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Dr.Gunjan Rana, G19620, Dr.Zia Chaudhuri

Abstract

Aim: To assess the functional visual parameters in patients with Alzheimer’s Dementia.

Method: Functional visual parameters like best corrected visual acuity (BCVA), contrast sensitivity (CS), speed of reading (SOR), stereopsis, colour vision defect (CVD), visual fields and ocular motility and alignment were assessed using various tests in 13 subjects diagnosed as Alzheimer’s dementia (AD, as per criteria for the same). The subjects were divided into two groups. Group A consisted of patients having equal vision in both eyes and Group B consisted of patients having unequal vision in both eyes i.e a better eye [BE] and worse eye [WE].

Results: Best Corrected Visual Acuity (BCVA) in eyes with equal vision was mean of 0.6 and in BE and WE a mean of 0.43±0.26 and 0.72±0.39 respectively (p<0.01) suggesting global depression. CS was decreased in all cases as compared to normative data. In unilateral cases, these patients demonstrated better SOR in the BE when compared with other causes of acquired CVI (Ischemia-p=0.04, Trauma-p=0.01). Colour vision was affected in 3 out of 13 cases. Assessment of stereopsis by TNO, Lang, Titmus Fly and Frisby Davis tests was equivocal.

Conclusions: There was a global depression of BCVA, contrast sensitivity (CS) and speed of reading (SOR) in subjects with Alzheimer’s Dementia (AD). Visual fields were normal in the 9 subjects who could be reliably assessed. All except one subject demonstrated good binocularity. 3 subjects had colour vision defects (CVD) of the red-green variety.

Department of Ophthalmology, Lady Hardinge Medical College (LHMC) and associated Kalawati Saran Children’s Hospital (KSCH), University of Delhi1, PGIMER & Dr RML Hospital, New Delhi, India2(Study conducted at LHMC, New Delhi, India)

Key words– Alzheimer’s dementia, best corrected visual acuity, speed of reading, contrast sensitivity, TNO test, Frisby Davis test.

Key Message: Different parameters of functional vision is affected in subjects with Alzheimer’s dementia and need to be addressed in this vulnerable population

Introduction

Alzheimer’s Dementia (AD), is a degenerative disorder of the nervous system affecting approximately 10% of individuals aged 65 or over.[1]The pathology of AD includes the deposition in the brain of abnormal aggregates of β-amyloid (Aβ) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). The development of dementia involves a decline in short-term memory, impairment of judgment, and a loss of emotional control. 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.[1]

Subjects and Methods

This was a hospital-based, observational, cross-sectional study conducted in a hospital set-up in Northern India. An informed consent was obtained from the patients. A structured predesigned proforma was filled. The subject cohort consisted of 13 cases diagnosed as AD [as per criteria for the same] and who could co-operate for visual functions were included. Average age was 71.30±8.09 years. Males in the group were 8 and females were 5. Subjects were divided into

  1. Group A- patients having equal vision in both eyes.
  2. Group B- patients having unequal vision in both eyes i.e a better eye [BE] and   worse eye [WE].

Each recruited subject underwent the following tests-

  1. BCVA using LogMAR charts
  2. CS using Pelli-Robson charts
  3. SOR using MN Read Charts
  4. Stereopsis using
  5. Lang test
  6. Titmus Fly test

iii. TNO test

  1. Frisby Davis test
  2. CVD using
  3. Ishihara charts
  4. Hardy Rand Rittler {HRR} test
  5. Visual fields using
  6. Humphrey’s automated perimeter
  7. Confrontation fields
  8. Ocular motility and alignment evaluation
  9. Anterior and posterior segment ocular evaluation

All tests used were both standard and non-invasive.

Statistical analysis used:

  1. Tabulation of data was done using Microsoft Excel charts.
  2. Appropriate statistical tests like means, medians, modes, percentages and “t” test were applied to study the values of functional visual parameters comprising colour vision, speed of reading, stereopsis and contrast sensitivity performed by different standard modalities in age specific groups with acquired CVI and inter and intra group comparisons. Fischer’s exact test was performed where the sample size was small.

Results


Best Corrected Visual Acuity (BCVA) – In Group A, 7/13 subjects had symmetrical decrease in BCVA OU [0.6logMAR]. In Group B, 6/13 subjects had asymmetrical decrease in BCVA [0.4logMAR in the better eye [BE] vs 0.7logMAR in the worse eye [WE], p=0.11]. None of the subjects had significant ocular cause of decrease in BCVA [anterior or posterior segment] – 3 in Group B had nuclear sclerosis in one eye and 3 [2 in Group A and 1 in Group B] were bilaterally pseudophakic.

Contrast Sensitivity (CS) – In Group A, all subjects had symmetrical decrease in CS [1.4±0.41log Units]. In Group B, BE CS was 1.1±0.75log Units vs WE of 1.2±0.46log Units [p=0.63]. CS was reduced in all subjects for all frequencies.

Speed of Reading (SOR) – In Group A, all subjects had symmetrical decrease in SOR [122.5±44.8 words per minute [wpm]]. In Group B: BE CS was 156.25±34.5 wpm vs WE of 123±44.5 wpm [p=0.15]. SOR in Group B was at par in the WE with the bilateral SOR inGroup A.

Table 1 demonstrates comparison of BCVA, CS, SOR in Dementia cases. The difference in the visual acuity between the better eye and worse eye was not found to be significant (P-value>0.05). No significant difference was found between the CS and SOR between better eye and worse eye in subjects with unequal visual acuity or between the right eye and the left eye in patients with equal visual acuity.

TABLE 1: Comparison of BCVA, CS and SOR in Dementia cases
BCVA (logMAR) CS (log units) SOR (wpm)
Eyes with equal vision (n=14)

Mean (n=0.6)

 Right eye Left eye Right eye Left eye Right eye Left eye
Mean±SD

P-value

 0.6 0.6 1.4±0.41

 

0.5

 1.4±0.41 122.5±44.79

 

0.48

 123.33±43.36
Eyes with unequal vision (n=12)

Mean (n=0.56)

 Better eye Worse eye Better eye Worse eye Better eye Worse eye
Mean±SD

 

P-value

 0.43±0.26

 

 

0.11

 0.72±0.39 1.1±0.75

 

 

0.63

 1.2±0.46 156.25±34.52

 

 

0.15

 123±44.45

 

Steropsis– Titmus test is a contour stereotest. It has a 3-dimensional polaroid vectograph which consists of two plates in the form of a booklet viewed through polaroid spectacles. TNO random dot stereotest is an anaglyph test that uses random-dot stereograms with impositions of half-images and complementary colours for assessment of stereopsis. Titmus fly and Lang tests measure local stereopsis whereas TNO test measures fine stereopsis.

Lang test: 12/13 responded [416.66±128.01 arc seconds]

  1. Titmus Fly test: 12/13 responded [144.66±124.86 arc seconds]
  2. TNO test: 10/13 responded [294±132.68 arc seconds]; Two of these had a red-green colour vision defect.
  3. Frisby Davis screening test: 11/13 responded.

One of these subjects couldn’t respond to either test. All patients responded more to the Titmus Fly test but the TNO is more indicative of true binocular status.

Visual Fields- Neurological fields were performed on the Humphrey’s automated perimeter through full field 120 programme. This could be performed in nine subjects. It was normal OU in all but one subject, where there was generalized depression of visual fields in one eye with nuclear sclerosis. None of the subjects responded to clinical field examination by confrontation.

Ocular Motility and Strabismus- No strabismus was observed in any subject. Decreased pursuits were seen in three subjects.

Colour Vision Defect (CVD) – Pseudo-isochromatic plates of Ishihara and HRR were used for this purpose. The plates are pseudo-isochromatic and depict coloured numbers or figures that stand out from a background of coloured dots. These colour tests are accurate only in proper lighting, usually blue-white illumination that mimics sunlight. The colours of the test figure and background are purposely pale and are carefully chosen from hues that are difficult for a colour-deficient patient to distinguish. The pseudo-isochromatic plate tests can be performed quickly and are sufficiently sensitive for screening colour-deficient people. 3 subjects, all males demonstrated red-green CVD by both Ishihara and HRR tests. Out of these, bilateral CVD was present in 1 case and unilateral CVD in two cases. Though none of these subjects gave a history of known CVD, as all were males, the acquired genesis of the CVD cannot be emphasized.

Distribution of refractive error was also assessed in these cases. (Table 2) Out of a total of 13 cases, one subject’s retinoscopy could not be done because of irregular reflexes. The distribution differences between the rest of the subjects was not statistically significant. (P-value, Pearson chi-square test>0.05). In both Group A and Group B, hypermetropia was found to be more common.

TABLE 2: Distribution of refractive error in cases with equal vision and unequal vision in dementia cases
Right eye Left eye
Cases with equal vision (n=14) Myopia 3 3
Hypermetropia 4 4
Better eye Worse eye
Cases with unequal vision (n=12) Myopia 2 2
Hypermetropia 4 3

 Discussion

The clinical diagnosis of AD is based on criteria developed originally by the ‘National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association’ (NINCDS-ADRDA) work group[2]and modified by the National Institute on Aging (NIA) – Reagan Institute.[3]The definitive diagnosis requires biopsy of the brain which is possible .There is an increase in the life-span of the geriatric population because of the advent of new modalities of treatment in every field, thus necessitating that there is an effort made to improve their quality of life. Assessment of visual functions in these subjects can be difficult because of their impaired cognition and hence, inability to co-operate for the tests.[4][5][6]But decrease in colour vision,[4]decreased stereopsis,[7] slow pursuit movements,[8] decreased contrast sensitivity,[6][9][10] progression of visual field defects[11]have been reported in these subjects which makes it important to study the effect of AD on visual functions further. Also, studies pertaining to the Indian population are few.[12][13]

Visual acuity (VA) can be difficult to measure accurately in patients with AD during the later stages of the disease, but studies suggest that VA is normal in the early stages of the disease.[4][5][6]Our study showed an overall decrease in BCVA. Whether or not there is defective colour vision in AD is controversial, with some studies suggesting normal colour vision in patients with mild to moderate AD.[5]In other studies, however, defective colour vision may be present in approximately 50% of patients.[4]Here, all affected male subjects showed CVD of the red-green type by both Ishihara and HRR tests.

Some studies have reported no change in contrast sensitivity in AD.[6]While others report reduced contrast sensitivity over all spatial frequencies.[10]These differences may be attributed to the variable population groups and assessment methods. We found in our study that there was a decrease in contrast sensitivity at all frequencies.

Smooth pursuits may be affected in AD patients.[8]This finding is consistent with our study in which there were decreased pursuits in three subjects.

In regards to visual fields, Trick showed that there was a generalised progression of visual field defects in patients with AD especially for inferior fields.[11]In our study, only one patient had generalised depression of visual fields.

SOR is shown to be affected in AD patients.[14]It can also be normal if the words are presented in a high contrast.[14]Our study showed a generalised decrease in the SOR. Degenerative changes in the posterior parietal and inferior temporal cortex caused by AD are associated with reductions in stereo-acuity[15]that are related to regional decreases in parietal–occipital glucose metabolism.[16]In our study, subjects showed intact binocularity but less so with TNO test which is the measure of true binocularity.

A larger study population is needed to further study the effect of AD on visual functions more reliably. Studies in this field pertaining to the North Indian population are less which lays emphasis on the need for more such studies.

Conflicts of interest: There are no conflicts of interest.

References

  1. Armstrong R. Alzheimer’s Disease and the Eye. J. Optom. 2009;2(3):103-111.
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  3. Jellinger K, Brancher C. Neuropathology of Alzheimer’s Disease: A critical update. Neural. Trans. 1998;54:77-95.
  4. Cogan D. Alzheimer syndromes. Am. J. Ophthalmol. 1987;104(2):183.
  5. Wood S, Mortel K, Hiscock M, Breitmeyer B, Caroselli J. Adaptive and maladaptive utilization of color cues by patients with mild to moderate Alzheimer’s Disease. Arch. Clin. Neuropsych. 1997;12(5):483-489.
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  7. Kiyosawa M, Bosley T, Chawluk J, Jamieson D, Schatz N, Savino P et al. Alzheimer’s Disease with Prominent Visual Symptoms. Ophthalmol. 1989;96(7):1077-1086.
  8. Fletcher W, Sharpe J. Smooth pursuit dysfunction in Alzheimer’s disease. Neurol. 1988;38(2):272-272.
  9. Lakshminarayanan V, Lagrane J, Kean M, Dick M, Shankle R. Vision in Dementia: contrast effects. Neurol. Res. J. 1996;18:9-15.
  10. Crow R, Levin L, LaBree L, Rubin R, Feldon S. Sweep Visual Evoked Potential Evaluation of Contrast Sensitivity in Alzheimer’s Dementia. Invest. Ophthalmol. Vis. Sci. 2003;44(2):875.
  11. Trick G, Trick L, Morris P, Wolf M. Visual field loss in senile dementia of the Alzheimer’s type. Neurol. 1995;45(1):68-74.
  12. Pawar N, Ravindran M, Ramakrishnan R, Maheshwari D. Pediatric cortical visual impairment: Etiology, associated findings, and prognosis in a tertiary eye care setting in South India. J. Clin. Ophthalmol. Res. 2018;6(2):53-58.
  13. Peher N, Chougule P, Dutton G. Cerebral visual impairment in children: Causes and associated ophthalmological problems. Indian. Ophthalmol. 2018;66(6):812-815.
  14. Gilmore G, Groth K, Thomas C. Stimulus Contrast and Word Reading Speed in Alzheimer’s Disease. Exp. Ag. Res. 2005;31(1):15-33.

 

  1. Mittenberg W, Malloy M, Petrick J, Knee K. Impaired depth perception discriminates Alzheimer’s dementia from aging and major depression. Arch. Clin. Neuropsych. 1994;9(1):71-79.
  2. Kiyosawa M, Bosley T, Chawluk J, Jamieson D, Schatz N, Savino P et al. Alzheimer’s Disease with Prominent Visual Symptoms. Ophthalmol. 1989;96(7):1077-1086.

Acknowledgements:

We sincerely acknowledge the efforts of all our colleagues but specifically those we have named below in the conceptualization and actualization of this study

  1. Dr Rajinder K Dhamija, MD, DNB [Neurology], Director Professor of Neurology, Department of Neurology, Lady Hardinge Medical College, New Delhi
  2. Dr Vikas Dhikav, DM [Neurology], PhD Senior Research Associate, Department of Neurology, PGIMER, Dr RML Hospital, New Delhi
  3. Dr Rajesh Jain, MD, Ex-Director Professor, Department of Ophthalmology, Lady Hardinge Medical College, New Delhi
  4. Dr Satinder Aneja, MD, Ex-Director Professor, Department of Paediatrics [Paediatric Neurology], Kalawati Saran Children’s Hospital, Lady Hardinge Medical College, New Delhi

 

 

 

 

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