Visual signs and symptoms of multiple system atrophy

Multiple system atrophy (MSA) is a rare movement disorder and a member of the ‘parkinsonian syndromes’, which also include Parkinson's disease (PD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB) and corticobasal degeneration (CBD). Multiple system atrophy is a complex syndrome, in which patients exhibit a variety of signs and symptoms, including parkinsonism, ataxia and autonomic dysfunction. It can be difficult to separate MSA from the other parkinsonian syndromes but if ocular signs and symptoms are present, they may aid differential diagnosis. Typical ocular features of MSA include blepharospasm, excessive square‐wave jerks, mild to moderate hypometria of saccades, impaired vestibular‐ocular reflex (VOR), nystagmus and impaired event‐related evoked potentials. Less typical features include slowing of saccadic eye movements, the presence of vertical gaze palsy, visual hallucinations and an impaired electroretinogram (ERG). Aspects of primary vision such as visual acuity, colour vision or visual fields are usually unaffected. Management of the disease to deal with problems of walking, movement, daily tasks and speech problems is important in MSA. Optometrists can work in collaboration with the patient and health‐care providers to identify and manage the patient's visual deficits. A more specific role for the optometrist is to correct vision to prevent falls and to monitor the anterior eye to prevent dry eye and control blepharospasm.     

Visual signs and symptoms of progressive supranuclear palsy

Progressive supranuclear palsy is a rare, degenerative brain disorder and the second most common syndrome in which the patient exhibits ‘parkinsonism’, that is, a variety of symptoms involving problems with movement. General symptoms include difficulties with gait and balance; the patient walking clumsily and often falling backwards. The syndrome can be difficult to diagnose and visual signs and symptoms can help to separate it from closely related movement disorders such as Parkinson's disease, multiple system atrophy, dementia with Lewy bodies and corticobasal degeneration. A combination of the presence of vertical supranuclear gaze palsy, fixation instability, lid retraction, blepharospasm and apraxia of eyelid opening and closing may be useful visual signs in the identification of progressive supranuclear palsy. As primary eye‐care practitioners, optometrists should be able to identify the visual problems of patients with this disorder and be expected to work with patients and their carers to manage their visual welfare.     

Visual signs and symptoms of Parkinson's disease

Parkinson's disease (PD) is a common disorder of middle‐aged and elderly people, in which there is degeneration of the extra‐pyramidal motor system. In some patients, the disease is associated with a range of visual signs and symptoms, including defects in visual acuity, colour vision, the blink reflex, pupil reactivity, saccadic and smooth pursuit movements and visual evoked potentials. In addition, there may be psychophysical changes, disturbances of complex visual functions such as visuospatial orientation and facial recognition, and chronic visual hallucinations. Some of the treatments associated with PD may have adverse ocular reactions. If visual problems are present, they can have an important effect on overall motor function, and quality of life of patients can be improved by accurate diagnosis and correction of such defects. Moreover, visual testing is useful in separating PD from other movement disorders with visual symptoms, such as dementia with Lewy bodies (DLB), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Although not central to PD, visual signs and symptoms can be an important though obscure aspect of the disease and should not be overlooked.     

Visual system manifestations of Alzheimer's disease

Alzheimer's disease (AD) is an increasingly common disease with massive personal and economic costs. While it has long been known that AD impacts the visual system, there has recently been an increased focus on understanding both pathophysiological mechanisms that may be shared between the eye and brain and how related biomarkers could be useful for AD diagnosis. Here, were review pertinent cellular and molecular mechanisms of AD pathophysiology, the presence of AD pathology in the visual system, associated functional changes, and potential development of diagnostic tools based on the visual system. Additionally, we discuss links between AD and visual disorders, including possible pathophysiological mechanisms and their relevance for improving our understanding of AD.     

Past,present and future role of retinal imaging in neurodegenerative disease

Retinal imaging technology is rapidly advancing and can provide ever-increasing amounts of information about the structure, function and molecular composition of retinal tissue in humans in vivo. Most importantly, this information can be obtained rapidly, non-invasively and in many cases using Food and Drug Administration-approved devices that are commercially available. Technologies such as optical coherence tomography have dramatically changed our understanding of retinal disease and in many cases have significantly improved their clinical management. Since the retina is an extension of the brain and shares a common embryological origin with the central nervous system, there has also been intense interest in leveraging the expanding armamentarium of retinal imaging technology to understand, diagnose and monitor neurological diseases. This is particularly appealing because of the high spatial resolution, relatively low-cost and wide availability of retinal imaging modalities such as fundus photography or OCT compared to brain imaging modalities such as magnetic resonance imaging or positron emission tomography. The purpose of this article is to review and synthesize current research about retinal imaging in neurodegenerative disease by providing examples from the literature and elaborating on limitations, challenges and future directions. We begin by providing a general background of the most relevant retinal imaging modalities to ensure that the reader has a foundation on which to understand the clinical studies that are subsequently discussed. We then review the application and results of retinal imaging methodologies to several prevalent neurodegenerative diseases where extensive work has been done including sporadic late onset Alzheimer's Disease, Parkinson's Disease and Huntington's Disease. We also discuss Autosomal Dominant Alzheimer's Disease and cerebrovascular small vessel disease, where the application of retinal imaging holds promise but data is currently scarce. Although cerebrovascular disease is not generally considered a neurodegenerative process, it is both a confounder and contributor to neurodegenerative disease processes that requires more attention. Finally, we discuss ongoing efforts to overcome the limitations in the field and unmet clinical and scientific needs.     

Parkinson's disease: a review of the medical and optometric aspects

Parkinson's disease is relatively common in the elderly patients of optometrists. The general medical and ocular signs, symptoms and management of the disease are reviewed. Suggestions are made to improve the ocular examination and subsequent management of the special eye problems which these patients experience.     

Visual improvement with low vision aids in Stargardt's disease

We studied 71 patients with Stargardt's disease or fundus flavimaculatus to evaluate their potential for improvement in visual acuity with the use of low vision aids. The median visual acuity was 10/77 without an aid and 10/32 with a telescopic system. In 54 patients the best corrected reading acuity obtained was 4.0 point print. In all cases low vision aids improved visual acuity for both distance and reading.     

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.     

The flash and pattern VEP as a diagnostic indicator of dementia

Ninety-one patients with forgetfulness, confusion and depression were referred for visual evoked potential and electroencephalographic investigation. The patients were subdivided, on clinical symptoms alone, into a group of 41 with evidence of dementia and a patient control group of 50 with affective disorders. A second control group of 30 normal volunteers of equivalent age was used.In dementia the P2 component of the flash visual evoked potential is delayed, while the pattern reversal P100 component is of normal latency. This unusual combination of results from the two different visual stimuli is shown to be more specific than either the electroencephalogram or computerised tomography in the diagnosis of dementia.     

Visual and Refractive Status of Children With Down's Syndrome and Nystagmus

PurposeChildren with Down''s syndrome (DS) are known to have poorer visual acuity than neurotypical children. One report has shown that children with DS and nystagmus also have poor acuity when compared to typical children with nystagmus. What has not been established is the extent of any acuity deficit due to nystagmus and whether nystagmus affects refractive error within a population with DS.MethodsClinical records from the Cardiff University Down''s Syndrome Vision Research Unit were examined retrospectively. Binocular visual acuity and refraction data were available for 50 children who had DS and nystagmus and 176 children who had DS but no nystagmus. Data were compared between the two groups and with published data for neurotypical children with nystagmus.ResultsThe study confirms the deficit in acuity in DS, compared to neurotypical children, of approximately 0.2 logMAR and shows a deficit attributable to nystagmus of a further 0.2 logMAR beyond the first year of life. Children with both DS and nystagmus clearly have a significant additional impairment. Children with DS have a wide range of refractive errors, but nystagmus increases the likelihood of myopia. Prevalence and axis direction of astigmatism, on the other hand, appear unaffected by nystagmus.ConclusionsNystagmus confers an additional visual impairment on children with DS and must be recognized as such by families and educators. Children with both DS and nystagmus clearly need targeted support.     

Relationships between activated dendritic cells and dry eye symptoms and signs

PurposeTo examine whether “activated” dendritic cells (aDCs) could serve as a biomarker of systemic immune disorders in individuals with dry eye (DE) symptoms. Secondarily, to examine the impact of a topical anti-inflammatory agent on aDC number.MethodsRetrospective analysis was conducted to identify individuals with DE symptoms who had in-vivo confocal microscopy (IVCM) imaging between October 2018 and July 2020 at the Miami Veterans Hospital. aDCs were manually quantified based on morphology. Receiver operating curve (ROC) analysis examined relationships between aDC number and systemic immune disease status. Individuals were then grouped by aDC number (≥2 versus <2) and demographics and DE parameters were examined. Paired t-test was performed to evaluated aDC number pre-vs post-initiation of an anti-inflammatory agent.Results128 individuals were included. Their mean age was 57.1 ± 15.0 years; 71.1% were male, 53.1% self-identified as White and 24.2% as Hispanic. The mean number of aDCs in the central cornea was 1.28 ± 2.16 cells/image. The presence of ≥2 aDCs had a sensitivity of 60% and specificity of 77% for the diagnosis of a systemic immune disorder. Individuals with ≥2 aDCs were more likely to self-identify as Black, have Secondary Sjögren's, and have higher nerve fiber area and fractal dimension. In 12 individuals, aDC number decreased from 2.69 ± 2.36 to 0.58 ± 0.73 cells/image after initiation of an anti-inflammatory agent, p = 0.01.ConclusionsThe presence of ≥2 aDCs in the central cornea suggests a systemic immune disorder in individuals with DE symptoms. Topical anti-inflammatory therapy can reduce the number of aDCs in the central cornea.     

新疆喀什地区脑瘫儿童青少年视觉障碍特征分析

目的：首次全面精准分析新疆喀什地区脑瘫儿童青少年的视觉障碍特征和治疗情况,促进其视觉康 复和全身康复的早期开展。方法：横断面调查研究。选取2018年10月于新疆维吾尔自治区喀什地 区某综合医院集中行眼部筛查的脑瘫儿童青少年,对其进行眼科检查,包括屈光状态、眼位、眼前 节和眼底检查,并调查其眼科治疗情况。采用卡方检验对数据进行分析。结果：纳入176例脑瘫儿 童青少年,年龄0.8～12（6.4±2.7）岁,其中0.8～6岁有97例（55.1%）,维吾尔族169例（96.0%）,男 性104例（59.1%）。存在视觉障碍人数105例（59.7%）,3例（1.7%）同时伴有2种视觉障碍,视觉障碍 的发生率为108例（61.7%）,包括屈光不正（48例,27.3%）、斜视（43例,24.4%）和其他眼部疾病（17 例,9.7%）。所有脑瘫儿童青少年屈光不正以远视为主（20例,11.4%）,斜视以外斜视最常见（25例, 14.2%）,占比最高的前3种其他眼部疾病是视神经萎缩、先天性白内障和先天性青光眼,均为4例 （2.3%）。仅27例（15.3%）脑瘫儿童青少年以往接受过眼科检查,剩余149例（84.7%）均为第1次接受 眼科检查;105例视觉障碍者中仅6例（5.7%）以往接受过眼科检查。所有脑瘫儿童青少年近视发生 率为9.7%（17例）,不同性别、年龄段、民族以及是否斜视之间近视的发生率差异没有统计学意义。 结论：脑瘫儿童青少年视觉障碍发生率高于同年龄段儿童,且斜视发生率非常高。这也提示在脑瘫 儿童青少年中普及眼健康筛查的迫切性和重要性,可作为今后开展脑瘫患者康复工作的重点内容之 一。     

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。     

Visual acuity and endothelial cell density with respect to the graft thickness in Descemet's stripping automated endothelial keratoplasty:one year results

AIM: To evaluate the visual acuity and endothelial cell density according to thethickness in Descemet's stripping automated endothelial keratoplasty (DSAEK) one year after surgery.METHODS: DSAEK patients' data were reviewed. Thirty-seven eyes of 37 patients who underwent DSAEK for pseudophakic bullous keratopathy (PBK) were included in this study. Graft thickness was measured with optical coherence tomography (OCT) 12mo after DSAEK. Eyes were divided into 3 groups based on the graft thickness:thick (>200 μm), medium-thick (150-200 μm) and thin (<150 μm). Best corrected visual acuity (BCVA), endothelial cells density (ECD) and complications were assessed and comparisons were done between groups.RESULTS:There was no significant difference in age, sex, preoperative BCVA, or follow-up period between DSAEK groups. At postoperative 12mo, mean BCVA was 0.28±0.10 in thick graft group, 0.52±0.08 in medium-thick graft group, and 0.72±0.06 in thin graft group. Thin grafts showed better postoperative BCVA as compared with the medium-thick and thick grafts (P=0.001). Thick graft group had 1637.44±88.19-mm², medium thick graft had 1764.50±34.28-mm² and thin graft group had 1845.30±65.62-mm² ECD at 12mo after the surgery. Thin graft group had better ECD at 12mo after surgery (P=0.001).CONCLUSION: Thin grafts after DSAEK ensure better visual rehabilitation. Eyes with thin grafts had significantly lesser loss of ECD compared to eyes with medium-thick and thick grafts one year after surgery.     

Choroideremia,sensorineural deafness,and primary ovarian failure in a woman with a balanced X-4 translocation

We present clinical and cytogenetic studies of a female patient affected with choroideremia, mild sensorineural deafness, and primary amenorrhea showing a balanced translocation between chromosomes X and 4. The breakpoint was precisely defined applying FISH techniques: 46,X,t(X;4)(q21.2;p16.3).ish t(X;4)(D4S96+, D4F26+; wcpX+). The X-chromosomal breakpoint was located within a region where both the choroideremia locus and a deafness locus (DFN3/POU3F4) have been mapped. The presence of X-linked disorders in this balanced carrier of X-autosomal translocations (XAT) can be explained either by the disruption of the structural coding or regulatory sequences of the gene(s) or by the submicroscopic deletion of this region leading to a contiguous gene deletion syndrome. The primary ovarian failure (POF) found in the present case has been already observed in XAT when the breakpoint is within a previously defined critical region (Xq13-26). A position effect is postulated as a possible explanation.