Several environmental and genetic factors contribute to the pathogenesis of age-related macular degeneration, but many in the scientific community debate the role of diabetes mellitus in the more advanced neovascular age-related macular degeneration (nAMD), questioning whether it contributes to or protects against the disease progression. Using OCT-A to observe the morphological changes in type 1 exudative macular neovascularization (MNV) following one year of anti-VEGF therapy, researchers found patients with mild diabetic retinopathy had a divergent response in type 1 MNV lesion area.

Researchers report that during anti-VEGF therapy, macular neovascularization lesion size continued to decrease in the non-diabetic group over the course of 12 months, but had a smaller decrease in the diabetic group, suggesting the disease may be a risk factor to consider during anti-angiogenic treatment. Photo: Boscia G, et al. Invest Ophthalmol Vis Sci. August 2, 2024

According to their findings, recently published in the journal Investigative Ophthalmology & Visual Science,¹ although there was a significant reduction in lesion size between the baseline visit and the post-loading phase, there was no noticeable further reduction in lesion area at the 12-month follow-up visit. Alternatively, nAMD patients with no history of DM had a continuous reduction in MNV size. Researchers say this highlights the significance of DR as a potential modifier of treatment outcomes in nAMD management, with DM considered a risk factor during anti-angiogenic treatment.

The retrospective study included 45 eyes with exudative nAMD with type 1 MNV, all of whom were enrolled at the Medical Retina Service at the University of Bari Aldo Moro in Italy. Patients were divided into the Diabetic group, which included 21 eyes of 21 patients with mild DR; and Not Diabetic Group, which consisted of 24 eyes of 24 patients with no history of DM. The outcome measures included best corrected visual acuity changes, central macular thickness, MNV lesion area, and MNV flow area. All of these parameters showed significant improvement after the loading phase, according to the study.

“The most interesting finding pertained to the behavior of the neovascular lesion after one year of treatment initiation,” they wrote in the study. “Specifically, the Diabetic group did not exhibit a reduction in MNV after 12 months; instead, there was a lack of significant reduction of the area of the MNV. In contrast, the Not Diabetic group showed a continuous reduction in the size of the MNV. This last result appears to be highly significant, especially considering that the size of MNV evaluated with OCT-A serves as a valuable biomarker in assessing the response or lack of response to treatment.”

They speculated about the mechanisms that could be contributing to this result, including the possibility that the presence of DR alters the angiogenic pathways involved in MNV. “DR is associated with dysregulated VEGF signaling and increased levels of inflammatory cytokines, which could potentially lead to a different response to anti-VEGF therapy,” they said. “These altered pathways may result in a reduced responsiveness to anti-VEGF therapy, leading to a less pronounced reduction of neovascularization over time. Another possibility is that the microvascular changes associated with DR, such as capillary dropout and basement membrane thickening, create a less conducive environment for the resolution of neovascular complexes. The compromised vascular structure and function in diabetic eyes may impede the ability of anti-VEGF therapy to induce significant regression of the MNV, resulting in a lesser degree of reduction compared to non-diabetic eyes.”

The sample size was relatively small, noted the authors, which could have potentially limited the generalizability of their results. The lack of control group also means observed differences during the follow-up period could have occurred even without anti-angiogenic therapy. “Furthermore, the use of spectral-domain OCT-A, which utilizes shorter wavelength light compared to swept-source OCTA, may result in reduced signal penetration through the RPE, potentially affecting the accuracy of our imaging data,” they added.

Despite these factors, the authors say they felt confident in the strengths of their study, and say it’s the first comprehensive investigation of the impact of DR on longitudinal morphological and functional changes in type 1 MNV associated with AMD in patients undergoing anti-VEGF therapy for 1 year. The divergent response they discovered in this study highlights the role DR plays in treatment outcomes, and they concluded saying, “Future larger studies utilizing swept-source OCT-A and longer follow-up durations are necessary to validate our preliminary findings.”

^{1. Boscia G, Bacherini D, Vujosevic S, Grassi MO, Borrelli E, Giancipoli E, Landini L, Pignataro M, Alessio G, Boscia F, Viggiano P. Long-term impact of diabetic retinopathy on response to anti-VEGF treatment in neovascular AMD. Invest Ophthalmol Vis Sci. August 2, 2024. [Epub ahead of print.]}

New Aflibercept Biosimilar Approved

Sandoz recently received FDA approval for the company’s aflibercept biosimilar, Enzeevu (aflibercept-abzv) 2 mg vial kit and pre-filled syringe for intravitreal injection. The new drug is indicated to improve and maintain visual acuity in patients with wet age-related macular degeneration. Also, the company says the FDA provisionally determined Enzeevu would be interchangeable with the reference drug as it’s “currently subject to an unexpired exclusivity for the first interchangeable biosimilar products.” 

The approval was based on the company’s Mylight study.¹ Mylight was a prospective, double-masked, two-arm, parallel Phase III study. Participants with wet AMD were randomized 1:1 to receive eight injections of the biosimilar (n=244) or reference aflibercept (n=240) over 48 weeks. The primary endpoint was mean change in best-corrected visual acuity score from baseline to week eight. 

The researchers found similarity in mean change in BCVA score between the biosimilar (n=235) and reference aflibercept (n=226) at week eight, and out to Week 52. They reported no clinically meaningful differences between groups in terms of anatomical outcomes. The drugs’ safety profiles were similar, with comparable incidences of treatment-related adverse events (Enzeevu: 2.5 percent; reference aflibercept: 2.9 percent).

^{1. Bordon AF, Kaiser PK, Wolf A, et al. Efficacy and safety of the proposed biosimilar aflibercept, SDZ-AFL, in patients with neovascular age-related macular degeneration: 52-week results from the Phase 3 Mylight study. Retina 2024;10.1097/IAE.0000000000004174.}

New Metamorphopsia Tool Studied

It’s tough to know exactly what a patient sees, particularly if they have a visual disorder such as metamorphopsia. The symptom, often arising from displaced photoreceptors at the macula, is commonly present in AMD and vitreoretinal conditions; understanding the patient’s experience of it can be valuable to disease management. The tried-and-true Amsler grid isn’t able to map the exact image distortion experience in any way that a clinician can experience first-hand. Recently, however, researchers from London published a novel method of assessing this visual phenomenon called the Image Warping Test (IWT).¹ Their paper, published in Retina, found that this test compared favorably to established measurement tools. 

The IWT is a uniocular test in which the patient is presented with a grid of black lines on a white background displayed on a computer monitor. This background is dynamically warped by an operator until the grid lines appear straight to the patient and the metamorphopsia is canceled out. “The reversal of this correction generates a grid which represents the pattern of the participant’s metamorphopsia,” the researchers explained in their paper.

They analyzed metamorphopsia measurements of 25 volunteer subjects who had metamorphopsia secondary to vitreoretinal pathology. Tests included standard Amsler grid, a modified Amsler grid called Morphision (in which the central area is presented in a warped pattern), the M-Charts collection of grids and the IWT.

They reported no correlation between best-corrected distance visual acuity and IWT score or between M-Charts score and IWT score, but they did find several significant associations between subjective estimation of severity and IWT score; between Morphison result and IWT score; and between vitreoretinal pathology and IWT score.

The researchers wrote in their Retina paper that the value of the IWT over other established measures “is its ability to create a digital map of the metamorphopsia experienced. Such mapping opens the possibility of non-invasive treatment through inversely mapping the distortion onto images or video, providing personalized correction of distorted vision. Combined with a ‘see-through’ head mounted display with forward facing video cameras, live video feed and gaze tracking, there is the real potential to dynamically correct metamorphopsia in [the] future and improve quality of life as a result.” 

^{1. Suárez CV, Than J, Ling Y, et al. The image warping test: A novel method to quantify and quality metamorphopsia. Retina 2024. [Epub ahead of print].}