Visual and Physiological Optics: introduction to the joint feature issue in Biomedical Optics Express and Journal of the Optical Society of America A.

This feature issue collects articles presented at the tenth Visual and Physiological Optics meeting (VPO2022), held August 29-31, 2022, in Cambridge, UK. This joint feature issue between Biomedical Optics Express and Journal of the Optical Society of America A includes articles that cover the broad range of topics addressed at the meeting and examples of the current state of research in the field.

Introduction to Visual and Physiological Optics feature issue of Biomedical Optics Express and JOSA A.

This feature issue collects articles presented at the tenth Visual and Physiological Optics meeting (VPO2022), held August 29-31, 2022, in Cambridge, UK. This joint feature issue between Biomedical Optics Express and Journal of the Optical Society of America A includes articles that cover the broad range of topics addressed at the meeting and examples of the current state of research in the field.

Geometrical scaling of the developing eye and photoreceptors and a possible relation to emmetropization and myopia.

In this study the role of vergence in relation to age-dependent scaling of eye and photoreceptor parameters is studied. The underlying hypothesis is that the size and packing of outer segments is matched to the pupil size outdoors in photopic conditions. Vergence is analysed in relation to the angular spectrum of waves being incident using age-dependent data from the literature for the actual geometry and density of photoreceptor cones and rods. This approach is used to derive simple relations for the angular confinement of light along outer segments. Only with a small photopic pupil can leakage and crosstalk for both central and peripheral photoreceptors be entirely ruled out due to the finite length of the outer segments. A limiting 3 mm pupil size is found for children in the school age. Larger pupils will increase the likelihood of leakage and crosstalk that may therefore impact on emmetropization. This study has introduced a new paradigm in myopia research by considering vergence across the 3-D retina as being matched to the angular spectrum of waves being incident from the eye pupil. Emmetropization suggests a delicate balance between photoreceptor outer segment length and density in relation to pupil size. Only when balanced will leakage and crosstalk between adjacent outer segments be effectively suppressed thereby ensuring the highest possible light capture efficiency by visual pigments in the outer segments whether an image is formed on the retina or not.

Subjective measurement of the Stiles-Crawford effect with different field sizes.

The Stiles-Crawford effect of the first kind (SCE) is the phenomenon in which light entering the eye near the center of the pupil appears brighter than light entering near the edge. Previous investigations have found an increase in the directionality (steepness) of the effect as the testing location moves from the center of the visual field to parafoveal positions, but the effect of central field size has not been considered. The influence of field size on the SCE was investigated using a uniaxial Maxwellian system in which stimulus presentation was controlled by an active-matrix liquid crystal display. SCE directionality increased as field size increased from 0.5° to 4.7° diameter, although this was noted in four mild myopes and not in two emmetropes. The change with field size was supported by a geometric optics absorption model.

Monocular accommodation response to random defocus changes induced by a tuneable lens.

Accommodation of the human eye relies on multiple factors and visual cues that include object size, monochromatic and chromatic aberrations, and vergence. Yet, even in monocular conditions, accommodation corrects for defocus. Studies of eye growth in chicks have addressed whether the retina can decode the sign of defocus as this may play a role for emmetropization and possibly also accommodation. However, findings have not been unambiguous and questions remain. Here, we report on monocular accommodation studies of emmetropic and myopic human subjects to clarify whether foveal vision drives accommodation in the correct direction by removing out-of-focus blur potentially before relying on other cues. Subjects viewed monocularly a green target at 1-meter distance while being presented with a random sequence of negative defocus step changes induced by a pupil-conjugated current-driven tuneable lens. The natural pupil was constricted by a pupil-conjugated motorized iris using three different diameters and target brightness was set with a liquid crystal variable attenuator. A Hartmann-Shack wavefront sensor with an infrared beacon captured real-time changes of defocus and Zernike polynomial coefficients up to 4th radial order. We find that the young adult eye accommodates reliably in the correct direction but with a latency of 300-700 ms. The findings are discussed in relation to an absorption model of light in outer segments that breaks the defocus symmetry and thus may serve as a plausible guide for accommodation and emmetropization.

Directional light-capture efficiency of the foveal and parafoveal photoreceptors at different luminance levels: an experimental and analytical study.

A gradual drop in visibility with obliquely incident light on retinal photoreceptors is namely described by the Stiles-Crawford effect of the first kind and characterized by a directionality parameter. Using a digital micromirror device in a uniaxial flicker system, here we report on variations of this effect with luminance levels, wavelengths within the visible and near-infrared spectrum and retinal regions ranging from the fovea to 7.5° parafoveal. Results show a consistent directionality in mesopic and photopic conditions. Higher directionality is measured for longer wavelengths, and a decrease with retinal eccentricity is observed. Results are discussed in relation to an absorption model for the visual pigments taking the outer-segment packing and thickness of the neural retina into account. Good correspondence is found without enforcing photoreceptor waveguiding.

Method to reduce undesired multiple fundus scattering effects in double-pass systems.

Double-pass systems rely on backscattering of light by the human ocular fundus to assess the optical quality of the eye. In this work, we present a method to reduce double-pass image degradation caused by undesired multiple scattering effects in the eye fundus. The reduction is based on combined data processing of simultaneous measurements using two different configurations: one symmetric with equal entrance and exit pupils and another asymmetric with unequal entrance and exit pupils. Under certain conditions, such scattering effects may be effectively suppressed. Measurements of human eyes show that, although multiple fundus scattering imposes a shift on the estimations, double-pass systems can be used to predict the optical quality of the eye within a population.

Measuring Ocular Aberrations Sequentially Using a Digital Micromirror Device.

The Hartmann⁻Shack wavefront sensor is widely used to measure aberrations in both astronomy and ophthalmology. Yet, the dynamic range of the sensor is limited by cross-talk between adjacent lenslets. In this study, we explore ocular aberration measurements with a recently-proposed variant of the sensor that makes use of a digital micromirror device for sequential aperture scanning of the pupil, thereby avoiding the use of a lenslet array. We report on results with the sensor using two different detectors, a lateral position sensor and a charge-coupled device (CCD) scientific camera, and explore the pros and cons of both. Wavefront measurements of a highly aberrated artificial eye and of five real eyes, including a highly myopic subject, are demonstrated, and the role of pupil sampling density, CCD pixel binning, and scanning speed are explored. We find that the lateral position sensor is mostly suited for high-power applications, whereas the CCD camera with pixel binning performs consistently well both with the artificial eye and for real-eye measurements, and can outperform a commonly-used wavefront sensor with highly aberrated wavefronts.

Hartmann-Shack wavefront sensing without a lenslet array using a digital micromirror device.

The common Hartmann-Shack wavefront sensor makes use of a lenslet array to sample in-parallel optical wavefronts. Here, we introduce a Hartmann-Shack wavefront sensor that employs a digital micromirror device in combination with a single lens for serial sampling by scanning. Sensing is analyzed numerically and validated experimentally using a deformable mirror operated in closed-loop adaptive optics with a conventional Hartmann-Shack wavefront sensor, as well as with a set of ophthalmic trial lenses, to generate controllable amounts of monochromatic aberrations. The new sensor is free of crosstalk and can potentially operate at kilohertz speed. It offers a reconfigurable aperture that can exclude unwanted parts of the wavefront.

Analysing the impact of myopia on the Stiles-Crawford effect of the first kind using a digital micromirror device.

PURPOSE: Photoreceptor light acceptance is closely tied to the Stiles-Crawford effect of the first kind (SCE-I). Whether the SCE-I plays a role in myopic development remains unclear although a reduction in directionality has been predicted for high myopia. The purpose of this study is to analyse the relationship between foveal SCE-I directionality, axial eye length, and defocus for emmetropic subjects wearing ophthalmic trial lenses during psychophysical measurements and for myopic subjects with their natural correction. METHOD: A novel uniaxial flicker system has been implemented making use of a Digital Micromirror Device (DMD) to flicker between a 2.3 visual degrees circular reference and a set of circular test patterns in a monocular Maxwellian view at 0.5 Hz. The brightness of the test is adjusted by the duty cycle of the projected light to an upper limit of 22 727 Hz. The wavelength and bandwidth are set by a tuneable liquid-crystal filter centred at 550 nm. A total of four measurement series for 11 pupil entrance points have been realized for the right eye of 6 emmetropic and 10 myopic subjects whose pupils were dilated with tropicamide. Five of the emmetropic subjects wore ophthalmic trial lenses in the range of -3 to +9 dioptres to mimic hyperopic to highly myopic vision and resulting visibility plots have been fitted to a Gaussian SCE-I function. In turn, the myopic subjects wore their natural correction during the analysis of the SCE-I. All subjects had their axial eye length determined with an ultrasound device. RESULTS: A SCE-I directionality parameter in the range of 0.03 to 0.06/mm2 was found for the emmetropic subjects with corrected vision in fair agreement to values in the literature. The results also revealed a marked reduction in directionality in the range from 16% to 30% with every 3 dioptre increase of simulated myopia, as well as a 10% increased directionality in simulated hyperopic eyes. For both emmetropic and myopic subjects, a decrease in directionality with increase in axial length was found in agreement with theoretical expectations. CONCLUSION: The study confirms a clear link between SCE-I directionality, uncorrected defocus, and axial eye length. This may play a role for emmetropization and thus myopic progression as cone photoreceptors capture light from a wider pupil area in elongated eyes due to a geometrical scaling.

Differential detection of retinal directionality.

An adaptive optics fundus camera has been developed that uses simultaneous capture of multiple images via adjacent pupil sectors to provide directional sensitivity. In the chosen realization, a shallow refractive pyramid prism is used to subdivide backscattered light from the retina into four solid angles. Parafoveal fundus images have been captured for the eyes of three healthy subjects and directional scattering has been determined using horizontal and vertical differentials. The results for the photoreceptor cones, blood vessels, and the optic disc are discussed. In the case of cones, the observations are compared with numerical simulations based on a simplistic light-scattering model. Ultimately, the method may have diagnostic potential for diseases that perturb the microscopic structure of the retina.

Volumetric integration model of the Stiles-Crawford effect of the first kind and its experimental verification.

The integrated Stiles-Crawford function is commonly used as apodization model for vision through the natural eye pupil. However, this method does not account for possible effects related to the retinal thickness, the large length-to-diameter aspect ratio of the photoreceptors, or the use of nonMaxwellian illumination. Here, we introduce a geometrical optics model to calculate the fraction of overlap between light at the retina and the photoreceptor outer segments where absorption triggers vision. The model, which does not account for photoreceptor waveguiding, is discussed for both Maxwellian and nonMaxwellian illumination. The integrated Stiles-Crawford effect is analyzed experimentally with a uniaxial pupil-size flicker methodology and we find that the psychophysical measurements match better to the geometrical optics predictions than direct integration of a Stiles-Crawford function.

Retina-simulating phantom produced by photolithography.

Cone photoreceptors have a narrow acceptance angle that is well matched to the size of the eye pupil and dampens the visual impact of aberrations and scattering. However, the structure of the human retina is not replicated in existing eye models used to test refractive designs or retinal implants that restore partial vision to the blind. Here, we report on an artificial waveguide-based retinal phantom manufactured by photolithography in photoresist film with dimensions and refractive index contrast similar to the retinal receptor layer. The optical performance of the waveguide array is analyzed in terms of angular coupling efficiency, and it is experimentally verified that the structure leads to improved resolution and contrast of optical images transmitted through the layer when defocus is present.

Virtual pyramid wavefront sensor for phase unwrapping.

Noise affects wavefront reconstruction from wrapped phase data. A novel method of phase unwrapping is proposed with the help of a virtual pyramid wavefront sensor. The method was tested on noisy wrapped phase images obtained experimentally with a digital phase-shifting point diffraction interferometer. The virtuality of the pyramid wavefront sensor allows easy tuning of the pyramid apex angle and modulation amplitude. It is shown that an optimal modulation amplitude obtained by monitoring the Strehl ratio helps in achieving better accuracy. Through simulation studies and iterative estimation, it is shown that the virtual pyramid wavefront sensor is robust to random noise.

Rate of riboflavin diffusion from intrastromal channels before corneal crosslinking.

PURPOSE: To determine the diffusion of riboflavin from intrastromal channels through the effective diffusion coefficients compared with traditional axial diffusion with epithelium on or off. SETTING: Advanced Optical Imaging Laboratory, University College Dublin, and Wellington Eye Clinic, Sandyford, Dublin, Ireland. DESIGN: Experimental study. METHODS: The rate of diffusion in whole-mounted porcine eyes was monitored for a 30 minutes using an optical setup with a charge-coupled device camera and a bandpass filter (central wavelength 550 nm and 40 nm bandpass) to image the fluorescence under ultraviolet illumination (365 nm wavelength). For comparison, an isotropic corneal stroma with an annular channel was modeled numerically for different diffusion constants and boundary conditions. RESULTS: Numerical and experimental results were compared, allowing determination of the effective diffusion coefficient for each case. Experimental results for 6 different riboflavin solutions were in all cases found to be higher than for the common crosslinking (CXL) riboflavin protocol, where the diffusion constant is D0 = 6.5 × 10(-5) mm(2)/sec. For the intrastromal channel, 2 isotonic solutions containing riboflavin 0.1% correlated with a diffusion constant of 5D0 = 32.5 × 10(-5) mm(2)/sec. Hypotonic solutions and transepithelium had a higher diffusion coefficient approaching 10D0 = 65.0 × 10(-5) mm(2)/sec, which is an order-of-magnitude increase compared with the typical diffusion coefficient found in standard CXL. CONCLUSIONS: In this study, riboflavin had a faster stromal diffusion when injected into a corneal channel than when applied as drops to the anterior corneal surface. Further numerical modeling might allow optimization of the channel structure for any specific choice of riboflavin.

Phase unwrapping with a virtual Hartmann-Shack wavefront sensor.

The use of a spatial light modulator for implementing a digital phase-shifting (PS) point diffraction interferometer (PDI) allows tunability in fringe spacing and in achieving PS without the need for mechanically moving parts. However, a small amount of detector or scatter noise could affect the accuracy of wavefront sensing. Here, a novel method of wavefront reconstruction incorporating a virtual Hartmann-Shack (HS) wavefront sensor is proposed that allows easy tuning of several wavefront sensor parameters. The proposed method was tested and compared with a Fourier unwrapping method implemented on a digital PS PDI. The rewrapping of the Fourier reconstructed wavefronts resulted in phase maps that matched well the original wrapped phase and the performance was found to be more stable and accurate than conventional methods. Through simulation studies, the superiority of the proposed virtual HS phase unwrapping method is shown in comparison with the Fourier unwrapping method in the presence of noise. Further, combining the two methods could improve accuracy when the signal-to-noise ratio is sufficiently high.

Wavefront sensing using a liquid-filled photonic crystal fiber.

A novel wavefront sensor based on a microstructural array of waveguides is proposed. The method is based on the sensitivity in light-coupling efficiency to the wavefront gradient present at the entrance aperture of each waveguide in an array, and hence the amount of incident light that couples is influenced by wavefront aberrations. The concept is illustrated with wavefront measurements that have been performed using a liquid-filled photonic crystal fiber (LF-PCF) working as a coherent fiber bundle. The pros and cons of the LF-PCF based sensor are discussed.

Simultaneous drift, microsaccades, and ocular microtremor measurement from a single noncontact far-field optical sensor.

We report on the combined far-field measurement of the three involuntary eye movements, drift, microsaccades, and ocular microtremor (OMT), using a noncontact far-field optical method. We review the significance of the smallest and least measured, and thus least understood, of the three, OMT. Using modern digital imaging techniques, we perform detailed analysis, present experimental results, and examine the extracted parameters using a noncontact far-field sensor. For the first time, in vivo noncontact measurements of all fixational in-plane movements of the human eye are reported, which simultaneously provide both the horizontal (left-right) and vertical (up-down) displacement results.

Closed-loop adaptive optics using a spatial light modulator for sensing and compensating of optical aberrations in ophthalmic applications.

Sensing and compensating of optical aberrations in closed-loop mode using a single spatial light modulator (SLM) for ophthalmic applications is demonstrated. Notwithstanding the disadvantages of the SLM, in certain cases, this multitasking capability of the device makes it advantageous over existing deformable mirrors (DMs), which are expensive and in general used for aberration compensation alone. A closed-loop adaptive optics (AO) system based on a single SLM was built. Beam resizing optics were used to utilize the large active area of the device and hence make it feasible to generate 137 active subapertures for wavefront sensing. While correcting Zernike aberrations up to fourth order introduced with the help of a DM (for testing purposes), diffraction-limited resolution was achieved. It is shown that matched filter and intensity-weighted centroiding techniques stand out among others. Closed-loop wavefront correction of aberrations in backscattered light from the eyes of three healthy human subjects was demonstrated after satisfactory results were obtained using an artificial eye, which was simulated with a short focal length lens and a sheet of white paper as diffuser. It is shown that the closed-loop AO system based on a single SLM is capable of diffraction-limited correction for ophthalmic applications.

Directional sensitivity of the retina: A layered scattering model of outer-segment photoreceptor pigments.

Photoreceptor outer segments have been modeled as stacked arrays of discs or membrane infoldings containing visual pigments with light-induced dipole moments. Waveguiding has been excluded so fields diffract beyond the physical boundaries of each photoreceptor cell. Optical reciprocity is used to argue for identical radiative and light gathering properties of pigments to model vision. Two models have been introduced: one a macroscopic model that assumes a uniform pigment density across each layer and another microscopic model that includes the spatial location of each pigment molecule within each layer. Both models result in highly similar directionality at the pupil plane which proves to be insensitive to the exact details of the outer-segment packing being predominantly determined by the first and last contributing layers as set by the fraction of bleaching. The versatility of the microscopic model is demonstrated with an array of examples that includes the Stiles-Crawford effect, visibility of a focused beam of light and the role of defocus.