well as common eye conditions like diabetic retinopathy and macular degeneration.

Chirag Jhaveri, MD
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