Welcome back to Retina Mentor Moments. In this episode, John W. Kitchens, MD, sits down with Ehsan Rahimy, MD, to discuss the impact of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on diabetic retinopathy and NAION, the efficacy of curcumin supplements for proliferative retinal disease, and how ophthalmologists can use electronic health record (EHR) databases to investigate clinical questions.
Dr. Rahimy is a retina specialist and adjunct clinical associate professor of ophthalmology at the Stanford University School of Medicine in Palo Alto, California, who has authored over 100 peer-reviewed publications and numerous book chapters in retina.
Management of dislocated premium IOLs
Intraocular lens (IOL) dislocation is an uncommon but serious post-operative complication of cataract surgery, with a reported incidence rate of 0.2 to 3%.1 Of note, the actual incidence rate may be even higher, as the number of patients undergoing cataract surgery has grown exponentially in recent years.1
Finding a solution for a growing problem
Dr. Rahimy has observed more patients with premium (i.e., multifocal or toric) lenses experience IOL dislocation, and in fact, one patient with a dislocated multifocal IOL (the enVista Envy) even approached him to ask if he could suture the IOL to her eye. In response, he mentioned that scleral fixation of the IOL may be an option to maintain the patient’s quality of vision.
Scleral fixation with Gore-Tex sutures is Dr. Rahimy’s preferred technique for Akreos AO60 (Bausch+Lomb) and enVista (Bausch+Lomb) IOLs because it allows for relative ease of insertion and fixation via small corneal incisions, minimized IOL tilt, avoidance of iris contact, and potentially lower risk of lens dislocation.2
The patient was interested in the procedure, and although the lens couldn’t be rescued, fortunately, Dr. Rahimy obtained the IOL for an affordable price through a Bausch+Lomb program. He recently saw this patient for a follow-up, and she currently has a best-corrected visual acuity of 20/25 and is recovering well.
He added that this procedure will not be an option for every patient, but he is cautiously optimistic that it is a potential solution for patients with dislocated premium IOLs. As such, he plans to collect and analyze the data of five to 10 more patients who undergo this procedure before drawing more concrete conclusions about its efficacy.
To learn more about Dr. Rahimy’s scleral fixation technique for IOL dislocation, watch the interview!
Promising results on the role of curcumin in retinal conditions
Curcumin supplements for PVR
Curcumin is the main component of turmeric (Curcuma longa), a flowering plant in the ginger family that exhibits anti-inflammatory, antioxidant, antibacterial, and neuroprotective properties—making it a promising candidate for ocular therapy.3
Dr. Kitchens highlighted a recent proof-of-concept clinical study published in Retina that evaluated the outcomes of patients who underwent rhegmatogenous retinal detachment (RRD) repair and started oral curcumin for proliferative vitreoretinopathy (PVR) prevention.4 They found that oral curcumin was well tolerated and warranted further investigation for its potential to reduce the risk of PVR after RRD repair in eyes at higher risk of PVR.
Curcumin supplements for AMD
With this growing interest in curcumin, Dr. Rahimy co-authored a study published in JAMA Ophthalmology that assessed the outcomes of patients with and without age-related macular degeneration (AMD) who took curcuma-based nutritional supplements (CBNS).5
The research team used TriNetX to collect EHR data from 2004 to 2024 and stratified patients with and without AMD by instances of CBNS prescription records. They included 66,804 patients taking CBNS and 1,809,440 patients not taking CBNS in the analysis.5
The study found that compared to matched patients not taking CBNS, patients without a history of AMD (aged 50 years and older) who took CBNS were associated with lower rates of developing:5
- Blindness (relative risk [RR]: 0.46)
- Exudative AMD (RR: 0.28, P<0.001)
- Nonexudative AMD (RR: 0.23, P<0.001)
- Requiring intravitreal anti-VEGF therapy (RR: 0.15, P<0.001)
- Advanced nonexudative AMD or GA (RR: 0.11, P<0.001)
In addition, for patients with early nonexudative AMD, subsequent instances of CBNS prescription records were associated with lower rates of developing advanced nonexudative AMD or geographic atrophy (RR: 0.58, P<0.001).5
Dr. Rahimy noted that many of the patients on CBNS were likely health conscious, potentially contributing to the healthy user effect, which explains that people who are health conscious (i.e., take vitamin supplements, get regular checkups, etc.) typically fare better healthwise than those who do not or are unable to.6
To get more details about this study, check out the Glance story: Study proposes turmeric supplements reduce AMD risk!
The impact of GLP-1 receptor agonists on DR and NAION
Semaglutide and diabetic retinopathy
Interested in comparing the impact of GLP-1 RAs and sodium-glucose cotransporter-2 (SGLT2) inhibitors on vision-threatening complications of diabetic retinopathy, Dr. Rahimy contributed to a study published in the American Journal of Ophthalmology last year that also queried the TriNetX database.7
In total, 6,481 patients with an ICD-10 code of nonproliferative diabetic retinopathy (NPDR) and monotherapy treatment (excluding insulin) were included in both the GLP-1 RAs or SGLT-2 inhibitors cohorts. The rate of progression to proliferative diabetic retinopathy (PDR) and development of diabetic macular edema (DME) were compared between the propensity-score-matched cohorts.7
At 1 and 3 years after initiation of therapy, a higher rate of progression of PDR was noted in the GLP-1 RA group compared to the SGLT-1 inhibitor group (RR: 1.28, P = 0.002).7
In addition, there was a higher rate of DME noted in the GLP-1 receptor agonist cohort at:7
- 3 months (RR: 1.192, P = 0.002)
- 6 months (RR: 1.22, P < 0.001)
- 1 year (RR: 1.24, P < 0.001)
- 3 years (RR: 1.29, P < 0.001)
Semaglutide and NAION in the news
Shortly after the publication of that research, a study in JAMA Ophthalmology on the connection between GLP-1 RA use and the development of nonarteritic anterior ischemic optic neuropathy (NAION) garnered significant media attention.8 The study used the EHR data from 16,827 neuro-ophthalmic patients who presented to Massachusetts Eye and Ear between December 2017 and November 2023.
The study suggested an association between semaglutide and NAION based on key findings such as:8
- In the population with type 2 diabetes mellitus (T2DM), the cumulative incidence of NAION for the semaglutide and non-GLP-1-RA cohorts over 36 months was 8.9% and 1.8%, respectively
- There was a higher risk of NAION for patients receiving semaglutide (hazard ratio [HR]: 4.28, P<0.001)
- In the population of patients who were overweight or obese, the cumulative incidence of NAION for the semaglutide vs non-GLP-1-RA cohorts over 36 months was 6.7% and 0.8%, respectively
- There was a higher risk of NAION for these patients receiving semaglutide (HR: 7.64, P<0.001)
However, the study's limitations and design prevented the authors from establishing causality between GLP-1 receptor agonist use and NAION.8 The American Academy of Ophthalmology (AAO) and North American Neuro-Ophthalmology Society (NANOS) weighed in on the results in a joint statement that noted “the intriguing finding should inspire more research that will help clarify if semaglutide does cause NAION.”9
Discussing the potential connection between semaglutide and DR/NAION with patients
Dr. Rahimy explained that while rare, a paradoxical effect of worsening diabetic retinopathy has been reported in patients with drastic drops in A1c levels caused by rapid improvement in systemic glucose control.10 Of note, this phenomenon has also been reported in trials for insulin treatment and bariatric surgery.11
With this in mind, he explained that, in his opinion, this rebound effect is likely why physicians see diabetic retinopathy progression in patients with recent tight glycemic control. As such, GLP-1 RAs may have less of a direct impact on the retina, with the association being more likely a byproduct of how the medication impacts the individual’s overall health and glycemic control.
This means that physicians should keep an eye out for a large drop in HbA1c levels in diabetic patients. When it comes to GLP-1 receptor agonists and NAION, Dr. Rahimy noted that the relationship remains unclear, and it affects a relatively small number of patients.
Consequently, he tells patients, “We don’t understand exactly everything about this connection. There have been some cases, but if you are doing well on this medication, I’m not going to tell you to stop it.” However, if a patient already has risk factors for NAION, such as a crowded disc, or if they have had NAION before, he takes more time to thoroughly discuss the potential risks associated with semaglutide medications.
Any more recent studies on GLP-1 RAs and NAION?
This year, a research team from the Cole Eye Institute used TriNetX to investigate the relationship between GLP-1 receptor agonists and NAION.12
They analyzed the data of 120,000 T2DM patients with a semaglutide prescription and 220,000 prescribed any GLP-1 RA compared to matched T2DM controls. In patients with high body mass indexes (BMIs), 58,000 were prescribed semaglutide, and 66,000 were on any GLP-1 RA, which were compared to matched controls.12
The team found no significant increase in the risk of NAION or ischemic optic neuropathy (ION) in patients taking semaglutide or GLP-1 RAs compared to T2DM or high BMI controls.12
Conclusion: Using aggregate EHR databases for retina research
As briefly mentioned earlier, TriNetX is a global health research network that features EHR data from over 250 million patients globally (and 117 million in the US) that enables researchers to design patient cohorts using inclusion and exclusion criteria to query population attributes.7
Dr. Rahimy emphasized the importance of artificial intelligence (AI) and big data EHR platforms for researchers, as they allow for streamlined queries by integrating the processing power of AI with clinical information.
Improved access to these platforms has allowed for further democratization, enabling more doctors to uncover valuable insights that can be further investigated.
