Central project 1 Eye Imaging

Cologne Experimental Eye Imaging Center (CEE-IC)


In the first funding period, a multimodal experimental imaging facility for mice, the Cologne Experimental Eye Imaging Center (CEE-IC), was established. In combination with specific acquisition and processing algorithms, which were developed for and adapted to the needs of the individual projects, the monitoring and classification of inflammatory ocular diseases have been made possible. In experimental studies using models for e.g. corneal inflammation, corneal edema and retinal degeneration, quantitative analyses including the three-dimensional quantification of pathological blood vessels in the same animals over time were carried out. In the planned second funding period, the facility will be extended with the aim of establishing specific optical coherence tomography (OCT) imaging on a cellular level. For this purpose, a microscopic OCT (mOCT) system will be installed, which allows for non-invasive in vivo investigation of murine eyes in three dimensions with a resolution down to 1 μm. Furthermore, the use of specifically addressed nanoparticles for quantification of ocular surface inflammation will be explored. The potential for the clinical translation of the innovative hardware and software approaches will be evaluated. Altogether, the new possibilities will bring advantages for all involved projects. For example, non-invasive imaging of clinically invisible lymphatic vessels including the visualization of intraluminal cells will be possible in the same animals over time. Using mOCT will make structural and angiographic OCT imaging more competitive to invasive histology and consequently has the potential to significantly reduce the number of animals in preclinical research.

The central aim of the proposed research consortium is the identification and analysis of inflammation-associated mechanisms of ocular diseases. As all projects investigate cellular processes of inflammation in particular non- or minimally-invasive intravital imaging techniques are necessary, which in real time can capture and follow up the induced alterations both in in vitro and in vivo experiments. The CEE-IC will provide an experimental imaging facility equipped with different OCT and fluorescence angiography devices together with stereomicroscopy that will enable state-of-the-art examination of the target structures without tampering the results by tissue probing or phototoxic effects. Furthermore the C1-project will provide well-established advanced vessel and particle analysis methods and will develop further standardized, highly qualitative data analysis methods in close cooperation with the individual projects. Thereby highly reliable and innovative data sets will be generated.

Selected Key Publications of Central Project C1

Horstmann J, Schulz-Hildebrandt H, Bock F, Siebelmann S, Lankenau E, Huttmann G, Steven P, Cursiefen C (2017) Label-Free In Vivo Imaging of Corneal Lymphatic Vessels Using Microscopic Optical Coherence Tomography. Investigative ophthalmology & visual science 58: 5880-5886

Horstmann J, Siebelmann S, Schulz-Hildebrandt H, Glasunow I, Schadschneider A, Huttmann G (2017) [Understanding OCT – Part 1: Basic Knowledge]. Klinische Monatsblatter fur Augenheilkunde 234: 131-143

Horstmann J, Siebelmann S, Schulz-Hildebrandt H, Glasunow I, Schadschneider A, Huttmann G (2017) [Understanding OCT – Part 2: State of the Practice]. Klinische Monatsblatter fur Augenheilkunde 234: 233-247

Hos D, Bukowiecki A, Horstmann J, Bock F, Bucher F, Heindl LM, Siebelmann S, Steven P, Dana R, Eming SA, Cursiefen C (2017) Transient Ingrowth of Lymphatic Vessels into the Physiologically Avascular Cornea Regulates Corneal Edema and Transparency. Scientific reports 7: 7227

Le VNH, Hou Y, Horstmann J, Bock F, Cursiefen C (2017) Novel Method to Detect Corneal Lymphatic Vessels In Vivo by Intrastromal Injection of Fluorescein. Cornea

Osae AE, Gehlsen U, Horstmann J, Siebelmann S, Stern ME, Kumah DB, Steven P (2017) Epidemiology of dry eye disease in Africa: The sparse information, gaps and opportunities. The ocular surface 15: 159-168

Horstmann J, Spahr H, Buj C, Munter M, Brinkmann R (2015) Full-field speckle interferometry for non-contact photoacoustic tomography. Physics in medicine and biology 60: 4045-58

Horstmann J, Brinkmann R (2014) Optical full-field holographic detection system for non-contact photoacoustic tomography. Proceedings of SPIE – The International Society for Optical Engineering 8943

Horstmann J, Brinkmann R (2013) Non-contact photoacoustic tomography using holographic full field detection. Proceedings of SPIE – The International Society for Optical Engineering 8800

Frank J, Matrisch J, Horstmann J, Altmeyer S, Wernicke G (2011) Refractive index determination of transparent samples by noniterative phase retrieval. Applied optics 50: 427-33

More Publications of Central Project C1

Cursiefen C, Bock F, Clahsen T, Regenfuss B, Reis A, Steven P, Heindl LM, Bosch JJ, Hos D, Eming S, Grajewski R, Heiligenhaus A, Fauser S, Austin J, Langmann T. [New Therapeutic Approaches in Inflammatory Diseases of the Eye – Targeting Lymphangiogenesis and Cellular Immunity: Research Unit FOR 2240 Presents Itself]. Klin Monbl Augenheilkd. 2017 May;234(5):679-685.

Steven P, Braun T, Krösser S, Gehlsen U. [Influence of Aging on Severity and Anti-Inflammatory Treatment of Experimental Dry Eye Disease]. Klin Monbl Augenheilkd. 2017 May;234(5):662-669.

Gehlsen U, Braun T, Notara M, Krösser S, Steven P. A semifluorinated alkane (F4H5) as novel carrier for cyclosporine A: a promising therapeutic and prophylactic option for topical treatment of dry eye. Graefes Arch Clin Exp Ophthalmol. 2017 Apr;255(4):767-775.

Siebelmann S, Gehlsen U, Le Blanc C, Stanzel TP, Cursiefen C, Steven P. Detection of graft detachments immediately following Descemet membrane endothelial keratoplasty (DMEK) comparing time domain and spectral domain OCT. Graefes Arch Clin Exp Ophthalmol. 2016 Dec;254(12):2431-2437.

Siebelmann S, Bachmann B, Lappas A, Dietlein T, Hermann M, Roters S, Cursiefen C, Steven P. [Intraoperative optical coherence tomography in corneal and glaucoma surgical procedures]. Ophthalmologe. 2016 Aug;113(8):646-50.

Siebelmann S, Bachmann B, Lappas A, Dietlein T, Steven P, Cursiefen C.[Intraoperative optical coherence tomography for examination of newborns and infants under general anesthesia]. Ophthalmologe. 2016 Aug;113(8):651-5.

Siebelmann S, Steven P, Cursiefen C. [Intraoperative Optical Coherence Tomography In Deep Anterior Lamellar Keratoplasty]. Klin Monbl Augenheilkd. 2016 Jun;233(6):717-21.

Tahmaz V, Gehlsen U, Sauerbier L, Holtick U, Engel L, Radojska S, Petrescu-Jipa VM, Scheid C, Hallek M, Gathof B, Cursiefen C, Steven P. Treatment of severe chronic ocular graft-versus-host disease using 100% autologous serum eye drops from a sealed manufacturing system: a retrospective cohort study. Br J Ophthalmol. 2016 Jun 6. pii: bjophthalmol-2015-307666.

Siebelmann S, Steven P, Cursiefen C (2015) Intraoperative Optical Coherence Tomography: Ocular Surgery on a Higher Level or Just Nice Pictures? JAMA Ophthalmol.

Engel LA, Wittig S, Bock F, Sauerbier L, Scheid C, Holtick U, Chemnitz JM, Hallek M, Cursiefen C, Steven P (2015) Meibography and meibomian gland measurements in ocular graft-versus-host disease. Bone Marrow Transplant.50(7):961-7.

Gehlsen U, Szaszák M, Gebert A, Koop N, Hüttmann G, Steven P (2015) Non-Invasive Multi-Dimensional Two-Photon Microscopy enables optical fingerprinting (TPOF) of immune cells. J Biophotonics. 8(6):466-79.

Siebelmann S, Gehlsen U, Hüttmann G, Koop N, Bölke T, Gebert A, Stern ME, Niederkorn JY, Steven P (2013) Development, alteration and real time dynamics of conjunctiva-associated lymphoid tissue. PLoS One. 8:e82355.

Steven P, Le Blanc C, Velten K, Lankenau E, Krug M, Oelckers S, Heindl LM, Gehlsen U, Hüttmann G, Cursiefen C (2013) Optimizing descemet membrane endothelial keratoplasty using intraoperative optical coherence tomography. JAMA Ophthalmol. 131:1135-42.

Gehlsen U, Oetke A, Szaszák M, Koop N, Paulsen F, Gebert A, Huettmann G, Steven P (2012) Two-photon fluorescence lifetime imaging monitors metabolic changes during wound healing of corneal epithelial cells in vitro. Graefes Arch Clin Exp Ophthalmol. 250:1293-302.

Steven P, Bock F, Hüttmann G, Cursiefen C (2011) Intravital two-photon microscopy of immune cell dynamics in corneal lymphatic vessels. PLoS One. 6:e26253.

Steven P, Rupp J, Hüttmann G, Koop N, Lensing C, Laqua H, Gebert A (2008) Experimental induction and three-dimensional two-photon imaging of conjunctiva-associated lymphoid tissue. Invest Ophthalmol Vis Sci. 49:1512-7.