Optical coherence tomography in the investigation of systemic neurologic disease

Optical coherence tomography (OCT) is a well‐established technique for the clinical examination, diagnosis, severity staging and monitoring of ophthalmic disorders. The application of this technology has more recently been extended beyond ophthalmic disease, whereby it has been demonstrated that OCT can serve as an ophthalmic marker for a range of systemic neurodegenerative disorders, such as Parkinson's disease, multiple sclerosis, Alzheimer's disease and diabetic peripheral neuropathy. This review will focus on the clinical utility of OCT‐derived retinal measures for the investigation of these conditions.     

Imaging retina to study dementia and stroke

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.     

阿尔茨海默病视功能损伤及机制研究进展

阿尔茨海默病(Alzheimer''s disease,AD)是神经退行性疾病,是痴呆最常见的类型。患者的个人生活质量受到了严重的影响,给其家庭和整个社会带来了较大的经济和社会负担。认知障碍的患者会出现一些与认知能力下降相关的眼科改变。但目前视功能与AD之间的关系仍未得到充分研究。当认知能力下降时,患者会用其视觉等感官感知周围的世界,然而大脑却无法将感知的信息整合到一起来理解周围的环境。由于视功能损伤为AD患者感官功能损伤中较为明显的一种,对其损伤的认识能够帮助我们对AD患者进行早期诊断。为了进一步探究其视功能变化,现通过各种文献复习,对AD患者视功能损伤及其机制进行综述。     

基于眼部影像的神经退行性疾病分析研究进展

由于视网膜与视神经的发展起源于大脑,因此具有类似大脑的结构和功能特性。研究中枢视神经系统疾病在视网膜上的表现有利于探索脑眼的互动机制。作为中枢神经系统的延伸,视网膜包含神经节细胞,其轴突形成视神经并进入中枢神经系统。因此,视网膜在结构性、功能性上可作为神经退行性疾病的观察镜像。随着成像技术的发展,光学相干断层(血流)成像技术以其易操作、低成本的特性成为眼科临床诊断的主流工具。近年来,探寻神经退行性疾病,尤其是阿尔兹海默症、帕金森病和多发性硬化等疾病,在眼部光学相干断层图像中生物标记逐渐成为一个新兴研究方向。本文归纳总结了近十年来基于视网膜影像的神经退行性疾病分析研究进展,并进行了展望,为后续研究提供铺垫和启发。     

How strong is the relationship between glaucoma,the retinal nerve fibre layer,and neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis?

Glaucoma is a neurodegenerative disorder with established relationships with ocular structures such as the retinal nerve fibre layer (RNFL) and the ganglion cell layer (GCL). Ocular imaging techniques such as optical coherence tomography (OCT) allow for quantitative measurement of these structures. OCT has been used in the monitoring of glaucoma, as well as investigating other neurodegenerative conditions such as Alzheimer''s disease (AD) and multiple sclerosis (MS). In this review, we highlight the association between these disorders and ocular structures (RNFL and GCL), examining their usefulness as biomarkers of neurodegeneration. The average RNFL thickness loss in patients with AD is 11 μm, and 7 μm in MS patients. Most of the studies investigating these changes are cross-sectional. Further longitudinal studies are required to assess sensitivity and specificity of these potential ocular biomarkers to neurodegenerative disease progression.     

Spectralis optical coherence tomography findings in Welder's maculopathy

Welder''s maculopathy is a form of photochemical damage to the retina and is typically characterized by involvement of the outer retinal layers. Spectral domain optical coherence tomography (SD-OCT) imaging was performed in three eyes of two patients with clinical findings suggestive of Welder''s maculopathy in occupational welders. A faceted foveal lesion characterized clinical examination and the SD-OCT line scans images showed a distinct discontinuity of the photoreceptor inner and outer segment (IS/OS) junction. The external limiting membrane (ELM) and the retinal pigment epithelial (RPE) layer remained intact at the site of IS/OS defect. SD-OCT imaging offers a noninvasive way of evaluating the microstructural changes at the fovea in Welder''s maculopathy.     

Advanced retinal imaging and applications for clinical practice: A consensus review

Imaging is an integral part of the evaluation and management of retinal disorders. Each imaging modality has its own unique capabilities and can show a different aspect or perspective of disease. Multimodal retinal imaging provides a wealth of substantive and insightful information; however, the integration of all this complex data can be overwhelming. We discuss the applications and the strengths and limitations of the many different retinal imaging tools that are approved for clinical use. These modalities include color fundus photography, widefield imaging, fundus autofluorescence, near infrared reflectance, optical coherence tomography angiography, and en face optical coherence tomography. We also cover the advantages and disadvantages of a multimodal approach.     

Alzheimer's disease: Visual system review

BackgroundTen million baby boomers in the United States will get Alzheimer's disease. Optometrists can benefit from understanding the impact the Alzheimer's disease process has on the visual system. This can result in more effective management of the condition and in more effective communication with members of the Alzheimer's disease multidisciplinary team.MethodsThis is a review of the literature but by no means a completely exhaustive review. Alzheimer's disease is a complex disease. A rapidly expanding body of knowledge covers multiple disciplines.ResultsThe visual system shows deficits early in the degenerative process of Alzheimer's disease. Biomarkers through the visual system such as nerve fiber deficits, lens opacities, and functional losses in the magnocellular pathway, such as contrast sensitivity and temporal processing, may prove to not only help detect Alzheimer's disease early but also detect it before there are the classic cognitive and memory losses.ConclusionsThe effects of Alzheimer's disease are devastating. Optometrists, as primary care clinicians, can make critical contributions in the diagnosis, treatment, and management of this neurodegenerative disease.     

Visual signs and symptoms of dementia with Lewy bodies

Dementia with Lewy bodies (‘Lewy body dementia’ or ‘diffuse Lewy body disease’) (DLB) is the second most common form of dementia to affect elderly people, after Alzheimer's disease. A combination of the clinical symptoms of Alzheimer's disease and Parkinson's disease is present in DLB and the disorder is classified as a ‘parkinsonian syndrome’, a group of diseases which also includes Parkinson's disease, progressive supranuclear palsy, corticobasal degeneration and multiple system atrophy. Characteristics of DLB are fluctuating cognitive ability with pronounced variations in attention and alertness, recurrent visual hallucinations and spontaneous motor features, including akinesia, rigidity and tremor. In addition, DLB patients may exhibit visual signs and symptoms, including defects in eye movement, pupillary function and complex visual functions. Visual symptoms may aid the differential diagnoses of parkinsonian syndromes. Hence, the presence of visual hallucinations supports a diagnosis of Parkinson's disease or DLB rather than progressive supranuclear palsy. DLB and Parkinson's disease may exhibit similar impairments on a variety of saccadic and visual perception tasks (visual discrimination, space‐motion and object‐form recognition). Nevertheless, deficits in orientation, trail‐making and reading the names of colours are often significantly greater in DLB than in Parkinson's disease. As primary eye‐care practitioners, optometrists should be able to work with patients with DLB and their carers to manage their visual welfare.     

早期原发性开角型青光眼与帕金森患者SD-OCT检查结果的比较

目的:使用光学相干断层扫描(SD-OCT)比较早期帕金森病(PD)和原发性开角型青光眼(POAG)患者黄斑和视网膜神经纤维层(RNFL)厚度参数。方法:回顾性分析。选取48例早期POAG患者、34例早期PD患者和37例年龄及性别相匹配的健康志愿者(对照组),使用SD-OCT分别测量RNFL和9个象限的黄斑厚度(ETDRS分区)。本研究纳入的早期POAG患者视野检测MD<-6 dB。PD组患者采用Hoehn和Yahr(H&Y)及统一帕金森病分级量表(UPDRS)评估PD的严重程度,纳入H&Y I-III期患者。结果:除颞侧RNFL外,三组间RNFL厚度均有显著差异(P<0.05)。三组间黄斑中心凹厚度、平均黄斑厚度和黄斑外侧象限厚度均有显著差异(P<0.05)。POAG组和PD组患者黄斑内侧象限厚度无显著差异(P>0.05)。PD组患者病程、UPDRS评分与黄斑厚度和RNFL厚度均呈负相关。结论:通过SD-OCT对早期POAG和PD患者黄斑和RNFL厚度参数进行检测,发现两者出现相似的变薄现象,而在早期POAG组这种现象更为明显,推测青光眼引起的黄斑神经退行性变比PD更具破坏性,但PD患者黄斑中央凹区变薄更为显著。     

One glasses too many: A case report of Benson's syndrome

We report a case of Benson''s Syndrome, a form of occipital Alzheimer''s disease, with posterior cortical atrophy on magnetic resonance imaging, in a 62-year-old male, who presented with visual problems, ascribed to the eyes, and had even undergone cataract/intraocular lens surgery in the right eye; and change of glasses 21 times over the past 2 years, with no apparent benefit. This case is of interest both on account of its rarity, and to highlight its features since the diagnosis may be missed in an ophthalmological setting where such patient may go for first consult.     

Can the retina be used to diagnose and plot the progression of Alzheimer's disease?

Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of senile dementia. It impairs the quality of life of a person and their family, posing a serious economic and social threat in developed countries. The fact that the diagnosis can only be definitively made post‐mortem, or when the disease is fairly advanced, presents a serious problem if novel therapeutic interventions are to be devised and used early in the course of the disease. There is therefore a pressing need for more sensitive and specific diagnostic tests with which we can detect AD in the preclinical stage. The tau proteins and beta‐amyloid proteins start to accumulate 20 years before the symptoms begin to manifest. Detecting them in the preclinical stage would be a potential breakthrough in the management of AD. A high degree of clinical suspicion is needed to correlate problems in cognition with the changes in the eye, particularly the retina, pupil and ocular movements, so that the disease can be detected early and managed in the prodromal phase. In this systematic review, we ask the question whether the retina can be used to make a specific and early diagnosis of AD.     

Fast circulation of cerebrospinal fluid: an alternative perspective on the protective role of high intracranial pressure in ocular hypertension

As ocular hypertension refers to a condition in which the intraocular pressure is consistently elevated but without development of glaucoma, study of it may provide important clues to factors that may play a protective role in glaucoma. β‐amyloid, one of the key histopathological findings in Alzheimer's disease, has been reported to increase by chronic elevation of intraocular pressure in animals with experimentally induced ocular hypertension and to cause retinal ganglion cell death, pointing to similarities in molecular cell death mechanisms between glaucoma and Alzheimer's disease. On the other hand, recent studies have reported that intracranial pressure is higher in patients with ocular hypertension compared with controls, giving rise to the idea that elevated intracranial pressure may provide a protective effect for the optic nerve by decreasing the trans‐lamina cribrosa pressure difference. The speculation that the higher intracranial pressure reported in ocular hypertension patients may protect against glaucoma mainly through a lower trans‐lamina cribrosa pressure difference remains at least questionable. Here, we present an alternative viewpoint, according to which the protective effect of higher intracranial pressure could be due, at least in part, to a pressure‐independent mechanism, namely faster cerebrospinal fluid production leading to increased cerebrospinal fluid turnover with enhanced removal of potentially neurotoxic waste products that accumulate in the optic nerve. This suggests a new hypothesis for glaucoma, which, just like Alzheimer's disease, may be considered then as an imbalance between production and clearance of neurotoxins, including β‐amyloid. If confirmed, then strategies to improve cerebrospinal fluid flow are reasonable and could provide a new therapeutic approach for stopping the neurotoxic β‐amyloid pathway in glaucoma.     

A Case of Pseudo-Duane's Retraction Syndrome With Old Medial Orbital Wall Fracture

We report a case of pseudo-Duane''s retraction syndrome with entrapment of the medial rectus muscle in an old medial orbital wall fracture presenting identical clinical symptoms as Duane''s retraction syndrome. A 15-year-old boy presented with persistent limited right eye movement since a young age. Examination showed marked limited abduction, mildly limited adduction, and globe retraction accompanied by narrowing of the palpebral fissure during attempted adduction in the right eye. He showed a right esotropia of 16 prism diopters and his head turned slightly to the right. A slight enophthalmos was noted in his right eye. A computed tomography scan demonstrated entrapment of the medial rectus muscle and surrounding tissues in an old medial orbital wall fracture. A forced duction test revealed a marked restriction of abduction in the right eye. A 5 mm recession of the right medial rectus muscle was performed. Postoperatively, the patient''s head turn and esotropia in the primary position were successfully corrected, but there was still some limitations to his ocular movement. The importance of several tests such as the forced duction test and an imaging study should be emphasized in making a diagnosis for limitation of eye movement.     

Longitudinal saccadic changes in Huntington's disease and Alzheimer's disease

Saccadic latency and velocity-amplitude relationships were examined over approximately six years in two patients, one with Huntington's disease (HD) and one with Alzheimer's disease (AD). In both cases this was a period that began relatively early in the course of the disorder and included significant clinical deterioration. The HD patient showed markedly slow saccades upon initial recording; subsequent studies showed some velocity fluctuations without a clear trend. Latency varied similarly, generally being close to normal.

In contrast to the HD patient, the AD patient's first two studies showed normal saccadic latencies and velocities. Also, the latency suddenly became significantly prolonged one year prior to the time that her dementia progressed.

Both patients showed a significant correlation, from session to session, between latency and peak velocity asymptote; this, despite the marked differences in the way their diseases affected these saccadic characteristics. Longer latencies corresponded to lower peak velocities, suggesting a common source, arising in the frontal eye fields, for difficulties in both saccadic initiation and motor programming.     

Optical coherence tomography assessed retinal nerve fiber layer thickness in patients with Alzheimer’s disease: a meta-analysis

AIM: To investigate the difference of retinal nerve fiber layer (RNFL) thickness between Alzheimer’s disease patients and normal people, so as to provide clue for the early diagnosis of Alzheimer’s disease. METHODS: The articles on the association of RNFL thickness and Alzheimer’s disease were retrieved by searching international and national databases. The qualified articles were assessed by meta analysis with Stata11.0 software. The results were pooled using weighted mean difference (WMD) with a corresponding 95% confidence interval (CI). RESULTS: Totally 7 studies enrolled 324 eyes were included in the meta-analysis. The results of meta analysis showed that in AD patients, there was a significant average RNFL thickness reduction compared with the control group [WMD=-17.561, 95%CI: (-23.971, -11.151)]. There were significant differences in superior, inferior, nasal and temporal RNFL thickness between the two groups. WMD with a 95%CI were [-18.829, 95%CI:(-25.915, -11.743); P<0.05], [-25.775, 95%CI:(-34.304, -17.247); P<0.05], [-16.877, 95%CI: (-29.141, -4.613); P<0.001] and [-14.565, 95%CI:(-28.002, -1.128); P<0.001] respectively. Begg’s test and Egger’s test did not show significant difference, funnel plot was basically symmetrical, indicating that there was no publication bias existed. CONCLUSION: There are significant differences in the RNFL thickness in all quadrants between the two groups. RNFL thickness is reduced in AD patients compared with the control group.     

蓝莓花青素在眼科疾病的研究进展

蓝莓又名越橘,它还有很多别名,如笃斯,都柿等,是营养价值极高的浆果,在我国主要种植于山东半岛和大小兴安岭等地区。它具有超强的抗氧化活性和清除自由基能力,归根结底是因为蓝莓中富含丰富的花青素。它还有许多优点,例如高效率、低毒和对人体的生物利用率为100%。蓝莓花青素可以降血压、降血脂,对由于糖尿病引起的毛细血管病有治疗作用,抗炎症、抗癌、预防老年痴呆、增强视力,消除眼睛疲劳、促进眼周微血管循环、延缓脑神经衰老,增强心肺功能等功效。本文主要以蓝莓的提取物花青素为代表来综述花青素的性质、药理作用以及在主要眼病如缓解视疲劳、屈光不正、眼表疾病、白内障、青光眼、视网膜病变等方面应用的最新研究进展。在未来发展进程中,如果能更加深入地研究出其药物作用机制,将会为眼科临床应用提供更多既有效又经济的药物,为广大患者带来福音。     

OCTA在检测阿尔茨海默症临床前期视网膜微血管改变中的应用

阿尔茨海默病(Alzheimer''s disease,AD)是老年痴呆症最常见的病因之一,症状往往在大脑退化性改变数年后才出现,早期诊断困难,既往诊断方法一般为侵入性的检查。大部分AD患者伴有视觉障碍,利用近年来兴起的光学相干断层扫描血管成像技术(optical coherence tomography angiography,OCTA),可以无创、快速地评估视网膜和脉络膜不同血管丛内的结构,将视网膜作为观察大脑的窗口以提高我们对神经系统疾病的认识,可能有助于AD患者的早期诊断。本文将对OCTA应用于神经系统疾病研究的特点,以及在AD患者大脑和视网膜结构、功能研究的相关文献进行综述。     

Actualización sobre alteraciones de función visual y espesores coriorretinianos en la enfermedad de Parkinson

Parkinson's disease (PD) is a neurodegenerative process that affects 7.5 million people around the world.Since 2004, several studies have demonstrated changes in various retinal layers in PD using optical coherence tomography (OCT). However, there are some discrepancies in the results of those studies. Some of them have correlated retinal thickness with the severity or duration of the disease, demonstrating that OCT measurements may be an innocuous and easy biomarker for PD progression. Other studies have demonstrated visual dysfunctions since early phases of the disease. Lastly, the most recent studies that use Swept Source OCT technology, have found choroidal thickness increase in PD patients and provide new information related to the retinal degenerative process in this disease.The aim of this paper is to review the literature on OCT and PD, in order to determine the altered retinal and choroidal parameters in PD and their possible clinical usefulness, and also the visual dysfunctions with higher impact in these patients.     

Optical coherence tomography in paediatric clinical practice

Optical coherence tomography is a non‐invasive ocular imaging technique that is frequently used in the diagnosis and monitoring of optic nerve or retinal disease. Advances in optical coherence tomography speed and image processing capability allow increased use of the modality in clinical practice, especially in younger children. This review outlines the challenges involved in imaging children, highlights the technological progress, the importance of acquiring normative data and, finally, focuses on the clinical applicability of optical coherence tomography in our paediatric population with various ocular conditions.