Project Title:

Preventing glaucoma blindness – a new drug to control postoperative scarring

Chief Investigator:

Dr Jen Fan Gaskin

Co-Investigators:

Dr Elsa Chan

Aim

To compare the efficacy of DiOHF eye drops against MMC in preventing inflammation and scarring in a preclinical rabbit model of Glaucoma Filtration Surgery (GFS).

Methods

GFS was performed in New Zealand white rabbits receiving 1) 3-times daily eye drops of DiOHF, 2) vehicle eye drops after surgery, or 3) a single intraoperative treatment of MMC.
Blebs were imaged immediately following surgery and on days 7, 15, 21 and 28 for clinical examination. On day 28 eyes were harvested to assess collagen deposition, expression of -SMA, oxidative stress, angiogenesis, fibroblast activity and inflammation in the conjunctiva/Tenon’s layer.

Key results

At 7-days and 28-days post-GFS, MMC-treated blebs were more ischaemic than DiOHF- or Vehicle-
treated blebs. At day 28, DiOHF treatment significantly suppressed collagen accumulation, CD31
expression (angiogenesis), Vimentin expression (fibroblast activity) and CD45 expression (inflammation)
compared to vehicle control. No difference was observed in 3-Nitrotyrosine (oxidative stress) or -SMA
expression (myofibroblast activation) between treatment groups.

 

Implications for Clinical Practice/Science and Future Research

The results of this study provide compelling evidence that DiOHF is an effective wound modulating
agent for GFS. We are exploring the efficacy of DiOHF in other forms of preclinical GFS models such as
conjunctival minimally- invasive glaucoma surgery to strengthen the validity of our data. We are also
exploring different drug preparations to optimise delivery of DiOHF in preparation for a clinical trial.

Conclusion

Treatment with DiOHF reduced conjunctival scarring and angiogenesis in rabbits with GFS that was
comparable to MMC. Oxidative stress levels did not vary between the treatment groups. DiOHF may be
a safer and more effective wound modulating agent than conventional antifibrotic therapy in GFS.

 

Lay Summary of Outcomes

Scarring is the commonest cause of failure of glaucoma filtration surgery. In our study, novel antioxidant
DiOHF reduces inflammation and scarring in this operation to a similar degree to conventional treatment
and causes less cell death, indicating it may be a safer and more effective solution to glaucoma surgery
scarring.

 

This research project was funded by AVR in 2023