4Ocularhaemodynamics parameters of asymptomatic HAART experienced HIV infected under five children

Niger J Paed 2016; 43 (1): 20 – 25

ORIGINAL

Ajulo MO

Ocularhaemodynamics parameters of

Omole MK

asymptomatic HAART experienced

Moody JO

Olusanya BA

HIV-infected under-five children

DOI:http://dx.doi.org/10.4314/njp.v43i1.4

Accepted: 3rd August 2015

Abstract :

Objectives:

Study

experienced HIV-infected children

aimed at evaluating the impacts of

was 12.2cm/s while that of sero-

Ajulo MO

(

)

HAART on retinal blood flow of

negative children was 13.4 cm/s.

Department of Clinical Pharmacy and

a s y m p t o m a t i c

H A A R T -

The PI and RI of blood flow in

Biopharmacy,

University of Uyo,

experienced HIV-infected under-

CRA of asymptomatic HAART-

Uyo. Akwa-Ibom State.

five children.

experienced HIV-infected children

Nigeria.

Method: Ethical approval and

were 0.8 and 0.5 respectively

Email: ajugbeng@gmail.com

patient consents were obtained

while those of the seronegative

before commencement of the

children were 0.6 and 0.4 respec-

Omole MK

study in the selected hospitals.

tively. Reduced Vmax of blood

Department of Clinical Pharmacy and

Thirty asymptomatic HAART-

flow of CRA was significantly

Pharmacy Administration,

experienced HIV-infected chil-

associated with both increased PI

Faculty of Pharmacy

dren and three seronegative chil-

and RI of asymptomatic HAART-

University of Ibadan,

Ibadan. Oyo State. Nigeria.

dren aged 0-5 year-old fulfilled

experienced HIV-infected under-

conditions for ocular ultrasono-

five children.

Moody JO

graphy among 60 convenience-

Discussion: Vmax of CRA of as-

Department of Pharmacognosy,

sampled under-fives. Ocular ultra-

ymptomatic HAART-experienced

University of Ibadan,

sonography was done on the pa-

HIV-infected children was reduced

Ibadan. Oyo State. Nigeria.

tients in supine position with eyes

because of their increased PI and

closed as instructed by the radi-

RI suggesting an increased resis-

Olusanya BA

ologist.

Maximum

velocity

tance to blood flow in asympto-

Department of Ophthalmology,

(Vmax), pulsatility index (PI),

matic HAART-experienced HIV-

College of Medicine,

University of Ibadan,

resistive index (RI), optic nerve

infected children.

University College Hospital,

diameter, lens thickness and axial

Conclusion: Reduced Vmax of

Ibadan. Oyo State. Nigeria.

diameter were measured. Results

blood flow to CRA was signifi-

of HAART-experienced children

cantly associated with increased PI

were not compared with the con-

and RI of asymptomatic HAART-

trol children because of unequal

experienced HIV-infected chil-

size. Data were analysed by using

dren.

ANOVA and level of significance

was considered at p<0.05.

Keywords : Ophthalmic artery,

Results: Vmax of blood flow in

Central retina artery, Maximum

central retinal artery (CRA) of

velocity, Seropositive children,

a s y m p t o m a t i c

H A A R T -

HAART

Introduction

sub-Saharan Africa are women. HIV-infection rates

among pregnant women in Africa range from 1% in

HIV/AIDS is a leading cause of childhood mortality and

Senegal to 40% in Botswana. In 2006, World Health

morbidity in Africa. In under-five children, HIV /AIDS

Organization (WHO) proposed that 2.3 million children

now accounts for 7.7% of mortality worldwide. AIDS

were living with Human Immunodeficiency Virus (HIV)

already accounts for a 36% rise in under- five’s mortal-

infection mostly acquired through mother to child trans-

mission, about 90% of them live in sub-Saharan Africa .

ity. In a state of declining immunisation, HIV/AIDS

threatens recent gains in infant and child survival and

health. The increased paediatric HIV infection rate in

AIDS affects children in many ways in Africa, about

Africa resulted from both increased HIV infection rate

400,000 children below 15 years died of AIDS in 2003.

in childbearing women and the competence of Mother to

Demographic data from sub-Saharan Africa showed the

Child transmission (MTCT). Forty million persons were

impact of HIV on childhood mortality. Maternal ill

living with HIV in 2003, 70% of them lived in sub-

health such as HIV infection has a negative effect on

Saharan Africa while 60% of HIV-infected persons in

infant survival. Infant and early childhood mortality

among seronegative children of HIV-infected mothers is

study were children who were already above five years

2 to 5 times higher than that among seronegative chil-

and HIV-infected children who were not asymptomatic.

dren of HIV-negative mothers.

Recruitment of participants: Forty (40) HAART-

It is assumed that over 1500 children are infected with

experienced HIV-infected children and 20 seronegative

HIV every day all over the world. HIV is responsible for

children were enrolled for the study. Thirty (30)

6% of deaths in under-five children in Sub – Saharan Af-

HAART-experienced HIV-infected children met the

rica. Recent data indicate that 40,000 HIV positive Afri-

criteria for ultrasonography while 3 seronegative chil-

can children received highly active antiretroviral therapy

dren met the criteria. The children who failed to meet

(HAART) in 2005. Nigeria has the highest burden of

criteria for ocular ultrasonography were due to their age

Mother- to- Child Transmission rates and Paediatric

which was slightly below four years and inability to stop

HIV disease in the world. Report on the Global AIDS

blinking the eyes during procedure. The participants

Epidemic showed that there are an estimated 240,000

were purposefully not sedated for the study.

HIV-infected children below 15 years old representing

Data collection: Data were obtained from successful

14% of the total African burden. In 2005, the Federal

ocular procedures on 30 HAART-experienced under-

Ministry of Health conducted biennial antenatal clinic

five HIV-infected children and 3 under-five seronega-

sentinel surveys, which showed HIV prevalence of 4.4%

tive children. As a result of unequal size, the result of

and 4.6% in 2007.

HAART-experienced HIV-infected children could not

be compared with the seronegative children. Hence, the

The eye had been shown to be an important indicator of

association of hemodynamic parameters such Vmax, PI

the effects of teratogenic compounds, such as thalido-

and RI of the asymptomatic HAART-experienced HIV-

mide. Alcohol caused fetal alcohol syndrome which

infected children was determined.

was linked to structural abnormalities of the eye such as

microphthalmos, buphthalmos, coloboma, optic nerve

Ocular Ultrasonography

hypoplasia and increased tortuosity of the retinal ves-

sels.

5,6

This investigation was done for the detection of effects

of HAART on retinal blood flow of seropositive chil-

The WHO commissioned systematic reviews on antiret-

dren. This investigation was performed only on thirty

roviral drug toxicities and laboratory monitoring strate-

asymptomatic seropositive children who had received

gies which include monitoring of potential increased

HAART for more than a year and three seronegative

risk of toxicity associated with the long-term use of anti-

children who were not on drugs. These children fulfilled

retroviral medicines in pregnancy, breastfeeding moth-

criteria for ocular ultrasonography procedures. Maxi-

ers andtheir children. It is important to monitor the use

mum velocity (Vmax), pulsatility index (PI) and resis-

of antiretroviral drugs in poor economy countries where

tive index (RI) of blood flow in central retinal artery and

toxicities may present a different pattern in association

ophthalmic artery were examined. Optic nerve diameter,

with either environmental or behavioural factors.

axial diameter and lens thickness of the eyes were also

This study aimed at evaluating the impacts of HAART

examined. Medical personnel in radiology unit of the

on retinal blood flow of 0-5 year-old asymptomatic HIV

University College Hospital had software on ultrasono-

-infected children on HAART in Southern Nigeria.

graphy equipment which could only perform assessment

of Vmax, PI, RI and optic nerve diameter while those in

University of Uyo Teaching Hospital could only do as-

sessment of axial diameter and lens thickness. In this

Method

respect, data from the two centers were analysed sepa-

rately. Due to failure of majority of the study control

Study design: In order to observe effects of HAART on

participants to meet the criteria for ocular ultrasonogra-

heamodynamic parameters of the eyes of asymptomatic

phy such as keeping the eyes closed during procedure

HAART-experienced HIV-infected under-five children,

and absence of primary standard parameters in Nigeria

a quantitative, observational approach was used.

and Africa, standard parameters from similar study in

Study setting: Forty (40) HIV-infected children aged 0-

USA and Sweden were adopted.

5 years old, who had been on HAART for more than a

year and 20 seronegative children were recruited for the

Ocular ultrasonography procedure

study in University College Hospital, Ibadan and Uni-

versity of Uyo Teaching Hospital. Consent of care-

The ultrasonography scans were performed with the

givers of participants was obtained after ethical approval

patient in supine position, eyes closed and directing gaze

was received from the study centers.

towards the ceiling. Ultrasound scanners and 5-10MHz

Study population: Convenience sampling was used to

linear array transducers were used. Transducers were

enrol 60 participants aged 0-5 years old who attended

applied with contact jelly through the closed upper eye-

either HIV clinic or the general outpatient department.

lid while the examiner’s hand rested upon the orbital

Inclusion criteria: Selection of participations for the

margin to minimize the pressure on the globe. Blood

study was based on age 0-5 years, both male and female,

flow in the retrobulbar orbit was detected by the produc-

asymptomatic HIV-infected children in WHO Stage 1

tion of colour pixel on the visual display unit. The mini-

and seronegative children from seronegative mothers.

mum size of sample gate used was 1.2mm X 1.2mm

Exclusion criteria: Those who were not included in the

with the Siemens machine. It was directed to a blood

vessel. The spectra analysis of the resultant frequency

tic nerve diameter of the right eye of asymptomatic sero-

shift was used to obtain a velocity waveform. The wave-

positive children on HAART was 0.5 cm while that of

form consisted of multiple velocities, the peak velocity

seronegative children was 0.4 cm (Fig. 3), (Table 2).

values were used in the analyses. In artery, the peak sys-

The ocular ultrasonography measurements of asympto-

tolic velocity (PSV) and end diastolic velocity (EDV)

matic seropositive children on HAART in UUTH

were used. Since these measures provided no informa-

showed that the mean of axial diameter of right eye was

tion of the waveform, two indices were used:

2.2 cm while that of the left eye was 2.3 cm (Fig. 4).

Resistive index (Pourcelot’s ratio) = PSV-EDV

Lens thickness of right eye of seropositive children on

PSV.

HAART was 0.1 cm (Fig. 5) and that of the left eye was

Pulsatility index =

PSV-EDV

0.1 cm (Table 2).

Tmax.

NB:

Fig 1: Comparison of blood flow in central retinal artery of

Tmax: Is the time averaged peak velocity

children on HAART and seronegative children (control)

Resistive index is usually quoted from 0-100% (0-1)

with 0 representing no resistance and 100 representing

high resistance.

Data management and analysis: Data was stored using

Microsoft Office 2008. Data was analysed by using de-

scriptive statistics and analysis of variance (ANOVA).

Statistical significance was considered at level p < 0.05.

Statistical Package for the Social Sciences (SPSS) soft-

ware version 20.0 (SPSS Inc. Chicago, III, USA) was

used for the analysis.

Results

Ocular ultrasonography measurement

The mean age of study participants was 4.71±0.59 years,

Table 2: Ocular ultrasonography measurement

15 (45.45%) boys and 18 (54.55%) girls successfully

S/n

Region

Eye

Pars

Mean

Control

performed ocular ultrasonography (Table 1).

Children on

(cm)

HAART (cm)

Table 1: Demographic characteristics of participants

Central

Right

Vmax

12.2±3.6

13.4±1.5

retinal

0.8±0.3

0.6±0.1

s/n

Character

Frequency

Artery

0.5±0.1

0.4±0.0

Age (years)

4.71±0.59

Left

Vmax

13.2±4.5

13.1±0.0

Male

15 (45.45%)

0.8±0.3

0.7±0.0

iii

Female

18 (54.55%)

0.5±0.1

0.3±0.0

Total

Oph-

Right

Vmax

23.6±9.1

33.8±4.0

thalmic

1.4±0.4

0.8±0.5

The ocular ultrasonography measurements of asympto-

artery

0.7±0.1

0.4±0.2

Left

Vmax

24.0±8.1

42.1±0.0

matic seropositive children on HAART in UCH showed

1.5±0.4

1.5±0.0

that the mean of maximum velocity (Vmax) of blood

0.7±0.0

flow in Central retinal artery (CRA) of eyewas12.2 cm/s

Optic

Right

Diameter

0.5±0.1

0.4±0.1

while that of seronegative children was 13.4 cm/s

nerve

Left

Diameter

0.5±0.1

0.6±0.0

axis

Right

Diameter

2.2±0.0

2.2±0.1

(Fig. 1). The pulsatility index (PI) of blood flow in CRA

Left

Diameter

2.3±0.0

2.2±0.1

of eye of asymptomatic HIV-infected children on

Lens

Right

Thickness

0.1±0.0

0.3±0.1

0.30.1

HAART was 0.8while that of the seronegative children

Left

Thickness

0.1±0.0

was 0.6. The Resistive index (RI) of blood flow in CRA

Obtained from Swedish study.

14,15

of eyeof asymptomatic HIV-infected children on

Obtained from United States study.

HAART was 0.5while that of the seronegative children

Vmax- maximum velocity, PI- pulsatility index, RI- resistive index

was 0.4 (Table 2).

The Vmax of blood flow in ophthalmic artery of eye of

Fig 2: Comparison of

asymptomatic seropositive children on HAART was

blood flow in ophthal-

23.6 cm/s while that of the seronegative children was

mic artery of children

on HAART and sero-

33.8 cm/s (Fig. 2). PI of blood flow in ophthalmic artery

negative children

of eye of asymptomatic HIV-infected children on

(control)

HAART was 1.4 while that of seronegative children was

0.8. RI of blood flow in ophthalmic artery of eye of as-

ymptomatic seropositive children on HAART was0.7

while that of the seronegative children was 0.4. The op-

Discussion

Fig 3: Comparison of

optic nerve diameter

Maximum velocity of central retina artery (CRA) of the

between children on

eye of seropositive children on HAART was reduced

HAART and seronega-

because of their increased pulsatility index (PI) and re-

tive (control) children

sistive index (RI). This possibly suggested that increased

pulsatility index indicated an increased resistance to

ocular blood flow in children receiving HAART. This

finding in asymptomatic HAART-experienced HIV-

infected under-fives supports the claims of previous

studies.

9,10

Williamson had documented in their study

Fig 4: Compari-

that reduced velocity was detected in the central retinal

son of axial di-

artery of patients with progressive non-arteritic ischemic

ameter of children

optic neuropathy when compared with unaffected con-

on HAART and

tralateral eyes. The central retinal artery velocity was

control children

increased while the pulsatility index in the posterior

ciliary arteries was reduced after optic nerve sheath de-

compression following an immediate postoperative pe-

riod. Observation of patients with chronic papilledema

from pseudotumor cerebri indicated reduced velocities

in the central retinal and posterior ciliary arteries with an

increased pulsatility index in the central retinal artery

when compared to controls. Following optic nerve

sheath decompression after 48 hours, an increase in the

blood velocities was observed in patients with improved

Fig 5: Comparison

vision which was due to increased perfusion of the

of lens thickness of

blood vessels.

children on HAART

and control children

Maximum velocity of ophthalmic artery (OA) of the eye

of asymptomatic seropositive children on HAART was

reduced because of their increased PI and RI. The in-

creased PI and RI possibly suggested an increased resis-

tance to blood flow. This finding in asymptomatic

HAART-experienced HIV-infected under-fives supports

claim of previous study.

9,10

Williamson in their study

affirmed that both pulsatility and resistive indices pro-

Maximum velocity (Vmax) of blood flow of both central

vide an indication of the effects of resistance on blood

retinal artery and ophthalmic artery was compared with

flow in the retinal blood vessels.

both pulsatility index (PI) and resistive index (RI) in

Increased optic nerve diameter of the eye was observed

eyes of asymptomatic seropositive children on HAART.

among asymptomatic seropositive children on HAART

Axial diameter was compared with lens thickness in

regimens which may suggest effect of HAART. Earlier

eyes of asymptomatic seropositive children on HAART.

study showed that increased optic nerve diameter was

The results were significant (Table 3).

associated with elevated cerebrospinal fluid pressure and

intracranial pressure.

11,12,13

Ballantyne in their study ex-

Table 3: Comparison of ocular parameters of children on

HAART

plained that the optic nerve diameter in children below 1

year is indicated to have normal values from 0.21-

Ocular parameters

p-value

0.40cm and for children above 1 year of age is 0.24-

Central

Right

Vmax

P<0.001

0.43cm. The normal range of values for children of age

retina ar-

eye

P<0.001

1-15 years is close to the normal values of optic nerve

tery

Left eye

Vmax

P<0.001

diameter in adult. An optic nerve diameter greater than

P<0.001

0.4cm in infants less than 1 year of age, while 0.45 cm

Ophthalmic

Right

Vmax

P<0.001

or greater in older children are considered as abnormal.

artery

eye

P<0.001

Increasedoptic nerve sheath diameter was indicated in

Left eye

Vmax

P<0.001

patients suffering from intracranial hypertension which

Axial di-

Right

Axial

Lens

P<0.001

returned to normal values after surgical or medical treat-

ameter

eye

diameter

thickness

ment. An increased optic nerve diameter was also indi-

Left eye

Axial

Lens

P<0.001

cated in elevated cerebrospinal fluid pressure and intrac-

ranial pressure. However, there is a need to determine

diameter

thickness

Vmax- maximum velocity, PI- pulsatility index, RI- resistive index

normal values of ocular hemodynamic parameters for

under-fives in Nigeria.

In absence of control group and lack of normal data,

axial diameter of the eye of asymptomatic seropositive

diameter of the eyes of asymptomatic seropositive chil-

children on HAART was compared with a Swedish nor-

dren who were on HAART.

mal value for age 3-5 years (2.07-2.34 cm). Comparing

the mean, it could be suggested that the axial diameter of

children on HAART was normal.

14,15

Conclusion

In spite of all the differences in ocular parameters be-

tween the asymptomatic seropositive children on

This study has shown significant association between

HAART and control children, there was no physical

reduced maximum velocity of blood flow in both oph-

observation of abnormality in the vision of the asympto-

thalmic artery and central retinal artery with increased

matic seropositive children on HAART. This observa-

pulsatility and resistive indices of the eyes of asympto-

tion was in support of findings obtained by Ogunbosi et

matic seropositive children on HAART. Similarly, lens

al., in their study on clinical pattern of HIV-infection

thickness was significantly linked to the axial diameter

among children at the same site of this study. In their

of the eyes of 0-5year old asymptomatic seropositive

study, there was no indication of cytomegalovirus infec-

children on HAART.

tion and any other ocular diseases among clinical pattern

of HIV infection illustrated in children with advanced

Recommendation

stage of AIDS .Similar observation was made by Fetuga

et al in their ten year review of paediatric HIV/AIDS

Vision test should be incorporated in the monitoring of

among hospitalized children in another study site in

adverse events in under-five children on HAART. More

Southwest Nigeria. This obviously rules out involve-

studies involving a large number of HIV-infected chil-

ment of HIV infection in reduced blood velocity of oph-

dren on HAART should be done to evaluate impacts on

thalmic artery and central retinal artery. Yung et al.,

ocular hemodynamic parameters.

observed that adult HIV positive patients with AIDS

showed a statistically significant reduction of perifoveal

capillary blood flow velocity in a study performed in

Authors’ contribution

United States of America. In this study, asymptomatic

AMO designed the study, performed field work, wrote

HAART-experienced HIV-infected under-five children

manuscript, OMK and MJO participated in designing

were involved. Therefore, HIV infection appears not to

the study, supervised work and edited the manuscript;

have been the cause of reduced blood velocity in both

OBA took care of technical aspect of the study and ed-

ophthalmic and central retinal arteries. However, the

ited the manuscript.

observed differences could have serious implication in

Conflict of interest: None

the future of these children.

Funding : None

The association of reduced maximum velocity (Vmax)

with pulsatility index (PI) and resistive index (RI) of

both central retinal artery and ophthalmic artery of the

Acknowledgement

eyes of asymptomatic seropositive children on HAART

were statistically significant. Similarly, there was sig-

The supports of staff of radiology department and HIV

nificant association between lens thickness and axial

centres were appreciated.

References

Tindyebwa D, Kayita J, Musoke

Stromland K and Miller MT. Re-

Constantino R., Patrizia P, Enrico

P , Eley B, Nduati R, Coovadia H,

fractive evaluation of thalidomide

Z, Carmen G, Maria C and

Bobart R, Mbori- Ngacha D and Kief-

embryopathy . Graef Arch Clin Exp

Giuseppe T. Normal neonatal val-

fer MP. Handbook on Pædiatric AIDS

Ophthalmol 1992; 230: 140- 149.

ues of ophthalmic and central reti-

in Africa by the African Network for the

Stromland K. Ocular abnormalities

Care of Children Affected by AIDS. 2006

nal artery blood flow velocities. J.

in the fetal alcohol syndrome. Acta

available at www. anecca. org and

Peadiat Ophthalmology Strabis-

www.rcqhc.org, retrieved on 23/06/2015.

Ophthalmol (Copenh) 1985; 63:

mus 2001; 38(4): 213-217 .

Federal Ministry of Health. Na-

(Suppl 171).

Williamson TH and Harris A. Col-

tional guidelines for paediatric

Hellstrom A, Jansson C, Bo-

our doppler ultrasound imaging of

HIV and AIDS treatment and care.

guszewski M, Olegird M, Laegreid

the eye and orbit. Survey Ophthal-

2007. Retrieved on 23/06/2015.

L and Albertsson- Wikland K.

mology 1996; 40(4): 255-267.

Ogunbosi BO, Oladokun RE,

Growth hormone status in six chil-

10. Baxter GM, Williamson TH,

Brown BJ and Osinusi KI (2011).

dren with fetal alcohol syndrome .

Mckillop G and Dutton GN. Col-

Prevalence and clinical pattern of

Acta Pediatr 1996; 85: 1456-

our Doppler

ultrasound of orbital

paediatric HIV infection at the Univer-

1462.

and optic nerve blood flow: Effects

sity College Hospital, Ibadan, Nigeria:

World Health Organisation. Con-

of posture and timolol 0.5%. Inves-

a prospective cross-sectional study.

solidated guidelines on the use of

Italian Journal of Pediatrics 2011; 37(29): 1-

tigative Ophthalmol Visual Science

antiretroviral drugs for treating and

6 http://www.ijponline.net/content/37/1/29.

1992; 33: 604-610.

retrieved on 23/06/2015.

preventing HIV-Infection. Recom-

mendations for a public health

approach. 2013. www.who.int

11. Ballantyne J, Hollman AS, Hamil-

14. Hellstrom A, Svensson E, Strom-

17. Yung C-W, Harris A, Massicotte

ton R et al.Transorbital optic nerve

land K. Eye size in healthy Swed-

S, Chioran G, Krombach G, Danis

shealth ultrasonography in normal

ish children and in children with

R and Wolf S. Retinal blood flow

children. Clinical Radiology 1999;

fetal alcohol syndrome. Acta Oph-

indices in patients infected with

54: 740-742.

thalmologica Scandinavica 1997;

human immunodeficiency virus.

12. Galetta S, Byrne SF and Smith JL.

75:423-428.

British J. Ophthalmology 1996;

Echographic correlation of optic

15. Youn DH, Yu YS and Park IW.

80: 723-727.

nerve shealth size and cerebrospi-

Intraocular pressure and axial

18. Lehman BM, Bernstein DA, Bailey

nal fluid pressure. J. Clinical

length in children. Korean J Oph-

MD and Zadnik K. Validation of

Neuro-ophthalmology 1989; 9:79-

thalmology 1990; 4: 26-29.

OCT – based crystalline lens thick-

82.

16. Fetuga MB, Ogunfowora OB,

ness measurements in children.

13. Cennamo G, Gangemi M and

Oyegunle VN and Thanni LOA. A

Optometry Vision Science 2009; 86

Stella L. The correlation between

ten year review of paediatric HIV/

(3): 181-197.

endocrinal pressure and optic

AIDS among hospitalized children

nerve diameter: an ultrasonogra-

in a Nigerian teaching hospital.

phy study. In: Ossoinig KC. Ed.

Niger J. Paediat 2005; 32 (3): 29-

Ophthalmic echography 1987; 603

32.

-606.