July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Subthreshold Micropulse Laser Treatment of Human Diabetic Macular Edema: the Role of Müller Cells, Retinal Pigment Epithelium and the Inflammatory Cascade
Author Affiliations & Notes
  • Edoardo Midena
    Ophthalmology, University of Padova, Padova, Italy
    IRCCS Bietti Foundation, Rome, Italy
  • Silvia Bini
    Ophthalmology, University of Padova, Padova, Italy
  • Alessandra Micera
    IRCCS Bietti Foundation, Rome, Italy
  • Graziana Esposito
    IRCCS Bietti Foundation, Rome, Italy
  • Luisa Frizziero
    IRCCS Bietti Foundation, Rome, Italy
  • Raffaele Parrozzani
    Ophthalmology, University of Padova, Padova, Italy
  • Elisabetta Pilotto
    Ophthalmology, University of Padova, Padova, Italy
  • Footnotes
    Commercial Relationships   Edoardo Midena, None; Silvia Bini, None; Alessandra Micera, None; Graziana Esposito, None; Luisa Frizziero, None; Raffaele Parrozzani, None; Elisabetta Pilotto, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3861. doi:https://doi.org/
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      Edoardo Midena, Silvia Bini, Alessandra Micera, Graziana Esposito, Luisa Frizziero, Raffaele Parrozzani, Elisabetta Pilotto; Subthreshold Micropulse Laser Treatment of Human Diabetic Macular Edema: the Role of Müller Cells, Retinal Pigment Epithelium and the Inflammatory Cascade. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3861. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The pathophysiology of the effect of subthreshold micropulse laser (SMPL) treatment of diabetic macular edema /DME) is still unknown. We investigated the effect of SMPL in DME eyes using retinal morphology data and the quantification of specific intraocular biomarkers.

Methods : Previously untreated, center-involving DME eyes (central retinal thickness: CRT< 400 μm) underwent BCVA and layer-by-layer OCT quantification. Moreover, specific retinal Müller cells and RPE biomarkers (Glial Fibrillary Acidic Protein: GFPA, Inwardly Rectifying Potassium Channel ( Kir ) 4.1, VEGF for Müller cells, and Pigment Epithelium Derived Factor: PEDF and Erythropoyetin: EPO for RPE ), and multiple inflammatory cascade biomarkers were quantified (every three months) , versus healthy controls, in the aqueous humor (AH). SMPL was applied in a standardized fashion over all edematous areas. Fundus autofluorescence and microperimetry were used to evaluate both morphologic and functional SMPL side effects.

Results : Nineteen previously untreated DME eyes and ten controls were studied (minimum follow-up 12 months). At baseline, AH values of GFAP, Kir 4.1 and VEGF, and inflammatory biomarkers showed increased concentration in DME eyes versus controls (p< 0.005, for all). After SMPL: BCVA increased (mean: 5.6 ETDRS letters); OCT documented significant regression of CRT ( p< 0.005) mostly at the level of the inner nuclear layer (p< 0.002), where the bodies of Müller cells are located. No side effects were documented. A significant reduction of Müller cells biomarkers was found ( baseline vs 12 months data: GFAP: 1581.8 vs 982.1 pg/μl, p= 0.02; Kir 4.1: 177.0 vs 118.5 OD, p= 0.008; VEGF: 164.3 vs 134.7 Fl, p= 0.04 ), with final restoration to normal values.The biomarkers of the inflammatory cascade also showed a significant reduction ( p < 0.004). Retinal pigment epithelium biomarkers (PEDF and EPO) remained unchanged during follow-up (p> 0.2).

Conclusions : These results offer fully new insights about the effect of SMPL treatment of DME eyes. The resolution of DME by SMPL seems (mainly) to depend on the restoration of the activity of Müller cells and stabilization of the diabetic retinal inflammatory condition. These data strongly support the hypothesis of the key importance of Müller cells in the pathophysiology of DME.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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