Welcome back to Retina Mentor Moments! In this episode, John W. Kitchens, MD, sits down with Jordana Fein, MD, MS, to discuss how to implement clinical research in a retina practice, clinical pearls for managing geographic atrophy (GA), and findings from a post hoc analysis of the CANDELA study.
Dr. Fein is a retina specialist at The Retina Group of Washington (RGW) in Fairfax, Virginia, and an assistant clinical professor of ophthalmology at the Georgetown University School of Medicine in Washington, DC.
Incorporating teaching and clinical research into a retina career
Dr. Fein explained that RGW leads and administers a clinical and research fellowship program with four total spots in collaboration with Georgetown University and the Washington Hospital Center.1 As faculty, she supervises third-year residents in the Lions Eye clinic performing cataract surgery and fellow ORs, while also leading clinical trials at RGW as a principal investigator (PI).
This blend of teaching and research is unique to the practice and keeps her on the cutting edge of retina care, as there is cross-pollination in surgical techniques that allow both trainees and attendings to develop a tailored approach to patient care while expanding their armamentarium.
During her residency and fellowship, Dr. Fein learned how to organize and lead clinical trials from mentors and gained hands-on experience as a sub-investigator. Consequently, when she began practicing at RGW’s busiest research site, she was well-prepared to take on the unique opportunity to participate in clinical research.
With consistent engagement, time, and encouragement from mentors at the practice, she eventually transitioned to leading studies as a PI, which had a domino effect that led to presenting study outcomes at conferences and building relationships with other researchers across the country.
Implementing clinical trial research in a private retina practice
Both Drs. Kitchens and Fein highlighted the importance of experienced research coordinators and certified technicians to administer the day-to-day work at a busy research center. RGW covers a large territory that includes Maryland, Washington, DC, and Virginia, so initially there were two full-time research sites, with one in Maryland and the other located in Virginia.
However, the practice is currently in the process of developing a third center, which presents unique challenges in terms of staffing, as the site requires masked and unmasked study coordinators and certified photographers, VA testers, and machines.
Below are logistical factors to consider when determining the feasibility of integrating clinical research into a private practice:2,3
- Patient population: Having a robust patient network is necessary to meet screening and recruitment requirements for clinical trial enrollment.
- Clinical trial processes and resources: It is necessary to have a strong understanding of how to handle regular practice duties in addition to supervising clinical trials, meeting with the institutional board review, developing budgets, and managing audits and inspections.
- This includes observing good clinical practices (GCPs) to protect the rights and welfare of study participants.
- Staffing the site: Leading a successful clinical trial requires time to handle the administrative duties associated with coordination, recruitment, follow-up, and documentation. This can be completed by a study coordinator who can be a technician or other staff member from the practice that is invested in clinical research.
- A dedicated team of clinicians to run the studies and meet with patients is needed as well as site staff consistency for efficient enrollment and optimal trial execution.
- Preparing the practice space: A study’s sponsor typically inspects a study site before it is approved and again prior to the start of the study, so it is important to ensure that the practice is well-equipped and prepared to execute the trial effectively and efficiently.
- The areas and examination rooms where the study participants are seen should be tidy, accommodating, and well-organized.
- Most studies require a secure room for the investigational product, which needs to be kept separate from the practice’s normal drugs.
- Some drugs may require a fridge, freezer, or additional shelving for storage, and machinery must be maintained, calibrated, and certified according to the manufacturer’s requirements.
- Keeping a dedicated space to house research data and study supplies can be helpful for monitoring visits from the trial sponsor and reviewing data during the study.
New research: Post hoc analysis of CANDELA
Dr. Fein recently led a post hoc analysis of the phase 2 CANDELA trial that provided further insights into previously reported findings by assessing the effect of aflibercept 8mg on total retinal fluid as measured by the proportion of eyes without intraretinal fluid (IRF), subretinal fluid (SRF), and subretinal pigment epithelium (subRPE) fluid in the central subfield at weeks 16 through 44.4
The research team also performed a quartile analysis of central subfield thickness (CST) change from baseline to week 44. For patients who completed the week 44 visit, the change in best-corrected visual acuity (BCVA) from baseline to week 44, the proportion of eyes achieving BCVA 20/40 and 20/20 at week 44, and the proportion of eyes with baseline BCVA < 20/40 that achieved 10- and 15-letter gains at week 44 were calculated.4
Some of the key findings from the study include:4
- In spite of a lower mean CST at baseline in the aflibercept 8mg group (702.2mm) compared to the 2mg group (788.2mm), more eyes treated with high-dose aflibercept achieved CST reductions of > 239mm.
- This suggests that aflibercept 8mg may have a greater effect in patients with thicker retinas.
- A greater number of eyes treated with aflibercept 8mg (38%) vs. aflibercept 2mg (19%) achieved absence of fluid when additionally evaluating sub-RPE fluid together with IRF and SRF at week 16.
- This was maintained through week 44, suggesting an enhanced drying effect and potential therapeutic benefit of aflibercept 8mg as early as week 16.
- When comparing the effect of aflibercept 8mg vs. 2mg on functional outcomes, more eyes achieved 15-letter gains, whereas fewer eyes had any letter loss or no change.
- More eyes in the aflibercept 8mg compared to the 2mg group achieved clinically meaningful BCVA (20/40 and 20/20) at week 44.
In addition, the data from this study confirmed that the difference in volume between 2mg and 8mg aflibercept made no difference in long-term intraocular pressure (IOP) measurements, explained Dr. Fein.
Watch the interview to learn more about the implications of this data on complement inhibitor therapies for GA.
Treating GA patients with concomitant nAMD
GA patients with concomitant neovascular age-related macular degeneration (nAMD) require extra consideration when balancing patient burden with slowing the progression of both diseases with anti-VEGF and complement inhibitor therapies. Dr. Fein emphasized that she does not perform complement inhibitor and anti-VEGF injections on the same day.
Consequently, she aims for these patients (when appropriate) to receive second-generation anti-VEGF agents that allow for extended treatment intervals (ideally every 16 weeks). This simplifies the process of adding a complement inhibitor treatment in alternating months—thereby reducing the risk of patient burnout.
Clinical Pearl: There tends to be a pachychoroid phenomenon in patients with idiopathic polypoidal choroidal vasculopathy (IPCV). The EVEREST study found that these patients tend to have better outcomes with photodynamic therapy (PDT) combined with anti-VEGF compared to anti-VEGF monotherapy.5
To learn more about managing GA in a busy practice and the clinical relevance of choroidal thickness for retinal diseases, watch the full interview!
Conclusion
Dedicated clinical researchers, thoughtful trial design, and careful patient management are transforming how retina specialists approach both GA and nAMD.
By combining evidence-based insights like those from the CANDELA study with practical strategies for implementing research in practice, retina specialists can expand treatment options while simultaneously reducing patient burden and improving overall outcomes.
