Morphological changes in intraretinal microvascular abnormalities after anti-VEGF therapy visualized on optical coherence tomography angiography

Abstract

Background: To examine the baseline morphological characteristics and alterations in intraretinal microvascular abnormalities (IRMAs) in response to anti-vascular endothelial growth factor (anti-VEGF) treatment, documented by optical coherence tomography angiography (OCTA) in diabetic eyes.

Methods: In this retrospective study, IRMAs were evaluated with multimodal imaging (fundus photography, fluorescein angiography, OCTA) in treatment-naïve diabetic eyes before and after anti-VEGF treatment for diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR) and compared to diabetic control eyes with similar diabetic retinopathy (DR) severity that did not receive anti-VEGF therapy. The morphological characteristics of IRMAs on enface OCTA imaging were graded by masked readers at baseline, then after anti-VEGF therapy in treated eyes or after observation in control eyes. Characterization of interval changes in an IRMA were based on the following parameters: branching, vessel caliber and area of adjacent capillary non-perfusion.

Results: The treated group included 45 IRMA foci from 15 eyes of 11 patients, while the control group included 27 IRMA foci from 15 eyes of 14 patients. Following anti-VEGF treatment, enface OCTA demonstrated that 14 foci of IRMA (31%) demonstrated regression with normalization of appearance of the capillary bed, 20 IRMAs (44%) remained unchanged, six IRMAs (13%) progressed with enlargement or development of new IRMAs and five IRMAs (11%) demonstrated complete obliteration defined as IRMA disappearance with advancing capillary drop-out. In the control group, 17 IRMA (63%) remained stable, 8 IRMAs (29.6%) progressed and 2 experienced total obliteration (7.4%). The difference in rank order between the two groups was statistically significant (p = 0.022).

Conclusions: In eyes with DR status post anti-VEGF therapy, foci of IRMAs have a variable course demonstrating one of four possible outcomes: regression, stability, progression or complete obliteration. In contrast, none of the untreated control diabetic eyes demonstrated regression of IRMAs, consistent with known progression of DR severity in high risk eyes. Morphologic evaluation of IRMAs with OCTA may help to monitor changes in retinal blood flow as well as the response to anti-VEGF treatment.

Keywords: Anti-VEGF; DME; Ischemia; OCTA; PDR; Retina.

Fig. 1

Improvement in IRMA with anti-VEGF treatment (Regressed IRMAs). The upper row demonstrates foci of IRMAs (arrows) prior to intervention and the lower row demonstrates improvement of the same IRMA foci after anti-VEGF injection. Note that IRMA branches become incorporated into the surrounding capillary bed with a decrease in convolution of vessels to form a more normal branching pattern. There is also a reduction in the surrounding adjacent area of non-perfusion. Improvement may be partial (red and green arrows) or very marked (yellow and purple arrows)

Fig. 2

Worsening and stability of IRMAs after anti-VEGF treatment. The upper row demonstrates foci of IRMAs (arrows) prior to intervention and the lower row demonstrates the same IRMA foci after anti-VEGF injection. Panels (a, b, g & h) represent progression of IRMAs (yellow and green arrows). The surrounding area of non-perfusion has enlarged with loss of previously adjacent capillaries (white arrow heads). IRMAs in this category either developed more branching (green arrows) or a newly formed IRMAs appeared (yellow arrow). Panels (c, d, i & j) represent IRMA obliteration (drop-out), which is an end-stage progression of ischemia leading to massive obliteration of the vascular bed (white arrow heads), which eventually included the IRMAs itself (purple and orange arrows). Panels e, f, k & l demonstrate stable IRMAs (red and light blue arrows) where there is no change in the area of non-perfusion, IRMAs caliber, or branching

Fig. 3

A graph representing difference of change in IRMAs foci between anti-VEGF-treated and control eyes. Note regressed IRMAs were only observed in the treatment group

Fig. 4

Baseline morphological appearances of IRMAs. Row 1: Dilated trunk IRMA (red arrow) has increased caliber compared to the surrounding capillary bed and end blindly, with either a straight or a slightly curved shape. Row 2: Looped IRMA (green arrow) is a circular loop vascular channel originating from and draining into the same vessel. Row 3: Twisted loop or pigtail IRMA (yellow arrow) is a loop with self-rolling to resemble single or adjacent figures-of-eight with a more irregular twisting pigtail appearance. Row 4: Sea-fan shaped IRMA (blue arrow) has a branching pattern of vascular growth and the feeding and draining vessels are confined to a narrow base, forming the outline of a triangle. Row 5: Net-shaped IRMA (purple arrow) has a complex shape such that the feeding and draining vessels are not confined to a narrow base and cannot be accurately identified, and this IRMA has a rectangular or irregular outline

Fig. 5

Diffrence in IRMAs changes in after anti-VEGF treatment across various baseline morphological shapes. There was no significant difference in the grading, across all parameters, pre- and post-treatment between IRMAs morphologies (all p > 0.4), suggesting no clinical prognostic significance to the different morophologies