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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 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 -
Health Informatics Journal 2024In this article, we provide a database of nonproliferative diabetes retinopathy, which focuses on early diabetes retinopathy with hard exudation, and further explore its...
OBJECTIVES
In this article, we provide a database of nonproliferative diabetes retinopathy, which focuses on early diabetes retinopathy with hard exudation, and further explore its clinical application in disease recognition.
METHODS
We collect the photos of nonproliferative diabetes retinopathy taken by Optos Panoramic 200 laser scanning ophthalmoscope, filter out the pictures with poor quality, and label the hard exudative lesions in the images under the guidance of professional medical personnel. To validate the effectiveness of the datasets, five deep learning models are used to perform learning predictions on the datasets. Furthermore, we evaluate the performance of the model using evaluation metrics.
RESULTS
Nonproliferative diabetes retinopathy is smaller than proliferative retinopathy and more difficult to identify. The existing segmentation models have poor lesion segmentation performance, while the intersection over union () value for deep lesion segmentation of models targeting small lesions can reach 66.12%, which is higher than ordinary lesion segmentation models, but there is still a lot of room for improvement.
CONCLUSION
The segmentation of small hard exudative lesions is more challenging than that of large hard exudative lesions. More targeted datasets are needed for model training. Compared with the previous diabetes retina datasets, the NDRD dataset pays more attention to micro lesions.
Topics: Diabetic Retinopathy; Humans; Deep Learning; Databases, Factual; Mass Screening; Male; Female
PubMed: 38864242
DOI: 10.1177/14604582241259328 -
BioRxiv : the Preprint Server For... May 2024By combining an external display operating at 360 frames per second with an Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO) for human foveal imaging, we...
By combining an external display operating at 360 frames per second with an Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO) for human foveal imaging, we demonstrate color stimulus delivery at high spatial and temporal resolution in AOSLO psychophysics experiments. A custom pupil relay enables viewing of the stimulus through a 3-mm effective pupil diameter and provides refractive error correction from -8 to +4 diopters. Performance of the assembled and aligned pupil relay was validated by measuring the wavefront error across the field of view and correction range, and the as-built Strehl ratio was 0.64 or better. High-acuity stimuli were rendered on the external display and imaged through the pupil relay to demonstrate that spatial frequencies up to 54 cycles per degree, corresponding to 20/11 visual acuity, are resolved. The completed external display was then used to render fixation markers across the field of view of the monitor, and a continuous retinal montage spanning 9.4 by 5.4 degrees of visual angle was acquired with the AOSLO. We conducted eye-tracking experiments during free-viewing and high-acuity tasks with polychromatic images presented on the external display. Sub-arcminute eye position uncertainty was achieved, enabling precise localization of the line of sight on the monitor while simultaneously imaging the fine structure of the human central fovea. This high refresh rate display overcomes the temporal, spectral, and field of view limitations of AOSLO-based stimulus presentation, enabling natural monocular viewing of stimuli in psychophysics experiments conducted with AOSLO.
PubMed: 38854135
DOI: 10.1101/2024.05.26.595808 -
BioRxiv : the Preprint Server For... Jun 2024High resolution retinal imaging paired with intravitreal injection of a viral vector coding for the calcium indicator GCaMP has enabled visualization of activity...
High resolution retinal imaging paired with intravitreal injection of a viral vector coding for the calcium indicator GCaMP has enabled visualization of activity dependent calcium changes in retinal ganglion cells (RGCs) at single cell resolution in the living eye. The inner limiting membrane (ILM) is a barrier for viral vectors, restricting transduction to a ring of RGCs serving the fovea in both humans and non-human primates (NHP). We evaluate peeling the ILM prior to intravitreal injection as a strategy to expand calcium imaging beyond the fovea in the NHP eye in vivo. Five Macaca fascicularis eyes (age 3-10y; n=3 individuals; 2M, 1F) underwent vitrectomy and 5 to 6-disc diameter ILM peel centered on the fovea prior to intravitreal delivery of 7m8:SNCG:GCaMP8s. Calcium responses from RGCs were recorded using a fluorescence adaptive optics scanning laser ophthalmoscope. In all eyes GCaMP was expressed throughout the peeled area, representing a mean 8-fold enlargement in area of expression relative to a control eye. Calcium recordings were obtained up to 11 degrees from the foveal center. RGC responses were comparable to the fellow control eye and showed no significant decrease over the 6 months post ILM peel, suggesting that RGC function was not compromised by the surgical procedure. In addition, we demonstrate that activity can be recorded directly from the retinal nerve fiber layer. This approach will be valuable for a range of applications in visual neuroscience including pre-clinical evaluation of retinal function, detecting vision loss, and assessing the impact of therapeutic interventions.
PubMed: 38854047
DOI: 10.1101/2024.06.02.597041 -
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 -
Ophthalmology Science 2024To utilize ultrawidefield (UWF) imaging to evaluate retinal and choroidal vasculature and structure in individuals with mild cognitive impairment (MCI) compared with...
PURPOSE
To utilize ultrawidefield (UWF) imaging to evaluate retinal and choroidal vasculature and structure in individuals with mild cognitive impairment (MCI) compared with that of controls with normal cognition.
DESIGN
Prospective cross sectional study.
PARTICIPANTS
One hundred thirty-one eyes of 82 MCI patients and 230 eyes of 133 cognitively normal participants from the Eye Multimodal Imaging in Neurodegenerative Disease Study.
METHODS
A scanning laser ophthalmoscope (California, Optos Inc) was used to obtain UWF fundus color images. Images were analyzed with the Vasculature Assessment Platform for Images of the Retina UWF (VAMPIRE-UWF 2.0, Universities of Edinburgh and Dundee) software.
MAIN OUTCOME MEASURES
Imaging parameters included vessel width gradient, vessel width intercept, large vessel choroidal vascular density, vessel tortuosity, and vessel fractal dimension.
RESULTS
Both retinal artery and vein width gradients were less negative in MCI patients compared with controls, demonstrating decreased rates of vessel thinning at the periphery ( < 0.001; = 0.027). Retinal artery and vein width intercepts, a metric that extrapolates the width of the vessel at the center of the optic disc, were smaller in MCI patients compared with that of controls ( < 0.001; = 0.017). The large vessel choroidal vascular density, which quantifies the vascular area versus the total choroidal area, was greater in MCI patients compared with controls ( = 0.025).
CONCLUSIONS
When compared with controls with normal cognition, MCI patients had thinner retinal vasculature manifested in both the retinal arteries and the veins. In MCI, these thinner arteries and veins attenuated at a lower rate when traveling toward the periphery. MCI patients also had increased choroidal vascular density.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 38827032
DOI: 10.1016/j.xops.2024.100480 -
Cureus May 2024This case report describes a complicated case of giant cell arteritis (GCA) with tongue necrosis and bilateral central retinal artery occlusion (CRAO). An 81-year-old...
This case report describes a complicated case of giant cell arteritis (GCA) with tongue necrosis and bilateral central retinal artery occlusion (CRAO). An 81-year-old male patient with a history of recent retinal artery occlusion, ischemic stroke, and hypertensive emergency was evaluated. Clinical examination, including a visual acuity assessment, fundus evaluation, and oral examination, was performed. Laboratory investigations, such as erythrocyte sedimentation rate (ESR), were conducted. A temporal artery biopsy was performed to confirm the diagnosis of GCA. The patient presented with sudden vision loss in the left eye following a prior episode of retinal artery occlusion in the right eye. Ophthalmoscopic examination revealed CRAO in the left eye. Additionally, tongue necrosis, a rare manifestation of GCA, was observed. The ESR was significantly elevated. A temporal artery biopsy supported the diagnosis of GCA. The patient was promptly referred for immunologist consultation and initiated on intravenous methylprednisolone therapy. This case highlights the diverse and potentially devastating nature of GCA, involving ocular and systemic manifestations. Bilateral CRAO and tongue necrosis are rare but significant complications of GCA. Prompt diagnosis and early initiation of corticosteroid therapy are crucial to prevent irreversible visual loss and further complications. A multidisciplinary approach involving ophthalmologists and other specialists is essential for the comprehensive management of GCA.
PubMed: 38826883
DOI: 10.7759/cureus.59554 -
Investigative Ophthalmology & Visual... May 2024To demonstrate the first near-infrared adaptive optics fluorescence lifetime imaging ophthalmoscopy (NIR-AOFLIO) measurements in vivo of the human retinal pigment...
PURPOSE
To demonstrate the first near-infrared adaptive optics fluorescence lifetime imaging ophthalmoscopy (NIR-AOFLIO) measurements in vivo of the human retinal pigment epithelial (RPE) cellular mosaic and to visualize lifetime changes at different retinal eccentricities.
METHODS
NIR reflectance and autofluorescence were captured using a custom adaptive optics scanning light ophthalmoscope in 10 healthy subjects (23-64 years old) at seven eccentricities and in two eyes with retinal abnormalities. Repeatability was assessed across two visits up to 8 weeks apart. Endogenous retinal fluorophores and hydrophobic whole retinal extracts of Abca4-/- pigmented and albino mice were imaged to probe the fluorescence origin of NIR-AOFLIO.
RESULTS
The RPE mosaic was resolved at all locations in five of seven younger subjects (<35 years old). The mean lifetime across near-peripheral regions (8° and 12°) was longer compared to near-foveal regions (0° and 2°). Repeatability across two visits showed moderate to excellent correlation (intraclass correlation: 0.88 [τm], 0.75 [τ1], 0.65 [τ2], 0.98 [a1]). The mean lifetime across drusen-containing eyes was longer than in age-matched healthy eyes. Fluorescence was observed in only the extracts from pigmented Abca4-/- mouse.
CONCLUSIONS
NIR-AOFLIO was repeatable and allowed visualization of the RPE cellular mosaic. An observed signal in only the pigmented mouse extract infers the fluorescence signal originates predominantly from melanin. Variations observed across the retina with intermediate age-related macular degeneration suggest NIR-AOFLIO may act as a functional measure of a biomarker for in vivo monitoring of early alterations in retinal health.
Topics: Humans; Retinal Pigment Epithelium; Ophthalmoscopy; Adult; Middle Aged; Animals; Female; Mice; Male; Young Adult; Optical Imaging; Reproducibility of Results; Infrared Rays; ATP-Binding Cassette Transporters; Fluorescein Angiography
PubMed: 38758638
DOI: 10.1167/iovs.65.5.27 -
Translational Vision Science &... May 2024
PubMed: 38709503
DOI: 10.1167/tvst.13.5.4