Faculty Bibliography

PURPOSE/OBJECTIVE:To investigate the biomechanical properties of ex vivo human paired corneas after hyperopic correction via cap-based versus flap-based laser-assisted refractive surgery. METHODS:In this prospective experimental study, 13 pairs of human corneas unsuitable for transplantation were equally divided into two groups. The pachymetry was performed in each eye just before the laser procedure. Corneas from the right eye were treated with small incision lenticule extraction (SMILE), whereas corneas from the left eye of the same donor were treated with femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). All corneas were subjected to a refractive correction of +6.00 diopters (D) sphere with a 6.5-mm zone under a 120-µm cap (SMILE) or a 7-mm zone under a 110-µm flap (FS-LASIK). For two-dimensional biomechanical measurements, the corneoscleral buttons underwent two testing cycles (preconditioning stress-strain curve from 0.03 to 9.0 N and stress-relaxation at 9.0 N during 120 seconds) to analyze the elastic and viscoelastic material properties. The effective elastic modulus was calculated. Statistical analysis was performed with a confidence interval of 95%. RESULTS:= .841) between SMILE (124 ± 20 kPa) and FS-LASIK (126 ± 21 kPa). CONCLUSIONS:.

PURPOSE/OBJECTIVE:To validate and evaluate the use of a new biomechanical index known as the Corvis biomechanical index-laser vision correction (CBI-LVC) as a method for separating stable post-LVC eyes from post-LVC eyes with ectasia. SETTING/METHODS:10 clinics from 9 countries. DESIGN/METHODS:Retrospective, multicenter, clinical study. METHODS:The study was designed with 2 purposes: to develop the CBI-LVC, which combines dynamic corneal response (DCR) parameters provided by a high-speed dynamic Scheimpflug camera (CorVis ST; OCULUS Optikgeräte GmbH) and then to evaluate its ability to detect post-LVC ectasia. The CBI-LVC includes integrated inverse radius, applanation 1 (A1) velocity, A1 deflection amplitude, highest concavity and arclength, deformation amplitude ratio of 2 mm, and A1 arclength in millimeters. Logistic regression with Wald forward stepwise approach was used to identify the optimal combination of DCRs to create the CBI-LVC and then separate stable from LVC-induced ectasia. Eighty percentage of the database was used for training the software and 20% for validation. RESULTS:736 eyes of 736 patients were included (685 stable LVC and 51 post-LVC ectasia). The receiver operating characteristic curve analysis showed an area under the curve of 0.991 when applying CBI-LVC in the validation dataset and 0.998 in the training dataset. A cutoff of 0.2 was able to separate stable LVC from ectasia with a sensitivity of 93.3% and a specificity of 97.8%. CONCLUSIONS:The CBI-LVC was highly sensitive and specific in distinguishing stable from ectatic post-LVC eyes. Using CBI-LVC in routine practice, along with topography and tomography, can aid the early diagnosis of post-LVC ectasia and allow intervention prior to visually compromising progression.

PURPOSE/OBJECTIVE:To evaluate the safety and efficacy of reduced fluence CXL (lower dose of UV-A irradiation) in mild to moderate keratoconus. SETTING/METHODS:Farabi Eye Hospital, Tehran, Iran. DESIGN/METHODS:Non-randomized prospective comparative interventional case series. Every eligible patient included in the study (mild to moderate progressive keratoconus) was randomly allocated to case (reduced fluence) and control (standard) groups, except for bilateral patients. In these patients the eye with more advanced disease was allocated to control group and the other eye was randomly assigned in either case or control group. Operators performing refraction and images and the data analyst were masked, but patients and physicians were not. METHODS:). Visual, keratometric and biomechanical outcomes were compared between groups. RESULTS:-values < 0.05). CONCLUSION/CONCLUSIONS:accelerated CXL in mild to moderate keratoconus. Should the results of this study be confirmed in longer follow-ups, using a reduced fluence setting could be considered as an alternative to standard treatment in these patients.

Ehlers-Danlos syndrome (EDS) is a genetic disease leading to abnormalities in mechanical properties of different tissues. Here we quantify corneal biomechanical properties in an adult classic EDS mouse model using two different measurement approaches suited for murine corneal mechanical characterization and relate differences to stromal structure using Second Harmonic Generation (SHG) microscopy. Quasi-static Optical Coherence Elastography (OCE) was conducted non-invasively during ambient pressure modulation by - 3 mmHg. 2D-extensometry measurements was conducted invasively consisting of a pre-conditioning cycle, a stress-relaxation test and a rupture test. In a total of 28 eyes from a Col5a1^+/- mouse model and wild-type C57BL/6 littermates (wt), Col5a1^+/- corneas were thinner when compared to wt, (125 ± 11 vs 148 ± 10 μm, respectively, p < 0.001). Short-term elastic modulus was significantly increased in OCE (506 ± 88 vs 430 ± 103 kPa, p = 0.023), and the same trend was observed in 2D-extensometry (30.7 ± 12.1 kPa vs 21.5 ± 5.7, p = 0.057). In contrast, in stress relaxation tests, Col5a1^+/- corneas experienced a stronger relaxation (55% vs 50%, p = 0.01). SHG microscopy showed differences in forward and backward scattered signal indicating abnormal collagen fibrils in Col5a1^+/- corneas. We propose that disturbed collagen fibril structure in Col5a1^+/- corneas affects the viscoelastic properties. Results presented here support clinical findings, in which thin corneas with global ultrastructural alterations maintain a normal corneal shape.

PURPOSE:To compare the elastic modulus of thin corneal lamellas using 2D stress-strain extensometry in healthy ex vivo human corneal lamellas with or without the presence of Bowman layer. SETTING:Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Switzerland; ELZA Institute, Dietikon, Switzerland; Department of Ophthalmology, Philipps University of Marburg, Germany. DESIGN:Prospective experimental laboratory study. METHODS:Healthy human corneas were stripped of Descemet membrane and the endothelium for Descemet membrane endothelial keratoplasty. After epithelium removal, corneas were divided into 2 groups. In Group 1, Bowman layer was ablated with an excimer laser (20 μm thick, 10 mm). In Group 2, Bowman layer was left intact. Then, a lamella was cut from the anterior cornea with an automated microkeratome. Elastic and viscoelastic material properties were analyzed by 2D stress-strain extensometry between 0.03 and 0.70 N. RESULTS:Twenty-six human corneas were analyzed. The mean lamella thickness was 160 ± 37 μm in corneas with Bowman layer and 155 ± 22 μm in corneas without. No statistically significant differences between flaps with and without Bowman layer were observed in the tangential elastic modulus between 5% and 20% strain (11.5 ± 2.9 kPa vs 10.8 ± 3.7 kPa, P > .278). CONCLUSIONS:The presence or absence of Bowman layer did not reveal a measurable difference in corneal stiffness. This may indicate that the removal of Bowman layer during photorefractive keratectomy does not represent a disadvantage to corneal biomechanics.

PURPOSE/OBJECTIVE:accelerated crosslinking (ACXL) in the treatment of progressive keratoconus (KC) over a span of 5 years. METHODS:ACXL at the Siena Crosslinking Centre, Italy. The mean age was 18.05 ± 5.6 years. The 20-min treatments were performed using the New KXL I (Avedro, Waltham, USA), 10 min of 0.1% HPMC Riboflavin soaking (VibeX Rapid, Avedro, Waltham, USA) and 10 min of continuous-light UV-A irradiation. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), Kmax, coma, minimum corneal thickness (MCT), surface asymmetry index (SAI), endothelial cell count (ECC) were measured, and corneal OCT performed. RESULTS:UDVA and CDVA improved significantly at the 3rd (P = 0.028), Δ + 0.17 Snellen lines and 6th postoperative month, respectively (P < 0.001), Δ + 0.23 Snellen lines. Kmax improved at the 6th postoperative month (P = 0.03), Δ - 1.49 diopters from the baseline value. Also, coma aberration value improved significantly (P = 0.004). A mild temporary haze was recorded in 14.77% of patients without affecting visual acuity and without persistent complications. Corneal OCT revealed a mean demarcation line depth at 332.6 ± 33.6 μm. CONCLUSION/CONCLUSIONS:ACXL is a candidate to be  the natural evolution of Epi-Off CXL treatment for the management of early progressive corneal ectasia, and thus optimize clinic workflow.

PURPOSE:To assess whether optimized technical settings for accelerated epithelium-off corneal cross-linking may lead to increases in biomechanical stiffness similar to the benchmark 30-minute epithelium-off Dresden protocol. METHODS:Three-hundred porcine eyes were divided equally into six groups for analysis. All samples underwent epithelial debridement and soaking with 0.1% iso-osmolar riboflavin solution for 20 minutes. Corneal cross-linking (CXL) was performed using epithelium-off protocols varying in acceleration and total fluence (intensity in mW/cm² * time in minutes, total fluence in J/cm²): standard (S)-CXL (3*30, 5.4), accelerated (A)-CXL (9*10, 5.4), A-CXL (9*13'20″, 7.2), A-CXL (18*6'40″, 7.2), and A-CXL (18*9'15″, 10). Control corneas were not irradiated. The elastic modulus of 5-mm wide corneal strips was measured as an indicator of corneal stiffness. RESULTS:All irradiated groups had significantly higher elastic modulus than controls (P < 0.05), with a stiffening effect of 133% S-CXL (3*30, 5.4), 122% A-CXL (9*10, 5.4), 120% A-CXL (9*13'20″, 7.2), 114% A-CXL (18*6'40″, 7.2) and 149% A-CXL (18*9'15″, 10). The high-fluence accelerated epithelium-off protocol (18*9'15″, 10) showed the highest stiffening effect. Elastic modulus at 5% strain (1%-5% strain) showed significant differences between A-CXL (18*9'15″, 7.2) and three other accelerated protocols: A-CXL (9*10, 5.4; P = 0.01), A-CXL (9*13'20″, 7.2; P = 0.003), and A-CXL (18*6'40″, 10; P = 0.0001). CONCLUSIONS:An accelerated high-fluence epithelium-off CXL protocol (18 mW/cm² for 9'15″) was identified to provide a significantly greater stiffening effect than any other accelerated protocols and is indistinguishable from the Dresden protocol, with accelerating irradiation times ranging from 30 to 9 minutes; by combining gentle acceleration with higher fluence, such a protocol does not require supplemental oxygen. TRANSLATIONAL RELEVANCE:This A-CXL (18*9'15″, 10) protocol has the potential to become a new standard in epithelium-off CXL, delivering Dresden protocol-like strengthening over a shorter period.