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We investigated how long-term visual experience with habitual spherical aberration (SA) influences subjective depth of focus (DoF). Nine healthy cycloplegic eyes with habitual SAs of different signs and magnitudes were enrolled. An adaptive optics (AO) visual simulator was used to measure through-focus high-contrast visual acuity after correcting all monochromatic aberrations and imposing + 0.5 μm and − 0.5 μm SAs for a 6-mm pupil. The positive ( n  = 6) and negative ( n  = 3) habitual SA groups ranged from 0.17 to 0.8 μm and from − 1.2 to – 0.12 μm for a 6-mm pupil, respectively. Although all optical conditions were identical, and the subjective DoFs were expected to be the same for all participants, the DoFs of individuals differed between the positive and negative habitual SA groups. For the positive habitual SA group, the mean DoF with positive AO-induced SA (2.14 D) was larger than that with negative AO-induced SA (1.88 D); for the negative habitual SA group, a smaller DoF was measured with positive AO-induced SA (1.94 D) than that with negative AO-induced SA (2.14 D). Subjective DoF tended to be larger when the induced SA in terms of sign and magnitude was closer to the participant’s habitual SA. Our findings suggest that neural adaptation to habitual SA compensated for optical blur at multiple object distances, perceptually expanding DoF. As a result, the outcomes of optical treatments for presbyopia may differ due to the neural compensation mechanism influenced by an individual’s visual experience with their habitual optics.

Densitometry is a powerful tool for the biophysical assessment of the retina. Until recently, this was restricted to bulk spatial scales in living humans. The application of adaptive optics (AO) to the conventional fundus camera and scanning laser ophthalmoscope (SLO) has begun to translate these studies to cellular scales. Here, we employ an AOSLO to perform dynamic photopigment densitometry in order to characterize the optical properties and spectral types of the human cone photoreceptor mosaic. Cone-resolved estimates of optical density and photosensitivity agree well with bulk estimates, although show smaller variability than previously reported. Photopigment kinetics of individual cones derived from their selective bleaching allowed efficient mapping of cone sub-types in human retina. Estimated uncertainty in identifying a cone as long vs middle wavelength was less than 5%, and the total time taken per subject ranged from 3-9 hours. Short wavelength cones were delineated in every subject with high fidelity. The lack of a third cone-type was confirmed in a protanopic subject. In one color normal subject, cone assignments showed 91% correspondence against a previously reported cone-typing method from more than a decade ago. Combined with cone-targeted stimulation, this brings us closer in studying the visual percept arising from a specific cone type and its implication for color vision circuitry.

Human cone outer segment (COS) length changes in response to stimuli bleaching up to 99% of L- and M-cone opsins were measured with high resolution, phase-resolved optical coherence tomography (OCT). Responses comprised a fast phase (∼5 ms), during which COSs shrink, and two slower phases (1.5 s), during which COSs elongate. The slower components saturated in amplitude (∼425 nm) and initial rate (∼3 nm ms−1) and are well described over the 200-fold bleaching range as the sum of two exponentially rising functions with time constants of 80 to 90 ms (component 1) and 1,000 to 1,250 ms (component 2).Measurements with adaptive optics reflection densitometry revealed component 2 to be linearly related to cone pigment bleaching, and the hypothesis is proposed that it arises from cone opsin and disk membrane swelling triggered by isomerization and ratelimited by chromophore hydrolysis and its reduction to membrane-localized all-trans retinol. The light sensitivity and kinetics of component 1 suggested that the underlying mechanism is an osmotic response to an amplified soluble by-product of phototransduction. The hypotheses that component 1 corresponds to G-protein subunits dissociating from the membrane, metabolites of cyclic guanosine monophosphate (cGMP) hydrolysis, or by-products of activated guanylate cyclase are rejected, while the hypothesis that it corresponds to phosphate produced by regulator of G-protein signaling 9 (RGS9)-catalyzed hydrolysis of guanosine triphosphate (GTP) in G protein–phosphodiesterase complexes was found to be consistent with the results. These results provide a basis for the assessment with optoretinography of phototransduction in individual cone photoreceptors in health and during disease progression and therapeutic interventions.

Crowding is the substantial interference of neighboring items on target identification. Crowding with letter stimuli has been studied primarily in the visual periphery, with conflicting results for foveal stimuli. While a cortical locus for peripheral crowding is well established (with a large spatial extent up to half of the target eccentricity), disentangling the contributing factors in the fovea is more challenging due to optical limitations. Here, we used adaptive optics (AO) to overcome ocular aberrations and employed high-resolution stimuli to precisely characterize foveal lateral interactions with high-contrast letters flanked by letters. Crowding was present, with a maximal edge-to-edge interference zone of 0.75-1.3 minutes at typical unflanked performance levels. In agreement with earlier foveal contour interaction studies, performance was non-monotonic, revealing a recovery effect with proximal flankers. Modeling revealed that the deleterious effects of flankers can be described by a single function across stimulus sizes when the degradation is expressed as a reduction in sensitivity (expressed in Z-score units). The recovery, however, did not follow this pattern, likely reflecting a separate mechanism. Additional analysis reconciles multiple results from the literature, including the observed scale invariance of center-to-center spacing, as well as the size independence of edge-to-edge spacing.

Color vision requires the activity of cone photoreceptors to be compared in post-receptoral circuitry. Decades of psychophysical measurements have quantified the nature of these comparative interactions on a coarse scale. How such findings generalize to a cellular scale remains unclear. To answer that question, we quantified the influence of surrounding light on the appearance of spots targeted to individual cones. The eye’s aberrations were corrected with adaptive optics and retinal position was precisely tracked in real-time to compensate for natural movement. Subjects reported the color appearance of each spot. A majority of L-and M-cones consistently gave rise to the sensation of white, while a smaller group repeatedly elicited hue sensations. When blue sensations were reported they were more likely mediated by M- than L-cones. Blue sensations were elicited from M-cones against a short-wavelength light that preferentially elevated the quantal catch in surrounding S-cones, while stimulation of the same cones against a white background elicited green sensations. In one of two subjects, proximity to S-cones increased the probability of blue reports when M-cones were probed. We propose that M-cone increments excited both green and blue opponent pathways, but the relative activity of neighboring cones favored one pathway over the other.

Purpose: To investigate the optical performance of a large-stroke deformable mirror in correcting large aberrations in highly aberrated eyes. Methods: A large-stroke deformable mirror (Mirao 52D; Imagine Eyes) and a Shack-Hartmann wavefront sensor were used in an adaptive optics system. Closed-loop correction of the static aberrations of a phase plate designed for an advanced keratoconic eye was performed for a 6-mm pupil. The same adaptive optics system was also used to correct the aberrations in one eye each of two moderate keratoconic and three normal human eyes for a 6-mm pupil. Results: With closed-loop correction of the phase plate, the total root-mean-square (RMS) over a 6-mm pupil was reduced from 3.54 to 0.04 µm in 30 to 40 iterations, corresponding to 3 to 4 seconds. Adaptive optics closed-loop correction reduced an average total RMS of 1.73±0.998 to 0.10±0.017 µm (higher order RMS of 0.39±0.124 to 0.06±0.004 µm) in the three normal eyes and 2.73±1.754 to 0.10±0.001 µm (higher order RMS of 1.82±1.058 to 0.05±0.017 µm) in the two keratoconic eyes. Conclusions: Aberrations in both normal and highly aberrated eyes were successfully corrected using the large-stroke deformable mirror to provide almost perfect optical quality. This mirror can be a powerful tool to assess the limit of visual performance achievable after correcting the aberrations, especially in eyes with abnormal corneal profiles. [J Refract Surg. 2007;23:947–952.]

The human eye suffers from higher order aberrations, in addition to conventional spherical and cylindrical refractive errors. Advanced optical techniques have been devised to correct them in order to achieve superior retinal image quality. However, vision is not completely defined by the optical quality of the eye, but also depends on how the image quality is processed by the neural system. In particular, how neural processing is affected by the past visual experience with optical blur has remained largely unexplored. The objective of this thesis was to investigate the interaction of optical and neural factors affecting vision. To achieve this goal, pathological keratoconic eyes were chosen as the ideal population to study since they are severely afflicted by degraded retinal image quality due to higher order aberrations and their neural system has been exposed to that habitually for a long period of time. Firstly, we have developed advanced customized ophthalmic lenses for correcting the higher order aberration of keratoconic eyes and demonstrated their feasibility in providing substantial visual benefit over conventional corrective methodologies. However, the achieved visual benefit was significantly smaller than that predicted optically. To better understand this, the second goal of the thesis was set to investigate if the neural system optimizes its underlying mechanisms in response to the long-term visual experience with large magnitudes of higher order aberrations. This study was facilitated by a large-stroke adaptive optics vision simulator, enabling us to access the neural factors in the visual system by manipulating the limit imposed by the optics of the eye. Using this instrument, we have performed a series of experiments to establish that habitual exposure to optical blur leads to an alteration in neural processing thereby alleviating the visual impact of degraded retinal image quality, referred to as neural compensation. However, it was also found that chronic exposure to poor optics caused neural insensitivity to fine spatial detail thus adversely limiting the achievable visual benefit when improving the eye's optical quality. Finally, we demonstrated that the altered, but plastic visual system could be re-adapted to improved optics such that it partially recovers its normal mechanism. These findings not only provide vast clinical implications for advanced customized vision correction methodologies for normal, pathologic and presbyopic eyes but also vital scientific insight into the neural processing of the visual system in response to the aberrated optics of the eye.

The distribution of long (L), middle (M), and short (S) wavelength sensitive cones in the retina determines how different frequencies of incident light are sampled across space and has been hypothesized to influence spatial and color vision. We examined how the detection and color naming of small, short-duration increment stimuli (λ = 543 or 680 nm) depend on the local spectral topography of the cone mosaic. Stimuli were corrected for optical aberrations by an adaptive optics system and targeted to locations in the parafovea where cone spectral types were known. We found that sensitivity to 680 nm light, normalized by sensitivity to 543 nm light, grew with the proportion of L cones at the stimulated locus, though intra- and intersubject variability was considerable. A similar trend was derived from a simple model of the achromatic (L+M) pathway suggesting that small spot detection mainly relies on a non-opponent mechanism. Most stimuli were called achromatic, with red and green responses becoming more common as stimulus intensity increased and as the local L/M ratio became more symmetric. The proximity of S cones to the stimulated region did not influence the likelihood of eliciting a chromatic percept. Our detection data confirm earlier reports that small spot psychophysics can reveal information about local cone topography, and our color naming findings suggest that chromatic sensitivity may improve when the L/M ratio approaches unity.