Increasing Awareness & Screening Efforts Against Diabetic Keratopathy

Tejus Pradeep, BA

Diabetes, with all of its systemic disease manifestations, may cause more corneal damage than we previously understood. The latest findings concerning diabetic keratopathy were discussed this past weekend during a special interest group session conducted at the Association for Research in Vision and Ophthalmology (ARVO) 2019 Annual Meeting in Vancouver, BC.

The Sunday workshop session, “Diabetic Keratopathy: An Understudied Corneal Disease,” featured research by Dimitrios Karamichos, PhD, of the University of Oklahoma Health Sciences Center; Fushin Yu, PhD, of Wayne State University School of Medicine; Mitchell Watsky, PhD, of Augusta University; and Alexander Ljubimov, PhD, of UCLA.

Diabetes mellitus is the leading cause of blindness in adults of working age worldwide, with over 23 million Americans suffering from the disease. While diabetic retinopathy and neovascularization are well-characterized pathophysiologic entities, participants at ARVO 2019 raised awareness about the increased risk of keratopathy, including corneal erosions, epithelial defects, endothelial dysfunction, and punctate keratitis brought upon by the disease.

Previous findings showed that keratopathy may impact 47% to 64% of diabetics and that hyperglycemia causes subtle changes in all 5 layers of a patient’s cornea. However, despite these findings, research suggests that these diabetic changes are underdiagnosed.

Further research is needed to characterize why these changes occur, as the mechanisms are not well understood. In the workshop sessions, Karamichos spoke about the role of peroxisome proliferator-activated receptor alpha (PPARa) in diabetes models, with agonists like fenofibrate showing possible therapeutic effects. Additionally, the therapeutic potential of topical Vitamin D in reducing chronic inflammation and promoting corneal wound healing was discussed by Watsky.

The sheer breadth of corneal involvement in diabetes is often under-represented, encompassing abnormalities in the epithelium, corneal nerves, stroma, endothelium, and tear film. The implications for this are significant. Poor corneal sensation increases the risk of corneal injury and hinders normal protective responses, while endothelial changes disrupt fluid regulation. Even the most common eye conditions like dry eyes may be exacerbated by tear film changes.

With these impacts in mind, Ljubimov pointed towards future experimental therapeutics such as topical naltrexone, insulin, aldose reductase inhibitors, advanced glycosylation end product (AGEs) inhibitors, and gene therapies. Yu’s work with genome-wide cDNA microarrays highlighted over 1800 differentially expressed genes in diabetic corneal epithelial cells compared to normal controls, and suggests TGF-β3 as an especially promising therapeutic target.

Additionally, this understudied area is especially important in the field of corneal transplantation, where roughly 18% of transplanted corneas are from diabetic donors, leading to possible issues stemming from epigenetic changes.

For surgical techniques like Descemet’s membrane keratoplasty, corneal edema is increased in diabetics, possibly due to background dysfunction. It is therefore unsurprising that diabetics are responsible for 80% of corneal complications after cataract and refractive surgery, vitrectomy, and PRP.

Taken collectively, this session at ARVO 2019 highlighted the need for conscientious corneal screening during yearly diabetic eye visits and the prioritization of diabetic keratopathy prevention as a tangible predictor of surgical and visual outcomes.

Tejus Pradeep is a rising fourth-year medical student at Johns Hopkins University, School of Medicine in Baltimore, MD. In 2016, he graduated from Rutgers University with a Bachelor of Arts in cell biology and neuroscience, and a Bachelor of Arts in psychology. After graduating medical school, Tejus would like to pursue a career in the field of ophthalmology. The piece reflects his views, not necessarily those of the publication.Health care professionals and researchers interested in responding to this piece or similarly contributing to MD Magazine® can reach the editorial staff by submitting a request here.