Recent advances in corneal cross-linking (CXL) and biomechanical diagnostics have expanded the treatment horizon for advanced keratoconus and post-LASIK ectasia.
At the recent Egyptian Society of Cataract and Refractive Surgery (EgSCRS) conference, CEO of ELZA, Nikki Kristoffersen-Hafezi, MAS IP ETHZ and CMO of ELZA, Prof. Farhad Hafezi, MD, PHD, FARVO, explained why portable and cost-effective screening and treatment of preventable blinding corneal diseases is so important. They also explained why they developed novel protocols such as ELZA-sub400, ELZA-PACE, and ECO-CAIRS to offer new therapeutic options for treating ultrathin keratoconus corneas, highly irregular cones, and biomechanical stabilization without tissue removal. This post outlines a stepwise, biomechanically informed approach to keratoconus rehabilitation, integrating diagnostics, AI-assisted screening, and a pyramid of staged interventions.
Addressing Preventable Blindness with Scalable Technology
The global burden of undiagnosed keratoconus – especially in children and adolescents – is staggering. I have witnessed firsthand how access remains a major barrier. To address this, the Light for Sight Foundation developed a cloud-integrated, AI-supported diagnostic platform built around a miniaturized version of the CSO MS-39 and rapid upload architecture. This system, shown to EgSCRS delegates, and depicted in Figure 1, enables mass screening in under-resourced settings and integrates with machine learning platforms.
Figure 1: The 2020 prototype of the portable screening unit.
The importance of treatment access is critical: diagnosis without the possibility of intervention may do more harm than good. We have emphasized this point repeatedly—if a child is diagnosed with keratoconus, treatment must follow irrespective of financial capacity. Screening only has value when it leads to action.
Rethinking Biomechanical Diagnostics
EgSCRS delegates heard that standard Scheimpflug tomography remains foundational, but its limitations in early or subclinical keratoconus are well established. Tools such as the Corvis ST offer valuable biomechanical insights, but emerging technologies such as Brillouin microscopy and OCT elastography are ushering in a new era.
One of our key research directions has been developing true biomechanical heatmaps based on localized deformation and subsequent corneal response. These maps, which can reveal regional stiffness differences in keratoconic corneas, are now entering early human trials.
Figure 2: OCT elastography image differential stiffness across cone vs. periphery in a keratoconic cornea.
ELZA-sub400: Tailoring Fluence to Residual Stromal Thickness
Traditional guidelines held that CXL in corneas thinner than 400 µm was unsafe. However, as attendees at EgSCRS heard, this threshold is an oversimplification. The key variable is fluence depth, not absolute pachymetry. In 2016, we introduced a fluence-modulation algorithm that adjusts total UV-A energy based on corneal thickness and oxygen diffusion kinetics.
This model, now integrated into the EMAGine C-eye device, allows safe cross-linking in corneas as thin as 200 µm. The protocol, termed ELZA-sub400, has now reached its second generation. Clinical results show an 82% stabilization rate at 2 years, even in corneas with Kmax >90 D and stromal thickness <300 µm. Importantly, endothelial cell density remains unaffected when using appropriately titrated fluence.
Figure 3: The ELZA-sub400 algorithm modulates UV-A fluence based on residual stromal thickness, reducing energy delivery in ultrathin corneas.
PACE: Precision Topographic Modulation Without Stromal Ablation
While Athens and CREST protocols have demonstrated excellent outcomes in reshaping the cornea through combined excimer ablation and CXL, they involve stromal removal—a concern in advanced keratoconus.
ELZA-PACE (PTK-assisted customized epi-on cross-linking) is a fundamentally different approach. Using the MS-39’s epithelial thickness map and height profile analysis, we define a topographically customized epithelial removal zone over the cone apex using PTK. No stromal tissue is ablated.
EgSCRS delegates were told that this creates a highly controlled epi-off window, setting up gradients in oxygen, riboflavin concentration, and fluence—all of which amplify the flattening effect centrally. PACE has been used in more than 300 eyes with results including up to six Snellen lines gained with glasses. Astigmatic regularity improves via a coupling effect, with RMS values significantly reduced postoperatively.
Figure 4: Example of ELZA-PACE treatment: customized epithelial PTK ablation map (left) and post-CXL topography showing cone flattening and regularization (right).
Importantly, because no stromal tissue is removed, transPRK can be performed later as a refinement step. The procedure requires:
- MS-39 for epithelial mapping
- Schwind AMARIS excimer platform
- C-eye device
- RIBO-Ker riboflavin with penetration enhancers
ECO-CAIRS: Rethinking ICRS With Cross-Linked Allogenic Segments
Allogenic corneal ring segments (CAIRS), as introduced by Susan Jacob, offer a biologic alternative to PMMA ICRS. However, donor variability and intraoperative handling challenges have limited adoption. We introduced ECO-CAIRS, applying extracorporeal cross-linking to donor segments with ultra-high fluence (up to 62 J/cm²) prior to implantation.
This offers multiple advantages:
- Increased segment stiffness for biomechanical efficacy
- Reduced swelling and easier implantation
- Elimination of keratocytes for immunologic safety
Experimental data confirms stiffness increases and swelling resistance. Insertions are technically easier, and segments remain stable postoperatively. ECO-CAIRS is now the foundation of the ELZA Surgical Pyramid:
- ECO-CAIRS: for mechanical support in advanced cones
- ELZA-PACE: for targeted topographic normalization
- Wavefront-guided transPRK: for optical refinement
This staged approach enables vision rehabilitation even in eyes previously considered suitable only for keratoplasty.
Figure 5: The ELZA Surgical Pyramid
Conclusion
Attendees at EgSCRS were told how the management of keratoconus is entering a new era—one defined by customization, staged biomechanical modulation, and minimal invasiveness. With AI-supported diagnostics, fluence-adaptive CXL (ELZA-sub400), non-ablative topographic remodeling (ELZA-PACE), and ex vivo–enhanced ICRS (ECO-CAIRS), we can now offer tailored interventions for nearly every disease stage.
These innovations are not isolated—they represent an integrated strategy. The pyramid approach aligns diagnostics with therapeutics, leveraging technology to restore stability and vision in cases previously deemed not possible.
