June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
The use of Topical Spironolactone in Treatment of Ocular Graft-Versus-Host Disease
Author Affiliations & Notes
  • Calvin Wong
    The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, United States
  • Xiaowen Lu
    Augusta University, Augusta, Georgia, United States
  • Mitchell Watsky
    Augusta University, Augusta, Georgia, United States
  • Richard W Yee
    The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   Calvin Wong None; Xiaowen Lu None; Mitchell Watsky None; Richard Yee US20190328753A1, Code P (Patent)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3288. doi:
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    • Get Citation

      Calvin Wong, Xiaowen Lu, Mitchell Watsky, Richard W Yee; The use of Topical Spironolactone in Treatment of Ocular Graft-Versus-Host Disease. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3288.

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

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Abstract

Purpose : The aim of this two-part study was to investigate the therapeutic potential of topical spironolactone in ocular Graft-versus-Host Disease (oGVHD). Preclinically, we tested the hypothesis that spironolactone induces corneal lipid synthesis in a mouse model. Clinically, we assessed patient response to spironolactone with a retrospective observational design.

Methods : Both immortalized and primary human corneal epithelial cells were stained with oil red O after 9 days of treatment with spironolactone. C57BL/6 mice were dosed with one drop in each eye three times daily for 18 days. Corneal tissue was stained with oil red O and BODIPY.

Twenty eyes with oGVHD as defined by the International Chronic Ocular GVHD Consensus Group were studied. Corneal fluorescein staining, lid margin vascularity, meibomian gland obstruction, meibum turbidity, zone A posterior lid margin vascularity, and oGVHD diagnostic criteria severity grading were compared in a pre-post study. Follow-up times ranged from 7 to 21 weeks, with a median time of 12 weeks. Statistical analysis was done with STATA 17 by fitting data to a non-parametric model.

Results : In vitro results showed increased number and density of oil red O staining granules in the treatment group versus control in both primary and immortalized human corneal epithelium (Figure 1). In vivo results showed translation to the mouse model with increased corneal epithelial BODIPY signal compared to untreated control (Figure 2). oGVHD Patients had improved lid margin vascularity (p=0.046), corneal fluorescein staining (p = 0.021), and diagnostic criteria severity scores (p=0.011) after treatment with topical spironolactone.
Clinically, spironolactone has been used off label since 2014 for dry eye. Patients generally show improved overall ocular comfort and lower lid margin inflammation scores after just two weeks. Minimal adverse effects have been noted, with the most common being mild stinging lasting less than a minute after instillation.

Conclusions : oGVHD patients showed improved severity scores, lid margin inflammation, and corneal fluorescein staining after weeks of spironolactone treatment. Spironolactone-induced lipid production by the corneal epithelium may have a protective effect against ocular surface erosive disease in oGVHD. A mineralocorticoid analog, spironolactone may offer therapeutic benefit in oGVHD while avoiding undesirable side effects of topical glucocorticoids.

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

 

 

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