PURPOSE:Ten years after the first Global Consensus on Keratoconus and Ectatic Diseases, this updated edition revisits key issues, incorporates advances in new technologies, and integrates the expertise of corneal and refractive surgeons from 12 international societies. This initiative aimed to establish a consensus among global ophthalmology experts, including corneal and refractive specialists from 6 continents, on the definition, diagnosis, staging, clinical management, and surgical treatment of keratoconus and ectatic corneal diseases. METHODS:The Delphi method consisted of 4 rounds of questionnaires, supplemented by a face-to-face meeting. A total of 128 ophthalmologists participated, with 3 main coordinators and 125 keratoconus experts distributed across 7 panels: definition/diagnosis/staging, clinical treatment and noninvasive visual rehabilitation, cross-linking for progression, and invasive visual rehabilitation (including therapeutic approaches, improved corrected distance visual acuity, keratoplasty techniques, and cataract surgery in keratoconus). The consensus threshold was defined as at least two-thirds agreement. RESULTS:A significant consensus was reached on topics such as definitions, diagnostic and progression criteria, and management strategies for keratoconus and other ectatic corneal disorders. A comprehensive approach was outlined, encompassing both nonsurgical and surgical treatments, organized in a group-based approach. In addition, major agreements and disagreements across the 7 subcommittees are outlined in individual tables. CONCLUSIONS:This updated Global Consensus provides revised definitions, expert statements, and recommendations for diagnosing and managing keratoconus and other ectatic corneal diseases. It benefits from broader participation, with more refractive surgeons and greater representation from major ophthalmic societies across 6 continents, capturing a wider range of global clinical perspectives than the prior report.
Corneal cross-linking (CXL) has emerged as an important therapeutic strategy for enhancing the biomechanical stability of corneal tissues. Originally introduced to slow or halt the progression of keratoconus (KC), its indications have expanded to include a variety of corneal ectatic and infectious disorders, alongside a growing interest in scleral reinforcement for progressive myopia. Recent advances in cross-linking technologies focused on optimizing reagent formulations, refining delivery strategies, and incorporating functional biomaterials such as nanoparticles, hydrogels, and microneedle-based systems to enhance stromal penetration, achieve controlled release, and reduce procedural invasiveness. Despite these developments, key challenges remain, particularly in achieving consistent treatment depth, maintaining long-term biosafety, and ensuring stable clinical outcomes. This review summarizes the mechanisms of action and classification of contemporary ophthalmic cross-linking methods and agents, evaluating their clinical and experimental outcomes in corneal and scleral cross-linking while weighing their respective strengths and limitations. Furthermore, this review identifies key constraints of current protocols and highlights emerging strategies aimed at improving treatment precision, safety, and reproducibility, thereby providing a conceptual framework for the development of next-generation ophthalmic cross-linking therapies.
Das korneale Crosslinking (CXL) nach dem Dresden-Protokoll setzt eine minimale Hornhautdicke von 400 µm voraus, um das Endothel vor UV(ultraviolett)-Schäden zu schützen. Viele Patienten mit fortgeschrittener kornealer Ektasie weisen jedoch dünnere Hornhautzustände auf und werden von der Behandlung ausgeschlossen. Frühere Ansätze zur Umgehung dieser Limitation – hypoosmolare Quellung, kontaktlinsengestützte Verfahren – zeigten relevante Einschränkungen. Das ELZA-sub400-Protokoll verfolgt einen grundlegend anderen Ansatz: Die UV-Fluenz wird individuell an die Pachymetrie angepasst. Die Übersichtsarbeit basiert auf aktueller Literatur und aktuellen klinischen Daten des ELZA Institute. Dargestellt werden die photochemischen Grundlagen, der Algorithmus des sub400-Protokolls, klinische Ergebnisse und die praktische Durchführung. Das sub400-Protokoll basiert auf einem Algorithmus, der das Fick-Diffusionsgesetz für Riboflavin und Sauerstoff sowie das Lambert-Beer-Gesetz für die UV-Absorption integriert. Durch individuelle Anpassung der UV-Bestrahlungsdauer an die pachymetrisch gemessene Stromadicke wird ein effektives Crosslinking erzielt und gleichzeitig ein 70-µm-Sicherheitsabstand zum Endothel gewährleistet. In einer ersten prospektiven Studie mit 39 Augen (Hornhautdicke 214–398 µm) und Folgestudien wurde eine Erfolgsrate von 90
BACKGROUND:Infectious keratitis remains a major cause of blindness worldwide. Conventional antimicrobial treatment is not always sufficient, particularly against drug-resistant pathogens. Photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) offers a promising adjunctive or alternative treatment. METHODS:Narrative review based on the current literature and clinical experience, covering mechanisms of action, clinical evidence, protocol selection and practical decision-making criteria for PACK-CXL. RESULTS:The PACK-CXL acts via three mechanisms: direct killing of pathogens through reactive oxygen species (ROS), increased resistance to protease digestion through steric hindrance and anti-inflammatory effects. Clinical studies demonstrated that adjuvant PACK-CXL shortens the healing time and as monotherapy achieves approximately 89% success in small bacterial ulcers. Higher total radiation doses (high fluence, ≥ 7.2 J/cm2) are more effective than the standard protocol (5.4 J/cm2). For Acanthamoeba keratitis, a sequential dual chromophore strategy (riboflavin/UV followed by Rose bengal/green light) shows promising results. CONCLUSION:The use of PACK-CXL enables rapid, largely pathogen-independent treatment of infectious keratitis. Protocol selection should be guided by ulcer size, depth and pathogen type. Accelerated high-fluence protocols are particularly suitable for antimicrobial use.
Purpose: To evaluate the impact of high oxygen concentration using a novel oxygen chamber on epi-off corneal cross-linking (CXL) efficacy and patients’ perceived pain during the procedure. Setting: Farabi Eye Hospital, Tehran, Iran. Design: Interventional randomized clinical trial. Methods: Forty-eight eyes with progressive keratoconus were enrolled. The high-oxygen group (24 eyes) underwent accelerated epi-off CXL (9 mW/cm 2 UV-A, 5.4 J/cm 2 for 10 minutes) in a controlled high-oxygen environment (∼60%) using a novel oxygen chamber, while the control group (24 eyes) underwent the same protocol under ambient air oxygen (∼21%). Visual acuity, manifest refraction, and keratometry values were measured at baseline, 1 month, and 12 months post-CXL. Demarcation line depth and endothelial cell density were recorded at 1 month postoperatively. Pain was assessed intraoperatively using the Wong-Baker FACES scale (WBF). Results: The high-oxygen group demonstrated significantly deeper demarcation line depth (307 ± 14 µm vs 279 ± 23 µm, p<0.001) and greater reductions in keratometry values (K1 and K2) at 12 months (p=0.04 and p=0.02, respectively). Compared to baseline, significant improvements in K1 (p=0.02), K2 (p=0.02), and Kmax (p<0.01) were observed in the high-oxygen group, whereas only K1 showed a significant improvement in the ambient oxygen group (p=0.02). Endothelial cell count remained stable in both groups. Patient reported intraoperative pain scores were significantly lower in the high-oxygen group (Wong-Baker FACES scale (2.4 ± 0.9 vs 3.4 ± 0.7, p=0.003). Conclusion: Use of the oxygen chamber to create a high-oxygen environment during accelerated epi-off CXL was associated with deeper stromal demarcation and improved keratometric outcomes, while also reducing intraoperative pain. This approach may improve clinical outcomes and patient experience during CXL.
