Topical low-dose heparin in ocular Stevens Johnson Syndrome and associated molecular correlations: A randomized controlled pilot study

Abstract

Purpose

To elucidate the efficacy of topical low dose heparin (LDH) as an adjuvant therapy in of sub -chronic and chronic ocular Stevens-Johnson Syndrome (SJS) and its effect on Neutrophil extracellular traps (NETs) associated markers.

Design

A prospective randomized controlled pilot trial.

Methods

72 clinically diagnosed SJS cases were recruited into sub-chronic and chronic groups. Both groups were randomly given either LDH eye drops with conservative treatment (CT) or CT alone for one month. Visual acuity, Schirmer's test, fluorescein and lissamine staining, OSDI score and ocular surface severity were evaluated. Tear and conjunctival cells were collected to detect NET-MPO complexes and NET-gene markers (TNFSF14, TLR9, IL-6, MyD88, C3a gene).

Main outcome measures

Improvement in ocular surface severity scores.

Results

Sub-chronic group showed significant improvement with topical LDH in TBUT (p = 0.0001), Lissamine stain score (p = 0.0162), corneal vascularisation score (p = 0.0001), conjunctival hyperaemia score (p = 0.001) and total severity score (p = 0.001) when compared to the LDH treated chronic group. No significant improvement was seen in visual acuity in either group after one month of therapy. Qualitative ELISA confirmed higher presence of NET-MPO complex in sub-chronic cases. Both groups showed upregulation of TNFSF14, TLR9, and MyD88, which significantly decreased post topical LDH treatment (p = 0.0038,0.002 and 0.043 respectively).

Conclusion

The presence of NETs mediated upregulated immune markers on sub-chronic and chronic SJS cases sheds newer light on its unresolved ocular pathology. Subsequent administration of topical LDH revealed a notable mitigation of NET associated immune markers, highlighting its promising anti-inflammatory effects within the ocular microenvironment.