Evaluating spatial dependency of the spectral efficiency in trans-palpebral illumination for widefield fundus photography.

Multi-spectral widefield fundus photography is valuable for the clinical diagnosis and management of ocular conditions that may impact both central and peripheral regions of the retina and choroid. Trans-palpebral illumination has been demonstrated as an alternative to transpupillary illumination for widefield fundus photography without requiring pupil dilation. However, spectral efficiency can be complicated due to the spatial variance of the light property through the palpebra and sclera. This study aims to investigate the effect of light delivery location on spectral efficiency in trans-palpebral illumination. Four narrow-band light sources, covering both visible and near infrared (NIR) wavelengths, were used to evaluate spatial dependency of spectral illumination efficiency. Comparative analysis indicated a significant dependence of visible light efficiency on spatial location, while NIR light efficiency is only slightly affected by the illumination location. This study confirmed the pars plana as the optimal location for delivering visible light to achieve color imaging of the retina. Conversely, spatial location is not critical for NIR light imaging of the choroid.

Light color efficiency-balanced trans-palpebral illumination for widefield fundus photography of the retina and choroid.

A wide-field fundus camera, which can selectively evaluate the retina and choroid, is desirable for better detection and treatment evaluation of eye diseases. Trans-palpebral illumination has been demonstrated for wide-field fundus photography, but its application for true-color retinal imaging is challenging due to the light efficiency delivered through the eyelid and sclera is highly wavelength dependent. This study is to test the feasibility of true-color retinal imaging using efficiency-balanced visible light illumination, and to validate multiple spectral imaging (MSI) of the retina and choroid. 530 nm, 625 nm, 780 nm and 970 nm light emission diodes (LED)s are used to quantitatively evaluate the spectral efficiency of the trans-palpebral illumination. In comparison with 530 nm illumination, the 625 nm, 780 nm and 970 nm light efficiencies are 30.25, 523.05, and 1238.35 times higher. The light efficiency-balanced 530 nm and 625 nm illumination control can be used to produce true-color retinal image with contrast enhancement. The 780 nm light image enhances the visibility of choroidal vasculature, and the 970 nm image is predominated by large veins in the choroid. Without the need of pharmacological pupillary dilation, a 140° eye-angle field of view (FOV) is demonstrated in a snapshot fundus image. In coordination with a fixation target, the FOV can be readily expanded over the equator of the eye to visualize vortex ampullas.

Understanding the relationship between visual-angle and eye-angle for reliable determination of the field-of-view in ultra-wide field fundus photography.

Visual-angle has been used as the conventional unit to determine the field-of-view (FOV) in traditional fundus photography. Recently emerging usage of eye-angle as the unit in wide field fundus photography creates confusion about FOV interpretation in instrumentation design and clinical application. This study aims to systematically derive the relationship between the visual-angle θv and eye-angle θe, and thus to enable reliable determination of the FOV in wide field fundus photography. FOV conversion ratio θe/θv, angular conversion ratio Δθe/Δθv, retinal conversion ratio Δd/Δθv, retinal distance and area are quantitatively evaluated. Systematic analysis indicates that reliable conversion between the θv and θe requires determined nodal point and spherical radius of the eye; and the conversion ratio is not linear from the central field to peripheral region. Based on the eye model with average parameters, both angular conversion (Δθe/Δθv) and retinal conversion (Δd/Δθv) ratios are observed to have a 1.51-fold difference at the central field and far peripheral region. A conversion table, including θe/θv, Δθe/Δθv, Δd/Δθv, retinal area and percentage ratio, is created for reliable assessment of imaging systems with variable FOV.

Portable ultra-widefield fundus camera for multispectral imaging of the retina and choroid.

Multispectral imaging (MSI) of the retina and choroid has increasing interest for better diagnosis and treatment evaluation of eye diseases. However, currently available MSI systems have a limited field of view (FOV) to evaluate the peripheral retina. This study is to validate trans-pars-planar illumination for a contact-mode ultra-widefield MSI system. By freeing the available pupil for collecting imaging light only, the trans-pars-planar illumination enables a portable, non-mydriatic fundus camera, with 200° FOV in a single fundus image. The trans-pars-planar illumination, delivering illumination light from one side of the eye, naturally enables oblique illumination ophthalmoscopy to enhance the contrast of fundus imaging. A broadband (104 nm) 565 nm light-emitting diode (LED) is used for validating color fundus imaging first. Four narrowband (17-60 nm) 530 nm, 625 nm, 780 nm, and 970 nm LEDs are tested for MSI. With 530 nm illumination, the fundus image reveals retinal vasculature predominantly. 625 nm and 780 nm illuminations enhance the visibility of choroidal vasculature. With further increased wavelength of 970 nm, the fundus image is predominated by large veins in the choroid, with multiple vortex ampullas observed simultaneously in a single fundus image.

Transfer Learning for Automated OCTA Detection of Diabetic Retinopathy.

Purpose: To test the feasibility of using deep learning for optical coherence tomography angiography (OCTA) detection of diabetic retinopathy. Methods: A deep-learning convolutional neural network (CNN) architecture, VGG16, was employed for this study. A transfer learning process was implemented to retrain the CNN for robust OCTA classification. One dataset, consisting of images of 32 healthy eyes, 75 eyes with diabetic retinopathy (DR), and 24 eyes with diabetes but no DR (NoDR), was used for training and cross-validation. A second dataset consisting of 20 NoDR and 26 DR eyes was used for external validation. To demonstrate the feasibility of using artificial intelligence (AI) screening of DR in clinical environments, the CNN was incorporated into a graphical user interface (GUI) platform. Results: With the last nine layers retrained, the CNN architecture achieved the best performance for automated OCTA classification. The cross-validation accuracy of the retrained classifier for differentiating among healthy, NoDR, and DR eyes was 87.27%, with 83.76% sensitivity and 90.82% specificity. The AUC metrics for binary classification of healthy, NoDR, and DR eyes were 0.97, 0.98, and 0.97, respectively. The GUI platform enabled easy validation of the method for AI screening of DR in a clinical environment. Conclusions: With a transfer learning process for retraining, a CNN can be used for robust OCTA classification of healthy, NoDR, and DR eyes. The AI-based OCTA classification platform may provide a practical solution to reducing the burden of experienced ophthalmologists with regard to mass screening of DR patients. Translational Relevance: Deep-learning-based OCTA classification can alleviate the need for manual graders and improve DR screening efficiency.

Trans-pars-planar illumination enables a 200° ultra-wide field pediatric fundus camera for easy examination of the retina.

This study is to test the feasibility of using trans-pars-planar illumination for ultra-wide field pediatric fundus photography. Fundus examination of the peripheral retina is essential for clinical management of pediatric eye diseases. However, current pediatric fundus cameras with traditional trans-pupillary illumination provide a limited field of view (FOV), making it difficult to access the peripheral retina adequately for a comprehensive assessment of eye conditions. Here, we report the first demonstration of trans-pars-planar illumination in ultra-wide field pediatric fundus photography. For proof-of-concept validation, all off-the-shelf optical components were selected to construct a lab prototype pediatric camera (PedCam). By freeing the entire pupil for imaging purpose only, the trans-pars-planar illumination enables a 200° FOV PedCam, allowing easy visualization of both the central and peripheral retina up to the ora serrata. A low-cost, easy-to-use ultra-wide field PedCam provides a unique opportunity to foster affordable telemedicine in rural and underserved areas.

Holographic waveguide based optometer for the quantitative monitoring of ocular refractive error.

Oculomotor disorders are known to have profound impacts on a patients' quality of life. However, current clinical practice lacks the capability to provide simultaneous assessment of three tightly coupled oculomotor control components, i.e. eye movement, lens accommodation, and pupil response. In this study, a holographic waveguide (HW) based benchtop optometer was constructed and evaluated with a model eye. Experimental result and quantitative analysis indicate that a HW can convey high quality retinal images to a camera at an illumination level safe for human subjects and support high accuracy measurements of ocular refractive error over a wide range. Further development of a HW-based system promises a wearable, see-through device for comprehensive assessment of oculomotor control components while the subject is engaged in normal daily activities and thus enable advanced research and clinical management of oculomotor disorders.

Is age-related macular degeneration a local manifestation of systemic disorder? Changes in nailfold capillaries at age-related macular degeneration.

AIMS: Determining whether nailfold capillary involvement is present in patients with Age-related macular degeneration (AMD) and whether there are different nailfold capillaroscopy findings between wet and dry types. METHODS: From January 2016 to December 2017, with an initial diagnosis of AMD, 53 consecutive adult patients (AMD group) and 91 age- and sex-matched healthy individuals were studied prospectively. There was no history of any other ocular disease and other disease affecting nailfold capillaries. All subjects underwent a complete ophthalmic examination. The classified and advanced stages of wet and dry types were not included. All nailfold capillaroscopy examinations were performed by the same rheumatologist. RESULTS: It was found that the frequency of major capillaroscopic findings such as capillary ectasia, micro-hemorrhage, tortuosity, neo-formation, bizarre capillary, and bushy capillaries increased in the AMD group according to the normal group, but no significant relationship was found for capillary aneurysm. In dry or wet type of AMD in terms of ectasia, micro-hemorrhage, tortuosity, neo-formation, bizarre structure, bushy structure, or aneurism of nailfold capillaries, no significant correlation was found. CONCLUSIONS: Nailfold capillaroscopy can detect microvascular changes in the nailfold capillary, in early and late stages of AMD. There were morphological changes in the nailfold capillaries of AMD patients, suggesting that there are systemic superficial microvascular changes that may be due to the systemic nature of the disease.

OCT feature analysis guided artery-vein differentiation in OCTA.

Differential artery-vein analysis promises better sensitivity for retinal disease detection and classification. However, clinical optical coherence tomography angiography (OCTA) instruments lack the function of artery-vein differentiation. This study aims to verify the feasibility of using OCT intensity feature analysis to guide artery-vein differentiation in OCTA. Four OCT intensity profile features, including i) ratio of vessel width to central reflex, ii) average of maximum profile brightness, iii) average of median profile intensity, and iv) optical density of vessel boundary intensity compared to background intensity, are used to classify artery-vein source nodes in OCT. A blood vessel tracking algorithm is then employed to automatically generate the OCT artery-vein map. Given the fact that OCT and OCTA are intrinsically reconstructed from the same raw spectrogram, the OCT artery-vein map is able to guide artery-vein differentiation in OCTA directly.

Differential Artery-Vein Analysis Improves the Performance of OCTA Staging of Sickle Cell Retinopathy.

PURPOSE: We test if differential artery-vein analysis can increase the performance of optical coherence tomography angiography (OCTA) detection and classification of sickle cell retinopathy (SCR). METHOD: This observational case series was conducted in a tertiary-retina practice. Color fundus and OCTA images were collected from 20 control and 48 SCR subjects. Fundus data were collected from fundus imaging devices, and SD-OCT and corresponding OCTA data were acquired using a spectral-domain OCT (SD-OCT) angiography system. For each patient, color fundus image-guided artery-vein classification was conducted in the OCTA image. Traditional mean blood vessel tortuosity (m-BVT) and mean blood vessel caliber (m-BVC) in OCTA images were quantified for control and SCR groups. Artery BVC (a-BVC), vein BVC (v-BVC), artery BVT (a-BVT), and vein BVT (v-BVT) were calculated; and then the artery-vein ratio of BVC (AVR-BVC) and artery-vein ratio of BVT (AVR-BVT) were quantified for comparative analysis. RESULTS: We evaluated 40 control and 85 SCR images in this study. The color fundus image-guided artery-vein classification had 97.02% accuracy for differentiating arteries and veins in OCTA. Differential artery-vein analysis provided significant improvement (P < 0.05) in detecting and classifying SCR stages compared to traditional mean blood vessel analysis. AVR-BVT and AVR-BVC showed significant (P < 0.001) correlation with SCR severity. CONCLUSIONS: Differential artery-vein analysis can significantly improve the performance of OCTA detection and classification of SCR. AVR-BVT is the most sensitive feature that can classify control and mild SCR. TRANSLATIONAL RELEVANCE: SCR and other retinovascular diseases result in changes to the caliber and tortuosity appearance of arteries and veins separately. Differential artery-vein analysis can improve the performance of SCR detection and stage classification.

Color Fundus Image Guided Artery-Vein Differentiation in Optical Coherence Tomography Angiography.

Purpose: This study aimed to develop a method for automated artery-vein classification in optical coherence tomography angiography (OCTA), and to verify that differential artery-vein analysis can improve the sensitivity of OCTA detection and staging of diabetic retinopathy (DR). Methods: For each patient, the color fundus image was used to guide the artery-vein differentiation in the OCTA image. Traditional mean blood vessel caliber (m-BVC) and mean blood vessel tortuosity (m-BVT) in OCTA images were quantified for control and DR groups. Artery BVC (a-BVC), vein BVC (v-BVC), artery BVT (a-BVT), and vein BVT (a-BVT) were calculated, and then the artery-vein ratio (AVR) of BVC (AVR-BVC) and AVR of BVT (AVR-BVT) were quantified for comparative analysis. Sensitivity, specificity, and accuracy were used as performance metrics of artery-vein classification. One-way, multilabel ANOVA with Bonferroni's test and Student's t-test were employed for statistical analysis. Results: Forty eyes of 20 control subjects and 80 eyes of 48 NPDR patients (18 mild, 16 moderate, and 14 severe NPDR) were evaluated in this study. The color fundus image-guided artery-vein differentiation reliably identified individual arteries and veins in OCTA. AVR-BVC and AVR-BVT provided significant (P < 0.001) and moderate (P < 0.05) improvements, respectively, in detecting and classifying NPDR stages, compared with traditional m-BVC analysis. Conclusions: Color fundus image-guided artery-vein classification provides a feasible method to differentiate arteries and veins in OCTA. Differential artery-vein analysis can improve the sensitivity of OCTA detection and classification of DR. AVR-BVC is the most-sensitive feature, which can classify control and mild NPDR, providing a quantitative biomarker for objective detection of early DR.

Spontaneous Macular Hole Closure after Valsalva Retinopathy and Nd:YAG Laser Treatment.

PURPOSE: The purpose of this report is to present a case who had spontaneous macular hole closure after Nd:YAG laser membranotomy applied to premacular haemorrhage associated with Valsalva retinopathy. METHODS: Case report. RESULTS: A 19-year-old young male patient presented to our clinic with sudden vision loss in his right eye, which had occurred 2 weeks before, following push-up and sit-up exercise. The patient was found to have premacular haemorrhage associated with Valsalva retinopathy. Nd:YAG laser membranotomy was performed. During his follow-up at week 1, full-thickness MH was observed and he was put under observation. At month 6, his vision acuity improved, laser coagulation sites in the fundus disappeared, and macular hole closed spontaneously. CONCLUSION: Macular hole that develops after Nd:YAG laser treatment of Valsalva retinopathy may spontaneously be closed like in our case. However, there is a need for further research to understand the mechanism of closure.

Automated classification and quantitative analysis of arterial and venous vessels in fundus images.

It is known that retinopathies may affect arteries and veins differently. Therefore, reliable differentiation of arteries and veins is essential for computer-aided analysis of fundus images. The purpose of this study is to validate one automated method for robust classification of arteries and veins (A-V) in digital fundus images. We combine optical density ratio (ODR) analysis and blood vessel tracking algorithm to classify arteries and veins. A matched filtering method is used to enhance retinal blood vessels. Bottom hat filtering and global thresholding are used to segment the vessel and skeleton individual blood vessels. The vessel tracking algorithm is used to locate the optic disk and to identify source nodes of blood vessels in optic disk area. Each node can be identified as vein or artery using ODR information. Using the source nodes as starting point, the whole vessel trace is then tracked and classified as vein or artery using vessel curvature and angle information. 50 color fundus images from diabetic retinopathy patients were used to test the algorithm. Sensitivity, specificity, and accuracy metrics were measured to assess the validity of the proposed classification method compared to ground truths created by two independent observers. The algorithm demonstrated 97.52% accuracy in identifying blood vessels as vein or artery. A quantitative analysis upon A-V classification showed that average A-V ratio of width for NPDR subjects with hypertension decreased significantly (43.13%).

Contact-free trans-pars-planar illumination enables snapshot fundus camera for nonmydriatic wide field photography.

In conventional fundus photography, trans-pupillary illumination delivers illuminating light to the interior of the eye through the peripheral area of the pupil, and only the central part of the pupil can be used for collecting imaging light. Therefore, the field of view of conventional fundus cameras is limited, and pupil dilation is required for evaluating the retinal periphery which is frequently affected by diabetic retinopathy (DR), retinopathy of prematurity (ROP), and other chorioretinal conditions. We report here a nonmydriatic wide field fundus camera employing trans-pars-planar illumination which delivers illuminating light through the pars plana, an area outside of the pupil. Trans-pars-planar illumination frees the entire pupil for imaging purpose only, and thus wide field fundus photography can be readily achieved with less pupil dilation. For proof-of-concept testing, using all off-the-shelf components a prototype instrument that can achieve 90° fundus view coverage in single-shot fundus images, without the need of pharmacologic pupil dilation was demonstrated.

Near-infrared light-guided miniaturized indirect ophthalmoscopy for nonmydriatic wide-field fundus photography.

A portable fundus imager is essential for emerging telemedicine screening and point-of-care examination of eye diseases. However, existing portable fundus cameras have limited field of view (FOV) and frequently require pupillary dilation. We report here a miniaturized indirect ophthalmoscopy-based nonmydriatic fundus camera with a snapshot FOV up to 67° external angle, which corresponds to a 101° eye angle. The wide-field fundus camera consists of a near-infrared light source (LS) for retinal guidance and a white LS for color retinal imaging. By incorporating digital image registration and glare elimination methods, a dual-image acquisition approach was used to achieve reflection artifact-free fundus photography.

A New Objective Parameter in Hydroxychloroquine-Induced Retinal Toxicity Screening Test: Macular Retinal Ganglion Cell-Inner Plexiform Layer Thickness.

OBJECTIVES: This study aims to detect hydroxychloroquine (HCQ)-induced retinal toxicity at an earlier stage through the use of spectral-domain optical coherence tomography device, especially by measuring macular retinal ganglion cell-inner plexiform layer (RGC-IPL) thickness. PATIENTS AND METHODS: In this study, 92 eyes of 46 Caucasian female patients (mean age 53.6±8.1 years; range 32 to 69 years) who were taking HCQ were assigned to group 1, while 80 eyes of 40 age-matched Caucasian female control subjects (mean age 56.1±10.7 years; range 34 to 71 years) were assigned to group 2. RGC-IPL thickness and retinal nerve fiber layer thickness were measured in all subjects by Cirrus high-definition optical coherence tomography model 5000 device using macular cube 512¥128 and optic disc cube 200¥200 protocols. We performed an evaluation to see if there was any difference between the measured values of the groups. The correlation between average RGC-IPL thickness measures and cumulative dose of HCQ and duration of use was analyzed. RESULTS: Retinal ganglion cell-inner plexiform layer of group 1 was found to be statistically thinner than that of group 2 both on average and in all segments (superior, superonasal, inferonasal, inferotemporal and superotemporal) except inferior segment when segmented (p<0.05). Additionally, a statistically significant negative correlation was found between the average RGC-IPL thickness and cumulative dose of HCQ (r= -0.371, p=0.001) as well as the duration of use (r= -0.308, p=0.006). CONCLUSION: Patients taking HCQ were found to have decreased RGC-IPL thickness at an early stage due to retinal toxicity induced by the drug. We think that measuring the RGC-IPL thickness may become an important objective in HCQ screening tests.

Functional optical coherence tomography of neurovascular coupling interactions in the retina.

Quantitative evaluation of retinal neurovascular coupling is essential for a better understanding of visual function and early detection of eye diseases. However, there is no established method to monitor coherent interactions between stimulus-evoked neural activity and hemodynamic responses at high resolution. Here, we report a multimodal functional optical coherence tomography (OCT) imaging methodology to enable concurrent intrinsic optical signal (IOS) imaging of stimulus-evoked neural activity and hemodynamic responses at capillary resolution. OCT angiography guided IOS analysis was used to separate neural-IOS and hemodynamic-IOS changes in the same retinal image sequence. Frequency flicker stimuli evoked neural-IOS changes in the outer retina; that is, photoreceptor layer, first and then in the inner retina, including outer plexus layer (OPL), inner plexiform layer (IPL), and ganglion cell layer (GCL), which were followed by hemodynamic-IOS changes primarily in the inner retina; that is, OPL, IPL, and GCL. Different time courses and signal magnitudes of hemodynamic-IOS responses were observed in blood vessels with various diameters.

Combining ODR and Blood Vessel Tracking for Artery-Vein Classification and Analysis in Color Fundus Images.

PURPOSE: This study aims to develop a fully automated algorithm for artery-vein (A-V) and arteriole-venule classification and to quantify the effect of hypertension on A-V caliber and tortuosity ratios of nonproliferative diabetic retinopathy (NPDR) patients. METHODS: We combine an optical density ratio (ODR) analysis and blood vessel tracking (BVT) algorithm to classify arteries and veins and arterioles and venules. An enhanced blood vessel map and ODR analysis are used to determine the blood vessel source nodes. The whole vessel map is then tracked beginning from the source nodes and classified as vein (venule) or artery (arteriole) using vessel curvature and angle information. Fifty color fundus images from NPDR patients are used to test the algorithm. Sensitivity, specificity, and accuracy metrics are measured to validate the classification method compared to ground truths. RESULTS: The combined ODR-BVT method demonstrates 97.06% accuracy in identifying blood vessels as vein or artery. Sensitivity and specificity of A-V identification are 97.58%, 97.81%, and 95.89%, 96.68%, respectively. Comparative analysis revealed that the average A-V caliber and tortuosity ratios of NPDR patients with hypertension have 48% and 15.5% decreases, respectively, compared to that of NPDR patients without hypertension. CONCLUSIONS: Automated A-V classification has been achieved by combined ODR-BVT analysis. Quantitative analysis of color fundus images verified robust performance of the A-V classification. Comparative quantification of A-V caliber and tortuosity ratios provided objective biomarkers to differentiate NPDR groups with and without hypertension. TRANSLATIONAL RELEVANCE: Automated A-V classification can facilitate quantitative analysis of retinal vascular distortions due to diabetic retinopathy and other eye conditions and provide increased sensitivity for early detection of eye diseases.