June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
A Clinico-Pathological Study of the Structural and Functional Changes to the Retina and Optic Nerve following anti-VEGF Treatments for Diabetic Macular Edema
Author Affiliations & Notes
  • Richard Filek
    Pathology and Laboratory Medicine, Western University, London, Ontario, Canada
    Ophthalmology , St. Joseph's Health Care London, London, Ontario, Canada
  • Phil Hooper
    Ophthalmology , St. Joseph's Health Care London, London, Ontario, Canada
  • Thomas G Sheidow
    Ophthalmology , St. Joseph's Health Care London, London, Ontario, Canada
  • John R Gonder
    Ophthalmology , St. Joseph's Health Care London, London, Ontario, Canada
  • Subrata Chakrabarti
    Pathology and Laboratory Medicine, Western University, London, Ontario, Canada
  • Cindy M L Hutnik
    Ophthalmology , St. Joseph's Health Care London, London, Ontario, Canada
  • Footnotes
    Commercial Relationships   Richard Filek, None; Phil Hooper , None; Thomas Sheidow, None; John Gonder, None; Subrata Chakrabarti, None; Cindy Hutnik, None
  • Footnotes
    Support  Studentship Award – Spring 2015 Lawson Internal Research Fund (IRF) Competition
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2024. doi:
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      Richard Filek, Phil Hooper, Thomas G Sheidow, John R Gonder, Subrata Chakrabarti, Cindy M L Hutnik; A Clinico-Pathological Study of the Structural and Functional Changes to the Retina and Optic Nerve following anti-VEGF Treatments for Diabetic Macular Edema. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2024.

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

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Abstract

Purpose : To evaluate and analyze the safety and efficacy of anti-VEGF drugs on the retina and optic nerve in patients with DME and varying levels of diabetic retinopathy (DR)

Methods : DR patients with underlying DME underwent pre-injection, 6, 12 and 24 month follow-up tests using visual fields, Heidelberg retinal tomography, optical coherence tomography and OPTOS fluorescein angiography. In vitro, rat retinal cell cultures were exposed to 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL of ranibizumab (Lucentis) for 48 hours. Cytotoxicity was measured by LDH, apoptosis by cell death ELISA and MTT assay for cellular metabolic activity.

Results : A total of 31 patients were enrolled in the study. From baseline the average macular thickness significantly decreased (p<0.0001) at 6 months (-33.3 μm), and 12 months (-35.0 μm) compared to baseline. Average retinal nerve fiber layer thickness significantly decreased (P<0.0001) by 12 months (6 months -9.5 μm; 12 months -11.4 μm). Visual field mean deviation (MD) improved non-significantly compared to baseline (6 months +1.59 dB; 12 months +0.90 dB). Average cup to disk ratio (+0.045) and vertical cup to disk ratio (+0.049) significantly increased (p<0.0001) by 12 months. Cup volume significantly increased (p<0.009) at 6 months (+0.0060 mm3), and 12 months (+0.0066 mm3) compared to baseline. In vitro, MTT showed a significant decrease (p<0.003) in cellular metabolic activity at the clinical dose (0.125 mg/mL -5.6%) and double the clinical dose (0.25 mg/mL -4.4%) compared to control. LDH showed a significant increase (p<0.004) in cytotoxicity at the clinical dose (0.125 mg/mL +36.6%) and double the clinical dose (0.25 mg/mL +39.2%) compared to control.

Conclusions : Clinically, anti-VEGF appears to be potentially detrimental to the optic nerve by decreasing retinal nerve fiber layer thickness, increasing cup/disk ratio and cup volume over time. In vitro, anti-VEGF treatment appears to be detrimental to the retina by decreasing cellular metabolic activity and increasing cytotoxicity of retinal cells. The results provide a cautionary note to monitor both the retina and optic nerve status in patients undergoing frequent injections.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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