Faculty Bibliography

Keratoconus (KC) is a progressive corneal disorder that typically manifests during adolescence characterized by corneal thinning and irregularity. Recent studies have revealed that pathoanatomical abnormalities may not be limited to the anterior segment. Posterior segment alterations may also occur in KC patients. This study aims to provide a comprehensive review of the posterior segment changes in KC and assess the role of optical coherence tomography (OCT) in detecting these alterations. An initial systematic search of PubMed, EMBASE, and Web of Science was conducted on November 28, 2024. To identify any newly published literature, the search was updated on September 1, 2025. Random-effects models were employed to calculate pooled effect estimates. A total of 38 studies involving 4584 eyes were reviewed and 26 studies (3124 eyes) met our eligibility criteria for meta-analysis. The remaining 12 studies, although not included in the quantitative synthesis, were reviewed and their findings integrated. Our systematic analysis revealed significant reductions in several macular measurements, including average and temporal parafoveal (inner ring) thickness as well as temporal and superior perifoveal (outer ring) thickness. Peripapillary parameters also showed notable decreases, specifically in lamina cribrosa thickness, average retinal nerve fiber layer (RNFL) thickness, and RNFL thickness in the superior, temporal, and inferior quadrants. By contrast, subfoveal choroidal thickness was significantly increased in KC patients. Additionally, optic nerve head parameters, including cup area and cup volume, showed significantly greater values. When comparing different stages of the disease, patients with moderate KC exhibited significantly higher superotemporal RNFL thickness than those with severe disease. This meta-analysis underscores the concept that keratoconus, primarily a corneal disease, is associated with retinal and choroidal structural abnormalities. Changes in the posterior segment were similar across mild and advanced stages of the corneal disease. OCT monitoring in KC patients can facilitate detection of these alterations.

PURPOSE/UNASSIGNED:To describe a new surgical technique to treat corneal allogenic ring segments (CAIRS) shaped by a femto-second laser with extracorporeal ultra-high-fluence corneal cross-linking (CXL) before insertion into the corneal stroma (ECO-CAIRS). METHODS/UNASSIGNED:ultraviolet (UV) light fluences, and inserted without air-drying or extended dehydration. RESULTS/UNASSIGNED:Insertion was uneventful in all cases. CAIRS subjected to ultra-high-fluence CXL remained stiff during the entire insertion process and showed no tendency to soften. The initial ring segment thickness was approximately halved immediately after the high-fluence CXL treatment compared to pre-CXL levels; thickness levels increased within days after insertion. CONCLUSIONS/UNASSIGNED:This new technique may provide multiple advantages over unmodified or air-dried CAIRS, including an easier insertion due to greater stiffness and resistance to re-swelling during insertion. The high UV fluences used should eliminate viable keratocytes, essentially transforming the segment into an acellular collagen scaffold. Finally, the marked transitory decrease in thickness may allow for the insertion of ring segments with greater overall volume, potentially increasing the corneal topographical effect. Further clinical research is required to assess the extent to which the effect on corneal topography is driven by the CAIRS volume and/or by its intrinsic stiffness.

PURPOSE/UNASSIGNED:To validate an existing finite element model (FEM) for predicting the flattening effect of corneal cross-linking (CXL) in a clinical scenario and to use this model to investigate the parameters that most influence CXL-induced flattening effects. METHODS/UNASSIGNED:Retrospective data were collected from two clinical cohorts, each with 20 patients receiving either standard or customized CXL. Data were collected before surgery and at the six-month follow-up. Both CXL treatments were simulated with a FEM calibrated on experimental data. Standard anterior corneal geometry indexes (e.g., sphere, cylinder), as well as the curvature changes observed at follow-up were compared to those predicted by FEM simulations. RESULTS/UNASSIGNED:At follow-up, patients who underwent customized CXL exhibited more corneal flattening compared to those who received standard CXL (Kmax-t: -2.28 ± 1.4 D vs. -0.81 ± 1.5 D; P < 0.001). The FEM-predicted curvature reduction in the central CXL regions showed a significant correlation with the follow-up data for both standard (R2 = 0.48, P < 0.01) and customized CXL (R2 = 0.59, P < 0.01). Compared to follow-up data, standard CXL model showed concordance correlation coefficients > 0.9 for nine corneal geometry parameters and customized CXL model for three. Sensitivity analysis demonstrated that a 3 mm Hg increase in intraocular pressure (IOP) combined with a 10% weaker keratoconus region alters flattening outcomes by up to 20%. CONCLUSIONS/UNASSIGNED:Customized CXL induces a flattening of about 2 diopters in the cone region six months after surgery. The model adequately captured the curvature corrections induced by the treatment in the keratoconus cone region, but showed reduced accuracy in predicting global corneal metrics, particularly for customized CXL. The induced flattening effects depend on the IOP, keratoconus-induced biomechanical weakening, and the fluence delivered to the cone.

PURPOSE/OBJECTIVE:To investigate the corneal endothelial integrity in patients who underwent corneal cross-linking (CXL) with the Sub400 protocol, which treats progressive ectasia not eligible for standard CXL due to a stromal thickness of less than 400 µm. METHODS:This was an investigator-initiated, retrospective, single-center study conducted at the Department of Ophthalmology at the University Hospital Zurich in collaboration with the ELZA Institute in Zurich, Switzerland. Confocal endothelial measurements were performed before and up to 24 months after CXL. We applied a linear mixed-effect model to compare endothelial cell density (ECD) differences depending on time and treatment. At the 1-month follow-up visit, the demarcation line (DL) depth was assessed using anterior segment optical coherence tomography. RESULTS:= .09). CONCLUSIONS:.

PURPOSE/OBJECTIVE:To assess the biomechanical strength of a new transepithelial corneal cross-linking (epi-on CXL) protocol without iontophoresis and additional oxygen, and to compare it to the most broadly used accelerated epithelium-off (epioff) CXL protocol. METHODS:). Stress-strain extensiometry was performed to determine corneal biomechanics. RESULTS:= .005, respectively). CONCLUSIONS:.

PURPOSE/UNASSIGNED:To assess corneal resistance to enzymatic digestion after rose bengal (RB)/green light and RB/green light followed by riboflavin (RF)/ultraviolet A (UV-A) cross-linking (CXL), with or without oxygen. METHODS/UNASSIGNED:Ex vivo porcine corneal buttons (n = 144) underwent CXL with RB/green or RB/green-RF/UV-A under atmospheric 21% oxygen conditions or in a nitrogen chamber with 0.1% oxygen (hypoxic conditions) to test 10- and 15-J/cm2 fluences. After CXL, corneas were digested with 0.3% collagenase A, and mean digestion times (MDTs) were recorded. RESULTS/UNASSIGNED:For the non-irradiated control group, the MDT was 19.75 ± 1.34 hours. Under atmospheric oxygen conditions, RB/green CXL yielded MDTs of 33.69 ± 1.4 and 34.38 ± 1.31 hours with fluences of 10 and 15 J/cm2, respectively. RB/green + RF/UV-A showed MDTs of 39.56 ± 1.93 and 51.94 ± 4.2 hours for combined fluences of 10 + 10 J/cm2 and 15 + 15 J/cm2, respectively. Hypoxic RB/green MDTs were 33.88 ± 1.02 and 34.06 ± 1.57 hours, and RB/green + RF/UV-A MDTs were 39.62 ± 2.5 and 50.35 ± 1.59 hours for the same respective fluences. No significant differences were observed between the control groups and corresponding intervention groups (all P > 0.05). CONCLUSIONS/UNASSIGNED:CXL via RB/green and RB/green-RF/UV-A significantly enhanced corneal collagenase digestion resistance, irrespective of oxygen presence. These findings could help optimize infectious keratitis therapy CXL protocols. TRANSLATIONAL RELEVANCE/UNASSIGNED:Our findings aid the understanding of the molecular mechanisms underlying the therapeutic effect of CXL and may contribute to refining accelerated PACK-CXL protocols and other CXL treatment strategies.

PURPOSE/OBJECTIVE:To evaluate the outcomes of patients treated with corneal allogeneic intrastromal ring segments cut with femtosecond laser (Femto-CAIRS) without concomitant corneal crosslinking. METHODS:Patients with keratoconus treated with Femto-CAIRS at the American University of Beirut Medical Center were included (May 2022-January 2023). A proprietary software program was developed on the femtosecond laser to cut allogeneic segments. Visual, refractive, tomographic, aberrometric, and epithelial data by anterior segment optical coherence tomography were measured at baseline and 1, 3, 6, and 12 months postoperatively. RESULTS:20 eyes of 15 patients were included and followed up for 12 months. The manifest refraction spherical equivalent and cylinder improved from -6.79 ± 4.9 diopter (D) and -4.25 ± 1.8 D to -1.88 ± 2.9 D (P < 0.001) and -2.64 ± 1.4 D (P = 0.01) 12 months postoperatively, respectively. 75% of eyes gained 3 or more corrected distance visual acuity lines, most of which (65%) gained 4 lines or more 12 months postoperatively. The maximum keratometry and vertical coma decreased by 5.2 D (P < 0.001) and 1 μm (P = 0.001), respectively, 3 months postoperatively and remained stable until 12 months. The largest anterior stromal elevation over the central 5-mm diameter decreased from 36.0 ± 18.2 μm preoperatively to 19.9 ± 9.25 μm at 1 week postoperatively (P < 0.001) and remained relatively stable. Epithelial thickness over the cone increased relative to baseline starting 1 month postoperatively and becoming stable after 6 months while the mean epithelial thickness central to the ring peaked at 1 month after which it decreased to reach a plateau at 6 months. CONCLUSIONS:The Femto-CAIRS procedure improves visual and tomographic parameters and allows repeatable and safe results with the possibility of customization for individualized management.

PURPOSE/OBJECTIVE:To investigate the light transmission (LT) of UV-A and green light through infected corneas saturated with riboflavin or rose bengal in an ex vivo porcine model for infectious keratitis. SETTING/METHODS:University of Zurich and EMPA. DESIGN/METHODS:Laboratory study. METHODS:Ex vivo porcine eyes (n=162) were divided into three groups: control eyes, eyes infected with Staphylococcus aureus, and eyes infected with Pseudomonas aeruginosa. Corneas remained either uninfected, or were infected with S. aureus, and P. aeruginosa, respectively, and were either left untreated, or were instilled with 0.1% riboflavin or 0.1% rose bengal. Corneal buttons were prepared, and corneal LT was measured at 365 nm and 522 nm using a spectrophotometer. LTs were calculated and compared. Transmission electron microscopy (TEM) was used to visualize structural damage and bacteria within infected corneas. RESULTS:Riboflavin-saturated corneas infected by S. aureus or P. aeruginosa (LT = 0.77% [0.41-1.87] and 0.81% [0.23, 1.46]) exhibited 3.18-fold and 3.02-fold lower LTs than uninfected corneas (LT = 2.45% [2.15, 5.89]) (both p-values < 0.001). No LT difference was found between rose bengal-saturated corneas infected by S. aureus or P. aeruginosa and uninfected corneas (all LTs = 0.01% [0.01-0.01]; both p-values = 0.08). TEM showed bacteria on corneal stroma borders and occasionally inside the stroma. CONCLUSION/CONCLUSIONS:Our results indicate that the amount of light arriving at the corneal endothelium is substantially reduced in infected corneas. The total fluence of clinical PACK-CXL protocols can be safely increased substantially while maintaining a low risk of corneal endothelial damage.

BACKGROUND:Acanthamoeba keratitis (AK) is the most challenging corneal infection to treat, with conventional therapies often proving ineffective. While photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) with riboflavin/UV-A has shown success in treating bacterial and fungal keratitis, and PACK-CXL with rose bengal/green light has demonstrated promise in fungal keratitis, neither approach has been shown to effectively eradicate AK. This case study explores a novel combined same-session treatment approach using both riboflavin/UV-A and rose bengal/green light in a single procedure. CASE PRESENTATION/METHODS:) in a single setting. The procedure was repeated twice due to persistent signs of inflammation and infection. After three combined same-session PACK-CXL treatments, the patient's cornea converted to a quiescent scar, and symptoms of ocular pain, photophobia, epiphora, and blepharospasm resolved. Confocal microscopy revealed no detectable Acanthamoeba cysts. The patient currently awaits penetrating keratoplasty. CONCLUSIONS:The same-session combination of riboflavin/UV-A and rose bengal/green light PACK-CXL effectively treated a patient with confirmed AK that was resistant to conventional medical therapy, suggesting that using two chromophores in a single procedure may represent a future treatment alternative for AK.

Corneal cross-linking (CXL) has profoundly changed the management of keratoconus and other ectatic corneal diseases. Introduced in the late 1990s, CXL marked the first effective intervention to halt disease progression. This chapter describes the history of CXL, beginning with its conceptual foundations and preclinical studies conducted at the University of Dresden. Early experiments established the efficacy of riboflavin and UV-A light to induce collagen cross-linking, which improved corneal stiffness. Clinical translation followed with the Dresden protocol, demonstrating safety and efficacy. Long-term studies confirm sustained benefits, with advances in accelerated protocols and modifications for thin corneas extending eligibility to more patients. Additionally, CXL has expanded into infectious keratitis treatment and refractive surgery. Emerging innovations, such as customized and two-photon CXL, promise further applications. By examining the milestones in its evolution, this paper highlights the transformative impact of CXL on corneal disease management.