Faculty Bibliography

OBJECTIVE:UV-A/riboflavin cross-linking (CXL) of corneal collagen fibers is an established, highly promising therapy for corneal melting in physician-based ophthalmology. A prospective pilot study was conducted to demonstrate proof of principle of this novel method for the treatment of melting corneal ulcers in dogs and cats. PROCEDURES/METHODS:After obtaining owner consent, CXL was performed in three cats and three dogs with corneal melting, which either affected the entire corneal surface or was resistant to conventional antibiotic and anticollagenolytic therapy, and affected parts or all of the corneal surface. Medical therapy was continued in all patients. The available follow-up ranged from 2 to 22.5 months and involved slit-lamp examination, fluorescein staining, and photographic documentation during all rechecks. RESULTS:Surgical stabilization of the cornea was not necessary in any case, because progression of corneal melting was arrested in all cases within 1-20 days of CXL treatment. Corneal re-epithelization occurred within 7-40 days in all eyes. At 40 days after CXL, all eyes presented a quiescent corneal state without signs of active inflammation and with beginning scar formation. The complications observed in three of the six animals included a corneal sequestrum, superficial corneal stromal pigmentation, and bullous keratopathy. CONCLUSIONS:This study shows the feasibility of CXL to treat progressive corneal melting in veterinary patients. CXL may represent a cost-efficient and safe alternative therapy in the treatment for corneal melting in veterinary ophthalmology. More investigations comparing the effectivity and complication rate of CXL to those of standard medical treatment are necessary.

PURPOSE/OBJECTIVE:To introduce a constant-force technique for the analysis of corneal biomechanical changes induced after collagen cross-linking (CXL) that is better adapted to the natural loading in the eye than previous methods. METHODS:For the biomechanical testing, a total of 50 freshly enucleated eyes were obtained and subdivided in groups of 5 eyes each. A Zwicki-Line Testing Machine was used to analyze the strain of 11 mm long and 5 mm wide porcine corneal strips, with and without CXL. Before material testing, the corneal tissues were pre-stressed with 0.02 N until force stabilization. Standard strip extensiometry was performed as control technique. For the constant-force technique, tissue elongation (Δ strain, %) was analyzed for 180 seconds while different constant forces (0.25 N, 0.5 N, 1 N, 5 N) were applied. RESULTS:Using a constant force of 0.5 N, we observed a significant difference in Δstrain between 0.26±0.01% in controls and 0.12±0.03% in the CXL-treated group (p = 0.003) over baseline. Similarly, using a constant force of 1 N, Δstrain was 0.31±0.03% in controls and 0.19±0.02% after CXL treatment (p = 0.008). No significant differences were observed between CXL-treated groups and controls with 0.25 N or 5 N constant forces. Standard stress-strain extensiometry failed to show significant differences between CXL-treated groups and controls at all percentages of strains tested. CONCLUSION/CONCLUSIONS:We propose a constant-force technique to measure corneal biomechanics in a more physiologic way. When compared to standard stress-strain extensiometry, the constant-force technique provides less variability and thus reaches significant results with a lower sample number.

PURPOSE/OBJECTIVE:To compare a femtosecond laser with a microkeratome for flap creation during laser in situ keratomileusis (LASIK) in terms of flap thickness predictability and visual outcomes. PATIENTS AND METHODS/METHODS:This was a prospective, randomized, masked, paired-eye study. Forty-four patients (34 females) who received bilateral LASIK were included. Patients were stratified by ocular dominance, and they then underwent randomization of flap creation using the femtosecond laser on one eye and undergoing the microkeratome procedure on the other one. The visual outcome differences between the corrected distance visual acuity (CDVA) at baseline and the uncorrected distance visual acuity (UDVA) on the first day postoperatively were set as the efficiency index for both groups. All visual acuity outcome results and the deviation of flap thickness were evaluated. P-values <0.05 were considered statistically significant. RESULTS:The index of efficiency regarding the postoperative visual outcomes in the microkeratome group was lower (P<0.0001). This result was correlated with the difference between intended and achieved flap thickness (P=0.038; r=0.28), and a negative relationship in the regression analysis was confirmed (P<0.04; R (2)=0.1428). The UDVA in the microkeratome group improved significantly by the end of the first month (P<0.0271) in comparison to the baseline CDVA. The deviation between intended and postoperative flap thickness using either optical coherence pachymetry or Heidelberg Retinal Tomography II confocal microscopy was statistically significant (paired t-test; P<0.001) between the groups. The flap thickness deviation in the microkeratome group was higher. In the femtosecond laser group, the efficiency index was stable postoperatively (P=0.64) The UDVA improved significantly by the end of the first postoperative week (P=0.0043) in comparison to the baseline CDVA. Six months after surgery, improvement in the UDVA was significant in both groups (all P<0.001; one way analysis of variance). CONCLUSION/CONCLUSIONS:Femtosecond laser was superior to microkeratome-assisted LASIK in terms of flap thickness predictability and the speed of visual acuity recovery. A negative relationship in the regression analysis between increasing flap thickness deviation and visual acuity recovery was confirmed.

PURPOSE/OBJECTIVE:To investigate the effect of high-fluence corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A in the management of progressive keratoconus. METHODS:Preliminary results from a prospective cohort study. Seven eyes from 7 patients with progressive keratoconus subjected to CXL were included. CXL was performed as a standard epithelium-off procedure, irradiating with high-fluence settings (18 mW/cm(2) for 5 minutes). Endothelial cell density (ECD), speed of postoperative epithelial healing, maximal and average keratometric readings (Kmax and Kmean, respectively) of the anterior corneal surface, and corrected distance visual acuity (CDVA) were evaluated preoperatively and at 1 and 6 months after CXL. One-way analysis of variance was applied for statistical analysis. P values less than .05 were considered significant. RESULTS:ECD did not change significantly postoperatively and complete epithelial healing occurred in all eyes within 96 hours postoperatively. No morphological alterations in the corneal limbus were observed. Kmax, Kmean, and CDVA showed no significant changes at 1 and 6 months postoperatively. No complications were observed postoperatively. CONCLUSIONS:Although the preliminary results are not sufficient for a valid evaluation of the biomechanical effect and the overall safety profile of high-fluence CXL in vivo, they demonstrate that CXL at 18 mW/cm(2) for 5 minutes affects neither endothelial cell density nor the speed of epithelial healing, an indirect indicator of limbal stem cell function.

PURPOSE/OBJECTIVE:To investigate the effect of fluorescein on the antimicrobial efficacy of photoactivated riboflavin in corneal collagen cross-linking (CXL) in vitro. METHODS:The ultraviolet light-A (UVA) absorption by fluorescein and riboflavin in different concentrations was analyzed with a spectrophotometer. The killing rate of Staphylococcus aureus strains after CXL with UV-A irradiation using different solutions containing riboflavin and/or fluorescein, was evaluated in vitro. RESULTS:Fluorescein absorbed UV-A to a significant extent, which augmented with increasing concentration. Moreover, addition of fluorescein to the riboflavin solution contributed to a significant reduction of the killing rate of S. aureus strains after 30 minutes of UV-A irradiation in vitro with a killing rate of 85%, whereas it was 47% in the presence of 2% fluorescein (P = .0247). CONCLUSIONS:The results indicate that fluorescein competes with riboflavin for the absorption of UV-A during CXL and reduces the antimicrobial effect of the procedure. The authors recommend that physicians treating infectious ulcerative keratitis by CXL should not stain the cornea with fluorescein for visualization of the corneal ulceration prior to CXL

PURPOSE/OBJECTIVE:In an attempt to reduce treatment time in corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A (UV-A), recent protocol modifications include shorter irradiation times at higher fluence, while maintaining constant total applied energy (Bunsen-Roscoe law of reciprocity). While such parameter changes might produce similar biological results within a certain range, the limits of reciprocity are unknown. Limitations in the corneal oxygen diffusion capacity and its potential impact on the efficacy of CXL, raise concerns regarding the efficiency of high-fluence CXL, and also of transepithelial CXL. METHODS:= 20 each). Five-millimeter corneal stripes were prepared and biomechanical stiffness was measured using an extensometer. RESULTS:Corneas cross-linked under normal oxygen levels showed a significant increase in biomechanical stability (14.36 MPa ± 2.69 SD), whereas corneas treated similarly, but in a low-oxygen atmosphere showed a Young's modulus similar to untreated controls (11.72 MPa ± 2.77 SD). CONCLUSIONS:The biomechanical effect of CXL seems to be oxygen dependent. This dependency will be of particular importance in high-fluence and transepithelial CXL and will most likely require major protocol modifications to maintain the efficiency of the method. TRANSLATIONAL RELEVANCE/CONCLUSIONS:The oxygen dependency of CXL shown here raises concerns about the effectiveness of high-fluence and transepithelial CXL. Both methods were introduced to clinical ophthalmology without thorough validation.

The large majority of patients undergoing ophthalmic surgery are elderly and take systemic medications on a regular basis, including antiplatelet and anticoagulant treatments. It is current practice for many physicians to discontinue antithrombotic treatment prior to surgery to reduce bleeding complications that may lead to retrobulbar haemorrhage and, ultimately, to loss of vision. However, discontinuation of antithrombotic treatment in such patients may lead to thromboembolic events with serious consequences. The present narrative review highlights the risk of thrombosis when discontinuing antithrombotic drugs and the risk of bleeding when continuing them. The published literature on this topic shows that discontinuation of antiplatelet or anticoagulant treatment leads to a substantially increased risk of arterial or venous thromboembolic events and related complications, especially in patients with atrial fibrillation, prosthetic heart valves or recent coronary stenting. This risk is distinctly higher than the risk of significant local haemorrhage. Ophthalmic bleeding events reported in the literature are usually minor, without serious consequences, even if antiplatelet or anticoagulant treatments are continued, provided that the anticoagulation level is within the therapeutic range. Thus, the current data are in favour of maintaining antiplatelet and anticoagulant drugs for most ophthalmic procedures, regardless of the anaesthetic techniques.