Reflections on the Utility of the Retina as a Biomarker for Alzheimer's Disease: A Literature Review.

As a part of the central nervous system, the retina may reflect both physiologic processes and abnormalities related to diseases of the brain. Indeed, a concerted effort has been put forth to understand how Alzheimer's disease (AD) pathology may manifest in the retina as a means to assess the state of the AD brain. The development and refinement of ophthalmologic techniques for studying the retina in vivo have produced evidence of retinal degeneration in AD diagnosed patients. In this review, we will discuss retinal imaging techniques implemented to study the changes in AD retina as well as highlight the recent efforts made to correlate such findings to other clinical hallmarks of AD to assess the viability of the retina as a biomarker for AD

In-vivo high resolution imaging of optic nerve head drusen using spectral-domain Optical Coherence Tomography

<p>Abstract</p> <p>Background</p> <p>Optic nerve head drusen (ONHD) are white calcareous deposits, seen either superficially on the optic nerve head or buried within it. Diagnosis of ONHD is made by one or more ways: clinical exam, autofluorescence, ultrasound of the optic nerve, CT scan and/or visual field examination. The present study describes features of ONHD based on another diagnostic modality, the spectral-domain OCT (Spectralis).</p> <p>Methods</p> <p>This is a retrospective case series of 5 patients with bilateral ONHD with a best-corrected visual acuity of 20/20 and no other posterior segment pathology. All the patients underwent fundus photography, fundus autofluorescence, B-scan ultrasonography, Spectralis OCT and Humphrey 30-2 threshold visual fields.</p> <p>Results</p> <p>All 5 patients had surface ONHD which were autofluorescent and echodense on B-scan ultrasonography. Spectralis OCT findings in the corresponding areas include 'scattered spots with high reflectivity' casting a shadow underneath. The reflectivity can be distinctly differentiated from the blood vessels on the optic nerve. Two patients had an arcuate scotoma on the Humphrey visual fields. No correlation was found between the changes on Spectralis OCT with that of visual field.</p> <p>Conclusions</p> <p>Spectralis OCT is another useful ancillary investigation in the diagnosis of ONHD and we describe the features in the present study.</p

In Vivo Multimodal Imaging of Drusenoid Lesions in Rhesus Macaques.

Nonhuman primates are the only mammals to possess a true macula similar to humans, and spontaneously develop drusenoid lesions which are hallmarks of age-related macular degeneration (AMD). Prior studies demonstrated similarities between human and nonhuman primate drusen based on clinical appearance and histopathology. Here, we employed fundus photography, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and infrared reflectance (IR) to characterize drusenoid lesions in aged rhesus macaques. Of 65 animals evaluated, we identified lesions in 20 animals (30.7%). Using the Age-Related Eye Disease Study 2 (AREDS2) grading system and multimodal imaging, we identified two distinct drusen phenotypes - 1) soft drusen that are larger and appear as hyperreflective deposits between the retinal pigment epithelium (RPE) and Bruchs membrane on SD-OCT, and 2) hard, punctate lesions that are smaller and undetectable on SD-OCT. Both exhibit variable FAF intensities and are poorly visualized on IR. Eyes with drusen exhibited a slightly thicker RPE compared with control eyes (+3.4 μm, P=0.012). Genetic polymorphisms associated with drusenoid lesions in rhesus monkeys in ARMS2 and HTRA1 were similar in frequency between the two phenotypes. These results refine our understanding of drusen development, and provide insight into the absence of advanced AMD in nonhuman primates

Imaging of the human fundus in the clinical setting:past present and future

The human fundus is a complex structure that can be easily visualized and the world of ophthalmology is going through a golden era of new and exciting fundus imaging techniques; recent advances in technology have allowed a significant improvement in the imaging modalities clinicians have available to formulate a diagnostic and treatment plan for the patient, but there is constant on-going work to improve current technology and create new ideas in order to gather as much information as possible from the human fundus. In this article we shall summarize the imaging techniques available in the standard medical retina clinic (i.e. not limited to the research lab) and delineate the technologies that we believe will have a significant impact on the way clinicians will assess retinal and choroidal pathology in the not too distant future

Diagnosis of papilledema and pseudopapilledema using optical coherence tomography

Background: Papilledema is a common clinical problem where the ophthalmologist plays an important role in its diagnosis. Optical coherence tomography (OCT) provides high resolution images of the retina and the retinal nerve fiber layer (RNFL).Objective: The aim of the work was early and non- invasive diagnosis of papilledema and differentiating it from pseudopapilledema using optical coherence tomography (OCT).Patients and methods: This observational case control study included a total of 45 eyes stratified into 3 equally groups, 15 each, (Group-1): eyes of healthy normal subjects, (Group-2) eyes with papilledema and (Group-3) eyes with pseudo-papilledema. Patients presented at Ophthalmology Outpatient Clinic, Zagazig University Hospitals. Follow-up visits included an interview with the patient for assessing the presence of ocular symptoms, and for ophthalmologic examination to register all the clinical findings.Results: There is statistically significant difference between the studied groups regarding result of fundus examination. Normal control group had normal appearance of fundus. Concerning pseudo papilledema, 73.3% had crowded disc and 26.7% had dusen. Concerning papilledema, 40% had mild lesion, 20% had moderate and remaining 40% had severe lesion. There is statistically significant difference between the studied groups regarding morphological changes. Crowded disc and buried optic disc drusen occurred in 73.3% and 26.7% of pseudopapilledema group respectively). There is statistically significant difference between the studied groups regarding superior RNFL. On LSD comparison, the difference is significant between each individual groups. There is statistically significant difference between the studied groups regarding inferior RNFL.Conclusion: It could be concluded that spectral domain optical coherence tomography can differentiate between papilledema, pseudopapilledema, and a normal disc

Enhanced Depth Imaging Optical Coherence Tomography of Optic Nerve Head Drusen: A Comparison of Cases with and without Visual Field Loss

PURPOSE: Enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD OCT) has been recognized as the most sensitive tool to diagnose optic nerve head drusen (ONHD). The relationship between OCT characteristics and visual loss has not been well documented. This study compares EDI SD OCT-determined morphologic characteristics of drusen in eyes with or without visual field (VF) defects. DESIGN: Descriptive study of patients attending the neuro-ophthalmology service of Moorfields Eye Hospital between January 2013 and October 2014. SUBJECTS: Patients with diagnosed ONHD and EDI SD OCT imaging of the optic nerve head. METHODS: Eyes with and without VF defects were compared with regard to retinal nerve fiber layer (RNFL) thickness, drusen morphology, size, extent, visibility on funduscopy, ultrasound, and fundus autofluorescence. MAIN OUTCOME MEASURES: Difference in OCT characteristics of ONHD between patients with or without VF defects. RESULTS: Of 38 patients, 69 eyes with ONHD were included. Thirty-three eyes had a normal VF with average mean deviation (MD) -0.96 (±1.2) dB and pattern standard deviation (PSD) 1.6 (±0.3) dB (group I), and 36 eyes had VF defects with MD -13.7 (±10.4) dB and PSD 7.2 (±3.6) dB (group II). Mean global RNFL thickness was 62 (±20.9) μm in the latter group and 99.0 (±12.9) μm in group I. In group I, the predominant drusen type was peripapillary drusen, of variable size. In group II, most eyes had confluent (P 500 μm; P < 0.003) drusen, and drusen were more commonly visible on funduscopy (P = 0.001), ultrasound (P = 0.013), and autofluorescence (P = 0.002). Differences between the 2 groups reached statistical significance in a clustered analysis. RNFL thinning and autofluorescence showed relative sparing of the temporal sector. Sixty-four percent of patients with a VF defect in 1 eye also had a VF defect in their fellow eye. CONCLUSIONS: Drusen size and drusen type as classified by OCT morphologic characteristics are significantly different in patients with or without VF defects. Confluent, large, and autofluorescent drusen were more commonly found in patients with VF defects. These findings may assist in clarifying how drusen give rise to visual loss, which is currently not known

Optical Coherence Tomography in the Management of Glaucoma and Macular Diseases

Optical coherence tomography (OCT) is a non contact, non invasive and reproducible imaging technique that produces thin slices of tissue section images. OCT identifies retinal nerve fiber damage before detection of visual field changes making it a handy and effective tool in early detection and monitoring in glaucoma. Retinal fiber layer thickness measurements provide vital knowledge of extent of neural damage. This enables the clinician to counsel the patient and take the best decision towards achieving glaucoma control. Early and quantifiable macular thickness measurements are obtained, allowing for detection of clinically significant diabetic macular edema. OCT allows monitoring of the impact of laser or other interventions. Changes in age-related macular degeneration are relatively easily determined and impact of treatment interventions monitored. In conclusion, OCT is a vital emerging tool in the evaluation and management glaucoma and macular diseases in all parts of the World, including low income countries of sub-Saharan Africa