New options for solving corneal medicine’s toughest challenges are popping up by the day—and a symposium at the 42nd Congress of the European Society of Cataract and Refractive Surgeons (ESCRS 2024) convened on Day 4 to help delegates sort through recent developments in cornea collagen cross-linking (CXL).
The symposium in Barcelona was a collaboration between experts at two of the world’s most premiere ophthalmic societies—the American Academy of Ophthalmology (AAO) and host society, ESCRS.
Experts explored both breakthroughs and ongoing debates in CXL, including new paradigms for treating keratoconus and infectious keratitis.
A second look at Epi-on CXL
The session kicked off with Swiss expert Prof. Farhad Hafezi, who has emerged as a champion of Epi-on CXL. He took the audience on a journey through the ups and downs of Epi-on crosslinking for keratoconus, shedding light on the past, present and future of this promising technique.
“Epi-on crosslinking has the potential to revolutionize keratoconus treatment, but it’s had a rocky road,” Prof. Hafezi admitted, noting the method’s challenging reputation over the last 15 years.
But that hasn’t swayed Prof. Hafezi, who pointed to one key advantage that tips the scales for him. “The real game-changer? Epi-on could take crosslinking out of the operating room, making it more accessible and affordable.”
The secret to making Epi-on work, according to Dr. Hafezi, lies in perfecting the balance of three key factors: light, oxygen and riboflavin. “Early failures stemmed from insufficient oxygen and riboflavin delivery,” he said. But over the past decade, these issues have been painstakingly resolved.
By 2019, a functioning Epi-on protocol was in place, yet it was “still too complex,” Dr. Hafezi noted. It wasn’t until recent tweaks by Dr. Cosimo Mazzotta, who optimized oxygen supply and riboflavin stabilization, that the Epi-on puzzle finally came together.
Now, with a simplified, pulsed Epi-on procedure that requires no additional oxygen or iontophoresis, Dr. Hafezi is as confident as ever. “We’ve seen improvements in CDVA by up to 6 lines. And for stable keratoconus, this procedure holds significant promise.”
Taking CXL and keratoconus to new heights
Next, Dr. Jose De la Cruz (USA) shed light on the ever-evolving field of corneal cross-linking for keratoconus, tackling the key questions of when, why and how best to intervene.
He explained that the main indications for CXL remain ectasia after excimer laser refractive surgery and progressive keratoconus. In the United States, the go-to method is still the tried-and-true Dresden protocol, which he outlined as a central 7 mm epithelial removal, followed by 30 minutes of riboflavin and another 30 minutes of UVA light exposure.
According to Dr. De la Cruz, “This has been proven over time to be effective.”
However, the field isn’t standing still. “To reduce treatment duration, accelerated protocols have been developed,” Dr. De la Cruz noted, emphasizing that these new methods rely on photochemical reciprocity.
“Increased UV light and decreased exposure time result in the same cumulative energy,” he continued before saying that these strategies offer quicker alternatives to the standard method.
Dr. De la Cruz presented studies comparing the Dresden protocol with accelerated options, revealing that “comparable results were found in topographic, visual acuity, refractive, and safety outcomes.”
He concluded with a balanced view: “Both standard and accelerated protocols are safe and clinically equivalent. But let’s not forget—variables like age, risk factors, family history, and even allergic conjunctivitis can sway the decision.”
In summary, cross-linking isn’t a one-size-fits-all procedure, but both protocols seem to provide reliable outcomes, leaving the door open for individualized treatment strategies.
Crosslinking pros and cons
Dr. Paolo Vinciguerra (Italy) cast a more detailed light on the pros and cons of this technique, offering fresh perspectives on improving outcomes.
“Crosslinking has its drawbacks,” Dr. Vinciguerra remarked. “It’s time-consuming, with unpredictable corneal shape improvements and months of waiting before patients regain their best corrected visual acuity.”
To better understand CXL, Dr. Vinciguerra emphasized the role of the epithelium: “The epithelium is thinner over the cone apex and thicker at the base. Crosslinking reduces the corneal curvature gradient, which lowers higher-order aberrations.”
However, he warned that once crosslinking’s compensatory effects reach their limit, these aberrations become more noticeable.
Dr. Vinciguerra then addressed slower recoveries often associated with the procedure. “After epithelial abrasion, it takes weeks for the layers to reorganize. Collagen crosslinking’s flattening effect typically appears after about three months, once the epithelium returns to normal.”
So, how does one optimize results? “We use high-resolution systems like the SCHWIND PERAMIS (Schwind eye-tech-solutions; Kleinostheim, Germany), which allows total corneal wavefront custom ablation linked to an excimer laser,” Dr. Vinciguerra said.
He shared promising outcomes. “We’ve treated 23 patients, with about 30% being pediatric cases. In adults, corneal flattening continued even after ten years, with stable epithelial and pachymetric changes. This is just the beginning!”
New frontiers in infectious keratitis
In the symposium’s final session, Dr. Jennifer Rose-Nussbaumer (USA) addressed the ongoing battle against infectious keratitis with a simple but impactful truth: “For anyone who treats infectious keratitis, you all know we need better treatments than just topical antibiotics.”
Dr. Rose-Nussbaumer kicked off her talk with a challenging case involving a patient suffering from pseudomonas keratitis.
“This infection was unresponsive to vancomycin, tobramycin, and oral levofloxacin,” she explained. Despite performing a rare therapeutic transplant, the infection persisted, revealing itself to be multidrug-resistant.
“It turned out the patient had used a contaminated eye drop formulation that had been recalled due to multidrug-resistant bacteria,” she lamented, noting the unfortunate outcome: loss of vision in the affected eye.
This case sparked Dr. Rose-Nussbaumer’s interest in collagen crosslinking as a potential solution. She explained, “Why collagen crosslinking? It offers direct antimicrobial effects, reduces inflammation and increases resistance to enzymatic degradation.”
Her research into PDT crosslinking has shown promise as an adjuvant therapy for bacterial keratitis. Dr. Rose-Nussbaumer also highlighted its potential in treating fungal keratitis based on a study of 111 patients utilizing the Dresden protocol. “We look forward to sharing results from our ongoing clinical trials soon,” she concluded.
Editor’s Note: Reporting for this story took place at the 42nd Congress of the European Society of Cataract and Refractive Surgery (ESCRS 2024), held from 6-10 September in Barcelona, Spain.
