Storage-induced mechanical changes of porcine lenses assessed with optical coherence elastography and inverse finite element modeling.

Introduction: In an effort of gaining a better understanding of the lens mechanics, ex vivo lenses samples are often used. Yet, ex vivo tissue might undergo important postmortem changes depending on the unavoidable preservation method employed. The purpose of this study was to assess how various storage conditions and the removal of the lens capsule affect the mechanical properties of ex vivo porcine lens samples. Methods: A total of 81 freshly enucleated porcine eyes were obtained and divided into six groups and preserved differently. In the first three groups, the lens within the intact eye was preserved for 24 h by: (i) freezing at -80°C (n = 12), (ii) freezing at -20°C (n = 12), and (iii) refrigeration at +8°C (n = 12). In the remaining groups, the lenses were immediately extracted and treated as follows: (iv) kept intact, no storage (n = 12), (v) decapsulated, no storage (n = 21), and (vi) immersed in Minimum Essential Medium (MEM) at +8°C (n = 12) for 24 h. Frozen lenses were thawed at room temperature. Each lens was compressed between two glass lamella and subjected, first to a period of relaxation during which the compression force was recorded and second to an oscillating micro-compression while the deformation was recorded with a total of 256 subsequent B-scans via optical coherence tomography. The corresponding axial strain was retrieved via phase-sensitive image processing and subsequently used as input for an inverse finite element analysis (iFEA) to retrieve the visco-hyperelastic material properties of the lenses. Results: After freezing at temperatures of -80°C and -20°C, the cortical strains increased by 14% (p = 0.01) and 34% (p < 0.001), and the nuclear strains decreased by 17% (p = 0.014) and 36% (p < 0.001), compared to the lenses tested immediately after postmortem, respectively. According to iFEA, this resulted from an increased ratio of the nuclear: cortical E-modulus (4.06 and 7.06) in -80°C and -20°C frozen lenses compared to fresh lenses (3.3). Decapsulation had the largest effect on the material constant C10, showing an increase both in the nucleus and cortex. Preservation of the intact eye in the refrigerator induced the least mechanical alterations in the lens, compared to the intact fresh condition. Discussion: Combining iFEA with optical coherence elastography allowed us to identify important changes in the lens mechanics induced after different preserving ex vivo methods.

Optomechanical assessment of photorefractive corneal cross-linking via optical coherence elastography.

Purpose: Corneal cross-linking (CXL) has recently been used with promising results to positively affect corneal refractive power in the treatment of hyperopia and mild myopia. However, understanding and predicting the optomechanical changes induced by this procedure are challenging. Methods: We applied ambient pressure modulation based optical coherence elastography (OCE) to quantify the refractive and mechanical effects of patterned CXL and their relationship to energy delivered during the treatment on porcine corneas. Three different patterned treatments were performed, designed according to Zernike polynomial functions (circle, astigmatism, coma). In addition, three different irradiation protocols were analyzed: standard Dresden CXL (fluence of 5.4 J/cm2), accelerated CXL (fluence of 5.4 J/cm2), and high-fluence CXL (fluence of 16.2 J/cm2). The axial strain distribution in the stroma induced by ocular inflation (Δp = 30 mmHg) was quantified, maps of the anterior sagittal curvature were constructed and cylindrical refraction was assessed. Results: Thirty minutes after CXL, there was a statistically significant increase in axial strain amplitude (p < 0.050) and a reduction in sagittal curvature (p < 0.050) in the regions treated with all irradiation patterns compared to the non-irradiated ones. Thirty-6 hours later, the non-irradiated regions showed compressive strains, while the axial strain in the CXL-treated regions was close to zero, and the reduction in sagittal curvature observed 30 minutes after the treatment was maintained. The Dresden CXL and accelerated CXL produced comparable amounts of stiffening and refractive changes (p = 0.856), while high-fluence CXL produced the strongest response in terms of axial strain (6.9‰ ± 1.9‰) and refractive correction (3.4 ± 0.9 D). Tripling the energy administered during CXL resulted in a 2.4-fold increase in the resulting refractive correction. Conclusion: OCE showed that refractive changes and alterations in corneal biomechanics are directly related. A patient-specific selection of both, the administered UV fluence and the irradiation pattern during CXL is promising to allow customized photorefractive corrections in the future.

Localized Refractive Changes Induced by Symmetric and Progressive Asymmetric Intracorneal Ring Segments Assessed with a 3D Finite-Element Model.

To build a representative 3D finite element model (FEM) for intracorneal ring segment (ICRS) implantation and to investigate localized optical changes induced by different ICRS geometries, a hyperelastic shell FEM was developed to compare the effect of symmetric and progressive asymmetric ICRS designs in a generic healthy and asymmetric keratoconic (KC) cornea. The resulting deformed geometry was assessed in terms of average curvature via a biconic fit, sagittal curvature (K), and optical aberrations via Zernike polynomials. The sagittal curvature map showed a locally restricted flattening interior to the ring (Kmax -11 to -25 dpt) and, in the KC cornea, an additional local steepening on the opposite half of the cornea (Kmax up to +1.9 dpt). Considering the optical aberrations present in the model of the KC cornea, the progressive ICRS corrected vertical coma (-3.42 vs. -3.13 µm); horizontal coma (-0.67 vs. 0.36 µm); and defocus (2.90 vs. 2.75 µm), oblique trefoil (-0.54 vs. -0.08 µm), and oblique secondary astigmatism (0.48 vs. -0.09 µm) aberrations stronger than the symmetric ICRS. Customized ICRS designs inspired by the underlying KC phenotype have the potential to achieve more tailored refractive corrections, particularly in asymmetric keratoconus patterns.

A short screening tool identifying systemic barriers to distress screening in cancer care.

INTRODUCTION: International guidelines on cancer treatment recommend screening for early detection and treatment of distress. However, screening rates are insufficient. In the present study, a survey was developed to assess perceived systemic barriers to distress screening. METHODS: A three-step approach was used for the study. Based on qualitative content analysis of interviews and an expert panel, an initial survey with 53 questions on barriers to screening was designed. It was completed by 98 nurses in a large comprehensive cancer center in Switzerland. From this, a short version of the survey with 24 questions was derived using exploratory principal component analysis. This survey was completed by 150 nurses in four cancer centers in Switzerland. A confirmatory factor analysis was then performed on the shortened version, yielding a final set of 14 questions. RESULTS: The initial set of 53 questions was reduced to a set of 14 validated questions retaining 53% of the original variance. These 14 questions allow for an assessment within 2-3 min that identifies relevant barriers to distress screening from the perspective of those responsible for implementation of distress screening. Across several hospitals in Switzerland, the timing of the first distress screening, lack of capacity, patient and staff overload, and refusal of distressed patients to be referred to support services emerged as major problems. CONCLUSION: The validated 14 questions on barriers to screening cancer patients for distress enable clinicians and hospital administrators to quickly identify relevant issues and take action to improve screening programs.

Viscoelastic properties of porcine lenses using optical coherence elastography and inverse finite element analysis.

The mechanical properties of the crystalline lens are crucial in determining the changes in lens shape that occur during the accommodation process and are also a major factor in the development of the two most prevalent age-related diseases of the lens, presbyopia and cataracts. However, a comprehensive understanding of these properties is currently lacking. Previous methods for characterizing the mechanical properties of the lens have been limited by the amount of data that could be collected during each test and the lack of complex material modeling. These limitations were mainly caused by the lack of imaging techniques that can provide data for the entire crystalline lens and the need for more complex models to describe the non-linear behavior of the lens. To address these issues, we characterized the mechanical properties of 13 porcine lenses during an ex vivo micro-controlled-displacement compression experiment using optical coherence elastography (OCE) and inverse finite element analysis (iFEA). OCE allowed us to quantify the internal strain distribution of the lens and differentiate between the different parts of the lens, while iFEA enabled us to implement an advanced material model to characterize the viscoelasticity of the lens nucleus and the relative stiffness gradient in the lens. Our findings revealed a pronounced and rapid viscoelastic behavior in the lens nucleus (g1 = 0.39 ± 0.13, τ1 = 5.01 ± 2.31 s) and identified the lens nucleus as the stiffest region, with a stiffness 4.42 ± 1.20 times greater than the anterior cortex and 3.47 ± 0.82 times greater than the posterior cortex. However, due to the complex nature of lens properties, it may be necessary to employ multiple tests simultaneously for a more comprehensive understanding of the crystalline lens.

Corneal crosslinking with riboflavin using sunlight.

PURPOSE: To assess whether sunlight might be used to induce a biomechanical stiffening effect in riboflavin-soaked corneas similar to the effect observed in corneal crosslinking (CXL) using riboflavin and UV-A light. SETTING: Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland. DESIGN: Experimental study. METHODS: 52 porcine eyes were assayed. The concentration of riboflavin in the corneal stroma was estimated using UV-A transmission in a preliminary experiment. Then, the duration of sunlight exposure to achieve a fluence of 7.2/cm 2 was calculated. Finally, de-epithelialized corneas were divided equally into 3 groups and soaked with riboflavin 0.1% (control group and Group 1) or 0.5% (Group 2). Eyes from Groups 1 and 2 were then exposed to sunlight. The elastic modulus was calculated as an indicator of stiffness. RESULTS: Riboflavin concentration in Group B was higher by a factor of 2.8 than Group A. According to live illuminance measurements and stromal riboflavin concentration, the sunlight exposure duration varied between 16 minutes and 45 minutes. Groups 1 and 2 had higher elastic modulus than controls ( P < .0001) but did not differ between them ( P = .194). The stiffening effect was 84% and 55%, respectively. CONCLUSIONS: Sunlight exposure of ex vivo corneas soaked in both riboflavin 0.1% and 0.5% resulted in increased corneal stiffness. Specifically, riboflavin 0.1% with longer UV-A exposure showed a trend for a greater stiffening effect, which might open new alleys for the use of oral riboflavin and fractioned sunlight exposure as less invasive CXL techniques.

Intracorneal Ring Segment Implantation Results in Corneal Mechanical Strengthening Visualized With Optical Coherence Elastography.

PURPOSE: To quantify the mechanical impact of intracorneal ring segment (ICRS) implantation of different dimensions in an ex vivo eye model. METHODS: A total of 30 enucleated porcine eyes were assigned to ICRS implantation (thickness: 300 µm, angle: 120°, 210°, or 325°), tunnel creation only, or virgin control groups. For mechanical evaluation, each globe was mounted on a customized holder and intraocular pressure (IOP) was increased in steps of 0.5 mm Hg from 15 to 17 mm Hg, simulating physiologic diurnal IOP fluctuations. At each step, an optical coherence tomography volume scan was recorded. Deformations between subsequent scans and the locally induced axial strains were analyzed using a vector-based phase difference method. The effective E-modulus was derived from the overall induced strain as a measure of global mechanical impact. RESULTS: ICRS implantation increased the effective E-modulus from 146 and 163 kPa in virgin and tunnel-only eyes to 149, 192, and 330 kPa in eyes that received a 5-mm optical zone ICRS with 120°, 210°, and 325° arc length, respectively; and to 209 kPa in a 6-mm optical zone ICRS with 325° arc length. The most consistent effect was a shift toward positive strains in the posterior stroma by 0.1% to 0.46% (factor 1.15 to 2.15) after ICRS surgery. CONCLUSIONS: ICRS implantation reduces the overall tissue strain under the load of the IOP and provokes posterior tissue relaxation. This effect is more prominent the longer the arc length and the smaller the optical zone of the ICRS is. ICRS have not only a geometrical, but also a mechanical impact on corneal tissue. This behavior might have clinical implications when ICRS implantation is performed in biomechanically weakened keratoconic corneas. [J Refract Surg. 2022;38(7):459-464.].

Corneal Strain Induced by Intracorneal Ring Segment Implantation Visualized With Optical Coherence Elastography.

PURPOSE: To record the axial strain field in the cornea directly after creating a stromal tunnel and implanting an intracorneal ring segment (ICRS). METHODS: Freshly enucleated porcine eyes were obtained and assigned to either ICRS implantation, tunnel creation only, or virgin control groups. Immediately after manual tunnel creation and ICRS positioning, the entire eye globe was mounted on a customized holder and intraocular pressure (IOP) was adjusted to 15 mm Hg. Then, IOP was inreased to 20 mm Hg, in steps of 1 mm Hg. At each step, an optical coherence tomography volume scan was recorded. Displacements between subsequent scans were retrieved using a vector-based phase difference method. The induced corneal strain direction was determined by taking the axial gradient. In addition, corneal surface was detected and sagittal curvature maps computed. RESULTS: Corneal tissue presented a localized compressive strain in the direct vicinity of the stromal tunnel, which was independent of IOP change. The central and peripheral (exterior to the ICRS) cornea demonstrated compressive strains on IOP increase, and tensile strains on IOP decrease. ICRS implantation induced an annular-shaped tensile strain at its inner border, particularly during IOP increase. The compressive strains close to the tunnel remained after ICRS implantation. Corneal curvature changes were concentrated on regions where strain was induced. CONCLUSIONS: ICRS implantation induces localized strains in the regions subjected to refractive changes, suggesting that corneal strain and curvature are directly related. Studying corneal strain in response to surgical intervention may provide new insights on underlying working principles. [J Refract Surg. 2022;38(3):210-216.].

In-Vivo Measurement of Ocular Deformation in Response to Ambient Pressure Modulation.

A novel approach is presented for the non-invasive quantification of axial displacement and strain in corneal and anterior crystalline lens tissue in response to a homogenous ambient pressure change. A spectral domain optical coherence tomography (OCT) system was combined with a custom-built set of swimming goggles and a pressure control unit to acquire repetitive cross-sectional scans of the anterior ocular segment before, during and after ambient pressure modulation. The potential of the technique is demonstrated in vivo in a healthy human subject. The quantification of the dynamic deformation response, consisting of axial displacement and strain, demonstrated an initial retraction of the eye globe (-0.43 to -1.22 nm) and a subsequent forward motion (1.99 nm) in response to the pressure change, which went along with a compressive strain induced in the anterior crystalline lens (-0.009) and a tensile strain induced in the cornea (0.014). These mechanical responses appear to be the result of a combination of whole eye motion and eye globe expansion. The latter simulates a close-to-physiologic variation of the intraocular pressure and makes the detected mechanical responses potentially relevant for clinical follow-up and pre-surgical screening. The presented measurements are a proof-of-concept that non-contact low-amplitude ambient pressure modulation induces tissue displacement and strain that is detectable in vivo with OCT. To take full advantage of the high spatial resolution this imaging technique could offer, further software and hardware optimization will be necessary to overcome the current limitation of involuntary eye motions.

Hyperopic SMILE Versus FS-LASIK: A Biomechanical Comparison in Human Fellow Corneas.

PURPOSE: 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: In stress-strain measurements, the effective elastic modulus was not significantly different (P > .311) between SMILE (13.5 ± 12.8 MPa) and FS-LASIK (7.56 ± 17.9 MPa). In stress-relaxation measurements, the remaining stress was not significantly different (P = .841) between SMILE (124 ± 20 kPa) and FS-LASIK (126 ± 21 kPa). CONCLUSIONS: Unlike myopic correction, after hyperopic correction the cap-based procedure (SMILE) and the flap-based technique (FS-LASIK) may be considered equivalent in terms of biomechanical stability when measured experimentally in ex vivo human fellow eye corneas. [J Refract Surg. 2021;37(12):810-815.].

Refractive changes of a new asymmetric intracorneal ring segment with variable thickness and base width: A 2D finite-element model.

PURPOSE: To evaluate the local geometric effects of a unilateral intrastromal ring segment with a combined variation of ring thickness and base width in a finite element simulation, and to compare it against the isolated effect of thickness or base width variation alone. METHODS: A two-dimensional finite-element model of a transversely isotropic cornea was created assuming either axisymmetric stress or plane strain condition. The model geometry was composed of a three-layered corneal tissue (epithelium, anterior and posterior stroma) fixed at the limbus. The implantation of a triangular-shape asymmetric ring segment with varying ring thickness (150 to 300 µm) and base width (600 to 800 µm) was simulated. Also, changes induced by thickness or base width alone were studied and compared their combined effect in the asymmetric ring segment. Geometrical deformation of the simulated cornea and sagittal curvature were the main parameters of study. RESULTS: Increasing ring thickness and base width along the arc of the asymmetric ring segment produced a more pronounced flattening in this part of the ring. The asymmetric design did find a good balance between maximizing corneal flattening at one end and minimizing it at the other end, compared to the isolated effect of ring thickness and width. Ring thickness was the most robust parameter in flattening both, the central and peripheral cornea. CONCLUSION: The finite-element model permitted a theoretical study of corneal deformation undergoing implantation of realistic and hypothetical ring geometries. Intracorneal asymmetric ring segments with varying thickness and base width can be a good alternative in corneas with asymmetric keratoconus phenotypes.

Collagen V insufficiency in a mouse model for Ehlers Danlos-syndrome affects viscoelastic biomechanical properties explaining thin and brittle corneas.

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.

Different needs in patients with schizophrenia spectrum disorders who behave aggressively towards others depend on gender: a latent class analysis approach.

BACKGROUND: There is limited research with inconsistent findings on differences between female and male offender patients with a schizophrenia spectrum disorder (SSD), who behave aggressively towards others. This study aimed to analyse inhomogeneities in the dataset and to explore, if gender can account for those. METHODS: Latent class analysis was used to analyse a mixed forensic dataset consisting of 31 female and 329 male offender patients with SSD, who were accused or convicted of a criminal offence and were admitted to forensic psychiatric inpatient treatment between 1982 and 2016 in Switzerland. RESULTS: Two homogenous subgroups were identified among SSD symptoms and offence characteristics in forensic SSD patients that can be attributed to gender. Despite an overall less severe criminal and medical history, the female-dominated class was more likely to receive longer prison terms, similarly high antipsychotic dosages, and was less likely to benefit from inpatient treatment. Earlier findings were confirmed and extended in terms of socio-demographic variables, diseases and criminal history, comorbidities (including substance use), the types of offences committed in the past and as index offence, accountability assumed in court, punishment adjudicated, antipsychotic treatment received, and the development of symptoms during psychiatric inpatient treatment. CONCLUSIONS: Female offender patients with schizophrenia might need a more tailored approach in prevention, assessment and treatment to diminish tendencies of inequity shown in this study.

Childhood Maltreatment, Psychopathology, and Offending Behavior in Patients With Schizophrenia: A Latent Class Analysis Evidencing Disparities in Inpatient Treatment Outcome.

Background: Extant research has provided evidence for disparities between patients with schizophrenia spectrum disorder (SSD) who have and have not experienced childhood maltreatment (CM) in terms of treatment outcome, psychopathology and their propensity to engage in offending behavior. However, research addressing all phenomena is scarce. Objective: The current study aims to explore differences between offender patients with SSD and CM and those with SSD and no CM in terms of their offending, psychopathology at different points in time and treatment outcome. Method: In the present explorative study, latent class analysis was used to analyze differences between 197 offender patients with SSD and CM and 173 offender patients with SSD and no CM, who were admitted to forensic psychiatric inpatient treatment between 1982 and 2016 in Switzerland. Results: Three distinct homogenous classes of patients were identified, two of which were probable to have experienced significant CM. One third of patients with SSD and CM were probable to benefit from inpatient treatment, even surpassing results observable in the group without CM, whereas the other group with SSD and CM was probable to benefit less. Patients with SSD and no CM displayed more psychopathology at first diagnosis and prior to their index offense. Interclass differences in offending behavior were minimal. Conclusions: Offender patients with SSD and CM differ not only from offender patients with SSD and no CM, but also amongst themselves. While some with SSD and CM experience a remission in psychopathology and improve their prognosis for future offending behavior, others do not. Directions for future research on SSD and CM are discussed.

Impact of hypothermia on the biomechanical effect of epithelium-off corneal cross-linking.

BACKGROUND: The corneal cross-linking (CXL) photochemical reaction is essentially dependent on oxygen and hypothermia, which usually leads to higher dissolved oxygen levels in tissues, with potentially greater oxygen availability for treatment. Here, we evaluate whether a reduction of corneal temperature during CXL may increase oxygen availability and therefore enhance the CXL biomechanical stiffening effect in ex vivo porcine corneas. METHODS: One hundred and twelve porcine corneas had their epithelium manually debrided before being soaked with 0.1% hypo-osmolaric riboflavin. These corneas were equally assigned to one of four groups. Groups 2 and 4 underwent accelerated epithelium-off CXL using 9 mW/cm2 irradiance for 10 min, performed either in a cold room temperature (group 2, 4 °C) or at standard room temperature (group 4, 24 °C). Groups 1 and 3 served as non-cross-linked, temperature-matched controls. Using a stress-strain extensometer, the elastic moduli of 5-mm wide corneal strips were analyzed as an indicator of corneal stiffness. RESULTS: Accelerated epithelium-off CXL led to significant increases in the elastic modulus between 1 and 5% of strain when compared to non-cross-linked controls (P < 0.05), both at 4 °C (1.40 ± 0.22 vs 1.23 ± 0.18 N/mm) and 24 °C (1.42 ± 0.15 vs 1.19 ± 0.11 N/mm). However, no significant difference was found between control groups (P = 0.846) or between groups in which CXL was performed at low or standard room temperature (P = 0.969). CONCLUSIONS: Although initial oxygen availability should be increased under hypothermic conditions, it does not appear to play a significant role in the biomechanical strengthening effect of epithelium-off CXL accelerated protocols in ex vivo porcine corneas.

Individuals with schizophrenia who act violently towards others profit unequally from inpatient treatment-Identifying subgroups by latent class analysis.

BACKGROUND: People with schizophrenia show a higher risk of committing violent offenses. Previous studies indicate that there are at least three subtypes of offenders with schizophrenia. OBJECTIVES: Employing latent class analysis, the goals of this study were to investigate the presence of homogeneous subgroups of offender patients in terms of remission in psychopathology during inpatient treatment and whether or not these are related to subtypes found in previous studies. Results should help identify patient subgroups benefitting insufficiently from forensic inpatient treatment and allow hypotheses on possibly more suitable therapy option for these patients. METHODS: A series of latent class analyses was used to explore extensive and detailed psychopathological reports of 370 offender patients with schizophrenia before and after inpatient treatment. RESULTS: A framework developed by Hodgins to identify subgroups of offenders suffering from schizophrenia is useful in predicting remission of psychopathology over psychiatric inpatient treatment. While "early starters" were most likely to experience remission of psychopathology over treatment, "late late starters" and a subgroup including patients from all three of Hodgins' subgroups in equal proportions benefited least. Negative symptoms generally seemed least likely to remit. CONCLUSION: Psychiatric treatment may have to be more tailored to offender patient subgroups to allow them to benefit more equally.

Individualized Corneal Cross-linking With Riboflavin and UV-A in Ultrathin Corneas: The Sub400 Protocol.

PURPOSE: To determine whether corneal cross-linking (CXL) with individualized fluence ("sub400 protocol") is able to stop keratoconus (KC) progression in ultrathin corneas with 12-month follow-up. DESIGN: Retrospective, interventional case series. METHODS: Thirty-nine eyes with progressive KC and corneal stromal thicknesses from 214 to 398 µm at the time of ultraviolet irradiation were enrolled. After epithelium removal, ultraviolet irradiation was performed at 3 mW/cm2 with irradiation times individually adapted to stromal thickness. Pre- and postoperative examinations included corrected distance visual acuity (CDVA), refraction, Scheimpflug, and anterior segment optical coherence tomography imaging up to 12 months after CXL. Outcome measures were arrest of KC progression at 12 months postoperatively and stromal demarcation line (DL) depth. RESULTS: Thirty-five eyes (90%) showed tomographical stability at 12 months after surgery. No eyes showed signs of endothelial decompensation. A significant correlation was found between DL depth and irradiation time (r = +0.448, P = .004) but not between DL depth and change in Kmax (r = -0.215, P = .189). On average, there was a significant change (P < .05) in thinnest stromal thickness (-14.5 ± 21.7 µm), Kmax (-2.06 ± 3.66 D) and densitometry (+2.00 ± 2.07 GSU). No significant changes were found in CDVA (P = .611), sphere (P = .077), or cylinder (P = .915). CONCLUSIONS: The "sub400" individualized fluence CXL protocol standardizes the treatment in ultrathin corneas and halted KC progression with a success rate of 90% at 12 months. The sub400 protocol allows for the treatment of corneas as thin as 214 µm of corneal stroma, markedly extending the treatment range. The DL depth did not predict treatment outcome. Hence, the depth is unlikely related to the extent of CXL-induced corneal stiffening but rather to the extent of CXL-induced microstructural changes and wound healing.

Contribution of Bowman layer to corneal biomechanics.

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.