Intrathecal Vector Delivery in Juvenile Rats via Lumbar Cistern Injection.

Gene therapy is a powerful technology to deliver new genes to a patient for the treatment of disease, be it to introduce a functional gene, inactivate a toxic gene, or provide a gene whose product can modulate the biology of the disease. The delivery method for the therapeutic vector can take many forms, ranging from intravenous infusion for systemic delivery to direct injection into the target tissue. For neurodegenerative disorders, it is often desirable to skew transduction towards the brain and/or spinal cord. The least invasive approach to target the entire central nervous system involves injection into the cerebrospinal fluid (CSF), allowing the therapeutic to reach a large fraction of the central nervous system. The safest approach to deliver a vector into the CSF is the lumbar intrathecal injection, where a needle is introduced into the lumbar cistern of the spinal cord. This technique, also known as a lumbar puncture, has been widely used in neonatal and adult rodents and in large animal models. While the technique is similar across species and developmental stages, subtle differences in size, structure, and elasticity of tissues surrounding the intrathecal space require accommodations in the approach. This article describes a method for performing lumbar puncture in juvenile rats to deliver an adeno-associated serotype 9 vector. Here, 25-35 µL of vector were injected into the lumbar cistern, and a green fluorescent protein (GFP) reporter was used to evaluate the transduction profile resulting from each injection. The benefits and challenges of this approach are discussed.

Home vision therapy and prism prescription in presbyopic persons with convergence insufficiency: study protocol for a randomized controlled trial.

BACKGROUND: Convergence insufficiency is a common issue in the field of binocular vision. Various treatment options have been suggested for managing this condition, but their efficacy in individuals with presbyopia remains unclear. The objective of this study is to compare the effectiveness of home-based vision therapy and prism prescription, in presbyopic patients with convergence insufficiency. METHODS/DESIGN: It is a randomized, prospective, double-blind clinical trial, with total of 150 participants randomly assigned to the three groups. The Control Group will receive a new near glasses as a conventional prescription, along with aimless and random eye movement exercises that do not have any convergence or accommodation effects. The Home Vision Therapy Group will receive new near glasses with accommodative and convergence eye exercises. The Prism Group will receive a near prismatic glasses prescribed using the Sheard's criterion. All treatments will be administered for a period of 2 months, and measurements of the modified convergence insufficiency symptoms survey (CISS), near point convergence, near phoria, and positive fusional vergence will be taken at baseline, one month later, and at the end of the treatment. DISCUSSION: We aim to identify which component - either the prism prescription or the home vision therapy - is more effective in improving binocular abilities and reducing patients' symptom scores. TRIAL REGISTRATION: ClinicalTrials.gov NCT05311917 with last update on 04/22/2023.

Vergence-Accommodation Conflict: Increased Presbyopia in Virtual Reality.

BACKGROUND: Performance and symptoms in completing a visual search task on a PC monitor and using a head-mounted display (HMD) were compared for different viewing conditions and between users of different ages. PATIENTS AND METHODS: Twenty-three young (M = 30 y, SD = 7 y) and 23 older (M = 52 y, SD = 5 y) participants performed a visual search task presented on a PC monitor. The task was repeated using an HMD for a near and a far virtual viewing distance. Reaction times (RT), detection sensitivity (d'), and symptoms were recorded for the three different viewing conditions. RESULTS: RT and d' were not affected by the viewing condition (p > 0.05). In contrast, symptoms significantly depended on the viewing condition but were, in part, not significantly affected by age. It is interesting to note that although not significant, young participants reported more ocular symptoms than older participants in the near vision task carried out using the HMD. DISCUSSION: HMD increases visual symptoms. However, HMD could be, in part, a remedy to problems when using visual aids for near work, in particular for presbyopes.

The relationship between accommodative and binocular function with myopia progression in myopic children undergoing orthokeratology.

PURPOSE: To determine the relationship between changes in accommodative and binocular function with myopia progression in myopic children over a two-year follow-up period, and to determine when changes in visual functions stabilized after switching from spectacles to orthokeratology (Ortho-K). METHODS: This prospective, self-controlled study followed thirty-six participants (aged 8-14 years) for two years after they switched from spectacles to Ortho-K. Accommodative and binocular function were assessed prior to and 1, 3, 6, 12, 18 and 24 months after commencing Ortho-K. Measurements included accommodative amplitude, accommodative response, accommodative facility, accommodative convergence/accommodation (AC/A), ocular alignment, positive relative accommodation (PRA), negative relative accommodation (NRA), horizontal vergence range, reading ability and stereoacuity. Myopia progression was quantified by the change in axial length. RESULTS: Ocular alignment, monocular and binocular accommodative facility, and PRA stabilized after 1 month. The distance blur point in the convergence range, the distance break and recovery point in the divergence range, accommodative amplitude, calculated AC/A, stereoacuity and reading ability stabilized within 6 months. After two years of Ortho-K, NRA significantly increased (p = 0.044), while it showed no significant difference after one-year of lens wear (p = 0.49). The distance break point in the convergence range showed no significant difference (p = 0.20), but significantly decreased after one-year (p = 0.005). There were no significant correlations between the change in axial length with changes in accommodative or binocular function (p > 0.05). CONCLUSION: Accommodative and binocular function changed significantly after switching from spectacles to Ortho-K and most of the parameters stabilized within the first 6 months. There was no association between the change in accommodative or binocular function and myopia progression.

Sex as a risk factor regarding presbyopia in the rhesus monkey.

PURPOSE: To determine the effect of sex as a risk factor regarding presbyopia. METHODS: Maximum accommodation was pharmacologically induced (40% cabachol corneal iontophoresis) in 97 rhesus monkeys (49 males and 48 females) ranging in age from 8 to 36 years old. Accommodation was measured by Hartinger coincidence refractometry. RESULTS: Accommodative amplitude measured refractometrically decreased with age, and the rate of change was not different between males and females (p = 0.827). CONCLUSIONS: Presbyopia is essentially sex neutral, and no one is spared. There may be modest variations between different populations for various reasons, but essentially it is monotonously predictable. At present there is no biological therapeutic.

Perceptual Thresholds for Radial Optic Flow Distortion in Near-Eye Stereoscopic Displays.

We provide the first perceptual quantification of user's sensitivity to radial optic flow artifacts and demonstrate a promising approach for masking this optic flow artifact via blink suppression. Near-eye HMOs allow users to feel immersed in virtual environments by providing visual cues, like motion parallax and stereoscopy, that mimic how we view the physical world. However, these systems exhibit a variety of perceptual artifacts that can limit their usability and the user's sense of presence in VR. One well-known artifact is the vergence-accommodation conflict (VAC). Varifocal displays can mitigate VAC, but bring with them other artifacts such as a change in virtual image size (radial optic flow) when the focal plane changes. We conducted a set of psychophysical studies to measure users' ability to perceive this radial flow artifact before, during, and after self-initiated blinks. Our results showed that visual sensitivity was reduced by a factor of 10 at the start and for ~70 ms after a blink was detected. Pre- and post-blink sensitivity was, on average, ~O.15% image size change during normal viewing and increased to ~1.5- 2.0% during blinks. Our results imply that a rapid (under 70 ms) radial optic flow distortion can go unnoticed during a blink. Furthermore, our results provide empirical data that can be used to inform engineering requirements for both hardware design and software-based graphical correction algorithms for future varifocal near-eye displays. Our project website is available at https://gamma.umd.edu/ROF/.

Accommodation response and spherical aberration during 1-Year of orthokeratology lens wear and after discontinuation.

BACKGROUND: To assess accommodation and spherical aberration changes during one year of orthokeratology lens wear and one month after lens cessation. METHODS: A prospective, randomized, longitudinal study was conducted on forty-seven young healthy subjects at the Optometry Clinic of the Complutense University of Madrid (Spain). Non-cycloplegic refraction, high and low uncorrected visual acuity, high and low best corrected visual acuity, accommodative lag, horizontal near phoria, corneal topography, and high-order aberrations were performed at baseline, 1-day, 1-week, 1-, 6- and 12-months of lens wear and after one month of wash out period. p < 0.05 was considered as statistically significant. RESULTS: Spherical equivalent refraction (SE) was -3.23 ± 1.57D at baseline and -0.36 ± 0.64D after 12-months of lens wear, while accommodative lag changed from 0.53 ± 0.39D to 0.15 ± 0.29D after one year of lens wear. No significant differences were found when comparing SE at baseline and after one month of lens cessation (p > 0.05). A high correlation was found between the accommodative lag at baseline and after 12 M of lens wear. 22 out of 25 subjects with exophoria at baseline showed a significant reduction in the deviation at 12-months (p < 0.05). Total spherical aberration increased during all visits due to the lens wear (p < 0.05) although internal spherical aberration showed a significant decrease for 1-week, 1-month and 12-month visits (p < 0,05). CONCLUSION: Orthokeratology lenses may change the accommodative response of the patient as a reduction on accommodative lag on exophoric patients and an overall increase on the internal spherical aberrations was found during treatment but return to nearly baseline values when cessation.

Understanding accommodative control in the clinic: Modeling latency and amplitude for uncorrected refractive error, presbyopia and cycloplegia.

Accommodation is the process of adjusting the eye's optical power so as to focus at different distances. Uncorrected refractive error and/or functional presbyopia mean that sharp focus may not be achievable for some distances, so observers experience sustained defocus. Here, we identify a problem with current models of accommodative control: They predict excessive internal responses to stimuli outside accommodative range, leading to unrealistic adaptation effects. Specifically, after prolonged exposure to stimuli outside range, current models predict long latencies in the accommodative response to stimuli within range, as well as unrealistic dynamics and amplitudes of accommodative vergence innervation driven by the accommodative neural controller. These behaviors are not observed empirically. To solve this issue, we propose that the input to blur-driven accommodation is not retinal defocus, but correctable defocus. Predictive models of accommodative control already estimate demand from sensed defocus, using a realistic "virtual plant" to estimate accommodation. Correctable defocus can be obtained by restricting this demand to values physically attainable by the eye. If we further postulate that correctable defocus is computed using an idealized virtual plant that retains a young accommodative range, we can explain why accommodative-convergence responses are observed for stimuli that are too near-but not too far-to focus on. We model cycloplegia as a change in gain, and postulate a form of neural myopia to explain the additional relaxation of accommodation often seen with cycloplegia. This model produces plausible predictions for the accommodative response and accommodative convergence signal in a wide range of clinically relevant situations.

Anterior Segment Biometry During Accommodation After Posterior Chamber Phakic Implantable Collamer Lens Implantation.

PURPOSE: To evaluate the dynamic changes in anterior segment parameters during accommodation following Implantable Collamer Lens (ICL) implantation with swept-source optical coherence tomography (SS-OCT). METHODS: Under the accommodation of 0.00 diopters (D), 3.00 D, and maximum amplitude, SS-OCT was used to examine the anterior segment parameters, including ICL vault, ICL depth (the distance between the corneal endothelium and the posterior surface of ICL), crystalline lens thickness, anterior chamber depth, and various parameters of the anterior chamber angle, comprising angle opening distance, angle recess area, trabecular iris space area, and trabecular iris angle. RESULTS: During accommodation, the ICL vault showed a significant decrease from baseline (536 ± 278 µm) to 3.00 D (522 ± 281 µm), followed by an increase from 3.00 D to maximum amplitude (548 ± 306 µm) (analysis of variance [ANOVA], P < .001). Four eyes (2.61%) exhibited a decrease in ICL vault to less than 100 µm (47 ± 32 µm) at maximum accommodation. The ICL depth decreased significantly as accommodation increased (ANOVA, P < .001). Crystalline lens thickness increased, whereas anterior chamber depth decreased during accommodation (ANOVA, P < .001). The anterior chamber angle widened during 3.00 D of accommodation but narrowed at maximum accommodation, leading to significant changes in the angle opening distance, angle recess area, trabecular iris space area, and trabecular iris angle during accommodation (ANOVA, P < .001 for all). CONCLUSIONS: The anterior segment, including ICL vault and anterior chamber angle, undergo significant dynamic changes during accommodation. These accommodative changes may require careful monitoring for the surgery design of ICL implantation. [J Refract Surg. 2024;40(3):e164-e172.].

Model of zonular forces on the lens capsule during accommodation.

How the human eye focuses for near; i.e. accommodates, is still being evaluated after more than 165 years. The mechanism of accommodation is essential for understanding the etiology and potential treatments for myopia, glaucoma and presbyopia. Presbyopia affects 100% of the population in the fifth decade of life. The lens is encased in a semi-elastic capsule with attached ligaments called zonules that mediate ciliary muscle forces to alter lens shape. The zonules are attached at the lens capsule equator. The fundamental issue is whether during accommodation all the zonules relax causing the central and peripheral lens surfaces to steepen, or the equatorial zonules are under increased tension while the anterior and posterior zonules relax causing the lens surface to peripherally flatten and centrally steepen while maintaining lens stability. Here we show with a balloon capsule zonular force model that increased equatorial zonular tension with relaxation of the anterior and posterior zonules replicates the topographical changes observed during in vivo rhesus and human accommodation of the lens capsule without lens stroma. The zonular forces required to simulate lens capsule configuration during in vivo accommodation are inconsistent with the general belief that all the zonules relax during accommodation.

Digital device viewing behaviour in children.

INTRODUCTION: Habitual viewing behaviour is widely believed to be an important contributing factor to the onset and progression of myopia and may be task dependent. The purpose of this study was to quantify the habitual viewing distance of children performing five different tasks on a smartphone digital device. METHODS: The real-time viewing distance in 38 children with their habitual correction was measured using software (MyopiaApp) on a handheld (Google Pixel 3) device. Five tasks were performed in a randomised sequence: playing a game, watching video in a light (680 lux) and dark (5.5 lux) environment and reading small (8 pt) and large (16 pt) text. ANCOVA statistical analysis was used to evaluate the effect of task, group (myope vs. non-myope) and arm length on the median relative viewing distance. RESULTS: Arm length was not correlated with viewing distance in any of the tasks, and there was no significant difference in viewing distance between any of the tasks. Specifically, a two-way mixed ANCOVA indicated that task, refractive group (myopic vs. non-myopic), age and arm length, as well as all two-way interactions were not significantly associated with viewing distance. Overall, 60% of the total variance in viewing distance was accounted for by individual differences. CONCLUSIONS: The average handheld viewing distance was similar across a variety of everyday tasks in a representative sample of myopic and emmetropic children. Neither arm length, age nor refractive group were associated with viewing distance in any of the tasks. Importantly, myopic children of a given size did not hold the smartphone digital device at a different distance for any task than their equally sized non-myopic peers. However, both groups exhibited high inter-individual variability in mean viewing distance, indicating some subjects performed all tasks at further distances while other subjects used at nearer distances.

Anterior Chamber and Retinal Morphological Changes During Accommodation in Different Age Ranges.

PURPOSE: Accommodation mainly affects the lens, a structure of the eyeball that degrades with age. The aim of this work was to study the morphological changes of different ocular structures during accommodation, both in the anterior pole and the posterior pole, which may also be involved in the accommodation process. METHODS: The study will be carried out by stimulating accommodation through lenses of -1.00, -3.00 and -5.00 D starting from the spherical equivalent (M) of each participant in different age groups, from 18 to 66 years. To obtain the M value, aberrometry was achieved, and retinal optical coherence tomography and anterior pole tomography were performed to evaluate the possible structural modifications (central and peripheral), while accommodation was progressively stimulated. RESULTS: It showed that as the accommodative demand increased, morphological changes were produced in retinal thickness, both in the central and peripheral retina, in all age groups. A thinning of the retina was observed in the central 3 mm, while significant progressive thickening was observed closer to the periphery (up to 6 mm from the fovea) as the required accommodative power increased. A decrease in the anterior chamber depth (ACD) and anterior chamber volume (ACV) was observed with increasing lens power. CONCLUSION: Structural changes were observed in the central and peripheral retina, as well as in the ACD and ACV, while progressively greater accommodation was stimulated, showing that these structures were modified in the accommodation process even in advanced presbyopes.

Pupillary dynamics, accommodation and vergence in concussion.

Concussion, which is usually associated with head injuries, has received considerable attention in recent years because of its possible long-term cognitive and visual consequences. The review summarised the mild traumatic brain injury literature. Pupillary dynamics, which are primarily mediated by the autonomic nervous system, play an important function in regulating the amount of light entering the eye, but they can be dramatically impacted after a concussion. This can result in aberrant pupillary responses, which may have ramifications for light sensitivity, a common post-concussion symptom. In concussed individuals, accommodation and vergence - the visual processes responsible for focusing on near and distant objects - might be interrupted, potentially leading to fuzzy vision, eyestrain, and difficulty with tasks that require precise visual coordination. Understanding the delicate interplay between these three components of vision in the setting of concussions is critical for creating more targeted diagnostic and rehabilitative techniques, ultimately enhancing the quality of life for those who have had head injuries.

Ciliary muscle and anterior segment characteristics in pre-presbyopic adults with Down syndrome.

PURPOSE: Previous research has shown that accommodation deficits are common in individuals with Down syndrome (DS), but the origin and mechanisms behind these deficits are still unknown. The aim of this study was to investigate the characteristics of different ocular structures involved in accommodation, in particular the ciliary muscle (CM), in a population of individuals with DS to further understand this deficit and its mechanisms. METHODS: Thirty-two volunteer participants of pre-presbyopic age with (n = 16) and without DS (n = 16) were recruited. Temporal and nasal images of the CM were acquired using anterior segment optical coherence tomography (AS-OCT) while participants fixated an eccentrically located target. Analysis of CM parameters was undertaken using validated semi-automated software. Axial length, anterior chamber depth, lens thickness and corneal curvature were obtained with the Topcon Aladdin Optical Biometer and Corneal Topographer. Non-cycloplegic refractive error and accommodative ability were obtained with an open-field autorefractor and dynamic retinoscopy, respectively. Independent t-tests were conducted to determine differences in CM and other anterior segment parameters between participants with and without DS. RESULTS: No significant differences were found in the CM parameters studied between participants with and without DS (p > 0.05). In contrast, significant differences were found in visual acuity (p < 0.001), accommodative response (p < 0.001) and corneal curvature (K1 p = 0.003 and K2 p < 0.001) between participants with and without DS. CONCLUSIONS: Despite having poorer accommodation, pre-presbyopic adults with DS do not have a different CM morphology to that found in typically developing adults. These findings suggest that the accommodative deficit found in this population is not due to a mechanical deficit of the CM.

Ocular accommodation and wavelength: The effect of longitudinal chromatic aberration on the stimulus-response curve.

The longitudinal chromatic aberration (LCA) of the eye creates a chromatic blur on the retina that is an important cue for accommodation. Although this mechanism can work optimally in broadband illuminants such as daylight, it is not clear how the system responds to the narrowband illuminants used by many modern displays. Here, we measured pupil and accommodative responses as well as visual acuity under narrowband light-emitting diode (LED) illuminants of different peak wavelengths. Observers were able to accommodate under narrowband light and compensate for the LCA of the eye, with no difference in the variability of the steady-state accommodation response between narrowband and broadband illuminants. Intriguingly, our subjects compensated more fully for LCA at nearer distances. That is, the difference in accommodation to different wavelengths became larger when the object was placed nearer the observer, causing the slope of the accommodation response curve to become shallower for shorter wavelengths and steeper for longer ones. Within the accommodative range of observers, accommodative errors were small and visual acuity normal. When comparing between illuminants, when accommodation was accurate, visual acuity was worst for blue narrowband light. This cannot be due to the sparser spacing for S-cones, as our stimuli had equal luminance and thus activated LM-cones roughly equally. It is likely because ocular LCA changes more rapidly at shorter wavelength and so the finite spectral bandwidth of LEDs corresponds to a greater dioptric range at shorter wavelengths. This effect disappears for larger accommodative errors, due to the increased depth of focus of the eye.

Impact of focus cue presentation on perceived realism of 3-D scene structure: Implications for scene perception and for display technology.

Stereoscopic imagery often aims to evoke three-dimensional (3-D) percepts that are accurate and realistic-looking. The "gap" between 3-D imagery and real scenes is small, but focus cues typically remain incorrect because images are displayed on a single focal plane. Research has concentrated on the resulting vergence-accommodation conflicts. Yet, incorrect focus cues may also affect the appearance of 3-D imagery. We investigated whether incorrect focus cues reduce perceived realism of 3-D structure ("depth realism"). Experiment 1 used a multiple-focal-planes display to compare depth realism with correct focus cues vs. conventional stereo presentation. The stimuli were random-dot stereograms, which isolated the role of focus cues. Depth realism was consistently lower with incorrect focus cues, providing proof-of-principle evidence that they contribute to perceptual realism. Experiments 2 and 3 examined whether focus cues play a similar role with realistic objects, presented with an almost complete set of visual cues using a high-resolution, high-dynamic-range multiple-focal-planes display. We also examined the efficacy of approximating correct focus cues via gaze-contingent depth-of-field rendering. Improvements in depth realism with correct focus cues were less clear in more realistic scenes, indicating that the role of focus cues in depth realism depends on scene content. Rendering-based approaches, if anything, reduced depth realism, which we attribute to their inability to present higher-order aspects of blur correctly. Our findings suggest future general 3-D display solutions may need to present focus cues correctly to maximise perceptual realism.

Objective and subjective assessment of accommodative insufficiency.

SIGNIFICANCE: A variety of subjective and objective procedures are available to measure the amplitude of accommodation. However, it is unclear whether the standard criterion of Hofstetter's minimum minus 2 D can be used to diagnose accommodative insufficiency with each of these techniques. PURPOSE: The use of objective dynamic retinoscopy and three subjective techniques to diagnosis accommodative insufficiency was examined. METHODS: A total of 632 subjects between 8 and 19 years of age were enrolled. Accommodative lag, monocular accommodative facility, and subjective (push-up, modified push-down, and minus lens) and objective (dynamic retinoscopy) amplitude of accommodation were quantified. Accommodative insufficiency was diagnosed based on Hofstetter's minimum minus 2 D for each subjective method, as well as adding an additional subjective criterion (either accommodative lag exceeding 0.75 D or monocular accommodative facility falling below the age-expected norms). RESULTS: The prevalence of accommodative insufficiency was lowest and highest with the push-up (7.9 and 1%) and dynamic retinoscopy (94 and 12%) procedures when measured without and with the additional subjective criteria, respectively. Comparing the validity of dynamic retinoscopy against the traditional criterion, moderate to low sensitivity and high specificity were found. However, adding the additional subjective criteria improved the findings with moderate to high sensitivity and high specificity. Using a cutoff for dynamic retinoscopy of 7.50 D showed moderate diagnostic accuracy based on likelihood ratios. CONCLUSIONS: It is clear that a revised definition of accommodative insufficiency is required, which must include the method of assessing accommodation. The various objective and subjective methods for quantifying the amplitude of accommodation are not interchangeable, and subjective assessment does not provide a valid measure of the accommodative response.

Intracapsular accommodation mechanism in terms of lens curvature gradient.

The intracapsular accommodation mechanism (IAM) may be understood as an increase in the lens equivalent refractive index as the eye accommodates. Our goal was to evaluate the existence of an IAM by analysing observed changes in the inner curvature gradient of the lens. To this end, we fitted a gradient index and curvature lens model to published experimental data on external and nucleus geometry changes during accommodation. For each case analysed, we computed the refractive power and equivalent index for each accommodative state using a ray transfer matrix. All data sets showed an increase in the effective refractive index, indicating a positive IAM, which was stronger for older lenses. These results suggest a strong dependence of the lens equivalent refractive index on the inner curvature gradient.