Analysis of Biomechanical Response After Corneal Crosslinking with Different Fluence Levels in Porcine Corneas.

PURPOSE To evaluate corneal stiffening of porcine corneas induced by corneal crosslinking (CXL) with constant irradiance as a function of total fluence. METHODS Ninety corneas from freshly enucleated porcine eyes were divided into five groups of 18 eyes. Groups 1-4 underwent epi-off CXL using a dextran-based riboflavin solution and an irradiance of 18 mW/cm2, group 5 served as the control group. Groups 1 to 4 were treated with a total fluence of 20, 15, 10.8, and 5.4 J/cm2, respectively. Thereafter, biomechanical measurements were performed on 5 mm wide and 6 mm long strips using an uniaxial material tester. Pachymetry measurements were performed on each cornea. RESULTS At 10% strain, the stress was 76, 56, 52, and 31% higher in groups 1-4, respectively compared to the control group. The Young's modulus was 2.85 MPa for group 1, 2.53 MPa for group 2, 2.46 MPa for group 3, 2.12 MPa for group 4, and 1.62 MPa for the control group. The difference between groups 1 to 4 and the control group 5 were statistically significant (p = <0.001; p = <0.001; p = <0.001; p = 0.021). In addition, group 1 showed significantly more stiffening than group 4 (p = <0.001), no other significant differences were found. Pachymetry measurements revealed no statistically significant differences among the five groups. CONCLUSION Additional mechanical stiffening can be achieved by increasing the fluence of the CXL. There was no threshold detected up to 20 J/cm2. A higher fluence could compensate the weaker effect of accelerated or epi-on CXL procedures

Innovations in Corneal Crosslinking.

PURPOSE Corneal Crosslinking (CXL) strengthens the keratoconus cornea and prevents further disease progression. Modified crosslinking protocols and different riboflavin solutions have been proposed to optimize the procedure and improve treatment success. METHODS PubMed research of relevant publications and report of own experiences with different CXL protocols. RESULTS Accelerated CXL shows comparable efficiency with shorter surgery time and similar complication rates. Customized CXL provides improved results with faster epithelial healing. CXL in a hyperoxic environment seems to be a safe and effective transepithelial alternative with presumably less complications and fewer side effects. Thin corneas (<400 µm) can be treated safely by corneal swelling using hypoosmolar riboflavin solutions and reducing the applied UV-energy. The combination of CXL with photorefractive keratectomy (PRK) can be considered in patients with contact lens intolerance improving visual acuity, however, with increased risk of visual loss compared to CXL alone. Two-Photon (2Ph) CXL is a promising new technology enabling three-dimensional CXL. DISCUSSION Recently developed CXL protocols offer advantages over the standard "Dresden-protocol" and should be considered in patients with progressive keratectasia

Biomechanical Response After Corneal Cross-linking With Riboflavin Dissolved in Dextran Solution Versus Hydroxypropyl Methylcellulose

Purpose: To evaluate corneal stiffening in porcine eyes induced by corneal cross-linking (CXL) using riboflavin dissolved in either aqueous dextran or hydroxypropyl methylcellulose (HPMC) solution. Methods: Fifty-one porcine corneas were divided into three groups of 17 each. After deepithelialization, the first (Dresden) group was treated for 30 minutes with 0.1% riboflavin (riboflavin-5-monophosphate in 0.9% NaCl) dissolved in hypertonic 20% dextran and the second (HPMC) group for 30 minutes with isotonic solution containing 0.1% riboflavin and 1.1% HPMC. Thereafter, corneas of both groups were irradiated using 5.4 J/cm2 (irradiance of 9 mW/cm2 for 10 minutes; 10*9). After CXL, all corneas were kept in an isotonic 16% dextran bath for 2 hours to obtain an equal hydration state. The third group served as the control group. Stress-strain measurements were performed on 5-mm-wide strips. Corneal thickness was monitored throughout the entire course of the experiments. Results: The required stress for a 10% strain was increased by 83% in the Dresden group and 35% in the HPMC group compared to the control group. Resultant Young's modulus (at 10% strain) was 2.53 ± 0.73, 1.87 ± 0.50, and 1.47 ± 0.44 Pa for the Dresden, HPMC, and control groups, respectively. The differences between the Dresden and HPMC groups (P = .006), the Dresden and control groups (P < .001), and the HPMC and control groups (P = .014) were statistically significant. Pachymetry measurements showed a significantly increased corneal thickness after application of HPMC compared with the Dresden group (P = .002) and control group (P = .041). Conclusions: The biomechanical stiffening of the cornea by CXL can be achieved using dextran- and HPMC-based riboflavin solutions in porcine corneas with an application time of 30 minutes. Dextran-based riboflavin solutions seem to induce a slightly stronger biomechanical response in this setting. HPMC solutions induce less thinning than dextran solutions

Corneal crosslinking (CXL) with 18-mW/cm irradiance and 5.4-J/cm radiant exposure-early postoperative safety.

PURPOSE To investigate safety of accelerated corneal crosslinking during the first postoperative month. METHODS In this retrospective study, 76 eyes of 60 patients with verified progressive keratectasia were enrolled in this study and followed for 1 month after accelerated CXL (18 mW/cm for 5 min, radiant exposure 5.4 J/cm) (A-CXL(5*18)). Preoperatively, objective refraction, slit lamp inspection, and corneal tomography were performed. Early postoperative slit lamp examinations were performed on days 1 and 4. At 1 month, objective refraction, slit lamp inspection, and corneal tomography were performed. RESULTS Gender distribution was m:f = 55:21, OD:OS was 40:36, and the average age was 26.5 ± 8.6 years at surgery. Only 71 of the 76 eyes completed the 1-month follow-up, indicating a dropout rate of 6.6%. In 7.0% (n = 5), sterile infiltrates were observed; 5.6% of eyes (n = 4) showed delayed epithelial healing (> 4 days) in 2.8% (n = 2); an infection occurred and in 1 eye (1.4%), a stromal scar was detected; no other complications, neither a loss of two or more Snellen lines at 1 month postoperatively, were observed. As a risk factor for sterile infiltrates, thin preoperative pachymetry could be identified (p = 0.027). CONCLUSIONS This study revealed no difference in early postoperative safety between CXL using 18 mW/cm and standard corneal CXL. Thinner preoperative pachymetry could be identified predicting a higher rate of postoperative sterile infiltrates

Customized Corneal Cross-linking: One-Year Results.

PURPOSE To compare the efficacy of customized corneal cross-linking (CXL) with standard CXL. DESIGN Prospective, nonrandomized comparative clinical study. METHODS In a prospective study at the Institut für Refraktive und Ophthalmo-Chirurgie (IROC), Zurich, Switzerland, 40 eyes of 40 patients with documented progressive primary keratoconus were treated with customized CXL (n = 20) or standard CXL (n = 20) and followed for 1 year. Customized irradiation patterns had an energy fluence of 9 mW/cm(2) and total energy levels ranging from 5.4 J/cm(2) up to 10 J/cm(2) and were centered on the maximum of the posterior float. The control group received homogenous irradiation with a fluence of 9 mW/cm(2) and a total energy of 5.4 J/cm(2). Scheimpflug tomographies, endothelium cell count, best spectacle-corrected visual acuity (BSCVA), and anterior segment optical coherence tomography (OCT) were compared preoperatively and 1 year postoperatively. RESULTS Pachymetry and ΔKmax showed significant changes 1 year postoperatively within each group. Epithelial healing time, ΔKmax, and regularization index (RI) were significantly better in the customized CXL group. Two out of 19 eyes (11%) in the standard group but 7 out of 19 eyes (37%) in the customized CXL group showed a flattening of 2 or more diopters (P = .03). The RI was 5.2 ± 2.7 D in the customized group vs 4.1 ± 3.1 D in the control group (P = .03). Statistically significant correlations between RI and preoperative Kmax, preoperative pachymetry, and preoperative posterior float were found only in the customized group. CONCLUSIONS Customized CXL seems to be as safe as standard CXL with stronger flattening in Kmax and RI, and a faster epithelial healing period

Comparison of Corneal Riboflavin Gradients Using Dextran and HPMC Solutions.

PURPOSE To determine the riboflavin concentration gradient in the anterior corneal stroma when using hydroxypropyl methylcellulose (HPMC) or dextran as the carrier agent. METHODS Four different groups of porcine corneas (5 each) were compared regarding the riboflavin concentration in the anterior stroma. Prior to all experiments, stable hydration conditions were established for the corresponding solution. The dextran groups were treated with 0.1% riboflavin in 20% dextran for 10 and 30 minutes and the HPMC groups with 0.1% riboflavin in 1.1% HPMC for 10 and 30 minutes. After imbibition, nonlinear microscopy and consecutive image analysis were used to determine two-photon fluorescence intensities. To determine the riboflavin concentration, corneas were saturated and measured a second time by two-photon microscopy. With this measurement, a proper correction for absorption and scattering could be performed. Ultraviolet-A (UVA) transmission was measured after the application time for each group. RESULTS Riboflavin concentration decreased with increasing depth and increased with longer application times in all groups. Comparing the dextran for 30 minutes and HPMC for 10 minutes groups, a significantly higher stromal riboflavin concentration was found within the most anterior 70 µm in the dextran group for 30 minutes, whereas deeper than 260 µm HPMC-assisted imbibition for 10 minutes yielded higher concentrations. In dextran-treated corneas, values obtained from pachymetry were substantially reduced, whereas HPMC-assisted imbibition led to a decent swelling. UVA transmission values were higher in dextran-assisted imbibition than in HPMC-assisted imbibition. CONCLUSIONS Stromal riboflavin gradients are similar when applied in dextran for 30 minutes and HPMC for 10 minutes. When using HPMC solutions, a shallower cross-linked volume is expected due to a higher corneal hydration. [J Refract Surg. 2016;32(12):798-802.]

Spectral behavior of second harmonic signals from organic and non-organic materials in multiphoton microscopy

Multimodal nonlinear microscopy allows imaging of highly ordered biological tissue due to spectral separation of nonlinear signals. This requires certain knowledge about the spectral distribution of the different nonlinear signals. In contrast to several publications we demonstrate a factor of 1 2 2 relating the full width at half maximum of a gaussian laser pulse spectrum to the corresponding second harmonic pulse spectrum in the spatial domain by using a simple theoretical model. Experiments on monopotassium phosphate crystals (KDP-crystals) and on porcine corneal tissue support our theoretical predictions. Furthermore, no differences in spectral width were found for epi- and trans-detection of the second harmonic signal. Overall, these results may help to build an optimized multiphoton setup for spectral separation of nonlinear signals

Erratum: Spectral behavior of second harmonic signals from organic and non-organic materials in multiphoton microscopy (vol 5, 084903, 2015)

Erratum to: “Spectral behavior of second harmonic signals from organic and non-organic materials in multiphoton microscopy” in: AIP Advances 5, 084903 (2015

Characteristics of surgically induced astigmatism after standardized microincisional cataract surgery with a superior limbal incision.

PURPOSE To determine 1) if measurements of surgically induced astigmatism (SIA) as measured by keratometry (K) and total keratometry (TK) differ 2) if SIA affects the magnitude and/or meridian of keratometric astigmatism 3) if SIA evolves over time. SETTING Tertiary care center. DESIGN Retrospective data analysis. METHODS A swept-source OCT (SS-OCT) biometry dataset (IOLMaster700) consisting of 498 eyes (327 patients) from a tertiary care center was analyzed. For all eyes preoperative and postoperative biometric measurements at 1-, 3-, and 6-months postoperative visits were considered for vector analysis of SIAK and SIATK. RESULTS Centroids in right and left eyes were 0.26 dpt @5°/ 0.31 dpt @1° for SIAK and 0.27 dpt @4°/ 0.34 dpt @1° for SIATK. Centroids for difference vectors (DV) K-TK in right and left eyes were 0.02 dpt @ 176°/ 0.03 dpt @6°. The mean SIA magnitudes in right and left eyes were 0.48±0.41 dpt and 0.50±0.37 dpt for SIAK and 0.53±0.42 dpt and 0.54±0.40 dpt for SIATK. In eyes with ATR astigmatism, an increase in postoperative astigmatism magnitude was more common than a decrease. More than 30% of eyes showed changes in the meridian of more than 15°. CONCLUSION Overall, we observed differences in K- and TK-derived SIA, and changes in SIA magnitude over time. For post-surgical interventions, postoperative astigmatism meridian values should be measured to base treatments. Astigmatism magnitude showed a tendency to decrease for steep-meridian incisions and to increase in flat-meridian incisions