A CLINICAL STUDY OF GLAUCOMA IN

PSEUDOEXFOLIATION SYNDROME.

Dissertation submitted to

THE TAMILNADU Dr.M.G.R MEDICAL UNIVERSITY

In partial fulfilment of the

regulations for the award of the degree of

M.S.OPHTHALMOLOGY

BRANCH – III

Thanjavur Medical College and Hospital

The Tamilnadu Dr. M.G.R Medical University

Chennai,India

APRIL 2016

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CERTIFICATE

This is to certify that this Dissertation entitled “ A CLINICAL STUDY

OF GLAUCOMA IN PSEUDOEXFOLIATION SYNDROME” is a bonafide original work done by Dr.P.ANURADHA , under my guidance and supervision in the Department of ophthalmology, Thanjavur Medical College,

Thanjavur doing her Postgraduate course from 2013 -2016.

Dr. M, SINGARAVELU M.D., DCH., Dr.J.GNANASELVAN M.S., D.O.,

The Dean, The Professor and HOD,

Thanjavur Medical College, Department of Ophthalmology,

Thanjavur – 613004. Thanjavur Medical College,

Thanjavur – 613004.

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CERTIFICATE

This is to certify that this Dissertation entitled “ A CLINICAL STUDY

OF GLAUCOMA IN PSEUDOEXFOLIATION SYNDROME” is a bonafide original work done by Dr.P.ANURADHA, under my guidance and supervision in the Department of Ophthalmology, Thanjavur Medical College,

Thanjavur doing her Postgraduate course from 2013 -2016.

Dr.J.GNANASELVAN M.S.,D.O.,

The Professor and HOD,

Department of Ophthalmology,

Thanjavur Medical College,

Thanjavur – 613004.

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DECLARATION

I Dr.P.ANURADHA solemnly declare that this Dissertation “ A

CLINICAL STUDY OF GLAUCOMA IN PSEUDOEXFOLIATION

SYNDROME” is a bonafide record of work done by me in the Department of Ophthalmology, Thanjavur Medical College, and Hospital, Thanjavur under the Guidance and Supervision of my Professor Dr.J.GNANASELVAN

M.S.,D.O., The Head of the Department, Department of Ophthalmology,

Thanjavur Medical College, Thanjavur between 2013 and 2016.

This Dissertation is submitted to The Tamilnadu Dr. M.G.R

Medical University , Chennai in partial fulfilment of University regulations for the award of M.S Degree (Branch – III) in Ophthalmology to be held in

April 2016.

Dr.P.ANURADHA,

Postgraduate Student,

Thanjavur Medical College.

Thanjavur.

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ACKNOWLEDGEMENT

I thank the All Mighty God for the abundant grace & Blessings and making me successful in every field to complete my dissertation work.

I would like to thank the Dean, Thanjavur Medical College, Thanjavur

for granting me permission to conduct this study at Thanjavur Medical College ,

Thanjavur .

It is my bounden duty to offer my sincere gratitude to my Professor &

HOD Dr.J.GNANASELVAN M.S.,D.O., Head of the department of

Ophthalmology for his motivation, meticulous guidance and encouragement throughout the period of study.

I express my heartful thanks and gratitude to my teachers Dr.R.Raja M.S.,

Dr.S.Amudhavadivu M.S., Dr.T.Anbuselvi.M.S., Dr.Thaialnayagi.M.S.,

Dr.K.Rajasekaran.M.S.,D.O., for the constant guidance, immense support,

suggestions and for being a great source of inspiration throughout the study.

I acknowledge the support from all my colleagues and friends in completing this study.

I am thankful to my family for their support and help throughout this study.

I am deeply indebted to the cogwheels of my study, the patients without whom the study would not have been completed for their participation and cooperation to conduct this study.

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CONTENTS

SI.No. TITLE PAGE NO

PART I

1 INTRODUCTION 1

2 REVIEW OF LITERATURE 2

3 AQUEOUS HUMOUR DYNAMICS 8

4 PSEUDOEXFOLIATION SYNDROME 24

5 GLAUCOMA AND PSEUDOEXFOLIATION 33

MANAGEMENT OF PSEUDOEXFOLIATION 6 42 GLAUCOMA

PART II

7 AIM OF THE STUDY 50

8 MATERIALS AND METHODS 51

9 OBSERVATION AND RESULTS 54

10 DISCUSSION 82

11 CONCLUSION 85

PART III

12 BIBLIOGRAPHY 87

13 APPENDIX I,II

14 KEY TO MASTER CHART

15 MASTER CHART

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INTRODUCTION

Glaucoma is one of the leading causes of irreversible blindness worldwide. Pseudoexfoliation is one of the common causes of secondary open angle glaucoma worldwide. It is noted to be a more aggressive disease with a mean progression rate higher than primary open angle glaucoma.

Pseudoexfoliation syndrome is a systemic micro fibrillopathy which targets ocular tissues through gradual deposition of proteinaceous material. This fibrillar material is produced by cells in the anterior segment in response to oxidative stress. Clumps of fibrillar material released into extracellular spaces gets deposited into corneal endothelium, ciliary epithelium, trabecular meshwork, iris, anterior capsule of lens, zonules, anterior vitreous face and conjunctiva. Clinically these appear as greyish white flakes. This pseudoexfoliative material gets accumulated in the trabecular meshwork and leads to elevated intra ocular pressure which leads to glaucoma.

Systemically this exfoliative fibrillopathy has also been reported in skin, visceral organs and associated with an increasing number of vascular disorders, sensori neural hearing loss and Alzheimer disease.

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REVIEW OF LITERATURE

In1917, Lindberg described as pseudoexfoliation for the first time in a finish population. He believed that this material was created by earlier inflammation.

The main and full description of pseudoexfoliation was made by a swiss ophthalmologist ALFRED VOGT. In 1918 he described pseudoexfoliation as a film on the anterior lens capsule due to remnants of pupillary membrane. In

1925 full description as exfoliation of the lens capsule and its deposition over lens capsule, iris, back of the cornea and its association with glaucoma capsulare was made.

The histological studies done by DAVOK-THEOBALD differentiated between true exfoliation seen in glass blowers and senile exfoliation. Senile exfoliation was then termed as pseudoexfoliation.

Prevalence of pseudoexfoliation:

Prevalence of pseudoexfoliation ranges from 0 in Eskimos to 21% in

Icelanders. In India prevalence rate of pseudoexfoliation is around 2 %

(Hiller et al). In South India the prevalence rate is 6 % in >40years of age as per

Krishnadas et al in 2003.

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In 2003 study by Aravind H Raju B, Paul B G showed there was a

significant increase in prevalence with age but no sex predilection 1. There was a

Significantly higher prevalence of cataract among the people with pseudoexfoliation .The prevalence of glaucoma is among 30% in patients with pseudoexfoliation.

In a study by Shazly et al in Egypt glaucoma was found in 30.31% of patients with pseudoexfoliation.

AGE:

According to Framingham study,

52-64 years 0.6%

65-74 years 2.6%

75-85 years 5.0%

Aasved study reported 0.4% of prevalence in the age of 50-59, and 7-9 % of prevalence in the age of 80-89.

In South India Aravind et al 2 reported 3.8% rate in patients of more than

40 years of age.

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HEREDITY:

Pseudoexfoliation syndrome appears to be sporadic mostly, but

Allingham and associates found X linked inheritance pattern in Icelandic families. They identified one out of three members in a family over 70 years of age having pseudoexfoliation and in each of these families, at least one in next generation had exfoliation and glaucoma. In all cases the parent always is the mother.

A study by Hewitt and co-workers suggests that the LOXL 1 family of proteins are associated with extra cellular matrix formation and stability, so the formation of abnormal protein by genetic variants might affect trabecular outflow and the lens epithelium.

Glaucoma in pseudoexfoliation syndrome:

Prevalence of glaucoma in pseudoexfoliation syndrome was 30 % according to Indian studies by Lamba and Giridhar 2.

Marium and Aurora reported prevalence rate of 22.6% and Sood and

Rathnaraj reported prevalence rate of 34 % in pseudoexfoliation syndrome patients.

According to Blue Mountains Eye Study, The prevalence of glaucoma in exfoliation syndrome was 14.7%.

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In south India, Krishna Das et al reported 7.5% of patients having glaucoma in pseudoexfoliation syndrome in 2003.

In pseudoexfoliation syndrome 12% of patients presenting with glaucoma

at diagnosis.5% of patients having no glaucoma at initial presentation, they

develop increase in IOP after 5 years and 15% of them develop elevated IOP

after 10 years.

In Blue mountain study, pseudoexfoliation glaucoma was seen in 14.2%

of patients. A study by Henry JC, Kruplin et al reported patients with

pseudoexfoliation having greater incidence of raised IOP against control group.

IOP AND PSEUDOEXFOLIATION:

In pseudoexfoliative eyes without glaucoma having mean IOP is usually

higher than the age matched controls.

Davenger et al found that mean IOP of primary open angle glaucoma

cases were 25.5mmHg and that of pseudoexfoliative patients were as high as

31.5mmHg 3.

Futa et al reported that 25.5% of pseudoexfoliation glaucoma cases with intraocular pressure of 30mmHg as compared to POAG only 15% of them having IOP of more than 30mm Hg.

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Optic nerve head damage:

Laden and Shaffer reported

Patient with unilateral pseudoexfoliation patient without exfoliation

64% of patients had CD ratio of 0.4, 85% had CD ratio of 0.4

36% of patients had CD ratio of 0.7; 15% had CD ratio of 0.7

KUCHLE et al found that aqueous protein concentration in pseudoexfoliation syndrome was higher than normal and POAG patients. He also quantified flare using Laser Flare Cell Meter (LFCM) and found it to be significantly increased in pseudoexfoliation patients 4.

A study by RINGVOLD et al showed 74% of pseudoexfoliation syndrome is not associated with glaucoma. If glaucoma is present, it is usually unilateral in18%and bilateral in 8%.SZKLAI et al reported that 34% of pseudoexfoliation glaucoma are unilateral and 66% are bilateral. Unilateral was always in the eye with pseudoexfoliation. LAMBA and GIRIDHAR reported that 46% of their pseudoexfoliation patients had unilateral glaucoma and 54% had bilateral glaucoma.

VISUAL FIELD DEFECTS:

Horven et al found that visual field defects of 61.4% in patients with pseudoexfoliation as compared to 35.75% in patients with POAG.

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TREATMENT OF PSEUDOEXFOLIATION:

In reviewing the literature regarding treatment of pseudoexfoliation glaucoma initial medical management is effective in reducing IOP with most agents.

A prospective study revealed prostaglandin analogue with beta blocker combination lowers IOP ranging from 8-11 mmHg, and another comparative study suggested combination of timolol & brimonidine and timolol & prostaglandin analogue is equally effective in lowering intra ocular pressure.

Jacobi et al described a non filtering procedure trabecular aspiration with

or without cataract extraction having better results 5.

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AQUEOUS HUMOUR DYNAMICS

Aqueous humour is a transparent colourless fluid which is continuously secreted by ciliary epithelium. The dynamics of the aqueous humour includes formation and drainage of the aqueous. The two main structures related to dynamics of aqueous are 1) ciliary body (site of aqueous production)

2) limbal region which includes trabecular meshwork (Principle site of outflow).

BIOLOGY OF AQUEOUS FORMATION:

Aqueous humour is an ultrafiltrate of plasma and the ciliary processes are the site of aqueous production.

Ciliary body:

It is the middle portion of the uveal tract. It is the continuation of choroid at oraserrata. It is composed of cilliary body muscle, vessels, cilliary processes and autonomic nerves.

Ciliary processes:

Ciliary processes are the functional unit responsible for aqueous secretion. It composed of capillaries, stroma and two layers of epithelium. The stroma is very thin and seperates the capillary network from epithelial layers.

The two layers of epithelium are outer pigment and inner non pigment

17 epithelium. The intercellular junctions connect the adjacent cells of the pigment and non pigment epithelium is called gap junctions. The adjacent non pigment epithelial cells are interconnected by tight junctions or zonula occuludentes which forms part of blood aqueous barrier.

MOLECULAR DYNAMICS OF AQUEOUS FORMATION:

Aqueous humor is derived from the plasma within the capillary network of cilliary processes. Aqueous humor is produced by diffusion, ultrafiltration and secretion 6.

Diffusion:

It is a biophysical process in which molecules of a gas or solution distributes uniformly throughout the space in which they are contained. In this there is a net flux of particles from high concentration to low concentration.

In aqueous formation, the lipid soluble substances are transported across the lipid portion of cell membrane of ciliary processes proportional to a concentration gradient. It accounts for 10% of aqueous production.

ULTRAFILTRATION:

It refers to phenomena of dialysis under hydrostatic pressure. In aqueous

formation water and water soluble substances pass through the theoretical

micropores in protein part of cell membrane in response to osmotic gradient or

hydrostatic pressure. 18

SECRETION:

It is an active process that selectively transports some substances across cell membrane in which energy is consumed and the substances can be moved across concentration gradient in direction opposite of passive mechanism.

In aqueous formation water soluble substance of larger size or greater charge are actively transported across the membrane. It is mediated by globular proteins. It is the major factor in aqueous production (80%).

STEPS OF AQUEOUS PRODUCTION:

1) Formation of stromal pool:

Most substances pass easily from the capillaries of cilliary process

across the stroma by ultrafiltration and getting accumulated between the

epithelial cells. This filtrate is containing more of proteins because of

fenestrated nature of chorio capillaries.

2) Active transport of stromal infiltrates:

Active transport occurs at non pigmented epithelial cells, in the

cell membrane of the lateral interdigitations. This active transport consists of

selective transcellular movement of cations, anions and other substances like

ascorbic acid.

3) Passive transport across non pigmented epithelium:

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Biology of Aqueous humour outflow:

The aqueous humor leaves the eye at the anterior chamber angle through the trabecular meshwork, schlemm’s canal, intra scleral channels episcleral veins and conjunctival veins. This is called conventional or trabeculo canalicular outflow. The uveo scleral or unconventional pathway is passage of aqueous through the root of iris, between ciliary muscle bundle , then through the supro choroidal tissues 7.

Anatomy of Aqueous Outflow:

Anterior chamber is a space filled with aqueous humour, bounded

anteriorly by the back of the Cornea and posteriorly by anterior surface of the

Iris. Its peripheral recess is known as angle of anterior chamber which is

bounded anteriorly by corneosclera and posteriorly by root of iris and cilliary

body. Angle of anterior chamber plays a vital role in process of aqueous

drainage.

Anatomy of angle of anterior chamber:

Angle of anterior chamber is formed by – cillary band, scleral spur, trabecular meshwork, schwalbe’s line.

Cillary band:

It forms posterior most part of angle recess and formed by anterior part of cilliary body. Its size depends upon level of insertion of iris. It tends to be wider 20 in myopes and narrow in hypermetropes. It appears as dark brown or grey color band.

Scleral spur :

Posterior portion of scleral sulcus forms scleral spur. It appears as a white line between ciliary band posteriorly and trabecular meshwork anteriorly. It is composed of collagen fibres I and III with few elastin fibres. The scleral spur prevents collapse or narrowing of schlemm’s canal during cilliary muscle contraction.

Trabecular meshwork:

Trabecular meshwork extends between schwalbe’s line and scleral spur.

It appears as a band anterior to scleral spur. At birth there is no pigment at trabecular meshwork, but it gets pigmented with increasing age. Its colour varies from faint tan to dark brown.

In meridonial section, trabecular meshwork is triangular in shape with its apex at schwalbe’s line and base at scleral spur. It is the main structure which allows aqueous outflow from eye.

The inner layer of trabecular meshwork which borders the anterior chamber is called uveal meshwork . The next superficial layer is corneoscleral meshwork and the outermost part that lies adjacent to the inner wall of schlemm’s canal is called juxtacanalicular meshwork.

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Figure 1: anatomy of angle of anterior chamber

Uveal meshwork:

It is the innermost part of the trabecular meshwork and merges with ciliary body and root of iris posteriorly and schwalbe’s line anteriorly. It consists of interconnecting trabecular beams or bands which are cord or rope like structures. The central core of trabeculae contains collagenous fibres with few elastic fibres. It is lined by trabecular endothelial cells which are resting on a thick basement membrane. The arrangement of these bands creates openings,

25 to 75 microns in diameter.

Corneoscleral meshwork:

It is the large middle main portion of the trabecular meshwork. It consists of 8- 14 flattened parallel sheets or lamellae which are anchored anteriorly to schwalbe’s line and posteriorly to scleral spur. The anterior tendon of the longitudinal cilliary muscle fibre gets attachment to corneoscleral meshwork

22 and to the sclera spur. The inner trabecular lamellae are thicker than the outer ones and they are arranged in a circumferential manner parallel to limbus. The trabecular sheets are perforated by elliptical openings and the pores are smaller than uveal meshwork with a size of 1-2 microns.

Juxtacanalicular meshwork:

It is the outermost part, lies adjacent to inner wall of schlemm’s canal.

This part offers maximum resistance to aqueous outflow. It consists of fine fibrils, elongated fibroblast like cells arranged in layers and embedded in extracellular matrix. It is also called as endothelial meshwork or cribriform layer.

Schwalbe’s line:

It is seen as fine ridge just in front of trabecular meshwork. It represents the prominent end of descemet’s membrane of the cornea. This line marks the transition zone from trabecular endothelium to corneal endothelium. It forms the anterior limit of the angle of anterior chamber. It lies on the plane of posterior corneal surface. The secretory cells present in the line are called schwalbe’s line cells which produce phospholipid, thought to facilitate the aqueous outflow.

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Schlemm’s canal:

It is an endothelial lined circular channel embedded in the scleral sulcus.

Its diameter varies from 350 to 500 microns. The endothelial cells of inner wall are irregular, elongated, spindle cells and contain giant vacuoles and outer wall are smooth and flat and supported by a basement membrane. The canal is not uniform in size and shape and split by septa and bridges which helps to keep the canal open.

Interscleral collector channels:

The outer wall of schlemm’s canal contains 25 to 30 openings for collector channels which connect the schlemm’s canal to the episcleral and conjunctival veins.

From schlemm’s canal aqueous is drained via the collector channels, into episcleral veins. A pressure gradient between intra ocular pressure and intrascleral venous pressure is responsible for unidirectional flow of aqueous.

These collector channels leave schlemm’s canal at oblique angles and terminate into episcleral veins. Valves are absent in collector channels. These can be divided into direct and indirect system.

Direct system: Intrascleral vessels drains directly into episcleral veins

Indirect system: In this fine collector channels which drains into deep

24 intrascleral plexus, mid intra scleral plexus and episcleral venous plexus – before entering in to episcleral veins.

Episcleral and conjunctival veins:

The episcleral veins drain into the cavernous sinus, via anterior ciliary and superior ophthalmic veins.

Summary of aqueous humour outflow:

Ciliary processes

Aqueous in posterior chamber

Anterior chamber

trabecular meshwork ciliary body

schlemm’s canal supra choroidal space

Collector channels Venous circulation of ciliary body , sclera.

Episcleral veins.

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PHYSIOLOGY OF AQUEOUS OUTFLOW:

Aqueous flows from the posterior chamber to the anterior chamber through the pupil. It leaves the eye by uveoscleral and trabecular outflow.

Uveo scleral outflow:

This is responsible for 10% of aqueous outflow. It is approximately 0.3 microlitre / min and independent of intra ocular pressure. Aqueous passes across ciliary body into suprachoridal space and drained by venous circulation in ciliary body, sclera and choroid.

The pressure in the suprachoroidal space is 2 mm Hg lower than the anterior chamber pressure that augments the leads uveo scleral outflow.

Prostaglandins increases uveo scleral outflow thereby decreases intraocular pressure.

Figure 2: Aqueous outflow system

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Trabecular outflow:

It is responsible for 90 % of total aqueous outflow. It is main outflow of aqueous from anterior chamber. The activity of trabecular meshwork cells which lines the aqueous channels promotes aqueous outflow.

Control of aqueous formation:

1) Adrenergic innervation:

Dense adrenergic innervations present in the vessels of ciliary

process may influence the aqueous formation by influencing permeability of

vessels.

2) Role of vasopressin:

At physiological level vasopressin, supports active transport of

sodium across ciliary epithelium.

3) Role of Adenyl cyclase:

Adenyl cyclase present in the tips of ciliary process and catecholamines cause increased formation of cAMP by stimulating adenylcyclase.

Adrenergic receptors regulate IOP via adenyl cyclase:

The majority of receptors in ciliary body are alpha 2, more than 90% beta

receptors are beta 2.

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Stimulation of alpha 2 receptors produce inhibition of adenyl cyclase , leads to reduction in aqueous production there by reduces the Intra ocular pressure.

Stimulation of beta 2 receptors produces active secretion of aqueous by

activation of adenyl cyclase and leads to an increase in intra ocular pressure.

The dual control of aqueous secretion through adenyl cyclase is mediated by

regulatory G proteins.

INTRA OCULAR PRESSURE

It is defined as the pressure exerted by intra ocular contents on the coats of eyeball. The major factor controlling intra ocular pressure is the dynamic balance between aqueous formation, outflow and episcleral venous pressure.

Normal Intra ocular pressure varies from 11 to 21 mmHg.

Prolonged changes in intraocular pressure are caused by:

i) An alteration in the forces determining the formation of the aqueous

humor.

ii) Alteration in the resistance to aqueous out flow either by blockage of

aqueous outflow into schlemm’s canal (sclerosis of trabeculae or their

obstruction by exudates or organised tissues) or by an increase in

episcleral venous pressure.

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Other factors are:

i) Variation in hydrostatic pressure in the capillaries

ii) An increase in permeability of capillaries

iii) A change in osmotic pressure of the blood

iv) Volumetric changes in the globe

v) A blockage of the circulation of aqueous

a) At the pupil b) At the angle of anterior chamber

Intraocular pressure is measured with tonometry.

Applanation tonometry:

Principle:

Goldmann applanation tonometry works on the principle of Imbert Fick law, which states that the pressure inside the thin walled sphere is equal to the force (F) needed to flatten, divided by the area of flattening(A).

P = F/A

When the area of flattening is 3.06mm diameter corneal rigidity and capillary attraction of tear meniscus cancels each other. Hence in goldmann applanation tonometer prism having 3.06 mm contact surface is used.

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Technique:

After instillation of topical anaesthesia and fluorescein in the conjunctival

sac, patient is positioned at slit lamp. Using cobalt blue filter the brightest beam

is projected at prism obliquely and the prism is centred in front of apex of

cornea. The dial is adjusted between 1 and 2 (ie 10 -20 mm Hg), the prism is

advanced till it touches apex of cornea. Fluorescein stained two types of

semicircles will be noted one above and one below horizontal midline. Adjust

the dial of tonometer till the inner edge of both semicircles coincides. Now the

reading in the dial is multiplied by 10 gives the intraocular pressure.

Figure 3 : fluorescein stained semicircle in applanation tonometer

Corneal thickness has an impact on accuracy of IOP measurement by

applanation tonometry. Normal central corneal thickness (CCT) varies between

0.49 -0.56mm. Increased CCT values >0.545 mm overestimates IOP and lower

CCT values underestimates IOP 8. Ehlers et al reported that applanation tonometer overestimates or underestimates approximately 5 mmHg for every 70 mm difference in mean CCT.

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GLAUCOMA

It is a chronic progressive optic neuropathy which is associated with

visual field loss as damage progresses, and in which intra ocular pressure is a

key modifying factor 2.

Prevalence:

Glaucoma affects 2 %of those over the age of 40 years and up to 10 %

over the age of 80 years. 50 % may be undiagnosed.

Classification:

Glaucoma is classified into Congenital and Acquired.

Based on the aqueous outflow impairment with respect to angle

configuration, it is sub classified into

a) Open angle glaucoma b) Angle closure glaucoma

It is further divided into primary and secondary glaucoma.

Secondary glaucoma’s have a recognisable ocular or non ocular disorder

that contributes to elevation of intra ocular pressure.

Pathogenesis of glaucomatous damage:

a) Mechanical changes due to the rise of intraocular pressure.

b) Changes in Vascular perfusion of the optic nerve head.

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Mechanical changes:

The coats of the eyeball withstand fairly high intra ocular pressure except at lamina cribrosa. Lamina cribrosa is a fenestrated region through which optic nerve enters the eye and the nerve fibres are supported by glial tissues.

A rise in intraocular pressure causes mechanical pressure on lamina cribrosa and decreasing axoplasmic flow in earlier stages, later leads to narrowing of openings in lamina cribrosa through which axons pass and directly damaging nerve bundles.

Vascular perfusion:

A rise in intra ocular pressure decreases capillary blood flow due to mechanical compression of vessels at lamina cribrosa or a decreased flow in annulus of Zinn, which supplies nutrition to laminar and post laminar optic nerve head 9.

This mechanical and vascular changes produces dysfunctional

axoplasmic transport which leads to damage and death of ganglion cells. This

loss of nerve fibres in the retina occurs initially at superior and inferior poles

and produces characteristic field defects.

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PSEDOEXFOLIATION SYNDROME

Pseudoexfoliation syndrome is a systemic disorder with primary ocular manifestations. Schlotzer and Streeten found pseudoexfoliative material like fibrils in skin, myocardium, liver, lung, kidney and meninges 10 .

It is a greyish white extracellular material which is composed of a protein

core surrounded by glycosaminoglycans and produced by abnormal basement

membrane of aging epithelial cells in trabeculum, equatorial lens capsule, iris

and ciliary body. This material is deposited over anterior lens capsule, zonules,

ciliary body, iris, trabeculum, anterior vitreous face and conjunctiva.

The clinical diagnosis of pseudoexfoliation is based on the finding of

dandruff like material in pupillary margin or sugar frosting of the anterior lens

capsule.

Histology of pseudoexfoliative material:

The histological nature of pseudoexfoliative material is, homogenous,

eosinophilic material positive for periodic acid shiff analysis and rich in

polysaccharides 11 . It is composed of randomly arranged fibrils and filaments

which are derived from elastin and basement membrane.

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Figure 4: Pseudoexfoliation fibres on lens capsule

ELASTIN:

On light microscopy pseudoexfoliative material is PAS positive indicative of material rich in polysaccharides. On electron microscopy it is found to be a fibrillar protein arranged in an irregular meshwork.

Immunoelectron microscopy has revealed elastin and tropoelastin.

An electron microscopic study done found a site specific elastosis in lamina cribrosa of pseudoexfoliative syndrome patients and suggested an abnormal regulation of elastin synthesis in optic nerve head of patients with pseudoexfoliative syndrome.

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BASEMENT MEMBRANE:

Immunohistological studies revealed heparin sulphate, chondrotin sulphate, laminin, fibronectin, and amyloid P to be the integral constituents of pseudoexfoliative material. This suggests that pseudoexfoliative material may be a basement membrane proteoglycon.

EPIDEMIOLOGY:

AGE:

Pseudoexfoliation syndrome is common in the age of more than 50 years

SEX:

Pseudoexfoliation syndrome is more common in females than males. But combination of exfoliation syndrome and glaucoma has greater predilection for males.

HEREDITY:

Pseudoexfoliation syndrome is usually sporadic. Recently a polymorphism in exon 1 of Lysyl Oxidase like 1 (LOXL1) gene found to be associated with exfoliative syndrome. The same polymorphism is not associated with POAG and appears specific for exfoliation syndrome and glaucoma, but they appear frequently in normal population also, so not used for diagnostic purpose. But this polymorphism in normal individuals is true marker of future

35 development of exfoliative syndrome and glaucoma remains unknown at this time.

Inhibitors of matrix metalloproteinases have been found to be upregulated and matrix metalloproteinases have been found to be downregulated in the aqueous of eyes with exfoliative syndrome as compared to normal populations 12 .

NON GENETIC FACTORS:

Ultra violet light rays, slow virus infection, auto immunity have been

found to be associated with pseudoexfoliative syndrome.

LATERALITY:

One third to half of patients are unilateral at the time of detection and 20-

45% of them become bilateral over 5-10 years. The patients presenting with

exfoliation in one eye will invariably show exfoliative material in other eye in

conjunctival biopsy 13 .

Clinical features of pseudoexfoliation syndrome:

CONJUNCTIVA:

Conjunctiva appears clinically normal in pseudoexfoliation syndrome.

Fluorescein angiography shows loss of regular limbal vascular pattern. The elastic fibres present in bulbar and palpaberal conjunctival stroma are found to be the source of pseudoexfoliative material. 36

CORNEA:

Dandruff like scattered flakes of exfoliative material on endothelium were observed in Slit lamp examination and reduction in endothelial cell density and pleomorphism demonstrated in specular microscopy 14 .

Increased incidence of corneal decompensation was observed in patients with pseudoexfoliation. In pseudoexfoliation central corneal thickness is increased compared to normal age matched individuals.

ANTERIOR CHAMBER:

Floating of exfoliative material in aqueous leads to breakdown of iris blood aqueous barrier and producing mild aqueous flare. Pigment dispersion is often seen following mydriasis. Anterior chamber depth is normal in most of the patients with pseudoexfoliation.

ANTERIOR CHAMBER ANGLE:

Trabecular hyperpigmentation is a common sign, which is more marked inferiorly. Patchy hyper pigmentation lies on the surface of the trabeculum which precedes the appearance of pseudoexfoliation. A wavy scalloped band of pigmentation on or anterior to Schawalbe line called sampaolesi line 15 .

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IRIS and PUPIL:

Pseudoexfoliative material settles on the surface of iris at pupillary margin which is the second common site next to lens and mostly seen in miotic state. This deposition of exfoliative material on sphincter and pigment loss from sphincter region gives to a characteristic ‘moth eaten’ appearance transillumination defects at pupillary margin. Absence of pupillary ruff is commonly seen in exfoliation syndrome 16 .

Figure 5: Pseudoexfoliation of Iris

Transillumination defects are detected by using a fibro optic light placed on the sclera in a dark room. Best way to see the transillumination defects is retroillumination with low magnification at slit lamp.

38

Fluorescein angiography of iris in pseudoexfoliative patients showed hypoperfusion, peripupillary leakage, iris hypoxia associated with atrophy of pigment epithelium and muscle cells. This accounts for poor mydriasis 17 .

Histopathological studies of iris sphincter and dilator muscle showed

fibrotic disorganised degenerative muscle tissue.

Pupil response to mydriatics in pseudoexfoliation :

Pupillary dilatation to mydriatics is reduced due to infiltration of

pseudoexfoliative material in iris stroma causing iris rigidity and atrophy of iris

leads to mechanical obstruction during mydriasis and mechanical restriction of

pupillary movements.

ZONULES and CILLIARY BODY:

Pseudoexfoliative material gets deposited in the cillary body and zonules

and produces peripheral granular zone in the zonules. It leads to degeneration of

zonules near their attachment to cilliary body. These exfoliative material

aggregates erupt through basement membrane and invades zonular lamellae.

The proteolytic enzymes which present in pseudoexfoliative material

disintegrate the zonules and leads to weakening of zonules 18 .

Weakened zonular attachment at ciliary body can lead to subluxation or dislocation of the lens and phacodonesis may be present

39

LENS:

A granular pseudoexfoliative material deposited over the anterior surface of lens is most common feature 19 .

VOGT describes this as three zones

ZONE I (CENTRAL DISK):

It is a homogenous white zone which is like a sheet lying on the anterior capsule. The size of central zone depends upon the pupil and serrations due to pupillary movements. Its size varies from 1.25 to 2.5 mm in diameter.

ZONE II (CLEAR ZONE):

It is the annular zone lies between zone I and zone III. It is created by constant rubbing of the pupil that scrapes the material off the midzone of the lens during physiological movement of the pupil.

B)

Figure 6: pseudoexfoliation of lens capsule with 3 zones

40

ZONE III (PERIPHERAL BAND):

It is a granular band seen in the periphery. It has a well delineated inner

border with multiple striations and its boundary ends on the equator of the lens.

Good mydriasis is essential to demonstrate the zone III.

To demonstrate this in early stages, placing slit beam at 45 degree to axis

of observation and reducing light source, focussing temporally 2-3 cm from

centre of lens highlights subtle deposits on lens surface 20 .

Cataract and pseudoexfoliation:

Nuclear cataract is commoner than cortical cataract in pseudoexfoliation and having greater incidence of zonular weakness 18 due to deposition of

pseudoexfoliative material over zonular fibres and ciliary processes producing

proteolytic disintegration of zonules resulting in phacodonesis spontaneous

subluxation or dislocation of lens. Incidence of phacodonesis and spontaneous

dislocation in pseudoexfoliation is found to be 8.4% to 10.6% 20 .

VITREOUS:

Exfoliative material is seen in anterior hyaloid face in aphakic eyes

41

GLAUCOMA AND PSEUDOEXFOLIATION:

Pseudoexfoliation is a common cause of secondary open angle glaucoma.

In contrast to primary open angle glaucoma in which pressure raises slowly and insidiously, in pseudoexfoliation syndrome pressure rises drastically.

Pathogenesis of glaucoma in pseudoexfoliation syndrome:

This fibrillary material is insoluble in aqueous, gets filtered and deposited in trabecular meshwork. It leads to clogging of trabecular meshwork and impairment of blood aqueous barrier in turn leads to decrease in aqueous out flow and increase in Intra Ocular Pressure. It is also accompanied by pigment release from iris caused by rubbing of iris against deposits in lens capsule, these released pigments also contributes to the blockage of trabecular meshwork 21 .

Type of glaucoma in pseudoexfoliation:

Evaluation of anterior chamber gives the information regarding the type of glaucoma. The anterior chamber angle is measured by gonioscopy.

Gonioscopy:

Normally the light from the angle of anterior chamber undergoes total internal reflection at the anterior surface of precorneal tear film. By using goniolens, tear film goniolens interface is formed which eliminates the total internal reflection and the angle structures are visualised.

42

Figure 7: Gonioscopic view of angles

There are two types in gonioscopy

Direct goniscopy:

Light rays from the angle are visualised directly without reflection in the lens.

Indirect gonioscopy:

Light rays from angle undergo reflection at the lens and visualised using mirror in indirect gonio lenses. So it gives the mirror image of the opposite angle.

Technique:

After instillaing topical anaesthesia, patient should be positioned in slit lamp. Coupling fluid is placed on the contact surface of goniolens. Ask the patient to look upwards and insert the lens then ask the patient to look straight.

Angle structures are visualised and graded.

43

Grading of angles: (Shaffer system)

Angle is graded according to visibility of angle structures in gonioscopy.

Grade 4 (35-45 0) - widely open angle, up to cilliary body is visible easily.

Grade 3(25- 35 0) - open angle, up to scleral spur is visible.

Grade 2 (20 0) - moderately narrow angle, only trabecular meshwork is

identified

Grade 1 (10 0) - very narrow angle , only schwalbe line is visible.

Slit angle - no angle structures are visible, no iridocorneal contact.

Grade 0 (0 0) - closed angle with iridocorneal contact present.

Figure 8: Angle grading by shaffer system

44

Other systems:

Other systems are spaeth system, scheie classification, van herick method.

Pseudoexfoliation syndrome commonly leads to open angle glaucoma and depth of the anterior chamber is found to be normal.

Angle closure glaucoma in pseudoexfoliation syndrome is rare. The mechanism of angle closure is pupillary and ciliary block 17 produced by posterior synechiae, increased rigidity of iris and anterior movement of lens due to zonular weakness 22 .

In pseudoexfoliation, iris is more rigid. When the posterior chamber pressure rises it produces bulging of iris at root of iris and producing pseudo plateau iris.

Optic nerve head damage:

Glaucoma produces characteristic appearance in optic nerve head.

The changes include increase in cup disc ratio, loss of neuroretinal rim, bayonneting of vessels, superior and /or inferior polar notching, laminar dot sign, disc haemorrhage and cupping of the disc 23 .

Retinal nerve fibre layer (RNFL) defect precedes the detectable optic

disc changes and the field changes. Two types are seen

a) Wedge shape defect b) diffuse pattern

45

Figure 9 : Optic disc changes in glaucoma

Retinal nerve fibre layer (RNFL) defect precedes the detectable optic disc changes and the field changes. Two types seen

b) Wedge shape defect b) diffuse pattern

Optical coherence tomography and scanning laser polarimetry are effective in quantifying the RNFL.

The pseudoexfoliation leads to high mean IOP and more liable for glaucomatous damage to the optic nerve head. They are associated with high degree of optic nerve damage.

In cases of unilateral pseudoexfoliation combined with bilateral glaucoma, glaucoma is worse in the eye with pseudoexfoliation. The presence of unilateral pseudoexfoliation with glaucoma in the other eye is the rarest 24 .

46

VISUAL FIELD DEFECTS:

Visual field defects in glaucoma are Para central scotoma, arcuate scotoma, ring scotoma, a nd the end stage of Small Island of central vision. The incidence is greater in pseudoexfoliation because eyes with pseudoexfoliation have poor tolerance to IOP raise.

a) b)

c)

d) e)

Figure 10 : Field defects in Glaucoma a) relative scotoma b)absolute glaucoma without involving blind spot c)arcuate scotoma d)double arcuate scotoma e)temporal island of vision.

47 Clinical difference between pseudoexfoliative glaucoma and POAG

1. Laterality – unilateral presentation of pseudoexfoliation against

bilateral in POAG.

2. Potential for rapid increase in IOP in pseudoexfoliation.

3. Rapid visual field loss

4. Refractory to antiglaucoma medications.

5. Better early responsiveness to laser trabeculoplasty.

6. Success rate of surgical treatment is similar to that of POAG.

Cataract surgery in pseudoexfoliation:

Recent studies suggested that eyes with pseudoexfoliation eyes have higher rate of complications during and after cataract surgery as against patients without pseudoexfoliation.

Zonular weakness and poorly dilated pupil are most important risk factors for surgical procedures, may cause capsular rupture and vitreous loss during surgery.

According to various studies, posterior capsular rupture having greater incidence up to 27%, as against having 2% in control eyes. Vitreous loss is also five times more in patients with pseudoexfoliation 25 .

48

Surgical complications in pseudoexfoliation syndrome:

Cornea - endothelial decompensation

Trabecular meshwork – post operative IOP rise

Iris – intra operative and post operative hyphema, posterior synechiae, pupillary block.

Lens & zonules – zonular dialysis, posterior capsule rupture, decentration of lens implant, anterior capsule fibrosis.

Differential diagnosis of pseudoexfoliation syndrome:

a) Pigment dispersion syndrome:

It is a bilateral condition affecting young males. Myopia is a common

risk factor.

Clinically krukenberg’s spindle in cornea is the hallmark of pigment

dispersion syndrome.

Classical radial slit like transillumination defects in the mid stroma of

iris as against in pupillary margin in pseudoexfoliation.

In gonioscopy, Hyperpigmentation of trabecular meshwork is more

marked in posterior trabeculum.

49 b) True exfoliation syndrome:

True exfoliation of the lens capsule is observed in those who are

exposed to high temperature like glass blowers. It is commonly associated

with cataract. Glaucoma is rare in these patients 26 .

In true exfoliation there is a thin membrane peeling off the anterior

capsule with a free edge floating in aqueous. c) Uveitic glaucoma:

Iritis produces pigment dispersion which gets and deposited in

trabecular meshwork, attachment of pupillary margin to anterior capsule of

lens producing posterior synechiae which differentiates from

pseudoexfoliation. d) Primary amyloidosis:

Amyloid material can get deposited in pupillary region and lens

capsule. Glaucoma can occur in primary amyloidosis.

50

MANAGEMENT OF PSEUDOEXFOLIATION GLAUCOMA

The higher incidence of glaucoma in pseudoexfoliation syndrome and more aggressive nature of the disease, sudden rise in IOP and recalcitrant to treatment, require management should be tailored to each patient.

Regular periodic IOP monitoring should be performed and detailed examination of optic disc, visual field assessment should be performed. IOP measurement should take into account the CCT values.

Treatment protocols:

Target IOP:

The intra ocular pressure level at which further damage is considered unlikely is called target pressure. It varies for each individual. Target pressure depends upon the pre existing damage, IOP level, CCT, age, rapidity of damage and general condition of the patient.

Monitoring is done by periodic optic nerve examination and field examination.

Medical management:

Treatment of pseudoexfoliation glaucoma traditional IOP lowering drugs are less effective in pseudoexfoliation.

51

Class Concentration Mechanism Ocular side effects Systemic side

of action effects

Beta blockers Decreased corneal punctuate bradycardia ,

Non selective : aqueous erosion, reduced hypotension,

Timolol maleate 0.25&0.5 % production aqueous tear bronchospasm,

by inhibition secretion, allergic CNS depression,

of cyclic conjunctivitis, reduced exercise

Selective : AMP tolerance

Betaxolol 0.5% increase in LDL

and decrease in

HDL

Prostaglandin Increased Burning and Myalgia, analogue outflow by stinging sensation, headache, flu

Latanoprost 27 0.005% acting on FP increase in iris like syndrome,

Travoprost 0.004% receptor pigmentation, paresthesia.

Bimatoprost 0.03% periocular Lengthening of

pigmentation, hair

reactivation of

herpes, anterior

uveitis.

Alpha agonists Decrease in allergic Hypotension,

52

Brimonidine 0.2% aqueous conjunctivitis and apnea, fatigue,

production granulomatous drowsiness

and increase uveitis

in

uveoscleral

Apraclonidine 0.5%,1% outflow ocular allergy, Syncope

Decreases conjunctival

episcleral blanching,

pressure mydriasis

Carbonic Decrease in Myopia , Gastero anhydrase HCO 3 ion in hypotension, instestinal side inhibitors posterior supra choroidal effects,

Topical chamber effusion. paresthesia,

Dorzolamide 2% leads to decresed libido,

Brinzolamide 1% decrease in urea stones,

Systemic aqueous thrombocytopne

Acetazolamide 250 mg tab humour ia

500 mg vial

powder

Miotics Increase in Miosis, browache, Salivation,

Pilocarpine 0.5 %, 1-4 % aqueous anterior chamber lacrimation,

53

outflow by chamber Bronchospasm,

ciliary inflammation. diarrhea,

muscle increased

contraction urination

Hyperosmotics 1-1.5g/ Reduces vitreous Diuresis, cardiac

Mannitol 10%,20% kgbw volume overload,

Glycerol 50% oral Osmorecetors in urinary retention

1-1.5g/kgbw hypothalamus

Laser trabeculoplasty:

Laser trabeculoplasty is highly successful in patients with

pseudoexfoliation

Argon laser trabeculoplasty:

Application of laser burns to the trabecular meshwork enhances aqueous

outflow and reduces intra ocular pressure.

A goniolens is used to visualise the angle, trabecular meshwork identified

and aiming beam of laser is focused at the junction of pigment and non pigment

epithelium , laser is delivered 28 . Transient blanching or appearance of minute

gas bubble occurs at the area of incidence.

54

Complications:

Peripheral anterior synechiae, small haemorrhage, acute elevation of

IOP, anterior uveitis.

Selective laser trabeculoplasty:

By using Frequency doubled Q switched 532 nm Nd –Yag laser selectively targeting on the pigment cells in the trabecular meshwork 29 .

Power of laser used – 0.5 – 1.2 mJ.

No of spots - 50-60 non overlapping spots over 1800 of trabecular meshwork .

Iop reduction with SLT: 3 – 18 mmHg.

Advantages of SLT:

No thermal tissue damage and safer than ALT.

Surgical management:

TRABECULECTOMY:

The procedure by which a fistulous tract is created and aqueous outflow is made from anterior chamber to sub conjunctival space and this protected by scleral flap 30 .

A limbal or fornix based conjunctival flap is made .triangular or rectangular superficial sclera flap is dissected till blue grey zone is reached,

55 anterior to this zone clear corneal zone is present. This is the external land mark of scleral spur. Anterior chamber entered and trabecular meshwork identified and block of it is removed. Peripheral iridectomy is performed. Superficial flap is sutured at its posterior corner. Anterior chamber is formed and conjunctival flap is sutured.

Figure 11: Trabeculectomy

Anti metabolites in filtration surgery:

Antimetabolites inhibit normal healing process that precludes filtering

successful trabeculectomy. Commonly used are Mitomycin c, 5 fluorouracil and

Daunorubicin 31 .

56

Mitomycin c 5 Fluorouracil

Inhibits DNA replication, Inhibit DNA synthesis in Mechanism of action mitosis &protein S phase of cell cycle synthesis

Dosage 0.2 -0.5 mg/ml 50mg/ ml

Intra operative and sub Intra operatively – conjunctival injection of Route of administration soaked in a sponge and 5 mg for 7 post operative kept for 5minutes days

Cataract , avascular bleb, Corneal and conjunctival

Complications bleb leak, hypotony, epithelial toxicity, wound

endophthalmitis leak, corneal ulcer.

Technique of application: 57

Anti metabolites soaked small cellulose sponge is placed under the dissected flap (avoid contact of sponge with conjunctiva), kept for 5 minutes then the sponge is removed. The area is washed with saline or Ringer lactate and the trabeculectomy is completed 32 .

Trabecular aspiration:

Using an irrigation aspiration device exfoliative material or pigments in

trabecular meshwork is aspirated along with cataract surgery or as a primary

procedure.

58

AIM OF THE STUDY

1) To study the demographic aspects of pseudoexfoliation.

2) To study the frequency of glaucoma in patients with

pseudoexfoliation syndrome.

3) To study the clinical spectrum of glaucoma in pseudoexfoliation

syndrome

4) To assess the treatment response in pseudoexfoliation glaucoma

INCLUSION CRITERIA:

a) All patients diagnosed as pseudoexfoliation syndrome with age

group of 40-80 years.

b) Both males and females were included.

c) Unilateral and bilateral pseudoexfoliation cases were included.

EXCLUSION CRITERIA:

a) Patients with less than 40 years of age.

b) Patient with previous history of uveitis or ocular trauma

c) Patients with history of exposure to intense infrared lights i.e.

glass blowing.

d) Patient with known cases of POAG and angle closure glaucoma

who were on medication.

59

MATERIALS AND METHODS

A total of 96 patients with pseudoexfoliation who attended the outpatient department of ophthalmology, Thanjavur medical college, Thanjavur from july

2014 to september 2015 were investigated. The study protocol was approved by the instituitional ethical committee.

Demographic details of all patients were noted. Patients were subjected to detailed clinical history and complete ocular examination. Case sheet profroma were drawn up and details of each patient were recorded.

Complete ocular examination includes:

a) Visual acuity:

Visual acuity and best corrected visual acuity by snellen’s visual acuity chart.

b) Anterior segment examination by slit lamp biomicroscopy and the

following details were observed

Conjunctiva –circum corneal congestion

Cornea – edema, pseudoexfoliation material in endothelium and pigmentation.

Anterior chamber - depth, aqueous flare, pseudoexfoliation materials.

60

Iris – transillumination defects, pattern.

Pupil – size, pseudoexfoliation material in papillary margin, reaction to light.

Lens – exfoliation material in anterior lens surface, cataract association, triple ring sign.

c) Intraocular pressure – measured with Goldmann applanation

tonometer. The values were taken after correcting the CCT.

d) Gonioscopy :

Status of angles of anterior chamber examined with

goldmann three mirror gonioscope – grading was done according to

Shaffer’s criteria and presence of pseudoexfoliation material or

pigmentation in angle is recorded.

e) Detailed fundus examination

By using direct ophthalmoscopy – changes in the optic disc,

cup disc ratio, retinal nerve fibre layer damage, thinning of

neuroretinal rim, shifting of retinal vessels were noted. Findings were

confirmed by slit lamp biomicroscopy with + 90 dioptre lens and

indirect ophthalmoscopy.

f) Central corneal thickness

Central corneal thickness measured by using pachymetry.

61

g) Visual field examination

Visual fields were assessed with automated perimeter (octopus

301).

h) Ultrasound B scan and ultrasound biomicroscopy in selected patients.

Complete ocular examination and measurements were done by a single person to avoid inter observer variations.

Pseudoexfoliation glaucoma was diagnosed on the basis of pseudoexfoliative material on slit lamp examination, IOP>21 mm Hg, glaucomatous cupping on fundus examination, pigmentation of trabecular meshwork on gonioscopy, glaucomatous field defects on perimetry.

62

OBSERVATION AND RESULTS

This study includes 96 patients with pseudoexfoliation who came to the

Department of Ophthalmology, Thanjavur Medical College from July 2014 to

September 2015. Out of 96 patients 55 patients were male and 41patients were females.

AGE DISTRIBUTION:

Table no 1: Age distribution of 96 patients:

AGE IN YEARS NO OF CASES PERCENTAGE (%)

41 -50 6 6

51 – 60 34 36

61 – 70 47 49

71 – 80 9 9

In this study of 96 patients, prevalence of pseudoexfoliation was higher among the age group of 61-70years , accounting for 49% (47cases), followed by

36% (34 cases) among51- 60 years. The youngest patient found in our study was 42 years and the oldest age of the patient was 80 years.

63

Figure 12:

AGE DISTRIBUTION

50 45 40 35 30 25 20 15 10 5 0 50 yrs 51-60 yrs 61-70 yrs 71-80 yrs

Age in years

SEX DISTRIBUTION:

Table no 2:

SEX NO OF CASES PERCENTAGE (%)

MALE 55 57

FEMALE 41 43

64 In this study of 96 patients, 55 males and 41 females were having pseudoexfoliation. There was mild male preponderance noted in our study.

Figure 13:

SEX DITRIBUTION :

SEX DISTRIBUTION

MALE FEMALE

In this study male preponderance some extent explained by the fact

Indian males are likely to have outdoor activities than females. Also in our region most of them are agricultural workers and exposure to ultraviolet exposure is high which may explain the male prepondarence.

65 LATERALITY:

Table 3:

LATERALITY NO OF CASES PERCENTAGE (%)

UNILATERAL 55 57

BILATERAL 41 43

In this study of 96 patients 55 (57%) were found to have unilateral pseudoexfoliation and 41(43%) were found to have bilateral pseudoexfoliation.

Unilateral pseudoexfoliation were having higher incidence than bilateral pseudoexfoliation.

Figure 14 : Pseudoexfoliation of lens capsule

66

FIGURE 15:

LATERALITY:

Laterality 60

50

40

30 Unilateral Bilateral 20

10

0 Unilateral Bilateral

In this study 55 patients were found to be having unilateral pseudoexfoliation, they are having the risk of developing pseudoexfoliation in other eye. Hence the unilateral pseudoexfoliation patients needs regular follow up.

67

AGE AND LATERALITY:

Table 4:

Age in years Unilateral Bilateral Total

No of % No of % No of %

cases cases cases

41-50 5 9.1 1 2.4 6 6

51-60 22 40.0 12 29.3 34 36

61-70 25 45.5 22 53.7 47 49

71-80 3 5.4 6 14.6 9 9

Total 55 100 41 100 96 100

In this study of 96 patients both unilateral pseudoexfoliation and bilateral pseudoexfoliation were common in the age group of 61 – 70 years.

Among the 41 patients of bilateral pseudoexfoliation 22 patients were found in the age group of 61-70 years.

68

Figure 16:

AGE AND LATERALITY:

AGE - LATERALITY

Unilateral Bilateral

53.7

45.4 40

29.3

14.6 9.1 5.4 2.4

41-50 51-60 61-70 71-80

Among the 9 patients in the age group of 71-80 years 6 patients had bilateral pseudoexfoliation. The percentage of bilateral pseudoexfoliation was higher in 71- 80 years. This signifies that the bilateral pseudoexfoliation is common as the age increases. Hence unilateral cases needs follow up.

69

GLAUCOMA ASSOCIATION:

Table 5:

Age in years Total No of Patients with Patients without

pseudoexfoliation glaucoma glaucoma

NO % NO %

41-50 6 0 6 100

51-60 34 12 35 22 65

61-70 47 19 40 28 60

71-80 9 4 44 5 56

In this study out of 96 patients, glaucoma was seen in 35 patients. The incidence of glaucoma according to this study was 36%.

70

Figure 17:

Age wise distribution of glaucoma in pseudoexfoliation :

50 45 40 35 30 totol no of PXF 25 Without glaucoma 20 With glaucoma 15 10 5 0 41 -50 51 -60 61 -70 71 -80

In this study, the incidence of glaucoma increases with age. More number of glaucoma patients are seen in the age group of 61 - 70 years. But the percentage (44%) of glaucoma is common in the age group of 71 - 80 years.

As the age increases, the persons hav ing pseudoexfoliation are more likely to develop glaucoma than younger ones.

71 Table 6:

Intra ocular pressure:

IOP No of patients PERCENTAGE

(mmHg) (%)

<20 61 63.5

21-30 22 22.9

>30 13 13.6

TOTAL 96 100

In our study of 96 patients, 61 patients had an intra ocular pressure less than 20 mmHg, 22 patients had an intra ocular pressure 21- 30 mmHg and

13 patients had an intra ocular pressure more than 30 mmHg.

According to our study the raised intra ocular pressure was found in

35 patients.

72

Figure 18:

Intraocular pressure:

Intra ocular pressure 70

60

50

40 <20

30 21-30 >30 20

10

0 <20 21-30 >30

73

Optic nerve damage:

Table 7:

CD ratio No of patients Percentage

(%)

0.3 42 43.8

0.4-0.6 30 31.2

>0.6 24 25.0

Total 96 100

In our study of 96 patients 42 patients had cup disc ratio of 0.3, 30 patients had cup disc ratio of 0.4 -0.6 and 24 patients had cup disc ratio of more than 0.6.

74

Figure 19:

Optic nerve damage:

Optic nerve damage - C:D ratio 45 40 35 30

25 0.3 20 0.4-0.6 15 >0.6 10 5 0 0.3 0.4-0.6 >0.6

According to our study the severe damage to optic disc (>0.6) was seen in

25% which is higher than the non pseudoexfoliation patient (15%). Hence pseudoexfoliation causes severe damage to the optic nerve and visual loss.

75

GRADING OF ANGLES:

Table 8:

Angle No of patients Percentage (%)

0-1 4 4.2

2 8 8.3

3 27 28.1

4 57 59.4

Total 96 100

In this study 57 patients had an angle of grade IV, 27 patients had an angle of grade III, 8 patients had an angle of grade II and 4 patients had an angle of grade I.

76

Figure 20:

Grading of angles:

Angle grading 60

50

40

30 Angle grading 20

10

0 0-1 2 3 4

Of these 96 patients 12 patients had narrow angle (defined by

Shaffer’s grading as grade 0-2) and 84 patients had an open angle. (defined by

Shaffer’s grading as grade 3-4).

Figure 22: Grade 4 open angle - by Shaffer system

77

TYPE OF GLAUCOMA:

Table 9:

Male Female Type of glaucoma NO % NO %

Open angle 22 63 9 25.6

Angle closure 2 5.7 2 5.7

Figure 21 :

TYPE OF GLAUCOMA:

25

20

15 male female 10

5

0 open angle closed angle

78 According to our study of 96 patients 31 patients had an open angle glaucoma 4 patients had narrow angles with glaucoma. In the 31 patients of open angle glaucoma 22 patients were males and 9 patients were females.

Hence pseudoexfoliation glaucoma is common among males.

TYPE OF GLAUCOMA ACCORDING TO ANGLES:

Table 10:

Type of glaucoma No of patients

Open angle glaucoma 31

Angle closure glaucoma 4

Angle closure suspect 8

Open angle without glaucoma 53

79

Figure 22:

Type of glaucoma according to Angles:

Angle grading 60 50 40 30 20 open angle withoutglaucoma 10 open angle glaucoma 0 angle closure suspect angle closure glaucoma

According to our study in pseudoexfoliation syndrome Open angle glaucoma is more common than the angle closure glaucoma. This is explained by the mechanism of rise in IOP in pseudoexfoliation and POAG are common.

80

OPEN ANGLE GLAUCOMA:

Open angle glaucoma and pseudoexfoliation:

Table 11:

Unilateral Bilateral Total Glaucoma Glaucoma

Unilateral PXF 13 1 14

Bilateral PXF 9 8 17

Total 22 9 31

Out of 22 patients with unilateral open angle glaucoma 13patients had unilateral pseudoexfoliation and 9 patients had bilateral pseudoexfoliation.In 9 patients with bilateral open angle glaucoma.

One patient had unilateral pseudoexfoliation and 8 patients had bilateral pseudoexfoliation.

81

Figure 23:

Open angle glaucoma and pseudoexfoliation:

14

12

10

8 unilateral glaucoma 6 Bilateral glaucoma

4

2

0 unilateral PXF Bilateral PXF

According to our study 71 % of patients had unilateral glaucoma and

29% had bilateral glaucoma. Hence unilateral glaucoma is more common than bilateral glaucoma in pseudoexfoliation syndrome.

82

ANGLE CLOSURE GLAUCOMA :

Table 12: Angle closure glaucoma:

Angle closure glaucoma NO OF PATIENTS

Secondary angle closure 2

Primary angle closure 2

Out of 4 patients with angle closure glaucoma, two patients had subluxated lens there was no trauma in these patient. Two patients had primary angle closure glaucoma. The possible mechanism of angle closure could be pupillary block by anterior shift of iris lens diaphragm due to weakened zonules.

83

Figure 24:

Angle closure glaucoma:

Angle closure glaucoma 2.5

2

1.5 primary 1 secondary

0.5

0 primary secondary

Out of 4 patients 2 patients had bilateral pseudoexfoliation. Two patients had unilateral pseudoexfoliation with clinical features of phacodonesis and subluxation of cataractous lens producing secondary angle closure.

84

FIELD DEFECTS:

Table 13:

Field defects No of patients Percentage (%)

Generalised depression 32 33

Arcuate scotoma 10 10

Double arcuate 7 7 scotoma

Tubular vision 4 4

Out of 96 patients 53 patients had field defects. Among them 32 patients had generalised depression, 10 patients had arcuate scotoma, 7 patients had double arcuate scotoma, and 4 patients had tubular vision.

In the remaining 43 patients fields were normal in 38 patients and not possible in 5 patients due to poor vision.

85

Figure 25:

Field defect :

Field defects 35

30

25

20 generalised depression

15 arcuate scotoma double arcuate scotoma 10 tubular vision 5

0 generalised arcuate double arcuate tubular vision depression scotoma scotoma

FIGURE 26: AUTOMATED PERIMETRY SHOWING ARCUATE DEFECT

86

CENTRAL CORNEAL THICKNESS:

Table 14:

Central corneal thickness(CCT) Value

Maximum CCT 0.580 mm

Minimum CCT 0.511mm

Mean CCT 0.539mm

In our study mean CCT value in patients with pseudoexfoliation was

0.539mm.

SYSTEMIC ASSOCIATION:

Out of 96 patients 6 patients had diabetes mellitus, 4 patients had

hypertension and 2 patients were associated with cardiovascular disease.

87

TREATMENT:

Table 15:

Treatment No of patients

Medical 23

Surgical 12

In the study two patients had phacodonesis, treated with cataract extraction & sclera fixation IOL during post operative follow up IOP is well controlled with medical treatment and glaucoma is non progressing.

Figure 27:

medical vs surgical treatment 25

20

15 medical 10 surgical

5

0 medical surgical

88

In this study 35glaucoma patients were started with 0.5% timolol eye drops two times per day. At the end of 2 months the patients were assessed regarding visual acuity, control of intra ocular pressure, glaucoma progression assessment by field and fundus examination.

After 2 months, among the 35patients 7 patients (20%) had reduction in intra ocular pressure and non progression of glaucoma during follow up with single drug.

Figure 28 :

comparision of single drug with combination of timolol and brimonidine

16 14 12 10 8 Timolol 6 4 Timolol & Brimonidine 2 0

Timolol Timolol & Brimonidine

Rest of the 28 patients had been started with combination of 0.5% timolol and 0. 2% brimonidine eye drops. The intra ocular pressure was well controlled among 16 patients (46%) and during the follow up visits these patients showed non progression of glaucoma.

89

Figure 29: Post trabecu lectomy with cystic bleb

Among the 35 patients, 12 patients (34%) had poor response to medical treatment either due to poor compliance of the patient or due to poor economic status to buy medicines. In these patients medical treatment was not sufficient t o control the intra ocular pressure. The intraocular pressure was controlled with filtering surgeries.

In these 12 patients combined surgery (trabeculectomy &cataract extraction with IOL implantation) was done. During the follow up period diffuse cystic filtering bleb was formed and intra ocular pressure was well controlled.

90 DISCUSSION

Glaucoma is the silent thief of sight, because vision loss occurs gradually over a period of time, symptoms occur only when disease is advanced, early detection is the best protection.

In this study of 96 patients with pseudoexfoliation who presented to our institute, all were subjected for detailed evaluation and analysis regarding the age at presentation, gender, laterality, glaucoma association, type of glaucoma and response to treatment.

In our study the pseudoexfoliation syndrome is common in the age group of 61-70 years. As age increases there is an increased incidence of pseudoexfoliation which is comparable to Framinghem study.

In our study Males were 57% and females were 43%.clements and Luntz found higher incidence among males. Taylor and Resnikoff et al reported pseudoexfoliation could be related to exposure to ultraviolet light and environmental factors. In our region most of the patients are agricultural workers and the ultraviolet light exposure is more which may explain the higher incidence in males.

In our study unilateral cases are having higher incidence than bilateral presentation, comparable to Henry et al study 34 . The unilateral cases have to be followed up due to possibility of becoming bilateral later in due course.

91

In our study glaucoma association was found to be 36%, the incidence of glaucoma increases with age which is similar to Lamba & Giridhar et al study.

According to our study 88.5 % had open angle glaucoma and 11.5% had angle closure glaucoma, thus open angle glaucoma is common in pseudoexfoliation syndrome 35 .

In our study unilateral glaucoma is more common than bilateral glaucoma. Hence pseudoexfoliation is the commonest cause of unilateral secondary open angle glaucoma.

In our study the cup disc ratio more than 0.6 was seen in 25% of patients.

Hence the optic nerve damage is more in pseudoexfoliation as compared to

POAG.

In our study 61 patients had an IOP less than 20 mmHg, 22 patients had an IOP between 21-30mmHg and the rest of 13 patients had an intra ocular pressure more than 30mm Hg.

In our study the mean value of CCT in patients was 0.539mm, the highest

CCT was 0.580 mm and lowest was 0.511mm which is similar to Hepsen et al study.

In our study, angles were wide open in 59.4%. 28.1% of patients had grade 3 angle 8.3% of them had grade 2 angle and 4.2 % had closed angles.

92

In our study, 60% of glaucoma patients had field defects out of which four patients had tubular vision.

In our study, out of 35 patients who have been diagnosed to have glaucoma, 23 patients responded to medical treatment and 12 patients IOP needed surgical treatment for IOP control. Out of 35 patients 20 % had control of IOP with single drug, 46% had control of IOP with combination drugs and 34

% patients responded well to surgical treatment.

Considering the poor economic status, poor compliance of the patients and average response to medical treatment surgical treatment is one of the best modes of treatment in pseudoexfoliation glaucoma.

93

CONCLUSION

To conclude the study, it was found that the prevalence of pseudoexfoliation increases as the age advances and pseudoexfoliation is most often unilateral at the time of presentation but eventually becomes bilateral, hence the unilateral cases needs periodic follow up.

The incidence of glaucoma is more in pseudoexfoliation and most of them have open angles.

The glaucoma is more common in bilateral pseudoexfoliation than unilateral pseudoexfoliation. The unilateral glaucoma is commoner than the bilateral glaucoma.

The intraocular pressure is having rapid rise, aggressive course and recalcitrant to treatment.

The severity of optic nerve damage is more as compared to the primary open angle glaucoma and having advanced field defects.

The pseudoexfoliation glaucoma has better response to combination drugs as compared to single drug. The need of surgical therapy to reduce intraocular pressure is high in pseudoexfoliation glaucoma.

All patients with pseudoexfoliation should undergo complete glaucoma evaluation and early detection of glaucoma. The patients should be frequently followed up. 94

The intra ocular pressure should be rechecked every 3-6 weeks in patients with pseudoexfoliation glaucoma. Pseudoexfoliation syndrome with no evidence of glaucoma patients should be followed every 6 months as they are having increased risk of developing glaucoma.

Pseudoexfoliation is an important cause of secondary open angle glaucoma. It is an important cause for ocular morbidity, because of high intra ocular pressure and difficult medical management it stands out and enigmatic clinical entity. In view of the high prevalence of glaucoma, severe damage to optic nerve increased need of surgical therapy and high risk of operative complications related to pseudoexfoliation Ophthalmologists should focus on the detection of pseudoexfoliation.

95

BIBLIOGRAPHY

1. Aravind H, Raju P, Poul PG, Baskaran M, Ramesh SV, George RJ et al.,

Pseudoexfoliation in South India. Br J Ophthalmol. 2003; 87(11):1321-

1323.

2. Lamba P. A Giridhar A : Pseudoexfoliation syndrome I.J.O.32:169,1984.

3. Davenger M, Ringvold A, Blika S. Pseudoexfoliation , IOP and glaucoma.

Acta Ophthalmol (copenh)1991;69:569-573.

4. Sakai K, Kojima K. Fluorescein angiography and electron microscopic

study of iris with pseudoexfoliation syndrome. Folia Ophthalmol

Jpn.1982;33.

5. Jacobi P C, Dietlein T S, Krieglstein GK. Comparative study of trabecular

aspiration vs trabeculectomy in glaucoma triple procedure to treat

pseudoexfoliation glaucoma, Arch Ophthalmology1999: 117:10.1311-8.

6. Kanski JJ, Bowling Brad. Clinical ophthalmology A systemic approach . 7 th

ed China: Elsevier saunders: 2011 p. 355 -56.

7. Shields MB. Clinical epidemiology of Glaucoma: In : AllinghamRR, Damji

KF, Freedman S, Moroi SE, Rhee DJ . Shield’s text book of Glaucoma. 6 th

ed. Philadephia. Lippincott Williams and Wilkins; 2011:248-261.

8. Hepsen et al : corneal curvature and thickness in PEX, Can J Opth 2007; 42:

677-680

96

9. Luntz MH, Prevalence of pseudoexfoliation syndrome in an urban South

African population: American Journal of Ophthalmology 1972, Vol 74, pg

581

10. Schlotzer – Schrehardt U, NAaumann GOH. Ocular and systemic exfoliation

syndrome. AMJ Ophthalmol. 2006; 141(5);921-937.

11. Kuchle M , Vinores SA, Mahalow J, GreenWR (1996) Blood aqueous

barrier in pseudoexfoliation syndrome: evaluation by immuno histochemical

staining of endogenous albumin. Graefes Arch Clin Exp Ophthalmol 234:

12-18.

12. Thomas et al . pseudoexfoliation in southern India. IOVS. 2001;46(4) :

1170-1175.

13. Tarkkanen A, Kivela T, John G. Lindberg : And the discovery of exfoliation

syndrome , Acta Ophthalmol Scand., 2002, 80: 151-154.

14. Miyake K, Matsuda M, Inaba M. Corneal endothelial changes in

pseudoexfoliation syndrome. AmJ Ophthalmol.1989;108:49-52.

15. Wishart PK,Spaeth GL, Poryzees,EM. Anterior chamber angle in exfoliation

syndrome. Br J Ophthal. 1985;69:103-107.

16. Latters W J , Samuelson T W. Pseudoexfoliation glaucoma. In: Yanoff M,

Duker J S.Editors:Ophthalmology , 2 nd ed. Vol 2. Newdelhi: Mosby; 2006.

P.1499-1503.

17. Aasved H . incidence of defects in pigmentary pupillary ruff in eyes with

without fibrillopathia epithelio capsularis ( so called senile exfoliation or

97

pseudoexfoliation of the anterior lens capsule ). Acta Ophthalmol.

1973:51:710-715.

18. Schlotzer – Schrehardt U , Naumann GO(1994) A histopathologic study of

zonular instability in pseudoexfoliation syndrome.Am J Ophthalmol

118:730-743.

19. Gifford H Jr. A clinical and pathologic study of exfoliation of lens capsule.

Trans Am Ophthalmol Soc. 1957 :189-216.

20. Lowe RF, Primary open angle glaucoma with capsular exfoliation of the

lens. Br J Ophthalmol. 1964 ;48:492-494.

21. Tarkkanen A . Treatment of chronic open angle glaucoma associated with

pseudoexfoliation. Acta Ophthalmol.1965;43:514-523 .

22. AAO OPH. Vol 108 pg1043: Ocular hemodynamics in pseudoexfoliation

syndrome and pseudoexfoliation glaucoma. June 2001.

23. Investigate Ophthal and visual sciences Nov 2005 pg 4170 vol 96, no 9:

pathophysiologic changes in optic nerves with primary open angle glaucoma

and pseudoexfoliation glaucoma.

24. Gottanka , Flugel –Koch C, Martus P, Johnson DH, Lutien –Drecoll E

(1997) Correlation of pseudoexfoliation material and optic nerve damage in

pseudoexfoliation syndrome. Invest Ophthalmol Vis Sci38:2435-2446.

25. Drolsum L, Ringvold A, Nicolaissen B (2007) Cataract and glaucoma

surgery in pseudoexfoliation syndrome : a review. Acta Ophthalmol scand

85:810-821.

98

26. Ringvold A. Epidemiology of pseudoexfoliation syndrome. Acta

Ophthalmol Scand 1999; 77 (4): 371-375.

27. Thomas R, Parikh R, Sood D et al . Efficacy and safety of latanoprost for

glaucoma treatment :a three month multicentic study in India . Indian J

Ophthalmol.2005;53:23-30.Henry C J , krupin T, Schmitt M et al ,Long term

follow up of pseudoexfoliation and the development of elevated pressure,

Ophthalmology,1987;94:545-52.

28. Ritch R,Podos S Laser trabeculoplasty in the exfoliation syndrome. Bull NY

Acad med 1983; 59:339-334.

29. Robin AL, Pollack IP.Argon laser trabeculoplasty in secondary forms of

open angle glaucoma. ArchOphthalmol. 1983;101:382-84.

30. Kontas AG, Jay JL, Marshall GE, Lee WR. Prevalence , diagnostic features

and responses to trabeculectomy in pseudoexfoliation glaucoma

Ophthalmology.1993 May. 100(5): 619-27.

31. Jerndal T, Kriisa V. Results of trabeculectomy for pseudoexfoliation

glaucoma. Br J Ophthalmol. 1974;58:927-930

32. Aasved H. The frequency of optic nerve damage an surgical treatment in

chronic simple glaucoma. Acta Ophthal .1971;49:489-600.

33. A L Young, W W T Tang, D S C lam: The prevalence of pseudoexfoliation

syndrome in Chinese population; Brittish Journal of Ophthalmology 2004:

193-195.

99

34. .Mitchell P Wang JJ, Hourihan F. The relationship between glaucoma and

pseudoexfoliation: Blue Mountain Eye Study. Arch Ophthalmol 1999; 117:

1319-1324

35. Prince and Ritch : Preclinical diagnosis of pseudoexfoliation: Arch oph.

105:1076,1987.

36. Von der Lippe I, kuchle M ,Naumann GO(1993) Pseudoexfoliation

syndrome as a risk factor for acute ciliary block angle closure glaucoma.

Acta Ophthalmol (Copenh) 71: 277-279.

37. Tyagi AK, Mcdonnell PJ(1998) Pseudoexfoliation syndrome and

spontaneous lens dislocation. Eye (Lond) 12: 1033-1034.

38. Gross Fj , Tingey D, Epstein DL . Increased prevalence of occuldable angle

closure glaucoma in patients with pseudoexfoliation. Amj Ophthalmol.

1994;117:333-336.

39. Kuchle M, Nguyen Nx, Horn F, et al . quantitive assessment of aqueous

flare and cells in pseudoexfoliation syndrome. Acta Ophthalmol(Copenh)

1992;70:201-208.

40. Tyagi AK, McDonnell PJ(1998) Pseudoexfoliation syndrome and

spontaneous lens dislocation Eye (Lond)12: 1033-1034.

100

APPENDIX I

A CLINICAL STUDY OF GLAUCOMA IN

PSEUDOEXFOLIATION SYNDROME

CASE SHEET PROFORMA

Name Age/ Sex: O.P/I.P .

Date:

Address:

Complaints : defective vision- sudden / gradual

Stationary / progressive/ transient

Associated pain

Pain ; nature

Site

Colored halos

Nausea & vomiting

Pressure upon the eyes & head ache

Frequent change of glasses

101

Presenting illness :

Past history:

Diabetes

Hypertension

Bronchial asthma

Any other systemic illness

Previous ocular surgery

Treatment history:

H/Oanti glaucoma medications – drugs , frequency, duration, regular/ irregular.

H/O chronic steroid use (topical)

Personal history:

Diet

H/O alcohol intake

Family history:

General Examination:

102

CVS:

RS :

Abdomen:

CNS :

Ocular examination

OD OS

Visual acquity :

Head posture:

Facial asymmetry:

Eye brows:

Eye lids :

SLE :

Conjunctiva : congestion- ccc / conjuctival / both

Filtering bleb + / -

If + - site diffuse/ flat/ encysted -

103 wall of bleb - vascularisation - functional / not -

Cornea :

Edema –

Bullae + /-

Pseudo exfoliation –

Kp’s

AC :

Depth - central & peripheral

Flare & cells

Pseudoexfoliation -

Iris :

Colur Pattern

Pseudoexfoliation -

Posterior synechiae

New vessels

104

Iridectomy / laser iridotomy

Iridodonesis

Trans illumination defects -

Pupil :

Size -

Shape -

Reaction to light – direct /consensual

Lens :

Pseudoexfoliation -

Cataractous Changes – stage

Position

Fundus (DO &IDO) :

Distant direct : media

Disc size

Shape

Colour

Margins

105

C;d ratio ,

Laminar dot sign

Margins steep / excavation

Neuro retinal rim : area – thinning + / -

Vessels over disc – bayoneting

Nasalisation

Haemorrhage

Macula & back ground retina

IOP (AT) :

Gonioscopy :

Grading of angles:

Pigmentation -

Pseudoexfoliation -

Sampaolesi line -

Pachymetry :

Automated perimetry :

Clinical diagnosis:

106

Treatment given:

1 . Medical :

2 . Surgical :

Follow up :

OD OS

Vision :

IOP :

Fundus :

107

APPENDIX II

KEY TO MASTER CHART

RE - Right Eye

LE - Left Eye

Vn - Vision

PXF - Pseudoexfoliation

CD - Cup Disc ratio

IOP - Intra Ocular Pressure

Gonio - Gonioscopic Angle Grading

Pac - Pachymetry

Fld - Fields

N - Normal

IMC - Immature Cataract

MC - Mature Cataract

NC - Nuclear Cataract

LC - Lens Changes

PCIOL - Posterior Chamber Intra Ocular Lens

N - Normal

(P) - Phacdonesis

PAC - Pachymetry

NP - Not Possible

GD - Generalised Depression

AS - Arcuate Scotoma

DAS - Double Arcuate Scotoma

TV - Tubular Vision 108

UPxf - Unilateral Pseudoexfoliation

BPxf - Bilateral Pseudoexfoliation

UOAG - Unilateral Open Angle Glaucoma

BOAG - Bilateral Open Angle Glaucoma

BACG - Bilateral Angle Closure Glaucoma

ACS - Angle Closure Suspect

UACG - Unilateral Angle Closure Glaucoma

BACS - Bilateral Angle Closure Suspect

ST - Sensitive to Timolol

STB - Sensitive to Timolol and Brimonidine

COMBSx - Combined Surgery

CATSx - Cataract Surgery

PI - Peripheral Iridotomy

FP - Follow Up

109

APPENDIX III

INFORMED CONSENT

I …………………………………………… hereby give consent to participate in the study conducted by the post graduate student in Department of Ophthalmology, Thanjavur Medical College, Thanjavur is doing the study entitled “ A CLINICAL STUDY OF GLAUCOMA IN PSEUDOEXFOLIATION SYNDROME”.

The procedure of this study is clearly explained to me in my own language. I understand that, this is an entirely a non-invasive and there is no risk involved in this procedure.

I hereby give my consent for participation in this study. The data obtained may be used for research and publication.

Station: Signature of the patient:

Date: Signature of the Investigator:

110

S S.I. Vn Vn CD CD Angle Angle PAC PAC FLD FLD Diagn Treat Name Age e (RE) (LE) (RE) (LE) (RE) (le) (RE) (LE) (RE) (LE) osis ment NO x IOP( LE) PXF(RE) PXF(LE) IOP (RE) IOP LENS(LE) LENS(RE)

1 Sivasamy 50 M 6\36 6\36 + - IMC IMC 0.3 0.3 16 14 IV III 0.54 0.538 N N UPxf Fp Govindasam Cat Sx 2 55 M 6\36 4\60 + + IMC IMC 0.3 0.5 12 16 IV III 0.545 0.538 N N BPxf y Fp 3 Prakasham 70 M 6\60 6\24 + - IMC NC 0.6 0.4 26 14 III III 0.542 0.535 GD GD UOAG ST Comb 4 Ayyavu 75 M 6\60 3\60 + + IMC IMC 0.5 0.8 20 30 III IV 0.548 0.534 GD NP UOAG Sx 5 Unnamalai 70 F 6\12 6\60 + + PCIOL IMC 0.3 0.4 14 14 II II 0.556 0.548 N N BACS FP

6 Ganesan 55 M 6\60 6/60 + + IMC PCIOL 0.3 0.6 16 28 IV IV 0.536 0.541 N GD UOAG STB

7 Papathi 65 F 6\60 6\60 + + IMC IMC 0.3 0.3 12 14 IV IV 0.538 0.536 N N BPxf Fp

8 Nallammal 60 F 2\60 6\18 - + IMC PCIOL 0.3 0.3 14 12 IV IV 0.543 0.538 GD N UPxf Fp

9 subramani 59 M 3\60 6\18 - + IMC NC 0.3 0.3 12 12 IV IV 0.535 0.541 GD N UPxf Fp

10 Ellammal 68 F 1\60 2\60 + - PCIOL IMC 0.7 0.4 22 16 IV III 0.542 0.542 NP NP UOAG ST Cat Sx 11 Arokiyasamy 68 M 3\60 6\60 + + IMC IMC 0.3 0.3 14 14 IV IV 0.541 0.54 GD GD BPxf Fp 12 Vellasamy 70 M 2\60 6\24 + + IMC PCIOL 0.3 0.5 14 16 IV IV 0.534 0.541 GD N BPxf Fp

13 DuraiRaj 57 M 1\60 6\60 + + IMC IMC 0.6 0.3 24 14 III III 0.536 0.535 NP GD UOAG STB

14 Vaduvambal 62 F 5\60 6\18 + - IMC PCIOL 0.5 0.3 16 14 IV IV 0.538 0.534 NP GD UPxf Fp

15 Anguraj 60 M 6\60 6\36 - + IMC IMC 0.3 0.3 14 12 IV IV 0.536 0.538 GD GD UPxf Fp Comb 16 Thangavel 58 M 6\18 3\60 + + PCIOL IMC 0.6 0.7 28 32 III III 0.554 0.545 GD DAS BOAG Sx 17 Lakshman 55 M 6\18 6\24 + - Lc Lc 0.3 0.3 14 14 IV IV 0.535 0.541 N N UPxf Fp

18 Bakiyam 58 F 6\36 6\12 + + Lc N 0.6 0.5 22 20 IV IV 0.543 0.54 AS N UOAG STB

19 Ahamed 61 M 6\24 6\60 + - Lc IMC 0.3 0.5 12 16 IV IV 0.541 0.548 N GD UPxf Fp

111

20 Vaithilingam 72 M 6\24 6\24 - + PCIOL PCIOL 0.4 0.6 18 24 III IV 0.534 0.536 GD AS UOAG STB Comb 21 Balakrishnan 75 M PL+ 6\36 + - NC PCIOL 0.9 0.3 42 16 III III 0.542 0.538 NP N UOAG Sx Cat Sx 22 Rajan 62 M 1\60 6\36 + + IMC IMC 0.5 0.3 16 14 IV IV 0.535 0.542 NP N BPxf Fp Subramaniya 23 59 M 6\36 6\18 + - Lc Lc 0.3 0.3 14 14 IV IV 0.54 0.541 N N UPxf Fp n Upxf 24 Maragatham 60 F 4\60 6\36 + - IMC Lc 0.3 0.3 12 14 II III 0.541 0.535 GD N Fp ACS 25 Rajendiran 70 M 5\60 6\60 + + IMC IMC 0.3 0.6 12 22 IV IV 0.534 0.538 GD AS UOAG ST

26 Maniappan 67 M 6\60 6\24 + - IMC PCIOL 0.3 0.3 16 16 IV IV 0.538 0.534 GD N Upxf Fp Comb 27 Kunjammal 75 F 1/60 Hm + + IMC IMC 0.3 0.9 36 34 III III 0.542 0.536 NP NP BOAG Sx 28 Natarajan 60 M 6\36 6\60 + - IMC IMC 0.3 0.3 14 14 IV IV 0.538 0.542 N N Upxf Fp

29 Adhimoolam 67 M 3\60 6\24 + - IMC PCIOL 0.3 0.3 16 16 IV IV 0.54 0.542 GD N Upxf Fp

30 Velayudam 80 M 6\18 6\18 + + PCIOL PCIOL 0.3 0.3 12 14 IV IV 0.545 0.538 N N BPxf Fp

31 Sarojini 42 F 6\18 6\18 + - N N 0.3 0.3 14 14 IV IV 0.538 0.534 N N UPxf Fp

32 Muthu 68 M 6\18 4\60 - + PCIOL IMC 0.3 0.7 16 26 III IV 0.562 0.54 N DAS UOAG STB

33 Venkadesan 59 M 6\18 6\24 - + Lc Lc 0.3 0.5 20 18 III III 0.548 0.538 GD GD UPxf Fp

34 vadivel 60 M 6\24 6\60 + - PCIOL IMC 0.7 0.5 20 18 III III 0.565 0.538 AS GD UOAG TB PI+ST 35 Saroja 65 F 6\60 3\60 + - IMC IMC 0.8 0.5 26 18 I II 0.535 0.528 TV GD UACG B 36 Chinnaponnu 50 F 6\36 6\60 - + PCIOL IMC 0.4 0.4 14 14 IV IV 0.536 0.541 N GD UPxf Fp Dhanabakiya Upxf 37 65 F 6\60 6\60 - + IMC IMC 0.3 0.3 14 18 II II 0.54 0.536 GD GD Fp m ACS 38 Balaiyan 65 M 3\60 6\18 + - IMC PCIOL 0.3 0.3 14 14 IV IV 0.538 0.546 NP N UPxf Fp Mariya Comb 39 70 F HM HM + + MC IMC 0.9 0.7 32 24 III IV 0.534 0.54 NP NP BOAG Puspam Sx

112

40 Muthan 65 M 3\60 6\60 + + IMC IMC 0.7 0.5 24 20 III III 0.542 0.54 DAS N UOAG ST

41 Karuthapillai 68 M 6\60 6\36 + - IMC IMC 0.3 0.3 16 14 III III 0.58 0.535 GD N Upxf Fp Comb 42 Sambandam 55 M HM 6\60 + + MC IMC 0.9 0.6 32 20 IV IV 0.534 0.541 NP GD UOAG Sx Muthu Cat Sx 43 60 M 3\60 6\60 - + IMC IMC 0.4 0.3 16 14 IV IV 0.542 0.436 NP GD UPxf Krishnan Fp 44 Ayyammal 66 F 6\60 6/36 + - IMC IMC 0.6 0.6 24 22 III III 0.541 0.542 AS N BOAG STB

45 Arulappan 59 M 6\36 6/9 + + IMC Lc 0.3 0.3 14 12 IV IV 0.525 0.538 N N BPxf Fp Venkatachal 46 70 M 1\60 6\36 + + PCIOL IMC 0.8 0.5 26 16 IV IV 0.538 0.546 AS GD UOAG STB am PI+ST 47 Thamburaj 65 M 2\60 1\60 + + IMC IMC 0.6 0.7 26 28 I I 0.532 0.54 Np Np BACG B 48 Sethuraman 59 M 6\36 6\18 - + IMC Lc 0.3 0.5 18 18 IV IV 0.535 0.536 GD N Upxf Fp

49 Nadesan 62 M 3\60 HM - + IMC IMC 0.3 0.7 16 26 III III 0.538 0.528 GD AS UOAG STB

50 Vimalraj 56 M 6\18 6\18 - + N N 0.3 0.3 14 12 IV IV 0.538 0.542 N N Upxf Fp Cat Sx 51 Vembu 70 F 6\60 2\60 + - IMC IMC 0.3 0.3 14 14 IV IV 0.54 0.541 GD NP Upxf Fp Thiraviyama Cat Sx 52 80 F 1\60 6\18 + - IMC PCIOL 0.3 0.3 14 14 IV IV 0.541 0.536 GD N Upxf ni Fp 53 Valliammal 75 F 6\36 6\24 + + PCIOL PCIOL 0.3 0.3 12 14 II II 0.534 0.536 N N BPxf Fp

54 Balaiyan 68 M 3\60 6\36 + - PCIOL IMC 0.8 0.4 30 16 III III 0.542 0.538 TV GD UOAG STB

55 Murugaiyan 70 M 6\60 6\18 + + IMC PCIOL 0.4 0.5 14 16 IV IV 0.568 0.54 N N BPxf Fp

56 Sundarajan 62 M 6/60 6\36 + - IMC LC 0.6 0.4 24 14 IV IV 0.535 0.538 GD N UOAG ST Cat Sx 57 Maniathal 74 F 3\60 6\24 + + IMC Lc 0.3 0.3 14 14 IV IV 0.542 0.536 NP GD BPxf Fp 58 Nallammal 67 F 6\18 6\18 + - PCIOL PCIOL 0.3 0.5 14 18 IV IV 0.54 0.542 N N Upxf Fp

59 Mariappan 60 M 2\60 4\60 + + IMC IMC 0.7 0.4 22 16 III IV 0.536 0.542 NP GD UOAG STB

113

Comb 60 Rajangam 64 M 2\60 6\36 + + IMC(P) IMC 0.9 0.5 34 22 I I 0.538 0.543 NP GD BACG Sx 61 Chindamani 60 F 4\60 6\36 - + IMC IMC 0.3 0.3 14 14 IV IV 0.538 0.538 GD N UPxf FP Comb 62 Chinnaponnu 68 F 6\24 HM - + IMC IMC(P) 0.3 0.3 22 36 I I 0.536 0.551 GD NP BACG Sx 63 Marriammal 80 F 6\36 6\36 + + IMC IMC 0.3 0.3 14 14 IV IV 0.552 0.535 N N BPxf Fp Upxf 64 Vanitha 48 F 6\12 6\18 + - LC Lc 0.3 0.3 12 12 II II 0.541 0.536 GD GD Fp ACS Comb 65 Panganam 60 F 6\60 Hm + + IMC IMC 0.8 0.9 26 32 III III 0.554 0.538 DAS NP BOAG Sx Anthony Comb 66 70 M 1/60 3\60 + + IMC IMC 0.9 0.8 36 28 IV IV 0.534 0.554 NP TV BOAG Samy Sx 67 Umaidurai 67 M 6\60 4\60 - + IMC IMC 0.3 0.6 17 24 III IV 0.536 0.511 GD AS UPxf STB

68 Prakasam 70 M 6\24 6\36 + + PCIOL Lc 0.4 0.4 16 16 IV IV 0.54 0.542 N N BPxf Fp Comb 69 Mahalingam 70 M 6\18 1/60 + + PCIOL IMC 0.6 0.9 22 38 III III 0.535 0.538 N NP BOAG Sx 70 Ganesan 65 M 6\60 6\60 + + IMC IMC 0.4 0.4 16 16 IV IV 0.538 0.526 N N BPxf Fp Govindasam Cat Sx 71 55 M 6\36 4\60 + - IMC IMC 0.4 0.4 16 14 IV IV 0.542 0.535 N GD UPxf y Fp 72 Sivasamy 56 M 6\36 6\36 + - LC LC 0.4 0.4 18 16 IV IV 0.536 0.54 N N Upxf Fp BPxf 73 Chandra 65 F 6\36 6\60 + + IMC IMC 0.4 0.5 18 20 III II 0.542 0.534 N GD PI+Fp ACS 74 Saroja 48 F 6\18 6\18 + + Lc Lc 0.3 0.3 12 14 IV IV 0.538 0.528 N N UPxf Fp

75 Karupaiyan 68 M 6\18 6\18 + - PCIOL PCIOL 0.4 0.4 12 14 IV IV 0.538 0.536 N N UPxf Fp

76 Unnamalai 60 F 6\24 6\60 + - PCIOL IMC 0.6 0.5 28 16 III IV 0.532 0.535 AS GD UOAG STB Thirugnasam Comb 77 55 M HM 6\36 + + IMC IMC 0.9 0.7 34 24 IV IV 0.538 0.546 NP DAS BOAG bandam Sx 78 Ayyavu 67 M 6\36 6\18 + + IMC Lc 0.3 0.3 14 14 IV IV 0.535 0.534 N N BPxf Fp BPxf 79 Chinnaiyan 70 M 6\12 6\60 + + PCIOL IMC 0.3 0.3 14 14 III II 0.54 0.554 N N Fp ACS

114

80 Jagnathan 58 M 6\18 6\60 + - Lc IMC 0.4 0.5 16 16 IV IV 0.541 0.535 N N UPxf Fp Sundramoort 81 60 M 3\60 Hm + + PCIOL PCIOL 0.6 0.9 24 34 III IV 0.536 0.536 DAS Np BOAG STB hi 82 Poongothai 69 F 6\18 6\18 + + PCIOL PCIOL 0.4 0.5 14 14 IV IV 0.534 0.538 N N BPxf Fp

83 Venugopal 62 M 6\36 6\36 + - IMC IMC 0.3 0.3 12 14 Iv III 0.556 0.562 N N UPxf Fp

84 Thillaiammal 65 F 6\60 6\36 - + IMC IMC 0.3 0.3 14 14 IV IV 0.541 0.536 NP N UPxf Fp Cat Sx 85 Lakshmi 64 F 3\60 6\60 - + IMC IMC 0.4 0.5 12 14 IV IV 0.542 0.54 Np N UPxf Fp 86 Krishnammal 59 F 6\60 2\60 - + IMC IMC 0.5 0.7 16 22 IV IV 0.535 0.534 GD TV UOAG ST BPxf 87 Thilagam 69 F 4\60 6\60 + + IMC IMC 0.3 0.3 16 16 II II 0.541 0.542 Np Np Fp ACS 88 Arokiyamary 56 F 6\18 6\36 + + Lc IMC 0.4 0.5 16 18 IV III 0.562 0.54 N N BPxf Fp Chandraman 89 60 F 6\60 6\60 + - IMC IMC 0.3 0.3 16 16 IV IV 0.538 0.535 N N UPxf Fp i 0.53 Cat Sx 90 Jagathambal 69 F 6/36 6/60 + + IMC IMC 0.3 0.3 18 16 IV IV 0.532 0.526 N BPxf 5 Fp 91 Krishnammal 62 F 6\60 6\36 + - IMC IMC 0.6 0.4 26 16 IV IV 0.546 0.532 AS GD UOAG ST Pitchaiamma 92 60 F 6/18 6/60 + - Lc IMC 0.4 0.4 14 14 IV IV 0.56 0.552 N N UPxf Fp l 93 Vembu 50 F 6/12 6/12 + - N N 0.4 0.4 14 14 IV IV 0.551 0.548 N N UPxf Fp

94 Achiponnu 68 F 6/36 6/24 - + IMC Lc 0.3 0.3 14 14 IV IV 0.548 0.541 N N UPxf Fp

95 Thillaiammal 54 F 6/18 6/24 + - Lc Lc 0.3 0.3 14 14 IV IV 0.532 0.546 N N UPxf Fp

96 Valliammal 55 F 6/60 6/18 + - IMC LC 0.3 0.3 16 16 IV IV 0.542 0.538 N N UPxf Fp

115