Havla Lab – Neuro\Vision
The Neuro\Vision lab is focused on the evaluation of new biomarkers for the quantification of neuro-axonal degeneration in patients with inflammatory and degenerative diseases of the central nervous system (CNS). From an evolutionary point of view, the retina is part of the brain. Therefore, optical coherence tomography (OCT) is particularly suitable for the quantification and analysis of measurable inflammation and neurodegeneration of the CNS. The overall goal of the @NeuroVisionLab is to establish OCT as a marker of diagnosis, disease activity and disease progression in neuroimmunological and neurodegenerative diseases. This goal can only be achieved with large amounts of data. Therefore we as a group are particularly committed to the build-up of structured, homogenized and integrated data sets for use in clinical research.
From an evolutionary point of view, the retina is part of the brain. Together with EFFIGOS AG we have created this 3D animation to show you what we see when we look deep into the eyes of our patients.
© Neuro\Vision - Havla Lab
We use a neurovisual test battery to visualize and quantify retinal neuro-axonal inflammation and degeneration. As the core of the test battery we use the retinal optical coherence tomography (OCT). OCT uses light of short coherence length to create cross-sectional 3D-images of the retina with high axial resolution. With the current standard of spectral domain (SD) OCT technology, a fixed reference mirror and simultaneous analysis of all echoes of the various retinal layers can significantly reduce the rate of motion artifacts, improve reproducibility and speed up the procedure. In order to use this as a biomarker for the prediction of the future course of the disease, we evaluate the technique of OCT together and against the diagnostic standard such as magnetic resonance imaging of the brain and spinal cord, electrophysiological examinations of the visual pathway (VEP) and complementary neuroophthalmological examinations.
Some of our current projects
Mechanisms and monitoring of antibody induced primary retinopathy in patients with multiple sclerosis and neuromyelitis optica spectrum disorders (NMOSD)
In collaboration with the Institute of Physiological Genomics (Prof. Grosche) we aim to test the hypotheses whether a relapse-independent retinal neuro-axonal degeneration is detectable in both a RRMS and an AQP4-abs-positive NMOSD cohort and may correspond to a primary retinopathy.
Optical coherence tomography (OCT) for the characterization of retinal axonal and neuronal degeneration of clinically asymptomatic twins in the identical multiple sclerosis (MS) twin cohort - Friedrich-Baur Foundation (66/17)
This is a pilot study to characterize neuronal and axonal retinal degeneration in identical twins in whom one twin has MS. In this subproject of the national twin cohort we want to investigate if and to what extent asymptomatic, non-MS-affected twins show axonal or neuronal retinal degeneration.
Multimodal Differential Diagnosis of Acute Optic Neuritis: A Pilot Study in Multiple Sclerosis, Neuromyelitis Optica Spectrum and MOG-IgG Associated Diseases - Friedrich-Baur Foundation (73/20)
Here we will investigate whether digital perimetry can increase the sensitivity and specificity of the visual test battery. This will help to define further predictors of diagnosis and disease progression.
In the figure you see a 3D visualization of the structural organization of the retina (EFFIGOS; NeuroVisionLab).
Optical coherence tomography (OCT) in neuroimmunology: a teaching project to establish the method in everyday neurological practice – LMU (DCP)
In cooperation with the 3D visualization expert EFFIGOS, we plan to create several 3D animations to explain the OCT method, its possibilities and its practical application in daily neurological practice.
These explanatory videos should meet educational requirements and be used especially as an introduction to scientific results in the field of OCT.
Environmental and digital behavioral markers in progressive multiple sclerosis (SPASS project) – Merck Neuro Academy Award 2019 (MDG 0110011330)
This is a prospective cohort study of patients with progressive MS. Together with an industry partner we use motion data from smartphones and fitness trackers to assess disability progression in PMS. In a first project, the usability in clinical everyday life will be tested.
Liu J, Mori M, Zimmermann H, Brandt A, Havla J, Tanaka S, Sugimoto K, Oji S, Uzawa A, Asseyer S, Cooper G, Jarius S, Bellmann-Strobl J, Ruprecht K, Siebert N, Masuda H, Uchida T, Ohtani R, Nomura K, Meinl E, Kuempfel T, Paul F, Kuwabara S. Anti-MOG antibody-associated disorders: differences in clinical profiles and prognosis in Japan and Germany. J Neurol Neurosurg Psychiatry. 2020 Nov 20:jnnp-2020-324422.
Specovius S, Zimmermann HG, Oertel FC, Chien C, Bereuter C, Cook LJ, Lana Peixoto MA, Fontenelle MA, Kim HJ, Hyun JW, Jung SK, Palace J, Roca-Fernandez A, Diaz AR, Leite MI, Sharma SM, Ashtari F, Kafieh R, Dehghani A, Pourazizi M, Pandit L, Dcunha A, Aktas O, Ringelstein M, Albrecht P, May E, Tongco C, Leocani L, Pisa M, Radaelli M, Martinez-Lapiscina EH, Stiebel-Kalish H, Hellmann M, Lotan I, Siritho S, de Seze J, Senger T, Havla J, Marignier R, Tilikete C, Cobo Calvo A, Bichuetti DB, Tavares IM, Asgari N, Soelberg K, Altintas A, Yildirim R, Tanriverdi U, Jacob A, Huda S, Rimler Z, Reid A, Mao-Draayer Y, de Castillo IS, Yeaman MR, Smith TJ, Brandt AU, Paul F; GJCF International Clinical Consortium for NMOSD. Cohort profile: a collaborative multicentre study of retinal optical coherence tomography in 539 patients with neuromyelitis optica spectrum disorders (CROCTINO). BMJ Open. 2020 Oct 29;10(10):e035397.
Völk S, Unterrainer M, Albert NL, Havla J, Gerdes LA, Schumacher M, Brendel M, Kaiser L, Adorjan K, Rupprecht R, Bartenstein P, Kümpfel T, Danek A. TSPO PET With 18F-GE-180 to Differentiate Variants of Multiple Sclerosis: Relapsing-Remitting Multiple Sclerosis, Tumefactive Demyelination, and Baló's Concentric Sclerosis. Clin Nucl Med. 2020 Oct;45(10):e447-e448.
Havla J, Moser M, Sztatecsny C, Lotz-Havla AS, Maier EM, Hizli B, Schinner R, Kümpfel T, Strupp M, Bremova-Ertl T, Schneider SA. Retinal axonal degeneration in Niemann-Pick type C disease. J Neurol. 2020 Jul;267(7):2070-2082.
Aly L, Havla J, Lepennetier G, Andlauer TFM, Sie C, Strauß EM, Hoshi MM, Kümpfel T, Hiltensperger M, Mitsdoerffer M, Mühlau M, Zimmer C, Hemmer B, Korn T, Knier B. Inner retinal layer thinning in radiologically isolated syndrome predicts conversion to multiple sclerosis. Eur J Neurol. 2020 Jun 26.
Mulazzani E, Wagner D, Havla J, Schlüter M, Meinl I, Gerdes LA, Kümpfel T. Neurological phenotypes in patients with NLRP3-, MEFV-, and TNFRSF1A low-penetrance variants. J Neuroinflammation. 2020 Jun 20;17(1):196. doi: 10.1186/s12974-020-01867-5.
Motamedi S, Oertel FC, Yadav SK, Kadas EM, Weise M, Havla J, Ringelstein M, Aktas O, Albrecht P, Ruprecht K, Bellmann-Strobl J, Zimmermann HG, Paul F, Brandt AU. Altered fovea in AQP4-IgG-seropositive neuromyelitis optica spectrum disorders. Neurol Neuroimmunol Neuroinflamm. 2020 Jun 23;7(5):e805.
Abdelhak A, Huss A, Stahmann A, Senel M, Krumbholz M, Kowarik MC, Havla J, Kümpfel T, Kleiter I, Wüstinger I, Zettl UK, Schwartz M, Roesler R, Friede T, Ludolph AC, Ziemann U, Tumani H. Explorative study of emerging blood biomarkers in progressive multiple sclerosis (EmBioProMS): Design of a prospective observational multicentre pilot study. Contemp Clin Trials Commun. 2020 May 19;18:100574.
Thaler FS, Bangol B, Biljecki M, Havla J, Schumacher AM, Kümpfel T. Possible link of genetic variants to autoimmunity in GAD-antibody-associated neurological disorders. J Neurol Sci. 2020 Jun 15;413:116860.
Kleiter I, Ayzenberg I, Havla J, Lukas C, Penner IK, Stadelmann C, Linker RA. The transitional phase of multiple sclerosis: Characterization and conceptual framework. Mult Scler Relat Disord. 2020 May 29;44:102242. doi: 10.1016/j.msard.2020.102242.
Dietrich M, Koska V, Hecker C, Göttle P, Hilla AM, Heskamp A, Lepka K, Issberner A, Hallenberger A, Baksmeier C, Steckel J, Balk L, Knier B, Korn T, Havla J, Martínez-Lapiscina EH, Solà-Valls N, Manogaran P, Olbert ED, Schippling S, Cruz-Herranz A, Yiu H, Button J, Caldito NG, von Gall C, Mausberg AK, Stettner M, Zimmermann HG, Paul F, Brandt AU, Küry P, Goebels N, Aktas O, Berndt C, Saidha S, Green AJ, Calabresi PA, Fischer D, Hartung HP, Albrecht P. Protective effects of 4-aminopyridine in experimental optic neuritis and multiple sclerosis. Brain. 2020 Apr 1;143(4):1127-1142.
Ringelstein M, Harmel J, Zimmermann H, Brandt AU, Paul F, Haarmann A, Buttmann M, Hümmert MW, Trebst C, Schroeder C, Ayzenberg I, Kleiter I, Hellwig K, Havla J, Kümpfel T, Jarius S, Wildemann B, Rommer P, Weber MS, Pellkofer H, Röpke L, Geis C, Retzlaff N, Zettl U, Deppe M, Klotz L, Young K, Stellmann JP, Kaste M, Kermer P, Marouf W, Lauda F, Tumani H, Graf J, Klistorner A, Hartung HP, Aktas O, Albrecht P; Neuromyelitis Optica Study Group (NEMOS). Longitudinal optic neuritis-unrelated visual evoked potential changes in NMO spectrum disorders. Neurology. 2020 Jan 28;94(4):e407-e418.
Balk LJ, Coric D, Knier B, Zimmermann HG, Behbehani R, Alroughani R, Martinez-Lapiscina EH, Brandt AU, Sánchez-Dalmau B, Vidal-Jordana A, Albrecht P, Koska V, Havla J, Pisa M, Nolan RC, Leocani L, Paul F, Aktas O, Montalban X, Balcer LJ, Villoslada P, Outteryck O, Korn T, Petzold A; IMSVISUAL consortium. Retinal inner nuclear layer volume reflects inflammatory disease activity in multiple sclerosis; a longitudinal OCT study. Mult Scler J Exp Transl Clin. 2019 Sep 5;5(3):2055217319871582.
Nolan-Kenney RC, Liu M, Akhand O, Calabresi PA, Paul F, Petzold A, Balk L, Brandt AU, Martínez-Lapiscina EH, Saidha S, Villoslada P, Al-Hassan AA, Behbehani R, Frohman EM, Frohman T, Havla J, Hemmer B, Jiang H, Knier B, Korn T, Leocani L, Papadopoulou A, Pisa M, Zimmermann H, Galetta SL, Balcer LJ; International Multiple Sclerosis Visual System Consortium. Optimal intereye difference thresholds by optical coherence tomography in multiple sclerosis: An international study. Ann Neurol. 2019 May;85(5):618-629.
Oertel FC, Outteryck O, Knier B, Zimmermann H, Borisow N, Bellmann-Strobl J, Blaschek A, Jarius S, Reindl M, Ruprecht K, Meinl E, Hohlfeld R, Paul F, Brandt AU, Kümpfel T, Havla J. Optical coherence tomography in myelin-oligodendrocyte-glycoprotein antibody-seropositive patients: a longitudinal study. J Neuroinflammation. 2019 Jul 25;16(1):154.
Graetz C, Gröger A, Luessi F, Salmen A, Zöller D, Schultz J, Siller N, Fleischer V, Bellenberg B, Berthele A, Biberacher V, Havla J, Hecker M, Hohlfeld R, Infante-Duarte C, Kirschke JS, Kümpfel T, Linker R, Paul F, Pfeuffer S, Sämann P, Toenges G, Weber F, Zettl UK, Jahn-Eimermacher A, Antony G, Groppa S, Wiendl H, Hemmer B, Mühlau M, Lukas C, Gold R, Lill CM, Zipp F. Association of smoking but not HLA-DRB1*15:01, APOE or body mass index with brain atrophy in early multiple sclerosis. Mult Scler. 2019 Apr;25(5):661-668.
Klotz L, Havla J, Schwab N, Hohlfeld R, Barnett M, Reddel S, Wiendl H. Risks and risk management in modern multiple sclerosis immunotherapeutic treatment. Ther Adv Neurol Disord. 2019 Apr 1;12:1756286419836571.
Förster M, Küry P, Aktas O, Warnke C, Havla J, Hohlfeld R, Mares J, Hartung HP, Kremer D. Managing Risks with Immune Therapies in Multiple Sclerosis. Drug Saf. 2019 May;42(5):633-647.
Oertel FC*, Havla J*, Roca-Fernández A, Lizak N, Zimmermann H, Motamedi S, Borisow N, White OB, Bellmann-Strobl J, Albrecht P, Ruprecht K, Jarius S, Palace J, Leite MI, Kuempfel T, Paul F, Brandt AU. Retinal ganglion cell loss in neuromyelitis optica: a longitudinal study. J Neurol Neurosurg Psychiatry. 2018 Dec;89(12):1259-1265. (*joint first-authors)
Kleiter I, Gahlen A, Borisow N, Fischer K, Wernecke KD, Hellwig K, Pache F, Ruprecht K, Havla J, Kümpfel T, Aktas O, Hartung HP, Ringelstein M, Geis C, Kleinschnitz C, Berthele A, Hemmer B, Angstwurm K, Stellmann JP, Schuster S, Stangel M, Lauda F, Tumani H, Mayer C, Krumbholz M, Zeltner L, Ziemann U, Linker R, Schwab M, Marziniak M, Then Bergh F, Hofstadt-van Oy U, Neuhaus O, Zettl UK, Faiss J, Wildemann B, Paul F, Jarius S, Trebst C; NEMOS (Neuromyelitis Optica Study Group). Apheresis therapies for NMOSD attacks: A retrospective study of 207 therapeutic interventions. Neurol Neuroimmunol Neuroinflamm. 2018 Sep 26;5(6):e504.
Unterrainer M, Mahler C, Vomacka L, Lindner S, Havla J, Brendel M, Böning G, Ertl-Wagner B, Kümpfel T, Milenkovic VM, Rupprecht R, Kerschensteiner M, Bartenstein P, Albert NL. TSPO PET with [18F]GE-180 sensitively detects focal neuroinflammation in patients with relapsing-remitting multiple sclerosis. Eur J Nucl Med Mol Imaging. 2018 Jul;45(8):1423-1431.
Brendel M, Schönecker S, Höglinger G, Lindner S, Havla J, Blautzik J, Sauerbeck J, Rohrer G, Zach C, Vettermann F, Lang AE, Golbe L, Nübling G, Bartenstein P, Furukawa K, Ishiki A, Bötzel K, Danek A, Okamura N, Levin J, Rominger A. [18F]-THK5351 PET Correlates with Topology and Symptom Severity in Progressive Supranuclear Palsy. Front Aging Neurosci. 2018 Jan 17;9:440.
Trillsch F, Eichhorn P, Oliveira-Ferrer L, Kuempfel T, Burges A, Mahner S, Havla J. No need for NMDA receptor antibody screening in neurologically asymptomatic patients with ovarian teratomas. J Neurol. 2018 Feb;265(2):431-432.
Meinl I, Havla J, Hohlfeld R, Kümpfel T. Recurrence of disease activity during pregnancy after cessation of fingolimod in multiple sclerosis. Mult Scler. 2018 Jun;24(7):991-994.
Stellmann JP, Krumbholz M, Friede T, Gahlen A, Borisow N, Fischer K, Hellwig K, Pache F, Ruprecht K, Havla J, Kümpfel T, Aktas O, Hartung HP, Ringelstein M, Geis C, Kleinschnitz C, Berthele A, Hemmer B, Angstwurm K, Young KL, Schuster S, Stangel M, Lauda F, Tumani H, Mayer C, Zeltner L, Ziemann U, Linker RA, Schwab M, Marziniak M, Then Bergh F, Hofstadt-van Oy U, Neuhaus O, Zettl U, Faiss J, Wildemann B, Paul F, Jarius S, Trebst C, Kleiter I; NEMOS (Neuromyelitis Optica Study Group). Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response. J Neurol Neurosurg Psychiatry. 2017 Aug;88(8):639-647.
Hohlfeld R, Havla J, Kümpfel T. Patient-to-patient transmission of natalizumab-associated PML? Mult Scler. 2017 Oct;23(11):1564-1565.
Havla J, Kümpfel T, Schinner R, Spadaro M, Schuh E, Meinl E, Hohlfeld R, Outteryck O. Myelin-oligodendrocyte-glycoprotein (MOG) autoantibodies as potential markers of severe optic neuritis and subclinical retinal axonal degeneration. J Neurol. 2017 Jan;264(1):139-151.
Joachim Havla, PI
In my scientific projects we pursue to create Neuro\Vision in my @NeuroVisionLab. In addition I am a neurologist and am dedicated to the care of neuroimmunological patients. To better link clinical routine and scientific work I have been involved in the Medical Informatics Initiative (MII; https://www.medizininformatik-initiative.de/en/start) within the DIFUTURE consortium since 2017. As the person responsible for the use case (UC) multiple sclerosis at the LMU Hospital, we are shaping the future university medicine treating patients with MS by optimizing internal clinical processes, making the best possible use of our limited resources, make routine clinical data useful for research, and increasing the quality of our internal processes.
Luise Böhm, Medical Student
After I graduated High School in Hesse in 2016 I moved to Munich to study medicine. Since 2017 I’ve been working for the Institute of Clinical Neuroimmunology under Dr. Havla. My work concentrates on OCT examinations and creating a data bank for our OCT data and analyses.
In October 2019 I started my doctoral thesis under Dr. Havla. My dissertation revolves around investigating the OCT as a liable predictor in a cohort of progressive multiple sclerosis patients.
Tara Christmann, Medical Student
I started studying Medicine in Munich in October 2018 and have been performing OCT exams since January 2020. Additionally, I manage and maintain the corresponding database.
Christopher Hemingway, Medical Student
I’m a final-year medical student from Munich. At the Institut for Clinical Neuroimmunology I focus on CSF-Biomarkers of synapse damage in progressive MS. To this end we pursued a translational approach - from mouse model to human samples. At the outpatient-clinic I also perform Optical Coherence Tomography and work on data-integration to further broaden the availability of (anonymous) patient information. After my medical studies I’m going to enroll in a residency in Neurology and continue my scientific efforts.
Alice Pasquini, Biology Student
I was born in Santiago de Chile and moved to Munich in my first years of life. I am a second-year undergraduate biology student at the Ludwig Maximilian University of Munich. Previously, I was a law student at the Humboldt-University in Berlin, but I decided that life science is so much more fascinating than law textbooks. I am particularly interested in the field of neuroimmunology, and I am looking forward to becoming an expert in multiple sclerosis. I have developed several skills through my work at the Institute of Clinical Neuroimmunology. Not only have I acquired scientific knowledge on data science, I have also learned to interact with diverse and multidisciplinary teams. In my free time, I like to spend time with my friends, reading books, and taking care of my dog.
Leon Nedelcev, Student Bachelor of Science in Bioprocess Engineering (TUM)
I am currently attending classes at the Technical University of Munich for my B.Sc. degree in pharmaceutical bioprocess engineering. I joined the Institute of Clinical Neuroimmunolgy in July 2020, because I am very interested in neurology as well as immunobiology and so far it has been very exciting, interesting and instructive experience. For my M.Sc. degree I am looking forward to studying neurology, if everything goes as planned. When I am not studying for my exams or working at the institute, I like to go cycling and hiking in the Bavarian mountains and its countryside. Whenever I get the chance I try to visit my family which is scattered around the globe. This is a great way to keep in touch, as well as travel around the world.
PD. Dr. med. Joachim Havla
2002 – 2008 Medical studies at the Ludwig-Maximilians University Munich, MECUM Munich, Clinical and research fellowships in Galveston (USA), Zürich (Switzerland), Bern (Switzerland) and New York (USA).
Nov 2008 Approbation, approval as a physician by the Bavarian State Medical Association
Jan 2017 Medical specialist neurology
May 2018 Consultant in neurology
Jan 2020 Habilitation (Priv.-Doz.)
2009 – today Physician and research associate, Institute of Clinical Neuroimmunology (Prof. M. Kerschensteiner) in association with the Department of Neurology (Prof. M. Dieterich) of the LMU Hospital Munich
GCP-certified study physician in numerous Phase II and Phase III therapy studies in multiple sclerosis, CO-Principal Investigator (PI) in therapy studies in multiple sclerosis and Niemann-Pick type C disease and Tay-Sachs disease
Active participation in national and international neurological and neuroimmunological congresses
Active participation in teaching at the Medical Faculty of the LMU Munich
Active memberships: Lindau-Nobel, German Society of Neurology (DGN), IMSVISUAL, NEMOS, GENERATE, EUPON, ICC of the Guthy Jackson Foundation, Cochrane Membership
2018 Staff member at the Center for Medical Data Integration and Analysis (MeDICLMU –Medical Data Integration Center)
PD Dr. B. Knier, Neurology, TUM, Munich
Prof. Dr. P. Albrecht, Neurology, University Hospital Düsseldorf, Düsseldorf
Dr. F. Oertel, Neurology, University of California, San Francisco
Dr. O. Outteryck, Neurology, Université de Lille, Lille
Prof. Dr. F. Paul, Neurology, Charite, Berlin
PD Dr. I. Ayzenberg, Neurology, Ruhr-University, Bochum
Prof. Dr. E. Maier/Dr. A. Lotz-Havla, Dr. von Hauner Children's Hospital, LMU Hospital, Munich