Abstract
Purpose :
Topical immunomodulators have recently gained popularity in treatment of inflammatory dry eye disease (DED). In our tertiary DED population, ocular surface inflammatory signs and symptoms refractory to conventional treatments remains a diagnostic and therapeutic challenge. This two-part in vitro toxicity and in vivo clinical off-label treatment study aims to determine the safety and therapeutic potential of topical methotrexate (MTX).
Methods :
Aim 1, in vitro toxicity assay: primary human corneal epithelial/stromal cells (HCE and HCSCs respectively) were established from de-identified donor corneal rims. Epithelial cells were separated and cultured in DMEM. Stromal tissue was purified, cultured, and sub-cultured in DMEM. HCEs and HCSCs were exposed to 1 mg/ml, 2 mg/ml or 3 mg/ml MTX. HCEs were also treated with 10 mg/ml of MTX. Cells were photographed at 24 and 96 hours post-treatment.
Aim 2, MTX treatment in recalcitrant surface inflammation: Retrospective chart review was done on patients diagnosed with recalcitrant ocular surface disease (OSD) and treated with off-label topical 1 mg/mL MTX 4 times a day bilaterally. Ocular Surface Disease Index (OSDI), Symptom Assessment in Dry Eye (SANDE), Visual Analog Scale (VAS) of eyedrop tolerability, visual acuity (VA), Schirmer’s 1, and intraocular pressure (IOP) were recorded.
Results :
In vitro results for treated HCEs and HCSCs showed increased viability relative to control across 1 mg/ml, 2 mg/ml, and 3 mg/ml MTX at 24 hours (Fig. 1 and 2). Decreased cell survival of HCEs, but not HCSCs, was noted after 96 hours of 1, 2, and 3 mg/ml MTX exposure. At 10 mg/ml MTX, loss of HCE cells was noted at 72 hours.
Clinically, 10 patients were studied consecutively. Follow-up times ranged from 4 to 8 weeks, with a median of 6 weeks.OSDI improved in 70% of the cohort with 30% unchanged. Ocular irritation based on SANDE improved in 60% with 40% unchanged. MTX VAS tolerability scores ranged from 1-9 (0 = tolerable, 100 = intolerable). Schirmer’s 1 increased in 40%, improving from a range of 3-5 mm, and 60% showing no change. VA and IOP remained stable throughout each visit.
Conclusions :
Topical MTX demonstrated minimal cytotoxicity in vitro and appears to be well tolerated in our patient cohort. Topical MTX may play a role in the treatment of recalcitrant DED and OSD signs and symptoms, and further study with larger sample sizes is warranted and in progress.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.