Optical Coherence Tomography Angiography Biomarkers Predict Anatomical Response to Bevacizumab in Diabetic Macular Edema

Abstract

To identify biomarkers that may predict an early anatomical response to the treatment of diabetic macular edema (DME) with intravitreal bevacizumab (IVB) by means of optical coherence tomography angiography (OCTA). Methods: This study is a retrospective study of treatment-naïve patients with DME who underwent 6 × 6 mm OCTA imaging of the macula at baseline and after three monthly IVB injections. Thirty-six eyes of 23 patients were included. Eyes that demonstrated evidence of an early anatomical response, consisting of a >10% decrease in central macular thickness (CMT) (n = 18), were compared with those eyes that failed to show such an improvement (n = 18). Results: At baseline, early-response eyes had worse starting best-corrected visual acuity (BCVA, LogMAR 0.84 ± 0.41 versus LogMAR 0.51 ± 0.15, p = 0.004) and a larger CMT (490 ± 135 µm versus 356 ± 33 µm, p = 0.001), but smaller foveal avascular zones (FAZ) (0.309 ± 0.098mm versus 0.413 ± 0.095 mm, p = 0.003) compared with eyes that proved refractory to three monthly injections of IVB. The vascular density (VD) in both the foveal superficial and deep capillary plexuses was significantly greater in eyes that showed an early-treatment response compared with eyes that were non-responders (24.86 ± 6.90% versus 19.98 ± 7.13%, p = 0.045 and 32.30 ± 4.88% versus 26.95 ± 7.25%, p = 0.028, respectively). Early-treatment response to IVB was predicted by starting CMT (r 2 = 0.266, p = 0.001), FAZ size (r 2 = 0.234, p = 0.003), and VD in the superficial parafovea (r 2 = 0.217, p = 0.004) and deep fovea (r 2 = 0.157, p = 0.037). Conclusion: Projection-resolved OCTA may be useful in predicting an early anatomical response of DME to treatment with IVB.

Predictive factors for treatment outcomes with intravitreal anti-vascular endothelial growth factor injections in diabetic macular edema in clinical practice

“…Apart from OCT, other imaging modalities like FA and more recently OCT-A can be incorporated in evaluation of DME [ 83 , 84 ]. Both these imaging modalities especially help in assessment of DME including, macular microvasculature, foveal avascular zone, and ischemic maculopathy; factors which need to be considered when assessing poor treatment outcomes in DME [ 32 , 85 ]. FA while is considered an invasive procedure was not performed in majority of our study participants, and OCT-A (a non-invasive modality) was not available in any of the centers at the time of data collection.…”

“…Response to anti-VEGF injections has also been reported to be influenced by different morphological subtypes of DME, with the sub-type diffuse retinal thickening showing the least improvement and serous retinal detachment showing the most improvement [ 30 ]. Diabetic macular ischemia (characterized by increased foveal avascular zone), which often occurs alongside DME also contribute to poor treatment outcome [ 31 , 32 ]. While fluorescein angiography (FA), an invasive imaging modality is commonly used to evaluate FAZ [ 33 ], more recently FA is being replaced by OCT angiography (OCT-A), a non-invasive imaging technology [ 34 , 35 ].…”

“…Most studies on predictors of treatment response are from post-hoc analysis of randomized trials [6,7,9,10,26,[36][37][38][39][40][41], with limited studies from real-world practice exclusively designed to examine the prognostic factors [11,12,42]. The majority of the real-world studies were retrospective [11,43], performed at a single medical center [20,23], had limited sample size (sample size as low as 15 eyes) [28,32], and limited follow-up [23,32]. An additional issue with these studies is the lack of consistency in results across studies, such as hyper-reflective foci being a favourable predictor by some [43,44] and a negative predictor by others [45,46].…”

Comparison of Optical Coherence Tomography Biomarkers between Bevacizumab Good Responders and Nonresponders Who were Switched to Dexamethasone Implant in Diabetic Macular Edema

“…The intermediate and deep capillary plexuses are located above and below the inner nuclear layer 24,25 . Elnahry and colleagues 26 compared the deep capillary plexus vessel density between bevacizumab responsive and refractory groups and found significantly greater vascular density in the bevacizumab responsive group. As such, low capillary plexus density may have led to the lack of response to bevacizumab but response to corticosteroids.…”

REal-world treatment outcomes after delayed intRavitreal therapy in center-involving diabetic macular edema – RETORT study

“…In the management of DME, poor response or resistance to routine anti-VEGF agents is a reality. A recent study by Elnahry et al found that OCT and OCT-angiography markers, such as a higher CSFT and a smaller foveal avascular zone area, as well as increased vessel densities in superficial parafovea and deep fovea, were associated with a better response to monthly intravitreal bevacizumab injections than in non-responders [ 24 ]. Patients who do not respond adequately to standard anti-VEGF medications may benefit from treatment with new and potent anti-VEGF molecules such as brolucizumab and faricimab [ 25 , 26 ].…”