Pupil research

The pupil regulates the amount of light entering the retina and is controlled exclusively by the autonomic nervous system. Examinations and recordings of pupil behavior provide objective information not only about the functions of the retina and visual pathway, but also about the level of central nervous system activation, emotion, and cognition.

The aim of the working group is to gain fundamental scientific knowledge about pupil function and, building on this, to develop clinical biomarkers for characterizing and distinguishing between different neuro-retinal diseases, thereby establishing pupillography in routine clinical practice in the long term.

Contact

management

frontend.sr-only_#{element.icon}: Prof. Dr. Carina Kelbsch


E-mail address: carina.kelbsch@med.uni-tuebingen.de



In recent years, a large standard database of pupil responses to specific stimulation protocols for selective stimulation of cones or rods in the human retina has been developed. This uses chromatic pupil campimetry (CPC), which was developed by the working group and offers the additional advantage of enabling reliable local functional assessment at different points in the visual field.

The working group is interested in different methodological approaches and investigates a variety of clinical pictures. The focus is on curiosity to explore the pupil as a window into neurophysiological processes and as an objective functional parameter – both in international collaboration and on an interdisciplinary basis, especially at the interfaces with neurology.

Initiated at the International Pupil Colloquium 2017, an international team of pupil researchers was assembled under the leadership of Tübingen, from which the now established standards in pupillography* emerged .

Research projects / Studies


To assess the local function of theretina and theneural network, pupil responses to light stimuli of different wavelengths and intensities are measured at different locations in the visual field. Measurements from patients with retinal or optic nerve diseases are compared with those from healthy individuals.

Black and white drawing of an eye

Current Studies

The aim of this project is to investigate how the reduced pupillary light reflex in the blind hemifield of patients with hemianopia depends on the light intensity of the stimulus. The study will also examine whether retrograde ganglion cell degeneration is present in this group and whether it correlates with the pupillary light reflex, the age of the lesion, or stroke treatment. Furthermore, the study aims to investigate the extent to which visual field defects regress following ischemia and how this correlates with the aforementioned factors. Based on these findings, a reliable CPC protocol for patients with hemianopia due to posterior ischemia will be developed. To this end, patients with hemianopia will be examined initially, as well as 1, 3, 6, 12, and 18 months after the stroke event.

Preliminary work:

The goal is to analyze pupillary escape in patient groups with pathologies of the inner retinal layers or disruptions in the synaptic connections between the inner and outer retina, with the long-term aim of potentially establishing escape as an additional diagnostic pupillographic marker. To this end, patients with X-linked retinoschisis (XLRS) with central involvement, patients with congenital stationary night blindness (CSNB), and patients with retinal arterial occlusion (ZAV/AAV) will be examined.

Preliminary work:

The aim is to distinguish between different types of acute optic neuropathies using pupillography, as well as to differentiate them from healthy individuals, and to investigate “pupillary escape” as a potential marker of dysfunction in the inner retinal layers. To this end, patients with acute optic neuritis (NNO), symptom onset < 2 weeks; patients with acute anterior ischemic optic neuropathy (AION), symptom onset < 2 weeks; and patients with Leber’s hereditary optic neuropathy (LHON) (molecularly confirmed diagnosis) will be examined.

Preliminary work:

The PupilPanda project emerged from a series of studies that investigated how perception-based stimuli can be used to study visual function at various physiological levels. The work is based on investigations of the Panda illusion, a visual stimulus that relies on the principle of pulse-width modulation. We were able to demonstrate that the illusion is decoded by the visual system through spatial low-pass filters. This explains why reduced visual resolution can improve the visibility of the embedded panda (Straßer et al., Scientific Reports, 2020). This perceptual property established a direct relationship between the detectability of the illusion and spatial frequency.

Building on this concept, the illusion was initially evaluated as a tool for determining visual acuity. It was found that the detection thresholds systematically vary with spatial frequency and blur. This enables the estimation of functional visual acuity using a perception-based stimulus instead of conventional optotypes (Kelbsch et al., British Journal of Ophthalmology, 2023). These results established the panda illusion as a controllable probe of visual resolution.

In the next step, the paradigm was extended from psychophysics to objective electrophysiology. In the study “Seeing the Panda,” the illusion was embedded in a visual oddball design to elicit both visual evoked potentials (VEP) and P300 responses (Nikolaidou & Strasser, ISCEV 2025 Conference). This approach enabled the simultaneous investigation of early sensory processing and higher-level cognitive evaluation of the stimulus. The results showed that the amplitudes of VEP and P300 covary with optical blur and spatial frequency. This supports the assumption that refractive and cognitive aspects of visual acuity can be captured within a unified neural framework. Following the demonstration of robust cortical effects, the paradigm was extended to pupillography. In the study “Your pupil knows better: Functional Pupillography with the Panda Illusion” (Nikolaidou, Schedel & Strasser, ARVO 2026 Conference), the illusion reliably elicited event-related pupillary responses. Notably, the pupil dilation patterns differed from the reactions recorded via button press. This suggests that autonomic responses follow stimulus-driven perceptual processing even when conscious perception is inconsistent. These results suggest that pupil dynamics offer an additional, objective window into visual processing.

Previous work:

  • Straßer, T., Kurtenbach, A., Langrová, H. et al. The perception threshold of the panda illusion, a particular form of 2D pulse-width-modulated halftone, correlates with visual acuity. Sci Rep 10, 13095 (2020). https://doi.org/10.1038/s41598-020-69952-6
  • Kelbsch C, Spieth B, Zrenner E, et al. PandAcuity in pediatrics: a novel clinical measure of visual function based on the panda illusion. British Journal of Ophthalmology 2023;107:582-586.


Method development

Method development of the Tübingen Pupil Research Group

This long-term recording (11 minutes) of pupil diameter under standardized conditions, combined with quantitative analysis, utilizes the direct correlation between spontaneous pupil oscillations in darkness and the sympathetic locus coeruleus—which regulates wakefulness—to provide an objective measure of central nervous system activation. The PST was developed, patented, and brought to market by Prof. Barbara Wilhelm and Prof. Helmut Wilhelm in the 1990s and introduced into routine sleep medicine and sleep research. We continuously conduct scientific studies using the PST.

Publication:

  • by Lukowicz H, Poets CF, Peters T, Wilhelm B, Schlarb A, Urschitz MS. Validity of the Pupillographic Sleepiness Test for the diagnosis of daytime sleepiness in children and adolescents and its relationship to sleepiness-associated outcomes. Sleep Med. 2021 Jul;83:145-150. doi: 10.1016/j.sleep.2021.04.030. Epub 2021 Apr 28. PMID: 34015717.

Light stimuli are presented at various locations within the visual field on a screen, and pupil diameter is continuously recorded using an infrared video camera. By selecting the size, intensity, and color of the light stimuli, as well as different states of retinal adaptation, various retinal cells can be activated. This allows conclusions to be drawn about the local function of the retina’s cones and rods, which is also utilized in the evaluation of novel therapeutic approaches. Both the hardware and software of the campimetry prototype were developed by our research group. The device is being used in several scientific studies at our clinic.

Publications:

For further publications, see Chromatic Pupillary Campimetry (CPC) in Hereditary Retinal Degenerations and Neuro-Ophthalmological Diseases

Building on the pupillograph from AmTech, we have added a Ganzfeld stimulator and an external stimulation unit, enabling large-area stimulation of the retina with colored light within a narrow wavelength range.

Publications:

  • Kelbsch CB, Maeda F, Strasser T, Peters TM, Wilhelm BJC, Wilhelm HM. Color Pupillography in Dorsal Midbrain Syndrome. J Neuroophthalmol. 2017 Sep;37(3):247-252. doi:10.1097/WNO.0000000000000527. PMID: 28708670
  • Kelbsch C, Maeda F, Lisowska J, Lisowski L, Strasser T, Stingl K, Wilhelm B, Wilhelm H, Peters T. Analysis of retinal function using chromatic pupillography in retinitis pigmentosa and the relationship to electrically evoked phosphene thresholds. Acta Ophthalmol. 2017 Jun;95(4):e261-e269. doi: 10.1111/aos.13259. Epub 2016 Sep 29. PMID: 27683070.
  • Maeda F, Kelbsch C, Straßer T, Skorkovská K, Peters T, Wilhelm B, Wilhelm H. Chromatic pupillography in hemianopia patients with homonymous visual field defects. Graefes Arch Clin Exp Ophthalmol. 2017 Sep;255(9):1837-1842. doi: 10.1007/s00417-017-3721-y. Epub 2017 Jun 30. PMID: 28687871
  • Kelbsch C, Maeda F, Strasser T, Blumenstock G, Wilhelm B, Wilhelm H, Peters T. Pupillary responses driven by ipRGCs and classical photoreceptors are impaired in glaucoma. Graefes Arch Clin Exp Ophthalmol. July 2016;254(7):1361-70. doi: 10.1007/s00417-016-3351-9. Epub 2016 Apr 21. PMID: 27099948.
  • Richter P, Wilhelm H, Peters T, Luedtke H, Kurtenbach A, Jaegle H, Wilhelm B. The diagnostic accuracy of chromatic pupillary light responses in diseases of the outer and inner retina. Graefes Arch Clin Exp Ophthalmol. 2017 Mar;255(3):519-527. doi: 10.1007/s00417-016-3496-6. Epub 2016 Oct 26. PMID: 27785596.
  • Stingl KT, Kuehlewein L, Weisschuh N, Biskup S, Cremers FPM, Khan MI, Kelbsch C, Peters T, Ueffing M, Wilhelm B, Zrenner E, Stingl K. Chromatic Full-Field Stimulus Threshold and Pupillography as Functional Markers for Late-Stage, Early-Onset Retinitis Pigmentosa Caused by CRB1 Mutations. Transl Vis Sci Technol. 2019 Dec 20;8(6):45. doi: 10.1167/tvst.8.6.45. PMID: 31879567; PMCID: PMC6927735.

Automated swinging flashlight test using binocular pupillography and precise quantitative analysis.

Selected publications

  • Standards in Pupillography

    Kelbsch C, Strasser T, Chen Y, Feigl B, Gamlin PD, Kardon R, Peters T, Roecklein KA, Steinhauer SR, Szabadi E, Zele AJ, Wilhelm H, Wilhelm BJ. Front Neurol. 2019 Feb 22;10:129. doi: 10.3389/fneur.2019.00129. eCollection 2019. PMID: 30853933 Free PMC article. Review. Pubmed
  • Influencing Factors on Pupillary Light Responses as a Biomarker for Local Retinal Function in a Large Normative Cohort.

    Jendritza R, Stingl K, Strasser T, Jung R, Tonagel F, Richter P, Sonntag A, Peters T, Wilhelm H, Wilhelm B, Kelbsch C. Invest Ophthalmol Vis Sci. 2024 Jun 3;65(6):3. doi: 10.1167/iovs.65.6.3. Erratum in: Invest Ophthalmol Vis Sci. 2024 Dec 2;65(14):44. doi: 10.1167/iovs.65.14.44. PMID: 38829669; PMCID: PMC11156203. Pubmed
  • Chromatic pupil campimetry as objective diagnostic tool for progressive optic neuropathies.

    Edelmayer MV, Strasser T, Jung R, Sonntag A, Jendritza R, Tonagel F, Peters T, Wilhelm H, Wilhelm B, Kelbsch C. Doc Ophthalmol. 2025 Oct 15. doi: 10.1007/s10633-025-10054-x. Online ahead of print. PMID: 41094347 Pubmed
  • How lesions at different locations along the visual pathway influence pupillary reactions to chromatic stimuli.

    Kelbsch C, Stingl K, Jung R, Kempf M, Richter P, Strasser T, Peters T, Wilhelm B, Wilhelm H, Tonagel F. Graefes Arch Clin Exp Ophthalmol. 2022 May;260(5):1675-1685. doi: 10.1007/s00417-021-05513-5. Epub 2021 Dec 13. PMID: 34902059 Free PMC article. Pubmed
  • Rod and Cone Function Measured Objectively by Chromatic Pupil Campimetry Show a Different Preservation Between Distinct Genotypes in Retinitis Pigmentosa.

    Kelbsch C, Kempf M, Jung R, Kortüm F, Reith M, Kuehlewein L, Kohl S, Strasser T, Peters T, Wilhelm H, Wilhelm B, Stingl K, Stingl K. Invest Ophthalmol Vis Sci. 2023 Aug 1;64(11):18. doi: 10.1167/iovs.64.11.18. PMID: 37578425 Free PMC article. Pubmed

Siehe auch

Siehe auch

Certificates and Associations