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Midena, Edoardo MD, PhD, FEBO, FARVO*,†; Bini, Silvia MD, FEBO*; Martini, Ferdinando MD, FEBO; Enrica, Convento MSc*; Pilotto, Elisabetta MD, FEBO*; Micera, Alessandra PhD; Esposito, Graziana MSc; Vujosevic, Stela MD, FEBO§

doi: 10.1097/IAE.0000000000002356
Original Study: PDF Only

Purpose: To evaluate the changes in activity of biomarkers of Mu[Combining Diaeresis]ller cells (MC) in aqueous humor of patients with diabetic macular edema after subthreshold micropulse laser, over 1 year.

Methods: Patients with untreated diabetic macular edema and central retinal thickness ≤ 400 μm were enrolled. Best-corrected visual acuity, full ophthalmic examination, and optical coherence tomography were performed. Subthreshold micropulse laser was applied every 3 months. Glial fibrillary acidic protein and inwardly rectifying potassium channel (Kir 4.1), MC activity markers, and vascular endothelial growth factor were quantified in the aqueous humor collected at baseline and at 1, 3, and 12 months after laser. Changes in the macular thickness and inner nuclear layer thickness, where MC bodies are located, were measured.

Results: Ten eyes of 10 patients were included. Best-corrected visual acuity improved at 3 months (P = 0.047) and remained stable. Inner nuclear layer thickness significantly reduced at 12 months (P = 0.012). Glial fibrillary acidic protein, Kir 4.1, and vascular endothelial growth factor decreased at 1 and/or 3 and/or 12 months compared with baseline (P < 0.05).

Conclusion: Subthreshold micropulse laser improves visual function in diabetic macular edema. Kir 4.1 and glial fibrillary acidic protein decrease and inner nuclear layer thickness reduction demonstrate that subthreshold micropulse laser may restore MC function. Subthreshold micropulse laser also reduces vascular endothelial growth factor concentration. The effect of subthreshold micropulse laser in diabetic macular edema may in part be due to changes of MC metabolic activity.

Müller cells' biomarkers and vascular endothelial growth factor were measured in diabetic patients with macular edema after subthreshold micropulse laser. Deactivation of Müller cells and decreased levels of vascular endothelial growth factor, quantified in aqueous humor, were found. These data may help in elucidating the metabolic retinal changes induced by subthreshold micropulse laser.

*Department of Neuroscience, Ophthalmology Unit, University of Padova, Padova, Italy;

GB Bietti Foundation, IRCCS, Rome, Italy;

Department of Ophthalmology, Camposampiero Hospital, Padova, Italy; and

§Department of Ophthalmology, University Hospital Maggiore della Carità, Novara, Italy.

Reprint requests: Edoardo Midena, MD, PhD, FEBO, FARVO, Department of Ophthalmology, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; e-mail:

The contribution of the GB Bietti Foundation, IRCCS, has been supported by the Ministry of Health and Fondazione Roma.

None of the authors has any financial/conflicting interests to disclose.

© 2019 by Ophthalmic Communications Society, Inc.