Subthreshold Micropulse Laser in Diabetic Macular Edema: 1-Year Improvement in OCT/OCT-Angiography Biomarkers

Abstract

The aim of this study was to evaluate 1-year quantitative changes in specific inflammatory parameters on optical coherence tomography (OCT) / optical coherence tomography angiography (OCTA) in diabetic macular edema (DME) treated with subthreshold micropulse laser (SMPL). Methods: Thirty-seven patients / eyes with previously treatment-naïve DME treated with SMPL were prospectively evaluated at 3, 6, and 12 months. Fifteen fellow eyes with only microaneurysms (MAS) not eligible for treatment were controls. Evaluated OCT / OCTA parameters included: central macular thickness (CMT); hyper-reflective retinal spots (HRS); disorganization of inner retinal layers (DRILs); MA in the superficial / deep capillary plexuses (SCP/DCP); cysts in the area at the SCP / DCP; and macular perfusion parameters (MATLAB, version 2017b). Results: In the treated group, mean best corrected visual acuity (BCVA) progressively increased from 69.4 ± 12.0 to 76.0 ± 9.1 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (P < 0.001) at 12 months; HRS decreased from baseline (80.75 ± 20.41) at 3 (73.81 ± 17.1, P = 0.002), 6 (69.16 ± 16.48, P < 0.0001), and 12 months (66.29 ± 18.53, P < 0.0001). MA decreased at 3 months in the DCP (P = 0.015), at 6 and 12 months in both plexuses (P ≤ 0.0007). BCVA, HRS, and MA remained stable in the controls during all follow-ups. DRIL was present in 18 of 37 patients at baseline and progressively decreased from 557.0 ± 238.7 to 387.1 ± 282.1 μm (P = 0.01). The area of cyst decreased both in the SCP (P = 0.03) and the DCP (P = 0.02). CMT and perfusion parameters did not change. Conclusions: SMPL reduced the number of HRS (sign of activated microglia cells in the retina), MA, DRIL extension, and the area of cysts. Further studies are needed to confirm these preliminary data on the anti-inflammatory effect of SMPL, and to explore the mechanism of action. Translational Relevance: The follow-up of OCT/OCTA noninvasive biomarkers offers a unique insight in the mechanism of laser action, suggesting an anti-inflammatory effect of SMPL.

Subthreshold Micropulse Laser Modulates Retinal Neuroinflammatory Biomarkers in Diabetic Macular Edema

“…It has been proposed that microglia cells may be visualized in the retina using SD-OCT as discrete hyperreflective foci (HRF) [ 29 ]. Recently, SMPL was shown to reduce HRF even at a long-term follow-up (1 year), together with a reduction in the area of cysts, the disorganization of inner retinal layers and the number of microaneurysms [ 30 ].…”

“…As already mentioned, (neuro)inflammation has been recently recognized as one of the most important drivers in the pathogenesis of DME [ 2 ]. Therefore, these results strongly suggest that SMPL de-activates retinal glial cells and reduces the production of cytokines and chemokines, including VEGF, also restoring the integrity of the retinal structural and vascular morphology [ 1 , 14 , 30 ].…”

Diabetic Macular Edema Treated with 577-nm Subthreshold Micropulse Laser: A Real-Life, Long-Term Study

“…The cornerstones of subthreshold retinal laser therapy were established and defined using an 810-nm near-infrared micropulse laser [ 15 , 16 ]. The 577-nm yellow laser was later introduced and, although at present it is the most commercially available device, its efficacy has been evaluated by fewer studies involving smaller sample sizes and shorter follow-up periods [ 9 , 13 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. At present, a wide array of different duty cycle durations, spot sizes and power settings are employed by different clinicians, limiting, in our opinion, the diffuse clinical application of this technique [ 4 , 9 , 10 , 19 ].…”

“…A reduction in retinal thickness accompanied by fluid reabsorption can also be related to a de-activating effect on Müller cells [ 20 ]. Thus, SMPL probably initiates a wide curtailing of local inflammatory processes that is accompanied by cellular de-activation and return to morphological integrity, with the restoration of the retinal microvascular network, as evidenced by a reduction of the foveal avascular zone area in the deep capillary plexus [ 22 ]. In this study, we did not analyze macular and peripheral perfusion status.…”

Treatment of Macular Edema in Vascular Retinal Diseases: A 2021 Update

“…SML helps improve or stabilize visual function and decrease macular thickness in DME [31]. Vujosevic and colleagues performed a study that evaluated the effectiveness of SML treatment in patients with DME [31].…”