Publications by authors named "Thomas Reinhard"

214 Publications

Trends in Surgical Glaucoma Treatment in Germany Between 2006 and 2018.

Clin Epidemiol 2021 13;13:581-592. Epub 2021 Jul 13.

Eye Center, Medical Center - University of Freiburg, Freiburg, Germany.

Background/aims: Surgical procedures in ophthalmology underlie variations over different time periods and are strongly dependent on the technical process and the invention of innovative surgical techniques. Especially, in glaucoma surgery a lot of surgical devices and techniques have been introduced during the last years. Until now, the use of these newer techniques has not been shown on a robust data basis. We herein present the numbers of different types of glaucoma surgeries performed at German hospitals between 2006 and 2018.

Methods And Design: The quality reports of hospitals in Germany from 2006 to 2018 were analyzed concerning all procedural codes for glaucoma surgery and intervention. Especially, the change in usage of "classical" and "modern" surgical techniques (MIGS: "minimally invasive glaucoma surgery") or devices was compared.

Results: The number of glaucoma procedures performed increased by 75% from 27,811 in 2006 to 48,794 in 2018. Absolute numbers of trabeculectomies, goniotomies, ab externo trabeculotomies and to a certain level cyclodestructive procedures decreased during the examined years while use of MIGS has increased in absolute and relative numbers since 2012. From 2015 a strong increase in the usage of XEN implants could be seen. Drainage implants (such as Baerveldt/Ahmed) showed stable absolute numbers over the time period covered. Absolute numbers of laser trabeculoplasty peaked in 2014 and decreased afterwards. Iridotomies and iridectomies increased by 120%/248% over the whole period.

Conclusion: Our data show a trend towards the modern surgical options and especially MIGS during the recent years. Classical procedures showed a decrease in total numbers emphasized from 2013. These numbers confirm the assumption that modern glaucoma surgery is becoming more and more popular and established in German hospitals.
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http://dx.doi.org/10.2147/CLEP.S310542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286102PMC
July 2021

Time- and Stimulus-Dependent Characteristics of Innate Immune Cells in Organ-Cultured Human Corneal Tissue.

J Innate Immun 2021 Jun 28:1-14. Epub 2021 Jun 28.

Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.

Purpose: The pattern of immune cells infiltrating the corneal stroma has been extensively studied in mice, but data on human tissue have been far less elaborate. To further characterize the number and differentiation state of resident immune cells in organ-cultured human corneal tissue, we employed a comprehensive bioinformatic deconvolution (xCell) of bulk RNA-sequencing (RNA-seq) data, immunohistochemistry (IHC), and flow cytometry (FC).

Methods: A transcriptome-based analysis of immune cell types in human corneal samples was performed. The results were validated by IHC, focusing on the identification of pro-inflammatory (M1) and regulatory (M2) macrophages. A protocol was established to identify these 2 different macrophage populations in human corneal tissue by means of FC. Subsequently, corneal samples in organ culture were differentially stimulated by IL-10, IL-4 & IL-13, or LPS and macrophage populations were evaluated regarding their response to these stimuli. Furthermore, cell survival was analyzed in correlation with time in organ culture.

Results: xCell-based mathematical deconvolution of bulk RNA-seq data revealed the presence of CD8 T cells, Th17 cells, dendritic cells, and macrophages as the predominant immune cell types in organ-cultured human corneal tissue. Furthermore, RNA-seq allowed the detection of different macrophage marker genes in corneal samples, including PTPRC (CD45), ITGAM (CD11b), CD14, and CD74. Our RNA-seq data showed no evidence of a relevant presence of monocytes in human corneal tissue. The presence of different macrophage subtypes was confirmed by IHC. The disintegration and subsequent FC analysis of human corneal samples showed the presence of both M1 (HLA-DR+, CD282+, CD86+, and CD284+) and M2 (CD163+ and CD206+) macrophage subtypes. Furthermore, we found that the total number of macrophages in corneal samples decreased more than the total cell count with increasing tissue culture time. Treatment with IL-10 led to higher total cell counts per cornea and to an increased expression of the M2 marker CD163 (p < 0.05) while expression levels of various M1 macrophage markers were not significantly reduced by interleukin treatment.

Conclusions: Regarding different macrophage populations, untreated human corneas showed more M1 than M2 macrophages. With increasing organ culture time, these macrophages decreased. In terms of cell dynamics, adding interleukins to the organ culture medium influenced the phenotype of macrophages within the cornea as detected by FC. Modifying the immunomodulatory properties of human grafts appears a promising approach to further reduce the risk of graft rejection in patients. In this context, treatment with interleukins was more effective in upregulating M2 macrophages than in suppressing M1 macrophages in corneal tissue.
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http://dx.doi.org/10.1159/000516669DOI Listing
June 2021

Impact of the SARS-CoV-2 pandemic on ophthalmic care in Germany.

Ophthalmologe 2021 Jul 4;118(Suppl 2):166-175. Epub 2021 Jun 4.

Commission for Cross-Sectoral Ophthalmology of the DOG (German Ophthalmological Society e. V.) and BVA (Professional Association of German Ophthalmologists), Munich/Düsseldorf, Germany.

Background: Survey by the commission for cross-sectoral ophthalmology, as a joint commission of the German Ophthalmological Society (DOG) and the Professional Association of German Ophthalmologists (BVA) on the effects of the SARS-CoV‑2 pandemic on ophthalmological patient care in Germany.

Methods: Online-based survey.

Results: A total of 1190 questionnaires were (partly) answered. With respect to outpatient care and consultations from 15 March to 15 April 2020, a total of 69 (5.8%) participants indicated unlimited, 756 (63.5%) reduced and 330 (27.7%) emergency care only, independent of the type of institution. Outpatient surgery was restricted to emergency surgery in 68% of clinics, 42.0% of inpatient wards, 45.0% of surgical medical care centers and group practices and 33.0% of private practices. Inpatient procedures were limited to emergency care in 75.0% of inpatient wards and in 71.0% of clinics. With the exception of endophthalmitis (+8.2%), the number of urgent indications and emergencies declined: retinal detachment (-34.8%), perforating eyeball injuries (-7.3%), acute glaucoma (-17.8%), central retinal artery occlusion and anterior ischemic optic neuropathy (-31.0%), others (-30.9%), penetrating keratoplasty and amniotic membrane transplantation (-59.1%). Institutional or professional policy requirements (76.0%) and appointment cancellation by patients (84.0%) were the most common reasons for limitations in ophthalmic patient care.

Conclusion: The initial phase of the pandemic was characterized by a massive reduction in non-urgent conservative and surgical treatment that affected all areas of ophthalmology. Due to intensive care capacities required for COVID-19 patients, inpatient treatment was largely restricted to emergencies. Treatment of ophthalmological patients, including ocular emergencies and urgent treatment, was maintained across all sectors with a (considerable) decrease in the number of cases even in these groups.
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http://dx.doi.org/10.1007/s00347-021-01411-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176275PMC
July 2021

Hyperosmolar Eye Drops for Diurnal Corneal Edema in Fuchs' Endothelial Dystrophy: A Double-Masked, Randomized Controlled Trial.

Ophthalmology 2021 Apr 20. Epub 2021 Apr 20.

Eye Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address:

Purpose: The Eye Drops for Early Morning-Associated Swelling (EDEMAS) trial assessed the efficacy of hyperosmolar eye drops on corneal edema resolution.

Design: Double-masked, randomized controlled trial of hyperosmolar eye drops.

Participants: Participants with Fuchs' dystrophy scheduled for Descemet membrane endothelial keratoplasty.

Methods: One eye was randomized to hyperosmolar eye drops (treatment); the fellow eye was randomized to artificial tears (placebo). After baseline examination in the afternoon, corneas were examined using Scheimpflug tomography after eye opening in the morning. Participants received eye drops twice. Imaging was repeated every 30 minutes up to 4 hours.

Main Outcome Measures: Decrease in central corneal thickness 1 hour after eye opening (primary end point), corneal thickness, subjective visual function, glare, visual acuity, and adverse events (AEs) (secondary end points).

Results: A total of 68 participants received the allocated intervention (59 eyes received treatment; 55 eyes received placebo). All eyes had stromal edema; none had epithelial edema. Corneal thickness was 626 μm in the treatment arm and 622 μm in the placebo arm after eye opening, indicating an early morning edema compared with baseline of +21 μm and +24 μm, respectively. Decrease in corneal thickness after 1 hour was -10.5 μm in the treatment arm (95% confidence interval [CI], -12.8 to -8.2) and -11.2 μm (95% CI, -13.6 to -8.9) in the placebo arm (between-arm difference, 0.7 μm, 95% CI, -2.0 to 3.5; P = 0.59), indicating no clinically relevant effect of hyperosmolar eye drops on early morning corneal edema. Results were not compatible with a relevant treatment effect on corneal thickness, visual acuity, and glare over the entire course of the study. Increase in subjective visual function was less rapid in the treatment arm than in the placebo arm. Adverse events, most commonly burning after eye drop application, were more common with treatment (30 eyes) than placebo (1 eye; risk difference, 49 percentage points; 95% CI, 36-62).

Conclusions: In this double-masked, randomized controlled trial, resolution of early morning stromal edema was not accelerated by hyperosmolar eye drops, which more frequently caused AEs. These results are not compatible with a clinically relevant effect of hyperosmolar eye drops and do not support their routine use.
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http://dx.doi.org/10.1016/j.ophtha.2021.04.015DOI Listing
April 2021

[Crosslinking and Keratoconus].

Klin Monbl Augenheilkd 2021 Jun 19;238(6):733-747. Epub 2021 Apr 19.

Keratoconus leads to a progressive protrusion and thinning of the cornea. In order to stop this, corneal crosslinking can be performed if the progression of the disease is proven. Crosslinking according to the "Dresden protocol" includes abrasion of the corneal epithelium, application of riboflavin eye drops and irradiation with UV-A light of an intensity of 3 mW/cm² for 30 minutes. The efficacy has been shown in several prospective randomized studies. One of the more recent developments is accelerated crosslinking, which allows a shorter irradiation time. On the other hand, the possibility of transepithelial crosslinking was presented, which does not require an abrasion of the cornea. This should reduce the occurrence of postoperative pain. The range of indications has also been expanded. Corneal crosslinking is used for post-LASIK keratectasia as well. It is also being considered for use in infectious keratitis. Topographically controlled crosslinking can likewise be used to try to positively influence the refractive power of the cornea. The risks of crosslinking include the occurrence of pain, haze or scarring, endothelial cell damage and, rarely, the occurrence of keratitis.
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http://dx.doi.org/10.1055/a-1472-0411DOI Listing
June 2021

[Online examination course instead of classroom teaching: adaptation of medical student teaching during the COVID-19 pandemic].

Ophthalmologe 2021 Apr 6. Epub 2021 Apr 6.

Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Killianstr. 5, 79106, Freiburg, Deutschland.

Background: The coronavirus disease 2019 (COVID-19) pandemic restricted face-to-face interactions of medical students and teachers.

Objective: To develop and evaluate an online course for ophthalmology examination techniques for medical students and to determine the impact of the course on the practical objective structured clinical examination (OSCE).

Material And Methods: The online examination course was developed as a video-based tutorial according to the SMART (specific, measurable, activating, reasonable, time-bound) principle covering all topics of the National Competency-based Catalogue of Learning Objectives for Medical Education and made available to medical students in the ophthalmology course. At the end of the semester the students graded the online examination course on an ordinal scale from 1 (strongly agree) to 6 (strongly disagree) anonymously and were asked for comments. The grades of the OSCE (range 1-5) were compared with the OSCE results of the previous semester.

Results: Of the 164 students 67 participated in the online evaluation (41%). The students reported to be well-prepared for the OSCE (mean grade 2.0; SD 1.0). In the future, 70% of the students would prefer combined online and on-site teaching (47 out of 67 students). Among all 164 students, the mean OSCE results were excellent (mean grade 1.1; SD 0.2) and comparable to the previous semester (mean grade among 166 students, 1.1; SD 0.2; two-sided t-test, p = 0.86).

Conclusion: The online course on ophthalmology examination techniques allowed medical students to prepare for the OSCE. Beyond the COVID-19 pandemic, online teaching options can support on-site teaching.
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http://dx.doi.org/10.1007/s00347-021-01372-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023559PMC
April 2021

Rotational alignment of corneal endothelial grafts and risk of graft detachment after Descemet membrane endothelial keratoplasty: a double-masked pseudo-randomized study.

Acta Ophthalmol 2021 Mar 19. Epub 2021 Mar 19.

Eye Centre, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Purpose: The posterior cornea is rotationally asymmetric, and Descemet membrane endothelial keratoplasty (DMEK) grafts preferentially scroll vertically. This prospective study assessed whether graft attachment after DMEK differed depending on the rotational alignment of the donor graft in the recipient eye.

Methods: Pseudo-randomization and blinding of the graft orientation in the recipient's eye were possible by procedural separation: (1) The eye bank recorded the position of an orientation marker in the donor cornea; (2) the surgeon preparing the DMEK graft recorded an upside-down marker relative to the eye bank marker; and (3) the surgeon assessed the position of the upside-down marker in the recipient after DMEK. Surgeons were masked towards the eye bank marker. Using mixed-effects models, we assessed graft attachment relative to the rotational alignment of the donor graft.

Results: Postoperatively, the graft was not fully attached in 59 of 179 eyes (33%). A second air fill (rebubbling) was performed in 11%. The graft axis was in line with the recipient cornea axis in 40%, oblique in 28% and orthogonal in 32%. We did not detect an elevated risk of incomplete attachment (odds ratio [OR], 1.16; 95% CI, 0.61-2.20), risk of rebubbling (OR, 1.25; 95% CI, 0.47-3.31) or larger areas of graft detachment in non-aligned grafts compared to aligned grafts.

Conclusion: Rotational alignment was not strongly associated with the risk of incomplete graft attachment, although modestly elevated risks cannot be ruled out. Efforts are needed to reduce the need for rebubbling after DMEK and to identify modifiable risk factors for graft detachment.
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http://dx.doi.org/10.1111/aos.14849DOI Listing
March 2021

Genotype-phenotype correlation in von Hippel-Lindau disease.

Acta Ophthalmol 2021 Mar 15. Epub 2021 Mar 15.

Eye Centre, Medical Centre - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background/aims: Retinal haemangioblastomas (RH) remain a major cause of visual impairment in patients with von Hippel-Lindau (VHL) disease. Identification of genotype-phenotype correlation is an important prerequisite for better management, treatment and prognosis.

Methods: Retrospective, single-centre cohort study of 200 VHL patients. Genetic data and date of onset of RH, central nervous system haemangioblastomas (CNSH), pheochromocytoma/paraganglioma (PPGL), clear cell renal cell carcinoma (ccRCC) and pancreatic neuroendocrine neoplasm (PNEN) were collected. The number and locations of RH were recorded.

Results: The first clinical finding occurred at an age of 26 ± 14 years (y) [mean ± SD]. In 91 ± 3% (95% CI 88-94) of the patients, at least one RH occur until the age of 60y. A total of 42 different rare VHL gene variants in 166 patients were detected. A higher age-related incidence of RH, CNSH, ccRCC and PNEN was detected in patients with a truncating variant (TV) compared to patients with a single amino-acid substitution/deletion (AASD) (all p < 0.01), while it is reverse for PPGL (p < 0.01). Patients with a TV showed 0.10 ± 0.15 RH per y during their lifetime compared to 0.05 ± 0.07 in patients with AASD (p < 0.02). The median enucleation/phthisis-free survival time in patients with a TV was 56y (95% CI 50-62) compared to 78y (95% CI 75-81) in patients with AASD (p < 0.02).

Conclusion: Compared to patients with AASD, patients with a TV develop RH, CNSH, ccRCC and PNEN earlier. They experience a higher number of RH and bear a higher risk of enucleation/phthisis. Thus, patients with a TV might be considered for a more intensive ophthalmological monitoring.
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http://dx.doi.org/10.1111/aos.14843DOI Listing
March 2021

Isolation and Expansion of Human Limbal Epithelial Progenitor Cells.

Bio Protoc 2020 Sep 20;10(18):e3754. Epub 2020 Sep 20.

Department of Ophthalmology, University of Erlangen-Nürnberg, Erlangen, Germany.

Limbal stem cell transplantation has been used successfully to treat patients with limbal stem cell deficiency all over the world. However, long term clinical results often proved less satisfactory due to the low quality of the graft or inadequate properties of transplanted cells. To enhance the expansion of human limbal epithelial stem or progenitor cells (LEPC) by preserving stem cell phenotype and to improve subsequent transplantation efficiency, cell-matrix interactions should mimic the condition . The laminin isoforms preferentially expressed in the limbal niche can be used as a culture matrix for epithelial tissue engineering. We recently published the expansion of LEPC on various laminin isoforms and observed that laminin alpha 5-derived matrices support the efficient expansion of LEPC compared to tissue culture plates and other laminin isoforms by preserving stem/progenitor cell phenotype. Here, we describe an optimized protocol for the isolation of LEPC from cadaveric corneal limbal tissue by collagenase digestion and efficient expansion of LEPC using recombinant human laminin-511 E8 fragment (LN-511E8) as culture substrate.
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http://dx.doi.org/10.21769/BioProtoc.3754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842399PMC
September 2020

Estimating the Incidence of Conjunctivitis by Comparing the Frequency of Google Search Terms With Clinical Data: Retrospective Study.

JMIR Public Health Surveill 2021 03 3;7(3):e22645. Epub 2021 Mar 3.

Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background: Infectious conjunctivitis is contagious and may lead to an outbreak. Prevention systems can help to avoid an outbreak.

Objective: We aimed to evaluate if Google search data on conjunctivitis and associated terms can be used to estimate the incidence and if the data can provide an estimation for outbreaks.

Methods: We obtained Google search data over 4 years for the German term for conjunctivitis ("Bindehautentzündung") and 714 associated terms in 12 selected German cities and Germany as a whole using the Google AdWords Keyword Planner. The search volume from Freiburg was correlated with clinical data from the Freiburg emergency practice (Eye Center University of Freiburg).

Results: The search volume for the German term for conjunctivitis in Germany as a whole and in the 12 German cities showed a highly uniform seasonal pattern. Cross-correlation between the temporal search frequencies in Germany as a whole and the 12 selected cities was high without any lag. Cross-correlation of the search volume in Freiburg with the frequency of conjunctivitis (International Statistical Classification of Diseases and Related Health Problems [ICD] code group "H10.-") from the centralized ophthalmologic emergency practice in Freiburg revealed a considerable temporal association, with the emergency practice lagging behind the frequency. Additionally, Pearson correlation between the count of patients per month and the count of searches per month in Freiburg was statistically significant (P=.04).

Conclusions: We observed a close correlation between the Google search volume for the signs and symptoms of conjunctivitis and the frequency of patients with a congruent diagnosis in the Freiburg region. Regional deviations from the nationwide average search volume may therefore indicate a regional outbreak of infectious conjunctivitis.
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http://dx.doi.org/10.2196/22645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970297PMC
March 2021

Survey of Rejection Prophylaxis Following Suture Removal in Penetrating Keratoplasty in Germany.

Klin Monbl Augenheilkd 2021 May 25;238(5):591-597. Epub 2021 Feb 25.

Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Deutschland.

Background: Penetrating keratoplasty (PK) gets more and more reserved to cases of increasing complexity. In such cases, ocular comorbidities may limit graft survival following PK. A major cause for graft failure is endothelial graft rejection. Suture removal is a known risk factor for graft rejection. Nevertheless, there is no evidence-based regimen for rejection prophylaxis following suture removal. Therefore, a survey of rejection prophylaxis was conducted at 7 German keratoplasty centres.

Objective: The aim of the study was documentation of the variability of medicinal aftercare following suture removal in Germany.

Methods: Seven German keratoplasty centres with the highest numbers for PK were selected. The centres were sent a survey consisting of half-open questions. The centres performed a mean of 140 PK in 2018. The return rate was 100%. The findings were tabulated.

Results: All centres perform a double-running cross-stitch suture for standard PK, as well as a treatment for rejection prophylaxis with topical steroids after suture removal. There are differences in intensity (1 - 5 times daily) and tapering (2 - 20 weeks) of the topical steroids following suture removal. Two centres additionally use systemic steroids for a few days.

Discussion: Rejection prophylaxis following PK is currently poorly standardised and not evidence-based. All included centres perform medical aftercare following suture removal. It is assumed that different treatment strategies show different cost-benefit ratios. In the face of the diversity, a systematic analysis is required to develop an optimised regimen for all patients.
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http://dx.doi.org/10.1055/a-1353-6149DOI Listing
May 2021

Predicting Edema Resolution After Descemet Membrane Endothelial Keratoplasty for Fuchs Dystrophy Using Scheimpflug Tomography.

JAMA Ophthalmol 2021 Apr;139(4):423-430

Eye Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Importance: Predicting the extent of corneal edema resolution after Descemet membrane endothelial keratoplasty (DMEK) may help in preoperative decision-making by identifying patients who may benefit from restoring endothelial function.

Objective: To develop and validate a predictive model for edema resolution after DMEK using Scheimpflug tomographic imaging.

Design, Setting, And Participants: Two prospective studies recruited participants with advanced Fuchs dystrophy at a university-based tertiary referral center between July 1, 2017, and August 31, 2019. Analyses were designed in November 2019 and completed on June 30, 2020. Development of a predictive model using linear least absolute shrinkage and selection operator regression was conducted in a derivation cohort (100 eyes). Overall performance, discrimination, and calibration were tested in the separate validation cohort (32 eyes).

Exposures: Preoperative Scheimpflug parameters and patient-reported visual disability were considered as potential predictors of edema resolution: (1) tomographic features (irregularity of lines of equal corneal thickness, displacement of the thinnest point of corneal thickness from the inferior-temporal quadrant, and absolute amount of focal posterior corneal depression), (2) standardized anterior and posterior corneal backscatter, (3) preoperative central corneal thickness, and (4) Fuchs dystrophy-specific visual disability.

Main Outcomes And Measures: Decrease in central corneal thickness after DMEK indicative of edema resolution.

Results: Of the 88 patients included in the analysis, 54 were women (61%); median age was 68 years (interquartile range [IQR], 59-76 years). A median of 13 months after DMEK (IQR, 9-16 months), median corneal thickness was 77 μm lower (IQR, 51-94 μm) in the derivation cohort and 75 μm lower in the validation cohort (IQR, 54-96 μm) than before surgery. Per 10-μm edema resolution, eyes gained 0.66 Early Treatment Diabetic Retinopathy Study letters (95% CI, 0.09-1.23) in best-corrected visual acuity. Three tomographic features were present in 68 of 100 eyes (68%) in the derivation cohort and in 18 of 32 eyes (56%) in the validation cohort before DMEK and in only 1 of 132 eyes (1%) after DMEK. To predict edema resolution after DMEK based on preoperative assessment, 5 variables were selected by the statistical learning algorithm: nonparallel isopachs, focal posterior depression, anterior and posterior corneal backscatter, and central corneal thickness. In the separate validation cohort, the model showed high overall performance, discrimination, and calibration.

Conclusions And Relevance: These post hoc analyses of prospective cohorts support a model for use in the prediction of edema resolution after DMEK using Scheimpflug measurement to identify patients benefitting most from DMEK.
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http://dx.doi.org/10.1001/jamaophthalmol.2020.6994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893546PMC
April 2021

A decellularized human corneal scaffold for anterior corneal surface reconstruction.

Sci Rep 2021 Feb 4;11(1):2992. Epub 2021 Feb 4.

Eye Center, Medical Center - Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106, Freiburg, Germany.

Allogenic transplants of the cornea are prone to rejection, especially in repetitive transplantation and in scarred or highly vascularized recipient sites. Patients with these ailments would particularly benefit from the possibility to use non-immunogenic decellularized tissue scaffolds for transplantation, which may be repopulated by host cells in situ or in vitro. So, the aim of this study was to develop a fast and efficient decellularization method for creating a human corneal extracellular matrix scaffold suitable for repopulation with human cells from the corneal limbus. To decellularize human donor corneas, sodium deoxycholate, deoxyribonuclease I, and dextran were assessed to remove cells and nuclei and to control tissue swelling, respectively. We evaluated the decellularization effects on the ultrastructure, optical, mechanical, and biological properties of the human cornea. Scaffold recellularization was studied using primary human limbal epithelial cells, stromal cells, and melanocytes in vitro and a lamellar transplantation approach ex vivo. Our data strongly suggest that this approach allowed the effective removal of cellular and nuclear material in a very short period of time while preserving extracellular matrix proteins, glycosaminoglycans, tissue structure, and optical transmission properties. In vitro recellularization demonstrated good biocompatibility of the decellularized human cornea and ex vivo transplantation revealed complete epithelialization and stromal repopulation from the host tissue. Thus, the generated decellularized human corneal scaffold could be a promising biological material for anterior corneal reconstruction in the treatment of corneal defects.
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http://dx.doi.org/10.1038/s41598-021-82678-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862698PMC
February 2021

Influence of Pulse Wave Velocity on Atherosclerosis and Blood Flow Reversal in the Aorta: A 4-Dimensional Flow Magnetic Resonance Imaging Study in Acute Stroke Patients and Matched Controls.

J Thorac Imaging 2021 Jan 21. Epub 2021 Jan 21.

Departments of Neurology Radiology-Medical Physics, Medical Center Eye Center, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Germany Institute for Imaging Science and Computational Modelling in Cardiovascular Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Background: Aortic stiffness is associated with a higher incidence of cardiovascular events including stroke. The primary aim of this study was to evaluate whether increased pulse wave velocity (PWV), a marker of stiffness, is an independent predictor of aortic atheroma. The secondary aim was to test whether increased PWV reinforces retrograde blood flow from the descending aorta (DAo), a mechanism of stroke.

Methods: We performed a cross-sectional case-control study with prospective data acquisition. In all, 40 stroke and 60 ophthalmic patients matched for age and cardiovascular risk factors were included. Multicontrast magnetic resonance imaging (MRI) protocol of the aorta tailored to allow a detailed plaque analysis using 3-dimensional (D) T1-weighted bright blood, T2-weighted and proton density-weighted black blood, and hemodynamic assessment using 4D flow MRI was applied. Individual PWV was calculated based on 4D flow MRI data using the time-to-foot of the blood flow waveform. The extent of maximum retrograde blood flow from the proximal DAo into the arch was quantified.

Results: PWV was higher in stroke patients compared with controls (7.62±2.59 vs. 5.96±2.49 m/s; P=0.005) and in patients with plaques (irrespective of thickness) compared with patients without plaques (7.47±2.89 vs. 5.62±1.89 m/s; P=0.002). Increased PWV was an independent predictor of plaque prevalence and contributed significantly to a predictor model explaining 36.5% (Nagelkerke R2) of the variance in plaque presence. Maximum retrograde flow extent from the proximal DAo was not correlated with PWV.

Conclusions: Aortic stiffness was higher in stroke patients and associated with a higher prevalence of plaques. Increased PWV was an independent predictor of plaque presence. Accordingly, regional PWV seems to be a valuable biomarker for the assessment and management of aortic atherosclerosis. However, no association was found for increased retrograde flow extent from the DAo.
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http://dx.doi.org/10.1097/RTI.0000000000000580DOI Listing
January 2021

Negative Vessel Remodeling in Stargardt Disease Quantified with Volume-Rendered Optical Coherence Tomography Angiography.

Retina 2021 Jan 7. Epub 2021 Jan 7.

Eye Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany Pattern Recognition Lab, University Erlangen-Nürnberg, Erlangen, Germany Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland Department of Ophthalmology, University of Basel, Basel, Switzerland Vitreous Retina Macula Consultants, New York City, NY, US Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom.

Purpose: To quantify retinal vasculature changes in Stargardt disease1 with volume-rendered optical coherence tomography angiography (OCTA).

Methods: OCTA volumes from heathy subjects and two subgroups of STGD1 patients with the presence/absence of definitely decreased autofluorescence (DDAF) areas were compared. OCTA vessel surface area (VSA) and vessel volume (VV) were measured in central zones (Z) of 1, 2 and 3mm diameter.

Results: 29 eyes of 15 STGD1 patients (20/9 eyes with/without DDAF) and 30 eyes of 15 controls contributed data. An enlarged foveal avascular zone was found in STGD1 patients without and even more with DDAF associated with a vessel rarefication in central and also paracentral zones with unnoticeable autofluorescence. VSA and VV were reduced in both STGD1 subgroups for all zones (P<0.0001). STGD1 eyes with compared to without DDAF showed reduced VSA and VV in Z2+3 (both P<0.05).

Conclusion: Volume-rendering of OCTA in STGD1 shows a reduced retinal flow in the central macula. This is most likely secondary to loss of neurosensory tissue with disease progression and therefore not likely be favorably influenced by gene transfer and retinal pigment epithelial transplantation. Retinal blood flow assessed by 3D-volume rendered OCTA could serve as surrogate marker for vascular changes of the central retina.
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http://dx.doi.org/10.1097/IAE.0000000000003110DOI Listing
January 2021

[Subepithelial Opacities in the Corneal Stroma after Foreign Body Removal].

Klin Monbl Augenheilkd 2021 Jan 12. Epub 2021 Jan 12.

Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Deutschland.

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http://dx.doi.org/10.1055/a-1328-2982DOI Listing
January 2021

A comparison of optic disc area measured by confocal scanning laser tomography versus Bruch's membrane opening area measured using optical coherence tomography.

BMC Ophthalmol 2021 Jan 12;21(1):31. Epub 2021 Jan 12.

Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106, Freiburg, Germany.

Background: Precise optic disc size measurements based on anatomically exact disc margins are fundamental for a correct assessment of glaucoma suspects. Computerized imaging techniques, such as confocal-scanning-laser-tomography (CSLT), which applies operator defined boundaries and optical-coherence-tomography (OCT), which incorporates an alternative detectable landmark (Bruch's-membrane-opening (BMO)), have simplified the planimetry of the optic disc and BMO-area, respectively. This study's objectives are to compare both modalities for area and to define a threshold for macro-BMO using BMO-OCT.

Methods: Retrospectively, patients that simultaneously received CSLT and BMO-OCT scans were included. Their images were correlated and agreement was determined using Bland-Altman-analysis. The diagnostic power of a macro-BMO threshold using OCT was derived after creating a receiver-operating-characteristics-curve using the well-established analogous CSLT threshold (2.43 mm).

Results: Our study included 373 eyes with a median optic disc area by CSLT/ BMO-area by OCT of 2.56 mm and 2.19 mm respectively. The Bland-Altman-analysis revealed a systematic deviation with a diverging tendency with increasing area, which enabled the creation of the following mathematical relation: disc-area (CSLT)*0.73 + 0.3 = BMO-area (OCT). BMO-area of 2.19 mm showed the best diagnostic power for identifying macro-BMOs using OCT (sensitivity: 75%, specificity: 86%).

Conclusions: Area measurements (CSLT optic disc area vs. BMO-area by OCT) showed a systematic deviation with a divergent tendency with increasing size. Our mathematical equation offers an estimated comparison of these anatomically diverse entities. Considering BMO-OCT´ anatomical accuracy, the 2.19 mm threshold may improve discernment between glaucoma suspects and norm variants.
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http://dx.doi.org/10.1186/s12886-020-01799-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802149PMC
January 2021

Vertical Scrolling Axis of Corneal Endothelial Grafts for Descemet Membrane Endothelial Keratoplasty.

Cornea 2021 Apr;40(4):497-501

Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Germany.

Purpose: Heterogeneity in scrolling behavior of Descemet membrane endothelial keratoplasty (DMEK) grafts complicates DMEK surgery. This prospective observational study assessed scrolling axes of DMEK grafts relative to the donor's eye.

Methods: The eye bank randomly marked the rim of corneoscleral donor buttons during trephination and recorded the position relative to the donor's axis. Surgeons were masked to the absolute position of the eye bank marking and recorded the scrolling axis relative to the eye bank marking and DMEK upside-down orientation. The scrolling axis was categorized as vertical (0 to 30 degrees and 150 to 180 degrees), oblique (>30 to 60 degrees and 120 to <150 degrees), and horizontal (>60 to <120 degrees). Scrolling patterns of corneas from the same donor were assessed.

Results: Scrolling patterns of 202 donor corneas from 149 donors were determined. The donor graft scrolled predominantly vertically to the donor's cornea [75%; 95% confidence interval (CI), 68%-80%]. Horizontal axes (11%) and oblique axes (14%) were less common. The median deviation in scrolling axes after unfolding the grafts was 0 degrees from the original scrolling axis (interquartile range, 0-15), indicating that scrolling axes were stable. Fellow eyes of 46 donors had 3.55 times higher odds of a nonvertical scrolling pattern if the first eye had a nonvertical scrolling pattern (95% CI, 1.37-9.20), suggesting that donor factors influencing both eyes could contribute to scrolling patterns.

Conclusions: DMEK grafts have a natural and stable scrolling tendency at vertical axis of donor's cornea. Anticipating scrolling axes might help improve preparation techniques for DMEK grafts and outcomes.
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http://dx.doi.org/10.1097/ICO.0000000000002583DOI Listing
April 2021

MACE RNA sequencing analysis of conjunctival squamous cell carcinoma and papilloma using formalin-fixed paraffin-embedded tumor tissue.

Sci Rep 2020 12 4;10(1):21292. Epub 2020 Dec 4.

Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106, Freiburg, Germany.

Recent advances in the field of biomedical research allow for elucidation of the transcriptional signature of rare tumors such as conjunctival squamous cell carcinoma (SCC). In this study we compare its expression profile to conjunctival papilloma (Pap) and healthy conjunctival tissue (Ctrl) and develop a classification tool to differentiate these entities. Seven conjunctival SCC, seven Pap and ten Ctrl were formalin-fixed and paraffin-embedded (FFPE) and analyzed using Massive Analysis of cDNA Ends (MACE) RNA sequencing. Differentially expressed genes (DEG) and gene ontology (GO) clusters were explored and the abundance of involved cell types was quantified by xCell. Finally, a classification model was developed to distinguish SCC from Pap and Ctrl. Among the most prominent DEG in SCC a plethora of keratins were upregulated when compared to Pap and Ctrl. xCell analysis revealed an enrichment of immune cells, including activated dendritic cells and T-helper type 1 cells (Th1), in SCC when compared to Ctrl. The generated classification model could reliably discriminate between the three entities according to the expression pattern of 30 factors. This study provides a transcriptome-wide gene expression profile of rare conjunctival SCC. The analysis identifies distinct keratins, as well as dendritic and Th1 cells as important mediators in SCC. Finally, the provided gene expression classifier may become an aid to the conventional histological classification of conjunctival tumors in uncertain cases.
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http://dx.doi.org/10.1038/s41598-020-78339-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718249PMC
December 2020

Scrolling of the Donor Cornea in Dependence of Temperature and Osmolarity for Descemet Membrane Endothelial Keratoplasty.

Klin Monbl Augenheilkd 2020 Nov 17. Epub 2020 Nov 17.

Klinik für Augenheilkunde, Universitätsklinikum Freiburg.

Background: After preparation of a graft for Descemet membrane endothelial keratoplasty (DMEK), the diameter of the graft's scroll varies significantly. In particular, narrow scrolls may complicate DMEK surgery. In this study we investigated how temperature, osmolarity, and deswelling of the donor tissue influence scrolling diameter.

Material And Methods: In this study we examined donor corneas that could not be used for transplantation. The diameter of the DMEK donor scrolls was measured after graft preparation by reflected light microscopy under different conditions: (1) The diameter of the roll was measured in Ringer's solution at temperatures of 5 °C, 24 °C and 35 °C. (2) To study the effect of different culture conditions we used 6% dextran-containing medium for 10 min, 20 min, 16 h and 24 h, and hyper- and hypoosmolar fluids (5% NaCl or aqua dest) for 5 min each.

Results: The median donors age was 62 years. The median endothelial cell density of the donor corneas was 1679 cells/mm. The median diameter of the DMEK scroll was 1.35 mm in Ringer's solution at 24 °C (IQR, 1.04 - 1.89). In Ringer's solution at different temperatures, the scrolling diameter changed between 0.02 mm and 0.29 mm. The change in osmolarity resulted in a difference of 0.02 mm to 0.46 mm. Deswelling with dextran resulted in a change of scrolling diameter between 0.02 mm and 0.09 mm.

Summary: In this experimental case series, the diameter of the DMEK scroll did not change due to changes of temperature, osmolarity or deswelling. Influencing the graft's scroll to standardize and simplify the DMEK surgery remains an interesting goal for future studies.
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http://dx.doi.org/10.1055/a-1227-4748DOI Listing
November 2020

What is the significance of the conjunctiva as a potential transmission route for SARS-CoV-2 infections?

Ophthalmologe 2021 Jan;118(Suppl 1):85-88

Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Killianstr. 5, 79106, Freiburg, Germany.

Recent studies have described conjunctivitis in approximately 1% of COVID-19 patients and speculated that SARS-CoV‑2 can be transmitted via the conjunctiva. In this article we recapitulate the molecular mechanisms of host cell entry of SARS-CoV‑2 and discuss the current evidence for a potential conjunctival transmission of SARS-CoV‑2. The current body of evidence indicates that SARS-CoV‑2 requires the membrane-bound angiotensin-converting enzyme 2 (ACE2) and the membrane-bound serine protease TMPRSS2 to enter cells. Recent studies suggest that COVID-19 patients rarely exhibit viral RNA in tear film and conjunctival smears and that, ACE2 and TMPRSS2 are only expressed in small amounts in the conjunctiva, making conjunctival infection with SARS-CoV‑2 via these mediators unlikely. Nevertheless, we consider the current evidence to be still too limited to provide a conclusive statement and recommend appropriate protective measures for healthcare personnel who are in close contact with suspected and confirmed COVID-19 patients.
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http://dx.doi.org/10.1007/s00347-020-01255-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607541PMC
January 2021

Corneal tissue induces transcription of metallothioneins in monocyte-derived human macrophages.

Mol Immunol 2020 12 1;128:188-194. Epub 2020 Nov 1.

Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Germany. Electronic address:

Purpose: Immune reactions following corneal transplantation are the most common cause of transplant failure. However, the underlying mechanisms of corneal graft rejection are not yet fully understood but increasing evidence points to a crucial role of the innate immune system in this context. Using a human in vitro model, we aimed to assess the response of human macrophages to stimulation with human corneal tissue and whether corneal endothelial cells (CEC) have immune-modulating properties.

Methods: Human monocytes were isolated from peripheral blood mononuclear cells and differentiated into monocyte-derived macrophages (MDM). A standardized protocol was used for disaggregation of human corneas into fragments of defined sizes. MDMs were stimulated using processed corneal material with or without CEC. Lipopolysaccharide (LPS) or interferon-gamma (IFNγ) served as controls. RNA sequencing was applied to analyze the impact of differential stimulation of MDMs on their transcriptional profile. RNA sequencing results were validated using digital PCR.

Results: The transcriptional profile of MDMs was significantly modulated by the type of stimulus used for MDM activation as well as by the individual MDM donor. LPS- or IFNγ-stimulation resulted in distinct transcriptional alterations compared to unstimulated MDMs including an upregulation of various cytokines such as CCL3, 4, 5, 19 or CXCL9. Corneal tissue induced the differential expression of 45 genes when compared to unstimulated MDMs, with several metallothioneins (MTs) among the upregulated factors (MT1A, MT1E, MT1F, MT1G, MT1H, MT1L, MT1M, MT1X, MT2A). This effect was independent of the presence or absence of CEC. PCR validation confirmed induction of 3 different metallothioneins (MT1G, MT1H and MT2A) in MDMs stimulated by corneal tissue.

Conclusions: The MDM in vitro model proved to be a robust tool to study the effects of LPS, IFNγ and corneal tissue homogenates on the transcriptional activity of MDM. Human macrophages showed a distinct upregulation of various MTs when challenged with human corneal allogen with or without corneal endothelium, which might have an immune-modulatory effect. As a general observation, it appears that in MDM-based studies a significant donor-dependent effect on the transcriptional profile of MDMs needs to be considered and adjusted before downstream analysis.
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http://dx.doi.org/10.1016/j.molimm.2020.10.016DOI Listing
December 2020

Isolation and enrichment of melanocytes from human corneal limbus using CD117 (c-Kit) as selection marker.

Sci Rep 2020 10 16;10(1):17588. Epub 2020 Oct 16.

Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106, Freiburg, Germany.

Limbal melanocytes (LM) are located in the basal epithelial layer of the corneoscleral limbus and interact with adjacent limbal epithelial progenitor cells. The exploration of their biological role in the maintenance of the limbal stem cell niche has been limited by the difficulty of LM isolation and cultivation. Here, we report on a facile protocol for the efficient isolation and enrichment of pure populations of human LMs by fluorescence-activated cell sorting (FACS) using antibodies raised against the cell surface marker CD117 (c-Kit). The enriched LMs retain self-renewal capacity and sustained melanin production, and are suitable to study the potential of LMs in stem cell-based corneal tissue engineering.
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http://dx.doi.org/10.1038/s41598-020-74869-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567782PMC
October 2020

Transcriptional characterization of conjunctival melanoma identifies the cellular tumor microenvironment and prognostic gene signatures.

Sci Rep 2020 10 12;10(1):17022. Epub 2020 Oct 12.

Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106, Freiburg, Germany.

This study characterizes the transcriptome and the cellular tumor microenvironment (TME) of conjunctival melanoma (CM) and identifies prognostically relevant biomarkers. 12 formalin-fixed and paraffin-embedded CM were analyzed by MACE RNA sequencing, including six cases each with good or poor clinical outcome, the latter being defined by local recurrence and/or systemic metastases. Eight healthy conjunctival specimens served as controls. The TME of CM, as determined by bioinformatic cell type enrichment analysis, was characterized by the enrichment of melanocytes, pericytes and especially various immune cell types, such as plasmacytoid dendritic cells, natural killer T cells, B cells and mast cells. Differentially expressed genes between CM and control were mainly involved in inhibition of apoptosis, proteolysis and response to growth factors. POU3F3, BIRC5 and 7 were among the top expressed genes associated with inhibition of apoptosis. 20 genes, among them CENPK, INHA, USP33, CASP3, SNORA73B, AAR2, SNRNP48 and GPN1, were identified as prognostically relevant factors reaching high classification accuracy (area under the curve: 1.0). The present study provides new insights into the TME and the transcriptional profile of CM and additionally identifies new prognostic biomarkers. These results add new diagnostic tools and may lead to new options of targeted therapy for CM.
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http://dx.doi.org/10.1038/s41598-020-72864-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550331PMC
October 2020

Transcriptional Profiling Uncovers Human Hyalocytes as a Unique Innate Immune Cell Population.

Front Immunol 2020 11;11:567274. Epub 2020 Sep 11.

Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Purpose: To decipher the transcriptional signature of macrophages of the human vitreous, also known as hyalocytes, and compare it to the profiles of other myeloid cell populations including human blood-derived monocytes, macrophages, and brain microglia.

Methods: This study involves a total of 13 patients of advanced age with disorders of the vitreoretinal interface undergoing vitrectomy at the University Eye Hospital Freiburg between 2018 and 2019. Vitreal hyalocytes were analyzed by fluorescence-activated cell sorting (FACS) and isolated as CD45CD11bCX3CR1Mat-Mac cells using a FACS-based sorting protocol. RNA extraction, library preparation and RNA sequencing were performed and the sequencing data was analyzed using the Galaxy web platform. The transcriptome of human hyalocytes was compared to the transcriptional profile of human blood-derived monocytes, macrophages and brain microglia obtained from public databases. Protein validation for selected factors was performed by immunohistochemistry on paraffin sections from three human donor eyes.

Results: On average, 383 ± 233 hyalocytes were isolated per patient, resulting in 128 pg/μl ± 76 pg/μl total RNA per sample. RNA sequencing revealed that , , , and are among the most abundantly expressed genes in hyalocytes, which was confirmed by immunofluorescence for CD74, FTL, and HLA-DRA. Gene ontology (GO) enrichment analysis showed that biological processes such as "humoral immune response," "leukocyte migration," and "antigen processing and presentation of peptide antigen" (adjusted < 0.001) are dominating in vitreal hyalocytes. While the comparison of the gene expression profiles of hyalocytes and other myeloid cell populations showed an overall strong similarity ( > 0.637, < 0.001), hyalocytes demonstrated significant differences with respect to common leukocyte-associated factors. In particular, transcripts involved in the immune privilege of the eye, such as , , and , were significantly increased in hyalocytes compared to other myeloid cell subsets.

Conclusion: Human hyalocytes represent a unique and distinct innate immune cell population specialized and adapted for the tissue-specific needs in the human vitreous. Vitreal hyalocytes are characterized by a strong expression of genes related to antigen processing and presentation as well as immune modulation. Thus, hyalocytes may represent an underestimated mediator in vitreoretinal disease and for the immune privilege of the eye.
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http://dx.doi.org/10.3389/fimmu.2020.567274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517040PMC
May 2021

Comparison of two extended depth of focus intraocular lenses with a monofocal lens: a multi-centre randomised trial.

Graefes Arch Clin Exp Ophthalmol 2021 Feb 11;259(2):431-442. Epub 2020 Sep 11.

Hospital Universitario, Donostia, Spain.

Purpose: The AT LARA 829MP is a next-generation extended depth of focus (EDOF) intraocular lens (IOL) providing continuous vision over a range of distances. The aim of this prospective multi-centre randomised trial was to compare two EDOF IOLs and one monofocal IOL.

Methods: Cataract patients between 50 and 80 years were randomised for bilateral implantation with either the AT LARA 829MP (EDOF), the TECNIS Symfony (EDOF) or the CT ASPHINA 409MP (monofocal). Follow-up was at 1 to 2 weeks, 1 month and 4 to 6 months.

Results: A total of 211 patients were randomised and included in the final analysis. Monocular depth of focus was significantly better for AT LARA 829MP eyes compared with that for TECNIS Symfony at all thresholds (p = 0.024, 0.001 and 0.006, for 0.1, 0.2 and 0.3 logMAR respectively) with no significant difference for binocular depth of focus. LARA eyes had significantly better monocular depth of focus at all levels compared with ASPHINA eyes (all p < 0.0001), while there was no significant difference between Symfony and ASPHINA eyes at 0.1 logMAR and 0.2 logMAR. Both EDOF IOLs were significantly better than the monofocal ASPHINA at all levels for binocular depth of focus (LARA: all p < 0.0001; Symfony: all p = 0.002). Distance visual acuity was similar for all IOLs at 6 months; intermediate and near visual acuity were significantly better for the EDOF IOLs than for the monofocal (p < 0.0001). Refraction improved in all groups relative to baseline. Contrast sensitivity was higher with the CT ASPHINA 409MP but both EDOF lenses had a better spectacle independence rate. At 6 months, all IOLs were well centred with no cases of tilt. No general safety issues were raised for any of the groups.

Conclusion: The two EDOF intraocular lenses investigated provided good visual outcomes with comparable visual acuity at all distances. The AT LARA 829MP provided the widest monocular depth of focus at 0.1 and 0.2 logMAR, with a clear superiority compared with the monofocal IOL. TECNIS Symfony was superior to the monofocal control at 0.3 logMAR. Spectacle independence and patient satisfaction were comparable.

Trial Registration: Trial registered on https://clinicaltrials.gov/ under the identification NCT03172351 (date of registration 1 June May 2017).
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http://dx.doi.org/10.1007/s00417-020-04868-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843553PMC
February 2021

Different Innate Immune Responses in BALB/c and C57BL/6 Strains following Corneal Transplantation.

J Innate Immun 2021 9;13(1):49-59. Epub 2020 Sep 9.

Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany,

Purpose: To investigate immunological differences and the role of CD38+/F4/80 + M1 macrophages in C57BL/6J- and BALB/c-recipient mouse corneal transplantation models.

Methods: Allogeneic transplantation was performed crosswise in BALB/c mice and C57BL/6J mice; syngeneic transplantation was performed in both strains. Anterior chamber depth (ACD) was measured before and central corneal thickness (CCT) was measured both before and after transplantation. In vivo graft rejection was monitored using anterior eye segment optical coherence tomography (ASOCT) evaluating the CCT and grading of corneal oedema using a well-established clinical score (CS). Histology of corneal grafts was performed 18 or 21 days after surgery. Immunohistochemistry with anti-F4/80 antibody and anti-CD38 antibody was used for detecting M1 macrophages within the grafts.

Results: High CS and CCT values after allogeneic transplantation persisted in both BALB/c (n = 18) and C57BL/6J recipients (n = 20). After syngeneic transplantation, CS and CCT values increased in both models in the early phase after surgery due to the surgical trauma. Surprisingly, in the syngeneic C57BL/6J model, high CCT values persisted. Furthermore, anterior synechiae developed in C57BL/6 recipients after both syngeneic and allogeneic transplantation, whereas BALB/c recipients showed almost no synechiae - even though C57/BL6J animals tended to have a deeper anterior chamber (281 ± 11 pixels [mean ± SD]) compared with BALB/c animals of the same age (270 ± 9 pixels [mean ± SD]). Immunohistochemistry revealed numerous CD38+/F4/80 + M1 macrophages in grafts of C57BL/6J recipients following both syngeneic and allogeneic transplantation. However, in BALB/c-recipient mice only sparse M1 macrophages were detectable (CD38 + M1 macrophages relative to all F4/80 + cells: 75 vs. 17% [after allogeneic transplantation] and 66 vs. 17% [after syngeneic transplantation]; p < 0.05).

Conclusions: Allogeneic corneal transplants are rejected in BALB/c as well as C57BL/6J mice, but tissue alterations with anterior synechiae are more pronounced in C57BL/6J recipients. Following syngeneic transplantation, C57BL/6J-recipient animals show a persistent graft swelling with increased numbers of CD38+/F4/80 + M1 macrophages in grafted tissue, in contrast to the common model using BALB/c-recipient mice. Our data strongly suggest that strain-dependent differences convey different innate immune responses in BALB/c and C57BL/6J strains. Accordingly, in murine keratoplasty experiments, the mouse line of both donor and recipient animals must be carefully considered. C57BL/6J-recipient mice might be particularly suited to study corneal graft rejection in a clinical setting considered "high risk."
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http://dx.doi.org/10.1159/000509716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879253PMC
September 2020

Phototherapeutic keratectomy for anterior stromal fibrosis following DMEK.

Am J Ophthalmol Case Rep 2020 Sep 8;19:100849. Epub 2020 Aug 8.

Eye Center, University Hospital Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Purpose: Anterior stromal fibrosis is often seen in advanced cases of Fuchs endothelial dystrophy or secondary endothelial insufficiency. As Descemet membrane endothelial keratoplasty (DMEK) can completely eliminate the corneal edema and the guttae in these patients, anterior stromal fibrosis often remains leading to a reduction in visual function.

Observations: In such situations phototherapeutic keratectomy can be an effective tool to remove the opacifications in the anterior corneal stroma and improve the visual function as presented in two clinical cases.

Conclusion: DMEK can be the method of choice even in advanced cases of endothelial insufficiency with clinical significant fibrosis of the anterior corneal stroma.
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http://dx.doi.org/10.1016/j.ajoc.2020.100849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453103PMC
September 2020

Ophthalmic Care in Nursing Homes for the Blind: A Growing Challenge.

Klin Monbl Augenheilkd 2020 Nov 31;237(11):1326-1333. Epub 2020 Aug 31.

Klinik für Augenheilkunde, Universitätsklinikum Freiburg.

Background: The demographic change in Germany will lead to an increase in irreversible age-related eye diseases. This will increase the need for specialised care facilities for visually impaired people. Due to reduced mobility, residents in such facilities often do not receive adequate ophthalmological care. New concepts must therefore be considered for this group of patients. One approach is to set up an ophthalmological examination unit within the facility combined with regular visits by an ophthalmologist. We now present the experience with such a model in a home for the blind.

Patients And Methods: The project was initiated in 2009. Since then there have been visits by medical staff of the Eye Center at Medical Center, University of Freiburg, every two weeks. All patient records (2010 - 2017) were reviewed systematically. The following data were extracted in a structured and anonymous way: Age at first presentation, gender, ophthalmological diagnoses and if a therapy was initiated. This data set was finally analysed descriptively.

Results: Out of 130 residents aged between 48 and 100 years, half were between 78 and 90 years old. The youngest resident was 48, the oldest 100 years old. The median visual acuity was 0.2. Sixty percent of the residents had at least mild visual impairment according to the WHO (visual acuity < 0.5; category 1 - 6). In one of 6 - 7 residents, visual acuity could not be determined using Snellen charts. The most frequent ophthalmological diagnoses included cataract (44%), age-related macular degeneration (36%) and glaucoma (29%). In 67 residents (52%), the ophthalmological examination lead to treatment, such as application of local therapy or planning an operation.

Conclusion: In every second resident, the ophthalmologist's visit lead to treatment during the observation period. This underlines the difficulty of providing ophthalmological care even in specialised institutions for the blind and visually impaired, which is possibly due to the residents' mobility problems. The concept presented here has established a low-threshold, sustainable and high-quality ophthalmological service on site. These positive experiences indicate that corresponding measures may also be useful for other locations. However, in order to implement such a project on a larger scale, suitable financing and accounting modalities for the construction measures, the nursing staff and the ophthalmological procedure still need to be developed.
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http://dx.doi.org/10.1055/a-1194-5381DOI Listing
November 2020
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