An Investigation of Saccadic Eye Movement Abnormalities in Children

with HIV/AIDS on Highly Active Antiretroviral Therapy

MR. NASHUA NAICKER M.Optom (UKZN)Lecturer and Undergraduate Programme CoordinatorDepartment of OptometryUniversity of the Free State (South Africa)

HIV/AIDS PEADIATRIC STATISTICS:

Global and African Perspective

• Globally, 35.3 million people living with HIV: 2013 1

360 0002

2.8 mil (88%)

3.2 mil children

THE ACCEPTED PARADIGM

Quicker diagnosis

Earlier treatment intervention

Better clinical outcome

Improved quality of life and longevity

THE CHALLENGE

Preservation of the neurocognitive functions in children with HIV/AIDS is vital for a sustained, healthier living.

Probing the Central Nervous System (HIV sanctuary site)• Invasive• Costly• Resource limited settings• Late diagnosis late intervention blunted improvement

Key: find reliable and sensitive functional tests for early detection!

EYE MOVEMENT TESTING

• Used as a tool in a myriad of psychiatric, learning-related disorders and neurological diseases and disorders.3,4

• Eye movement testing – window to CNS functioning.

• Control centres - cerebral cortex, cerebellum and brainstem

WHAT IS THE LINK?

Saccadic eye

movement pathway

Brain areas damaged

by HIV

• O

6Gaymard, B (2012).

5Thompson, et al. (2005).

THE LINK

THE KEY VALUE

To find a reliable screening tool to detect CNS abnormalities in practice, that possibly may be an early indicator of a weakening immune system in the paediatric population affected by HIV/AIDS in the HAART era.

METHODOLOGY

RESEARCH INQUIRY

Could the detection of abnormal saccadic eye movements in children from 6 to 13 years with HIV/AIDS on HAART, be a predictor of the status of their immune system?

PRIMARY OBJECTIVES

1. Determine the prevalence of saccadic eye movement

abnormalities.

2. Evaluate the association between saccadic eye movement

abnormalities and the immunologic (CD4 count) and virologic

(viral load) parameters.

METHODOLOGY

Research Design Descriptive observational framework with a cross-sectional design

Study Population Children with HIV/AIDS on HAART from 6 years to 13 years 11 months

of age

Sample Size 128 subjects (185 subjects were accessible to the researcher)

Sampling Method Convenient Sampling

Data Collection Sites Six public health facilities that were accessed by the subjects

Data Analysis Statistical Analysis Software (SAS) version 9.2

Developmental Eye Movement Test (DEM)7

• Assesses Saccadic eye movement skills + Automaticity (rapid/fluid verbalisation)

INSTRUMENT OF CHOICE

DEM: CLASSIFICATION

OF BEHAVIOUR TYPES

BEHAVIOUR TYPE VERTICAL TIME HORIZONTAL TIME RATIO

Type 1 Normal Normal Normal

Type 2 Normal High High

Type 3 High High Normal

Type 4 High High High

BEHAVIOUR TYPE CHARACTERISTICS

Type 1 Normal automaticity and oculomotor skills

Type 2 Oculomotor dysfunction

Type 3 Deficiencies in automaticity/number calling skills

Type 4 Deficiencies in automaticity and oculomotor skills

DEMOGRAPHIC & CLINICAL PROFILE OF SUBJECTS

GENDER, AGE & LANGUAGE DISTRIBUTION

GENDER DISTRIBUTION

N Gender Frequency (n)

Percent (%)

128 Male 61 48

Female 67 52

AGE DISTRIBUTION

Age Frequency (n = 128)

Percent (%)

6 (0 – 11 months) 4 3

7 (0 – 11 months) 13 10

8 (0 – 11 months) 24 19

9 (0 – 11 months) 30 23

10 (0 – 11 months) 16 13

11 (0 – 11 months) 11 9

12 (0 – 11 months) 17 13

13 (0 – 11 months) 13 10

ENGLISH 1ST LANGUAGE DISTRIBUTION

N English Other Percent (%)

128 0 128 0

IMMUNE PROFILE

ABSOLUTE CD4 COUNT

Age n Mean Std. Dev. Min Max

6yrs 4 858.50 ±427.62 361 1263

7yrs 13 923.77 ±581.23 17 2131

8yrs 24 866.83 ±395.36 74 1588

9yrs 30 995.77 ±388.12 147 2101

10yrs 16 687.50 ±351.20 75 1266

11yrs 11 754.00 ±568.19 325 2210

12 yrs 17 670.65 ±299.01 183 1130

13yrs 13 584.54 ±245.46 20 1000

N CD4 Count Mean Std. Dev. Median Min Max

128 Absolute(cell/mm3)

815.73 ±419.50 778.5 17 2210

DEM TEST RESULTS

DEM TEST RESULTS SUMMARY

STUDY RESULTS COMPARISON TO NORM

n Parameter Mean Std. Dev. Min Max

128 V. Time 87.85 ±29.19 34 177

534 DEM Norm 44.17 ±8.39 - -

128 H. Time 111.72 ±47.48 44.2 257

534 DEM Norm 57.78 ±14.93 - -

128 Ratio 1.27 ±0.34 0.56 2.89

534 DEM Norm 1.28 ±0.22 - -

128 Error 6.64 ±6.37 0 24

534 DEM Norm 5.10 ±5.47 - -

SACCADIC DYSFUNCTION vs CD4 COUNT

< 200 > 200 < 500 > 500

Type 1 2 1 7

Type 2 0 0 4

Type 3 2 13 53

Type 4 0 4 24

Type 5 3 3 12

5152535455565758595

Number of

Subjects

CD4 Count

CD4 COUNT DISTRIBUTION

ImmuneCategories

Cd4 Count ( cells/mm3)

Frequency (n = 128)

(%)

Severe

suppression

<200 7 5

moderate

suppression

>200 ≤ 500 21 16

Minimal/no

suppression

≥ 500 100 78

FISHER’S EXACT TEST: [n = 128, p >0.05] p =

0.17

DISCUSSION

• None of the subjects were 1st language English-speaking. – Spanish-speaking children8

– Portuguese-speaking children9

– Cantonese-speaking children10

• Slower information processing speed11 • Socio-economic and educational development12

• Lower neurocognitive function in children with HIV/AIDS on HAART13,14

RECOMMENDATIONS

1. Develop population-specific DEM test norms2. DEM to be used as part of a battery of

neuropsychological testing3. Analytical study with HIV (-) subjects4. Use alternative eye movement tracking

systems (objective assessments)5. More research in paediatric HIV

neuropathogenesis.

REFERENCES

1. AIDS 2014: 20th International AIDS Conference. Global fact sheet:HIV/AIDS, July 20 -25, Melbourne, Australia http://www.aids2014.org/webcontent/file/AIDS2014_Global_Factsheet_April_2014.pdf

2. UNAIDS: HIV and AIDS estimates (2013) http://www.unaids.org/en/regionscountries/countries/southafrica3. Leigh, R.J. and, Kennard, C. (2004). Using saccades as a research tool in the clinical neurosciences. Brain, 127,

pp.460-4774. Kumra, S., Sporn, A., Hommer, D.W., Nicolson, R., Thaker, G., Israel, E., Lenane, M., Bedwell, J., Jacobson, L.K.,

Gochman, P. and Rapoport, J.L. (2001). Smooth pursuit tracking impairment in childhood-onset psychotic disorders. Am. J. Psychiatry, 158(8), pp. 1291-1298

5. Thompson, et al. (2005) Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline. PNAS, 102(43), pp. 15647–15652.

6. Gaymard, B (2012). Cortical and sub-cortical control of saccades and clinical application. Rev Neurol,168(10), pp. 734-40

7. Richman, J.E. and Garzia, R.P. (1987). Developmental Eye Movement Test (DEM) Version 1, Examiner’s Booklet. Mishawka, IN: Bernell.

8. Fernandez-Velazquez, F.J. and Fernandez-Fidalgo, M.J. (1995). Do DEM test scores change with respect to language? Norms for Spanish-speaking population. Optometry and Visual Science, 72(12), pp. 902-906

9. Baptista, A.M.G., De Sousa, R.A.R.C., Casal, C.C.D.M.G., Marques, R.J.R. and Da Silva, C.M.L.R. (2011). Norms for the Developmental Eye Movement test for Portuguese children. Optometry and Vision Science, 88(7), pp. 864-871

10. Pang, P.C., Lam, C.S. and Woo, G.C. (2010). The developmental eye movement (DEM) test and Cantonese-speaking children in Hong Kong SAR, China. Clin Exp Optom., 93(4), pp. 213–223

11. Blanchette, N., Lou Smith, M., King, S., Fernandes-Penny, A. and Read, S. (2002). Cognitive development in school-age children with vertically transmitted HIV infection. Developmental Neuropsychology, 21, pp. 223-241

REFERENCES

12. Smith, L., Adnams, C. and Eley, B.S. (2008). Neurological and Neurocognitive Function of HIV-infected Children Commenced on Antiretroviral Therapy. South African Journal of Child Health, 2(3), pp 108-113

13. Puthanakit, T., Aurpibul, L., Louthrenoo, O., Tapanya, P., Nadsasarn, R., Insee-ard, S. and Sirisanthana, V. (2010). Poor Cognitive Functioning of School-Aged Children in Thailand with Perinatally Acquired HIV Infection Taking Antiretroviral Therapy AIDS Patient Care and STDs, 24(3), pp.141–146

14. Martin, S.C., Wolters, P.L., Toledo-Tamula, M.A., Zeichner, S.L., Hazra, R. and Civitello, L. (2006). Cognitive functioning in school-aged children with vertically acquired HIV infection being treated with Highly Active Antiretroviral Therapy (HAART). Dev Neuropsychol, 30(2), pp. 633-57

Thank you!

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