Wolf Maximilian Harmening

Objective: To investigate the relationship between photopic pupil size, refractive state and foveal anatomy in healthy adults, in the context of emmetropisation and myopia. Methods and analysis: In this cross-sectional study, pupil sizes were recorded in 80 healthy adults (28±8 years/55 women) using a custom-built high-resolution pupil tracker (0.03 mm/pixel). Daylight lamps provided two high-luminance conditions (6.5k and 10k cd/m²). Objective refraction and axial length were measured, and additionally high-resolution optical coherence tomography (OCT) was applied to record retinal volume scans of the fovea. OCT B-scans were automatically segmented for the internal limiting membrane and retinal pigment epithelium layers by the instrument algorithm. Additionally, the ellipsoid and phagosome zones defining the outer segment lengths were determined by a custom-made algorithm. Associations between photopic pupil size, refractive state, axial length and foveal metrics were analysed with correlation and multivariable regression. Results: Photopic pupil sizes at 6.5k cd/m² ranged from 1.77 to 3.38 mm (2.33±0.26 mm). Spherical equivalent of refraction ranged from −9.4 to +4.9 D (−1.24±2.29 D), and axial length ranged from 21.0 to 27.0 mm (23.9±1.2 mm). Photopic pupil size was significantly correlated with axial length and refractive state (all p≤0.01), although the explained variance was modest (R ² up to 0.09). Outer segment length and foveal hill distance were significantly associated with refractive state (all p<0.05). Conclusion: The association of photopic pupil size with axial length and refractive state, alongside foveal parameters being linked to refractive state but not to pupil size (exception: nasal hill height), suggests a potential interplay between foveal architecture and emmetropisation. Further investigation via longitudinal studies of children will be required. The main limitation of this study is the under-representation of high-myopes.

Purpose: To quantify whether fundus tracking in microperimetry improves psychometric parameter estimation ( in vivo demonstration of improved stimulus-delivery precision), and to derive a psychometrically grounded criterion intensity for suprathreshold (defect-mapping) microperimetry. Methods: Twenty-five healthy volunteers underwent MAIA2-microperimetry at five loci: three outside and two inside the blind spot. Frequency-of-seeing (FoS) functions were measured in four blocks (2 tracking on; 2 tracking off). FoS-data were fit using cumulative-Gaussian psychometric functions estimating sensitivity parameters. Mixed-effect models assessed tracking effects, and posterior simulations defined the optimal criterion intensity for separating “seeing” from “non-seeing” loci. Results: Tracking had little effect on threshold estimates at loci outside the blind spot, but lowered threshold estimates within the blind spot (posterior median difference PMD [95% CrI] of −1.46 dB [−2.30, −0.62] at locus 4, and −1.02 dB [−1.94, −0.08] at locus 5). Tracking was associated with steeper psychometric slope parameters at loci 1–3 (PMD of −0.14 dB [−0.29, 0.01], −0.27 dB [−0.43, −0.12], and −0.22 dB [−0.40, −0.04]). Without tracking, false-positive responses were more frequent when fixation shifts displaced stimuli toward the “seeing” retina. Simulation-based analysis identified 13 dB as nominally optimal criterion for suprathreshold microperimetry (Youden index: 0.76 [0.74, 0.79], comparable to 10 dB (0.74 [0.72, 0.76]). Conclusions: Even in healthy volunteers with stable fixation, fundus tracking measurably reduced sensitivity estimates at “non-seeing” loci and sharpened FoS curves in the “seeing” retina. A criterion intensity of 10 to 13 dB is a defensible choice for separating “seeing” and “non-seeing” retina in suprathreshold (defect-mapping) perimetry paradigms.

The retinal area inspecting a visual stimulus and, consequently, the number of photoreceptors engaged in a visual task increase with presentation time, as fixational eye movements continuously move the retina across the retinal image. Here, we varied stimulus duration in a Tumbling-E visual acuity task while recording videos of the photoreceptor mosaic in seven participants with adaptive optics micro-psychophysical techniques to determine how far the retinal image must move across the cone mosaic before this motion begins to improve visual acuity. Five stimulus presentation durations were tested (3, 80, 220, 370, and 600 ms), while participants exhibited natural eye movements. Retinal slip amplitudes (i.e., the total displacement stimuli underwent) increased linearly with stimulus duration at individual rates. Higher cone density was associated with drift over smaller retinal areas, making the number of traversed cones more similar across participants at longer durations. At the shortest presentation duration, retinal slip was virtually absent and acuity was limited by retinal resolution, averaging to 1.07 ± 0.08 times the cone row-to-row spacing (Nyquist limit of sampling). At an 80-ms duration, corresponding to approximately two cone diameters of retinal slip, acuity thresholds improved significantly, reaching 0.90 ± 0.10 of the Nyquist limit. Thresholds continued to improve with longer durations at a lower rate, reaching 0.75 ± 0.10 times the Nyquist limit at 600 ms. These results demonstrate that humans can extract visual information with sub-cone precision within less than 100 ms, with a retinal slip approaching single foveal cone spacing.

Fine spatial vision relies on the foveola, the 1-degree retinal region with highest cone density. Despite its importance, the relationship between retinal anatomy, fixational behavior, and visual perception in the foveola is not fully understood. Using an Adaptive Optics Scanning Light Ophthalmoscope for high-resolution retinal imaging and stimulation, we studied the effect of a simulated subfoveolar ( ≈ 0.03 degrees ² ) scotoma on fine spatial vision and fixation behavior in healthy observers. Our findings show that the visuomotor system adapts to the scotoma with striking precision by shifting the preferred locus of fixation in a systematic fashion by minute ( ≈ 5 arcmin) amounts to bring stimuli into a region of visibility. These results reveal an unprecedented level of fine-scale plasticity in the human visuomotor system. Interestingly, this new retinal locus of fixation is characterized by lower cone density among those surrounding the scotoma, indicating that factors beyond spatial sampling maximization influence these fine-scale adjustments.

The human brain constructs a model of the world by processing sensory signals with distinct temporal characteristics that may differ in generation and transmission speed within a single sensory modality. To perceive simultaneous events as occurring at the same time, the brain must synchronize this sensory information, yet the mechanisms underlying such synchronization remain unclear. By combining human neural recordings, behavioral measurements and modeling, we show that in the human visual system, this process begins in the fovea centralis, the retinal region used for reading and recognizing faces. Reaction times to foveal single-cone photostimulation were similar across the central visual field, although visual information from neighboring foveal cones travels along axons of highly different lengths. From direct measurements of action potential propagation speeds, axon diameters and lengths in the human fovea centralis, we found that longer foveal axons have larger diameters and increased propagation speeds. We conclude that the human brain orchestrates axonal conduction speeds of unmyelinated axons in the retina to synchronize the arrival times of sensory signals. These results suggest a previously unknown mechanism by which the human brain synchronizes perception.

Perception and action are inherently entangled: our world view is shaped by how we explore our environment through complex and variable self-motion. Even when fixating stable stimuli, our eyes undergo small, involuntary movements. Fixational eye movements (FEM) render a stable world jittery on our retinae, which can be expected to harm neural coding. Yet, empirical evidence suggests that FEM help rather than harm human perception of fine detail. Here, we elucidate this paradox by uncovering under which conditions FEM improve or impair retinal coding and human acuity. We combine theory and experiment: model accuracy is directly compared to that of healthy human subjects in a visual acuity task. Acuity is modeled by applying an ideal Bayesian classifier to simulations of retinal spiking activity in the presence of FEM. In addition, empirical FEM are monitored using high-resolution eye-tracking by an adaptive optics scanning laser ophthalmoscope. FEM introduce variability in retinal ganglion cell activity, but they also effectively preprocess inputs to facilitate retinal information encoding. Based on an interplay of these mechanisms, our model predicts a relation between visual acuity, FEM amplitude, and single-trial stimulus size that quantitatively accounts for experimental observations and captures the beneficial effect of FEM. Moreover, we observe that while human subjects’ FEM statistics vary with stimulus size, our model suggests that subjects’ FEM amplitude remains within a near-optimal range, where acuity is enhanced compared to much larger or smaller amplitudes. Overall, our findings indicate that perception benefits from action even at the fine spatiotemporal scale of FEM.