The visual complications of Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disorder affecting middle-aged and elderly people. The disorder is of particular interest to Optometrists because it is associated with a range of visual problems including defects in eye movement and pupillary function. This article reviews the visual complications of PD and the pathological changes in the eye and brain which may explain these symptoms.

Degeneration of cortical neurons associated with diffuse beta-amyloid (Abeta) deposits in Alzheimer’s disease

The frequency of morphological abnormalities in neuronal perikarya which were in contact with diffuse beta-amyloid (Abeta) deposits in patients with Alzheimer’s disease (AD) was compared with neurons located adjacent to the deposits. Morphological abnormalities were also studied in elderly, non-demented (ND) cases with and without diffuse Abeta deposits. In AD and ND cases with Abeta deposits, an increased proportion of neurons in contact with diffuse deposits exhibited at least one abnormality compared with neurons located adjacent to the deposits. Neurons in contact with diffuse deposits exhibited a greater frequency of abnormalities of shape, nuclei, nissl substance and had a higher frequency of cytoplasmic vacuoles compared with adjacent neurons. A greater frequency of abnormalities of shape, nissl substance and in the frequency of displaced nuclei were also observed in neurons adjacent to diffuse deposits in AD compared with ND cases. With the exception of absent nuclei, morphological abnormalities adjacent to diffuse deposits in ND cases were similar to those of ND cases without Abeta deposits. These results suggest that neuronal degeneration is associated with the earliest stages of Abeta deposit formation and is not specifically related to the formation of mature senile plaques.

Neurological and ocular abnormalities in patients with Down's syndrome

Down's syndrome, first described by J. Langdon Down in 1866, is the most common chromosomal abnormality to occur in the human population. Its incidence is approximately 1/650 of all births although the risk of having a Down's child increases markedly with the age of the mother. It occurs with equal frequency in all racial groups. The risk to a mother 16-26 years old is 1 in 1,300 but the risk increases to 1 in 30 for a mother 45-47 years old. The life expectancy of people with Down's syndrome has risen since the 1920s and many individuals are now living to the 5th decade or beyond. Consequently optometrists are increasingly likley to see Down's patients of all ages in the practice.

Alzheimer’s disease and the eye

Dementia, including Alzheimer’s disease (AD), is a major disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of ß-amyloid (Aß) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA), colour vision and visual fields; changes in pupillary response to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP); and disturbances of complex visual functions such as reading, visuospatial function, and in the naming and identification of objects. Many of these changes are controversial with conflicting data in the literature and no ocular or visual feature can be regarded as particularly diagnostic of AD. In addition, some pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. The optometrist has a role in helping a patient with AD, if it is believed that signs and symptoms of the disease are present, so as to optimize visual function and improve the quality of life. (J Optom 2009;2:103-111 ©2009 Spanish Council of Optometry)

Visual signs and symptoms of Parkinson's disease

There are two aspects of PD of particular interest to optometrists. First, PD patients can develop a range of visual problems including those affecting eye movement, pupillary function, and in complex visual functions involving the ability to judge distance or make out the shape of an object. Second, the symptoms of PD can be treated successfully using a variety of drugs, some of which have significant ocular adverse reactions (OAR). This article describes the general features of PD, the dopamine neurotransmitter system and its relevance to eye symptoms, the visual symptoms reported in PD, and the OAR that have been reported.

Examination variability in short-wavelength automated perimetry

The study evaluated sources of within- and between-subject variability in standard white-on-white (W-W) perimetry and short-wavelength automated perimetry (SWAP). The Influence of staircase strategy on the fatigue effect in W-W perimetry was investigated for a 4 dB single step, single reversal strategy; a variable step size, single reversal dynamic strategy; and the standard 4-2 dB double reversal strategy. The fatigue effect increased as the duration of the examination Increased and was greatest in the second eye for all strategies. The fatigue effect was lowest for the 4dB strategy, which exhibited the shortest examination time and was greatest for the 4-2 dB strategy, which exhibited the longest examination time. Staircase efficiency was lowest for the 4 dB strategy and highest for the dynamic strategy which thus offers a reduced examination time and low inter-subject variability. The normal between-subject variability of SWAP was determined for the standard 4-2 dB double reversal strategy and the 3 dB single reversal FASTPAC strategy and compared to that of W-W perimetry, The decrease in sensitivity with Increase in age was greatest for SWAP. The between-subject variability of SWAP was greater than W-W perimetry. Correction for the Influence of ocular media absorption reduced the between-subject variability of SWAP, The FASTPAC strategy yielded the lowest between-subject variability In SWAP, but the greatest between-subject variability In WoW perimetry. The greater between-subject variability of SWAP has profound Implications for the delineation of visual field abnormality, The fatigue effect for the Full Threshold strategy in SWAP was evaluated with conventional opaque, and translucent occlusion of the fellow eye. SWAP exhibited a greater fatigue effect than W-W perimetry. Translucent occlusion reduced the between-subject variability of W-W perimetry but Increased the between-subject variability of SWAP. The elevation of sensitivity was greater with translucent occlusion which has implications for the statistical analysis of W-W perimetry and SWAP. The influence of age-related cataract extraction and IOL implantation upon the visual field derived by WoW perimetry and SWAP was determined. Cataract yielded a general reduction In sensitivity which was preferentially greater in SWAP, even after the correction of SWAP for the attenuation of the stimulus by the ocular media. There was no correlation between either backward or forward light scatter and the magnitude of the attenuation of W-W or SWAP sensitivity. The post-operative mean deviation in SWAP was positive and has ramifications for the statistical Interpretation of SWAP. Short-wavelength-sensitive pathway isolation was assessed as a function of stimulus eccentricity using the two-colour Increment threshold method. At least 15 dB of SWS pathway Isolation was achieved for 440 nm, 450 nm and 460 nm stimuli at a background luminance of 100 cdm-2, There was a slight decrease In SWS pathway Isolation for all stimulus wavelengths with increasing eccentricity which was not of clinical significance. Adopting a 450 nm stimulus may reduce between-subject variability In SWAP due to a reduction In ocular media absorption and macular pigment absorption.

Ambulatory EEG monitoring in the diagnosis and treatment of epilepsy and related disorders

Ambulatory EEG recording enables patients with epilepsy and related disorders to be monitored in an unrestricted environment for prolonged periods. Attacks can therefore be recorded and EEG changes at the time can aid diagnosis. The relevant Iiterature is reviewed and a study made of' 250 clinical investigations. A study was also made of the artefacts,encountered during ambulatory recording. Three quarters of referrals were for distinguishing between epileptic and non-epileptic attacks. Over 60% of patients showed no abnormality during attacks. In comparison with the basic EEG the ambulatory EEG provided about ten times as much information. A preliminary follow-up study showed that results, of ambulatory monitoring agreed with the final diagnosis in 8 of 12 patients studied. Of 10 patients referred, for monitoring the occurrence of absence seizures, 8 showed abnormality during the baslcJ EEG .and 10 during the ambulatory EEG. Other patients. were referred: for sleep recording and to clarify the seizure type. An investigation into once daily (OD) versus twice daily administration of sodium valproate in patients with absence seizures showed that an OD regime was equally as effective as a BD regime. Circadian variations in spike and wave activity in patients on and off treatment were also examined. There was significant agreement between subjects on the time of occurrence of abnormality during sleep only, This pattern was not ,affected with treatment nor was there any difference in the daily pattern of occurrence of abnormality between the two regimes. Overall findings suggested that ambulatory monitoring was a valuable tool in the diagnosis and treatment of epilepsy which with careful planning and patient selection could be used in any EEG department and would benefit a:wide range of patients.

Non-standard techniques for the investigation of the visual field

The study investigated the potential applications and the limitations of non-standard techniques of visual field investigation utilizing automated perimetry. Normal subjects exhibited a greater sensitivity to kinetic stimuli than to static stimuli of identical size. The magnitude of physiological SKD was found to be largely independent of age, stimulus size, meridian and eccentricity. The absence of a dependency on stimulus size indicated that successive lateral spatial summation could not totally account for the underlying mechanism of physiological SKD. The visual field indices MD and LV exhibited a progressive deterioration during the time course of a conventional central visual field examination both for normal subjects and for ocular hypertensive patients. The fatigue effect was more pronounced in the latter stages and for the second eye tested. The confidence limits for the definition of abnormality should reflect the greater effect of fatigue on the second eye. A 330 cdm-2 yellow background was employed for blue-on-yellow perimetry. Instrument measurement range was preserved by positioning a concave mirror behind the stimulus bulb to increase the light output by 60% . The mean magnitude of SWS pathway isolation was approximately 1.4 log units relative to a 460nm stimulus filter. The absorption spectra of the ocular media exhibited an exponential increase with increase in age, whilst that of the macular pigment showed no systematic trend. The magnitude of ocular media absorption was demonstrated to reduce with increase in wavelength. Ocular media absorption was significantly greater in diabetic patients than in normal subjects. Five diabetic patients with either normal or borderline achromatic sensitivity exhibited an abnormal blue-on-yellow sensitivity; two of these patients showed no signs of retinopathy. A greater vulnerability of the SWS pathway to the diabetic disease process was hypothesized.

Abnormal amygdala-prefrontal effective connectivity to happy faces differentiates bipolar from major depression

Background - Bipolar disorder is frequently misdiagnosed as major depressive disorder, delaying appropriate treatment and worsening outcome for many bipolar individuals. Emotion dysregulation is a core feature of bipolar disorder. Measures of dysfunction in neural systems supporting emotion regulation might therefore help discriminate bipolar from major depressive disorder. Methods - Thirty-one depressed individuals—15 bipolar depressed (BD) and 16 major depressed (MDD), DSM-IV diagnostic criteria, ages 18–55 years, matched for age, age of illness onset, illness duration, and depression severity—and 16 age- and gender-matched healthy control subjects performed two event-related paradigms: labeling the emotional intensity of happy and sad faces, respectively. We employed dynamic causal modeling to examine significant among-group alterations in effective connectivity (EC) between right- and left-sided neural regions supporting emotion regulation: amygdala and orbitomedial prefrontal cortex (OMPFC). Results - During classification of happy faces, we found profound and asymmetrical differences in EC between the OMPFC and amygdala. Left-sided differences involved top-down connections and discriminated between depressed and control subjects. Furthermore, greater medication load was associated with an amelioration of this abnormal top-down EC. Conversely, on the right side the abnormality was in bottom-up EC that was specific to bipolar disorder. These effects replicated when we considered only female subjects. Conclusions - Abnormal, left-sided, top-down OMPFC–amygdala and right-sided, bottom-up, amygdala–OMPFC EC during happy labeling distinguish BD and MDD, suggesting different pathophysiological mechanisms associated with the two types of depression.

The visual cortex in Alzheimer disease:laminar distribution of the pathological changes in visual areas V1 and V2

Alzheimer’s disease (AD) is an important neurodegenerative disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of ?-amyloid (A?) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA), colour vision and visual fields; changes in pupillary responses to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP); and disturbances in complex visual tasks such as reading, visuospatial function, and in the naming and identification of objects. In addition, pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. To better understand degeneration of the visual cortex in AD, the laminar distribution of the SP and NFT was studied in visual areas V1 and V2 in 18 cases of AD which varied in disease onset and duration. In area V1, the mean density of SP and NFT reached a maximum in lamina III and in laminae II and III respectively. In V2, mean SP density was maximal in laminae III and IV and NFT density in laminae II and III. The densities of SP in laminae I of V1 and NFT in lamina IV of V2 were negatively correlated with patient age. No significant correlations were observed in any cortical lamina between the density of NFT and disease onset or duration. However, in area V2, the densities of SP in lamina II and lamina V were negatively correlated with disease duration and disease onset respectively. In addition, there were several positive correlations between the densities of SP and NFT in V1 with those in area V2. The data suggest: (1) NFT pathology is greater in area V2 than V1, (2) laminae II/III of V1 and V2 are most affected by the pathology, (3) the formation of SP and NFT in V1 and V2 are interconnected, and (4) the pathology may spread between visual areas via the feed-forward short cortico-cortical connections.

The importance of optical coherence tomography examination of normal fellow eyes in neovascular age-related macular degeneration monitoring clinics

Purpose: To demonstrate the importance of OCT examination of fellow, normal eyes in unilateral nAMD follow up clinics. Methods: The authors present three cases of unilateral nAMD who were undergoing treatment with ranibizumab, in whom OCT evaluation of the previously unaffected, asymptomatic fellow eye allowed early diagnosis, treatment and preservation of vision. Fundus examination had previously failed to demonstrate abnormality. Results: Intravitreal anti-VEGF treatment for nAMD has caused a sharp increase in the number of subjects attending macular clinics, frequently overburdening the system. It may sometimes be tempting for hospitals to reduce the workload by for example, concentrating only on OCT examination of the affected eye in cases of unilateral nAMD. The three reported cases demonstrate that OCT scanning of the fellow, previously unaffected eye is essential in detecting asymptomatic nAMD, which gives a better chance of preservation of vision. Conclusions: Patients with unilateral neovascular AMD undergoing review in macular clinics should always undergo OCT scanning of normal, fellow eyes, as otherwise asymptomatic, “invisible” choroidal neovascular membranes may be missed.

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.

Brain connectivity in positive and negative syndrome schizophrenia

If, as is widely believed, schizophrenia is characterized by abnormalities of brain functional connectivity, then it seems reasonable to expect that different subtypes of schizophrenia could be discriminated in the same way. However, evidence for differences in functional connectivity between the subtypes of schizophrenia is largely lacking and, where it exists, it could be accounted for by clinical differences between the patients (e.g. medication) or by the limitations of the measures used. In this study, we measured EEG functional connectivity in unmedicated male patients diagnosed with either positive or negative syndrome schizophrenia and compared them with age and sex matched healthy controls. Using new methodology (Medkour et al., 2009) based on partial coherence, brain connectivity plots were constructed for positive and negative syndrome patients and controls. Reliable differences in the pattern of functional connectivity were found with both syndromes showing not only an absence of some of the connections that were seen in controls but also the presence of connections that the controls did not show. Comparing connectivity graphs using the Hamming distance, the negative-syndrome patients were found to be more distant from the controls than were the positive syndrome patients. Bootstrap distributions of these distances were created which showed a significant difference in the mean distances that was consistent with the observation that negative-syndrome diagnosis is associated with a more severe form of schizophrenia. We conclude that schizophrenia is characterized by widespread changes in functional connectivity with negative syndrome patients showing a more extreme pattern of abnormality than positive syndrome patients.

Fibre optics sensors in tear electrolyte analysis:towards a novel point of care potassium sensor

The diagnosis of ocular disease is increasingly important in optometric practice and there is a need for cost effective point of care assays to assist in that. Although tears are a potentially valuable source of diagnostic information difficulties associated with sample collection and limited sample size together with sample storage and transport have proved major limitations. Progressive developments in electronics and fibre optics together with innovation in sensing technology mean that the construction of inexpensive point of care fibre optic sensing devices is now possible. Tear electrolytes are an obvious family of target analytes, not least to complement the availability of devices that make the routine measurement of tear osmolarity possible in the clinic. In this paper we describe the design, fabrication and calibration of a fibre-optic based electrolyte sensor for the quantification of potassium in tears using the ex vivo contact lens as the sample source. The technology is generic and the same principles can be used in the development of calcium and magnesium sensors. An important objective of this sensor technology development is to provide information at the point of routine optometric examination, which would provide supportive evidence of tear abnormality.

Frontopolar cortical inefficiency may underpin reward and working memory dysfunction in bipolar disorder

Objectives. Emotional dysregulation in bipolar disorder is thought to arise from dysfunction within prefrontal cortical regions involved in cognitive control coupled with increased or aberrant activation within regions engaged in emotional processing. The aim of this study was to determine the common and distinct patterns of functional brain abnormalities during reward and working memory processing in patients with bipolar disorder. Methods. Participants were 36 euthymic bipolar disorder patients and 37 healthy comparison subjects matched for age, sex and IQ. Functional magnetic resonance imaging (fMRI) was conducted during the Iowa Gambling Task (IGT) and the n-back working memory task. Results. During both tasks, patients with bipolar disorder demonstrated a pattern of inefficient engagement within the ventral frontopolar prefrontal cortex with evidence of segregation along the medial-lateral dimension for reward and working memory processing, respectively. Moreover, patients also showed greater activation in the anterior cingulate cortex during the Iowa Gambling Task and in the insula during the n-back task. Conclusions. Our data implicate ventral frontopolar dysfunction as a core abnormality underpinning bipolar disorder and confirm that overactivation in regions involved in emotional arousal is present even in tasks that do not typically engage emotional systems. © 2012 Informa Healthcare.