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BioRxiv : the Preprint Server For... Feb 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...
OBJECTIVE OR 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 following 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 following photoreceptor ablation and compared to responses from RGCs that had lost photoreceptor input more than two years prior.
PARTICIPANTS
Three eyes received photoreceptor ablation, OD of a male (M1), OS of a female (M2) and OD of a male (M3). Two animals were used for recording, one for histological assessment.
METHODS
Cones were ablated with an ultrafast laser delivered through an adaptive optics scanning light ophthalmoscope (AOSLO). A 0.5 s pulse of 25Hz 660nm light optogenetically stimulated RGCs, and the resulting GCaMP fluorescence signal was recorded using 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
Following photoreceptor ablation, the mean decay constant of the calcium response in RGCs decreased 1.5 fold (1.6±0.5 s to 0.6±0.3 s SD) over the 10 week observation period in subject 1 and 2.1 fold (2.5±0.5 s to 1.2±0.2 s SD) 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 photoreceptor ablation. The mean decay constant of optogenetic mediated calcium responses decreased 1.5 - 2-fold. 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.
PubMed: 37398439
DOI: 10.1101/2023.05.30.542908 -
Vision Research Sep 2023High-density threshold perimetry has found that conventional static threshold perimetry misses defects due to undersampling. However, high-density testing can be both...
High-density threshold perimetry has found that conventional static threshold perimetry misses defects due to undersampling. However, high-density testing can be both slow and limited by normal fixational eye movements. We explored alternatives by studying displays of high-density perimetry results for angioscotomas in healthy eyes-areas of reduced sensitivity in the shadows of blood vessels. The right eyes of four healthy adults were tested with a Digital Light Ophthalmoscope that gathered retinal images while presenting visual stimuli. The images were used to infer stimulus location on each trial. Contrast thresholds for a Goldmann size III stimulus were measured at 247 locations of a 13°×19° rectangular grid, with separation 0.5°, extending from 11° to 17° horizontally and -3° to +6° vertically, covering a portion of the optic nerve head and several major blood vessels. Maps of perimetric sensitivity identified diffuse regions of reduced sensitivity near the blood vessels, but these showed moderate structure-function agreement that was only modestly improved when effects of eye position were accounted for. An innovative method termed slice display was used to locate regions of reduced sensitivity. Slice display demonstrated that many fewer trials could yield similar structure-function agreement. These results are an indication that test duration might be reduced dramatically by focusing on location of defects rather than maps of sensitivity. Such alternatives to conventional threshold perimetry have the potential to map the shape of defects without the extensive time demands of high-density threshold perimetry. Simulations illustrate how such an algorithm could operate.
Topics: Adult; Humans; Visual Field Tests; Visual Fields; Optic Disk; Vision Disorders; Algorithms
PubMed: 37285782
DOI: 10.1016/j.visres.2023.108259 -
Ophthalmology Science Sep 2023Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system. Recent evidence suggests that degeneration of the inner layers of the...
PURPOSE
Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system. Recent evidence suggests that degeneration of the inner layers of the retina occurs in MS. This study aimed to examine whether there are outer retinal changes in patients living with MS.
DESIGN
This was a single center, cross-sectional study.
PARTICIPANTS
Sixteen patients with MS and 25 controls (volunteers without diagnosed MS) were recruited for the study.
METHODS
We acquired volumetric spectral domain-OCT scans of the macula and a circular scan around the optic nerve head (ONH). We also captured adaptive optics (AO) images at 0° (centered on the foveola), 2°, 4°, and 6° temporal to the fovea.
MAIN OUTCOME MEASURES
We calculated the thickness of the different retinal layers in the macula and around the ONH using the inbuilt software of the OCT. We evaluated changes in cone photoreceptors by calculating cone density and spacing by the inbuilt AO automatic segmentation algorithm with manual correction. We compared patients with and without optic neuritis and controls.
RESULTS
We found significant thinning of the inner retina and a thickening of the outer retina in the eye with a history of optic neuritis (eyes of patients with MS with a history of optic neuritis; mean difference [MD]: -11.13 ± 3.61 μm, = 0.002 and MD: 2.86 ± 0.89 μm, = 0.001; respectively). We did not observe changes in retinal layers without optic neuritis in eyes of patients with MS without a history of optic neuritis. However, regional differences were detected in the peripapillary retinal nerve fiber layer. Analyzing AO images revealed a significantly lower cone outer-segment density at all eccentricities in all patients compared with control eyes ( < 0.05), independent of optic neuritis history.
CONCLUSIONS
Our results showed that all MS cases were associated with decreased cone densities. Future longitudinal studies will help to elucidate whether this is a specific and sensitive method to detect and monitor the development and progression of MS.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found after the references.
PubMed: 37214765
DOI: 10.1016/j.xops.2023.100308 -
Retina (Philadelphia, Pa.) Aug 2023To describe the clinical characteristics and multimodal imaging features of a distinctive subtype of active idiopathic multifocal choroiditis (iMFC) lesions with...
PURPOSE
To describe the clinical characteristics and multimodal imaging features of a distinctive subtype of active idiopathic multifocal choroiditis (iMFC) lesions with grey-yellow chorioretinal lesions surrounded by smaller satellite dots, a presentation referred to as "chrysanthemum lesions."
METHODS
Retrospective, observational, multicenter case series of eyes with active iMFC and chrysanthemum lesions. Multimodal imaging features were reviewed and presented.
RESULTS
Twenty-five eyes from 20 patients (12 women and 8 men), with a mean age of 35.8 ± 17.0 years (range, 7-78 years) were included. Chrysanthemum lesions were equally located in the macula (48.0%) or the mid/far periphery (52.0%). The number of lesions per eye varied from 1 (16.0%) to more than 20 (56.0%). On optical coherence tomography, chrysanthemum lesions showed typical features of iMFC, including subretinal hyperreflective material splitting the retinal pigment epithelium/Bruch membrane. Chrysanthemum lesions were hypoautofluorescent on fundus autofluorescence imaging, hyperfluorescent on fluorescein angiography, hypofluorescent on indocyanine green angiography, and associated with choriocapillaris flow signal deficit on optical coherence tomography angiography.
CONCLUSION
Active iMFC may present with findings resembling chrysanthemum lesions. The distinctive lesion morphology on ophthalmoscopic examination, the large number of lesions, and the high prevalence of exclusive midperipheral and far peripheral involvement may represent a distinctive phenotype of iMFC.
Topics: Humans; Multifocal Choroiditis; Retrospective Studies; Fundus Oculi; Choroiditis; Choroid; Fluorescein Angiography; Tomography, Optical Coherence
PubMed: 37071923
DOI: 10.1097/IAE.0000000000003815 -
The British Journal of Ophthalmology Feb 2024To improve the accuracy of pterygium screening and detection through smartphones, we established a fusion training model by blending a large number of slit-lamp image...
BACKGROUND/AIMS
To improve the accuracy of pterygium screening and detection through smartphones, we established a fusion training model by blending a large number of slit-lamp image data with a small proportion of smartphone data.
METHOD
Two datasets were used, a slit-lamp image dataset containing 20 987 images and a smartphone-based image dataset containing 1094 images. The RFRC (Faster RCNN based on ResNet101) model for the detection model. The SRU-Net (U-Net based on SE-ResNeXt50) for the segmentation models. The open-cv algorithm measured the width, length and area of pterygium in the cornea.
RESULTS
The detection model (trained by slit-lamp images) obtained the mean accuracy of 95.24%. The fusion segmentation model (trained by smartphone and slit-lamp images) achieved a microaverage F score of 0.8981, sensitivity of 0.8709, specificity of 0.9668 and area under the curve (AUC) of 0.9295. Compared with the same group of patients' smartphone and slit-lamp images, the fusion model performance in smartphone-based images (F score of 0.9313, sensitivity of 0.9360, specificity of 0.9613, AUC of 0.9426, accuracy of 92.38%) is close to the model (trained by slit-lamp images) in slit-lamp images (F score of 0.9448, sensitivity of 0.9165, specificity of 0.9689, AUC of 0.9569 and accuracy of 94.29%).
CONCLUSION
Our fusion model method got high pterygium detection and grading accuracy in insufficient smartphone data, and its performance is comparable to experienced ophthalmologists and works well in different smartphone brands.
Topics: Humans; Smartphone; Pterygium; Cornea; Slit Lamp; Conjunctiva
PubMed: 36858799
DOI: 10.1136/bjo-2022-322552 -
Veterinary Ophthalmology Nov 2023To evaluate anterior segment angiographic findings in hypertensive ADAMTS10-open-angle glaucoma (ADAMTS10-OAG) eyes as compared to normotensive control eyes.
OBJECTIVE
To evaluate anterior segment angiographic findings in hypertensive ADAMTS10-open-angle glaucoma (ADAMTS10-OAG) eyes as compared to normotensive control eyes.
ANIMALS STUDIED
Nine ADAMTS10-OAG beagles and four wild-type control dogs.
PROCEDURES
Anterior segment angiography was performed under general anesthesia following intravenous injection of indocyanine green (ICG; 1 mg/kg) and sodium fluorescein (SF; 20 mg/kg) using a Heidelberg Spectralis® confocal scanning laser ophthalmoscope. Time to onset of iridal angiographic phases and the presence/severity of dye leakage into the iris stromal and/or aqueous humor were recorded. Group findings were compared, and multiple linear regression analysis was performed to identify potential factor associations with disease status.
RESULTS
Time to onset of all angiographic phases visualized using ICG was significantly prolonged while time to onset of SF leakage into the aqueous humor was significantly reduced in glaucomatous eyes compared to controls. Only glaucomatous eyes (n = 9) demonstrated evidence of SF stromal leakage. Mean intraocular pressure (IOP) and age were significantly higher, while mean cardiac pulse was significantly lower in glaucomatous eyes compared to controls. Blood pressure and ocular perfusion pressure were not significantly different between groups. Multiple linear regression analysis, controlling for age, IOP, and pulse demonstrated glaucoma, was not predictive of the time to onset of any angiographic phase, stromal, or aqueous humor leakage. However, pulse was a significant factor contributing to the severity of aqueous humor leakage.
CONCLUSIONS
A compromised vascular supply to the anterior segment exists in dogs with ADAMTS10-OAG. These observations warrant further exploration of what role altered perfusion and/or disruption to the blood-aqueous barrier may play.
Topics: Animals; Dogs; Angiography; Dog Diseases; Glaucoma; Glaucoma, Open-Angle; Intraocular Pressure; Iris; ADAMTS Proteins
PubMed: 36855027
DOI: 10.1111/vop.13075 -
Medical Education Online Dec 2023To evaluate the effectiveness of smartphone ophthalmoscope (SO) in teaching ophthalmoscopy, compared with direct ophthalmoscope (DO). In this cross-over study, 45... (Randomized Controlled Trial)
Randomized Controlled Trial
To evaluate the effectiveness of smartphone ophthalmoscope (SO) in teaching ophthalmoscopy, compared with direct ophthalmoscope (DO). In this cross-over study, 45 final-year medical students attending sessions at a single institution were randomly allocated to two groups (A and B). Both groups attended two training sessions. In the first session, Group A students were taught ophthalmoscopy using DO and Group B students using SO. In the second session, the training sessions were crossed over. A series of eye models with 10 letters placed on the inner surface were designed to assess the students' skill on ophthalmoscopy. Students performed ophthalmoscopy on the eye models, recorded their findings, and completed a questionnaire of feedback on DO and SO. The main outcome measure was the score of ophthalmoscopy, assessed by the student correctly recording each letter (score 1 for each letter). For Group A, the mean score of ophthalmoscopy on the eye model using DO and SO was 3.9±2.4 and 8.2±2.2, respectively. For Group B, the mean score of ophthalmoscopy on the eye model using SO and DO 8.7±1.8 and 5.7±3.5 . Students scored significantly higher in ophthalmoscopy when using SO than DO (<0.001). They expressed better visualization of the fundus using SO than DO (4.49±0.65 vs 4.13±0.81, =0.004). Students' performance of ophthalmoscopy was better when SO was used compared with DO. The use of SO as an adjunctive tool is recommended to improve the effectiveness of teaching ophthalmoscopy.
Topics: Humans; Smartphone; Cross-Over Studies; Ophthalmology; Ophthalmoscopy; Ophthalmoscopes; Students, Medical; Teaching
PubMed: 36762913
DOI: 10.1080/10872981.2023.2176201