Diabetic Macular Edema
Initiating anti-VEGF treatment early for diabetic macular edema (DME) in patients with good baseline vision is associated with better long-term visual outcomes compared with delayed treatment in real-world settings.1 In these real-world scenarios, factors such as undertreatment and the burden of frequent visits lead to poor visual outcomes, highlighting the necessity for durable treatment options.2
First-line Treatment Considerations
There is significant variation in commercial coverage for FDA-approved anti-VEGF therapies used to treat DME. For some insurance plans, restrictions imposed are beyond the FDA label. Additionally, step therapy protocols are common and limit first-line treatment options, with many plans requiring patients to first try bevacizumab (off-label for many retinal conditions) as a treatment.3
These policies can create barriers to accessing necessary care promptly.3 Clinicians must balance effectiveness, safety, and visit frequency with payer policies and patient costs when selecting an anti-VEGF treatment.3,4
As ophthalmologists, we should be aware of available options to choose affordable therapies that effectively manage patients' conditions. The number of anti-VEGF injections administered has increased over the last decade. In particular, faricimab had a 5x higher utilization rate in 1 year (2022-2023) than other injections. This rapid uptake of farcimab shows strong demand for agents with greater or equivalent therapeutic efficacy, with less treatment and/or financial burden.5
Indication Awareness
There are several therapies, both off-label and approved, for diabetic macular edema (DME) that vary in efficacy, safety, and durability.6,7 These include faricimab, aflibercept, ranibizumab, and bevacizumab.6 Table 1 presents the current anti-VEGF therapies available for DME.
Table 1. Current anti-VEGF Therapies for DME6,7
Intravitreal faricimab holds the promise of increased efficacy with a lower treatment burden for patients, as it has dual action on both angiopoietin-2 and VEGF.5 Faricimab (Vabysmo) achieved non‑inferior year‑1 BCVA gains vs aflibercept in YOSEMITE and RHINE and maintained these gains through 2 years, supporting its use as a first‑line option in appropriate DME patients.8
Treatment Selection and Preference
Factors affecting first-line choice include the magnitude and persistence of visual or anatomical benefits, dosing options (e.g., every 8 to 16 weeks), safety profile, and the extent to which the schedule aligns with patient adherence.2,8 Evidence showing that faricimab can sustain vision with longer intervals in many DME patients highlights durability as a crucial factor in treatment preference discussions.8
Diabetic Retinopathy
Disease Progression From DR To DME
Severity of non‑proliferative diabetic retinopathy (NPDR) at presentation is a strong predictor of subsequent development of DME and proliferative diabetic retinopathy (PDR), highlighting the continuum from early DR to sight‑threatening complications. Long-term, practice-based studies demonstrate that the cumulative incidence of DME and PDR rises over time in eyes with more advanced baseline DR.9
Importance Of Early Diagnosis And Intervention
Early detection of high-risk DR enables timely referral and treatment, leading to better visual outcomes than delayed intervention. In eyes with moderate or severe NPDR at baseline, the use of anti-VEGF (with or without laser) resulted in a reduced incidence of PDR and a longer time to PDR.9
Monitoring Strategies And Evolving Management Paradigms
The growing application of anti-VEGF treatments for both DME and vision-threatening DR has led to a shift towards earlier, proactive intervention in high-risk eyes.9 Modern management now relies heavily on regular imaging, such as OCT and wide-field fundus photography, and on risk-stratified follow-up intervals, in both clinical trial protocols and everyday practice.8,9
DME is an endpoint in the diabetic retinopathy spectrum. It's crucial to emphasize the importance of systemic control, regular screening, and timely referral and treatment. Additionally, consider the availability of first-line treatment options and the clinical rationale for choosing a particular option, using comparative trial data.
Sustained Delivery & Long-Term Management
Slow-release delivery systems are crucial for the long-term treatment of retinal diseases such as DME and NPDR. Anti-VEGF therapy has been instrumental in managing choroidal neovascularization (CNV) in both wet AMD and DR. However, the methods used to deliver these therapies, as well as future treatments, raise significant concerns.10
Confidence And Safety
Intravitreal anti-VEGF therapy has been proven in clinical trials improving vision outcomes and quality of life for patients with DME. However, real-world studies show that vision outcomes often do not match trial results, mainly because of less frequent monitoring and treatments. Maintaining frequent visits is challenging and adds a substantial burden to patients, caregivers, and healthcare providers.11
The Port Delivery System (PDS) is a drug-delivery device featuring a surgically implanted, permanent, refillable ocular implant that continuously delivers a tailored ranibizumab formulation into the vitreous. The implant's reservoir can be refilled multiple times through a self-sealing septum located at the center of the flange, enabling drug replenishment via clinic-based refill-exchange procedures.11
Ocular adverse events related to the PDS are generally manageable. In the PAGODA trial, no cases of endophthalmitis or retinal detachment were reported, although one patient experienced implant dislocation, which required explantation. For a separate patient who had septum dislodgment, the implant was not removed and was instead monitored closely.11
Long-acting treatments are particularly valuable for patients who struggle with frequent injections or for practices with limited appointment slots.11 Patient selection should prioritize factors such as disease stability, surgical suitability, adherence history, and the patient's willingness to undergo device procedures to reduce the frequency of visits.12
Durability Of Treatment
Intravitreal injections often fail to achieve long-term efficacy due to several challenges, including the difficulty of overcoming biological barriers in the eye, insufficient bioavailability at target sites, and rapid drug clearance. To address these issues, biodegradable and non-biodegradable implants provide sustained drug release for durations ranging from 6 months to 3 years, respectively.10
In the PAGODA clinical trial for DME, PDS refilled every 24 weeks was as effective as monthly intravitreal ranibizumab injections over 64 weeks, with similar changes in mean best-corrected visual acuity (BCVA) and anatomical outcomes. About 96% of PDS-treated patients did not need any additional ranibizumab injections during refill interval 1 (weeks 16 to 40) and 97% for interval 2 (weeks 41 to 64), demonstrating the durability of this continuous delivery method.11
In the PAVILLION clinical trial for NPDR, PDS refills every 36 weeks improved diabetic retinopathy severity by 2 steps and lowered disease progression compared to patients who were only monitored. This study demonstrated that frequent prophylactic intravitreal anti–vascular endothelial growth factor injections can decrease the risk of progressing to vision-threatening complications.13
Chronic Disease Management
The PDS is refilled with ranibizumab at the clinic approximately every 6 months. Compared with the frequent intravitreal injections usually required, this approach has the potential to reduce treatment frequency and the number of monitoring visits. Patients' satisfaction with their treatment is connected to various aspects of their care and disease process, including in-clinic services and quality of life.11
In patients with DME, Lai et al. reported that 80% preferred PDS, compared to 5% who preferred intravitreal injections.14 For patients with DR, Regillo et al. reported that approximately 76% preferred PDS versus 4% who preferred intravitreal injections.15 Reasons for choosing PDS included fewer treatments, less discomfort, and less time needed for treatment.14,15
As seen in patients who received PDS with ranibizumab for neovascular age-related macular degeneration (nAMD), when patients receive their preferred treatment—whether through shared decision-making, personal choice, or assessed preferences—they tend to report higher satisfaction, increased adherence and compliance, and better clinical outcomes. Evaluating patient preferences is becoming increasingly important in determining the most appropriate treatment, particularly when various treatments are equally effective.16
