Advancing treatment strategies for retinal vascular diseases with durable therapies

(Image Credit: AdobeStock/Lili.Q)

In an Ophthalmology Times Case-Based Roundtable discussion, Talia R. Kaden, MD, described cases of polypoidal choroidal vasculopathy (PCV) with neovascular membranes, diabetic macular edema (DME), recurrent edema in retinal vein occlusions (RVOs), and neovascular age-related macular degeneration (nAMD) with persistent subretinal fluid and treatment with faricimab (Vabysmo; Genentech) and 8 mg aflibercept (Eylea; Regeneron Pharmaceuticals, Inc). Kaden is an assistant professor of ophthalmology at Manhattan Eye, Ear and Throat Hospital, Northwell Health, New York.

Many clinicians are using these drugs and have been satisfied with the results in DME, RVO, and nAMD; however, not all drugs are approved for every indication.

Case 1: PCV

A 90-year-old woman presented with decreased vision and was diagnosed with PCV. She was initially treated with faricimab and showed improvements in subretinal fluid, central subfoveal thickness, and vision. With monthly treatment, her presenting large, central pigment epithelial detachment (PED) resolved, and the patient reported a notable difference in symptoms with accompanying visual improvement. The patient was then lost to follow-up for 6 months, with subsequent treatment interruption. When she returned, her PED had recurred and enlarged. When therapy resumed, the PED again resolved and her vision improved. “This case underscores that these patients need chronic therapy, even when the PED has fully resolved,” Kaden said.

She and the other participants then discussed the risk of retinal pigment epithelial (RPE) tears and whether the risk increases with the use of more effective antivascular endothelial therapies. Some factors are associated with a higher risk of RPE tear, including the vertical height and the diameter of the PED. A debate ensued about whether a “stronger” drug should be avoided in these patients to minimize the risk of a tear. Many pointed out that there is a risk with any agent and emphasized the importance of specific counseling in patients with large PEDs.

Case 2: Treatment-naive DME

A previously untreated 74-year-old man had significant, bilateral DME. After treatment with faricimab, his edema resolved, allowing him to continue work as a truck driver.

“This patient presented with 20/100 vision and was unable to renew his commercial driver’s license,” Kaden said. “With treatment, [his vision] improved to 20/30. This meant the difference between forced retirement vs maintaining his job.”

She discussed the role of these anti-VEGF agents in the resolution of hard exudates. The data suggest that the more durable drugs result in greater improvement of the hard exudates. Kaden is paying close attention to this effect, especially when the exudates are near the fovea; in this scenario, patients are often acutely aware of the visual impact of the exudates. In addition, information about these exudates can suggest the disease’s chronicity and the need for aggressive treatment.

A roundtable discussion indicated that the new agents are more efficacious and durable. “Greater durability is only possible in the setting of greater efficacy,” she said. “When comparing drugs at the same time point, one drug may achieve more retinal dryness and effectiveness than another and allow longer treatment intervals.”

The use of biosimilars was another discussion point. Although some clinicians have access to the ranibizumab biosimilar, most do not due to lack of availability. Other issues may be the ability to store more drugs and the perceived benefit of adding another drug to the armamentarium, Kaden explained. However, as an aflibercept biosimilar becomes available, it may be used more widely.

The use of glucagon peptide (GLP) agonists was discussed in relation to increased or decreased diabetic retinopathy (DR). Kaden said no great data can support either. “Some of my patients have had worsened DR, but given the data [that] show the success of GLP agonists in treating systemic diseases, I always encourage my patients to continue with the care recommended by their primary doctors and endocrinologists,” she said. “We can manage any retinopathy that ensues.”

Kaden noted that “if DR does occur in patients treated with GLP agonists, they should have more frequent or regularly scheduled visits to treat that uptick in DR.”

Case 3: RVO

A 60-year-old man was a long-term patient of Kaden's and had a history of RVO. He reported that his vision at diagnosis was count fingers, and he was treated with bevacizumab (Avastin; Genentech) for 3 years. When he presented to Kaden, his vision was 20/40, with persistent intraretinal fluid, cysts, and some subretinal fluid.

Treatment with 7 injections of ranibizumab (Lucentis; Genentech) resulted in improved vision, but the treatment interval remained constant at 5 to 6 weeks. A large central cyst persisted over time, despite a switch to aflibercept 2 mg. A month after another switch to dexamethasone, the clinical scenario was the same; 2 months later, with a second dexamethasone injection, the IOP started to increase and later increased to over 40 mm Hg. The steroid was stopped and the patient was started on topical drops, which successfully lowered his IOP.

The initial take-home message here was that clinicians should be alert to a potential delayed increase in IOP with steroid use. In this case, the patient’s IOP eventually normalized off of drops, but his vision continued to worsen and the central cyst persisted.

The treatment was changed back to aflibercept 2 mg and then again to an off-label injection of faricimab. He continued to receive faricimab injections over time, and, after a cataract surgery, his vision improved, the cyst resolved, and the IOP was normal off of drops. The patient could then extend out to 10-week treatment intervals. Kaden pointed out that because different drugs may have differing effects, it is worth trying different drug options to arrive at the best choice for individual patients.

Case 4: nAMD

This 68-year-old man had a history of diabetes and nAMD. At presentation, he had some subretinal fluid and decreased vision to 20/50. Beginning with 2 mg aflibercept, the patient received several different treatments, including faricimab, during which the subretinal fluid kept recurring, thus preventing meaningful extension of his treatment intervals. Because of the risk of recurrent bleeding and intraretinal fluid, Kaden is more cautious about extension in nAMD compared with DME.

His treatment was then switched to 8 mg aflibercept, and although he was initially able to extend his treatment interval, more recently, his subretinal fluid again recurred. Because of such patients who appear resistant to significant extension, Kaden discussed the potential of other treatment options for patients that include gene therapies that are currently in clinical trials, and the reapproval of the Port Delivery System (PDS) with ranibizumab, both for nAMD.

“One of these options might be beneficial for patients like this one, because I have tried so many others that I thought would be more effective,” Kaden said. “[Although] he does well with the drugs, he cannot achieve extended treatment intervals. The PDS might be a more viable option in geographic regions [where] patients must travel great distances for care. This remains to be seen with increasing use of the device.”

Talia R. Kaden, MD

E: tkaden1@northwell.edu

Kaden is an assistant professor of ophthalmology, Manhattan Eye, Ear & Throat Hospital, Northwell Health, New York. She has served as a consultant to AbbVie; Alimera Sciences, Inc; Genentech; and Regeneron Pharmaceuticals, Inc.