Philipp Herrmann

University Hospital Bonn

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Frank G. Holz

University of Bonn

Peter Charbel Issa

Oxford University Hospitals NHS Trust

Johannes Birtel

Oxford University Hospitals NHS Trust

Martin Gliem

Roche (Switzerland)

Kristina Heß

University Hospital of Basel

Maximilian Pfau

University of Basel

Philipp L. Müller

University of Bonn

Steffen Schmitz-Valckenberg

University of Utah

Kristin Raming

University of Bonn

Hanno J. Bolz

University Hospital Cologne

Cooperative Institutions

University of Bonn

University Hospital Bonn

University College London

Universitäts-Augenklinik Bonn

Moorfields Eye Hospital

Moorfields Eye Hospital NHS Foundation Trust

Institute of Ophthalmology

University of Oxford

Oxford University Hospitals NHS Trust

John Radcliffe Hospital

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Trends in Shoulder Arthroplasty in Germany: A 10-Year Epidemiological Analysis of Patients with Primary Osteoarthritis of the Shoulder

Healthcare (2024)

Felix Hochberger Philipp Herrmann Maximilian Rudert Kilian List Ioannis Stratos

Shoulder arthroplasty has significantly gained popularity in orthopedic surgery, driven by progress in prosthesis design and surgical techniques. This study explored the epidemiology of shoulder arthroplasty, analyzing healthcare data from 2012 to 2022 for primary osteoarthritis of the shoulder. The data included patient demographics and types of surgical procedures. Data analysis indicates a higher utilization rate of reverse total shoulder arthroplasty (RTSA; n = 41,251) over total- (TSA; n = 18,679) and hemiarthroplasty (HSA; n = 12,827) for primary shoulder osteoarthritis. Overall, a significant increase in RTSA procedures from n = 2237 (2012) to n = 5415 (2022) was observed, representing more than a two-fold increase of 121.1%. The relative proportion of RTSA among all types of shoulder arthroplasty increased from 39% (2012) to 68.6% (2022), while HSA decreased and TSA essentially remained constant. Age analysis identified the following peaks: RTSA, 77 ± 7 y; HSA, 68 ± 12 y; and TSA, 67 ± 10 y. Among the over 60s, significantly more women were treated with any type of prosthesis, whereas in young patients (45 to 59 y), more men received HSA or TSA. Our study confirms that RTSA has become the preferred choice for elderly patients in Germany, reflecting the prevailing preference despite varying patient ages and conditions, with a noted difference in sex in treatment prevalence.

Demographics

10.3390/healthcare12090949

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DARK ADAPTATION IN MACULAR TELANGIECTASIA TYPE 2

Retina (2019)

Simone Tzaridis Kristina Heß Tjebo Heeren Jennifer Nadal Clarissa Mai

Purpose: To evaluate dark adaptation (DA) in patients with macular telangiectasia Type 2 (MacTel). Methods: After a local photobleach (4 × 4° size, 83% bleach), DA was measured using a test stimulus (2° diameter) projected at 5° eccentricity horizontal from the foveal center within the temporal parafovea. Cone plateau, rod intercept time, and rod recovery rate (S2) were calculated from the resulting DA curves. Findings were correlated with disease stages (according to Gass and Blodi), the area of ellipsoid zone loss in optical coherence tomography, and macular pigment loss (“MP-Classes 1–3”). Results: Fifty-nine eyes of 59 patients were compared with 18 eyes of 18 healthy controls. Dark adaptation was significantly impaired in patients with MacTel. Although differences were most pronounced for parameters indicating rod-mediated recovery, cone-mediated recovery was also decreased, yet to a lesser extent. Dark adaptation parameters were only weakly associated with disease stages and ellipsoid zone loss. A better association was found between rod-mediated recovery (S2 and rod intercept time) and macular pigment loss (Kendall's tau for rod intercept time: 0.69 and S2: −0.51; both P < 0.0001). Conclusion: Dark adaptation is significantly impaired in patients with MacTel. Our results indicate an association of reduced macular pigment and rod dysfunction in MacTel.

Macular telangiectasia

10.1097/iae.0000000000002694

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Comparison of Green Versus Blue Fundus Autofluorescence inABCA4-Related Retinopathy

Translational Vision Science & Technology (2018)

Philipp L. Müller Maximilian Pfau Matthias M. Mauschitz Philipp T. Möller Johannes Birtel

To investigate the interreader and intermodality agreement for grading of retinal pigment epithelium (RPE) atrophy lesion size in ABCA4-related retinopathy using green (GAF) and blue fundus autofluorescence (BAF) imaging.In this cross-sectional case series, 97 eyes of 49 patients with RPE atrophy secondary to ABCA4-related retinopathy underwent GAF- (518 nm excitation light) and BAF- (488 nm excitation light) imaging using confocal scanning laser ophthalmoscopy (Spectralis HRA, Heidelberg Engineering, Heidelberg, Germany). Lesions with definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence (QDAF) in GAF and BAF imaging were analyzed separately by five independent readers using semiautomated software (RegionFinder, Heidelberg Engineering). Intermodality and interreader agreements were assessed for the square-root lesion size, lesion perimeter, and circularity.GAF- and BAF-based measurements of DDAF and QDAF showed high intermodality and interreader agreement concerning square-root lesion size, as well as shape descriptive parameters (perimeter and circularity). Interreader agreement of square-root lesion size was slightly, hence not significantly higher for GAF-based grading ([95% coefficients of repeatability, intraclass correlation coefficient] DDAF: 0.215 mm, 0.997; QDAF: 0.712 mm, 0.981) compared to BAF-based grading (DDAF: 0.232 mm, 0.997; QDAF: 0.764 mm, 0.978). However, DDAF-measurements revealed distinctly more reproducible results than QDAF-measurements. Foveal sparing did not interfere with intermodality agreement.Both GAF- and BAF-based quantification of RPE atrophy showed very reliable results with possible superiority of GAF in the context of less energetic excitation light.The high interreader agreement qualifies the use of DDAF progression in GAF and BAF imaging as potential morphologic outcome measure for interventional clinical trials and disease monitoring.

Autofluorescence

10.1167/tvst.7.5.13

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Quantification of Retinal and Choriocapillaris Perfusion in Different Stages of Macular Telangiectasia Type 2

Investigative Ophthalmology & Visual Science (2019)

Simone Tzaridis Maximilian W. M. Wintergerst Clarissa Mai Tjebo Heeren Frank G. Holz

To quantify the retinal and choriocapillaris perfusion in different disease stages of macular telangiectasia type 2 (MacTel) using optical coherence tomography-angiography (OCT-A).We examined 76 eyes of 76 patients and 24 eyes of 24 age-related controls. Participants underwent multimodal imaging, including OCT and OCT-A. Patients' eyes were divided into three groups considering predefined criteria from funduscopy, OCT, and fluorescein angiography, thus reflecting the disease severity ("early," "advanced," and "neovascular"). Quantitative analyses of vessel density (VD), skeleton density (SD), and fractal dimension (FD) were conducted in the superficial and deep retinal plexus and in the avascular layer. The choriocapillaris was analyzed for mean signal intensity and percentage of nondetectable perfused choriocapillaris-area (PNPA).The deep retinal plexus showed a progressive decrease of mean VD, SD, and FD in the temporal parafovea in all disease stages. In the superficial layer, VD, SD, and FD were significantly decreased in the temporal parafovea of advanced and neovascular stages, while these parameters did not differ from controls in early stages. In MacTel, signals of blood flow were also detectable at the level of the avascular layer and showed a significant increase with disease progression. The choriocapillaris in MacTel showed a significant increase of mean PNPA and a decrease of mean signal intensity in comparison to controls. These findings were consistent in all disease stages.Quantitative OCT-A data show a progressive rarefication of the retinal microvasculature in MacTel. We propose an altered choriocapillaris perfusion as a possibly early alteration of the disease.

Macular telangiectasia

Plexus

10.1167/iovs.19-27055

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Comprehensive geno- and phenotyping in a complex pedigree including four different inherited retinal dystrophies

Investigative Ophthalmology & Visual Science (2020)

Johannes Birtel Martin Gliem Kristina Heß Theresa H. Birtel Frank G. Holz

Inherited retinal dystrophies (IRDs) are characterized by high clinical and genetic heterogeneity. A precise characterization is desirable for diagnosis and has impact on prognosis, patient counseling, and potential therapeutic options. Here, we demonstrate the effectiveness of the combination of in-depth retinal phenotyping and molecular genetic testing in complex pedigrees with different IRDs. Four affected Caucasians and two unaffected relatives were characterized including multimodal retinal imaging, functional testing, and targeted next-generation sequencing. A considerable intrafamilial phenotypic and genotypic heterogeneity was identified. While the parents of the index family presented with rod-cone dystrophy and ABCA4-related retinopathy, their two sons revealed characteristics in the spectrum of incomplete congenital stationary night blindness and ocular albinism, respectively. Molecular testing revealed previously described variants in RHO, ABCA4, and MITF as well as a novel variant in CACNA1F. Identified variants were verified by intrafamilial co-segregation, bioinformatic annotations, and in silico analysis. The coexistence of four independent IRDs caused by distinct mutations and inheritance modes in one pedigree is demonstrated. These findings highlight the complexity of IRDs and underscore the need for the combination of extensive molecular genetic testing and clinical characterization. In addition, a novel variant in the CACNA1F gene is reported associated with incomplete congenital stationary night blindness.

ABCA4

Pedigree chart

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Ocular phenotype and associations with systemic findings in patients with primary hyperoxaluria type I

Investigative Ophthalmology & Visual Science (2019)

Johannes Birtel Philipp Herrmann Sander F. Garrelfs Simon Dulz Yevgeniya Atiskova

Primary hyperoxaluria

Primary (astronomy)

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Mesopic and Scotopic Light Sensitivity and Its Microstructural Correlates in Pseudoxanthoma Elasticum

JAMA Ophthalmology (2020)

Kristina Heß Martin Gliem Peter Charbel Issa Johannes Birtel Philipp L. Müller

Correlates for Bruch membrane alterations are needed for interventional trials targeting the Bruch membrane in pseudoxanthoma elasticum (PXE).To quantify mesopic and scotopic light sensitivity and identify its microstructural correlates associated with a diseased Bruch membrane in patients with PXE.A prospective, single-center, cross-sectional case-control study was conducted at a tertiary referral center from January 31, 2018, to February 20, 2020. Twenty-two eyes of 22 patients with PXE and 40 eyes of 40 healthy individuals were included. Data analysis was completed March 15, 2020.Mesopic and dark-adapted 2-color fundus-controlled perimetry (microperimetry) and multimodal retinal imaging including spectral-domain optical coherence tomography (SD-OCT) and OCT angiography were performed. Perimetry thresholds were analyzed using mixed models, and structure-function correlation with SD-OCT data was performed using machine learning.Observed dark-adapted cyan sensitivity loss as measure of rod photoreceptor dysfunction, as well as mean absolute error between predicted and observed retinal sensitivity to assess the accuracy of structure-function correlation.Of the 22 patients with PXE included in this study, 15 were women (68%); median age was 56.5 years (interquartile range, 50.4-61.2). These patients exhibited mesopic (estimate, 5.13 dB; 95% CI, 2.89-7.38 dB), dark-adapted cyan (estimate, 9.08 dB; 95% CI, 6.34-11.82 dB), and dark-adapted red (estimate, 7.05 dB; 95% CI, 4.83-9.27 dB) sensitivity losses. This sensitivity loss was also evident in 9 eyes with nonneovascular PXE (mesopic: estimate, 3.21 dB; 95% CI, 1.28-5.14 dB; dark-adapted cyan: 5.93 dB; 95% CI, 3.59-8.27 dB; and dark-adapted red testing: 4.84 dB; 95% CI, 2.88-6.80 dB), showing a distinct centrifugal pattern of sensitivity loss with preserved function toward the periphery. Retinal function could be predicted from microstructure with high accuracy (mean absolute errors, of 4.91 dB for mesopic, 5.44 dB for dark-adapted cyan, and 4.99 dB for dark-adapted red). The machine learning-based analysis highlighted an association of a thinned inner retina and putative separation of the pigment-epithelium-photoreceptor complex with sensitivity loss.In this study, among 22 patients with PXE, those with and without choroidal neovascularization exhibited reductions of retinal sensitivity being most pronounced in dark-adapted cyan testing. This finding suggests that pathologic characteristics of this Bruch membrane disease may be dominated by rod photoreceptor degeneration and/or dysfunction. A putative pigment-epithelium-photoreceptor separation may further impair rod function, while inner retinal abnormalities appear to be correlated with overall dysfunction.

Mesopic vision

Microperimetry

Bruch's membrane

Pseudoxanthoma Elasticum

Angioid streaks

Scotopic vision

10.1001/jamaophthalmol.2020.4335

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Citations (21)

Partizipieren statt Konsumieren, oder: Lohnt sich Engagement in Q&A-Communities?

WIRTSCHAFTSINFORMATIK (2011)

Philipp Herrmann Dennis Kundisch

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Cd59a deficiency in mice leads to preferential innate immune activation in the retinal pigment epithelium–choroid with age

Neurobiology of Aging (2015)

Philipp Herrmann Jill A. Cowing Enrico Cristante Sidath E. Liyanage Joana Ribeiro

Dysregulation of the complement system has been implicated in the pathogenesis of age-related macular degeneration. To investigate consequences of altered complement regulation in the eye with age, we examined Cd59a complement regulator deficient (Cd59a(-/-)) mice between 4 and 15 months. In vivo imaging revealed an increased age-related accumulation of autofluorescent spots in Cd59a(-/-) mice, a feature that reflects accumulation of subretinal macrophages and/or microglia. Despite this activation of myeloid cells in the eye, Cd59a(-/-) mice showed normal retinal histology and function as well as normal choroidal microvasculature. With age, they revealed increased expression of activators of the alternative complement pathway (C3, Cfb, Cfd), in particular in the retinal pigment epithelium (RPE)-choroid but less in the retina. This molecular response was not altered by moderately-enhanced light exposure. Cd59a deficiency therefore leads to a preferential age-related dysregulation of the complement system in the RPE-choroid, that alone or in combination with light as a trigger, is not sufficient to cause choroidal vascular changes or retinal degeneration and dysfunction. This data emphasizes the particular vulnerability of the RPE-choroidal complex to dysregulation of the alternative complement pathway during aging.

Choroid

Blood–retinal barrier

Pathogenesis

10.1016/j.neurobiolaging.2015.05.019

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Correction: RPE65-associated retinal dystrophies: phenotypes and treatment effects with voretigene neparvovec

Klinische Monatsblätter für Augenheilkunde (2024)

Katarína Štingl Claudia Priglinger Philipp Herrmann

RPE65

10.1055/a-2514-0148

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