Cornea Landmark Studies

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Can corticosteroids get you aHEaD of the curve for HSV stromal keratitis? In the HEDS trial, patients with active herpes simplex stromal keratitis were randomly assigned to either a placebo group (n = 49) or topical prednisolone phosphate group (n = 57). Both groups received topical trifluridine and a 10-week tapered regimen of the treatment drug/placebo.

Key Points:

• Compared to placebo, the steroid group had a reduced risk of persistent stromal keratouveitis by 68%
• The time to resolution was significantly shorter in the steroid group
• At 6 months, there were no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease between both groups

Overall, this subset of the HEDS is a landmark study because it demonstrated how administering topical corticosteroids were efficacious in treating herpes simplex stromal keratitis. Before this trial, it was unclear whether topical corticosteroids were safe and effective for these patients. In the HEDS, researchers found steroids were specifically advantageous in hindering the progression of stromal inflammation and shortening the duration of stromal keratitis. 

Hinge, Tinder, HLA-subtypes- matches are everywhere, but do they matter?  The CCTS assessed the effectiveness of HLA matching, donor-recipient crossmatching, and ABO compatibility among high-risk patients receiving immunosuppressive therapy following corneal graft transplantation.

Key Points:  

• HLA subtype matching has no effect on corneal graft survival or incidence of rejection
• Positive donor-recipient crossmatch does not substantially increase risk of corneal graft failure
• ABO blood group matching may reduce risk of corneal graft failure

The CCTS proved that immunosuppressive therapy after corneal graft transplantation, instead of histocompatibility, is key to long-term graft survival. This study dispelled the prior notion that HLA matching must be considered before transplant in high-risk patients, thereby eliminating the very costly matching practice.

Is age really just a number? The Cornea Donor Study is a multicenter, double masked, controlled trial initiated in 2000 to provide data to eye banks about the outcomes of donor tissue from various aged donors used for penetrating keratoplasty (PKP). The initial data published in 2008 demonstrated no significant difference in the 12-65 and 66-75 donor age groups, with no significant association between donor age and graft success. The updated analysis reports data after 10 years of follow-up.

Key Points:

• There was no significant difference in the 10-year PKP graft success rate for donors aged 12-65 (77%) compared to donors aged 66-75 years old (71%), p=0.11
• Higher donor age was associated with lower graft success after the first 5 years (p<0.001), mostly in the donor aged 72-75 group

The results of this study show no difference in the 10-year PKP graft success rates between donors aged 12-65 and donors aged 66-75. Although the grafts from donors aged 72-75 showed lower success rates, this difference was small (success rates for donors 66-71: 87%, vs 72-75: 85%). The authors concluded that the donor pool should be expanded to donors up to 75 years old.

Can you count on corticosteroids to do the scutwork in bacterial keratitis? In the 2012 SCUT study, patients with known bacterial corneal ulcers were randomized to treatment with prednisolone (n = 250) and placebo (n = 250) 48 hours after receiving Vigamox. 

Key Points:

• In the full population, there was no statistical difference in outcomes between the two groups. 
• For patients with more severe presentation (e.g., CF or worse vision, central ulcers), corticosteroids led to an approximate 2-line improvement.

Overall, the SCUT study is a landmark study because it showed that topical corticosteroids were not dangerous in the treatment of bacterial corneal ulcers and actually led to improved outcomes in a subset of patients with more severe presentations.

In the alphabet soup of corneal transplant options, which surgery is best? At the time of the DETECT trial, Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) was the more common surgery used for endothelial keratoplasty, owing to the newness and lack of clear evidence of superior outcomes for Descemet Membrane Endothelial Keratoplasty (DMEK). The DETECT trial sought to provide level 1 evidence to support the expanded use of DMEK. They randomized 50 eyes to DMEK/DSAEK (25 each) to undergo these surgeries by 2 well-trained surgeons at 2 institutions, and sought to assess visual and surgical outcomes.

Key Points:

• DMEK led to improved BSCVA at 3, 6, 12 months (1.5 lines, 1.8 lines, 1.4 lines, respectively), all with statistically significant levels of improvement
• There was a non-statistically significant increase endothelial cell loss with DMEK compared to DSAEK (215 fewer cells/mm2at 12 months, P = 0.051)
• There was no statistically significant increase in adverse events, though the study may have been underpowered to assess for such differences

Overall, the DETECT study provided much needed evidence to support increased use of DMEK as a superior form of endothelial keratoplasty (EK). Before the DETECT trial, DMEKs accounted for less than 15% of EKs, and by the end of 2021, the number of DMEKs and DSAEKs completed in the US were approximately equal.