Many patients with diabetes can be stabilized with anti-VEGF biologics.
Reviewed by Daniel Kiernan, MD
When managing 2 complicated diabetic macular edema (DME) cases, 1 with DME with nonproliferative diabetic retinopathy (NPDR) and the other with diabetes and DME, each must be treated on an individual basis with consideration of the patients’ confounding factors, according to Daniel Kiernan, MD, a retina specialist at the Eye Associates in Sarasota, Florid, focusing on an Opthalmology Times Case-based Roundtable.
A 62-year-old man with long-term type 1 diabetes presented with decreased vision, wavy lines, and occasional floaters bilaterally. He took antidiabetic medication to control hemoglobin A1c, (HbA1c), which was 6.4.
His phakic right and left eye visual acuities (VAs) were 20/80 and 20/40, respectively, in September 2021, with normal IOPs, moderate cataracts, and dilated findings consistent with DR. Optical coherence tomography (OCT) showed microaneurysms, hemorrhages, and diffuse DME bilaterally, some center-involving, without neovascularization. The patient appeared to have PDR.
The patient’s insurance plan required step therapy, and bilateral bevacizumab (Avastin, Genentech) injections were started at the first visit, but the patient had a limited response to bevacizumab. Aflibercept (Eylea, Regeneron) was requested and approved for bilateral injection for vision below 20/40. He continued on aflibercept for several months with some improvements in vision but persistent fluid.
In December 2021, his VAs were 20/80 and 20/50 in the right and left eyes, respectively. The fluid had decreased but persisted and aflibercept was again administered bilaterally. In January 2022, his respective VAs were 20/100 and 20/50 with decreased but persistent fluid and aflibercept was again administered bilaterally. One month later, his VAs were 20/80 and 20/30.
In April 2022, his VAs were 20/70 and 20/40 in the right and left eyes, respectively. His right eye vision was likely affected by the cataract.
The OCT findings were stable and the treatment interval was extended to every 12 weeks bilaterally, with VAs of 20/60 and 20/30. Three months later, because of intra- retinal fluid and decreased VA in the left eye, the treatment interval was decreased to 4 to 5 weeks for that eye. The VA stabilized and the edema improved, and only the left eye was treated with aflibercept.
Ultimately, the patient reached maximal improvement and stabilized; the right eye was treated every 12 weeks, and the left eye every 6 weeks. The biggest factor, in this case, was the insurance barrier to aflibercept, which generally results in better responses compared with bevacizumab.
“Patients should be able to receive those products regardless of prior authorization or any other factors,” Kiernan emphasized. “Unfortunately, there is risk of vision loss when an inferior product is administered to a patient who needs something that works better, and the onus is on the insurance companies to let us do what is right for the patient.”
Kiernan said he believes that with VA worse than 20/40 for patients with DME, aflibercept or ranibizumab should be approved rather than bevacizumab.
A corticosteroid is another treatment option. The dexamethasone implant and the fluocinolone acetonide 0.19-mg implant are approved for recalcitrant edema, especially for chronic edema that might be more inflammatory in nature.
In this case, the patient was switched early to aflibercept and had a great response. His vision likely would improve with cataract surgery. It is important that the retina be stabilized first. DME can certainly worsen if it’s not controlled before cataract surgery, Kiernan said.
A 49-year-old man with type 2 diabetes was referred for DME with blurred vision bilaterally for 6 months that had worsened in the last 3 months. His HbA1c was uncontrolled at 10.5. His uncorrected VA was 20/200. OCT showed extensive intraretinal/subretinal edema and multiple microaneurysms with light paramacular leakage in the left eye. He received a diagnosis of extensive bilateral ME and active high-risk PDR.
Treatment started with bevacizumab followed by panretinal photocoagulation (PRP). As in case 1, this patient also had a poor response to multiple bevacizumab injections and with VAs of 20/80 and 20/200 in the right and left eyes, respectively, he received bilateral ranibizumab 0.3- mg injections but the edema persisted. He later received bilateral dexamethasone intravitreal implants. After 2 months, the ME was largely resolved and his VA improved substantially.
He was scheduled to continue with bilateral ranibizumab injections in a month but was nonadherent and the ME recurred extensively in both eyes, with VAs decreasing to 20/60 and 20/200 in the right and left eyes, respectively. After switching to bilateral aflibercept injections, 2 months later the edema had improved greatly, and his vision stabilized to 20/50 and 20/80. He continued on maintenance aflibercept in both eyes every 8 weeks to maintain a dry macula.
The required step therapy was an issue with this patient. He improved greatly with the combination therapy of ranibizumab and the dexamethasone corticosteroid implant. Switching to aflibercept allowed him to continue maintenance every other month without an additional cortico- steroid implant. Although corticosteroids reduce the cytokine storm seen in DME, they cause cataract progression and increased IOP.
Kiernan’s treatment for many patients with diagnosed diabetes is to stabilize them with anti–vascular endothelial growth factor (VEGF) biologics. If the patient’s response is less than desired, he said he will try a corticosteroid dexamethasone implant.
“If patients can be maintained on the original anti-VEGFs, that is an ideal scenario,” he said. According to Kiernan, if a patient has high-risk PDR, he uses PRP to stabilize that and prevent vitreous hemorrhages or other problems. He uses focal laser sparingly for DME that is not center-involved. Exudates with retinal thickening or large microaneurysms are great targets for focal laser. However, he emphasized that center-involved focal laser has no place in treating these patients, based on the Diabetic Retinopathy Clinical Research Network Protocol I. Delayed or concurrent focal laser is still not as beneficial as anti-VEGF therapy, he said.