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High-quality imaging of the retina is crucial to the diagnosis and monitoring of disease, as well as for evaluating the success of therapeutics in human patients and in preclinical animal models. Here, we describe the basic principles and methods for in vivo retinal imaging in rodents, including fundus imaging, fluorescein angiography, optical coherence tomography, fundus autofluorescence, and infrared imaging. After providing a concise overview of each method and detailing the retinal diseases and conditions that can be visualized through them, we will proceed to discuss the advantages and disadvantages of each approach. These protocols will facilitate the acquisition of optimal images for subsequent quantification and analysis. Additionally, a brief explanation will be given regarding the potential results and the clinical significance of the detected abnormalities., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The use of deep learning for OCT image classification could enhance the diagnosis and monitoring of retinal diseases. However, challenges like variability in retinal abnormalities, noise, and artifacts in OCT images limit its clinical use. Our study aimed to evaluate the performance of various deep learning (DL) architectures in classifying retinal pathologies versus healthy cases based on OCT images, under data scarcity and label noise. We examined five DL architectures: ResNet18, ResNet34, ResNet50, VGG16, and InceptionV3. Fine-tuning of the pre-trained models was conducted on 5526 OCT images and reduced subsets down to 21 images to evaluate performance under data scarcity. The performance of models fine-tuned on subsets with label noise levels of 10%, 15%, and 20% was evaluated. All DL architectures achieved high classification accuracy (> 90%) with training sets of 345 or more images. InceptionV3 achieved the highest classification accuracy (99%) when trained on the entire training set. However, classification accuracy decreased and variability increased as sample size decreased. Label noise significantly affected model accuracy. Compensating for labeling errors of 10%, 15%, and 20% requires approximately 4, 9, and 14 times more images in the training set to reach the performance of 345 correctly labeled images. The results showed that DL models fine-tuned on sets of 345 or more OCT images can accurately classify retinal pathologies versus healthy controls. Our findings highlight that while mislabeling errors significantly impact classification performance in OCT analysis, this can be effectively mitigated by increasing the training sample size. By addressing data scarcity and labeling errors, our research aims to improve the real-world application and accuracy of retinal disease management., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Self-supervised learning has become the cornerstone of building generalizable and transferable artificial intelligence systems in medical imaging. In particular, contrastive representation learning techniques trained on large multi-modal datasets have demonstrated impressive capabilities of producing highly transferable representations for different downstream tasks. In ophthalmology, large multi-modal datasets are abundantly available and conveniently accessible as modern retinal imaging scanners acquire both 2D fundus images and 3D optical coherence tomography (OCT) scans to assess the eye. In this context, we introduce a novel multi-modal contrastive learning-based pipeline to facilitate learning joint representations for the two retinal imaging modalities. After self-supervised pre-training on 153,306 scan pairs, we show that such a pre-training framework can provide both a retrieval system and encoders that produce comprehensive OCT and fundus image representations that generalize well for various downstream tasks on three independent external datasets, explicitly focusing on clinically pertinent prediction tasks. In addition, we show that interchanging OCT with lower-cost fundus imaging can preserve the predictive power of the trained models., (© 2024. The Author(s).)

While Alzheimer's disease and other neurodegenerative diseases have traditionally been viewed as brain disorders, there is growing evidence indicating their manifestation in the eyes as well. The retina, being a developmental extension of the brain, represents the only part of the central nervous system that can be noninvasively imaged at a high spatial resolution. The discovery of the specific pathological hallmarks of Alzheimer's disease in the retina of patients holds great promise for disease diagnosis and monitoring, particularly in the early stages where disease progression can potentially be slowed. Among various retinal imaging methods, hyperspectral imaging has garnered significant attention in this field. It offers a label-free approach to detect disease biomarkers, making it especially valuable for large-scale population screening efforts. In this review, we discuss recent advances in the field and outline the current bottlenecks and enabling technologies that could propel this field toward clinical translation., (© 2024. The Author(s).)

The incorporation of gold nanoparticles (GNPs) into retinal imaging signifies a notable advancement in ophthalmology, offering improved accuracy in diagnosis and patient outcomes. This review explores the synthesis and unique properties of GNPs, highlighting their adjustable surface plasmon resonance, biocompatibility, and excellent optical absorption and scattering abilities. These features make GNPs advantageous contrast agents, enhancing the precision and quality of various imaging modalities, including photoacoustic imaging, optical coherence tomography, and fluorescence imaging. This paper analyzes the unique properties and corresponding mechanisms based on the morphological features of GNPs, highlighting the potential of GNPs in retinal disease diagnosis and management. Given the limitations currently encountered in clinical applications of GNPs, the approaches and strategies to overcome these limitations are also discussed. These findings suggest that the properties and efficacy of GNPs have innovative applications in retinal disease imaging.

The retina is an emerging CNS target for potential noninvasive diagnosis and tracking of Alzheimer's disease (AD). Studies have identified the pathological hallmarks of AD, including amyloid β-protein (Aβ) deposits and abnormal tau protein isoforms, in the retinas of AD patients and animal models. Moreover, structural and functional vascular abnormalities such as reduced blood flow, vascular Aβ deposition, and blood-retinal barrier damage, along with inflammation and neurodegeneration, have been described in retinas of patients with mild cognitive impairment and AD dementia. Histological, biochemical, and clinical studies have demonstrated that the nature and severity of AD pathologies in the retina and brain correspond. Proteomics analysis revealed a similar pattern of dysregulated proteins and biological pathways in the retina and brain of AD patients, with enhanced inflammatory and neurodegenerative processes, impaired oxidative-phosphorylation, and mitochondrial dysfunction. Notably, investigational imaging technologies can now detect AD-specific amyloid deposits, as well as vasculopathy and neurodegeneration in the retina of living AD patients, suggesting alterations at different disease stages and links to brain pathology. Current and exploratory ophthalmic imaging modalities, such as optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy, and hyperspectral imaging, may offer promise in the clinical assessment of AD. However, further research is needed to deepen our understanding of AD's impact on the retina and its progression. To advance this field, future studies require replication in larger and diverse cohorts with confirmed AD biomarkers and standardized retinal imaging techniques. This will validate potential retinal biomarkers for AD, aiding in early screening and monitoring., Competing Interests: Declaration of competing interest HH declares no competing financial interests related to the present article. He is an employee of Eisai Inc. The present article has been initiated and prepared as part of his academic position at Sorbonne University, Paris, France, and reflects entirely and exclusively his own opinion. He serves as Senior Associate Editor for the Journal Alzheimer's & Dementia and does not receive any fees or honoraria since May 2019. He is inventor of 11 patents and has received no royalties: AV declares no competing financial interests related to the present article. AV contribution to this work relates to his previous academic position at Sorbonne University, Paris, France. AV was an employee of Eisai Inc. (Nov 2019–June 2021). AV does not receive any fees or honoraria since November 2019. Before November 2019 he had he received lecture honoraria from Roche, MagQu LLC, and Servier. YK and MKH are co-founding members and consultants of NeuroVision Imaging, Inc., 1395 Garden Highway, Suite 250, Sacramento, CA 95833, USA. KLB is chair and SV is CEO, co-founders and shareholders of NeuroVision Imaging, Inc., 1395 Garden Highway, Suite 250, Sacramento, CA 95833, USA. All other authors declare no competing interests related to this article., (Copyright © 2024. Published by Elsevier Ltd.)

Identifying unknown types of diseases is a crucial step in preceding retinal imaging classification for the sake of safety, which is known as anomaly detection of retinal imaging. However, the widely-used supervised learning algorithms are not suitable for this problem, since the data of the unknown category is unobtainable. Moreover, for retinal imaging with different types of anomalous regions, using a single-resolution input causes information loss. Therefore, we propose an unsupervised auto-encoder model with multi-resolution inputs and outputs. We provide a theoretical understanding of the effectiveness of reconstruction error and the improvement of self-supervised learning for anomaly detection. Our experiments on two widely-used retinal imaging datasets show that the proposed methods are superior to other methods, and further experiments verify the validity of each part of the proposed method., (© 2024. Australasian College of Physical Scientists and Engineers in Medicine.)

Significance: Optical coherence tomography (OCT) has emerged as the standard of care for diagnosing and monitoring the treatment of various ocular disorders due to its noninvasive nature and in vivo volumetric acquisition capability. Despite its widespread applications in ophthalmology, motion artifacts remain a challenge in OCT imaging, adversely impacting image quality. While several multivolume registration algorithms have been developed to address this issue, they are often designed to cater to one specific OCT system or acquisition protocol., Aim: We aim to generate an OCT volume free of motion artifacts using a system-agnostic registration algorithm that is independent of system specifications or protocol., Approach: We developed a B-scan registration algorithm that removes motion and corrects for both translational eye movements and rotational angle differences between volumes. Tests were carried out on various datasets obtained from two different types of custom-built OCT systems and one commercially available system to determine the reliability of the proposed algorithm. Additionally, different system specifications were used, with variations in axial resolution, lateral resolution, signal-to-noise ratio, and real-time motion tracking. The accuracy of this method has further been evaluated through mean squared error (MSE) and multiscale structural similarity index measure (MS-SSIM)., Results: The results demonstrate improvements in the overall contrast of the images, facilitating detailed visualization of retinal vasculatures in both superficial and deep vasculature plexus. Finer features of the inner and outer retina, such as photoreceptors and other pathology-specific features, are discernible after multivolume registration and averaging. Quantitative analyses affirm that increasing the number of averaged registered volumes will decrease MSE and increase MS-SSIM as compared to the reference volume., Conclusions: The multivolume registered data obtained from this algorithm offers significantly improved visualization of the retinal microvascular network as well as retinal morphological features. Furthermore, we have validated that the versatility of our methodology extends beyond specific OCT modalities, thereby enhancing the clinical utility of OCT for the diagnosis and monitoring of ocular pathologies., (© 2024 The Authors.)

An ophthalmic swept source-optical coherence tomography (SS-OCT) system based on a high-speed scanning laser at 1060 nm with a scanning rate of 100 KHz is constructed. Since the sample arm of the interferometer is comprised of multiple glass materials, the ensuing dispersion severely degrades imaging quality. In this article, second-order dispersion simulation analysis for various materials was performed first, and dispersion equilibrium was implemented utilizing physical compensation methods. After dispersion compensation, an imaging depth in air of 4.013 mm was achieved in model eye experiments, and signal-to-noise ratio was enhanced by 11.6%, with a value of 53.8 dB. In vivo imaging of the human retina was performed to demonstrate structurally distinguishable retinal images, characterized by an axial resolution improvement of 19.8%, with a value of 7.7 μm close to the theoretical value of 7.5 μm. The proposed physical dispersion compensation method enhances imaging performance in SS-OCT systems, enabling visualization of several low scattering mediums., (© 2023 Wiley-VCH GmbH.)

Digital retinal imaging is at the core of a revolution that is continually improving the screening, diagnosis, documentation, monitoring, and treatment of infant retinal diseases. Historically, imaging the retina of infants had been limited and difficult to obtain. Recent advances in photographic instrumentation have significantly improved the ability to obtain high quality multimodal images of the infant retina. These include color fundus photography with different camera angles, ultrasonography, fundus fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography. We provide a summary of the current literature on retinal imaging in infants and highlight areas where further research is required., Competing Interests: Conflicts of Interest All authors have no commercial or similar relationships to products or companies mentioned in or related to the subject matter of the article being submitted. All authors declare that there are no conflicts of interest and no financial interests., (Copyright © 2021. Published by Elsevier Inc.)

In vivo images of human cone photoreceptors have been shown to vary in their reflectance both spatially and temporally. While it is generally accepted that the unique anatomy and physiology of the photoreceptors themselves drives this behavior, the exact mechanisms have not been fully elucidated as most studies on these phenomena have been limited to the human retina. Unlike humans, animal models offer the ability to experimentally manipulate the retina and perform direct in vivo and ex vivo comparisons. The thirteen-lined ground squirrel and northern tree shrew are two emerging animal models being used in vision research. Both models feature cone-dominant retinas, overcoming a key limitation of traditional rodent models. Additionally, each possesses unique but well-documented anatomical differences in cone structure compared to human cones, which can be leveraged to further constrain theoretical models of light propagation within photoreceptors. Here we sought to characterize the spatial and temporal reflectance behavior of cones in these species. Adaptive optics scanning light ophthalmoscopy (AOSLO) was used to non-invasively image the photoreceptors of both species at 5 to 10 min intervals over the span of 18 to 25 min. The reflectance of individual cone photoreceptors was measured over time, and images at individual time points were used to assess the variability of cone reflectance across the cone mosaic. Variability in spatial and temporal photoreceptor reflectance was observed in both species, with similar behavior to that seen in human AOSLO images. Despite the unique cone structure in these animals, these data suggest a common origin of photoreceptor reflectance behavior across species. Such data may help constrain models of the cellular origins of photoreceptor reflectance signals. These animal models provide an experimental platform to further explore the morphological origins of light capture and propagation.

Aim: Flow-mediated dilatation (FMD) and retinal vascular analysis (RVA) may assist in predicting cardiovascular disease (CVD) but are poorly characterised in South Africa. We recorded baseline FMD and retinal vascular widths in healthy participants, and investigated associations with cardiovascular risk factors., Methods: Endothelial function (measured with FMD), microvascular structure (evaluated via fundus image analysis) and major CVD risk factors were assessed in 66 participants from Cape Town., Results: Median FMD% was 9.6%, with higher values in females. Mean retinal arteriolar and venular widths were ˜ 156 and ˜ 250 µm, respectively. FMD was not associated with CVD risk factors. Hypertension was associated with narrower retinal arterioles and venules., Conclusions: We report novel baseline FMD data in healthy South African adults from the Western Cape, and show that retinal microvascular calibres are associated with blood pressure. Our baseline FMD and RVA data could serve as a reference for future studies in South Africa.

The peripheral retina is affected in a variety of retinal disorders. Traditional fundus cameras capture only a part of the fundus even when montaging techniques are used. Ultra-wide field imaging enables us to delve into the retinal periphery in greater detail. It not only facilitates assessing color images of the fundus, but also fluorescein angiography, indocyanine green angiography, fundus autofluorescence, and red and green free images. In this review, a literature search using the keywords "ultra-widefield imaging", "widefield imaging", and "peripheral retinal imaging" in English and non-English languages was done and the relevant articles were included. Ultra-wide field imaging has made new observations in the normal population as well as in eyes with retinal disorders including vascular diseases, degenerative diseases, uveitis, age-related macular degeneration, retinal and choroidal tumors and hereditary retinal dystrophies. This review aims to describe the utility of ultra-wide field imaging in various retinal disorders., Competing Interests: None

Recent decade has seen a shift in the causes of childhood blinding diseases from anterior segment to retinal disease in both developed and developing countries. The common retinal disorders are retinopathy of prematurity and vitreoretinal infections in neonates, congenital anomalies in infants, and vascular retinopathies including type 1 diabetes, tumors, and inherited retinal diseases in children (up to 12 years). Retinal imaging helps in diagnosis, management, follow up and prognostication in all these disorders. These imaging modalities include fundus photography, fluorescein angiography, ultrasonography, retinal vascular and structural studies, and electrodiagnosis. Over the decades there has been tremendous advances both in design (compact, multifunctional, tele-consult capable) and technology (wide- and ultra-wide field and noninvasive retinal angiography). These new advances have application in most of the pediatric retinal diseases though at most times the designs of new devices have remained confined to use in adults. Poor patient cooperation and insufficient attention span in children demand careful crafting of the devices. The newer attempts of hand-held retinal diagnostic devices are welcome additions in this direction. While much has been done, there is still much to do in the coming years. One of the compelling and immediate needs is the pediatric version of optical coherence tomography angiography. These needs and demands would increase many folds in future. A sound policy could be the simultaneous development of adult and pediatric version of all ophthalmic diagnostic devices, coupled with capacity building of trained medical personnel., Competing Interests: None

We present an integrated delivery technology herein employing the aerosolized method to repurpose thioflavin S for imaging amyloid beta (Abeta) deposits in the retina as a surrogate of Abeta in the brain for early detection of Alzheimer's disease. The data showed that wild type (WT) mice also have Abeta deposits in the retinae, albeit much less than 5XFAD mice. Further, only in 5XFAD mice, significant Abeta deposits were found associated with retinal ganglion cells (RGCs) in whole-mount and cross-section data. Furthermore, the fluorescent signal depicted from thioflavin S corroborates with Abeta immunohistochemistry staining information. Overall, this probe delivery via inhalation method is also applicable to other Abeta-binding molecules, such as Congo red, curcumin, and thioflavin T. The advantage of imaging retinal amyloid deposits compared to the brain counterparts is that the eye is easily accessible by in vivo imaging and it reduces the effort to design a probe that must cross the formidable blood-brain barrier.

In this study, we report the results of a comprehensive phenotyping of the retina of the App NL-G-F mouse. We demonstrate that soluble Aβ accumulation is present in the retina of these mice early in life and progresses to Aβ plaque formation by midlife. This rising Aβ burden coincides with local microglia reactivity, astrogliosis, and abnormalities in retinal vein morphology. Electrophysiological recordings revealed signs of neuronal dysfunction yet no overt neurodegeneration was observed and visual performance outcomes were unaffected in the App NL-G-F mouse. Furthermore, we show that hyperspectral imaging can be used to quantify retinal Aβ, underscoring its potential as a biomarker for AD diagnosis and monitoring. These findings suggest that the App NL-G-F retina mimics the early, preclinical stages of AD, and, together with retinal imaging techniques, offers unique opportunities for drug discovery and fundamental research into preclinical AD.

Photoacoustic microscopy (PAM) has significant potential as a promising diagnostic method for eye diseases and can provide anatomic and functional information of the retinal and choroidal vasculature. However, there are no FDA-approved PAM systems for ophthalmic imaging. In this study, a comprehensive safety evaluation was performed to evaluate the safety of PAM retinal imaging and whether PAM causes damage to retinal structure or function in rabbit eyes. 12 Dutch-Belted pigmented rabbits received photoacoustic imaging to 57% of the retinal surface area with a laser energy of 5% of the ANSI safety limit for five consecutive days and followed before imaging and 3 days, 1, 2, 3, and 4 weeks post imaging. Retinal morphologic analyses using slit lamp examination, fundus photography, red free, FA, FAF, ICGA, and OCT showed no retinal hemorrhage, edema, detachment, vascular abnormalities, or pigmentary abnormalities in the retina or choroid after PAM imaging. Full-field ERG analysis showed no significant difference in scotopic or photopic a- and b-wave amplitudes or implicit times between the control and experimental eyes over time (n = 6, P values > 0.05). Retinal ultrastructural evaluation using TEM showed normal structure of organelles and nuclei, and no significant loss of cells after PAM. TUNEL assay showed no evidence of cells apoptosis in retina. Retinal histopathology indicated that the architecture and thickness of the retinal layers was well preserved in all experimental eyes. A positive control at 500% of the ANSI limit demonstrated significant damage. The comprehensive retinal safety evaluation demonstrated no damage to retinal structure or function for 4 weeks after PAM imaging in rabbits., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In the last 20 years, research focused on developing retinal imaging as a source of potential biomarkers for Alzheimer's disease and other neurodegenerative diseases, has increased significantly. The Alzheimer's Association and the Alzheimer's & Dementia: Diagnosis, Assessment, Disease Monitoring editorial team (companion journal to Alzheimer's & Dementia) convened an interdisciplinary discussion in 2019 to identify a path to expedite the development of retinal biomarkers capable of identifying biological changes associated with AD, and for tracking progression of disease severity over time. As different retinal imaging modalities provide different types of structural and/or functional information, the discussion reflected on these modalities and their respective strengths and weaknesses. Discussion further focused on the importance of defining the context of use to help guide the development of retinal biomarkers. Moving from research to context of use, and ultimately to clinical evaluation, this article outlines ongoing retinal imaging research today in Alzheimer's and other brain diseases, including a discussion of future directions for this area of study., (© 2020 Alzheimer's Association. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Diabetic retinopathy (DR), the most common cause of vision loss, is caused by damage to the small blood vessels in the retina. If untreated, it may result in varying degrees of vision loss and even blindness. Since DR is a silent disease that may cause no symptoms or only mild vision problems, annual eye exams are crucial for early detection to improve chances of effective treatment where fundus cameras are used to capture retinal image. However, fundus cameras are too big and heavy to be transported easily and too costly to be purchased by every health clinic, so fundus cameras are an inconvenient tool for widespread screening. Recent technological developments have enabled to use of smartphones in designing small-sized, low-power, and affordable retinal imaging systems to perform DR screening and automated DR detection using image processing methods. In this paper, we investigate the smartphone-based portable retinal imaging systems available on the market and compare their image quality and the automatic DR detection accuracy using a deep learning framework., Results: Based on the results, iNview retinal imaging system has the largest field of view and better image quality compared with iExaminer, D-Eye, and Peek Retina systems. The overall classification accuracy of smartphone-based systems are sorted as 61%, 62%, 69%, and 75% for iExaminer, D-Eye, Peek Retina, and iNview images, respectively. We observed that the network DR detection performance decreases as the field of view of the smartphone-based retinal systems get smaller where iNview is the largest and iExaminer is the smallest., Conclusions: The smartphone-based retina imaging systems can be used as an alternative to the direct ophthalmoscope. However, the field of view of the smartphone-based retina imaging systems plays an important role in determining the automatic DR detection accuracy.

Mitochondrial failure and hypoxia are key contributors to multiple sclerosis pathophysiology. Importantly, improving mitochondrial function holds promise as a new therapeutic strategy in multiple sclerosis. Currently, studying mitochondrial changes in multiple sclerosis is hampered by a paucity of non-invasive techniques to investigate mitochondrial function of the CNS in vivo. It is against this backdrop that the anterior visual system provides new avenues for monitoring of mitochondrial changes. The retina and optic nerve are among the metabolically most active structures in the human body and are almost always affected to some degree in multiple sclerosis. Here, we provide an update on emerging technologies that have the potential to indirectly monitor changes of metabolism and mitochondrial function. We report on the promising work with optical coherence tomography, showing structural changes in outer retinal mitochondrial signal bands, and with optical coherence angiography, quantifying retinal perfusion at the microcapillary level. We show that adaptive optics scanning laser ophthalmoscopy can visualize live perfusion through microcapillaries and structural changes at the level of single photoreceptors and neurons. Advantages and limitations of these techniques are summarized with regard to future research into the pathology of the disease and as trial outcome measures., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

With the use of digital imaging systems and the possibilities of data exchange, the second opinion is becoming increasingly more important in retinal imaging. For a meaningful application, technical imaging requirements and medical assessment quality requirements have to be fulfilled. Responsibilities should be clearly defined. The aim must be to achieve a significant contribution to ensure high-quality patient care.

Background: Retinal assessment has indicated the presence of neuronal loss in neurodegenerative disorders, but its role in schizophrenia remains unclear. We sought to synthesize the available evidence considering 3 noninvasive modalities: optical coherence tomography, electroretinography, and fundus photography, and examine their diagnostic accuracy based on unpublished individual participant data, when provided by the primary study authors., Methods: We searched MEDLINE, SCOPUS, clinicaltrials.gov, PSYNDEX, Cochrane Controlled Register of Trials (CENTRAL), WHO International Clinical Trials Registry Platform, and Google Scholar, up to October 30, 2018. Authors were contacted and invited to share anonymized participant-level data. Aggregate data were pooled using random effects models. Diagnostic accuracy meta-analysis was based on multiple cutoffs logistic generalized linear mixed modeling. This study was registered with PROSPERO, number CRD42018109344., Results: Pooled mean differences of peripapillary retinal nerve fiber layer thickness in micrometer between 694 eyes of 432 schizophrenia patients and 609 eyes of 358 controls, from 11 case-control studies, with corresponding 95% confidence intervals (CIs) by quadrant were the following: -4.55, 95% CI: -8.28, -0.82 (superior); -6.25, 95% CI: -9.46, -3.04 (inferior); -3.18, 95% CI: -5.04, -1.31 (nasal); and -2.7, 95% CI: -4.35, -1.04 (temporal). Diagnostic accuracy, based on 4 studies, was fair to poor, unaffected by age and sex; macular area measurements performed slightly better., Conclusion: The notion of structural and functional changes in retinal integrity of patients with schizophrenia is supported with current evidence, but diagnostic accuracy is limited. The potential prognostic, theranostic, and preventive role of retinal evaluation remains to be examined., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose of Review: Diabetic retinopathy (DR) is the leading cause of acquired vision loss in adults across the globe. Early identification and treatment of patients with DR is paramount for vision preservation. The aim of this review paper is to outline current and new imaging techniques and biomarkers that are valuable for clinical diagnosis and management of DR., Recent Findings: Ultrawide field imaging and automated deep learning algorithms are recent advancements on traditional fundus photography and fluorescein angiography. Optical coherence tomography (OCT) and OCT angiography are techniques that image retinal anatomy and vasculature and OCT is routinely used to monitor response to treatment. Many circulating, vitreous, and genetic biomarkers have been studied to facilitate disease detection and development of new treatments. Recent advancements in retinal imaging and identification of promising new biomarkers for DR have the potential to increase detection, risk stratification, and treatment for patients with DR.

Alzheimer's disease (AD) and age-related macular degeneration (AMD) are important disorders of aging, but significant challenges remain in diagnosis and therapy. Amyloid-beta (Aβ), found in the brain and a defining feature of AD, has also been observed in the retina in both AD and AMD. While current diagnostic modalities for detecting Aβ in the brain are costly or invasive, Aβ in the retina can be noninvasively and conveniently imaged using modern photonic imaging systems such as optical coherence tomography (OCT). Moreover, since many of these retinal changes occur before degenerative changes can be detected in the brain, ocular amyloid biomarkers could be utilized to detect AD as well as AMD in their earliest stages when therapy may be most effective in halting disease progression. Novel technologies to quantify retinal biomarkers have the potential to facilitate early diagnosis and noninvasive monitoring of disease progression with important therapeutic implications.

Brn3b ( Pou4f2 ) is a class-4 POU domain transcription factor known to play central roles in the development of different neuronal populations of the Central Nervous System, including retinal ganglion cells (RGCs), the neurons that connect the retina with the visual centers of the brain. Here, we have used CRISPR-based genetic engineering to generate a Brn3b-mCherry reporter mouse without altering the endogenous expression of Brn3b. In our mouse line, mCherry faithfully recapitulates normal Brn3b expression in the retina, the optic tracts, the midbrain tectum, and the trigeminal ganglia. The high sensitivity of mCherry also revealed novel expression of Brn3b in the neuroectodermal cells of the optic stalk during early stages of eye development. Importantly, the fluorescent intensity of Brn3b-mCherry in our reporter mice allows for noninvasive live imaging of RGCs using Scanning Laser Ophthalmoscopy (SLO), providing a novel tool for longitudinal monitoring of RGCs.

As data acquisition for retinal imaging with optical coherence tomography (OCT) becomes faster, efficient collection of photons becomes more important to maintain image quality. One approach is to use a larger aperture at the eye's pupil to collect more photons that have been reflected from the retina. A 2.8-mm beam diameter system with only seven reflecting surfaces was developed for low-loss retinal imaging. The larger beam size requires defocus and astigmatism correction, which was done in a closed loop adaptive optics method using a Shack-Hartmann wavefront sensor and a deformable mirror (DM) with 140 actuators and a ±2.75 μm stroke. This DM facilitates defocus correction ranging from approximately -3 D to +3 D. Comparing the new system with a standard 1.2-mm system on a model eye, a signal-to-noise gain of 4.5 dB and a 2.3 times smaller speckle size were measured. Measurements on the retinas of five subjects showed even better results, with increases in dynamic range up to 13 dB. Note that the new sample arm only occupies 30 cm × 60 cm, which makes it highly suitable for imaging in a clinical environment. Figure: B-scan images obtained over a width of 8 deg from the right eye of a 31-year-old Caucasian male. While the left side was imaged with a standard 1.2-mm OCT system, the right side was imaged with the 2.8-mm system. Both images were collected with the same integration time and incident power, after correction of aberrations. Using the dynamic range within the images, which is determined by comparing the highest pixel value to the noise floor, a difference in dynamic range of 10.8 dB was measured between the two systems., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection associated with impaired cerebral blood flow. Visualization of the eye vasculature, which is embryologically derived from that of the brain, is used clinically to diagnose the syndrome. Here, we introduce camera-phone laser speckle imaging as a new tool for in vivo, noncontact two-dimensional mapping of blood flow dynamics in the experimental cerebral malaria (ECM) murine model of Plasmodium berghei ANKA. In a longitudinal study, we show that the camera-phone imager can detect an overall decrease in the retinal blood-flow-speed (BFS) as ECM develops in P. berghei ANKA infected mice, with no similar change observed in uninfected control mice or mice infected with a non-ECM inducing strain (P. berghei NK65). Furthermore, by analyzing relative alterations in the BFS of individual retinal vessels during the progression of ECM, we illustrate the strength of our imager in identifying different BFS-change heterogeneities in the retinas of ECM and uninfected mice. The technique creates new possibilities for objective investigations into the diagnosis and pathogenesis of CM noninvasively through the eye. The camera-phone laser speckle imager along with measured spatial blood perfusion maps of the retina of a mouse infected with P. berghei ANKA-a fatal ECM model-on different days during the progression of the infection (top, day 3 after infection; middle, day 5 after infection; and bottom, day 7 after infection)., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recent developments in imaging technologies now allow the documentation, qualitative and quantitative evaluation of peripheral retinal lesions. As wide field retinal imaging, capturing both the central and peripheral retina up to 200° eccentricity, is becoming readily available the question is: what is it that we gain by imaging the periphery? Based on accumulating evidence it is clear that findings in the periphery do not always associate to those observed in the posterior pole. However, the newly acquired information may provide useful clues to previously unrecognised disease features and may facilitate more accurate disease prognostication. In this review, we explore the anatomy and physiology of the peripheral retina, focusing on how it differs from the posterior pole, recount the history of peripheral retinal imaging, describe various peripheral retinal lesions and evaluate the overall relevance of peripheral retinal findings to different diseases., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Spectral domain optical coherence tomography (SD-OCT) is used as a non-invasive tool for retinal morphological assessment in vivo. Information on the correlation of SD-OCT with retinal histology in the porcine retina, a model resembling the human retina, is limited. Herein, we correlated the hypo- and hyper-reflective bands on SD-OCT with histology of the lamellar architecture and cellular constituents of the porcine retina. SD-OCT images were acquired with the Heidelberg Spectralis HRA + OCT. Histological analysis was performed using epoxy resin embedded tissue and transmission electron microscopy. Photomicrographs from the histologic sections were linearly scaled to correct for tissue shrinkage and correlated with SD-OCT images. SD-OCT images correlated well with histomorphometric data. A hyper-reflective band in the mid-to-outer inner nuclear layer correlated with the presence of abundant mitochondria in horizontal cell processes and adjacent bipolar cells. A concentration of cone nuclei corresponded to a relative hypo-reflective band in the outer portion of the outer nuclear layer. The presence of 3 hyper-reflective bands in the outer retina corresponded to: 1) the external limiting membrane; 2) the cone and rod ellipsoid zones; and 3) the interdigitation zone of photoreceptor outer segments/retinal pigment epithelium (RPE) apical cell processes and the RPE. These correlative and normative SD-OCT data may be employed to characterize and assess the in vivo histologic changes in retinal vascular and degenerative diseases and the responses to novel therapeutic interventions in this large animal model., (Copyright © 2018. Published by Elsevier Ltd.)

Choroidal nevi are benign fundus lesions that require regular follow with documentation. Conventional color fundus photography (CFP) has traditionally been used to images these lesions. Multicolor imaging (MCI) available on Spectralis spectral domain optical coherence tomography system is increasingly been tested vis-à-vis conventional CFP in various retinal diseases. We present data of the right eye of a 59-year-old gentleman with choroidal nevus who underwent conventional CFP as well as MCI. Nevus appeared orange red on MCI and its size appeared larger than the same measured on conventional CFP. We also report infrared reflectance and near infrared autofluorescence features of choroidal nevus., Competing Interests: There are no conflicts of interest

By 2030, sub-Saharan Africa is forecast to see the steepest rise in the number of people with hypertension of any world region. Hypertensive retinopathy is known to be a common complication of hypertension in developed countries and some studies suggest it is associated with the presence of other hypertension-related end-organ damage (EOD) such as stroke and cardiovascular disease. In Tanzania hypertension is relatively more common than in other parts of sub-Saharan Africa, especially in the older population; however, the prevalence of hypertensive retinopathy and its association with EOD remain unknown. The authors conducted a cross-sectional study of elderly, community-dwelling, rural Tanzanians to determine the prevalence of hypertensive retinopathy and its association with hypertension and other forms of EOD. Hypertensive retinopathy was diagnosed based on retinal imaging. In a cohort of 61 patients with gradable images, the authors found the overall prevalence of hypertensive retinopathy to be 64% (n = 39), which was strongly associated with hypertension (X 2 [1] = 4.207, P = .004), with a significant trend towards more severe retinopathy with more severe hypertension (r = .377, P = .003). The authors did not find hypertensive retinopathy to be associated with other forms of EOD. Hypertensive retinopathy is highly prevalent in this population and is associated in most but not all cases with hypertension. These findings do not suggest that it could be used as a screening tool for EOD, but it is important to identify and educate patients with retinopathy about possible complications of the condition., (©2018 Wiley Periodicals, Inc.)

This article explores the development of retinal imaging, with particular emphasis on ultra-widefield imaging and the key concept of field of view. Two ultra-widefield imaging platforms are examined in detail-Optomap and Spectralis-noncontact imaging systems that include protocols for performing angiography in infants. Applications of ultra-widefield imaging are illustrated using case studies, including diagnosis, monitoring, and screening., (Copyright 2018 Asia-Pacific Academy of Ophthalmology.)

Morphological changes in the outer retina such as drusen are established biomarkers to diagnose age-related macular degeneration. However, earlier diagnosis might be possible by taking advantage of more subtle changes that accompany tissues that bear polarization-altering properties. To test this hypothesis, we developed a method based on polarization-sensitive optical coherence tomography with which volumetric data sets of the macula were obtained from 10 young (<25 years) and 10 older (>54 years) subjects. All young subjects and 5 of the older subjects had retardance values induced by the retinal pigment epithelium and Bruch's membrane (RPE-BM) complex that were just above the noise floor measurement (5°-13° at 840 nm). In contrast, elevated retardance, up to 180°, was observed in the other 5 older subjects. Analysis of the degree of polarization uniformity (DOPU) demonstrates that reduced DOPU (<0.4) in the RPE is associated with elevated double pass phase retardation (DPPR) below the RPE-BM complex, suggesting that the observed elevated DPPR in older subjects is the result of increased scattering or polarization scrambling. Collectively, our measurements show that the outer retina can undergo dramatic change in its polarization properties with age, and in some cases still retain its clinically normal appearance., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report an unusual phenotype in a child with a clinical diagnosis of recessive Stargardt disease (STGD1) and two pathogenic variants in the ABCA4 gene. Typically, the diagnosis of early-onset STGD1 is challenging because children may present with a variety of fundus changes and a variable rate of progression. At the time of his initial visit, the 6-year-old boy presented with 20/200 OD (right eye) and 20/150 OS (left eye), symmetrical mild foveal atrophy without flecks on fundus exam, and foveal hypoautofluorescence surrounded by a homogeneous hyperautofluorescent background on wide-field fundus autofluorescence. Over 4 years of follow-up, the retinal atrophy continued to progress, resulting in two well-defined and concentric hyperautofluorescent rings: one ring located at the posterior pole and the other located around the peripapillary region. Visual acuity also deteriorated to counting fingers at 4ft OD and 20/500 OS. To the best of our knowledge, this phenotype has not been previously described with the ABCA4 gene.

The purpose of this study was to evaluate the retina using near-infrared (NIR) two-photon scanning laser ophthalmoscopy. New Zealand white rabbits, albino rats, and brown Norway rats were used in this study. An autofluorescence image of the retina, including the retinal cells and its associated vasculatures was obtained by a real-time scan using the ophthalmoscope. Furthermore, the retinal vessels, nerve fiber layers and the non-pigmented retina were recorded with two-photon fluorescein angiography (FA); and the choroidal vasculatures were recorded using two-photon indocyanine green angiography (ICGA). Two-photon ICGA was achieved by exciting a second singlet state at ∼398 nm. Simultaneous two-photon FA and two-photon ICGA were performed to characterize the retinal and choroidal vessels with a single injection. The minimum laser power threshold required to elicit two-photon fluorescence was determined. The two-photon ophthalmoscope could serve as a promising tool to detect and monitor the disease progression in animal models. Moreover, these high-resolution images of retinal and choroidal vessels can be acquired in a real-time scan with a single light source, requiring no additional filters for FA or ICGA. The combination of FA and ICGA using the two-photon ophthalmoscope will help researchers to characterize the retinal diseases in animal models, and also to classify the types (classic, occult or mixed) of choroidal neovascularization (CNV) in macular degeneration. Furthermore, the prototype can be adapted to image the retina of rodents and rabbits., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We demonstrate a multimode detection system in a scanning laser ophthalmoscope (SLO) that enables simultaneous operation in confocal, indirect, and direct modes to permit an agile trade between image contrast and optical sensitivity across the retinal field of view to optimize the overall imaging performance, enabling increased contrast in very wide-field operation. We demonstrate the method on a wide-field SLO employing a hybrid pinhole at its image plane, to yield a twofold increase in vasculature contrast in the central retina compared to its conventional direct mode while retaining high-quality imaging across a wide field of the retina, of up to 200 deg and 20  μm on-axis resolution., ((2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).)

Imaging techniques based on retinal autofluorescence have found broad applications in ophthalmology because they are extremely sensitive and noninvasive. Conventional fundus autofluorescence imaging measures fluorescence intensity of endogenous retinal fluorophores. It mainly derives its signal from lipofuscin at the level of the retinal pigment epithelium. Fundus autofluorescence, however, can not only be characterized by the spatial distribution of the fluorescence intensity or emission spectrum, but also by a characteristic fluorescence lifetime function. The fluorescence lifetime is the average amount of time a fluorophore remains in the excited state following excitation. Fluorescence lifetime imaging ophthalmoscopy (FLIO) is an emerging imaging modality for in vivo measurement of lifetimes of endogenous retinal fluorophores. Recent reports in this field have contributed to our understanding of the pathophysiology of various macular and retinal diseases. Within this review, the basic concept of fluorescence lifetime imaging is provided. It includes technical background information and correlation with in vitro measurements of individual retinal metabolites. In a second part, clinical applications of fluorescence lifetime imaging and fluorescence lifetime features of selected retinal diseases such as Stargardt disease, age-related macular degeneration, choroideremia, central serous chorioretinopathy, macular holes, diabetic retinopathy, and retinal artery occlusion are discussed. Potential areas of use for fluorescence lifetime imaging ophthalmoscopy will be outlined at the end of this review., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hyperspectral retinal imaging captures the light spectrum from each imaging pixel. It provides spectrally encoded retinal physiological and morphological information, which could potentially benefit diagnosis and therapeutic monitoring of retinal diseases. The key challenges in hyperspectral retinal imaging are how to achieve snapshot imaging to avoid motions between the images from multiple spectral bands, and how to design a compact snapshot imager suitable for clinical use. Here, we developed a compact, snapshot hyperspectral fundus camera for rodents using a novel spectral resolving detector array (SRDA), on which a thin-film Fabry-Perot cavity filter was monolithically fabricated on each imaging pixel. We achieved hyperspectral retinal imaging with 16 wavelength bands (460 to 630 nm) at 20 fps. We also demonstrated false-color vessel contrast enhancement and retinal oxygen saturation (sO 2 ) measurement through spectral analysis. This work could potentially bring hyperspectral retinal imaging from bench to bedside., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

With increase in life expectancy, the number of persons suffering from common age-related brain diseases, including neurodegenerative (e.g., dementia) and cerebrovascular (e.g., stroke) disease is expected to rise substantially. As current neuro-imaging modalities such as magnetic resonance imaging may not be able to detect subtle subclinical changes (resolution <100-500 μm) in dementia and stroke, there is an urgent need for other complementary techniques to probe the pathophysiology of these diseases. The retina - due to its anatomical, embryological and physiological similarities with the brain - offers a unique and accessible "window" to study correlates and consequences of subclinical pathology in the brain. Retinal components such as the microvasculature and retinal ganglion cell axons can now be visualized non-invasively using different retinal imaging techniques e.g., ocular fundus photography and optical coherence tomography. Advances in retinal imaging may provide new and potentially important insights into cerebrovascular neurodegenerative processes in addition to what is currently possible with neuro-imaging. In this review, we present an overview of the current literature on the application of retinal imaging in the study of dementia and stroke. We discuss clinical implications of these studies, novel state-of-the-art retinal imaging techniques and future directions aimed at evaluating whether retinal imaging can be an additional investigation tool in the study of dementia and stroke., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Given the converging pathologic and epidemiologic data indicating a relationship between retinal integrity and neurodegeneration, including Alzheimer's disease (AD), we aimed to determine if retinal structure correlates with medial temporal lobe (MTL) structure and function in neurologically normal older adults. Spectral-domain optical coherence tomography, verbal and visual memory testing, and 3T-magnetic resonance imaging of the brain were performed in 79 neurologically normal adults enrolled in a healthy aging cohort study. Retinal nerve fiber thinning and reduced total macular and macular ganglion cell volumes were each associated with smaller MTL volumes (ps < 0.04). Notably, these markers of retinal structure were not associated with primary motor cortex or basal ganglia volumes (regions relatively unaffected in AD) (ps > 0.70), or frontal, precuneus, or temporoparietal volumes (regions affected in later AD Braak staging ps > 0.20). Retinal structure was not significantly associated with verbal or visual memory consolidation performances (ps > 0.14). Retinal structure was associated with MTL volumes, but not memory performances, in otherwise neurologically normal older adults. Given that MTL atrophy is a neuropathological hallmark of AD, retinal integrity may be an early marker of ongoing AD-related brain health., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Retinal imaging may serve as an alternative approach to monitor brain pathology in Alzheimer's disease (AD). In this study, we investigated the association between retinal vascular and structural changes and cerebral amyloid-β (Aβ) plaque load in an elderly cohort., Methods: We studied a total of 101 participants, including 73 elderly subjects (79 ± 5 years, 22 male) with no clinical diagnosis of AD but reporting some subjective memory change and an additional 28 subjects (70 ± 9 years, 16 male) with clinically established AD. Following a complete dilated ocular examination, the amplitude of retinal vascular pulsations and dynamic response, retinal nerve fibre layer thickness and retinal ganglion cell layer (RGCL) thickness were determined in all patients. Systemic blood pressure and carotid-to-femoral pulse wave velocity were measured. The elderly cohort also underwent magnetic resonance imaging and 18 F-florbetaben (FBB)-positron emission tomographic amyloid imaging to measure neocortical Aβ standardised uptake value ratio (SUVR), and this was used to characterise a 'preclinical' group (SUVR >1.4)., Results: The mean FBB neocortical SUVR was 1.35 ± 0.3. The amplitude of retinal venous pulsations correlated negatively with the neocortical Aβ scores (p < 0.001), whereas the amplitude of retinal arterial pulsations correlated positively with neocortical Aβ scores (p < 0.01). RGCL thickness was significantly lower in the clinical AD group (p < 0.05)., Conclusions: The correlation between retinal vascular changes and Aβ plaque load supports the possibility of a vascular component to AD. Dynamic retinal vascular parameters may provide an additional inexpensive tool to aid in the preclinical assessment of AD.

Objective: Accumulating evidence suggests that the eye can be used in the assessment of early on-set Alzheimer's disease (AD). The eye offers a natural window to the brain through the retina. The retina and brain share common developmental origins and patho-physiological origins and mechanisms, having been sequestered from it during early development, but retaining its connections with the brain via the optic nerve. Therefore, it is well understood that neurological abnormalities have a direct profound impact on the retina. Recent studies suggest an array of physiological and pathological changes in the retina in dementia and specifically in AD. There are also reports on imaging the two hallmark proteins of the disease, extracellular amyloid beta peptides and intracellular hyper phosphorylated tau protein, as a proxy to neuroimaging., Results: In this review, we summarise retinal structural, functional and vascular changes reported to be associated with AD. We also review techniques employed to image these two major hall mark proteins of AD and their relevance for early detection of AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Purpose: This study aims to investigate the ability of the ultra-wide-field scanning laser ophthalmoscope (UWF SLO) in clinically detecting and evaluating asymptomatic early-stage familial exudative vitreoretinopathy (FEVR)., Methods: We retrospectively reviewed 163 eyes of 83 asymptomatic family members of 48 patients with FEVR. UWF SLO imaging (Optos® PLC, Scotland, UK) was performed on asymptomatic family members as a preliminary screening test for fundus anomalies, and the findings were compared with subsequent examinations using indirect fundus ophthalmoscopy in full mydriasis, fluorescein angiography (FA), fundus autoflourescence, and genetic sequencing., Results: A total of 86 eyes of 43 asymptomatic family members were clinically diagnosed with early-stage FEVR, and 17 of the affected 43 family members were also genetically diagnosed. Compared with FA as a standard, the UWF SLO was highly effective in diagnosing FEVR with a sensitivity and specificity of 93.0 % and 97.5 %, respectively. The UWF SLO was able to diagnose early-stage FEVR in 93.0 % of eyes, and guided the selection of therapies in 46.5 % of the eyes studied., Conclusion: UWF SLO is a valuable imaging tool for detecting fundus anomalies related to early-stage FEVR, and this tool can assist in the clinical diagnosis and evaluation of early-stage FEVR in asymptomatic family members of patients with FEVR.

In the years since its introduction, retinal imaging has transformed our capability to visualize the posterior pole of the eye. Increasing practical advances in mobile technology, regular monitoring, and population screening for diabetic retinopathy management offer the opportunity for further development of cost-effective applications through remote assessment of the diabetic eye using portable retinal cameras, smart-phone-based devices and telemedicine networks. Numerous retinal imaging methods and mobile technologies in tele-ophthalmology applications have been reported for diabetic retinopathy screening and management. They provide several advantages of automation, sensitivity, specificity, portability, and miniaturization for the development of point-of-care diagnostics for eye complications in diabetes. The aim of this paper is to review the role of retinal imaging and mobile technologies in tele-ophthalmology applications for diabetic retinopathy screening and management. At large, although improvements in current technology and telemedicine services are still needed, telemedicine has demonstrated to be a worthy tool to support health caregivers in the effective management and prevention of diabetes and its complications.

Mitochondria play a key role in ageing and disease. Their membrane potentials and ATP production decline with age and this is associated with progressive inflammation, cell loss and death. Here we use broadband Near-Infrared Spectroscopy (NIRS) to non-invasively measure in-vivo changes in aged retinal mitochondrial respiration following exposure to 670 nm, which improves mitochondrial performance and reduces inflammation. Low power NIR light was shone into the eye via a fibre optic and the reflection monitored to measure signature changes in the oxidation of cytochrome c oxidase (COX) in complex IV of the electron transport chain. Changes in retinal haemodynamics and oxygenation were also recorded simultaneously with COX by measuring changes in oxygenated and deoxygenated haemoglobin (Δ[HbO 2 ] and Δ[HHb]). Retinae of aged rats exposed to 670 nm for 5 mins showed consistent progressive increases in oxidation of COX 5 mins post exposure. This remained significantly greater than baseline for up to 2 h. This was not seen when retinae were exposed to 420 nm light of the same power or when no light was applied. 670 nm exposure significantly increased total haemoglobin concentration (Δ[HbT] = Δ[HbO 2 ] +Δ[HHb]) but not haemoglobin difference (Δ[HbDiff] = Δ[HbO 2 ] -Δ[HHb]). There were no changes in blood metrics in association with 420 nm light or when no light exposure was given. Hence, brief 670 nm exposure that is associated with reduced inflammation has a significant positive impact on the redox state of COX in aged retinae. The relative redox state of retinal COX may provide a valuable biomarker in ageing and macular degeneration where declining mitochondrial function is implicated., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Emergence of the high-resolution optical coherence tomography has allowed better delineation of retinal layers, and many of the anatomical correlations of these layers have now been agreed upon. However, some anatomical correlates still remain contentious, such as the second hyper-reflective band, which is now termed ellipsoid zone. Despite the lack of consensus of the actual origin of the ellipsoid zone, there has been much interest in evaluating its integrity and intensity in different disease processes. This review paper aims to provide an overview of the ellipsoid zone and its clinical and research applications., (© 2015 Royal Australian and New Zealand College of Ophthalmologists.)

Background: Analysis of fast temporal changes on retinas has become an important part of diagnostic video-ophthalmology. It enables investigation of the hemodynamic processes in retinal tissue, e.g. blood-vessel diameter changes as a result of blood-pressure variation, spontaneous venous pulsation influenced by intracranial-intraocular pressure difference, blood-volume changes as a result of changes in light reflection from retinal tissue, and blood flow using laser speckle contrast imaging. For such applications, image registration of the recorded sequence must be performed., Methods: Here we use a new non-mydriatic video-ophthalmoscope for simple and fast acquisition of low SNR retinal sequences. We introduce a novel, two-step approach for fast image registration. The phase correlation in the first stage removes large eye movements. Lucas-Kanade tracking in the second stage removes small eye movements. We propose robust adaptive selection of the tracking points, which is the most important part of tracking-based approaches. We also describe a method for quantitative evaluation of the registration results, based on vascular tree intensity profiles., Results: The achieved registration error evaluated on 23 sequences (5840 frames) is 0.78 ± 0.67 pixels inside the optic disc and 1.39 ± 0.63 pixels outside the optic disc. We compared the results with the commonly used approaches based on Lucas-Kanade tracking and scale-invariant feature transform, which achieved worse results., Conclusion: The proposed method can efficiently correct particular frames of retinal sequences for shift and rotation. The registration results for each frame (shift in X and Y direction and eye rotation) can also be used for eye-movement evaluation during single-spot fixation tasks.

Purpose: To evaluate the clinical utility of ultra-widefield imaging as an adjunctive tool in the diagnosis, management, and follow-up of eyes with non-traumatic rhegmatogenous retinal detachment., Methods: Retrospective chart review of patients with a rhegmatogenous retinal detachment who received ultra-widefield imaging with the Optos® Optomap® P200Tx. Comparisons were made between UWF imaging and indirect ophthalmoscopy for features of detachments, including extent of detachment, holes, retinopexy, and related pathology., Results: Thirty-six eyes of 34 patients were included. Preoperatively, ultra-widefield imaging more precisely documented the extent of retinal detachments in the superior, inferior, and nasal quadrants in 13.9% of cases. Ultra-widefield imaging failed to detect retinal holes in the superior and inferior quadrants in 11.1% and 19.4% of cases, respectively. In postoperative imaging, UWF photos did not detect retinopexy which was ophthalmoscopy-visible both superiorly and inferiorly in 19.4% of cases. The mean differences in clock hours of the detachments as documented on the clinical exam compared to ultra-widefield imaging in the superior, inferior, temporal, and nasal quadrants were -0.18 ± 0.84, 0.41 ± 1.16, 0.08 ± 1.08, and -0.13 ± 2.25 hours, respectively., Conclusion: Ultra-widefield imaging is a useful adjunct for documentation of rhegmatogenous retinal detachments and their postoperative repair. However, detection of retinal holes, tears, and postoperative scarring is poor, especially in the inferior and superior periphery.

Introduction: When an eye is illuminated by a light coaxial with the observing eye or camera, the light is reflected by the back of the eye and a red reflex will be observed through the pupil. The intensity of this red reflex varies with the angle of eccentric gaze. The red reflex darkens as the eye fixates at the light source. Brückner described this principle in 1962. Although this effect has been used as a screening test for strabismus ever since, the mechanism that causes this effect is only partly known. None of the current explanations are accepted as conclusively proven. We developed an automated, high-resolution, continuously scanning Brückner device to study the mechanisms underlying the Brückner effect., Method: The right eyes of 6 subjects, students aged 22-31 years, were measured. A subject sat in front of a camera at a distance of about 0.75 m. The luminance of the red fundus reflex and the eye movements were measured continuously while the subject followed a fixation target that moved in two dimensions. Eye movement was also recorded objectively and in the analysis this was used in addition to the position of the fixation target. The eyes were illuminated coaxially using an infrared light source and a beam splitter., Result: By using two methods to record eye rotation and relating this to the continuously measured pupillary luminous intensity and pupillary area, we were able to construct 2-dimensional maps of pupillary luminance. All 6 subjects showed the expected general darkening of the pupil as fixation changed from eccentric fixation to foveal fixation at the center of the camera. However, there were many local fluctuations. The global minimum in pupillary luminance, the "dark spot," was often roughly circle-shaped with a radius of about 1°. The pupillary luminance kept increasing beyond 2° eccentricity., Discussion: We measured the Brückner effect continuously in two dimensions. Brückner's original explanation--absorption by the macular pigment--cannot explain our findings as the macular pigment hardly absorbs light beyond 600 nm wavelength. If one assumes that reflection by the inner limiting membrane or diffuse backscatter in the thick retinal nerve fiber layer increase the luminance of the pupil, one would expect the pupil to be brightest at 2° eccentricity, but the pupillary luminance continued to increase beyond that. We used a beam splitter and still found a dark pupil on coaxial fixation, implying that blocking the image that is projected back from the eye by the funduscope only plays a contributory role.

Aims: To quantitatively analyse cone photoreceptor matrices on images captured on an adaptive optics (AO) camera and assess their correlation to well-established parameters in the retinal histology literature., Methods: High resolution retinal images were acquired from 10 healthy subjects, aged 20-35 years old, using an AO camera (rtx1, Imagine Eyes, France). Left eye images were captured at 5° of retinal eccentricity, temporal to the fovea for consistency. In three subjects, images were also acquired at 0, 2, 3, 5 and 7° retinal eccentricities. Cone photoreceptor density was calculated following manual and automated counting. Inter-photoreceptor distance was also calculated. Voronoi domain and power spectrum analyses were performed for all images., Results: At 5° eccentricity, the cone density (cones/mm(2) mean±SD) was 15.3±1.4×10(3) (automated) and 13.9±1.0×10(3) (manual) and the mean inter-photoreceptor distance was 8.6±0.4 μm. Cone density decreased and inter-photoreceptor distance increased with increasing retinal eccentricity from 2 to 7°. A regular hexagonal cone photoreceptor mosaic pattern was seen at 2, 3 and 5° of retinal eccentricity., Conclusions: Imaging data acquired from the AO camera match cone density, intercone distance and show the known features of cone photoreceptor distribution in the pericentral retina as reported by histology, namely, decreasing density values from 2 to 7° of eccentricity and the hexagonal packing arrangement. This confirms that AO flood imaging provides reliable estimates of pericentral cone photoreceptor distribution in normal subjects., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)