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:
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.
Will antiviral save the day for those with HSV? The goal for HEDS part 2 was to evaluate the efficacy of oral antivirals in preventing progression (from epithelial to stromal) and recurrence of HSV keratitis. Two separate RCTs were completed to assess for this: 1) treatment dose acyclovir versus placebo in immunocompetent patients with active HSV keratitis (treated with trifluridine), and 2) prophylactic dose acyclovir in immunocompetent patients with a history of HSV keratitis in the prior year.
Key Points:
Overall, this subset of the HEDS provided valuable clinical data for the utility of oral antivirals for prevention of recurrent HSV keratitis. While the study also provided context as to the unclear efficacy of oral antivirals for progression of HSV epithelial keratitis, current treatment regimens still frequently use oral antivirals for this (due to the lack of widespread availability of topical antivirals in many places). Altogether, the HEDS2 studies are landmark studies in the management of the common corneal disease of HSV 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:
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:
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.
How long can corneal tissue be preserved prior to transplantation? The goal of this study was to establish a preservation timeframe of corneal tissue prior to corneal transplantation that would promote graft success and enlarge the available donor supply. Prior to this study, the accepted length of preservation time was 7 days or less. This was a prospective randomized multicenter double-masked trial to assess the effect of preservation time of donor corneal tissue prior to transplant on graft survival at 3 years after Descemet stripping automated endothelial keratoplasty (DSAEK). There were 1330 corneal donors (26% diabetic and 49% greater than 60 years of age) and 1090 recipients of corneal donation through DSAEK. Patients were randomized into two groups: donor cornea stored ≤7 days and donor cornea stored 8-14 days. The primary outcome was endothelial cell density at 3 years.
Key Points:
Overall, the CPTS study is a landmark study because it demonstrated that corneal tissue could be preserved up to 11 days prior to transplantation and still be grafted successfully. Thereby, substantially increasing the donor pool for corneal transplants.
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:
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.
Don’t get it MUTTled, which antifungal treatment should you use for fungal keratitis?
In the 2013 MUTT 1 study, patients with filamentous fungal keratitis were randomized to treatment with natamycin (n = 162) and voriconazole (n = 161).
Key Points:
Overall, the MUTT 1 study is a landmark study because it showed that natamycin was not dangerous in the treatment of filamentous fungal keratitis and actually led to improved clinical and microbiological outcomes.
Oral vs topical antifungals for corneal ulcers - MUTT ado about nothing? Following MUTT I, in which topical natamycin demonstrated superior efficacy compared to topical voriconazole, the Mycotic Ulcer Treatment Trial II was designed to determine the benefit of oral voriconazole in addition to topic anti-fungal regimens in cases of severe mycotic keratitis. 240 patients from 6 clinical sites in Nepal and India were randomized to the oral voriconazole treatment group (n=119) and the control, placebo group (n=121); both received topical natamycin and topical voriconazole.
Key Points:
Overall, the MUTT II demonstrated that oral voriconazole did lead to an appreciable decrease in the rates of perforation or need for therapeutic penetrating keratoplasty. in fact, its use was associated with increased risk for adverse events. Given the drug’s high-cost profile as well, adjunct oral voriconazole was not recommended in the treatment of mycotic keratitis after this study.
Did you know Steph Curry has keratoconus? Imagine how tough it would be for him if he couldn’t see the rim anymore. In the 2007 CLEK study, patients 1209 patients with keratoconus were enrolled to prospectively evaluate changes in vision, corneal status, corneal curvature, and vision-related quality of life (V-QoL) changes over time.
Key Points:
Overall, the CLEK study is a landmark study because it was a large-scale natural history study that provided clinicians with data on the natural progression of keratoconus. Furthermore, it highlighted that keratoconus is a debilitating disease, objectively measuring the patient-perceived significant impact it plays in progressively worsening quality of life.
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:
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.