Rose Bengal Photodynamic Therapy (RB-PDT) Modulates the Inflammatory Response in LPS-Stimulated Human Corneal Fibroblasts By Influencing NF-κB and p38 MAPK Signaling Pathways.

PURPOSE: To investigate the effect of rose bengal photodynamic therapy on lipopolysaccharide-induced inflammation in human corneal fibroblasts. Furthermore, to analyze potential involvement of the mitogen-activated protein kinase and nuclear factor kappa B signaling pathways in this process. METHODS: Human corneal fibroblast cultures underwent 0-2.0 µg/mL lipopolysaccharide treatment, and 24 h later rose bengal photodynamic therapy (0.001% RB, 565 nm wavelength illumination, 0.17 J/cm2 fluence). Interleukin-6, interleukin-8, intercellular adhesion molecule-1, interferon regulatory factor-3, interferon α2, and interferon ß1 gene expressions were determined by quantitative PCR. Interleukin-6, interleukin-8, and C-C motif chemokine ligand-4 concentrations in the cell culture supernatant were measured by enzyme-linked immunosorbent assays and intercellular adhesion molecule-1 protein level in human corneal fibroblasts by western blot. In addition, the nuclear factor kappa B and mitogen-activated protein kinase signaling pathways were investigated by quantitative PCR and phosphorylation of nuclear factor kappa B p65 and p38 mitogen-activated protein kinase by western blot. RESULTS: Rose bengal photodynamic therapy in 2.0 µg/mL lipopolysaccharide-stimulated human corneal fibroblasts triggered interleukin-6 and interleukin-8 mRNA (p < .0001) and interleukin-6 protein increase (p < .0001), and downregulated intercellular adhesion molecule-1 expression (p < .001). C-C motif chemokine ligand-4, interferon regulatory factor-3, interferon α2, and interferon ß1 expressions remained unchanged (p ≥ .2). Rose bengal photodynamic therapy increased IκB kinase subunit beta, nuclear factor kappa B p65, extracellular signal-regulated kinases-2, c-Jun amino terminal kinase, and p38 transcription (p ≤ .01), and triggered nuclear factor kappa B p65 and p38 mitogen-activated protein kinase phosphorylation (p ≤ .04) in lipopolysaccharide treated human corneal fibroblasts. CONCLUSION: Rose bengal photodynamic therapy of lipopolysaccharide-stimulated human corneal fibroblasts can modify the inflammatory response by inducing interleukin-6 and interleukin-8 expression, and decreasing intercellular adhesion molecule-1 production. C-C motif chemokine ligand-4, interferon regulatory factor-3, and interferon α and ß expressions are not affected by rose bengal photodynamic therapy in these cells. The underlying mechanisms may be associated with nuclear factor kappa B and p38 mitogen-activated protein kinase pathway activation.

Simulator-Based Versus Traditional Training of Fundus Biomicroscopy for Medical Students: A Prospective Randomized Trial.

INTRODUCTION: Simulation training is an important component of medical education. In former studies, diagnostic simulation training for direct and indirect funduscopy was already proven to be an effective training method. In this prospective controlled trial, we investigated the effect of simulator-based fundus biomicroscopy training. METHODS: After completing a 1-week ophthalmology clerkship, medical students at Saarland University Medical Center (n = 30) were block-randomized into two groups: The traditional group received supervised training examining the fundus of classmates using a slit lamp; the simulator group was trained using the Slit Lamp Simulator. All participants had to pass an Objective Structured Clinical Examination (OSCE); two masked ophthalmological faculty trainers graded the students' skills when examining patient's fundus using a slit lamp. A subjective assessment form and post-assessment surveys were obtained. Data were described using median (interquartile range [IQR]). RESULTS: Twenty-five students (n = 14 in the simulator group, n = 11 in the traditional group) (n = 11) were eligible for statistical analysis. Interrater reliability was verified as significant for the overall score as well as for all subtasks (≤ 0.002) except subtask 1 (p = 0.12). The overall performance of medical students in the fundus biomicroscopy OSCE was statistically ranked significantly higher in the simulator group (27.0 [5.25]/28.0 [3.0] vs. 20.0 [7.5]/16.0 [10.0]) by both observers with an interrater reliability of IRR < 0.001 and a significance level of p = 0.003 for observer 1 and p < 0.001 for observer 2. For all subtasks, the scores given to students trained using the simulator were consistently higher than those given to students trained traditionally. The students' post-assessment forms confirmed these results. Students could learn the practical backgrounds of fundus biomicroscopy (p = 0.04), the identification (p < 0.001), and localization (p < 0.001) of pathologies significantly better with the simulator. CONCLUSIONS: Traditional supervised methods are well complemented by simulation training. Our data indicate that the simulator helps with first patient contacts and enhances students' capacity to examine the fundus biomicroscopically.

Evaluation of dynamic corneal response parameters and the biomechanical E-staging after Intacs® SK implantation in keratoconus.

PURPOSE: This retrospective longitudinal study evaluated the biomechanical E-staging in KC corneas before and after intracorneal ring segment (ICRS) implantation (Intacs® SK, Addition Technology, Illinois, United States). METHODS: Biomechanical E-staging for ectatic corneal diseases was applied retrospectively on 49 KC corneas of 41 patients who underwent ICRS implantation. The main outcome parameters included the Corvis Biomechanical Factor (CBiF, the linearized Corvis Biomechanical Index and the biomechanical parameters included), the resulting biomechanical E-staging, the stress-strain index, thinnest corneal thickness (TCT), maximal anterior keratometry (Kmax), and the anterior radius of curvature (ARC). They were evaluated at 1.9 ± 1.1 months preoperatively and postoperatively after 2.8 ± 0.7, 5.8 ± 1.0, and 10.6 ± 2.3 months. RESULTS: The CBiF decreased (4.9 ± 0.5 | 4.7 ± 0.5, P = 0.0013), and the E-staging increased significantly (2.8 ± 0.8 | 3.1 ± 0.9, P = 0.0012, paired t-test) from preoperatively to the first postoperative follow-up. The difference remained significant after 6 months; however, there was no more difference after 11 months. TCT was stable, whereas Kmax and ARC significantly decreased after ICRS implantation (TCT: 464 ± 49, 470 ± 51, 467 ± 38, 461 ± 48; Kmax: 56.3 ± 4.5, 54.7 ± 4.5, 54.2 ± 4.8, 54.1 ± 4.3; ARC: 51.5 ± 3.4, 48.3 ± 3.8, 48.6 ± 3.0, 48.6 ± 3.2 preoperatively and 3, 6, and 11 months postoperatively, respectively). Besides Kmax and ARC, Ambrósio's relational thickness to the horizontal profile (ARTh) was the only parameter that was significantly lower than preoperatively at any follow-up (P ≤ 0.0024, Wilcoxon matched-pairs test). CONCLUSION: Intacs® SK implantation results in an increasing biomechanical E-staging in the first postoperative months with stabilization near preoperative values after 1 year. Significantly lower ARTh values at any follow-up document the ICRS effect and contribute to a slightly higher postoperative biomechanical E-staging value.

Long-Term Follow-Up of Pediatric Excimer Laser-Assisted Penetrating Keratoplasty for Congenital Stromal Corneal Dystrophy.

PURPOSE: The purpose of this study was to highlight characteristic clinical and microscopic findings and report the long-term follow-up of pediatric excimer laser-assisted penetrating keratoplasty (excimer-PKP) for congenital stromal corneal dystrophy (CSCD). METHODS: A 2-year-old Greek child presented with CSCD at our department. Clinical examination showed bilateral flake-like whitish corneal opacities affecting the entire corneal stroma up to the limbus. Genetic testing identified a mutation of the decorin gene (c.962delA). The variant was not present in the parents and represented a de novo mutation. The uncorrected visual acuity was 20/100 in both eyes. Excimer-PKP (8.0/8.1 mm) was performed on the right eye at the age of 2.5 years and on the left eye at the age of 3 years. Postoperatively, alternating occlusion treatment was performed. RESULTS: The light microscopic examination demonstrated a disorganized extracellular matrix of the corneal stroma characterized by a prominent irregular arrangement of stromal collagen lamellae with large interlamellar clefts containing ground substance, highlighted by periodic acid-Schiff- and Alcian blue-positive reaction detecting acid mucopolysaccharides. Electron microscopy showed disorganization and caliber variation of collagen lamellae and thin filaments within an electron-lucent ground substance. The postoperative course was unremarkable. Both grafts remained completely clear 14 years postoperatively. Corneal tomography showed moderate regular astigmatism with normal corneal thickness. The corrected distance visual acuity was 20/25 in both eyes. CONCLUSIONS: Excimer-PKP for CSCD might be associated with excellent long-term results and a good prognosis, particularly when the primary surgery is performed at a very young age. However, this requires close postoperative follow-up examinations by an experienced pediatric ophthalmologist to avoid severe amblyopia.

Severe ulcerative keratopathy following implantation of an acellular porcine corneal stromal lenticule in a patient with keratoconus.

PURPOSE: To report a case of ulcerative keratopathy following implantation of acellular porcine corneal stroma (APCS) in a patient with keratoconus (KC). METHODS: A 58 year-old patient initially presented with an ulcerative keratopathy in the left eye. Previously, several corneal procedures (including radial keratotomy, laser-in-situ keratomileusis, crosslinking) were performed for KC. Eight months ago, an APCS lenticule (Xenia corneal implant, Gebauer Medizintechnik GmbH, Neuhausen, Germany) was implanted into a stromal pocket because of progressive keratectasia. Visual acuity was hand movement. Anterior segment optical coherence tomography showed a space between the APCS lenticule and the host stroma. Excimer laser-assisted penetrating keratoplasty (PKP, 8.0/8.1 mm) was performed in the left eye. The corneal explant was investigated by light and transmission electron microscopy. RESULTS: Best-corrected visual acuity was 20/40 six weeks after PKP. Light microscopy demonstrated a stromal ulceration down to the APCS lenticule. No stromal cells could be found within the APCS lenticule eight months after implantation. The APCS lenticule did not show a green stain of the collagens with Masson-Goldner staining and exhibited a strong Periodic acid-Schiff positive reaction. Electron microscopy of the APCS lenticule revealed cross-linked collagen lamellae without cellular components. Close to the interface, corneal collagen lamellae of the host cornea were disorganized. Few vital keratocytes were present on the surface of the lenticule and appeared to cause mechanical disruption of the host stroma along the lenticule-stroma interface. CONCLUSION: APCS implantation may lead to severe complications such as ulcerative keratopathy in otherwise uncomplicated KC corneas. In such cases, excimer laser-assisted PKP or Deep Anterior Lamellar Keratoplasty are the methods of choice to restore visual acuity.

Endovascular aortic repair in patients with Marfan and Loeys-Dietz syndrome is safe and durable when employed by a multi-disciplinary aortic team.

OBJECTIVES: The aim of this study was to report on mid-term outcomes after endovascular aortic repair (EVAR) in patients with Marfan (MFS) or Loeys-Dietz (LDS) syndrome. METHODS: We analysed data from 2 European centres of patients with MFS and LDS undergoing EVAR. Patients were analysed based on (i) timing of the procedure (planned versus emergency procedure) and (ii) the nature of the landing zone (safe versus non-safe). The primary end-point was freedom from reintervention. Secondary end-points were freedom from stroke, bleeding and death. RESULTS: A population of 419 patients with MFS (n = 352) or LDS (n = 67) was analysed for the purpose of this study. Thirty-nine patients (9%) underwent EVAR. Indications for thoracic endovascular aortic repair or EVAR were aortic dissection in 13 (33%) patients, aortic aneurysm in 22 (57%) patients and others (intercostal patch aneurysm, penetrating atherosclerotic ulcer, pseudoaneurysm, kinking of frozen elephant trunk (FET)) in 4 (10%) patients. Thoracic endovascular repair was performed in 34 patients, and abdominal endovascular aortic repair was performed in 5 patients. Mean age at 1st thoracic endovascular aortic repair/EVAR was 48.5 ± 15.4 years. Mean follow-up after 1st thoracic endovascular aortic repair/EVAR was 5.9 ± 4.4 years. There was no statistically significant difference in the rate of reinterventions between patients with non-safe landing zone and the patients with safe proximal landing zone (P = 0.609). Furthermore, there was no increased probability for reintervention after planned endovascular intervention compared to emergency procedures (P = 0.916). Mean time to reintervention, either open surgical or endovascular, after planned endovascular intervention was in median 3.9 years (95% confidence interval 2.0-5.9 years) and 2.0 years (95% confidence interval -1.1 to 5.1 years) (P = 0.23) after emergency procedures. CONCLUSIONS: EVAR in patients with MFS and LDS and a safe landing zone is feasible and safe. Endovascular treatment is a viable option when employed by a multi-disciplinary aortic team even if the landing zone is in native tissue.

Analysis of Graft Detachments and Re-Bubblings After 450 Descemet Membrane Endothelial Keratoplasty Procedures.

PURPOSE: To objectify the indication for re-bubbling by analyzing graft detachments (GDs) after Descemet membrane endothelial keratoplasty. METHODS: In this retrospective monocentric observational study, re-bubbling cases of 450 Descemet membrane endothelial keratoplasties and the percentage of the residual gas filling (RGF) in the anterior chamber on the first postoperative day were collected. The number/location/extent of GDs and the corneal thickness above GDs were analyzed using anterior segment optical coherence tomography. RESULTS: From a total of 450 grafts, 384 (85.3%) had at least a minimal degree GD. One hundred twenty-two of 450 grafts (27.1%) underwent at least 1 re-bubbling. The mean RGF was significantly lower in eyes with GD (67.7 ± 12.6%) than in eyes without GD (74.2 ± 11.3%). GDs occurred most frequently in the inferotemporal quadrant (46.0%). GDs were significantly more likely to require a re-bubbling when the central parts of the graft were affected (94.0% vs. 35.7%). The number of detachments per graft was directly proportional to the re-bubbling rate. The GDs which required a re-bubbling were on average 56 µm higher and 461 µm wider than the untreated ones. The cornea above the GDs that needed a re-bubbling was significantly thicker than above the untreated GDs (mean 988 ± 102 µm vs. 951 ± 99 µm). CONCLUSIONS: The RGF seems to be a major influencing factor for graft attachment. The most susceptible location of the GD is inferotemporal. The main factors that need to be investigated to decide if a re-bubbling is required are the number of detachments per graft, their dimensions, whether the central portions of the graft are involved, and the corneal thickness above GDs.

IC3D Classification of Corneal Dystrophies-Edition 3.

PURPOSE: The International Committee for the Classification of Corneal Dystrophies (IC3D) was created in 2005 to develop a new classification system integrating current information on phenotype, histopathology, and genetic analysis. This update is the third edition of the IC3D nomenclature. METHODS: Peer-reviewed publications from 2014 to 2023 were evaluated. The new information was used to update the anatomic classification and each of the 22 standardized templates including the level of evidence for being a corneal dystrophy [from category 1 (most evidence) to category 4 (least evidence)]. RESULTS: Epithelial recurrent erosion dystrophies now include epithelial recurrent erosion dystrophy, category 1 ( COL17A1 mutations, chromosome 10). Signs and symptoms are similar to Franceschetti corneal dystrophy, dystrophia Smolandiensis, and dystrophia Helsinglandica, category 4. Lisch epithelial corneal dystrophy, previously reported as X-linked, has been discovered to be autosomal dominant ( MCOLN1 mutations, chromosome 19). Classic lattice corneal dystrophy (LCD) results from TGFBI R124C mutation. The LCD variant group has over 80 dystrophies with non-R124C TGFBI mutations, amyloid deposition, and often similar phenotypes to classic LCD. We propose a new nomenclature for specific LCD pathogenic variants by appending the mutation using 1-letter amino acid abbreviations to LCD. Pre-Descemet corneal dystrophies include category 1, autosomal dominant, punctiform and polychromatic pre-Descemet corneal dystrophy (PPPCD) ( PRDX3 mutations, chromosome 10). Typically asymptomatic, it can be distinguished phenotypically from pre-Descemet corneal dystrophy, category 4. We include a corneal dystrophy management table. CONCLUSIONS: The IC3D third edition provides a current summary of corneal dystrophy information. The article is available online at https://corneasociety.org/publications/ic3d .

A MassQL-Integrated Molecular Networking Approach for the Discovery and Substructure Annotation of Bioactive Cyclic Peptides.

The marine sponge-derived fungus Stachylidium bicolor 293 K04 is a prolific producer of specialized metabolites, including certain cyclic tetrapeptides called endolides, which are characterized by the presence of the unusual amino acid N-methyl-3-(3-furyl)-alanine. This rare feature can be used as bait to detect new endolide-like analogs through customized fragment pattern searches of tandem mass spectrometry data using the Mass Spec Query Language (MassQL). Here, we integrate endolide-specific MassQL queries with molecular networking to obtain substructural information guiding the targeted isolation and structure elucidation of the new proline-containing endolides E (1) and F (2). We showed that endolide F (but not E) is a moderate antagonist of the arginine vasopressin V1A receptor, a member of the G protein-coupled receptor superfamily.

Radiographic complicated and uncomplicated descending aortic dissections: aortic morphological differences by CT angiography and risk factor analysis.

OBJECTIVE: To identify radiographic differences between patients with uncomplicated and complicated descending aortic dissections. METHODS: Between 04/2009 and 07/2021, 209 patients with acute descending aortic dissections were analyzed as complicated (malperfusion, rupture, diameter progress, and diameter ≥55mm) or uncomplicated. Detailed CTA measurements (slice thickness ≤ 3mm) were taken in multiplanar reconstruction. A composite endpoint (early aortic failure) was defined as reoperation, diameter progression, and early mortality. RESULTS: Seventy-seven patients were female (36.8%) (complicated n=27 (36.5%); uncomplicated n=50 (37.0%) p=1.00). Seventy-four (35%) patients were categorized as morphologically complicated, and 135 (65%) as uncomplicated. In patients with complicated dissections, the dissection extended more frequently to the aortic bifurcation (p=0.044), the coeliac trunk (p=0.003), the superior mesenteric artery (p=0.007), and both iliac arteries (p<0.001) originated less frequently from the true lumen. The length of the most proximal communication (entry) in type B aortic dissection was longer, 14.0mm [12.0mm; 27.0mm] vs 6.0mm [4,0mm; 13.0mm] in complicated cases (p=0.005). Identified risk factors for adverse aortic events were connective tissue disease (HR 8.0 (1.9 - 33.7 95%CI HR)) length of the aortic arch (HR 4.7 (1.5 - 15.1 95%CI HR)) a false lumen diameter >19.38mm (HR 3.389 (1.1-10.2 95%CI HR) and origin of the inferior mesenteric artery from the false lumen (HR 4.2 (1.0 - 5.5 95%CI HR)). CONCLUSIONS: We identified significant morphological differences and predictors for adverse events in patients presenting complicated and uncomplicated descending dissections. Our morphological findings will help guide future aortic therapies, taking a tailored patient approach.

Short-Term Effect of Rose Bengal Photodynamic Therapy (RB-PDT) on Collagen I, Collagen V, NF-κB, LOX, TGF-ß and IL-6 Expression of Human Corneal Fibroblasts, In Vitro.

PURPOSE: To investigate collagen I, collagen V, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), lysyl oxidase (LOX), transforming growth factor ß1 (TGF-ß1) and interleukin-6 (IL-6) expression in healthy and keratoconus human corneal fibroblasts (HCFs and KC-HCFs), 24 h after Rose Bengal photodynamic therapy (RB-PDT). METHODS: HCFs were isolated from healthy human corneal donors (n = 5) and KC-HCFs from elective penetrating keratoplasties (n = 5). Both cell cultures underwent RB-PDT (0.001% RB concentration, 0.17 J/cm2 fluence) and 24 h later collagen I, collagen V, NF-κB, LOX, TGF-ß1 and IL-6 mRNA and protein expression have been determined using qPCR and Western blot, IL-6 concentration in the cell culture supernatant by ELISA. RESULTS: TGF-ß1 mRNA expression was significantly lower (p = 0.02) and IL-6 mRNA expression was significantly higher in RB-PDT treated HCFs (p = 0.01), than in HCF controls. COL1A1, COL5A1 and TGF-ß1 mRNA expression was significantly lower (p = 0.04; p = 0.02 and p = 0.003) and IL-6 mRNA expression was significantly higher (p = 0.02) in treated KC-HCFs, than in KC-HCF controls. TGF-ß1 protein expression in treated HCFs was significantly higher than in HCF controls (p = 0.04). IL-6 protein concentration in the HCF and KC-HCF culture supernatant after RB-PDT was significantly higher than in controls (p = 0.02; p = 0.01). No other analyzed mRNA and protein expression differed significantly between the RB-PDT treated and untreated groups. CONCLUSIONS: Our study demonstrates that RB-PDT reduces collagen I, collagen V and TGF-ß1 mRNA expression, while increasing IL-6 mRNA and protein expression in KC-HCFs. In HCFs, RB-PDT increases TGF-ß1 and IL-6 protein level after 24 h.

Surgical management of complicated Descemet's membrane detachment in corneas without prior endothelial keratoplasty.

PURPOSE: To provide insights into morphologic and functional features of eyes with complicated Descemet's membrane detachment (DMD) and report clinical outcomes after surgical intervention. METHODS: Retrospective study of 18 eyes with complicated DMD between 2010 and 2022. Complicated DMD was defined if any of the following criteria applied: prior penetrating keratoplasty (PKP), corneal thinning, total DMD or persistent DMD after Air/Gas-Descemetopexy. Causes, surgical management, and clinical outcomes were analyzed. Scheimpflug tomography, anterior segment optical coherence tomography (AS-OCT) and histologic examination were performed to characterize corneas with DMD. RESULTS: Fourteen eyes with prior PKP developed spontaneous DMD after 24.2 ± 12.9 years (range = 18 months - 47 years, median = 25.7 years). Complicated DMD without prior PKP was associated in three eyes after cataract surgery and in one eye after infectious keratitis. In cases with previous PKP, AS-OCT demonstrated rupture of Descemet's membrane (DM) in five eyes and spontaneous reattachment was found in four eyes within 8 weeks of initial diagnosis, with no rupture of DM in any of the cases. There was no rupture of DM in corneas without previous PKP. After prior keratoplasty, definitive surgical treatment was repeat PKP in 13 eyes and Air/Gas-Descemetopexy in one eye. In corneas without prior keratoplasty, three eyes underwent PKP and one eye Air/Gas-Descemetopexy. Histological examination of two corneal explants revealed a severely thinned graft-host junction and a disrupted DM close to the graft-host junction. Visual acuity improved from 1.80 ± 0.58 logMAR to 0.75 ± 0.69 logMAR after prior PKP and from 1.45 ± 0.65 logMAR to 0.85 ± 1.13 logMAR without prior PKP. The postoperative course was uneventful in 16 of 18 eyes. CONCLUSION: PKP is an effective treatment option for complicated DMD, especially in ectatic corneas, whereas Air/Gas-Descemetopexy or Descemet Membrane Endothelial Keratoplasty do not address the primary issue of the curvature anomaly.

Human corneal epithelial cell and fibroblast migration and growth factor secretion after rose bengal photodynamic therapy (RB-PDT) and the effect of conditioned medium.

PURPOSE: To investigate human corneal epithelial cell and fibroblast migration and growth factor secretion after rose bengal photodynamic therapy (RB-PDT) and the effect of conditioned medium (CM). METHODS: A human corneal epithelial cell line (HCE-T), human corneal fibroblasts (HCF) and keratoconus fibroblasts (KC-HCF) have been used. Twenty-four hours after RB-PDT (0.001% RB concentration, 565 nm wavelength illumination, 0.17 J/cm2 fluence) cell migration rate using scratch assay and growth factor concentrations in the cell culture supernatant using ELISA have been determined. In addition, the effect of CM has been observed. RESULTS: RB-PDT significantly reduced migration rate in all cell types, compared to controls (p≤0.02). Migration rate of HCE-T cultures without RB-PDT (untreated) was significantly higher using HCF CM after RB-PDT, than using HCF CM without RB-PDT (p<0.01). Similarly, untreated HCF displayed a significantly increased migration rate with HCE-T CM after RB-PDT, compared to HCE-T CM without treatment (p<0.01). Furthermore, illumination alone and RB-PDT significantly decreased keratinocyte growth factor (KGF) concentration in HCF and KC-HCF supernatant, and RB-PDT significantly decreased soluble N-Cadherin (SN-Cad) concentration in HCF supernatant, compared to controls (p<0.01 for all). In HCE-T CM, RB-PDT increased hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGFb) concentration (p≤0.02), while decreasing transforming growth factor ß (TGF-ß) concentration (p<0.01). FGFb concentration increased (p<0.0001) and TGF-ß concentration decreased (p<0.0001) in HCF CM, by RB-PDT. Epidermal growth factor (EGF), HGF, and TGF-ß concentration decreased (p≤0.03) and FGFb concentration increased (p<0.01) in KC-HCF CM, using RB-PDT. CONCLUSIONS: HCE-T, HCF and KC-HCF migration rate is reduced 24 hours after RB-PDT. In contrast, HCE-T migration is enhanced using HCF CM after RB-PDT, and HCF migration rate is increased through HCE-T CM following RB-PDT. Modulation of EGF, KGF, HGF, FGFb, TGF-ß and N-Cadherin secretion through RB-PDT may play an important role in corneal wound healing.

Anterior chamber intraocular lens removal combined with triple DMEK: Quadruple DMEK for bullous keratopathy.

PURPOSE: To present the outcomes of a patient with anterior chamber intraocular lens (ACIOL) related endothelial decompensation who underwent Descemet membrane endothelial keratoplasty (DMEK) and cataract surgery with intraocular lens (IOL) implantation in the capsular bag (so-called triple DMEK) combined with ACIOL removal (quadruple DMEK) in both eyes. METHODS: Case report. RESULTS: A 58-year-old female patient was referred due to decreased visual acuity within the last 18 months. She had a history of iris-claw ACIOL implantation 17 years before. The corrected distance visual acuity (CDVA) was 20/40 in both eyes. Due to low endothelial cell density and increased corneal thickness, ACIOL removal combined with triple DMEK (as quadruple DMEK) was performed for both eyes. Despite a graft detachment that was successfully managed with re-bubbling in the first eye, both eyes showed an increase in the CDVA (20/25 and 20/32, respectively) without any other significant complications in the follow-up of the patient. The corneas of both eyes were clear postoperatively. CONCLUSION: This case report demonstrated that quadruple DMEK may provide feasible management for chronic endothelial cell decompensation secondary to iris-claw ACIOL implantation.

Retrospective investigation of >400 patients undergoing thoracic endovascular aortic repair with or without cerebrospinal fluid drainage.

OBJECTIVES: The aim of this study was to analyse the risks and benefits of cerebrospinal fluid drainage (CSFD) placement in patients undergoing thoracic endovascular aortic repair. METHODS: Between 2009 and 2020, 411 patients underwent thoracic endovascular aortic repair in 1 institution where 236 patients (57%) received a preoperative CSFD. Patient and outcome characteristics were retrospectively analysed and compared between patients with and without preoperative CSFD placement. RESULTS: Preoperative CSFD was performed significantly more frequently in elective patients, especially those undergoing distal stent graft extension following frozen elephant trunk-stent placement (P < 0.001). Significantly fewer CSFD was placed in patients with acute aortic injury (P < 0.001). The incidence of permanent spinal cord ischaemia (SCI) was higher in patients without preoperative CSFD [10 patients (2%) vs 1 patient (0.2%), P = 0.001]. Postoperative CSFD was placed in 3 patients (0.7%). Severe CSFD-associated complications affected 2 patients (0.5%) namely, a subdural spinal haematoma causing permanent paraplegia in one of those 2 patients. CONCLUSIONS: CSFS placement is associated with low procedural risk and can potentially help to prevent SCI. However, the SCI incidence is most likely also associated with other preoperative factors including the patient's haemodynamics. Hence, a general recommendation for placing a preoperative CSFD cannot be made when relying on the present evidence.

In-Hospital Outcomes Following Surgical Revascularization of Chronic Total Coronary Occlusions.

Background and Objectives: Patients with chronic total occlusions of the coronary arteries are either treated with PCI or referred for surgical revascularization. We analyzed the patients with chronic occluded coronary arteries that were surgically treated and aimed to describe the anatomical characteristics, revascularization rates, and in-hospital outcomes achieved with coronary artery bypass grafting. Methods: Angiographic data of 2005 patients with coronary artery disease treated in our institution between January 2005 and December 2014 were retrospectively analyzed. A total of 1111 patients with at least one coronary total occlusion were identified. We reviewed the preoperative coronary angiograms and surgical protocols to determine the presence, localization, and revascularization of coronary occlusions. We also evaluated the perioperative data and in-hospital outcomes. Results: The median age of the study population was 68 years (25th-75th percentiles, 61.0-74.0). Three-vessel disease was present in 94.8% of patients and the rest (5.8%) had a two-vessel disease. The localizations of the occlusions were as follows: 68.4% in the RCA system, 26.4% in the LAD, and 28.5% in the LCX system. Multiple occlusions were present in 22.6% of the patients. Complete coronary total occlusion revascularization was achieved in 86.1% of the patients. The overall in-hospital mortality was 2.3%. The median in-hospital stay was 14.0 days. After logistic regression analysis, age (odds ratio 3.44 [95% confidence interval, 1.81-6.53], p < 0.001, for a 10-year increase) and the presence of peripheral artery disease (odds ratio 3.32 [1.39-7.93], p = 0.007) were the only statistically significant independent predictors of in-hospital mortality. Conclusions: A high revascularization rate and favorable in-hospital outcomes are achieved with coronary artery bypass surgery in patients with multi-vessel diseases and coronary total occlusions. Older age and the presence of peripheral artery disease are independent predictors of in-hospital mortality. A long-term follow-up and the type of graft (arterial vs. venous) used would bring more useful data for this type of revascularization.

Implantation of Intracorneal Ring Segments in Keratectasia: Effects on Corneal Biomechanics in 112 Eyes.

PURPOSE: The aim of this study was to analyze changes in corneal biomechanical properties after implantation of intracorneal ring segments (ICRSs) in keratectasia. METHODS: This retrospective single-center study included 112 patient eyes that underwent femtosecond laser-assisted ICRS implantation (Intacs SK; Addition Technology Inc, Des Plaines, IL) for keratectasia. Biomechanical analysis was performed using the Ocular Response Analyzer (ORA; Reichert Inc, Depew, NY), with determination of corneal resistance factor, corneal hysteresis, and Keratoconus Match Index, as well as by Corvis ST (OCULUS, Wetzlar, Germany), with determination of stiffness parameter A1, Ambrosio relational thickness to the horizontal profile (Arth), integrated radius, deformation amplitude ratio, and stress-strain index as well as Corvis Biomechanical Index and Tomographic Biomechanical Index. Data collection was performed preoperatively and 6 months postoperatively for ORA and Corvis ST and additionally after 1 and 2 years for ORA. RESULTS: The corneal resistance factor decreased significantly postoperatively (5.8 ± 1.7 mm Hg) compared with preoperatively (6.75 ± 3.7 mm Hg; P = 0.021) and increased again during follow-up (6.2 ± 1.9 mm Hg; P = 0.024), without regaining preoperative values. Corneal hysteresis and Keratoconus Match Index did not change significantly. Stiffness parameter A1 (P = 0.045) increased significantly after ICRS implantation and Arth decreased significantly from 181 ± 85 to 150 ± 92 (P = 0.016). However, there was no significant postoperative change for others Corvis parameters. CONCLUSIONS: Corneal biomechanical properties showed inconsistent changes after ICRS implantation. Classical corneal biomechanical parameters (using single central air-puff tonometers) do not seem to be suitable for follow-up after ICRS implantation.