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Translational Vision Science &... Jun 2024To assess longitudinal reproducibility of metrics of foveal density (peak cone density [PCD], cone density centroid [CDC], and 80th percentile centroid area) in...
PURPOSE
To assess longitudinal reproducibility of metrics of foveal density (peak cone density [PCD], cone density centroid [CDC], and 80th percentile centroid area) in participants with normal vision.
METHODS
Participants (n = 19; five male and 14 female) were imaged at two time points (average interval of 3.2 years) using an adaptive optics scanning light ophthalmoscope (AOSLO). Foveally centered regions of interest (ROIs) were extracted from AOSLO montages. Cone coordinate matrices were semiautomatically derived for each ROI, and cone mosaic metrics were calculated.
RESULTS
On average, there were no significant changes in cone mosaic metrics between visits. The average ± SD PCD was 187,000 ± 20,000 cones/mm2 and 189,000 ± 21,700 cones/mm2 for visits 1 and 2, respectively (P = 0.52). The average ± SD density at the CDC was 183,000 ± 19,000 cones/mm2 and 184,000 ± 20,800 cones/mm2 for visits 1 and 2, respectively (P = 0.78). The average ± SD 80th percentile isodensity contour area was 15,400 ± 1800 µm2 and 15,600 ± 1910 µm2 for visits 1 and 2, respectively (P = 0.57).
CONCLUSIONS
Foveal cone mosaic density metrics were highly reproducible in the cohort examined here, although further study is required in more diverse populations.
TRANSLATIONAL RELEVANCE
Determination of the normative longitudinal changes in foveal cone topography is key for evaluating longitudinal measures of foveal cone topography in patients with progressive retinal dystrophies.
Topics: Humans; Retinal Cone Photoreceptor Cells; Male; Fovea Centralis; Female; Adult; Reproducibility of Results; Middle Aged; Cell Count; Young Adult; Ophthalmoscopy; Tomography, Optical Coherence; Visual Acuity
PubMed: 38913007
DOI: 10.1167/tvst.13.6.18 -
Ophthalmology Science 2024Putative microglia were recently detected using adaptive optics ophthalmoscopy in healthy eyes. Here we evaluate the use of nonconfocal adaptive optics scanning light...
PURPOSE
Putative microglia were recently detected using adaptive optics ophthalmoscopy in healthy eyes. Here we evaluate the use of nonconfocal adaptive optics scanning light ophthalmoscopy (AOSLO) for quantifying the morphology and motility of presumed microglia and other immune cells in eyes with retinal inflammation from uveitis and healthy eyes.
DESIGN
Observational exploratory study.
PARTICIPANTS
Twelve participants were imaged, including 8 healthy participants and 4 posterior uveitis patients recruited from the clinic of 1 of the authors (M.H.E.).
METHODS
The Pittsburgh AOSLO imaging system was used with a custom-designed 7-fiber optical fiber bundle for simultaneous confocal and nonconfocal multioffset detection. The inner retina was imaged at several locations at multiple timepoints in healthy participants and uveitis patients to generate time-lapse images.
MAIN OUTCOME MEASURES
Microglia and macrophages were manually segmented from nonconfocal AOSLO images, and their morphological characteristics quantified (including soma size, diameter, and circularity). Cell soma motion was quantified across time for periods of up to 30 minutes and their speeds were calculated by measuring their displacement over time.
RESULTS
A spectrum of cell morphologies was detected in healthy eyes from circular amoeboid cells to elongated cells with visible processes, resembling activated and ramified microglia, respectively. Average soma diameter was 16.1 ± 0.9 μm. Cell movement was slow in healthy eyes (0.02 μm/sec on average), but macrophage-like cells moved rapidly in some uveitis patients (up to 3 μm/sec). In an eye with infectious uveitis, many macrophage-like cells were detected; during treatment their quantity and motility decreased as vision improved.
CONCLUSIONS
In vivo adaptive optics ophthalmoscopy offers promise as a potentially powerful tool for detecting and monitoring inflammation and response to treatment at a cellular level in the living eye.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 38881602
DOI: 10.1016/j.xops.2024.100475 -
Ophthalmology Science 2024Physiological changes in retinal ganglion cells (RGCs) have been reported in rodent models of photoreceptor (PR) loss, but this has not been investigated in primates. By...
PURPOSE
Physiological changes in retinal ganglion cells (RGCs) have been reported in rodent models of photoreceptor (PR) loss, but this has not been investigated in primates. By expressing both a calcium indicator (GCaMP6s) and an optogenetic actuator (ChrimsonR) in foveal RGCs of the macaque, we reactivated RGCs and assessed their response in the weeks and years after PR loss.
DESIGN
We used an calcium imaging approach to record optogenetically evoked activity in deafferented RGCs in primate fovea. Cellular scale recordings were made longitudinally over a 10-week period after PR ablation and compared with responses from RGCs that had lost PR input >2 years prior.
PARTICIPANTS
Three eyes received PR ablation, the right eye of a male (M1), the left eye of a female (M2), and the right eye of a male (M3). Two animals were used for recording, 1 for histological assessment.
METHODS
Cones were ablated with an ultrafast laser delivered through an adaptive optics scanning light ophthalmoscope (AOSLO). A 0.5 second pulse of 25 Hz 660 nm light optogenetically stimulated RGCs, and the resulting GCaMP fluorescence signal was recorded using an AOSLO. Measurements were repeated over 10 weeks immediately after PR ablation, at 2.3 years and in control RGCs.
MAIN OUTCOME MEASURES
The calcium rise time, decay constant, and sensitivity index of optogenetic-mediated RGC were derived from GCaMP fluorescence recordings from 221 RGCs (animal M1) and 218 RGCs (animal M2) .
RESULTS
After PR ablation, the mean decay constant of the calcium response in RGCs decreased 1.5-fold (standard deviation 1.6 ± 0.5 seconds to 0.6 ± 0.3 seconds) over the 10-week observation period in subject 1 and 2.1-fold (standard deviation 2.5 ± 0.5 seconds to 1.2 ± 0.2 seconds) within 8 weeks in subject 2. Calcium rise time and sensitivity index were stable. Optogenetic reactivation remained possible 2.3 years after PR ablation.
CONCLUSIONS
Altered calcium dynamics developed in primate foveal RGCs in the weeks after PR ablation. The mean decay constant of optogenetic-mediated calcium responses decreased 1.5- to twofold. This is the first report of this phenomenon in primate retina and further work is required to understand the role these changes play in cell survival and activity.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 38881601
DOI: 10.1016/j.xops.2024.100520 -
Translational Vision Science &... Jun 2024Both hypertension and diabetes are known to increase the wall-to-lumen ratio (WLR) of retinal arterioles, but the differential effects are unknown. Here, we study the...
PURPOSE
Both hypertension and diabetes are known to increase the wall-to-lumen ratio (WLR) of retinal arterioles, but the differential effects are unknown. Here, we study the timing and relative impact of hypertension versus diabetes on the WLR in diabetic retinopathy (DR) to address this unresolved question.
METHODS
This prospective cross-sectional study compared the retinal arteriolar WLR in 17 healthy eyes, 15 with diabetes but no apparent DR (DM no DR), and 8 with diabetic macular edema (DME) and either nonproliferative or proliferative DR. We imaged each arteriole using adaptive optics scanning laser ophthalmoscopy and measured the WLR using ImageJ. Multiple linear regression (MLR) was performed to estimate the effects of hypertension, diabetes, and age on the WLR.
RESULTS
Both subjects with DM no DR and subjects with DME had significantly higher WLR than healthy subjects (0.36 ± 0.08 and 0.42 ± 0.08 vs. 0.29 ± 0.07, 1-way ANOVA P = 0.0009). MLR in healthy subjects and subjects with DM no DR showed hypertension had the strongest effect (regression coefficient = 0.08, P = 0.009), whereas age and diabetes were not significantly correlated with WLR. MLR in all three groups together (healthy, DM no DR, and DME) showed diabetes had the strongest effect (regression coefficient = 0.05, P = 0.02), whereas age and hypertension were not significantly correlated with WLR.
CONCLUSIONS
Hypertension may be an early driver of retinal arteriolar wall thickening in preclinical DR, independent of age or diabetes, whereas changes specific to DR may drive wall thickening in DME and later DR stages.
TRANSLATIONAL RELEVANCE
We offer a framework for understanding the relative contributions of hypertension and diabetes on the vascular wall, and emphasize the importance of hypertension control early in diabetes even before DR onset.
Topics: Humans; Cross-Sectional Studies; Male; Diabetic Retinopathy; Female; Middle Aged; Prospective Studies; Arterioles; Hypertension; Ophthalmoscopy; Aged; Adult; Retinal Artery; Macular Edema
PubMed: 38874974
DOI: 10.1167/tvst.13.6.8 -
BMC Ophthalmology Jun 2024Refractive errors, amblyopia, strabismus, and low vision are more common among children with hearing impairments in comparison with their hearing peers. Neglecting...
BACKGROUND AND AIM
Refractive errors, amblyopia, strabismus, and low vision are more common among children with hearing impairments in comparison with their hearing peers. Neglecting visual disorders can pose educational and social problems for these children. The present study aimed to assess the prevalence of refractive errors, amblyopia, strabismus, and low vision among hearing-impaired and deaf students in Kermanshah.
MATERIALS AND METHODS
A total of 79 deaf and hearing impaired students within the age range of 7-20 years (mean age of 15.01 ± 2.72) underwent optometric examinations, including autorefractometry, retinoscopy, ophthalmoscopy, slit lamp, visual acuity measurement, and cover-uncover test. Those who needed further evaluation were referred to the Ophthalmology Clinic of Imam Khomeini Hospital.
RESULTS
Regarding the prevalence of refractive errors, 32 (40.5%) subjects had one or a combination of refractive errors, the most common of which was astigmatism (36.7%), followed by amblyopia (15.1%). The most common type of strabismus was latent strabismus (heterophoria) (88.6%), followed by exophoria (81%). Moreover, 3 (3.7%) cases had nystagmus. A significant difference was observed between the prevalence of amblyopia and the degree of hearing loss (P = 0.026), and no significant difference was detected in other cases.
CONCLUSION
As evidenced by the obtained results, refractive errors, amblyopia, strabismus, and low vision are more prevalent among deaf and hearing-impaired children compared to normal children because deaf and hearing-impaired children are not able to convey their vision problems and need to compensate for their poor hearing with an enhanced sense of sight, inattention to these disorders can present these children with serious educational and social problems. Therefore, eye screening examinations are of paramount importance in deaf and hearing-impaired children.
Topics: Humans; Strabismus; Child; Adolescent; Male; Female; Refractive Errors; Vision, Low; Amblyopia; Prevalence; Young Adult; Visual Acuity; Iran; Cross-Sectional Studies; Persons With Hearing Impairments; Deafness; Students
PubMed: 38867144
DOI: 10.1186/s12886-024-03515-5 -
Scientific Reports Jun 2024This study tested if a high-resolution, multi-modal, multi-scale retinal imaging instrument can provide novel information about structural abnormalities in vivo. The...
This study tested if a high-resolution, multi-modal, multi-scale retinal imaging instrument can provide novel information about structural abnormalities in vivo. The study examined 11 patients with very mild to moderate non-proliferative diabetic retinopathy (NPDR) and 10 healthy subjects using fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), adaptive optics scanning laser ophthalmoscopy (AO-SLO), adaptive optics OCT and OCTA (AO-OCT(A)). Of 21 eyes of 11 patients, 11 had very mild NPDR, 8 had mild NPDR, 2 had moderate NPDR, and 1 had no retinopathy. Using AO-SLO, capillary looping, inflections and dilations were detected in 8 patients with very mild or mild NPDR, and microaneurysms containing hyperreflective granular elements were visible in 9 patients with mild or moderate NPDR. Most of the abnormalities were seen to be perfused in the corresponding OCTA scans while a few capillary loops appeared to be occluded or perfused at a non-detectable flow rate, possibly because of hypoperfusion. In one patient with moderate NPDR, non-perfused capillaries, also called ghost vessels, were identified by alignment of corresponding en face AO-OCT and AO-OCTA images. The combination of multiple non-invasive imaging methods could identify prominent microscopic abnormalities in diabetic retinopathy earlier and more detailed than conventional fundus imaging devices.
Topics: Humans; Tomography, Optical Coherence; Diabetic Retinopathy; Female; Male; Ophthalmoscopy; Middle Aged; Capillaries; Adult; Retinal Vessels; Aged; Fluorescein Angiography
PubMed: 38862584
DOI: 10.1038/s41598-024-63749-7 -
Biomedical Optics Express May 2024The use of "quality" to describe the usefulness of an image is ubiquitous but is often subject to domain specific constraints. Despite its continued use as an imaging...
The use of "quality" to describe the usefulness of an image is ubiquitous but is often subject to domain specific constraints. Despite its continued use as an imaging modality, adaptive optics scanning light ophthalmoscopy (AOSLO) lacks a dedicated metric for quantifying the quality of an image of photoreceptors. Here, we present an approach to evaluating image quality that extracts an estimate of the signal to noise ratio. We evaluated its performance in 528 images of photoreceptors from two AOSLOs, two modalities, and healthy or diseased retinas. The algorithm was compared to expert graders' ratings of the images and previously published image quality metrics. We found no significant difference in the SNR and grades across all conditions. The SNR and the grades of the images were moderately correlated. Overall, this algorithm provides an objective measure of image quality that closely relates to expert assessments of quality in both confocal and split-detector AOSLO images of photoreceptors.
PubMed: 38855680
DOI: 10.1364/BOE.516477 -
BioRxiv : the Preprint Server For... May 2024In response to central nervous system (CNS) injury, tissue resident immune cells such as microglia and circulating systemic neutrophils are often first responders. The...
In response to central nervous system (CNS) injury, tissue resident immune cells such as microglia and circulating systemic neutrophils are often first responders. The degree to which these cells interact in response to CNS damage is poorly understood, and even less so, in the neural retina which poses a challenge for high resolution imaging in vivo. In this study, we deploy fluorescence adaptive optics scanning light ophthalmoscopy (AOSLO) to study fluorescent microglia and neutrophils in mice. We simultaneously track immune cell dynamics using label-free phase-contrast AOSLO at micron-level resolution. Retinal lesions were induced with 488 nm light focused onto photoreceptor (PR) outer segments. These lesions focally ablated PRs, with minimal collateral damage to cells above and below the plane of focus. We used in vivo (AOSLO, SLO and OCT) imaging to reveal the natural history of the microglial and neutrophil response from minutes-to-months after injury. While microglia showed dynamic and progressive immune response with cells migrating into the injury locus within 1-day after injury, neutrophils were not recruited despite close proximity to vessels carrying neutrophils only microns away. Post-mortem confocal microscopy confirmed in vivo findings. This work illustrates that microglial activation does not recruit neutrophils in response to acute, focal loss of photoreceptors, a condition encountered in many retinal diseases.
PubMed: 38854151
DOI: 10.1101/2024.05.25.595864 -
Journal of Vision Jun 2024The spectral locus of unique yellow was determined for flashes of different sizes (<11 arcmin) and durations (<500 ms) presented in and near the fovea. An adaptive...
The spectral locus of unique yellow was determined for flashes of different sizes (<11 arcmin) and durations (<500 ms) presented in and near the fovea. An adaptive optics scanning laser ophthalmoscope was used to minimize the effects of higher-order aberrations during simultaneous stimulus delivery and retinal imaging. In certain subjects, parafoveal cones were classified as L, M, or S, which permitted the comparison of unique yellow measurements with variations in local L/M ratios within and between observers. Unique yellow shifted to longer wavelengths as stimulus size or duration was reduced. This effect is most pronounced for changes in size and more apparent in the fovea than in the parafovea. The observed variations in unique yellow are not entirely predicted from variations in L/M ratio and therefore implicate neural processes beyond photoreception.
Topics: Humans; Photic Stimulation; Retinal Cone Photoreceptor Cells; Fovea Centralis; Color Perception; Retina; Adult; Ophthalmoscopy
PubMed: 38833255
DOI: 10.1167/jov.24.6.2