Martin S Zinkernagel

• Professor
• Inselspital, Universitätsspital Bern

Purpose: To evaluate the early real-world clinical outcomes regarding safety and efficacy after administering the aflibercept 2 mg biosimilar (Tyalia, Cinnagen, Tehran, Iran). Methods: A retrospective, uncontrolled observational study was conducted with a total of 499 Tyalia injections given in 189 eyes of 148 patients for variable indications. Al...

Purpose To determine the incidence, prognostic factors and management of macular edema (ME) associated with silicone oil (SO) tamponade. Methods This retrospective, comparative, observational study included patients who underwent pars plana vitrectomy (PPV) and SO tamponade for rhegmatogenous retinal detachment (RRD) or persistent full-thicknes...

Purpose Evaluating High-Resolution Optical Coherence Tomography (HR-OCT) versus standard spectral domain OCT in pigmented choroidal lesions. Methods We screened a total of 40 subjects with pigmented choroidal lesions. Lesions were imaged on HR-OCT and standard OCT devices with and without enhanced depth imaging (EDI) mode. Images were graded for q...

Purpose: The purpose of this study was to report a case of retinal alterations due to proven Vitamin A deficiency. Methods: We report a case of a 39-year-old woman who presented with progressing nyctalopia and mildly reduced visual acuity over a period of 1-2 years, despite being on oral Vitamin A supplementation, following a history of gastric byp...

Glia antigen‐presenting cells (APCs) are pivotal regulators of immune surveillance within the retina, maintaining tissue homeostasis and promptly responding to insults. However, the intricate mechanisms underlying their local coordination and activation remain unclear. Our study integrates an animal model of retinal injury, retrospective analysis o...

This paper addresses the domain adaptation challenge for semantic segmentation in medical imaging. Despite the impressive performance of recent foundational segmentation models like SAM on natural images, they struggle with medical domain images. Beyond this, recent approaches that perform end-to-end fine-tuning of models are simply not computation...

To describe the management and clinical course of 12 cases of pseudophakic aqueous misdirection syndrome (AMS). Twelve eyes of 12 Patients diagnosed with pseudophakic AMS between 2021 and 2022 were included. Best-corrected visual acuity, refraction, intraocular pressure (IOP), anti-glaucomatous medication, spectral domain ocular coherence tomograph...

Purpose To compare the anatomical and functional outcomes of pars plana vitrectomy (PPV) alone versus PPV with the addition of a scleral buckle in treating inferior rhegmatogenous retinal detachments (RRDs). Methods Comparative, retrospective cohort study including patients who were diagnosed with primary inferior RRD, defined as RRD with one or m...

Purpose To assess the accuracy of High-Resolution OCT in detecting biomarkers associated with central serous chorioretinopathy (CSC) compared to standard OCT. Methods We conducted a cross-sectional study involving CSC patients who underwent High-Resolution and standard OCT during the same visit. Using the SPECTRALIS High-Res OCT device (Heidelberg...

Purpose: To identify optical coherence tomography (OCT) biomarkers for macula-off rhegmatogenous retinal detachment (RRD) with artificial intelligence (AI) and to correlate these biomarkers with functional outcomes. Methods: Patients with macula-off RRD treated with single vitrectomy and gas tampon-ade were included. OCT volumes, taken at 4 to 6 we...

This editorial examines the transformative impact of the digital revolution on retinal practice, highlighting how technological advances are transforming patient care and pushing the boundaries of ophthalmology. It explores key areas of progress, including personalised medicine through big data, artificial intelligence and advanced imaging techniqu...

The integration of artificial intelligence (AI) into the management of neovascular age-related macular degeneration (nAMD) presents a transformative opportunity in ophthalmology. Specifically, deep learning (DL) models have shown remarkable accuracy in detecting nAMD, predicting disease progression, and forecasting treatment outcomes. This review p...

We evaluate the pharmacokinetics, safety, and optimal dosages of intravitreal agents in silicone oil (SO)-filled eyes, addressing challenges in administering such therapies. We assessed the pharmacological properties and safety profiles of intravitreal drugs in SO-filled eyes, deriving conclusions and guidance from available literature and expert c...

Purpose To assess the accuracy of High-Resolution OCT in detecting biomarkers associated with central serous chorioretinopathy (CSC) compared to standard OCT. Methods We conducted a cross-sectional study involving CSC patients who underwent High-Resolution and standard OCT during the same visit. Using the SPECTRALIS High-Res OCT device (Heidelberg...

Background/aims. This study reports on the long-term functional and anatomical outcomes of patients with central retinal vein occlusion (CRVO) treated under the Bern treat-and-extend (T&E) protocol. Methods. Observational study. Treatment-naive patients with CRVO and consecutive macular oedema treated with aflibercept were included. The T&E pro...

Although glaucoma is a leading cause of irreversible blindness worldwide, its pathogenesis is incompletely understood, and intraocular pressure (IOP) is the only modifiable risk factor to target the disease. Several associations between the gut microbiome and glaucoma, including the IOP, have been suggested. There is growing evidence that interacti...

Aim To adopt a novel artificial intelligence (AI) optical coherence tomography (OCT)-based program to identify the presence of biomarkers associated with central serous chorioretinopathy (CSC) and whether these can differentiate between acute and chronic central serous chorioretinopathy (aCSC and cCSC). Methods Multicenter, observational study wit...

This work explores the effectiveness of masked image modelling for learning representations of retinal OCT images. To this end, we leverage Masked Autoencoders (MAE), a simple and scalable method for self-supervised learning, to obtain a powerful and general representation for OCT images by training on 700K OCT images from 41K patients collected un...

Background The human gut microbiome (GM) is involved in inflammation and immune response regulation. Dysbiosis, an imbalance in this ecosystem, facilitates pathogenic invasion, disrupts immune equilibrium, and potentially triggers diseases including various human leucocyte antigen (HLA)-B27-associated autoinflammatory and autoimmune diseases such a...

Glia antigen-presenting cells (APCs) are pivotal regulators of immune surveillance within the retina, maintaining tissue homeostasis and promptly responding to insults. The intricate mechanisms underlying their local coordination and activation remain unclear. Our study integrates an animal model of retinal injury, retrospective analysis of human r...

Aim: To adopt a novel artificial intelligence (AI) optical coherence tomography (OCT)-based program to identify the presence of biomarkers associated with central serous chorioretinopathy (CSC) and whether these can differentiate between acute and chronic central serous chorioretinopathy (aCSC and cCSC). Methods: Multicenter, observational study wi...

In recent years, the landscape of computer-assisted interventions and post-operative surgical video analysis has been dramatically reshaped by deep-learning techniques, resulting in significant advancements in surgeons’ skills, operation room management, and overall surgical outcomes. However, the progression of deep-learning-powered surgical techn...

Purpose: The purpose of this study was to develop a deep learning algorithm, to detect retinal breaks and retinal detachments on ultra-widefield fundus (UWF) optos images using artificial intelligence (AI). Methods: Optomap UWF images of the database were annotated to four groups by two retina specialists: (1) retinal breaks without detachment,...

Introduction: The aim of this study is to investigate the role of an artificial intelligence (AI)-developed OCT program to predict the clinical course of central serous chorioretinopathy (CSC ) based on baseline pigment epithelium detachment (PED) features. Methods: Single-center, observational study with a retrospective design. Treatment-naïve pat...

Background Retinal degeneration results from disruptions in retinal homeostasis due to injury, disease, or aging and triggers peripheral leukocyte infiltration. Effective immune responses rely on coordinated actions of resident microglia and recruited macrophages, critical for tissue remodeling and repair. However, these phagocytes also contribute...

Background Dupilumab is used for the treatment of atopic dermatitis (AD). Approximately one third of AD patients develop a dupilumab‐associated ocular surface disease (DAOSD), of which the pathomechanism is poorly understood. This study aimed at investigating inflammatory markers in tear fluids of patients on dupilumab therapy. Methods Tear fluids...

Purpose Semantic segmentation plays a pivotal role in many applications related to medical image and video analysis. However, designing a neural network architecture for medical image and surgical video segmentation is challenging due to the diverse features of relevant classes, including heterogeneity, deformability, transparency, blunt boundaries...

Background To compare the intermediate-term efficacy of PRESERFLO (PF) MicroShunt implantation with trabeculectomy (TE) in patients with primary open-angle glaucoma, focusing on longitudinal changes of functional and structural parameters. Methods This retrospective comparative study included 104 eyes of 104 patients who underwent TE and 83 eyes o...

Introduction Age-related macular degeneration (AMD) affects millions of people globally, leading to a surge in online research of putative diagnoses, causing potential misinformation and anxiety in patients and their parents. This study explores the efficacy of artificial intelligence-derived large language models (LLMs) like in addressing AMD pati...

Recent developments in deep learning have shown success in accurately predicting the location of biological markers in Optical Coherence Tomography (OCT) volumes of patients with Age-Related Macular Degeneration (AMD) and Diabetic Retinopathy (DR). We propose a method that automatically locates biological markers to the Early Treatment Diabetic Ret...

Introduction Geographic atrophy (GA) is a progressive form of age-related macular degeneration (AMD) that leads to severe visual impairment and central vision loss. Traditional treatment options for GA are limited, highlighting the need for new therapeutic approaches. In recent years, targeting the complement system has emerged as a promising strat...

Purpose To identify optical coherence tomography (OCT) features to predict the course of central serous chorioretinopathy (CSC) with an artificial intelligence (AI) based program. Methods Multicenter, observational study with a retrospective design. Treatment-naïve patients with acute CSC and chronic CSC were enrolled. Baseline OCTs were examined...

Macrophages/monocytes, the primary contributors to chronic inflammation in degenerated retinas, orchestrate intricate immune responses. They remain enigmatic in their local coordination and activation mechanisms. Innovations in experimental systems enable real-time exploration of immune cell interactions and temporal dimensions in response. In prec...

Proliferative vitreoretinopathy (PVR) remains the main cause of failure in retinal detachment (RD) surgery and a demanding challenge for vitreoretinal surgeons. Despite the large improvements in surgical techniques and a better understanding of PVR pathogenesis in the last years, satisfactory anatomical and visual outcomes have not been provided ye...

Title: Inferior retinal detachments secondary to inferior breaks, clinical features, outcomes and surgical techniques Authors: Enrico Bernardi, Lorenzo Ferro Desideri, Martin Zinkernagel, Rodrigo Anguita – Purpose: To describe clinical features, prognostic factors, rate of success of surgery in patients with inferior retinal detachments secondary...

Models capable of leveraging unlabelled data are crucial in overcoming large distribution gaps between the acquired datasets across different imaging devices and configurations. In this regard, self-training techniques based on pseudo-labeling have been shown to be highly effective for semi-supervised domain adaptation. However, the unreliability o...

Although dry eye disease (DED) is one of the most common ocular surface diseases worldwide, its pathogenesis is incompletely understood, and treatment options are limited. There is growing evidence that complex interactions between the ocular surface microbiome (OSM) and tear fluid constituents, potentially leading to inflammatory processes, are as...

Purpose The low microbial abundance on the ocular surface results in challenges in the characterization of its microbiome. The purpose of this study was to reveal factors introducing bias in the pipeline from sample collection to data analysis of low-abundant microbiomes. Methods Lower conjunctiva and lower lid swabs were collected from six partic...

Models capable of leveraging unlabelled data are crucial in overcoming large distribution gaps between the acquired datasets across different imaging devices and configurations. In this regard, self-training techniques based on pseudo-labeling have been shown to be highly effective for semi-supervised domain adaptation. However, the unreliability o...

Purpose: To assess the clinical resolution capacities of a novel high-resolution optical coherence tomography (High-Res OCT). Methods: Eight healthy volunteers were included in this observational study. Using the SPECTRALIS High-Res OCT device (Heidelberg Engineering, Heidelberg) macular b-scans were taken and compared with b-scans acquired with...

Background: This study aimed to compare the thickness of different macular retinal layers in glaucomatous eyes and healthy controls, and evaluate the diagnostic performance of spectral domain optical coherence tomography (SD-OCT) parameters. Methods: In this cross-sectional comparative study, 48 glaucomatous eyes and 44 healthy controls were inc...

Purpose: A fundamental problem in designing safe machine learning systems is identifying when samples presented to a deployed model differ from those observed at training time. Detecting so-called out-of-distribution (OoD) samples is crucial in safety-critical applications such as robotically guided retinal microsurgery, where distances between th...

Background & aims: Oral lutein (L) and zeaxanthin (Z) supplementation enhances macular pigment optical density (MPOD) and plays a protective role in the development of age-related macular degeneration (AMD). Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a novel in vivo retinal imaging method that has been shown to correlate to classical M...

Purpose: A fundamental problem in designing safe machine learning systems is identifying when samples presented to a deployed model differ from those observed at training time. Detecting so-called out-of-distribution (OoD) samples is crucial in safety-critical applications such as robotically-guided retinal microsurgery, where distances between the...

Annotating new datasets for machine learning tasks is tedious, time-consuming, and costly. For segmentation applications, the burden is particularly high as manual delineations of relevant image content are often extremely expensive or can only be done by experts with domain-specific knowledge. Thanks to developments in transfer learning and traini...

The gut microbiome consists of more than thousand different microbes and their associated genes and microbial metabolites. It influences various host metabolic pathways and is therefore important for homeostasis. In recent years, its influence on health and disease was extensively researched. In case of a microbiome disequilibrium called dysbiosis,...

Background Clustering of microglia around the vasculature has been reported in the retina and the brain after systemic administration of lipopolysaccharides (LPS) in mice. LPS acts via activation of Toll-like receptor 4 (TRL4), which is expressed in several cell types including microglia, monocytes and vascular endothelial cells. The purpose of thi...

Subretinal fibrosis can occur during neovascular age-related macular degeneration (nAMD) and consequently provokes progressing deterioration of AMD patient's vision. Intravitreal anti-vascular endothelial growth factor (VEGF) injections decrease choroidal neovascularization (CNV), however, subretinal fibrosis remains principally unaffected. So far,...

While pathogens of the eye have been studied for a very long time, the existence of resident microbes on the surface of healthy eyes has gained interest only recently. It appears that commensal microbes are a normal feature of the healthy eye, whose role and properties are currently the subject of extensive research. This review provides an overvie...

Purpose To evaluate choriocapillaris (CC) and choroidal vascular changes in patients with posterior uveitis using swept-source (SS) wide-field optical coherence tomography angiography (OCTA). Method Consecutive patients with posterior uveitis were evaluated using 3×3 mm and 12×12 mm OCTA scan patterns and montage images of 5×12×12 mm or 2×15×9 mm,...

Purpose To investigate the influence of the lens status and to describe fundus autofluorescence lifetimes (FLT) in a large cohort of healthy eyes across a wide age range. Materials and methods FLT data were acquired from healthy phakic and pseudophakic eyes using fluorescence lifetime imaging ophthalmoscopy (FLIO). Retinal autofluorescence was exc...

Purpose: To assess whether macular fluorescence lifetimes may serve as a predictor for long-term outcomes in macula-off rhegmatogenous retinal detachment. Methods: A single-center observational study was conducted. Patients with pseudophakic macula-off rhegmatogenous retinal detachment were included and evaluated 1 and 6 months after successful...

This study aims to investigate the effect of a systemic lipopolysaccharide (LPS) stimulus in the course of laser-induced choroidal neovascularization (CNV) in C57BL/6 J mice. A group of CNV-subjected mice received 1 mg/kg LPS via the tail vein immediately after CNV induction. Mouse eyes were monitored in vivo with fluorescein angiography for 2 week...

Introduction: In this retrospective cohort study, we wanted to evaluate the performance and analyze the insights of an artificial intelligence (AI) algorithm in detecting retinal fluid in spectral-domain OCT volume scans from a large cohort of patients with neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME). Metho...

The gut microbiome is a complex ecosystem of microorganisms and their genetic entities colonizing the gastrointestinal tract. When in balanced composition, the gut microbiome is in symbiotic interaction with its host and maintains intestinal homeostasis. It is involved in essential functions such as nutrient metabolism, inhibition of pathogens and...

Aim: To compare choroidal neovascularization (CNV) lesion measurements obtained by in vivo imaging modalities, with whole mount histological preparations stained with isolectin GS-IB4, using a murine laser-induced CNV model. Methods: B6N.Cg-Tg(Csf1r-EGFP)1Hume/J heterozygous adult mice were subjected to laser-induced CNV and were monitored by fl...

Purpose To compare indocyanine green angiography (ICGA) and swept-source wide-field optical coherence tomography angiography (SS-OCTA) for the assessment of patients with posterior uveitis. Method SS-OCTA montage images of 5 x 12 x 12 mm or 2 x 15 x 9 mm, covering ~70–90 degree of the retina of consecutive patients with posterior uveitis were acqu...

Background: Intraocular lymphoma (IOL) presents a real challenge in daily diagnostics. Cyto- and/or histopathology of vitreous body represent the diagnostic cornerstones. Yet, false negative results remain common. Therefore, we analyzed the diagnostic significance of flow cytometry (FC) within the workup algorithm of IOL and compared its sensitivit...

The intestinal microbiome plays a central role in human health and disease. While its composition is relatively stable throughout adulthood, the microbial balance starts to decrease in later life stages. Thus, in order to maintain a good quality of life, including the prevention of age-associated diseases in the elderly, it is important to understa...

The photoreceptor-specific nuclear receptor Nr2e3 is not expressed in Nr2e3rd7/rd7 mice, a mouse model of the recessively inherited retinal degeneration enhanced S-cone sensitivity syndrome (ESCS). We characterized in detail C57BL/6J Nr2e3rd7/rd7 mice in vivo by fundus photography, optical coherence tomography and fluorescein angiography and, post...

Cataract surgery is a sight saving surgery that is performed over 10 million times each year around the world. With such a large demand, the ability to organize surgical wards and operating rooms efficiently is critical to delivery this therapy in routine clinical care. In this context, estimating the remaining surgical duration (RSD) during proced...

Purpose: The purpose of this study was to explore the interplay between the ocular surface microbiome and the tear proteome in humans in order to better understand the pathogenesis of ocular surface-associated diseases. Methods: Twenty eyes from 20 participants were included in the study. The ocular surface microbiome was sequenced by whole-meta...

Purpose: Short foveal fluorescence lifetimes (fFLT) in geographic atrophy are typically found in eyes with foveal sparing (FS) but may also occur in eyes without FS. We investigated whether short fFLT could serve as a functional biomarker for disease progression in geographic atrophy (GA). Methods: Thirty three eyes were followed over the course...

Cataract surgery is a sight saving surgery that is performed over 10 million times each year around the world. With such a large demand, the ability to organize surgical wards and operating rooms efficiently is critical to delivery this therapy in routine clinical care. In this context, estimating the remaining surgical duration (RSD) during proced...

Cataract surgery is a sight saving surgery that is performed over 10 million times each year around the world. With such a large demand, the ability to organize surgical wards and operating rooms efficiently is critical to delivery this therapy in routine clinical care. In this context, estimating the remaining surgical duration (RSD) during proced...

Purpose: To investigate and quantify the influence of imaging artifacts on retinal fluorescence lifetime (FLIO) values and to provide helpful hints and tricks to avoid imaging artifacts and to improve FLIO image acquisition quality. Methods: A systematic analysis of potential parameters influencing FLIO quality and/or fluorescence lifetime value...

Purpose To investigate the dependence of the ciliary body length (CBL) on the axial length (AL) and to draw conclusions on implications regarding safe pars plana access for intravitreal injections and vitreoretinal surgery. Methods A total of 200 individuals (mean age 42 years, SD ± 15.4) were enrolled in the study. Objective refraction and AL wer...

We genetically characterized 22 Swiss patients who had been diagnosed with Stargardt disease after clinical examination. We identified in 11 patients (50%) pathogenic bi-allelic ABCA4 variants, c.1760+2T>C and c.4496T>C being novel. The dominantly inherited pathogenic ELOVL4 c.810C>G p.(Tyr270*) and PRPH2-c.422A>G p.(Tyr141Cys) variants were identi...

Purpose To assess the potential of machine learning to predict low and high treatment demand in real life in patients with nAMD, RVO and DME treated according to a TER. Design Retrospective cohort study. Participants 377 eyes (340 patients) with nAMD, 333 eyes (285 patients) with RVO or DME, treated with anti-VEGF according to a predefined TER pr...

Purpose: To investigate the influence of lens opacifications on fluorescence lifetime imaging ophthalmoscopy (FLIO). Methods: Forty-seven eyes of 45 patients were included. Mean fluorescence lifetimes (Tm) were recorded with a fluorescence lifetime imaging ophthalmoscope in a short spectral channel (SSC) and a long spectral channel (LSC). Retina...

In this paper we analyse the performance of machine learning methods in predicting patient information such as age or sex solely from retinal imaging modalities in a heterogeneous clinical population. Our dataset consists of N = 135,667 fundus images and N = 85,536 volumetric OCT scans. Deep learning models were trained to predict the patient’s age...

Age-related macular degeneration (AMD) is a leading cause of severe vision loss in the aged population. The etiology of AMD is multifactorial including nutritional factors, genetic variants mainly in the complement pathway, environmental risk factors and alterations in the intestinal microbiome. However, it remains unexplored whether there is an in...

Aim To report long-term outcomes on best-corrected visual acuity (BCVA) and treatment intervals with a treat-and-extend (T&E) regimen in patients with neovascular age-related macular degeneration (nAMD). Methods This observational study included treatment-naïve patients with nAMD, treated with aflibercept. A specific T&E protocol without a loading...

To compare drusen volume between Heidelberg Spectral Domain (SD-) and Zeiss Swept-Source (SS) PlexElite Optical Coherence Tomography (OCT) determined by manual and automated segmentation methods. Thirty-two eyes of 24 patients with Age-Related Macular Degeneration (AMD) and drusen maculopathy were included. In the central 1 and 3 mm ETDRS circle dr...