Real-World Treatment Strategies Using Next-Generation Therapies for Neovascular AMD and DME

Summary of "Real World Treatment Strategies Using Next Generation Therapies for Neovascular AMD and DME"

This discussion among Dr Ehsan Rahimy, Dr David Miller, and Dr Michael Klufas covers practical strategies for managing neovascular AMD and DME with newer, more durable anti-VEGF therapies.

Real-world data supplements clinical trials by providing safety insights from larger patient populations

Clinical trials typically involve treatment-naive patients while physicians often use new agents in previously treated patients

Real-world practice often differs from trial protocols, especially regarding loading doses and switching therapies

For treatment-naive patients, physicians generally follow recommended loading doses to maximize vision gains

For previously treated patients switching to newer agents (faricimab, aflibercept 8 mg), complete reloading may not be necessary

Disease-specific considerations: AMD typically requires more strict adherence to loading protocols than DME

Both physicians have become more comfortable with 4-week extensions for DME patients

For neovascular AMD, especially in monocular patients, 1- to 2-week extensions remain standard practice due to risk of hemorrhage

Physicians note a sweet spot of 3- to 4-month intervals for most patients, as compliance drops significantly beyond this timeframe

Traditional 12-week caps are being reconsidered with newer agents

Some physicians now feel comfortable extending to 16 weeks in appropriate patients

For DME, extensions to 20 weeks may be appropriate, particularly when hemoglobin A

For neovascular AMD, most remain cautious about extending beyond 16 weeks due to monitoring concerns

Some patients prefer more frequent visits as a “security blanket” despite drug durability

Patient preferences and vision dependence should factor into treatment decisions

Physicians should balance optimal disease control with patient convenience

Extended intervals create challenges in monitoring fellow eyes for conversion

Home monitoring technologies (OCT) show promise but reimbursement and workflow concerns exist

Patient compliance decreases significantly with intervals beyond 4 months

When switching from aflibercept 2 mg to 8 mg, physicians typically see a 2- to 4-week extension in treatment intervals

Benefits of extension often improve over time rather than immediately after switching

Gene therapy shows promise, particularly subretinal injection approaches

Better geographic atrophy treatments remain an unmet need

Tyrosine kinase inhibitors may offer a balance between efficacy and delivery convenience

Suprachoroidal delivery for DME shows potential

This summary provides key clinical insights on treatment strategies using newer anti-VEGF agents, balancing protocol adherence with real-world considerations to optimize patient outcomes.

Ehsan Rahimy, MD; David G. Miller, MD; and Michael Klufas, MD, discuss how real-world treatment strategies for neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) with next-generation anti-VEGF therapies differ from clinical trials, including individualized loading dose approaches, extension interval considerations, and the challenges of balancing durability with appropriate monitoring.

Real-World Treatment Strategies Using Next-Generation Therapies for Neovascular AMD and DME 

David G. Miller, MD 

Head of the Referral Center for Sickle Cell Disease and Clinical Research Department at Hôpital Intercommunal de Créteil of the Université Paris-Est

Bernaudin discussed the Drepagreffe-1 and 2 studies and improvements seen over 10 years of follow-up.

Françoise Bernaudin, MD: A Decade of Follow-up Reveals allo-SCT Superiority Over SOC for Sickle Cell Anemia

Over 10 years of follow-up, allogeneic stem cell transplantation (allo-SCT) demonstrated improvements compared with standard of care (SOC) for patients with sickle cell anemia (SCA) in silent cerebral infarct (SCI) incidence and social quality of life (QoL), working memory, and processing speed.

These findings, from the DREPAGREFFE-2 study (NCT05053932), were presented at the

 66th American Society of Hematology (ASH) Annual Meeting and Exposition

, held December 7-10, 2024, in San Diego, California, by Françoise Bernaudin, MD, the head of the Referral Center for Sickle Cell Disease and Clinical Research Department at Hôpital Intercommunal de Créteil of the Université Paris Cité.

“It's important we have demonstrated that SCT does better than chronic transfusion and better than hydroxyurea, for the outcome of stenosis, to prevent SCI, and to give a better quality of life and higher cognitive performance,” Bernaudin told 

The original prospective DREPAGREFFE-1 trial (NCT01340404) showed modest improvements between allo-SCT and SOC arms, many of which have become significant over 10 years of follow-up.

Notably, Bernaudin and colleagues found that on MRI and MRA, of the 31 SOC group patients, 11 had reported SCIs—an increase of 5 incidences from 6 at enrollment—while there were no additional instances in the 28 patients in the allo-SCT group, which had 12 at enrollment. SCI were either no more visible or under 3 mm in 1 patient in the standard of care group and 4 in the allo-SCT group (

 = .010). Processing speed index (PSI) was higher for the allo-SCT group at 96.5 (SD, 21.9) compared with the standard of care group at 83.7 (SD, 14.4), which was significant (

 = .035), as well as social functioning QoL (allo-SCT: 93.8 [SD, 10.7]; standard of care: 86.4 [SD, 12.9]; 

Bernaudin F, Verlhac S, Ducros-Miralles E, et al. Outcome of Cerebral Vasculopathy and Cognitive Performances 10 Years Post-Enrollment in the Drepagreffe Trial Comparing Allogeneic Stem Cell Transplantation to Standard-Care in Children with Sickle Cell Anemia and History of Abnormal Cerebral Velocities. Presented at: ASH 2024 Annual Meeting. December 7-10, 2024; San Diego, CA. Abstract LBA-5

Françoise Bernaudin, MD

Greg Duck, PA-C is the Director of Internal Medicine and Cardiology Physician Assistant at Acclaim Physician Group in Fort Worth, Texas.

The APAC Recap: Cardiomyopathy at CAPP Live 2024 with Greg Duck, PA-C

, host Laura Ross, PA-C, clinical lipid specialist and president of the Academy of Physician Associates in Cardiology (APAC), interviewed Greg Duck, PA-C, co-chair of APAC’s heart failure committee and director of internal medicine and a cardiology PA at Acclaim Physician Group. Duck shared insights from his CAPP 2024 presentation on 

, a condition he frequently encounters in his practice with underserved populations.

Duck emphasized the importance of understanding the patient’s drug use patterns to tailor medical management and ensure effective treatment. He highlighted the need for careful use of beta blockers in patients actively using methamphetamines to avoid adverse events and promote adherence to therapy. Additionally, Duck shared key clinical pearls, such as medications like wellbutrin and mexiletine causing false-positive methamphetamine urine screens, underscoring the importance of avoiding stigma and mislabeling patients.

The conversation also touched on gaps in guidelines specific to methamphetamine-related heart failure, with Duck recommending adherence to established heart failure with reduced ejection fraction (HFrEF) protocols and regular follow-ups to optimize care. He advocated for transparency in monitoring strategies, such as routine urine drug screens, to build trust with this vulnerable population. Duck concluded with a discussion of the Heart Failure Society of America (HFSA) heart failure certification, encouraging advanced practice providers to pursue this credential to enhance patient care and professional expertise.

All episodes of The APAC Recap will be available on HCPLive.com and our 

Laura Ross, PA-C, interviewed Greg Duck, PA-C, on methamphetamine-induced cardiomyopathy, focusing on its management in underserved populations. Duck stressed understanding drug use patterns for effective treatment and highlighted the cautious use of beta blockers in active methamphetamine users. He noted medications like wellbutrin and mexiletine can cause false-positive urine screens, emphasizing the need to avoid stigma. Duck recommended following HFrEF protocols and regular follow-ups, advocating for transparency in monitoring. He encouraged pursuing HFSA heart failure certification to enhance care and expertise.

Greg Duck, PA-C shared insights from his CAPP 2024 presentation on tailoring medical management and effective treatment of methamphetamine-induced cardiomyopathy.

Greg Duck, PA-C

James Stoller, MD, MS, is a pulmonary/critical care physician at the Cleveland Clinic and Chairman of the Cleveland Clinic Education Institute.

Leveraging AI to Overcome Underrecognition of AATD, with James Stoller, MD

, a genetic condition that can lead to serious lung and liver disease, remains vastly underdiagnosed in the United States—despite clinical guidelines and an increasing need to identify patients eligible for emerging therapies.

chronic obstructive pulmonary disease (COPD)

 and/or liver disease due to AATD are indistinguishable from those without deficiency, necessitating additional tools to establish diagnosis. Research presented at 

the American Thoracic Society (ATS) International Conference 2025

 by James Stoller, MD, MS, a pulmonary/critical care physician at the Cleveland Clinic and Chairman of the Cleveland Clinic Education Institute, suggests a novel AI model may offer a potential tool for identifying symptomatic patients who likely have AATD but are unrecognized.

“[Recognition] is particularly important now, because, somewhat uniquely in the history of alpha-1, there's a pipeline of drugs being developed with very novel approaches. In order to do registrational trials with those drugs, companies need adequate numbers of patients to recruit,” Stoller explained to 

. “With only 15,000 patients recognized in the United States, most of whom are receiving augmentation therapy, many of whom, like my patients, are unlikely to go off augmentation therapy to participate in a randomized, placebo-controlled trial, there won't be enough patients to be able to conduct registrational trials.”

Leveraging claims data from the United States Komodo Health database, Stoller and a team of investigators previously reported an AI model to identify symptomatic patients who likely had AATD but were unrecognized. In the research presented at ATS, they used retrospective deidentified patient data generated from the Cleveland Clinic Electronic Medical Record (EMR) between January 1998 and August 2024 to define and characterize patient cohorts utilized to calibrate and refine the model.

Of 794 patients with AATD, 50.4% of patients were male and the median age was 63 years. A total of 290 (36.5%) patients were identified by genotype (genetic), and the remaining patients were characterized by serum AAT level in the severe (n=117, 14.7%) and mild (n=387, 48.7%) categories.

Investigators noted the prevalence of common comorbidities was lower in the mild subgroup versus the total population and other subgroups. Additionally, they pointed out 12.5% of patients had any AATD augmentation therapy drug in their records.

Investigators further analyzed the AI model’s performance using 21,166 records from the Cleveland Clinic EMR. The calibration and the validation datasets consisted of 582 positive and 5864 negative patients.

Results showed the calibrated model achieved high levels of performance (ROC-AUC=0.89, PR-AUC=0.62) on the hold-out validation subset in distinguishing AATD positive from negative cases. At a discrimination threshold of 0.90, the model achieved high sensitivity=0.70, high specificity=0.92, and balanced accuracy=0.81.

“Like any study, you know, it invites further inquiry,” Stoller said, describing plans to further test the model in clinical practice to determine its utility in these settings as well as to confirm its generalizability beyond this Cleveland Clinic dataset.

Editors’ note: Stoller has relevant disclosures with CSL Behring, Grifols, Metronic, Sanofi, Takeda, and Vertez.

Stoller JK, Khandelwal N, Esmaeili V, et al. Application of an Artificial Intelligence Model to Detect Alpha-1 Antitrypsin Deficiency: Characterizing the Study Population [abstract]. Am J Respir Crit Care Med 2025;211:A4200. 

https://doi.org/10.1164/ajrccm.2025.211.Abstracts.A4200

Stoller JK, Khandelwal N, Liakoni V, et al. Application of an Artificial Intelligence Model to Detect Alpha-1 Antitrypsin Deficiency: Model Performance [abstract]. Am J Respir Crit Care Med 2025;211:A4201. 

https://doi.org/10.1164/ajrccm.2025.211.Abstracts.A4201

Stoller describes the potential of a novel AI model to help address AATD underrecognition, citing findings from his research on its performance in a Cleveland Clinic cohort.

James Stoller, MD, MS

 In terms of avoiding complications, a family that is well educated about the disease, the treatments available, the preventive strategies for complications, including nonmedicinal strategies explicitly, such as mindfulness, good eating habits, exercise within moderation, and good sleep habits, they are going to do far better than the family that does not have these in their lives. Most providers are not well informed about sickle cell disease. Thus, a well-informed parent or adult with the disease who provides information in a nonthreatening fashion can improve their own health care. I would stay abreast of the research as another strategy, because treatment of sickle cell disease in 2020 is vastly different than treatment of sickle cell disease in 2010, and I would wager that curative therapy options in the next decade will be better. We will have improved outcomes with less toxicity. 

Lastly, I would consider all the FDA-approved drugs as potential options for treatment. Particularly for those individuals with hemoglobin SS and S beta-zero thalassemia, with each passing year, we learn more about the benefit of this drug. In my opinion, by far this drug should be in the stable of anyone with hemoglobin SS and S beta-zero thalassemia because the benefits far outweigh any of the toxicities or complications in taking the medication. For the other drug, I think it will take time before the research will demonstrate what the specific benefits are in decreasing the rate of CNS [central nervous system] disease, heart, lung, and kidney disease, as well as potentially priapism and other complications of the disease. But I would say stay tuned because we will learn more about how these additional drugs will prevent complications in organ function in the next decade. 

The first recognition for decreasing opioid dependency is acknowledgment that pain occurs. There should be trust between the provider and the patient, and the patient needs to develop a strategy to manage the pain that is not dependent on opioids but is dependent on first, understanding the triggers, and understanding how to use mindfulness and other strategies to decrease the severity and intensity of the pain. Then, the goal is to learn enough about their disease and enough about their treatment to use a stepwise approach to managing their disease when it comes to acute vaso-occlusive pain. That would include the use of nonsteroidal drug, the use of hydrocodone as a stepwise approach, and then eventually morphine. After the pain subsides, it’s important to stop the medications I just mentioned so the use of pain medications will not result in other complications.

Strategies to avoid complications of sickle cell disease and ensure non-dependency on opioids when treating patients for pain as a result of the disease. 

Unmet Needs in Sickle Cell Disease Management 

Michael R. DeBaun, MD, MPH, Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease 

Columbia University College of Physicians and Surgeons

For what it’s worth, I interview a lot of doctors. I’ve done a lot of panels. What struck me about you folks—the folks who deal with diabetics every day, or people with diabetes—I’m informed that diabetics is not the best term.

Not good—so, people with diabetes, people dealing with this disease. What I noticed is that you listen. Every 1 of you talks about listening to people. Doctors are bad at that, as a group, but not you. Did you select this because you like listening, or did you learn to listen because that’s what you do? I don’t know. It was just an observation. Call it a hunch. Look, we have come to the end of this discussion, but I don’t want to leave without giving each of you an opportunity to say something that you feel we may have omitted or something that you want to leave our audience with. Why don’t we go around, and each of you can take about 30 seconds and give us some final thoughts. Why don’t we start with you, Elaine?

 I’m just thinking back on the patients that I saw today. One of the biggest challenges of diabetes, and dealing with highs or lows, is that you could do everything perfectly Monday to Monday. With other things like saving money, or training for a marathon, you have something to build on. Maybe on the eighth day you can take a day off. That’s not the case with diabetes. You’ve got to start all over again that eighth day and do it all over again, and it may be the worst day of the eight. It’s such a marathon to run, and you don’t have an end line, or point, to look forward to. As a provider, you have to place yourself in that reality. You have to see through the patient’s eyes every day, and if you don’t do that, then you won’t understand their struggles and you miss the boat. That’s what I strive to do every day for them.

Wow, that was well said. Thank you. We really need to understand that, as Elaine has said, diabetes never gives the patient a break; it’s 24-7. Hypoglycemia is incredibly scary and really does limit so much of what the patient can and can’t do if we aren’t careful with educating our patients, assisting with quality of life, and making sure patients have a good understanding of their medications. We need to provide good education on prevention and treatment, and the use of continuous glucose monitoring [CGM] to try and help patients prevent hypoglycemia. We all need to take it seriously and make sure that we ask the right questions every time we touch the patient, so that hopefully we can have a better outcome for them.

I’m going to say something completely different, but I agree with what Elaine and Davida said. I want a system in which the pharmacist tells the patient and me every 2 years when their glucagon is going to expire, so I know to write a new prescription. Because what makes me crazy is when I’ve forgotten and the patient has forgotten to ask, and then they have a bad low and they don’t have their glucagon. Why can’t the pharmacists do this? I get bugged all the time about everything. Why can’t the pharmacist just say, “Patient X needs a prescription for glucagon”? That’s no skin off my back. They should probably just do it without a prescription. Why does this even have to require a prescription? That’s another issue. We need a system so patients and providers are reminded to do the refills. I don’t know why it doesn’t exist, so we need to create that solution.

Could that be built into the EMR [electronic medical record]?

When you click the prescription, it should pop up in 2 years.

 It should just say, “This is due.” Why not?

Jay Shubrook, DO, FACOFP, FAAFP, BC-ADM: 

Hypoglycemia is certainly something that’s very important to our patients, and most providers underestimate the frequency of it. Please ask your patient and the family at every visit about hypoglycemia. There’s no better time than today because we have plenty of tools to identify hypoglycemia, such as CGM, or continuous glucose sensors. We have ways that we can help patients have less hypoglycemia—particularly patients with type 2 diabetes—with novel therapies, and we have very effective treatments that can abort a hypoglycemic episode. Making sure you use the right treatment at the right time really is going to empower your patients not to be paralyzed by hypoglycemia but to be an informed and active crusader to prevent it and treat it earlier.

I want to thank all of you for being with us. This has been eye-opening for me because I don’t treat diabetes on a daily basis. I always thought, “It’s about sugar, for sure; usually it’s about hyperglycemia.” This hypoglycemic problem is real, significant, and tricky. These new therapies that I’ve learned about from you are strikingly interesting. Thank you all for being here.

I want to thank all of you at home for watching this 

. If you enjoyed the content, I want you to subscribe to our e-newsletter to receive upcoming Peer Exchanges and other great content right in your in-box.

Thought leaders in diabetes provide closing remarks about the importance of continuous awareness of glycemic control in patients as well as the need for effective communication between patients and providers. 

Final Thoughts: Awareness and Communication in Diabetes 

Peter Salgo, MD, Columbia University Irving Medical Center 

Riad Sherif, MD is the chief executive officer of Oculis.

New Insight: A Deep Dive into the Oculis Pipeline with Riad Sherif, MD

, host Veeral Sheth, MD, MBA, director of clinical research at University Retina and Macula Associates, spoke with Riad Sherif, MD, CEO of Oculis, about the company's groundbreaking advancements in 

Sherif shared his journey from physician to industry leader, detailing his experiences at Sanofi, Novartis, and Alcon before transitioning to venture investment and eventually leading Oculis. He highlighted how his medical background informs his leadership approach, emphasizing a patient-first philosophy that drives innovation and sustainable growth in drug development.

The discussion delved into Oculis' clinical pipeline, particularly OCS-05, a neuroprotective agent demonstrating promising results in acute optic neuritis. The Phase 2 ACUITY trial showed that OCS-05 preserved retinal ganglion cells (RGCs), reduced axonal loss, and improved low-contrast visual acuity. Importantly, patients receiving OCS-05 experienced significantly fewer multiple sclerosis relapses, suggesting broader neuroprotective potential. Administered intravenously alongside corticosteroids, the therapy could represent a paradigm shift in preserving vision in acute optic neuritis and beyond.

Sheth and Sherif also explored Oculis' lead candidate, OCS-01, a topical treatment for diabetic macular edema (DME) that uses an OPTIREACH® formulation of high-concentration dexamethasone to penetrate the retina. With two ongoing Phase 3 trials (DIAMOND 1 and 2), OCS-01 has the potential to offer a non-invasive alternative or adjunct to intravitreal injections, expanding treatment options for patients with DME. Additionally, Oculis' OCS-02, a TNF inhibitor for dry eye disease (DED), integrates a biomarker-driven precision medicine approach, ensuring targeted therapy for responders and potentially revolutionizing dry eye treatment.

Sherif provided insight into Oculis' international operations, highlighting its dual listings in the US and Iceland, the latter a strategic decision to engage Icelandic investors and maintain strong ties to the company’s research roots. He underscored the importance of assembling a high-caliber, mission-driven team to ensure successful execution in an unpredictable scientific landscape.

Looking ahead, Sherif noted that Oculis is focused on executing its clinical programs, particularly finalizing patient randomization in the DIAMOND trials, advancing precision medicine for inflammation, and expanding indications for OCS-05 in neuroprotection. In particular, he envisioned OCS-05 as a potential game-changer addressing significant unmet needs in ophthalmology by preserving vision and improving the quality of life for patients facing vision-threatening diseases.

Every episode of New Insight is available on HCPLive.com. Watch full episodes on our

and listen wherever you get your podcasts. Please direct all podcast-related inquiries to producer Connor Iapoce (ciapoce@mjhlifesciences.com)!

Veeral Sheth, MD, is joined by the CEO of Oculis to discuss the company's ophthalmic pipeline, including OCS-01 for DME and OCS-05 for acute optic neuritis.

Riad Sherif, MD

Steven R. Sarkisian, Jr., MD, is the founder and chief executive officer of Oklahoma Eye Surgeons.

Sustained IOP Reduction With iDose TR, With Steven R. Sarkisian, Jr., MD

Administration of a travoprost intracameral implant, 75 mcg (iDose® TR), led to a significant reduction in both intraocular pressure (IOP) and IOP-lowering medication burden at 36 months among individuals with 

American Society of Cataract and Refractive Surgery (ASCRS) Annual Meeting

, the mean IOP reductions hit 6.2 mmHg and 7.0 mmHg for the travoprost intracameral implant versus timolol, while a significantly higher number of eyes receiving the implant were on the same or fewer IOP-lowering medications.

“Basically, 80% of people were medication-free, and there was a significant drop in pressure that was sustainable out to three years in this particular data set from the clinical trial comparing timolol and the iDoseTR,” investigator Steven R. Sarkisian, Jr., MD, founder and chief executive officer of Oklahoma Eye Surgeons, told 

. “It demonstrated a 6.5 IOP mmHg pressure at a year and then maintained that 6-6.5 drop in pressure at 36 months.”

The study population comprised individuals with open-angle glaucoma or ocular hypertension from the prospective, randomized, multicenter Phase 3 trial, GC-010. Participants were treated with 0–3 IOP-lowering medications before the study, with a baseline unmedicated mean diurnal IOP ≥21 mmHg and IOP ≤36 at each baseline diurnal timepoint.

Participants received a slow-eluting travoprost intracameral implant (n = 197) or timolol 0.5% BID eyedrops (n = 193). Investigators also evaluated a fast-eluting travoprost implant (n = 200) in the trial.

An analysis measured the IOP-lowering treatment effect and the percentage of eyes in the commercially approved travoprost intracameral implant group, compared with the timolol group on the same or lower number of IOP-lowering medications. Analysis occurred at Months 12, 18, 24, 30, and 36, compared with the pre-study period.

Upon analysis, the mean IOP reductions for the travoprost intracameral implant and timolol cohorts were 6.5/7.0 mmHg at 12 months, 6.4/7.0 mmHg at 18 months, and 6.3/7.0 mmHg at 24 months, followed by 6.3/7.0 mmHg at 30 months, and 6.2/7.0 mmHg at 36 months, respectively. Reductions in all visits for both cohorts were statistically significant from baseline (

Further analysis found a significantly higher number of eyes receiving the travoprost intracameral implant vs timolol were on the same or fewer IOP-lowering medications at 12 months (92% vs. 70%; 

 =.0338), compared with the pre-study period.

“I think the iDose TR fits very nicely as a second-line therapy, and I know that it's going to be hard to shake the paradigm of eye drops not being second-line therapy,” Sarkisian told 

. “As we see this unfold over time and as insurance coverage improves, where it's not just Medicare patients that are getting reimbursed for this, I think that we're going to see a lot of eyes that are going to be be saved from blindness because they're going to have perfect compliance with the medication.”

Relevant disclosures for Sarkisian include AbbVie, Allergan, Bausch & Lomb, Glaukos, Novartis, Ocular Therapeutix, and others.

Singh IP, Sarkisian SR, Kothe AC, Katz LJ, et al. Reduction in IOP and Topical IOP-Lowering Medication Burden through 36 Months with the Travoprost Intracameral Implant. Paper presented at the 2025 American Society of Cataract and Refractive Surgery (ASCRS) Annual Meeting. April 25-28, 2025. Los Angeles, CA.

Travoprost intracameral implant significantly reduces intraocular pressure and medication use in patients with glaucoma over three years.

Steven R. Sarkisian, Jr., MD

Timothy McCulley, MD, is professor and chair of the Ruiz Department of Ophthalmology and Visual Science at McGovern Medical School at UTHealth Houston. He also holds the Richard S. Ruiz, M.D. Distinguished University Chair.

As glucagon-like peptide 1 receptor agonists (GLP-1 RAs) gain widespread use for diabetes and obesity, their ocular implications are becoming increasingly relevant for 

, Timothy McCulley, MD, a professor and chair of the Ruiz Department of Ophthalmology and Visual Science at McGovern Medical School at UTHealth Houston, outlined three key concerns related to these medications.

McCulley presented a talk entitled "Glucagon-like Peptide-1 (GLP-1) Receptor Agonists Update for the Ophthalmologist” at the 

Texas Ophthalmological Association (TOA) Annual Meeting

As GLP-1 RAs delay gastric emptying, McCulley highlighted the need for preoperative precautions to prevent surgery cancellations due to anesthesia risks. Although data remains inconclusive, reports suggest a potential link between GLP-1 RAs and optic nerve ischemia, prompting caution for patients with a history of ischemic optic neuropathy. Finally, a temporary worsening of diabetic retinopathy has been observed upon initiating GLP-1s, though the effect is generally mild and does not warrant avoiding the drug in affected patients.

McCulley emphasized the importance of patient counseling regarding these risks, particularly for those with optic nerve ischemia, both for their protection and to mitigate potential medicolegal concerns. Looking ahead to 2025, McCulley identified artificial intelligence as a dominant theme in ophthalmology, with its role in diagnostics and treatment still unfolding.

This transcript has been edited for clarity.

: With the expanding use of GLP-1 RAs for diabetes and obesity, what are some of the more significant ocular implications that more ophthalmologists should be aware of? What conditions should they be closely monitoring?

There are three main ones. One, it delays gastric emptying, so when we do surgery, anesthesiologists want patients to have stopped the GLP-1 inhibitors prior to the day of surgery. And if you don't know that and don't warn your patient, your surgeries get canceled.

Number two, there have been reports of optic nerve ischemia occurring in patients with GLP-1s. I don't know that there's enough data to say definitively that the association is real and not coincidental, but regardless, if you have a patient with an ischemic optic neuropathy in one eye, it's probably best to play it safe and tell them to stop their GLP-1 inhibitor.

In case there is an association, it can protect the other eye, and if nothing else, from a medical legal standpoint, you probably ought to tell them because if the other eye gets involved, and you didn't tell them that, it could be the source of a lawsuit.

And lastly, there is probably a mild, temporary worsening of diabetic retinopathy when patients start the GLP-1 inhibitors. And it is thought to be mild and not to the degree that you should avoid the drug in patients with diabetic retinopathy. And that pretty much sums it up.

: When discussing GLP-1 use and diabetic retinopathy risk, is it a patient-provider conversation, or does it involve their endocrinologist or primary care specialist?

It might be something for the folks that are prescribing the GPL-1 inhibitors to warn patients about and suggest that they go see their ophthalmologist, but I doubt they're going to get on the phone with us. It's not, how do I put this, that big of a deal?”

: What unanswered questions remain for an ophthalmologist? As GLP-1 use continues to grow, what should they keep an eye out for?

Be aware of when you have patients with ischemic optic neuropathy, about the potential association, and be sure to counsel your patients accordingly, for their sake and your sake.

: We're about a quarter of the way through 2025. What are some of the main storylines in ophthalmology that are unfolding?

In all of medicine, it is going to be artificial intelligence. That's going to be number one, seeing how that plays out. I don't know if excitement is the right word, but a whole lot of attention is on it. It's going to fall flat, or it's going to take over. But artificial intelligence is probably number one. The other thing that, not just in ophthalmology, but we have a lot of targeted therapy these days. We have these monoclonal antibodies that are specific for treating malignancy and inflammation, but targeted immunotherapy is revolutionizing how we treat a number of diseases.

McCulley reports no relevant disclosures.

McCulley TJ. Glucagon-like Peptide-1 (GLP-1) Receptor Agonists Update for the Ophthalmologist. Presented at Texas Ophthalmological Association (TOA) Annual Meeting. Houston, Texas. March 21-22, 2025.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), used for diabetes and obesity, have significant ocular implications. These include delayed gastric emptying, which necessitates preoperative precautions to avoid surgery cancellations. There is a potential, though inconclusive, link between GLP-1 RAs and optic nerve ischemia, warranting caution in patients with ischemic optic neuropathy. Additionally, a mild, temporary worsening of diabetic retinopathy may occur when initiating GLP-1 RAs. Patient counseling is crucial to address these risks and mitigate medicolegal concerns. Artificial intelligence is anticipated to play a significant role in ophthalmology by 2025.

McCulley examines the latest updates on GLP-1 receptor agonists relevant for ophthalmologists and patients with ophthalmic diseases at TOA 2025.

Unpacking the Ocular Impact of GLP-1s with Timothy McCulley, MD

Timothy McCulley, MD

 I’ve enjoyed the opportunity to talk with you because I’ve learned a ton. Your experience and acknowledge is outstanding. To wrap this up, what would be your take-home messages for health care providers treating opioid-induced constipation?

 One would be to open the conversation if you see it on their list. I find that being a PCP [primary care physician] these days is the hardest job. The patients are living longer and in and out of the hospital. With the amount of record review, interaction with the charts, and certain care measures, this may be 10th on the list. They may be doing well from a pain relief perspective. We ask that question, but it’s hard when they have a million other medical problems. But it’s a simple question.

Patients oftentimes don’t want to bring it up or talk about it. It’s embarrassing. But it can affect their quality of life. We’re happy to help. I’m happy to see patients and have the longer discussion with them, especially if we can initiate the appropriate-line therapies to start. It’s important to open that conversation and ask them the simple question: “I see you’re on opiates. How are your bowel habits?” If there’s an issue, then start to get them on the right track to treatment, because it’s very efficacious and safe, as we talked about. They don’t have to bear this burden. We can help fix it for them.

 Yes, the conversation or even the prompt to have that conversation is important. We transitioned to electronic intake forms, and we have smart responses, where if somebody is taking opioids, it starts to ask about all the things related to opioids, including feeling sleepy, being able to function at work, and driving. Constipation came up there, and we were surprised by the number of people who were responding to this. We had never thought to have that discussion. With the time that you have to be able to discuss this, it might be very low on the list. But if you’re able to screen and have the conversation based on that response, it cuts out a lot of time, and thankfully we have some great options to choose from that will make the conversation go quickly and smoothly.

 Excellent. Thank you once again for participating in 

Expert Perspectives in the Management of Opioid-Induced Constipation

A panel of experts discuss their key takeaways and the future of treating opioid-induced constipation. 

Authors