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Investigative Ophthalmology & Visual... Jul 2023Choroideremia (CHM) is an X-linked inherited retinal degeneration causing loss of the photoreceptors, retinal pigment epithelium, and choriocapillaris, although patients...
PURPOSE
Choroideremia (CHM) is an X-linked inherited retinal degeneration causing loss of the photoreceptors, retinal pigment epithelium, and choriocapillaris, although patients typically retain a central island of relatively preserved, functioning retina until late-stage disease. Here, we investigate cone photoreceptor morphology within the retained retinal island by examining cone inner segment area, density, circularity, and intercone space.
METHODS
Using a custom-built, multimodal adaptive optics scanning light ophthalmoscope, nonconfocal split-detection images of the photoreceptor mosaic were collected at 1°, 2°, and 4° temporal to the fovea from 13 CHM and 12 control subjects. Cone centers were manually identified, and cone borders were segmented. A custom MATLAB script was used to extract area and circularity for each cone and calculate the percentage of intercone space in each region of interest. Bound cone density was also calculated. An unbalanced two-way ANOVA and Bonferroni post hoc tests were used to assess statistical differences between the CHM and control groups and along retinal eccentricity.
RESULTS
Cone density was lower in the CHM group than in the control group (P < 0.001) and decreased with eccentricity from the fovea (P < 0.001). CHM cone inner segments were larger in area (P < 0.001) and more circular (P = 0.042) than those of the controls. Intercone space in CHM was also higher than in the controls (P < 0.001).
CONCLUSIONS
Cone morphology is altered in CHM compared to control, even within the centrally retained, functioning retinal area. Further studies are required to determine whether such morphology is a precursor to cone degeneration.
Topics: Humans; Retinal Cone Photoreceptor Cells; Choroideremia; Ophthalmoscopy; Retina; Retinal Pigment Epithelium; Tomography, Optical Coherence
PubMed: 37504961
DOI: 10.1167/iovs.64.10.36 -
BMJ Open Ophthalmology Jul 2023As more preterm infants survive, complications of preterm birth, including retinopathy of prematurity (ROP), become more prevalent. ROP rates and blindness from ROP are...
BACKGROUND
As more preterm infants survive, complications of preterm birth, including retinopathy of prematurity (ROP), become more prevalent. ROP rates and blindness from ROP are higher in low-income and middle-income countries, where exposure to risk factors can be higher and where detection and treatment of ROP are under-resourced or non-existent. Access to low-cost imaging devices would improve remote screening capabilities for ROP.
METHODS
Target product profiles (TPPs) are developed early in the medical device development process to define the setting, target user and range of product requirements. A Delphi-like process, consisting of an online survey and consensus meeting, was used to develop a TPP for an ROP imaging device, collecting feedback on a proposed set of 64 product requirements.
RESULTS
Thirty-six stakeholders from 17 countries provided feedback: clinicians (72%), product developers (14%), technicians (6%) and other (8%). Thirty-six per cent reported not currently screening for ROP, with cited barriers including cost (44%), no training (17%) and poor image quality (16%). Among those screening (n=23), 48% use more than one device, with the most common being an indirect ophthalmoscope (87%), followed by RetCam (26%) and smartphone with image capture (26%). Consensus was reached on 53 (83%) product requirements. The 11 remaining were discussed at the consensus meeting, and all but two achieved consensus.
CONCLUSIONS
This TPP process was novel in that it successfully brought together diverse stakeholders to reach consensus on the product requirements for an ROP imaging devices. The resulting TPP provides a framework from which innovators can develop prototypes.
Topics: Infant; Female; Infant, Newborn; Humans; Infant, Premature; Retinopathy of Prematurity; Resource-Limited Settings; Premature Birth; Poverty
PubMed: 37493654
DOI: 10.1136/bmjophth-2022-001197 -
Clinical Ophthalmology (Auckland, N.Z.) 2023To better understand the sensory impact of retinal exam components typically experienced by infants undergoing various retinopathy of prematurity staging examinations,...
PURPOSE
To better understand the sensory impact of retinal exam components typically experienced by infants undergoing various retinopathy of prematurity staging examinations, adults concerned for infant welfare and exam quality underwent similar exams to compare their perceived stress.
PATIENTS AND METHODS
Adults directly involved with ROP exams and infant stress reduction had cardiac monitoring and concomitant ordinal self symptom-score (1-10 Likert) during 15 components of the exam including lid speculum, various scleral depressors, indirect ophthalmoscopy, goniolens and direct ophthalmoscopy and retinal photography (Phoenix ICON) with or without topical anesthesia.
RESULTS
Nine adults provided impressions and cardiac rhythm gathered supine over 15 minutes. Pain score for topical anesthetic 2 was less than for tropicamide 4. Lid specula numb scored a median 2 level (from 1 to 10) pain but without anesthetic scored 6. The goniolens numb scored 3. Scleral depression numb scored 3-4 but increased to 7 without topical anesthesia. Direct ophthalmoscope scored 3 through the goniolens and the retinal camera scored 4 pain. Brightness with low 350 Lux indirect scored 6-8 numb and 9 brightness without anesthetic. Full bright indirect, direct ophthalmoscope and the retinal camera all had Lux of 3000-4000 and were scored brightness 9, 7 and 10, respectively. Adults had minimal oculocardiac reflex during on-globe retinal examination methods (range 98% to 102%).
CONCLUSION
Topical anesthesia provided a moderate reduction in pain during on-globe lid-speculum, scleral depressed indirect examination. There was a synergistic augmented sensory response between pain and brightness. Adults did not show the bradycardia typically elicited by retinal examinations in premature infants.
PubMed: 37465272
DOI: 10.2147/OPTH.S418150 -
Investigative Ophthalmology & Visual... Jul 2023To measure photoreceptor packing density and S-cone spatial resolution as a function of retinal eccentricity in patients with enhanced S-cone syndrome (ESCS) and to...
PURPOSE
To measure photoreceptor packing density and S-cone spatial resolution as a function of retinal eccentricity in patients with enhanced S-cone syndrome (ESCS) and to discuss the possible mechanisms supporting their supernormal S-cone acuity.
METHODS
We used an adaptive optics scanning laser ophthalmoscope (AOSLO) to characterize photoreceptor packing. A custom non-AO display channel was used to measure L/M- and S-cone-mediated visual acuity during AOSLO imaging. Acuity measurements were obtained using a four-alternative, forced-choice, tumbling E paradigm along the temporal meridian between the fovea and 4° eccentricity in five of six patients and in seven control subjects. L/M acuity was tested by presenting long-pass-filtered optotypes on a black background, excluding wavelengths to which S-cones are sensitive. S-cone isolation was achieved using a two-color, blue-on-yellow chromatic adaptation method that was validated on three control subjects.
RESULTS
Inter-cone spacing measurements revealed a near-uniform cone density profile (ranging from 0.9-1.5 arcmin spacing) throughout the macula in ESCS. For comparison, normal cone density decreases by a factor of 14 from the fovea to 6°. Cone spacing of ESCS subjects was higher than normal in the fovea and subnormal beyond 2°. Compared to the control subjects (n = 7), S-cone-mediated acuities in patients with ESCS were normal near the fovea and became increasingly supernormal with retinal eccentricity. Beyond 2°, S-cone acuities were superior to L/M-cone-mediated acuity in the ESCS cohort, a reversal of the trend observed in normal retinas.
CONCLUSIONS
Higher than normal parafoveal cone densities (presumably dominated by S-cones) confer better than normal S-cone-mediated acuity in ESCS subjects.
Topics: Humans; Retinal Cone Photoreceptor Cells; Retina; Retinal Degeneration; Visual Acuity; Fovea Centralis; Ophthalmoscopy
PubMed: 37459066
DOI: 10.1167/iovs.64.10.17 -
Investigative Ophthalmology & Visual... Jul 2023Capillary flow plays an important role in the nourishment and maintenance of healthy neural tissue and can be observed directly and non-invasively in the living human...
PURPOSE
Capillary flow plays an important role in the nourishment and maintenance of healthy neural tissue and can be observed directly and non-invasively in the living human retina. Despite their importance, patterns of normal capillary flow are not well understood due to limitations in spatial and temporal resolution of imaging data.
METHODS
Capillary flow characteristics were studied in the retina of three healthy young individuals using a high-resolution adaptive optics ophthalmoscope. Imaging with frame rates of 200 to 300 frames per second was sufficient to capture details of the single-file flow of red blood cells in capillaries over the course of about 3 seconds.
RESULTS
Erythrocyte velocities were measured from 72 neighboring vessels of the parafoveal capillary network for each subject. We observed strong variability among vessels within a given subject, and even within a given imaged field, across a range of capillary flow parameters including maximum and minimum velocities, pulsatility, abruptness of the systolic peak, and phase of the cardiac cycle. The observed variability was not well explained by "local" factors such as the vessel diameter, tortuosity, length, linear cell density, or hematocrit of the vessel. Within a vessel, a moderate relation between the velocities and hematocrit was noted, suggesting a redistribution of plasma between cells with changes in flow.
CONCLUSIONS
These observations advance our fundamental understanding of normal capillary physiology and raise questions regarding the potential role of network-level effects in explaining the observed flow heterogeneity.
Topics: Humans; Capillaries; Retina; Erythrocytes; Blood Flow Velocity; Veins; Retinal Vessels
PubMed: 37450310
DOI: 10.1167/iovs.64.10.15 -
Translational Vision Science &... Jul 2023To investigate the agreement between a fundus camera and a scanning laser ophthalmoscope in retinal vessel caliber measurements and to identify whether the presence of...
PURPOSE
To investigate the agreement between a fundus camera and a scanning laser ophthalmoscope in retinal vessel caliber measurements and to identify whether the presence of the central light reflex (CLR) explains potential discrepancies.
METHODS
For this cross-sectional study, we obtained fundus camera and scanning laser ophthalmoscope images from 85 eyes of 85 healthy individuals (aged 50-65 years) with different blood pressure status. We measured the central retinal artery equivalent (CRAE) and central retinal artery vein equivalent (CRVE) with the Knudtson-Parr-Hubbard algorithm and assessed the CLR using a semiautomatic grading method. We used Bland-Altman plots, 95% limits of agreement, and the two-way mixed effects intraclass correlation coefficient for consistency [ICC(3,1)] to describe interdevice agreement. We used multivariable regression to identify factors associated with differences in between-device measurements.
RESULTS
The between-device difference in CRAE (9.5 µm; 95% confidence interval, 8.0-11.1 µm) was larger than the between-device difference in CRVE (2.9 µm; 95% confidence interval, 1.3-4.5 µm), with the fundus camera yielding higher measurements (both P < 0.001). The 95% fundus camera-scanning laser ophthalmoscope limits of agreement were -4.8 to 23.9 µm for CRAE and -12.0 to 17.8 µm for CRVE. The corresponding ICCs(3,1) were 0.89 (95% confidence interval, 0.83-0.92) and 0.91 (95% confidence interval, 0.86-0.94). The between-device CRAE difference was positively associated with the presence of a CLR (P = 0.002).
CONCLUSIONS
Fundus cameras and scanning laser ophthalmoscopes yield correlated but not interchangeable caliber measurements. The CLR induces bias in arteriolar caliber in fundus camera images, compared with scanning laser ophthalmoscope images.
TRANSLATIONAL RELEVANCE
Refined measurements could yield better estimates of the association between retinal vessel caliber and ophthalmic or systemic disease.
Topics: Humans; Cross-Sectional Studies; Retinal Vessels; Retinal Vein; Retinal Artery; Reflex
PubMed: 37450282
DOI: 10.1167/tvst.12.7.16 -
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 -
Life (Basel, Switzerland) May 2023The purpose of the present study was to document pathological findings on retromode imaging in choroidal nevi and evaluate its diagnostic validity, using the confocal...
The purpose of the present study was to document pathological findings on retromode imaging in choroidal nevi and evaluate its diagnostic validity, using the confocal scanning laser ophthalmoscope Nidek Mirante (cSLO). A total of 41 choroidal nevi from 41 patients were included. All patients underwent multicolor fundus (mCF), infrared reflectance (IR), green fundus autofluorescence (FAF), dark-field (DF) and retromode (RM) imaging and optical coherence tomography (OCT) scans. We investigated retromode images to evaluate choroidal nevus features by comparing the results with those of mCF, IR, FAF, DF and OCT. In 100% of available images, retromode scanning laser ophthalmoscopy was able to detect choroidal nevi with a characteristic "hypo-retro-reflective" pattern, even the cases not visible on mCF, IR and FAF images. It also made it possible to delineate the margins of lesions with the highest rate of sharpness and accuracy among the imaging modalities examined. These findings seem to demonstrate how RM-SLO is an innovative diagnostic tool to detect and follow up choroidal nevi in a fast, reliable and non-invasive way.
PubMed: 37374036
DOI: 10.3390/life13061253