Retinal nerve fiber layer thinning in chronic fatigue syndrome as a possible ocular biomarker of underlying glymphatic system dysfunction

In a recent article published in Medical Hypotheses, my colleague and I speculated that glymphatic dysfunction, causing toxic build up within the central nervous system, may be responsible for at least some cases of chronic fatigue syndrome (CFS) [1]. We further postulated that cerebrospinal fluid diversion such as lumboperitoneal shunting may be beneficial to this subgroup of patients by restoring glymphatic transport and waste removal from the brain. In this context, it would be helpful to have a predictive biomarker that can identify CFS patients who are good candidates for this specific treatment. For reasons discussed below, I believe that retinal nerve fiber layer (RNFL) thinning may be a sign of underlying glymphatic system dysfunction in neurodegenerative diseases that result from protein toxicity.

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Visual aspects of reading performance in myalgic encephalomyelitis (ME)

Reprinted with the kind permission of ME Research UK.

Abstract:

People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) report vision-related reading difficulty, although this has not been demonstrated objectively. Accordingly, we assessed reading speed and acuity, including crowded acuity and acuity for isolated words using standardized tests of reading and vision, in 27 ME/CFS patients and matched controls. We found that the ME/CFS group exhibited slower maximum reading speed, and had poorer crowded acuity than controls. Moreover, crowded acuity was significantly associated with maximum reading speed, indicating that patients who were more susceptible to visual crowding read more slowly. These findings suggest vision-related reading difficulty belongs to a class of measureable symptoms for ME/CFS patients.

Publication

Wilson et al, Frontiers in Psychology, 2018 August 17; 9:1468

Authors

Rachel L. Wilson, Kevin B. Paterson, Victoria McGowan and Claire V. Hutchinson

Institution

Department of Neuroscience, Psychology and Behaviour, College of Life Sciences, University of Leicester, Leicester, UK

Funding

This work was funded by an ME Research UK (Grant No. SC036942) to CH and KP. VM was supported by an Economic and Social Research Council (Grant No. ES/L010836/1).

Comment by ME Research UK

Many people with ME/CFS suffer from problems with their eyes and vision, such as oversensitivity to light, troubles with focusing, and dry eyes. Reading can therefore be challenging, particularly for long periods, and pattern glare, headaches and difficulty tracking lines of text are commonly reported. However, before now, the reading performance of ME/CFS patients had not been assessed objectively.

Over the last few years, Dr Claire Hutchinson and her colleagues at the University of Leicester have been looking in depth at some of the vision-related problems associated with ME/CFS, supported in part by grants from ME Research UK.

The group has found that most ME/CFS patients experience a degree of eye pain and sensitivity to bright lights. Using sophisticated eye-tracking techniques, they have also shown that patients struggle to focus on one object and ignore irrelevant information, are slow in shifting attention between objects, are slower than normal and less accurate in their eye movements, and are vulnerable to pattern-related visual stress.

In their latest ME Research UK-funded study, published in the journal Frontiers in Psychology, the Leicester team set out to evaluate what impact ME/CFS has on reading performance. A total of 27 ME/CFS patients and 27 healthy control subjects took part in the research; all had normal vision or corrected-to-normal vision (i.e. they wore spectacles or contact lenses) and none had any history of eye disease.

Reading performance was assessed using two standardised tests, the Minnesota Reading Acuity Chart and the Radner Rate of Reading Chart, which between them produced the following measures:

  • Reading acuity (the smallest print size that can be read without significant mistakes),
  • Maximum reading speed (not limited by print size),
  • Average reading speed, and
  • Critical print size (the smallest print size that can be read at maximum speed).

As expected, the maximum reading speed was significantly slower in ME/CFS patients than in control subjects, and patients also tended to have a slower average reading speed. However, reading acuity and critical print size were not different between the two groups, indicating that the reading difficulties were not due to an inability to make out smaller print.

Furthermore, ME/CFS patients and control subjects performed similarly on a vocabulary test, showing that the differences in reading performance between the two groups were unlikely to be due to cognitive problems.

The researchers also looked at uncrowded visual acuity for individual words and letters (identifying a word or letter on its own) and crowded visual acuity (identifying a target letter surrounded by other letters), using the logMar Crowded Test.

While uncrowded visual acuity appeared to be similar in patients and controls, ME/CFS patients did have greater problems with visual crowding and performed less well on that test. Furthermore, those individuals who were more susceptible to visual crowding were also shown to read more slowly.

These findings build on a considerable body of work from Dr Hutchinson and her team in which they have detailed and explored the vision-related symptoms associated with ME/CFS. While many people with he illness know full well how difficult it can be to read comfortably, particularly for long periods, this is the first time these problems have been assessed objectively in a laboratory setting.

As the researchers conclude, ‘identifying and treating vision-related symptoms of ME/CFS could provide a means of improving the everyday lives of patients’.

________________

ME Research UK commissions and funds high-quality scientific (biomedical) investigation into ME/CFS. 

 

Visual Aspects of Reading Performance in Myalgic Encephalomyelitis (ME)

People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) report vision-related reading difficulty, although this has not been demonstrated objectively. Accordingly, we assessed reading speed and acuity, including crowded acuity and acuity for isolated words using standardized tests of reading and vision, in 27 ME/CFS patients and matched controls. We found that the ME/CFS group exhibited slower maximum reading speed, and had poorer crowded acuity than controls. Moreover, crowded acuity was significantly associated with maximum reading speed, indicating that patients who were more susceptible to visual crowding read more slowly. These findings suggest vision-related reading difficulty belongs to a class of measureable symptoms for ME/CFS patients.

Source: Rachel L. Wilson, Kevin B. Paterson, Victoria McGowan and Claire V. Hutchinson. Visual Aspects of Reading Performance in Myalgic Encephalomyelitis (ME). Front. Psychol., 17 August 2018 https://doi.org/10.3389/fpsyg.2018.01468 (Full article)

Ophthalmic correlates of Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, debilitating disorder. With the exception of disabling fatigue, there are few definitive clinical features of the condition. As a consequence, patients often have difficulty gaining an appropriate diagnosis. As such, identifying distinct clinical feature of ME/CFS is an important issue. One under researched area of ME/CFS associated symptoms concerns problems related to vision.

People with ME/CFS consistently report a range of symptoms related to the quality of their vision including pain in the eyes, hypersensitivity to light, difficulty focusing on images, slow eye movements, and difficulty tracking object movement. However, there has been little attempt to verify patients’ self-reports using objective methods. The purpose of the experiments presented in this thesis was to determine the effects of ME/CFS on: (i) performance on a range of tests of visual sensitivity and (ii) the morphology of the retina.

Compared to controls, the ME/CFS group exhibited reduced accommodation, larger pupil diameters, reduced colour discrimination and poorer contrast sensitivity towards lower spatial frequencies. Thinning in the photoreceptor layers of the retina (the Outer Segment & the Outer Nuclear layer) was also apparent. These findings support the claims of people with ME/CFS that they experience problems related to their vision and its function. They also represent a potential marker of ME/CFS that may aid in its diagnosis.

Source: Ahmed, Nadia Sultana. Ophthalmic Correlates of Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). Thesis, Univeristy of Leicester, 15-Feb-2018

Visual stress could be a symptom of Chronic Fatigue Syndrome, research suggests

University of Leicester research team discovers vision-related abnormalities that could help in diagnosis of illness

People suffering from Chronic Fatigue Syndrome (CFS) could experience higher levels of visual stress than those without the condition, according to new research from the University of Leicester.

CFS, also known as Myalgic Encephalomyelitis (ME), is a condition that causes persistent exhaustion that affects everyday life and doesn’t go away with sleep or rest. Diagnosis of the condition is difficult as its symptoms are similar to other illnesses.

A research team from the University of Leicester led by Dr Claire Hutchinson from the Department of Neuroscience, Psychology and Behaviour has examined patients with and without CFS and has found that those suffering from the condition are more vulnerable to pattern-related visual stress, which causes discomfort and exhaustion when viewing repetitive striped patterns, such as when reading text.

The results of the study, which is published in the journal Perception, could help in the diagnosis of CFS, as the findings suggest that there are visual system abnormalities in people with ME/CFS that may represent an identifiable and easily measurable behavioural marker of the condition.

Dr Hutchinson explained: “Diagnosis of ME/CFS is controversial. With the exception of disabling fatigue, there are few definitive clinical features of the condition and its core symptoms, overlap with those often prevalent in other conditions. As a result, ME/CFS is often a diagnosis of exclusion, being made as a last resort and possibly after a patient has experienced a series of inappropriate treatments of misdiagnosed disorders.

“It is imperative therefore that research focuses on identifying significant clinical features of CFS/ME with a view to elucidating its underlying pathology and delineating it from other illnesses. Doing so will help researchers and healthcare professionals gain important insights into the condition, aid diagnosis and, in the longer term, inform evidence-based therapeutic interventions.”

The study assessed vulnerability of ME/CFS patients to pattern-related visual stress using a standardised test called the pattern glare test, in which people report the number of visual distortions they experience when looking at three repetitive striped patterns of different levels of detail.

During the study twenty patients with CFS and twenty patients without the condition were recruited.

Participants viewed 3 patterns, the spatial frequencies (SF) of which were either 0.3 (low-SF), 2.3 (mid-SF) and 9.4 (high-SF) cycles per degree (c/deg). They then reported the number of distortions they experienced when viewing each pattern.

Patients with ME/CFS reported more distortions on the intermediate striped pattern (Pattern 2) than people without the condition.

Dr Hutchinson added: “The existence of pattern-related visual stress in ME/CFS may represent an identifiable and easily measurable behavioural marker of ME. This could, in conjunction with other diagnostic tests, help delineate it from other conditions.”

The work was funded by ME Research UK who provided funding for a 1-year MPhil studentship, awarded to Rachel Wilson, who was supervised by Drs Claire Hutchinson and Kevin Paterson from the University of Leicester’s Department of Neuroscience, Psychology and Behaviour.

Dr Neil Abbot, Research & Operations Director at ME Research UK, added: “Around three-quarters of people with ME/CFS report a range of eye and vision-related symptoms that interfere with their everyday lives, yet there has been very little scientific investigation of the problem.

“Dr Claire Hutchinson and her team have previously confirmed the existence of eye movement difficulties in ME/CFS patients, and that symptoms, including eye pain, can be severe. Her new report in Perception extends these findings and raises the possibility that vision anomalies, including pattern-related visual stress, may have a diagnostic role in the disease.”

The study ‘Increased vulnerability to pattern-related visual stress in Myalgic Encephalomyelitis’ was published in the journal Perception.

Journal Reference: Rachel L. Wilson, Kevin B. Paterson and Claire V. Hutchinson. Increased Vulnerability to Pattern-Related Visual Stress in Myalgic Encephalomyelitis. Perception, November 2015 DOI: 10.1177/0301006615614467

 

Source: University of Leicester. (2015, November 24). Visual stress could be a symptom of Chronic Fatigue Syndrome, research suggests. ScienceDaily. Retrieved March 4, 2017 from https://www.sciencedaily.com/releases/2015/11/151124082235.htm

 

Binocular Vision in Chronic Fatigue Syndrome

Abstract:

INTRODUCTION AND PURPOSE: To compare binocular vision measurements between Chronic Fatigue Syndrome (CFS) patients and healthy controls.

METHODS: Forty-one CFS patients referred by the Reference Centre for Chronic Fatigue Syndrome of the Antwerp University Hospital and forty-one healthy volunteers, matched for age and gender, underwent a complete orthoptic examination. Data of visual acuity, eye position, fusion amplitude, stereopsis, ocular motility, convergence, and accommodation were compared between both groups.

RESULTS: Patients with CFS showed highly significant smaller fusion amplitudes (P < 0.001), reduced convergence capacity (P < 0.001), and a smaller accommodation range (P < 0.001) compared to the control group.

CONCLUSION: In patients with CFS binocular vision, convergence and accommodation should be routinely examined. CFS patients will benefit from reading glasses either with or without prism correction in an earlier stage compared to their healthy peers. Convergence exercises may be beneficial for CFS patients, despite the fact that they might be very tiring. Further research will be necessary to draw conclusions about the efficacy of treatment, especially regarding convergence exercises. To our knowledge, this is the first prospective study evaluating binocular vision in CFS patients.

© 2016 Board of regents of the University of Wisconsin System, American Orthoptic Journal, Volume 66, 2016, ISSN 0065-955X, E-ISSN 1553-4448.

 

Source: Godts D, Moorkens G, Mathysen DG. Binocular Vision in Chronic Fatigue Syndrome. Am Orthopt J. 2016 Jan;66(1):92-97. https://www.ncbi.nlm.nih.gov/pubmed/27799582

 

Increased Vulnerability to Pattern-Related Visual Stress in Myalgic Encephalomyelitis

Abstract:

The objective of this study was to determine vulnerability to pattern-related visual stress in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A total of 20 ME/CFS patients and 20 matched (age, gender) controls were recruited to the study.

Pattern-related visual stress was determined using the Pattern Glare Test. Participants viewed three patterns, the spatial frequencies (SF) of which were 0.3 (low-SF), 2.3 (mid-SF), and 9.4 (high-SF) cycles per degree (c/deg). They reported the number of distortions they experienced when viewing each pattern.

ME/CFS patients exhibited significantly higher pattern glare scores than controls for the mid-SF pattern. Mid-high SF differences were also significantly higher in patients than controls. These findings provide evidence of altered visual perception in ME/CFS.

Pattern-related visual stress may represent an identifiable clinical feature of ME/CFS that will prove useful in its diagnosis. However, further research is required to establish if these symptoms reflect ME/CFS-related changes in the functioning of sensory neural pathways.

© The Author(s) 2015.

 

Source: Wilson RL, Paterson KB, Hutchinson CV. Increased Vulnerability to Pattern-Related Visual Stress in Myalgic Encephalomyelitis. Perception. 2015 Dec;44(12):1422-6. doi: 10.1177/0301006615614467. Epub 2015 Nov 3. https://www.ncbi.nlm.nih.gov/pubmed/26562880

 

Patterns of abnormal visual attention in myalgic encephalomyelitis

Abstract:

PURPOSE: To experimentally assess visual attention difficulties commonly reported by those with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

METHODS: Twenty-nine ME/CFS patients and 29 controls took part in the study. Performance was assessed using the Useful Field of View (UFOV), a spatial cueing task and visual search.

RESULTS: Patients and controls performed similarly on the processing speed subtest of the UFOV. However, patients exhibited marginally worse performance compared with controls on the divided attention subtest and significantly worse performance on the selective attention subtest. In the spatial cueing task, they were slower than controls to respond to the presence of the target, particularly when cues were invalid. They were also impaired, relative to controls, on visual search tasks.

CONCLUSIONS: We have provided experimental evidence for ME/CFS-related difficulties in directing visual attention. These findings support the subjective reports of those with ME/CFS and could represent a potential means to improve diagnosis.

 

Source: Hutchinson CV, Badham SP. Patterns of abnormal visual attention in myalgic encephalomyelitis. Optom Vis Sci. 2013 Jun;90(6):607-14. doi: 10.1097/OPX.0b013e318294c232. https://www.ncbi.nlm.nih.gov/pubmed/23689679

 

Pathology of the organ of vision in chronic fatigue syndrome

Abstract:

218 patients were examined and the chronic fatigue syndrome (CFS) was diagnosed in them on the basis of clinical-and-immunologic data. 126 somatically healthy persons of the same age and sex were in the control group. Vascular pathology of the vision organ was found in 153 (70.2%) persons, and dystrophic pathology was found in 115 (52.8%) persons. A combination of vascular and dystrophic pathologies of the vision organ was diagnosed in 46 (21.1%) patients. The detection of vision pathology in the CFS patients essentially exceeded the morbidity of similar pathology in the controls. No reliable differences of refraction anomalies were found between the CFS patients and the controls.

 

Source: Frolov VM, Petrunia AM. Pathology of the organ of vision in chronic fatigue syndrome. Vestn Oftalmol. 2003 Mar-Apr;119(2):45-7. [Article in Russian] http://www.ncbi.nlm.nih.gov/pubmed/13678013

 

 

 

Ocular manifestations of chronic fatigue and immune dysfunction syndrome

Abstract:

Chronic fatigue and immune dysfunction syndrome (CFIDS) is a disease presenting with systemic, sensory, cognitive, and psychological manifestations. Ocular symptomatology is reported in the visual, functional, perceptual, and pathological aspects of the visual system. The purpose of the research was to evaluate ocular symptoms in patients with CFIDS.

One hundred and ninety CFIDS patients [155 females, 35 males; mean age of 41 years (range 15 to 72)] and 198 healthy controls [133 females, 65 males; mean age of 42 years (range 8 to 89)] were surveyed via written questionnaire. Evaluation of data showed statistical significance at levels ranging from 0.0001 to 0.007 for all but one symptom surveyed. It appears that the ocular symptoms of CFIDS are genuine. Further research is needed to determine the etiology and appropriate treatment of this disease.

 

Source: Potaznick W, Kozol N. Ocular manifestations of chronic fatigue and immune dysfunction syndrome. Optom Vis Sci. 1992 Oct;69(10):811-4. http://www.ncbi.nlm.nih.gov/pubmed/1437004