June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Implication of antiglaucoma drug excipients on the corneal healing process in the Ex Vivo Eye Irritation Test (EVEIT) model
Author Affiliations & Notes
  • Laure Chauchat
    Horus Pharma, France
  • Claudia Panfil
    Aachen Centre Of Technology Transfer In Ophthalmology (ACTO), Germany
  • Jonathan Siboni
    Assistance Publique - hôpitaux de Paris (AP-HP), France
  • Camille Guerin
    Horus Pharma, France
  • Norbert Franz Schrage
    Aachen Centre Of Technology Transfer In Ophthalmology (ACTO), Germany
  • Footnotes
    Commercial Relationships   Laure Chauchat Horus Pharma, Code E (Employment); Claudia Panfil Horus Pharma, Code C (Consultant/Contractor), Aachen Centre Of Technology Transfer In Ophthalmology (ACTO), Code E (Employment); Jonathan Siboni None; Camille Guerin Horus Pharma, Code E (Employment); Norbert Schrage Horus Pharma, Code C (Consultant/Contractor), Aachen Centre Of Technology Transfer In Ophthalmology (ACTO), Code O (Owner)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 5194. doi:
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      Laure Chauchat, Claudia Panfil, Jonathan Siboni, Camille Guerin, Norbert Franz Schrage; Implication of antiglaucoma drug excipients on the corneal healing process in the Ex Vivo Eye Irritation Test (EVEIT) model. Invest. Ophthalmol. Vis. Sci. 2023;64(8):5194.

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

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Abstract

Purpose : The corneal epithelial toxicity of some excipients contained in various latanoprost formulations was previously evaluated in high frequency-application on the EVEIT model over 3 days. This study objective was to confirm the impact of eyedrop galenic formulations in terms of excipients composition and concentration (as MGHS (Macrogolglycerol hydroxystearate 40)) in corneal toxicity over an extended 5-day period.

Methods : Different Latanoprost 0.005% formulations were compared: A. preservative free (PF) without any solubilizing agent; B. PF with MGHS 2.5%; C. PF with MGHS 5%. MGHS 5% alone was tested (D). A control reference (CT) PF Hyaluronic acid eyedrop was used. Items were applied over 5 days, 6 times daily on controlled abrased rabbit corneas (n=5) cultured on an artificial anterior chamber EVEIT system, allowing to mimic the chronic use of treatment in long term diseases like glaucoma. All defects were monitored by fluorescein stains and photographs. Corneal integrity (fluorescein permeability) and vitality (lactate and glucose metabolism) were also quantified and assessed.

Results : Total epithelial healing was observed at day 3 (d3) for A, B and CT. Delayed healing of initial lesions was observed for C with clear reopening of the corneal surface from d3 to d5. Homogeneous and obvious results were found for all tested items (n=5). As expected, C showed statistically significant increase of the lesion opening areas compared to the baseline (p<0.05). Enlargement of corneal erosion was also noted for D but in a lesser extent compared to C. At d5, fluorescein values (permeability) were significantly higher compared to CT for items containing MGHS: C, D (p<0.01), and B (p<0.05). Glucose and lactate levels remained in physiological range for all corneas.

Conclusions : A clear and higher reopening of the corneal abrasions was highlighted for C containing MGHS 5%, compared to MGHS 5% alone (D). A complete healing was observed for all other items, even for B containing MGHS 2.5%. This suggests a stronger toxicity of MGHS at higher concentration and when associated to certain excipients. Indeed, thickening agents (i.e Macrogol 4000, carbomer) contained in C formulation could play a significant role in enhancing MGHS toxicity. Some excipients combination can be of concern for ocular surface health and should be considered by practicians for long term glaucoma treatment.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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