SONOGRAPHIC DETERMINATION OF OPTIC NERVE

SHEATH DIAMETER AND LENS THICKNESS IN

GLAUCOMA PATIENTS AT THE OAUTHC ILE-IFE.

BY

DR OMATIGA Achimugu Gabriel

(MB:BS, IBADAN)

A DISSERTATION SUBMITTED TO THE FACULTY OF

RADIOLOGY, NATIONAL POST GRADUATE MEDICAL COLLEGE

OF NIGERIA IN PARTIAL FULFILMENT FOR THE AWARD OF THE

FELLOWSHIP IN RADIOLOGY

(FMCR)

NOVEMBER 2016

ii

ATTESTATION

I, Dr Omatiga Achimugu Gabriel attest that this dissertation is my original work which was

carried out at the Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Osun

state.

……………………………………………………………………………………………..

Dr Omatiga Achimugu Gabriel

Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife,

Osun State.

iii

CERTIFICATION

I certify that this dissertation represents the original work of Dr Omatiga Achimugu Gabriel

and that it was done during his residency program at the department of Radiology Obafemi

Awolowo University Teaching Hospital Complex, Ile-Ife, Osun State.

Dr O C FAMUREWA (FWACS)

Head, Radiology Department

Obafemi Awolowo University Teaching Hospital Complex

Ile-Ife.

iv

ATTESTATION

We attest that this dissertation represents the original work of Dr Omatiga Achimugu

Gabriel which was done during his residency program at the Department of Radiology,

Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife and that it was supervised

and reviewed by us.

------------------------------------------------- ---------------------------------------------------

Dr O. O AYOOLA (MBChB, FMCR) DR O. H ONAKPOYA (FWACS, FMCOph)

Consultant Radiologist Consultant Ophthalmologist

Obafemi Awolowo University Obafemi Awolowo University

Teaching Hospital Complex Teaching Hospital Complex

v

Ile-ife. Ile-ife.

ACKNOWLEDGEMENT

My unreserved appreciation goes to God for His unfailing help. Special appreciations to

my supervisors, Dr O.O. Ayoola and Dr O.H Onakpoya. I appreciate and I am grateful to my

Head of Department Dr (Mrs) O.C. Famurewa. I also want to appreciate my teachers and

Consultants, Prof V.A Adetiloye, Dr (Mrs) C.M. Asaleye and Dr B.O. Ibitoye.

I am also grateful to all my colleagues and staff of the Department of Radiology especially Dr

Aderibigbe and the residents of the Department of ophthalmology, Obafemi Awolowo

University Teaching Hospital Complex for the invaluable assistance they rendered to me.

To Dr Simi Agbeleye, i am immensely grateful for your support and assistance.

vi

DEDICATION

I dedicate this work to my Heavenly Father who has been my Light and Guide at all times, to

my beautiful wife Idia Dawn Omatiga and our lovely Daughter Eleojo Isabel Omatiga, you are

the driving force in my life, God bless you. Also to the memory of my late dad Mr Isaac

Omatiga who sacrificed a lot for us to make a success of our lives.

vii

TABLE OF CONTENT

Title page i

Attestation

ii

Certification

iii

Attestation

iv

Acknowledgement

v

Dedication

vi

Table of contents

vii

List of abbreviations ix

List of figures

x

List of tables

xi

Summary 1

Introduction

3

Aims & Objectives

5

Justification

6

Gross anatomy

8

Sonographic anatomy

12

viii

Literature review

16

Materials and method

26

Ethical considerations

33

Results

34

Discussion 51

Limitation 55

Conclusion 56

Recommendation 57

References 58

Appendices 62

Subject information sheet 62

Consent form 64

Ethical clearance 65

Questionnaire 66

ix

LIST OF ABREVIATIONS

OAUTHC Obafemi Awolowo University Teaching Hospitals Complex

ONSD Optic Nerve Sheath Diameter

LT Lens Thickness

POAG Primary Open Angle Glaucoma

IOP Intraocular Pressure

OAG Open Angle Glaucoma

WHO World Health Organisation

BP Blood Pressure

CCT Central Corneal Thickness

NVG Neurovascular Glaucoma

SSA Sub-Sahara Africa

LDF Laser Doppler Flowmetry

C/D Cup Disc Ratio

ECM Extra Cellular Matrix

MRI Magnetic Resonance Imaging

CSF Cerebro-Spinal Fluid

MHZ Mega Hertz

SPSS Statistical Package for Social Sciences

BMI Body Mass Index

FBG Fasting Blood Glucose

DBP Diastolic Blood Pressure

x

ACG Angle Closure Glaucoma

RLT Right Lens Thickness

NTG Normal Tension Glaucoma

RNFL Retina Nerve Fibre Layer

LIST OF FIGURES

Fig. 1: A schematic diagrams of the anatomy of the eye and sonographic 10

Anatomy showing the anterior segment structures in A, and the posterior

segment structures in B

Fig 2: A schematic diagram of the human eye, showing the optic 11

nerve and the lens.

Fig. 3: A sonographic Anatomy of the Optic Nerve Axial section 14

Fig.4. Sonographic Anatomy of the Lens. 15

Fig. 5: Sonographic measurement of the Optic Nerve. 30

Fig. 6: Sonographic measurement of the lens thickness. 31

Fig. 7: Bar chart showing distribution of different types of glaucoma. 36

Fig. 8: A Boxplot showing the pattern of the right ONSD among glaucomatous

patients (p= 0.000). 39

Fig. 9: Boxplot showing the pattern of left ONSD among glaucomatous patients

(p =0.000) 40

Fig. 10: Boxplot showing no differences in Right lens thickness among study

participants (p = 0.109) 41

Fig. 11 Boxplot showing significantly higher Left lens thickness among Glaucoma

patients (p = 0.024) 42

xi

LIST OF TABLES

Table 1: A table showing Patients' General Characteristics 34

Table 2. A table showing the Differences in IOP, ONSD and Lens

thickness between the study groups. 37

Table 3: A table showing the Paired comparison of IOP, ONSD and Lens thickness

among study subjects 43

Table 4: A table showing, the Correlation between respondents' Age, ONSD and Lens

thickness. 45

Table 5: A table of the Regression analyses for predictors of lens thickness in

Glaucoma patients. 47

Table 6: A table showing Discordant / Regular pattern of the IOP

and ONSD 49

1

SUMMARY

BACKGROUND

Glaucoma is an optic neuropathy resulting in a characteristic appearance of the disc and a

specific pattern of irreversible visual field defect that are associated but not invariably with

raised intraocular pressure. It commonly leads to blindness if left untreated. This study was

designed to investigate the effect of glaucoma on optic nerve sheath diameter (ONSD) and Lens

thickness (LT).

AIM: This was a prospective case controlled study aimed at determining the optic nerve sheath

diameter and lens thickness among glaucoma patients using B-mode ultrasonography.

METHODS: 120 subjects were recruited, 60 glaucoma and 60 age and sex matched controls

screened by the Ophthalmologist and sent to the Radiology department of the Obafemi

Awolowo University Teaching Hospitals Complex Ile-Ife. Their ONSD and LT were measured

using linear high frequency 6.5-12MHz probe. The data acquired was analysed using SPSS

version 18.

RESULTS: The mean ONSD of the glaucomatous eyes were 3.57 ± 0.19mm and 3.59 ±

0.33mm on the right and left respectively while that for controls were 4.23 ± 0.34 mm and 4.26

± 0.30mm on the right and left respectively. The mean ONSD were statistical significantly

smaller in glaucomatous eyes than controls (p = 0.000). The (LT) of the glaucoma patients had

a mean of 4.15 ± 0.43mm and 4.18 ± 0.46mm on the right and left respectively while the controls

had a mean of 4.01 ± 0.56mm and 3.99 ± 0.45mm showing a statistically significant higher

mean LT between glaucomatous eyes and controls (p = 0.024). The Pearson correlation

coefficient between age and ONSD was negatively weak in both glaucomatous eyes at -0.230

(p = 0.077) and -0.119 (p = 0.144) for the right and left eye respectively; but was strongly

2

negative in controls at r = -0,549 and -0.548 on the right and left sides respectively (p = 0.000)

on either side. Mean intraocular pressure of both eyes of glaucoma subjects was significantly

higher than the mean for controls with glaucoma having 17.3 ± 8.1mmHg and 17.1 ± 7.6mmHg

on the right and left sides respectively and controls having 14.5 ± 3.1mmHg and 15.0 ±

3.3mmHg on the right and left respectively.

CONCLUSION: B-mode ultrasound is a reliable tool of assessing the nerve sheath diameter and

lens thickness in glaucoma. Optic nerve sheath diameter is reduced in glaucoma.

3

INTRODUCTION

Glaucoma is a devastating disease which has not been fully addressed. It is a major disease of

public health importance being a leading cause of blindness1. The suggested prevalence of

glaucoma in Sub Saharan Africa is 4% in people aged 40 years and above2.

Primary open-angle glaucoma (POAG), the most common form of glaucoma1, is a chronic,

progressive disease often, though not always, accompanied by elevated intraocular pressure

(IOP). Risk factors for glaucoma include old age, diabetes, Afro-Caribbean race, a family

history and myopia3,4. Angle-closure glaucoma also called closed-angle glaucoma; narrowangle

glaucoma, on the other hand usually occurs as an acute emergency as acute Angle closure

glaucoma. Glaucoma is predominantly open angle (OAG) in Nigeria and the rest of the West

African Sub region5.

In POAG, flow of aqueous humour is reduced through the trabecular meshwork, due to the

degeneration and obstruction of the trabecular meshwork, whose original function is to absorb

the aqueous humour. Reduced aqueous humour outflow leads to increased resistance and thus

a chronic, painless build-up of pressure in the eye. In close/narrow-angle, the iridocorneal angle

is completely closed because of forward displacement of the root of the iris against the cornea,

resulting in the inability of the aqueous fluid to flow from the posterior to the anterior chamber

and then out of the trabecular network. This accumulation of aqueous humour causes an acute

increase of pressure and pain6. The effect of the elevated IOP is mainly borne by the optic nerve

causing a characteristic optic atrophy which leads to a reduction in the ONSD. For some

unknown reasons, the LT has also been shown to be increased in close angle glaucoma

4

The imaging techniques for evaluating the optic nerve and lens biometry include

Ultrasonography, Computed Tomographic Scan and Magnetic Resonance Imaging. Ocular

sonography has been proven to be highly precise and more reliable at measuring the lens

thickness than optical measurements7. Sonographic measurement of the ONSD is also a very

effective method of investigating the optic nerve. Since the global target of WHO in Vision

2020 i.e. the “right to sight initiative” is ultimately to reduce blindness prevalence to less than

0.5% in all countries or less than 1% in any community (WHO, 2000)1,8, the government, the

public and public health officials face a big task in Nigeria.

Ultrasound when compared with the other imaging modalities, offers a non-invasive and direct

determination of the ONSD and LT in glaucomatous eyes. The measured nerve sheath thickness

correlates well with the level of axonal loss which leads to the optic atrophy seen in glaucoma.

To reduce the burden of the disease, early diagnosis and screening is important. Ocular

sonography offers quick and early assessment for glaucomatous eyes and screening for

glaucoma suspects where morphological and functional assessments are impossible.

The aim of the study was to determine the ONSD and the thickness of the lens with the aid

of ultrasound in patients with glaucoma.

5

AIM AND OBJECTIVES

BROAD AIM

To determine the ONSD and LT in subjects with glaucoma

SPECIFIC OBJECTIVES

1. To determine ONSD in Glaucoma subjects and control group

2. To determine the LT in Glaucoma subjects and control group.

3. To compare the ONSD and LT with control groups.

4. To determine the relationship between the degree of ONSD and LT with the age of

subjects.

HYPOTHESIS

Glaucoma causes a reduction in ONSD

SUBHYPOTHESIS

There is no reduction in ONSD in glaucoma

JUSTIFICATION

Glaucoma is an optic neuropathy ranking among the leading causes of acquired and

preventable blindness globally. The estimates by WHO suggest that depending on geographic

6

location, glaucoma is responsible for 5.7 to 22.7% of all blindness worldwide9. It may be fair

to estimate that around 10% of global blindness may be from glaucoma9.

Glaucoma has consistently ranked the second leading cause of blindness10-12 and the leading

cause of preventable and rather unfortunately, irreversible blindness globally11,13. The definition

of this disease continues to evolve, allowing for continual modification of detection methods,

treatment end-points and therapeutic options14. Glaucoma is traditionally assessed by the triad

of tonometry, visual field testing and optic nerve evaluation15,16. Several ocular and sometimes

non-ocular factors can however impair the usefulness of these morphological and functional

assessment variables in the evaluation of glaucoma suspects15. These factors include but are not

limited to an opaque media i.e. cataract, mental and sometimes physical limitations of patients15.

There arises a need therefore to look away from this traditional triad of assessment to a more

objective way of evaluating glaucoma, independently of IOP and optic nerve head morphology.

The optic nerve damage and nerve-fibre layer changes have been established to precede the visual

field and pressure changes in glaucoma neuropathy. These have made ocular sonography

invaluable in assessing glaucomatous eyes. Computed tomography is limited by its cost, non-

availability and the side effect of ionizing radiation. Magnetic Resonance imaging shows excellent

soft tissue resolution and is very good at imaging the optic nerve, cost and nonavailability are

however significant limitations especially in a country where majority of the populace live below

US $1.00 per day.

Ultrasound is cheap, fast, available and accessible in our environment and its sensitivity at

picking optic nerve sheath and lens changes are justification for this study. This study will also

seek to add to the existing body of knowledge on optic nerve sonography in our environment.

7

ANATOMY OF THE EYE

GROSS ANATOMY

The eye is the organ of vision and the principal component of the visual apparatus which also

includes various accessory ocular structures lodged in the orbit, the bony space in the front of the

skull17. The orbital fascia is the periosteum of the orbit which becomes continuous with the dura

mater and the optic nerve sheath at the back.

8

The eye ball is the dominant structure in the anterior orbit, embedded in fat but separated by a

membranous sac called the Tenon’s capsule18,19. The eye is divided into two segments of different

sized spheres. The smaller anterior segment which lies between the cornea and the lens and the

larger posterior segment lies between the lens and the retina (Fig.1 A and B). The anterior segment

forms 1/6th of the eyeball while the posterior segment is the larger sphere seen behind the lens and

contains the vitreous body19. The anterior segment of the eyeball is composed of two chambers

the anterior chamber which lies between the cornea and the iris, while the posterior chamber is

between the iris and the posterior lens capsule20.

The coat of the eye is composed of three layers (Fig. 2), the outermost layer is formed by the

tough white sclera posteriorly and the transparent cornea anteriorly. The junction between the

two is called the limbus20. The intermediate layer is a continuum of the vascular tissue known as

the uveal tract and is composed of choroid, ciliary body and iris. This layer may be considered as

an expansion of the arachnoid and pia of the optic nerve17. The inner layer is formed by the retina

which is a delicate nervous membrane of the eyeball.

Posteriorly the nerve fibres from the retina converge to form the optic nerve at the optic disc. The

nerve pierces both the choroid and sclera as it passes posteriorly through the optic canal and

continues as the optic nerve accompanied by the ophthalmic artery. The optic nerve, the second

cranial nerve, enters the orbit through the optic canal accompanied by the ophthalmic artery. The

nerve is really an extension of the white mater of the brain; it is covered by pia mater and lies

within a tube of arachnoid and dura mater as far as the back of the eye. The optic nerve is a

cylindrical structure between the retina and optic chiasma measuring approximately 5mm in

length and 4mm in average diameter with the sheath and 3mm in diameter without the sheath.

This can be divided into 4 main parts21:

1. Intraocular (the optic nerve head)

9

2. Intra-orbital (between globe and optic canal)

3. Intra-canalicular (within the optic canal)

4. Intracranial (between optic canal and chiasm)

The refractive media of the eye comprise of the cornea, the aqueous humour, lens and the vitreous

body. The crystalline lens lies right behind the iris (Fig.3A), it is biconvex in shape , measuring

about 9mm in diameter and 4mm in thickness18. The lens consists of three layers, the outer

capsule, inner epithelial layer and the lens nucleus. The optic axis is the line joining the anterior

pole (the central portion of the anterior curvature of the eyeball) to the posterior pole which is the

central portion of the posterior curvature. The axial length of the eye is approximately 24mm.

(A.)

10

Fig 1: Schematic diagrams of the anatomy of the eye and sonographic anatomy showing the

anterior segment structures in A, and the posterior segment structures in B. (Schematic diagram

is Courtesy; Frank H. Netter. Atlas of Human Anatomy, second edition)

) B. (

Cornea

Anterior

Chamber

Iri s

Lens

Vitreous

Chamber

Vitreous

Chamber

Optic

Nerve

11

Fig 2: Schematic diagram of the human eye, showing the optic nerve and the lens. Courtesy;

Stephanie Ryan, Michelle M, Stephen E. Anatomy for diagnostic Imaging second edition

SONOGRAPHIC ANATOMY

At the anterior pole of the eyeball, the eyelids and the conjunctiva abutting the cornea produce

a moderate echogenic structure which outlines the ventral part of the anterior chamber. With

high resolution transducers, the cornea and lens are echogenic and easily defined20. The anterior

and the vitreous chambers are anechoic spaces20(Fig 1 A and B). The pupil appears as a

translucent disruption of iris continuity. Posterior to it lies the anechoic lens with echogenic

posterior lens capsule (Fig. 3)The anterior margin of the lens is not apparent, and neither is the

posterior chamber, which is too thin to be visible. The human lens diameter is 10 mm with a

maximal thickness of 3-4 mm18. The posterior margin of the lens is convex towards the vitreous

cavity. The ciliary body produces a focal thickening of the eye wall, next to the margins of the

lens. The vitreous humour is echo free, homogeneous and occupies more than two thirds of the

12

eyeball volume. Since it only adheres to the posterior wall in a few points, movement of the

vitreous humour relative to the wall can be observed during real time scanning.

The posterior wall of the eyeball is echogenic, often with no inner layers. With high frequency

transducers and lowering of distal gain compensation, the choroid appears less echogenic than

neighbouring retina or sclera. Behind the eyeball, the intra-conal fat pad is hyperechoic19,

mainly due to acoustic enhancement in the vitreous humour. The optic nerve appears as a

sagittal hypoechoic structure, 4.5 – 5 mm thick, that runs from the outer part of the eyeball to

the tip of the orbit19 (Fig. 4). The length of the optic nerve is approximately 2.5cm. The extrinsic

muscles that form the intra-orbital muscular cone appear as hypoechoic bands with typical

longitudinal striations. The oblique muscles are almost never seen, due to their close relation to

the rectus muscles and thin belly. The rectus muscles can always be assessed, especially if

trapezoid emission of ultrasound at the surface of the transducer is used. They are oriented in a

sagittal plane and occupy the four cardinal points in the Orbit (superior, inferior, medial and

lateral).

13

14

Fig 3: Sonographic Anatomy, in B-mode, of the Lens (axial section

15

Fig. 4: Sonographic Anatomy, in B-mode, of the Optic Nerve (A) Axial section.

LITERATURE REVIEW

Glaucoma can be classified according to anterior chamber angle findings and the presence or

absence of disease causing elevated IOP and accompanying factors11. Basically, the disease can

be classified into Primary, Secondary and Developmental glaucoma. In Primary glaucoma, there

is no cause found for the elevated IOP, while in Secondary glaucoma, the elevation in IOP

results from other ocular diseases, systemic diseases, or drug use. In developmental glaucoma,

the elevation in IOP results from developmental anomalies in the anterior chamber angle

occurring during the embryonic period. Primary glaucoma is divided into primary open angle

glaucoma “broad definition” a disease concept that encompasses both conventional primary

open-angle glaucoma and normal-tension glaucoma) and primary angle-closure glaucoma11.

The primary functional and structural abnormality involved in glaucoma is glaucomatous

optic neuropathy. In recent years, the approach of including the presence or absence of

16

glaucomatous optic neuropathy in the classification of glaucoma and related diseases has

become internationally accepted.11

Primary open-angle glaucoma (POAG) is characterized by chronic progressive optic

neuropathy in which the optic disc and retinal nerve fiber layers show particular morphological

characteristics which includes thinning of the optic disc margin, retinal nerve fibre layer defects

and in which gonioscopy shows a normal anterior chamber angle. It is a disease type in which

other illnesses and congenital anomalies are absent. This is accompanied by progressive retinal

ganglion cell loss and corresponding visual field defects. Moreover, among cases of POAG,

genetic variations in myocilin or optineurin gene may be detected22.

A survey in south-eastern Nigeria, put the prevalence of glaucoma at 2.1% in people

30 years and older23. Another study in South-South Nigeria reported the prevalence of glaucoma suspects

as 2.7%24 , this correlated well with prevalence values of 2.7% in Ibadan South- West Nigeria25. A

prevalence of 1.02% was recorded amongst Hausa/Fulani ethnic extraction of North-western Nigeria26.

The suggested prevalence of glaucoma in sub Saharan Africa is 4% in people 40 years and older2 .

Risk factors for Primary Open Angle Glaucoma include increasing age, higher IOP, lower

systolic blood pressure (BP) to IOP ratio (BP/IOP), lower mean diastolic ocular perfusion

pressure (diastolic BP minus IOP), thinner central corneal thickness (CCT)27, and a positive

family history3. Racial variability of some of these risk factors at baseline has been

demonstrated; with higher IOP and thinner CCT in African-derived groups28. Age is an

important and consistent risk factor, with a higher prevalence of glaucoma associated with

increasing age1,22,24 The age-specific prevalence of POAG was higher with increasing age: From

1.7% to 5.6% in Kongwa, Tanzania, from 1.2% to 4.9% in Hlabisa, South Africa, and from

0.6% to 6.0% in Temba, South Africa in the age-group from 40-49 years to 70-79 years,

respectively1. Gender was not consistently associated with prevalent cases of glaucoma29.

However, some surveys reported a higher prevalence of POAG in men22. Men were also more

17

likely to have secondary glaucoma especially following trauma. Primary Angle Closure

Glaucoma was more common in women22

Higher IOP is another important factor associated with a higher prevalence of glaucoma

although IOP had a limited predictive value1. Hypertension was not significantly associated

with glaucoma prevalence, however, lower mean ocular perfusion pressure was associated with

a higher prevalence in the surveys in African-derived populations of Barbados and Baltimore22.

This was not reported in African-Caribbeans in London or in the only survey that this factor

was studied in Sub-Saharan Africa1. These factors associated with ocular blood flow i.e. systolic

BP, diastolic BP and ocular perfusion pressure were stronger in older people22.

A positive family history of glaucoma was associated with higher prevalence of glaucoma11,22.

The higher prevalence of glaucoma in blacks compared to whites has been consistently

demonstrated. Furthermore, those with darker skin and of African birth seemed

to have a higher risk1,22

Iris-lens channel heights <5μm would lead to pressure elevations in the posterior chamber that

would be a glaucoma risk6. This risk factor however contributed more to angle closure glaucoma

than open angle glaucoma.

Ashaye et al30 in their work which was done to determine the ocular and systemic factors

associated with neovascular glaucoma(NVG) in an African population , in a Hospital based

cross sectional study ,61 consecutively recruited patients with clinical diagnosis of NVG , had

a complete ocular evaluation. 61 subjects were studied with an identifiable aetiological factor

presumably causing neovascular glaucoma. Males outnumbered females among subjects with

NVG above 40 years, while females outnumbered males in the subjects below 40 years of age.

They therefore concluded that Medical conditions such as systemic hypertension, diabetes and

18

ocular conditions like retinal vein, retinal artery occlusion, couching and glaucoma were

associated with NVG.

A study by Quigley et al31 showed that up to 40% of the axons could be lost before a visual

field defect develops on Goldmann perimetry and that 20% of axons are lost before a 5 db loss

is detected on standard automated perimetry31. The current research efforts in the early

"preperimetric glaucoma" diagnosis are aimed either at psychological tests or alterations in the

optic nerve head morphology as assessed by scanning laser ophthalmoscope, digital image

processing of optic nerve head images or optical coherence tomography. While these advanced

technologies are relevant in glaucoma diagnosis and research, they are not practical in routine

clinical practice. It is estimated that 71% of blindness in the world is from three conditions:

cataract, trachoma, and glaucoma9. Approximately three fourths of all blind individuals reside

in Africa and Asia9. The estimates by WHO suggest that depending on geographic location,

glaucoma is responsible for 5.7 to 22.7% of all blindness worldwide. It may be fair to estimate

that around 10% of global blindness may be from glaucoma9.

Nwosu conducted a 1-year study looking for new cases of blindness at a teaching hospital

eye clinic in Anambra State, Nigeria. He found that of 257 patients with blindness, glaucoma

was responsible for 22.2% of visual impairment in at least one eye32 . In Africa, glaucoma

accounts for 15% of blindness and it is the region with the highest prevalence of blindness

relative to other regions world-wide1. Glaucoma blindness in Africa is, therefore, twice the

global figure; and eight times higher than in the Western Pacific sub-region1. However, the

numbers who are blind is just the tip of the iceberg as there are many more individuals with

glaucoma who are at the risk of blindness. Approximately 70% of glaucoma is found in

developing countries9. The commonest form of glaucoma in Nigerians is primary open angle

type found in individual ≥40 years of age33. It is estimated that two thirds of those

19

blind are cases of Primary Open Angle Glaucoma (POAG), with the majority of the remainder

being cases of angle-closure glaucoma (particularly common in China and the Far East)22.

Kyari et al1 in a study to review the epidemiology of different types of glaucoma relevant to

Sub-Saharan Africa (SSA) and to discuss the evidence regarding the risk factors for onset and

progression of glaucoma highlighted glaucoma in SSA as a public health problem with open-

angle glaucoma predominating1 They reported that glaucoma is also the second leading cause

of blindness, has a high prevalence, an early onset and progresses more rapidly than in

Caucasians1. It was learnt that these factors were further compounded by poor awareness and

low knowledge about glaucoma even by persons affected by the condition. In their conclusion

they asserted that Glaucoma care needs to be given high priority in Vision

2020 programs in Africa, and that questions remain unanswered and there is a need for further research in

glaucoma in sub-Sahara Africa. Prevalence of blindness was 4.2% (95% CI: 3.8-4.6%) in the largest study

on blindness survey done in Nigeria34 Blindness varied by age groups, sex, literacy level and geopolitical

zone. Furthermore, 84% of blindness was due to avoidable causes with cataract responsible for 43% of

blindness, glaucoma 16.7%34. There are several theories that attempt to explain the glaucomatous optic

nerve changes. The most prevalent theories attempting to explain glaucomatous optic neuropathy are the

mechanical theory and vascular theory9,14,35. In the mechanical theory emphasis is on the damage to the

optic nerve neurons at the level of the lamina cribrosa by the elevated IOP. Alternately, the raised IOP

may attenuate the sensitive microcirculation to the optic nerve head. On the other hand, the vascular theory

suggests that eyes with inherently poor vascular supply to the optic nerve head are more predisposed to

damage by elevated or normal IOP9 But the cause-and-effect relationship between nerve damage and

vascularity has not been established.

Sponsel and co-workers36 discovered that in patients with glaucoma or ocular hypertension, the

eye with the higher velocity of retinal leukocyte flow was associated with better visual function

with regard to visual fields and contrast sensitivity. It is controversial whether increased blood

velocity translates to enhanced perfusion pressure to a particular area. Further support for the

vascular theory came after the development of the laser Doppler flowmetry (LDF) technique to

evaluate the circulation of the optic nerve37. Studies have shown diminished blood flow in the

optic nerves of eyes with POAG9. As neither theory could explain all cases of glaucoma, the

trend is to combine the two views together.

20

There may be more than one mechanism of damage involved. Whatever the mechanism of

injury, there is a common result which is loss of optic nerve fibre. Genetic factors have also

been implicated in the aetiology of glaucoma38. Positive family history is a risk factor for

glaucoma. The relative risk of having POAG is increased approximately 2–4 folds for

individuals who have a sibling with glaucoma. Glaucoma, particularly POAG, is associated with

mutations in several different genes (including MYOC, ASB10, WDR36, NTF4, TBK1 genes),

although most cases of glaucoma do not involve these genetic mutations. Normal tension

glaucoma, which comprises one-third of POAG, is also associated with genetic mutations

(including OPA1 and OPTN genes).

The cup/disc (C/D) ratio of the optic nerve head enlarges with progression of glaucomatous

damage, reflecting loss of optic nerve fibres22 which are represented in the optic disc by the

neuro-retinal rim. Furthermore, investigation has shown that larger, nonglaucomatous; discs

have larger C/D ratios, and that glaucomatous optic neuropathy is more difficult to detect in

small disc. The development of glaucomatous optic neuropathy is attributed to loss of ganglion

cell axons in association with alterations in the connective tissue of the lamina cribrosa.

In POAG, which is primarily a disease of increasing age, increasing rigidity of the laminar

ECM with age has been implicated in this process. However, there is no consensus on whether

this loss of flexibility and resiliency by the lamina cribrosa is a consequence of raised lOP,

axonal loss or the ageing process alone. Increasing age is associated with axonal loss in the

retrobulbar optic nerve, but its effect on the ECM of the orbital nerve has yet to be established22.

Several researchers using different modalities have studied and documented the ocular changes

in glaucoma. The most consistent of these were the optic disc and optic nerve sheath changes

which include thinning of the optic disc margin and retinal nerve fibre layer defects. The lens is

also shown to be thickened as well as shallow anterior chamber 11. The optic nerve can be

21

imaged using methods such as A-scan ultrasonography, B-scan ultrasonography, three-

dimensional ultrasonography, computerized tomography and magnetic resonance imaging

(MRI).

However, data generated from these studies vary tremendously39. Factors contributing to this

variation are personal experience, inter-observer variability, test–retest variability, and eye

movement artefacts occurring during long acquisition times of up to several minutes in certain

MRI Protocols.

Lagre`ze et al40 in their work in normal subjects discovered that the optic nerve can be clearly

distinguished from its surrounding CSF sheath, which itself is bordered by the nerve sheath on

MRI. They showed that. MRI yielded mean optic nerve diameters of 3.23 mm at a position 5

mm behind the eye and dropped to 2.67 mm at a position 15 mm behind the eye. The same

applied to its sheath, with diameters declining from 5.72 to 3.98 mm, respectively. Compared

with MRI readings, ultrasonography consistently yielded smaller diameters. In the A-scan

mode, diameters were 2.31 mm for the retrobulbar optic nerve and 4.08 mm for the sheath.

Slightly larger diameters of the optic nerve and its sheath were obtained in the B-scan mode. In

straight gaze, the optic nerve diameters were 2.60 mm and

4.16 mm for the sheath, and in abduction they were 2.60 mm and 4.09 mm, respectively. Mean

diameters of the optic nerve and sheath obtained with all three methods (A-scan, Bscan, and

MRI) were statistically significantly different (p <0.05) and were normally distributed. In

comparisons of straight gaze and abduction, the nerve and sheath diameters obtained with B-

scan ultrasonography did not differ significantly36. ONSD was measured sonographically by

Ismail41 among Nigerian adult population , he reported a mean value of 4.11mm on the right

and 4.35mm on the left

22

Beatty and co-workers16, worked on a study designed to investigate whether measurements of

the optic nerve diameter (OND) and cross sectional area(ONCSA), as measured by B-scan

ultrasonography, are altered in glaucoma. One eye of 49 glaucoma patients and 90 control

subjects underwent five repeated echographic measurements of the maximal interpial diameter

and cross sectional area of the orbital optic nerve on two separate occasions. All measurements

were taken by one experienced ultrasonographer. The Mean ONSD for the control group was

found to be 2.86 +0.46 mm, and was independent of height, axial length, spherical equivalent,

sex, or race, but was inversely related to age. Reproducibility of OND readings in control

subjects was 0.149 mm (coefficient of repeatability). Test-retest variability of interpial diameter

was −0.02 (0.29) mm. They also found out the mean interpial diameter of the optic nerve to be

significantly smaller among glaucomatous eyes (2.58 (0.501) mm) than controls (Mann–

Whitney U test: p <0.0001). Glaucomatous optic nerves also had a significantly smaller cross

sectional area (6.68 +2.58 mm2) than those of healthy volunteers (8.25 +1.67 mm2) (p

=0.004).They finally concluded that echographic measurements of the orbital optic nerve are

highly reproducible and not subject to clinically meaningful test-retest variability. Optic nerve

interpial diameter and cross sectional area are reduced in glaucomatous eyes, reflecting nerve

fibre loss. They asserted that the technique may be useful in distinguishing between normal and

glaucomatous eyes where optic disc morphometry is inconclusive or impossible as a result of

opaque media. Beatty et al42 in another work correlated between the orbital and intraocular

portions of the optic nerve in glaucomatous and ocular hypertensive in their study. One eye of

20 volunteers (16 glaucoma subjects, 4 ocular hypertension subjects) underwent optic disc

analysis using Heidelberg retinal tomography, and echographic measurements of the retrobulbar

optic nerve. The male-to-female ratio was found to be 6.5:3.5, and the mean age of their sample

was 62.25+/-13.7 years. Orbital optic nerve diameter and cross-sectional area correlated

significantly and positively with the neuroretinal rim area (Spearman's rank correlation

23

coefficient; OND: r = 0.488,p = 0.0336; ONCSA: r = 0.619, P = 0.0079), but not with any other

topographical disc data.

The retrobulbar optic nerve cross-sectional area-to-disc area ratio (ONCSA/D) was found to have a

significant negative correlation with the cup area/disc area ratio (simple regression analysis; r = -

3.948, p = 0.046), and a statistically demonstrable positive correlation with the neuroretinal rim

area/disc area ratio (r = 0.451, p = 0.046). The results of their study indicated that orbital optic nerve

dimensions are a reflection of the neuroretinal rim area of the optic disc. Echographic measurements

of the retrobulbar nerve may be additive to the traditional triad of raised intraocular pressure, field

defects and glaucomatous optic neuropathy that suggests a diagnosis of glaucoma42.

Similar reduction in the ONSD was reported by Wang et al43 who measured the ONSD with

MRI using fat suppressed fast recovery fast spin echo T2Wi sequence. In contrast Pinto et al44

while using ultrasound found no statistically significant difference in the nerve sheath

measurements between glaucoma and normal subjects. Jaggi et al45 however demonstrated a

reduction in ONSD in glaucomatous eyes.

A study11 by the Japanese glaucoma society also showed abnormal lens findings associated

with glaucoma to include abnormal size or shape of the lens such as (lens swelling,

spherophakia) and abnormal lens position (lens luxation, lens subluxation, etc.). Abnormalities

of the ciliary zonule (congenital anomalies, trauma, exfoliative glaucoma, etc.) may play a role

in abnormal positioning of the lens11. Abnormal lens position and increased LT due to the

progression of cataracts may result in angle closure. In the case of mature or hypermature

cataracts, the complications of accompanying outflow of lens material and phacolytic glaucoma

may occur. Observation of the anterior surface of the lens is also important, and following laser

iridotomy and peripheral iridectomy, posterior synechiae may occur11. In exfoliative glaucoma,

24

deposits of white matter are observed on the anterior surface of the lens and the pupillary

margin.

In a previous study by Pinto et al46 to find out the relationship between IOP and ONSD in glaucoma,

intraocular pressure was compared with ONSD, there was a positive correlation between them in patients

with POAG (p = 0.03), borderline association with a p-value of 0.05 was however seen in patients with

normal tension glaucoma.

25

MATERIALS AND METHODS

STUDY DESIGN

The study is a prospective case control study which spanned a period of one year, from April

2015 to March 2016 in adults 30 years and above. at the Department of Radiology, Obafemi

Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State, Nigeria.

STUDY AREA

Ile-Ife is a Yoruba speaking town situated in the South Western Zone of Nigeria with a land

mass of 1902km2 and population of approximately 644,373 people excluding over 20,000

students (2006 National Population Commissions census). There are 4 local governments

namely Ife Central, Ife east, Ife north and Ife south with a total of about 50 wards (2006 Nigerian

population Commission census). The hospital is one of the tertiary referral centres serving

about 7.7 million population in the south western region of Nigeria and receiving patients from

Osun State where it is located, and adjacent neighbouring state like Ondo and Ekiti states. The

Obafemi Awolowo University Teaching Hospital Complex comprise of 3 units – located at Ile-

Ife, Ilesa and Imesi-Ile.

PATIENT SELECTION

All subjects diagnosed with glaucoma, with IOP >21mmHg and visual field showing the

glaucomatous pattern as determined by an Ophthalmologist at the Ophthalmology clinic of

OAUTHC were recruited into the study using consecutive random sampling technique

26

The control group were age and sex matched volunteers with normal IOP and optic disc with no

other ocular disease as determined by the ophthalmologist.

SAMPLE SIZE

The sample size was calculated using the Fisher’s formula; n =z2 p q/d2 Where:

n =Sample size z = Standard normal deviate =1.96 corresponding to 95%

confidence interval p = prevalence = 4%2 = 0.04 q = 1- p =0.96 d = degree of

accuracy =0.05 n = (1.96)2 x 0.04 x 0.96/ (0.05)2 n =59.007

60 study subjects with glaucoma and 60 healthy, age and sex matched control were recruited for

the study.

SELECTION CRITERIA FOR THE STUDY

The subjects group were patients diagnosed with glaucoma by an ophthalmologist.

The control group on the other hand were willing volunteers who were declared

nonglaucomatous by the ophthalmologist, with normal visual fields and normal intraocular

pressure <21mmHg. The control group were also similar in age and sex to the patients with

glaucoma.

EXCLUSION CRITERIA

• Hypertension

27

• Diabetes mellitus because it increases lens thickness

• Cataract • Ocular trauma or previous history of ocular trauma

• Smokers (because smoking also increases lens thickness )

• On-going eye infection

• Previous radiation therapy to the eye.

EQUIPMENT

The equipment will include the following

• Mindray Real time ultrasound Machine , Model DC-7 ,with 6.5-12MHz linear probe

• Coupling gel

• Blood pressure measuring apparatus

• Goldmann’s Applanation Tonometer, Ophthalmoscope, Pen torch, Gonio lens, Perimeter, Slit

Lamp biomicroscope

• Disposable gloves and wipes

• Weighing scale and a stadiometer for weight and height determination respectively..

TECHNIQUE

A clearly written consent form (Appendix 1) was administered to each subject to sign, upon

understanding and agreeing to the procedure. Each subject had their blood pressure taken and

the values were noted. Those with values >140mmHg and 90mmHg for systolic and diastolic

blood pressure respectively were excluded from the study. Those with fasting blood glucose in

excess of 5.5mmol/l were also excluded from the study. The referring ophthalmologist recruited

patients who met the inclusion criteria. Information such as duration of illness, subject age and

28

history of hypertension and smoking were obtained from each subject. The height and weight

of each subject was taken using a stadiometer and a weighing scale respectively. Their body

mass index (BMI) was calculated using the formula: Weight (Kg) /

Height (m2).

All subjects for the study were examined between 12 noon and 4pm, to eliminate the effects of

circadian rhythm on intraocular pressure. After thorough explanation of the procedure, each

patient was examined in the supine position. Trans-orbital scan of each eye was performed using

a 6.5 – 12MHZlinear probe. Subjects’ eyes were closed and copious acoustic gel was applied

to the closed upper lid. The transducer was then placed on the coupling gel on the temporal

region of the eye lid. Minimal pressure was applied during the examination to avoid any

discomfort to the patient as well as minimizing pressure to the globe. The probe was then moved

from the supero-temporal region toward the region of the optic nerve entry. Proper probe

angling was employed to see the optic nerve in its axial plane. To achieve this, patient was asked

to direct his or her gaze in primary position with the probe marker centred on the cornea.

Transverse (cross-section) and longitudinal scans of both optic nerves were obtained for

assessment of nerve sheath diameter. The transverse scan was done by placing the probe on the

globe with the marker parallel to the limbus in two directions either nasally or superiorly. The

longitudinal scan was performed by placing the probe peripheral to the limbus with the probe

marker perpendicular to the limbus.

The ONSD was measured by placing the cursor on the outer contours of the dural sheath in the

retrobulbal position at a distance 3mm behind the posterior wall of the eyeball A→B (Fig.5).

The ONSD was measured as the horizontal distance between the cursors. Bilateral ONSD was

measured three consecutive times and the mean value was documented.

29

Axial lens thickness was measured by placing the cursors on the outer part of the anterior and

posterior lens capsules A→B in (Fig.6). LT in both eyes was obtained 3 consecutive times and

documented. The mean value for each eye was obtained.

Fig. 5 B-mode sonographic measurement of the Optic Nerve (axial plane), seen as the

anechoic structure between cursors (A→B).

30

DATA AND STATISTICAL ANALYSIS Data was entered into a computer and analysed using Statistical Package for Social Sciences

(SPSS) for windows (SPSS INC. USA) version 18.0. Categorical variables such as

sociodemographic characteristics of respondents were presented on contingency tables for both

groups, and these variables were compared between the glaucomatous and control groups using

chi-square test. Continuous variables like LT and ONSD were presented by their means and

standard deviations (mean ± SD) for both glaucomatous and control groups. LT and ONSD in

both groups were compared statistically using independent sample t-test. Correlation and

regression analysis were used to evaluate the relationship between age, LT and ONSD in the

A

Fig 6 : B - s mode onographic m the of easurement LT ( axial plane) , ( A→B) seen as anechoic space the

between the echogenic capsules between the cursors.

31

glaucomatous group while controlling for other variables.. The level of statistical significance

was determined at p values less than 0.05 and the results were presented in frequency

distribution tables, charts and graphs.

ETHICAL CONSIDERATIONS

The Approval for this study (Appendix 11) was sought and obtained from the Ethical and

Research committee of the Obafemi Awolowo University Teaching Hospital Complex IleIfe, Osun

state, South-Western Nigeria.

32

RESULTS

Table I. Patients' General Characteristics

P

Variables Glaucoma Controls χ2 df value

(n = 60) (n = 60)

Age (years)

30 – 39 7 (11.7) 13 (21.7)

40 – 49

50 – 59

16 (26.7)

11 (18.3)

15 (25.0)

12 (20.0) 2.951 4 0.566

60 – 69 19 (31.7) 16 (26.7)

≥ 70 7 (11.7) 4 (6.7)

Mean ± SD 55.5 ± 11.9 52.1 ± 11.9 1.561 118 0.121*

(Min - Max)

Gender

33.0 - 79.0 31.0 - 78.0

Male 32 (53.3) 27 (45.0) 0.834 1 0.361

Female 28 (46.7) 33 (55.0)

Weight (Mean ± SD) (Kg) 64.8 ± 11.2 70.3 ± 16.0 -2.320 118 0.033*

Height (Mean ± SD) (m) 1.65 ± 0.10 1.63 ± 0.08 0.717 118 0.475*

BMI (Mean ± SD) (Kg/m2)

BMI categories

24.10 ± 4.83 26.21 ± 5.14 -2.320 118 0.022*

Underweight 6 (10.0) 4 (6.7)

Normal 33 (55.0) 25 (41.7) 3.673 3 0.299

Overweight 13 (21.7) 17 (28.3)

Patient category, n (%)

33

Obese

Duration of glaucoma (Mean ± SD)

8 (13.3) 14 (23.3)

(months) 1.2 ± 0.4 NA

χ2 - Chi square; df - degree of freedom; * independent samples t test; SD - Standard deviation

Table 1 summarises the age, sex and other characteristics of the participants of this study. In this

prospective case control study, a total of 120 subjects between the ages of 30 and 80 years were

included. They comprised 60 glaucoma subjects and 60 controls. Thirty-two (53.3%) of the

glaucomatous subjects were males and 28 (46.7%) were females while there were 27(45%) males

and 33(55%) females in the control subjects. This difference in their gender composition was

however not statistically significant (x2=0.834, df=1, p=0.361). The mean age of the glaucoma

subjects was 55±11.9 years while that of the control was 52.1±11.9 years (t = 1.561, df = 118, p =

0.121.). Participants in both study groups were also statistically similar in other general

characteristics except for their weight and BMI. The mean weight and BMI for the control subjects

were greater than those for glaucoma subjects, these values were statistically significant with p

values of 0.033 and 0.022 for weight and BMI respectively. However more than half of the subjects

investigated had normal weight with only a few being underweight, overweight and obese (x2 =

3.673, df = 3, p = 0.299) (Table 1). Of the 60 glaucomatous subjects, 54(90.0%) had POAG,

5(8.3%) had normal tension glaucoma and 1(1.7%) had angle closure glaucoma (Fig.7).

34

Fig. 7: Bar chart showing distribution of different types of glaucoma Table II. Differences in IOP, ONSD

and LT between the study groups

Patient category

Variables Glaucoma Controls t df P value

(n = 60) (n = 60)

Right IOP (mmHg) 17.3 ± 8.1 14.5 ± 3.1 2.560 118 0.012

Left IOP (mmHg) 17.1 ± 7.6 15.0 ± 3.3 2.034 118 0.045

(90.0 % 54 )

1 (1.7 % )

5 (8.3 % )

0

10

20

30

40

50

60

POAG Normal tension Glaucoma ACG

Type of Glaucoma

35

Right ONSD (mm) 3.57 ± 0.19 4.23 ± 0.34 -12.881 118 < 0.001

Left ONSD (mm) 3.59 ± 0.33 4.26 ± 0.30 -11.441 118 < 0.001

Right lens thickness (mm) 4.15 ± 0.43 4.01 ± 0.56 1.615 118 0.109

Left lens thickness (mm) 4.18 ± 0.46 3.99 ± 0.45 2.285 118 0.024

COMPARISON BETWEEN ONSD AND LT AMONG BOTH GROUPS

Table II shows the difference in, ONSD and LT between the glaucoma and control groups. The

mean ONSD in glaucoma patients was 3.57 ± 0.19 mm on the right and 3.59 ± 0.33mm on the

left. The mean ONSD among controls were 4.23 ± 0.34 mm and 4.26 ± 0.30mm on the right

and left respectively. The right ONSD of the glaucomatous patients had a lower mean of

3.57 ± 0.19 mm compared to that of the controls of mean of 4.23 ± 0.34 mm. Their left mean

ONSD was also lower (3.59 ± 0.33mm) than that of the controls (4.26 ± 0.30mm) (Table II).

36

These are also highlighted in figures 8 and 9 which showed statistically significant differences

between both groups (p = 0.000).

Right LT of the glaucomatous patients had a mean of 4.15 ± 0.43mm while the controls had a

mean of 4.01 ± 0.56mm (p = 0.109) (fig. 10). The mean left LT of the glaucomatous patients

was however higher at 4.18 ± 0.46mm compared to that of the controls at 3.99 ± 0.45mm (fig

11). In addition the mean intraocular pressure of both eyes of glaucoma subjects was

significantly higher than the mean for controls as shown on Table II.

37

Fig 8: Boxplot showing the pattern of Right ONSD among glaucomatous patients

(p = 0.000)

38

Fig 9: Boxplot showing the pattern of Left ONSD among glaucomatous

patients (p = 0.000)

39

Fig. 10: Boxplot showing pattern of right lens thickness among study

participants (p = 0.109)

40

Fig. 11: Boxplot showing pattern of left lens thickness among

glaucoma patients (p = 0.024)

.

41

Table III. Paired comparison of IOP, ONSD and Lens thickness among study subjects

Mean ± SD

Variables t* P value

Right Left

IOP (mmHg)

Glaucoma 17.3 ± 8.1 17.1 ± 7.6 0.218 0.828

Controls

ONSD (mm)

14.5 ± 3.1 15.0 ± 3.3 -2.259 0.028

Glaucoma 3.57 ± 0.19 3.59 ± 0.33 -0.513 0.610

Controls

Lens thickness (mm)

4.23 ± 0.34 4.26 ± 0.30 -1.413 0.163

Glaucoma 4.15 ± 0.43 4.18 ± 0.46 -0.967 0.338

Controls 4.01 ± 0.56 3.99 ± 0.45 0.341 0.734

* Paired-samples t test

42

As highlighted by a paired comparison of right and left eyes on Table III, there were no

statistically significant differences in both ONSD and LT of glaucoma subjects and controls.

The mean ONSD values were 3.57 ± 0.19mm and 3.59 ± 0.33mm for glaucomatous eyes on the

right and left (p = 0.610) while the control subjects had mean values of 4.23 ± 0.34mm and 4.26

± 0.3mm (p = 0.163) on the right and left respectively. Similarly, the mean LT were 4.15 ±

0.43mm and 4.18 ± 0.46mm for glaucomatous eyes on the right and left (p = 0.338) while the

control subjects had mean values of 4.01 ± 0.56mm and 3.99 ± 0.45mm (p = 0.734) on the right

and left respectively(Table III).

Table IV. Correlation between respondents' Age, ONSD and Lens thickness

43

Correlation –

Age vs. :

Glaucoma Controls

R P value r P value

Right ONSD -0.230 0.077 -0.549 0.000

Left ONSD -0.191 0.144 -0.548 0.000

Right lens thickness 0.456 0.000 0.068 0.603

Left lens thickness 0.408 0.001 -0.032 0.811

r - Pearson correlation coefficient,

44

RELATIONSHIP BETWEEN AGE, ONSD AND LENS THICKNESS

A weak and negative correlation was observed between the age and ONSD of glaucoma

patients in both eyes with Pearson correlation coefficients of -0.230 (p = 0.077) and -0.119

(p = 0.144) on the right and left respectively, while a strong and statistically significant

negative correlation was observed in the control subjects (p = 0.000) on either sides (Table

IV).

The LT strongly correlated with the age of the glaucoma patients on the right(r = 0.456, p =

0.000) and left (r = 0.408, p = 0.001) respectively. No significant correlation was observed

between the LT and age of control subjects on the right and left sides (Table IV).

45

Table V. Simple linear Regression analyses for predictors of lens thickness in Glaucoma patients

Model Dependent

variables

Independent

variables

B SE t P value R2

1

Right lens

thickness (RLT)

(mm)

(Constant) 3.235 0.208

2

Left lens

thickness (LLT)

(mm)

Age (years) 0.017 0.004 3.906 0.000

(Constant)

Age (years)

3.314

0.016

0.005

3.402

0.001

0.166

Regression equations

Mode1: RLT (mm) = 3.235 + 0.017*Age (years)

Mode2: LLT (mm) = 3.314 + 0.016*Age (years)

B - regression coefficients; SE - standard error; R2 - Model variance

46

As highlighted on Table V, bivariate analysis in glaucomatous patients showed weak but

significant positive correlation between right and left LT with age, and a weak negative

correlation with height for the left LT only (r = 0.456, p =0.000; r = 0.408, p = 0.001; r = 0.301,

p = 0.019 respectively). Consequently, linear regression analyses were performed to ascertain

the influence of age alone (Models 1 and 2) on the right and left LT as shown on

Table V. Age of the patients significantly predicted the respective lens thickness values in the

Models. In Model 1, Age was responsible for only 20.8% (Model variance, R2 = 0.208) of the

variation observed in right LT compared to 16.6% in Model 2 for the left LT.

47

Table VI. Discordant / Regular pattern of the IOP and ONSD

Variables Glaucoma Controls χ2 Df P value

(n = 60) (n = 60)

Discordant 40 (66.7) 29 (48.3)

4.126 1 0.042

Regular pattern 20 (33.3) 31 (51.7)

RELATIONSHIP BETWEEN IOP AND ONSD

Patient category, n (%)

48

Although no statistically significant difference was observed between the mean IOP values of

the right and left eyes of glaucomatous patients, the mean values of 14.1±0.31mm and

15.0±3.3mm on the right and left respectively among the controls showed a statistically

significant difference(t = -2.259, p = 0.028) as shown on Table III. A comparison of IOP with

ONSD showed a predominant discordant pattern of relationship among glaucomatous patients

(discordant meaning an increase IOP was associated with an increase in ONSD) accounting for

66.7% of all cases, meanwhile only about a third of glaucoma patients showed the regular

pattern (regular meaning an increase in IOP was related to a decreasing ONSD) (χ2 = 4.126, df

= 1; p = 0.042). Among the controls there was just a marginal increase of the regular pattern

over the discordant pattern as shown on Table VI.

DISCUSSION

49

Glaucoma has consistently ranked the second leading cause of blindness10-12 and the leading

cause of preventable and rather unfortunately, irreversible blindness globally11,13. The definition

of this disease continues to evolve, allowing for continual modification of detection methods,

treatment end-points and therapeutic options14. Glaucoma is traditionally assessed by the triad

of tonometry, visual field testing and optic nerve evaluation15,16. Several ocular and sometimes

non-ocular factors can however impair the usefulness of these morphological and functional

assessment variables in the evaluation of glaucoma suspects15. These factors include but are not

limited to an opaque media i.e. cataract, mental and sometimes physical limitations of patients15.

There arises a need therefore to look away from this traditional triad of assessment to a more

objective way of evaluating glaucoma, independently of IOP and optic nerve head morphology.

This present study set out to evaluate the ONSD with the aid of ultrasound. It was a prospective

study carried out among Nigerian adults between the ages of 30 and 80 years. There was a male

gender preponderance, a finding which was similar to other studies done in the past8,47,48.

However a study conducted by Kosoko-Lasaki et al49 reported that this finding was

inconsistent, this was corroborated by a study done in Ghana by Ntim-Amponsah et al50. POAG

was the predominant type observed in the present study accounting for 90% of all

cases, this also is consistent with the findings in previous works on glaucoma1,5,12. In fact

Yilchung et al13 reported that POAG has the highest prevalence in Africa and that male gender

and urban dwellers are more likely to have POAG compared to the female gender and rural

dwellers, the reason for this finding is unclear. It has also been documented that males are more

likely to have secondary glaucoma following trauma51 , this could not be established in this

study because ocular trauma was an exclusion criterion. The mean age of glaucoma subjects is

55.5 ± 11.9 years which is also comparable to the mean age in a previous studies8,52 that

documented mean age of 56years52. The highest number of glaucoma subjects was found among

the 60-69 years age group, which is in support of earlier documented age specific prevalence

50

of glaucoma1. The reason for this could be that advancing age is a risk factor for developing

glaucoma1,53.

The study also set out to see the relationship between the intraocular pressure and the size of the

optic nerve sheath. This study shows a statistically significant difference between the mean

ONSD of glaucoma group and control subjects. The measured mean ONSD in normal healthy

controls is comparable with results obtained from previous studies41 . The study reported a mean

ONSD of 4.18mm (SD 0.49) and 4.17mm (SD 0.44) on the right and left respectively. The mean

ONSD in glaucoma patients was statistical significantly reduced compared with the mean found

in normal healthy controls. This reduction in optic nerve diameter observed in this study in

glaucoma is comparable with those of previous

studies15,16,39,43 on ultrasound and MRI. Wang et al43 used MRI to study the eyes of glaucoma

patients, they measured the ONSD at 3mm, 9mm and 15mm behind the eye ball. At 3mm behind

the eye ball, ONSD of Normal tension glaucoma (NTG) group is significantly narrower than

control group (p<0.05). At 9mm, the ONSD of the NTG group and POAG group are both

significantly narrower than the control group (p<0.05). At 15mm, the ONSD of the NTG group

and POAG group are both significantly narrower than the control group (p<0.05). Contrary to

the reduction in ONSD reported in the present study Pinto et al44 reported no difference between

the measured ONSD of glaucoma patients and healthy controls. Jaggi et al45 however showed

an increase in the ONSD of glaucoma patients. These discrepancies in the ONSD values may

reflect differences in patient selection criteria such as age, head position, sample size and most

importantly imaging modality. While ultrasound was used in this study, Jaggi used computed

tomography and their sample size was only 18 subjects.

This study revealed an inverse, though weak, negative correlation between age and ONSD

among glaucoma patients as well as in control, indicating that the reduction in the ONSD could

not have been due to the disease process alone, but age may also play a part in the atrophy of

51

the optic nerve. This was also documented in previous study by Beatty et al15. This finding is

also consistent with histological studies, reporting an age related decrease in axonal count of

the human optic nerve15. This could also be due to older individuals having a more vulnerable

optic nerve or have suffered more frequent and prolonged insult to the nerve over their life time,

both mechanisms could also play a role in concert to cause atrophy of the optic nerve3. The

weak correlation in this study is contrary to what was observed by the aforementioned

researcher who recorded a strong correlation, the difference is possibly due to the different

geographical area where both studies were carried out and may also depend on the racial factors

as the present study was conducted among dark skinned Africans as opposed to the Caucasian

population in their study.

The mean LT was not statistically different in the glaucoma and control groups on the right, but

a statistically significant difference was observed on the left in this study with a p-value of

0.024. The reason for this unilateral difference cannot be established in this study. From

comprehensive literature search, it has been observed that the lens is thickened in closed angle

glaucoma11 when compared with controls but this has not been documented in other forms of

glaucoma. Furthermore this study has also shown a positive correlation between LT and age

among glaucoma patients with a p-value of 0.000 and 0.001 in the right and left eyes

respectively. A weak negative correlation was also noted on the left in controls, but no

correlation was observed on the right. By the forgoing, it may be possible to predict the lens

thickness using the age of patients with glaucoma and vis-versa. Age is however a weak

predictor of LT in controls. Hence by linear regression analysis it was demonstrated that age is

a significant predictor of lens thickness.

The glaucomatous optic neuropathy has been widely diagnosed; this optic nerve atrophy which

is due to loss of retinal fibre layer (RNFL) has also been demonstrated in glaucomatous eyes. It

is therefore not surprising to have observed this reduction in the optic nerve sheath diameter in

52

this study among glaucoma patients compared with healthy normal subjects. The result of this

study should assist the clinician in further evaluation of glaucoma patients and also assist in

screening of glaucoma suspects, especially in the setting of an opaque media where examination

of the fundus might prove difficult or impossible.

LIMITATIONS

Ultrasound being user dependent, may give rise to minor but negligible variation in values

obtained. Moreover all measurements were done by the same researcher; hence inter-observer

53

reliability was not evaluated. Most researchers used ultrasound machines with probe frequency

of 20MHz, this study however utilized a 6.5-12MHz machine, and the effect of this was

expected to be negligible as frequencies beyond 10MHz have shown equally reliable results.

54

CONCLUSION

Real time B-mode ultrasound scan has been shown by this study to be a useful tool in

determining the ONSD as well as LT in normal and glaucomatous subjects. It also demonstrated

the reduction of the ONSD in glaucomatous eyes. Hence it can be an alternative tool in the

assessment of eyes of patients with glaucoma as well as screening for glaucoma suspects where

the traditional triad of tonometry, visual field testing and optic nerve evaluation are impossible

or not available.

55

RECOMMENDATION

In resource poor regions like ours, B-mode ultrasound could be recommended as the initial

screening method for glaucoma suspects. Further studies to ascertain possible reason for the

differences in our result of ONSD values against those reported in previous literatures is also

recommended.

56

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APPENDIX I

OBAFEMI AWOLOWO UNIVERSITY TEACHING HOSPITALS COMPLEX, ILE-IFE.

SONOGRAPHIC DETERMINATION OF OPTIC NERVE SHEATH DIAMETER IN

GLAUCOMA IN NIGERIAN ADULTS AT THE OBAFEMI AWOLOWO

UNIVERSITY TEACHING HOSPITAL COMPLEX ILE-IFE.

SUBJECT INFORMATION SHEET

Principal Investigator: Omatiga Achimugu Gabriel Telephone No:- 08068885667

Institution: ObafemiAwolowo University Teaching Hospitals Complex, Ile-Ife

Title of Study.SONOGRAPHIC DETERMINATION OF OPTIC NERVE SHEATH

DIAMETER IN GLAUCOMA IN NIGERIAN ADULTS AT THE OBAFEMI

AWOLOWO UNIVERSITY TEACHING HOSPITAL COMPLEX ILE-IFE.

Co – Investigators: None

Sponsor (If any): Nil

61

Some general things to know about the study: From a random selection process you have been

chosen as one of the participants in a research study. This document is designed to provide you

with the necessary information about this study and obtain your consent to participate.

What is the purpose of this study: This is to determine the usefulness of ultrasound scanning

in determining your optic nerve sheath diameter and lens thickness, as a glaucoma patient,

and to see if your age has any effect on your lens thickness, which can help to predict chances

of you becoming blind from glaucoma and advice you on early institution of appropriate

therapy.

Procedures: You will be interviewed and questions will be asked about your demographic characteristics

and medical history. I will ask you a number of questions to solicit this information and the entire

interview should last no longer than two minutes. Then you will be sent to Ophthalmology department to

check if you are having glaucoma. You will be required to come fasting and I will obtain a drop of 0.1ml

of blood from you to check your fasting blood sugar level, and then do an ultrasound scan of your eyes.

The ONSD and the LT will be measured with your eyes closed, and then the values will be documented.

Benefits: If you agree to take part in this study, you will be able to know if your glaucoma has

affected your optic nerve sheath diameter and thickness of the lenses and to what degree, which

might cause you to develop blindness. This will help your doctors to give you appropriate early

treatment so that you will not have visual impairment from glaucoma. By participating in this

study, you will also be helping in adding to and improving on the existing medical knowledge

and care of individuals with glaucoma. Costs of Participation: There is no financial cost to

participation

Risks: Needle prick to obtain blood from you for blood glucose assessment (control group) will

cause some pain. There could also be minimal discomfort from the applied gel and slight

pressure on your eyes when probe is applied

Compensation: There will be no compensation for participating in the study.

62

Confidentiality: All information gathered in this study will be kept confidential. When findings

of this study are reported in scientific journals or meetings, you will not be identified. All

records and any other study materials will be protected with password and/or stored in the

locked cabinets which will be accessible to only authorized personnel.

Respondents’ Rights: you have a right to decline participation in the study and can also withdraw from

the study at any time.

Conflict of Interest: To the best of my knowledge, there is none.

For the Records: You will be given a copy of this form to keep.

OBAFEMI AWOLOWO UNIVERSITY TEACHING HOSPITALS COMPLEX, ILE-IFE.

SONOGRAPHIC DETERMINATION OF OPTIC NERVE SHEATH DIAMETER IN

GLAUCOMA IN NIGERIAN ADULTS AT THE OBAFEMI AWOLOWO UNIVERSITY TEACHING

HOSPITAL COMPLEX ILE-IFE.

Subject’s Agreement/Consent Form:

I have read the information provided in the Subject Information Sheet, or it has been read to me. I have had the opportunity to ask questions about the research and any questions I have asked have been answered to my satisfaction. I consent voluntarily to participate in this study and understand that a drop of blood will be taken from me and my eye will be screened. I have the right to withdraw from the study at any time. I have agreed to participate in the study.

Yes No

------------------------------------------------------------------------------------------------------

Signature/Thumb print of Research Respondent. Date:

Printed Name of Research Subject’s Legal Guardian.

Signature/thumb print of Person Obtaining Consent.

Date:

63

Printed Name of Person Obtaining Consent.

APPENDIXII

APPENDIXIII

64

QUESTIONNAIRE

DEMOGRAPHIC DATA

(1) DATE (4) SEX

(2) INITIALS. (5) HOSPITAL NO

(3) AGE (6) PHONE NO

MEDICAL HISTORY:

(7) HISTORY OF HYPERTENSION YES /NO

(8) HISTORY OF TRAUMA TO THE EYE YES / NO

(9) PREVIOUS EYE SURGERY YES / NO

(10) PREVIOUS RADIATION THERAPY TO THE EYE YES / NO

(11) ONGOING EYE INFECTION YES / NO

(12) HISTORY OF SMOKING YES / NO

(13) CHRONIC USE OF STEROIDS YES / NO

STUDY DATA

(14) INTRAOCULAR PRESSURE. RT. EYE; LT. EYE;

(15) CUP DISC RATIO RT.EYE; LT.EYE.

(16) WEIGHT

(17) HEIGHT

(18) BLOOD SUGAR

(19) BLOOD PRESSURE

OPTIC NERVE SHEATH DIAMETER (ONSD) ON ULTRASOUND

RIGHT EYE LEFT EYE

1 1

2 2

3 3

65

MEAN ONSD…………mm MEAN ONSD…………mm

LENS THICKNESS (LT) ON ULTASOUND

RIGHT EYE LEFT EYE

1 1

2 2

3 3

MEAN LT…………mm MEAN LT…………mm