Intensity-based optoretinography reveals sub-clinical deficits in cone function in retinitis pigmentosa.

Introduction: Clinical tools have been widely used in the diagnosis, description, and monitoring the progression of retinitis pigmentosa (RP); however, many of these methods have inherently low sensitivity and specificity, and significant photoreceptor disruption can occur before RP progression has clinically manifest. Adaptive optics scanning light ophthalmoscopy (AOSLO) has shown promise as a powerful tool for assessing photoreceptor disruption both structurally and functionally due to its increased resolution. Methods: Here we assess photoreceptor structure and function at the cellular level through AOSLO by acquiring intensity based optoretinography (iORG) in 15 individuals with no reported retinal pathology and 7 individuals with a prior clinical diagnosis of RP. Photoreceptor structure was quantified by calculating cone nearest neighbor distance (NND) across different retinal eccentricities from the AOSLO images. Cone outer segment length was measured across different retinal eccentricities using optical coherence tomography (OCT) derived longitudinal reflectivity profiles (LRPs). Finally, iORG measures of photoreceptor function were compared to retinal sensitivity as measured using the macular integrity assessment (MAIA) microperimeter. Results: Broadly, participants with RP exhibited increasing cone nearest neighbor distances and decreasing cone outer segment length as a function of retinal eccentricity, consistent with prior reports for both controls and individuals with RP. Nearly all individuals with RP had reduced iORG amplitudes for all retinal eccentricities when compared to the control cohort, and the reduction was greater in eccentricities further from the fovea. Comparing iORG amplitudes to MAIA retinal sensitivity, we found that the iORG was more sensitive to early changes in photoreceptor function whereas MAIA was more sensitive to later stages of disease. Discussion: This highlights the utility of iORG as a method to detect sub-clinical deficits in cone function in all stages of disease progression and supports the future use of iORG for identifying cells that are candidates for cellular based therapies.

Blue Wavelength of Scanning Laser Ophthalmoscope Potentially Detects Arteriosclerotic Lesions in Diabetic Retinopathy.

(1) Background: The fundus examination is one of the best and popular methods in the assessment of vascular status in the human body. Direct viewing of retinal vessels by ophthalmoscopy has been utilized in judging hypertensive change or arteriosclerosis. Recently, fundus imaging with the non-mydriatic scanning laser ophthalmoscope (SLO) has been widely used in ophthalmological clinics since it has multimodal functions for optical coherence tomography or angiography with contrast agent dye. The purpose of this study was to examine the utility in detecting arteriosclerosis of retinal vessels in SLO images; (2) Methods: Both color and blue standard field SLO images of eyes with diabetic retinopathy (DR) were examined retrospectively. Retinal arteriosclerosis in color SLO images was graded according to the Scheie classification. Additionally, characteristics of retinal arterioles in blue SLO images were identified and examined for their relevance to arteriosclerosis grades, stages of DR or general complications; (3) Results: Relative to color fundus images, blue SLO images showed distinct hyper-reflective retinal arterioles against a monotone background. Irregularities of retinal arterioles identified in blue SLO images were frequently observed in the eyes of patients with severe arteriosclerosis (Grade 3: 79.0% and Grade 4: 81.8%). Furthermore, the findings on arterioles were more frequently associated with the eyes of DR patients with renal dysfunction (p < 0.05); (4) Conclusions: While color SLO images are equally as useful in assessing retinal arteriosclerosis as photography or ophthalmoscopy, the corresponding blue SLO images show arteriosclerotic lesions with high contrast in a monotone background. Retinal arteriosclerosis in eyes of advanced grades or advanced DR frequently show irregularities of retinal arterioles in the blue images. The findings of low, uneven, or discontinuous attenuation were easier to find in blue than in color SLO images. Consequently, blue SLO images can show pathological micro-sclerosis in retinal arterioles and are potentially one of the safe and practical methods for the vascular assessment of diabetic patients.

Imaging the Area of Internal Limiting Membrane Peeling after Macular Hole Surgery.

Background: The aim of this study was to compare en-face optical coherence tomography (OCT) imaging and confocal scanning laser ophthalmoscopy (cSLO) imaging at different wavelengths to identify the internal limiting membrane (ILM) peeling area after primary surgery with vitrectomy and ILM peeling for macular hole (MH). Methods: In total, 50 eyes of 50 consecutive patients who underwent primary surgery with vitrectomy and ILM peeling for MH were studied. The true ILM rhexis based on intraoperative color fundus photography was compared to the presumed ILM rhexis identified by a blinded examiner using en-face OCT imaging and cSLO images at various wavelengths. To calculate the fraction of overlap (FoO), the common intersecting area and the total of both areas were measured. Results: The FoO for the measured areas was 0.93 ± 0.03 for en-face OCT, 0.76 ± 0.06 for blue reflectance (BR; 488 nm), 0.71 ± 0.09 for green reflectance (GR; 514 nm), 0.56 ± 0.07 for infrared reflectance (IR; 815 nm) and 0.73 ± 0.06 for multispectral (MS). The FoO in the en-face OCT group was significantly higher than in all other groups, whereas the FoO in the IR group was significantly lower compared to all other groups. No significant differences were observed in FoO among the MS, BR, and GR groups. In en-face OCT, there was no significant change in the ILM peeled area measured intraoperatively and postoperatively (8.37 ± 3.01 vs. 8.24 ± 2.81 mm2; p = 0.8145). Nasal-inferior foveal displacement was observed in 38 eyes (76%). Conclusions: En-face OCT imaging demonstrates reliable postoperative visualization of the ILM peeled area. Although the size of the ILM peeling remains stable after one month, our findings indicate a notable inferior-nasal shift of the overall ILM peeling area towards the optic disc.

Clinical and genetic features in autosomal recessive bestrophinopathy in Chinese cohort.

PURPOSE: To provide a genotype and phenotype characterization of the BEST1 mutation in Chinese patients with autosomal recessive bestrophinopathy (ARB) through multimodal imaging and next-generation sequencing (NGS). METHODS: Seventeen patients from 17 unrelated families of Chinese origin with ARB were included in a retrospective cohort study. Phenotypic characteristics, including anterior segment features, were assessed by multimodal imaging. Multigene panel testing, involving 586 ophthalmic disease-associated genes, and Sanger sequencing were performed to identify disease-causing variants. RESULTS: Among 17 ARB patients, the mean follow-up was 15.65 months and average onset age was 30.53 years (range: 9-68). Best corrected visual acuity ranged from light perception to 0.8. EOG recordings showed a typically decreased Arden ratio in 12 patients, and a normal or slightly decreased Arden ratio in two patients. Anterior features included shallow anterior chambers (16/17), ciliary pronation (16/17), iris bombe (13/17), iridoschisis (2/17), iris plateau (1/17), narrow angles (16/17) and reduced axial lengths (16/17). Sixteen patients had multiple bilateral small, round, yellow vitelliform deposits distributed throughout the posterior pole, surrounding the optic disc. Initial diagnoses included angle-closure glaucoma (four patients), Best disease (three patients), and central serous chorioretinopathy secondary to choroidal neovascularization (CNV) (one patient), with the remainder diagnosed with ARB. Fourteen patients underwent preventive laser peripheral iridotomy, four of whom also received combined trabeculectomy and iridotomy in both eyes for uncontrolled intraocular pressure. One patient received intravitreal conbercept for CNV. Overall, 15 distinct disease-causing variants of BEST1 were identified, with 14 (82.35%) patients having missense mutations. Common mutations included p. Arg255-256 and p. Ala195Val (both 23.68%), with the most frequent sites in exons 7 and 5. CONCLUSIONS: This study provides a comprehensive characterization of anterior segment and genetic features in ARB, with a wide array of morphological abnormalities. Findings are relevant for refining clinical practices and genetic counseling and advancing pathogenesis research.

Application of novel non-invasive ophthalmic imaging to visualize peripapillary wrinkles, retinal folds and peripapillary hyperreflective ovoid mass-like structures associated with elevated intracranial pressure.

Background: Elevated intracranial pressure (ICP) is a serious and potentially life-threatening condition, for which clinically useful non-invasive measures have been elusive, in some cases due to their inadequate sensitivity and specificity. Our aim was to evaluate novel non-invasive ophthalmic imaging of selected pathological features seen in elevated ICP, namely peripapillary hyperreflective ovoid mass-like structures (PHOMS), peripapillary wrinkles (PPW) and retinal folds (RF) as potential biomarkers of elevated ICP. Methods: This single-center pilot study included subjects with untreated or incompletely treated high ICP. The retinas of these subjects were evaluated with averaged en-face optical coherence tomography (OCT), OCT retinal cross-sections (OCT B-scans), adaptive optics scanning light ophthalmoscopy (AOSLO), and fundus photos. Results: Seven subjects were included in the study. 6 subjects with high ICP (5 idiopathic intracranial hypertension, 1 medication induced, 30.8 ± 8.6 years, 75% female, 5 with papilledema) and 1 control (20-25 years) were included. PHOMS, PPW and RF were present in all subjects with papilledema, but neither in the high ICP subject without papilledema nor in the control subject. Averaged en-face OCT scans and AOSLO were more sensitive for PPW and RF than OCT B-scans and commercial fundus photos. Conclusion: PPW, RF and PHOMS volume have potential as non-invasive biomarkers of ICP. Novel imaging modalities may improve sensitivity. However, lack of automated image acquisition and processing limits current widespread adoption in clinical settings. Further research is needed to validate these structures as biomarkers for elevated ICP and improve clinical utility.

Discrimination of multiple sclerosis using scanning laser ophthalmoscopy images with autoencoder-based feature extraction.

OBJECTIVE: Optical coherence tomography (OCT) investigations have revealed that the thickness of inner retinal layers becomes decreased in multiple sclerosis (MS) patients, compared to healthy control (HC) individuals. To date, a number of studies have applied machine learning to OCT thickness measurements, aiming to enable accurate and automated diagnosis of the disease. However, there have much less emphasis on other less common retinal imaging modalities, like infrared scanning laser ophthalmoscopy (IR-SLO), for classifying MS. IR-SLO uses laser light to capture high-resolution fundus images, often performed in conjunction with OCT to lock B-scans at a fixed position. METHODS: We incorporated two independent datasets of IR-SLO images from the Isfahan and Johns Hopkins centers, consisting of 164 MS and 150 HC images. A subject-wise data splitting approach was employed to ensure that there was no leakage between training and test datasets. Several state-of-the-art convolutional neural networks (CNNs), including VGG-16, VGG-19, ResNet-50, and InceptionV3, and a CNN with a custom architecture were employed. In the next step, we designed a convolutional autoencoder (CAE) to extract semantic features subsequently given as inputs to four conventional ML classifiers, including support vector machine (SVM), k-nearest neighbor (K-NN), random forest (RF), and multi-layer perceptron (MLP). RESULTS: The custom CNN (85 % accuracy, 85 % sensitivity, 87 % specificity, 93 % area under the receiver operating characteristics [AUROC], and 94 % area under the precision-recall curve [AUPRC]) outperformed state-of-the-art models (84 % accuracy, 83 % sensitivity, 87 % specificity, 92 % AUROC, and 94 % AUPRC); however, utilizing a combination of the CAE and MLP yields even superior results (88 % accuracy, 86 % sensitivity, 91 % specificity, 94 % AUROC, and 95 % AUPRC). CONCLUSIONS: We utilized IR-SLO images to differentiate between MS and HC eyes, with promising results achieved using a combination of CAE and MLP. Future multi-center studies involving more heterogenous data are necessary to assess the feasibility of integrating IR-SLO images into routine clinical practice.

Foveal Retinal Ganglion Cells Develop Altered Calcium Dynamics Weeks After Photoreceptor Ablation.

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 in vivo and assessed their response in the weeks and years after PR loss. Design: We used an in vivo 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 Macaca mulatta (M1), the left eye of a female Macaca fascicularis (M2), and the right eye of a male Macaca fascicularis (M3). Two animals were used for in vivo 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) in vivo. 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.

Detection sensitivity of fluorescence lifetime imaging ophthalmoscopy for laser-induced selective damage of retinal pigment epithelium.

PURPOSE: To investigate the sensitivity of fluorescence lifetime imaging ophthalmoscopy (FLIO) to detect retinal laser spots by comparative analysis with other imaging modalities. METHODS: A diode laser with a wavelength of 514 nm was applied with pulse durations of 5.2, 12, 20, and 50 µs. The laser pulse energy was increased so that the visibility of the laser spot by slit-lamp fundus examination (SL) under the irradiator's observation covers from the subvisible to visible range immediately after irradiation. The irradiated areas were then examined by fundus color photography (FC), optical coherence tomography (OCT), fundus autofluorescence (AF), FLIO, and fluorescein angiography (FA). The visibility of a total of over 2200 laser spots was evaluated by two independent researchers, and effective dose (ED) 50 laser pulse energy values were calculated for each imaging modality and compared. RESULTS: Among examined modalities, FA showed the lowest mean of ED50 energy value and SL the highest, that is, they had the highest and lowest sensitivity to detect retinal pigment epithalium (RPE)-selective laser spots, respectively. FLIO also detected spots significantly more sensitively than SL at most laser pulse durations and was not significantly inferior to FA. AF was also often more sensitive than SL, but the difference was slightly less significant than FLIO. CONCLUSION: Considering its high sensitivity in detecting laser spots and previously reported potential of indicating local wound healing and metabolic changes around laser spots, FLIO may be useful as a non-invasive monitoring tool during and after minimally invasive retinal laser treatment.

Algorithm of automatic identification of diabetic retinopathy foci based on ultra-widefield scanning laser ophthalmoscopy.

AIM: To propose an algorithm for automatic detection of diabetic retinopathy (DR) lesions based on ultra-widefield scanning laser ophthalmoscopy (SLO). METHODS: The algorithm utilized the FasterRCNN (Faster Regions with CNN features)+ResNet50 (Residua Network 50)+FPN (Feature Pyramid Networks) method for detecting hemorrhagic spots, cotton wool spots, exudates, and microaneurysms in DR ultra-widefield SLO. Subimage segmentation combined with a deeper residual network FasterRCNN+ResNet50 was employed for feature extraction to enhance intelligent learning rate. Feature fusion was carried out by the feature pyramid network FPN, which significantly improved lesion detection rates in SLO fundus images. RESULTS: By analyzing 1076 ultra-widefield SLO images provided by our hospital, with a resolution of 2600×2048 dpi, the accuracy rates for hemorrhagic spots, cotton wool spots, exudates, and microaneurysms were found to be 87.23%, 83.57%, 86.75%, and 54.94%, respectively. CONCLUSION: The proposed algorithm demonstrates intelligent detection of DR lesions in ultra-widefield SLO, providing significant advantages over traditional fundus color imaging intelligent diagnosis algorithms.

Retinal Changes in Patients With Covid-19 and Different Expressiveness of Metabolic Changes.

AIMS: To study the relationship between the severity of COVID-induced metabolic changes and the structure and frequency of retinal changes, according to funduscopy data in patients with different clinical courses of COVID-19. MATERIALS AND METHODS: 117 patients with COVID-19 were examined. While examining patients, severity of the course of COVID-19, the expressiveness of changes in the metabolic status were determined; fundus image registration was performed with portable fundus cameras Pictor Plus Fundus Camera and VistaView (Volk Optical). RESULTS: As a result of the research, retinal changes were found in 49 (41.9 %) patients with COVID-19. In 8 (16.3 %) cases, clinically significant (vitreous hemorrhage, prethrombosis of the central retinal vein or branches of the central retinal vein, thrombosis of the central retinal vein or branches of the central retinal vein) COVID-induced retinal and ophthalmological changes were observed, which caused a decrease in visual acuity. In 41 (83.7 %) cases, clinically insignificant changes (cotton wool spots, narrowed retinal vessels, intraretinal and petechial hemorrhages, tortuosity and dilatation of retinal venules) COVID-induced retinal changes were observed. Clinically significant retinal changes occur in patients with a statistically significantly higher level of D-dimer and a greater percentage of lung parenchyma lesion than in the group of patients with clinically insignificant retinal changes (p < 0.05). CONCLUSIONS: The structure of retinal changes in patients with COVID-19 correlates with the severity of the clinical course of the disease and changes in the metabolic status of patients. Metabolic changes are correlated with retinal changes and can be predictive for preventing general vascular complications in COVID-19.

Effectiveness of simulation models and digital alternatives in training ophthalmoscopy: A systematic review.

PURPOSE: Traditional direct ophthalmoscopy (TDO) is the oldest method of fundus examination; however, it has fallen out of use due to its technical difficulty and limitations to clinical utility, amidst the advent of potentially better options. A spectrum of new technologies may help in addressing the shortcomings of TDO: simulation mannequins with non-tracked TDO, simulation models with tracked TDO, and smartphone ophthalmoscopy (SFO). METHODOLOGY: A systematic search of PubMed, Embase, and Cochrane databases for all studies evaluating usage of simulation mannequins/models and SFO in ophthalmology education was performed, from inception till April 2023 with no language restriction. We ensured that we included all possible relevant articles by performing backward reference searching of included articles and published review articles. RESULTS: We reviewed studies on non-tracked TDO (n = 5), tracked TDO (n = 3) and SFO (n = 12). Non-tracked TDO and SFO were superior in training competency relative to control (TDO on real eyes). Intriguingly, tracked TDO was non superior to controls. SFO appears to enhance the learning effectiveness of ophthalmoscopy, due to real-time projection of the retina view, permitting instantaneous and targeted feedback. Learners reported improved ergonomics, including a wider field of view and more comfortable viewing distance. Retention of images and recordings permitted the audit of learning and paves the way for storage of such images in patients' electronic medical record and rapid dissemination for specialist referral. CONCLUSIONS: Smartphone ophthalmoscopy (SFO) permits integration of both the practice and learning of ophthalmoscopy, and the auditing of both. These advantages over traditional methods (with simulation or otherwise) may lead to a paradigm shift in undergraduate ophthalmology education. However, the nascency of SFO necessitates preservation of traditional techniques to tide through this period of transition.

Artificial intelligence-enabled ophthalmoscopy for papilledema: a systematic review protocol.

Papilledema is a pathology delineated by the swelling of the optic disc secondary to raised intracranial pressure (ICP). Diagnosis by ophthalmoscopy can be useful in the timely stratification of further investigations, such as magnetic resonance imaging or computed tomography to rule out pathologies associated with raised ICP. In resource-limited settings, in particular, access to trained specialists or radiological imaging may not always be readily available, and accurate fundoscopy-based identification of papilledema could be a useful tool for triage and escalation to tertiary care centres. Artificial intelligence (AI) has seen a rise in neuro-ophthalmology research in recent years, but there are many barriers to the translation of AI to clinical practice. The objective of this systematic review is to garner and present a comprehensive overview of the existing evidence on the application of AI in ophthalmoscopy for papilledema, and to provide a valuable perspective on this emerging field that sits at the intersection of clinical medicine and computer science, highlighting possible avenues for future research in this domain.

Quantitative Analysis of the Vasculature and Cone Photoreceptors in Subjects With Diabetes Without Diabetic Retinopathy.

PURPOSE: To characterize any differences in the vasculature and cone photoreceptor packing geometry (CPG) between subjects with diabetes without/no diabetic retinopathy (NDR) and healthy controls. METHODS: Eight NDR and five controls were enrolled. Optical coherence tomography angiography (OCTA) taken at the macula was used to measure vessel density, vessel length density, and vessel density index (VDI) in three vascular plexuses, namely, the superficial vascular plexus, intermediate capillary plexus, and deep capillary plexus (DCP). The choriocapillaris (CC) flow deficit (FD) was also measured. OCTA images were binarized and processed to extrapolate the parafovea and parafoveal quadrants and the OCTA indices mentioned above. The CC was processed with six different radii to quantify FD. Adaptive optics - scanning laser ophthalmoscopy images were acquired and processed to extract CPG indices, i.e., cone density (CD), cone-to-cone spacing (CS), linear dispersion index, heterogeneity packing index and percent of cells with six neighbors at 3.6° in the temporal retina. RESULTS: In all eyes, statistically significant differences were found (i) in parafoveal FD across the six radii (p < 0.001) and (ii) in the correlation between the parafoveal temporal quadrant (PTQ) DCP VDI and CS (r = 0.606, p = 0.048). No other significant correlations were found. For OCTA or CPG indices, no significant differences were found between the cohorts in the parafovea or parafoveal quadrants. CONCLUSIONS: CS is the most sensitive CPG index for detecting alterations in the cone mosaic. The DCP and the cone photoreceptors are significantly correlated, indicating that alterations in the DCP can affect the cones. Future work elucidating the vascular alterations and neurodegeneration present in diabetic eyes should focus on the DCP and multiple CPG indices, not solely CD. Moreover, such alterations are highly localized, hence using larger regions e.g. parafovea versus smaller areas, such as the PTQ, will potentially mask significant correlations.

Artificial Intelligence in Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO) Data Analysis-Toward Retinal Metabolic Diagnostics.

The purpose of this study was to investigate the possibility of implementing an artificial intelligence (AI) approach for the analysis of fluorescence lifetime imaging ophthalmoscopy (FLIO) data even with small data. FLIO data, including the fluorescence intensity and mean fluorescence lifetime (τm) of two spectral channels, as well as OCT-A data from 26 non-smokers and 28 smokers without systemic and ocular diseases were used. The analysis was performed with support vector machines (SVMs), a well-known AI method for small datasets, and compared with the results of convolutional neural networks (CNNs) and autoencoder networks. The SVM was the only tested AI method, which was able to distinguish τm between non-smokers and heavy smokers. The accuracy was about 80%. OCT-A data did not show significant differences. The feasibility and usefulness of the AI in analyzing FLIO and OCT-A data without any apparent retinal diseases were demonstrated. Although further studies with larger datasets are necessary to validate the results, the results greatly suggest that AI could be useful in analyzing FLIO-data even from healthy subjects without retinal disease and even with small datasets. AI-assisted FLIO is expected to greatly advance early retinal diagnosis.

Non-invasive in vivo imaging of brain and retinal microglia in neurodegenerative diseases.

Microglia play crucial roles in immune responses and contribute to fundamental biological processes within the central nervous system (CNS). In neurodegenerative diseases, microglia undergo functional changes and can have both protective and pathogenic roles. Microglia in the retina, as an extension of the CNS, have also been shown to be affected in many neurological diseases. While our understanding of how microglia contribute to pathological conditions is incomplete, non-invasive in vivo imaging of brain and retinal microglia in living subjects could provide valuable insights into their role in the neurodegenerative diseases and open new avenues for diagnostic biomarkers. This mini-review provides an overview of the current brain and retinal imaging tools for studying microglia in vivo. We focus on microglia targets, the advantages and limitations of in vivo microglia imaging approaches, and applications for evaluating the pathogenesis of neurological conditions, such as Alzheimer's disease and multiple sclerosis.

Diagnostic Accuracy of Pediatrician-performed Digital Retinal Imaging with 3nethra neo for ROP Screening.

OBJECTIVES: To evaluate the accuracy of pediatrician-performed wide-field digital retinal imaging (WFDRI) for diagnosing Retinopathy of prematurity (ROP), as compared to binocular indirect ophthalmoscopy (BIO) as the reference standard. METHODS: Eligible infants undergoing ROP screening were enrolled consecutively. BIO was performed by trained ophthalmologists, followed by WFDRI (using "3nethra neo" camera) by a pediatrician. An expert pediatric ophthalmologist reviewed de-identified images for quality, presence, and severity of ROP. She was masked to the findings of BIO and the pediatrician. Diagnostic accuracy for detecting any ROP, ROP requiring treatment (Type 1), and ROP requiring referral (Type 1 or 2) were calculated for WFDRI, considering BIO as the reference standard. RESULTS: The analysis included 427 eyes. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic accuracy, and diagnostic odds ratio of WFDRI were 0.88 (95% CI: 0.81, 0.93), 0.89 (0.85, 0.92), 7.8 (5.7, 10.9), 0.14 (0.09, 0.21), 0.89 (0.85, 0.91), and 58.3 (31, 110) respectively for detection of 'any ROP'. For detecting ROP requiring treatment (Type 1), the sensitivity, specificity, NLR, and diagnostic accuracy were 0.90 (0.75, 0.97), 1.00 (0.99, 1.00), 0.11 (0.04, 0.27), and 0.99 (0.98, 1.00) respectively. For ROP requiring referral, the sensitivity, specificity, NLR, and diagnostic accuracy of pediatrician-performed WFDRI were 0.92 (0.80, 0.98), 1.00 (0.99, 1.00), 0.08 (0.03, 0.21), and 0.99 (0.98, 1.00) respectively. No serious adverse events were noted. The pediatrician and ophthalmologist had a near-perfect (k-1.00) and strong (k-0.88) agreement for ROP requiring treatment and any ROP, respectively. CONCLUSIONS: Pediatrician-performed WFDRI is feasible, safe, and has excellent diagnostic accuracy for identifying ROP requiring treatment.

Scanning Laser Ophthalmoscopy Demonstrates Pediatric Optic Disc and Peripapillary Strain During Horizontal Eye Rotation.

Purpose: We employed automated analysis of scanning laser ophthalmoscopy (SLO) to determine if mechanical strains imposed on disc, and retinal and choroidal vessels during horizontal duction in children differ from those of adults.Methods: Thirty-one children aged 11.3 ± 2.7 (standard deviation) years underwent SLO in central gaze, and 35° ab- and adduction. Automated registration with deep learning-based optical flow analysis quantified vessel deformations as horizontal, vertical, shear, and equivalent strains. Choroidal vessel displacements in lightly pigmented fundi, and central disc vessel displacements, were also observed.Results: As in adults, strain in vessels during horizontal duction was greatest at the disc and decreased with distance from it. Strain in the pediatric disc was similar to published values in young adults,1 but in the peripapillary region was greater and propagated significantly more peripherally to at least three disc radii from it. During adduction in children, the nasal disc was compressed and disc vessels distorted, but the temporal half experienced tensile strain, while peripapillary tissues were compressed. The pattern was similar but strains were less in abduction (p < .001). Choroidal vessels were visualized in 24 of the 62 eyes and shifted directionally opposite overlying retinal vessels.Conclusions: Horizontal duction deforms the normal pediatric optic disc, central retinal vessels, peripapillary retina, and choroid, shearing the inner retina over the choroid. These mechanical effects occur at the sites of remodeling of the disc, sclera, and choroid associated with typical adult features that later emerge later, including optic cup enlargement, temporal disc tilting, and peripapillary atrophy.

Motion Contrast, Phase Gradient, and Simultaneous OCT Images Assist in the Interpretation of Dark-Field Images in Eyes with Retinal Pathology.

The cellular-level visualization of retinal microstructures such as blood vessel wall components, not available with other imaging modalities, is provided with unprecedented details by dark-field imaging configurations; however, the interpretation of such images alone is sometimes difficult since multiple structural disturbances may be present in the same time. Particularly in eyes with retinal pathology, microstructures may appear in high-resolution retinal images with a wide range of sizes, sharpnesses, and brightnesses. In this paper we show that motion contrast and phase gradient imaging modalities, as well as the simultaneous acquisition of depth-resolved optical coherence tomography (OCT) images, provide additional insight to help understand the retinal neural and vascular structures seen in dark-field images and may enable improved diagnostic and treatment plans.

Visualization and Identification of Silicone Oil Emulsification Using Dynamic Infrared Confocal Scanning Laser Ophthalmoscopy.

Introduction: Silicone oil (SO) is a crucial agent used as an intraocular tamponade in the treatment of complex vitreoretinal diseases. Despite its effectiveness, SO is prone to emulsification, which can lead to significant and sometimes irreversible complications in both the anterior and posterior segments of the eye. The detection and monitoring of SO emulsification are therefore of paramount importance. Traditional imaging modalities have limitations in visualizing SO, leading to the exploration of more advanced imaging techniques. This study introduces the application of dynamic infrared confocal scanning laser ophthalmoscopy (IRcSLO) for this purpose and evaluates its effectiveness. Case Presentation: We report on 2 patients who underwent pars plana vitrectomy with subsequent SO injection for the management of retinal detachment. Postsurgery, both patients were imaged using the Heidelberg Retina Tomography Spectralis IRcSLO. The focus was on the visualization of the SO status, including the presence and distribution of emulsified SO droplets. The IRcSLO imaging technique demonstrated its capability to effectively visualize emulsified SO droplets. Interestingly, this was also true for cases where the SO had been removed. The emulsified droplets were observed as micron-sized, spherical entities with a nonuniform distribution throughout the vitreous cavity. Conclusion: Dynamic IRcSLO has proven to be an effective imaging modality for visualizing the emulsification of SO, offering a novel perspective into the characterization of SO droplets. It facilitates the analysis of droplet count, motility, and precise localization within the vitreous cavity. The findings from the case presentations underscore the variability of SO emulsification patterns and the sensitivity of IRcSLO in detecting even minuscule emulsified droplets. This imaging technique has significant potential for future research, particularly in understanding the timing of emulsification, the factors contributing to it, and the development of possible preventive strategies. Additionally, it allows for a more in-depth analysis of the behavior of emulsified SO droplets across different SO viscosities, which could be instrumental in optimizing patient outcomes.