Abstract
Purpose :
Ocular graft-versus-host disease (oGVHD), a common finding of chronic graft-versus-host disease (cGVHD), can manifest with scleroderma-like changes to the eyelids, entropion, lagophthalmos, dry eyes, meibomian gland (MG) dropout, and epithelial keratitis. We hypothesized the addition of topical spironolactone to the ocular surface can reduce the immune mediated complication of oGVHD.
Methods :
cGVHD mouse models were created via allogeneic bone marrow transplantation (BMT) with male B10.D2/nSnSlc donors and female BALB/cCrSlc mice recipients (Fig 1a, left). Male BALC/cCrSlc mice stem cells were transplanted into female BALC/cCrSlc mice to form a syngeneic (syn) control group (Fig 1a, left). Allogeneic BMT recipients received either 0.005 mg/cc topical spironolactone or vehicle, with one drop instilled bilaterally every 5 minutes thrice daily for the first three days after BMT as a loading dose and twice a day for 24 days (Fig 1a, right). After 28 days post-BMT, the right eyelids were harvested and photographed with light microscopy. MG dropout was assessed as a ratio between the total area (eyelid margin to the most distal point of the MG) and the area with MG absence. Ocular surfaces were evaluated for corneal fluorescein staining (CFS) following the NEI scoring scheme.
Results :
The topographical MG area% in vehicle-treated (VT) mice were significantly decreased when compared with the syn control mice (p = 0.0031) and spironolactone-treated (ST) mice (p = 0.0213). The syn control (83.73±1.28%) and ST (77.65±2.22%) groups retained significantly larger MG area% (Figures 1b, middle, and Figure 1c) in comparison to the VT group (68.46±2.18%). The VT group exhibited higher corneal damage on average (Fig 1b, right). CFS score of the VT group was higher compared to the syn control (p = 0.0475) and ST group (p = 0.0383), respectively (Fig 1d).
Conclusions :
Use of topical spironolactone was associated with reduction of MG dropout in cGVHD mouse models and contributed to structural stability of the ocular surface, shown by CFS. Prospective trials need to be conducted to determine the efficacy of spironolactone in treating oGVHD patients.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.