Glaucoma

Angle of anterior chamber is formed by root of iris, anterior-most part

of ciliary body, scleral spur, trabecular meshwork and Schwalbe’s line
(prominent end of Descemet’s membrane of cornea). The angle width
varies in different individuals and plays a vital role in the
pathomechanism of different types of glaucoma. Clinically, the angle
structures can be visualised by gonioscopic examination.
Aqueous outflow system. It includes the trabecular meshwork,
Schlemm’s canal, collector channels, aqueous veins and the episcleral
veins.
1. Trabecular meshwork. It is a sieve-like structure through which
aqueous humour leaves the eye. It consists of three layers, which from
inside out are uveal meshwork, corneoscleral meshwork and
juxtacanalicular meshwork.
2. Schlemm’s canal. This is an endothelial lined oval channel
present circumferentially in the scleral sulcus. The endothelial cells of
its inner wall are irregular, spindle-shaped and contain giant vacuoles
and or aqueous valve. The outer wall of the canal is lined by smooth flat
cells and contains the openings of collector channels.
3. Collector channels. These, also called intrascleral aqueous
vessels, are about 25–35 in number and leave the Schlemm’s canal at
oblique angles to terminate into episcleral veins in a laminated fashion.
Functions and composition of aqueous humour
Volume. The aqueous humour is a clear watery fluid filling the
anterior chamber (0.25 ml) and posterior chamber (0.06 ml) of the
eyeball.
Functions of aqueous humour are:
• Maintenance of a proper intraocular pressure.
• Metabolic and nutritional role. It plays an important metabolic role
by providing substrates (nutrition) and by removing metabolites from
the avascular cornea and lens.
• Clearing function. Aqueous humour serves as a mechanism to clear
blood, macrophages, remnants of lens matter and products of
inflammation from anterior chamber.
Drainage of Aqueous Humour. Aqueous humour flows from the
posterior chamber into the anterior chamber through the pupil
against slight physiologic resistance. From the anterior chamber the
aqueous is drained out by two routes:
1. Trabecular outflow. Trabecular meshwork is the main outlet
for aqueous from the anterior chamber. Approximately 70–80% of
the total aqueous is drained out via this route. Free flow of aqueous
occurs from trabecular meshwork up to inner wall of Schlemm’s
canal which appears to provide some resistance to outflow.
2. Uveoscleral outflow. It is responsible for about 20 to 30% of
the total aqueous outflow. The aqueous enters the ciliary body
through the iris root, ciliary body face and uveal trabecular
meshwork. Aqueous passes across the ciliary body between the
bundles of ciliary muscles into the suprachoroidal space and is
drained by the venous circulation of the ciliary body, choroid and
sclera.
Trabecular and uveoscleral outflow
The intraocular pressure (IOP) refers to the pressure exerted by
intraocular fluids on the coats of the eyeball. The normal IOP varies
between 10 and 21 mm of Hg. The normal level of IOP is essentially
maintained by a dynamic equilibrium between the formation and
outflow of the aqueous humour.
Glaucoma is a group of disorders characterized by a progressive
optic neuropathy resulting in a characterstic appearance of the
optic disc and a specific pattern of irreversible visual field defects
that are associated frequently but not invariably with raised
intraocular pressure (IOP).
Clinico-etiologically glaucoma may be
classified as follows:
A. Congenital/developmental glaucomas
1. Primary congenital glaucoma (without
associated anomalies).
2. Developmental glaucoma (with associated
anomalies).
B. Primary adult glaucomas
1. Primary open-angle glaucomas (POAG)
2. Primary angle-closure glaucoma (PACG)
3. Primary mixed mechanism glaucoma
C. Secondary glaucomas
Pathogenesis of Retinal Ganglion Cell. Death Retinal
ganglion cell (RGC) death is initiated when some
pathologic event blocks the transport of growth factors
(neurotrophins) from the brain to the RGCs. The blockage
of these neurotrophins initiate a damaging cascade, and the
cell is unable to maintain its normal function. The RGCs
losing their ability to maintain normal function undergo
apoptosis and also trigger apoptosis of adjacent cells.
Retinal ganglion cell death is associated with loss of retinal
nerve fibres. As the loss of nerve fibres extends beyond the
normal physiological overlap of functional zones, the
characteristic optic disc changes and specific visual field
defects become apparent over the time.
A. Primary insults
1. Raised intraocular pressure (Mechanical theory). Raised
intraocular pressure causes mechanical stretch on the lamina cribrosa
leading to axonal deformation and ischaemia by altering capillary blood
flow. As a result of this, neurotrophins (growth factors) are not able to
reach the retinal ganglion cell bodies in sufficient amount needed for
their survival.
 2. Vascular insuffciency theory. The retina and optic nerve
share a peculiar mechanism of autoregulation of blood flow with rest of
the central nervous system. Once the autoregulatory mechanisms are
compromised, blood flow may not be adequate beyond some critical
range of IOP (which may be raised or in normal range).
B. Excitotoxicity theory. Neuronal degeneration is believed to be
driven by toxic factors such as glutamate (excitatory toxin), oxygen-free
radicals, or nitric oxide which are released when RGCs undergo death
due to primary insults. In this way, the secondary insult leads to
continued damage-mediated apoptosis, even after the primary insult
has been controlled.
The congenital glaucomas are a group of diverse disorders in which
abnormal high intraocular pressure results due to developmental
abnormalities of the angle of anterior chamber obstructing the
drainage of aqueous humour.
Primary congenital glaucoma (PCG) refers to abnormally
high IOP which results due to developmental anomaly of the angle
of the anterior chamber, not associated with any other ocular or
systemic anomaly. Depending upon the age of onset the
developmental glaucomas are termed as follows:
1. Newborn glaucoma, also called as true congenital glaucoma,
is labelled when IOP is raised during intrauterine life and child is
born with ocular enlargement.
2. Infantile glaucoma is labelled when the disease manifests
prior to the child’s third birthday.
3. Juvenile primary open angle glaucoma(POAG) usually
occurs between 10 to 35 years of age. About 35% of patients with
juvenile POAG are myopes. The disease has a strong autosomal
dominant inheritance .
Buphthalmos. When the disease manifests prior to age of 3
years, the eyeball enlarges and so the term ‘buphthalmos’ (bull-like
eyes) is used. As it results due to retention of aqueous humour
(watery solution), the term ‘hydrophthalmos’, has also been
suggested.
Pathogenesis. Maldevelopment, from neural crest
derived cells, of trabeculum including the iridotrabecular
junction (trabeculodysgenesis) is responsible for impaired
aqueous outflow resulting in raised IOP. In primary
congenital glaucoma, the trabeculodysgenesis is not
associated with any other major ocular anomalies.
Clinically, trabeculodysgenesis is characterized by absence
of the angle recess with iris having a flat insertion. In it
the iris inserts flatly and abruptly into the thickened
trabeculum either at or anterior to scleral spur (more
often) or posterior to scleral spur. It is often possible to
visualize a portion of ciliary body and scleral spur.
Clinical features
1. Lacrimation, photophobia and blepharospasm often occur
together and form the classic triad of symptoms of congenital
glaucoma.
2. Corneal signs include its oedema, enlargement and Descemet’s
breaks. Normal infant cornea measures 10.5 mm. A diameter of more
than 13 mm confirms enlargement. Prognosis is usually poor in infants
with corneal diameter of more than 16 mm.
3. Sclera becomes thin and appears blue due to underlying uveal
tissue.
4. Anterior chamber becomes deep.
5. Iris may show iridodonesis and atrophic patches in late stage.
6. Lens becomes flat due to stretching of zonules and may even
subluxate backward.
7. Optic disc may show variable cupping and atrophy especially after
third year.
8. IOP is raised which is neither marked nor acute.
The examination should include following:
1. Measurement of IOP
2. Measurement of corneal diameter
3. Slit-lamp examination
4. Ophthalmoscopy to evaluate optic disc
5. Gonioscopic examination of angle of anterior chamber
reveals trabeculodysgenesis with either flat or concave iris
insertion.
Medical treatment. Medications are not very effective and
so treatment of congenital glaucoma is primarily surgical.
However, IOP must be lowered by medical treatment with
hyperosmotic agents, acetazolamide and betablockers till
surgery is taken up. Alpha-2 agonist (brimonidine) causes
CNS depression in children and is contraindicated.
Surgical procedures for congenital glaucoma
I. Incisional angle surgery, which can be performed by the
internal approach (goniotomy) or by external approach
(trabeculectomy).
II. Filteration surgery (trabeculectomy) with antimetabolites
gives good results.
Primary open-angle glaucoma is a type of
primary glaucoma, where there is no obvious
systemic or ocular cause of rise in the intraocular
pressure. Primary open-angle glaucoma (POAG),
also known as chronic simple glaucoma of adult
onset, is typically characterised by:
• Slowly progressive raised intraocular pressure (>21
mm Hg recorded on at least few occasions)
associated with,
• Open normal appearing anterior chamber angle,
• Characteristic optic disc cupping, and
• Specific visual field defects.
Predisposing and risk factors.
1. Family history (Heredity).
2. Age. The risk increases with increasing age. The POAG is more
commonly seen in elders between 5th and 7th decades.
3. Myopes are more predisposed than the normals.
4. Diabetics have a higher prevalence of POAG than nondiabetics.
5. Cigarette smoking is also thought to increase its risk.
6. Thyrotoxicosis is also not the cause of rise in IOP, but the
prevalence of POAG is more in patients suffering from Graves’
ophthalmic disease than the normals.
7. Corticosteroid responsiveness. Patients with POAG and their
offspring and sibilings are more likely to respond to 6 weeks
topical steroid therapy with a significant rise of IOP.
Pathogenesis of rise in IOP. It is certain that rise in IOP occurs
due to decrease in the aqueous outflow facility. Recently it has
been proposed that reduced aqueous outflow facility occurs due to
failure of aqueous outflow pump mechanism owing to trabecular
meshwork stiffening and apposition of Schlemm’s canal wall. Such
changes are caused by:
• Thickening and sclerosis of trabecular meshwork with faulty
collagen tissue.
• Narrowing of intertrabecular spaces.
Symptoms
1. Asymptomatic. The disease is insidious and usually
asymptomatic, until it has caused a significant loss of visual field.
Therefore, periodic eye examination is required after middle age.
2. Headache and eye ache of mild intensity may be
experienced in the course of the disease.
3. Scotoma (defect in the visual field) may be noticed
occasionally by some observant patients.
4. Difficulty in reading and close work, often persistently
increasing, is experienced by most patients. This occurs due to
increasing accommodative failure as a result of constant pressure
on the ciliary muscle and its nerve supply. Therefore, patients
usually complain of, frequent changes in presbyopic glasses.
5. Significant loss of vision and blindness is the end result
of untreated cases of POAG.
Signs
I. Anterior segment signs. Slit- lamp examination may reveal
normal anterior segment.
II. lntraocular-pressure changes. In the initial stages, the IOP
may not be raised permanently, but there is an exaggeration of the
normal diurnal variation. Therefore, repeated observations of IOP
(every 3–4 hour), for 24 hours is required during this stage (Diurnal
variation test). In most patients, IOP falls during the evening, contrary
to what happens in angle-closure glaucoma.
III. Optic disc changes. These are typically progressive, asymmetric
and present a variety of characteristic clinical patterns. Glaucomatous
changes in the optic disc can be described as early changes, advanced
changes and glaucomatous optic atrophy. Advanced glaucomatous
changes in the optic disc include: marked cupping excavation may even
reach the disc margin, and nasal shifting of retinal vessels which have
the appearance of being broken off at the margin.
IV. Visual field defects appear only after about 40% of axons have
been damaged and subsequently the field defects usually run parallel to
the changes at the optic nerve head and continue to progress if IOP is
not controlled. These can be described as early and late field defects.
Nomenclature of glaucomatous field defects. Visual field
defects in glaucoma are initially observed in Bjerrum’s area (10–25
degree from fixation) and correlate with optic disc changes. The natural
history of the progressive glaucomatous field loss, more or less, takes
the following sequence:
1. Small wing-shaped paracentral scotoma is the earliest clinically
significant field defect. It may appear either below or above the blind
spot in Bjerrum’s area (an arcuate area extending above and below the
blind spot between 10° and 20° of fixation point).
2. Seidel’s scotoma. With the passage of time paracentral scotoma joins
the blind spot to form a sickle-shaped scotoma known as Seidel’s
scotoma.
3. Arcuate or Bjerrum’s scotoma. It is formed at a later stage by the
extension of Seidel’s scotoma in an area either above or below the
fixation point to reach the horizontal line. Damage to the adjacent
fibres causes a peripheral breakthrough.
4. Ring or double arcuate scotoma. It develops when the two arcuate
scotomas join together.
5. Roenne’s central nasal step. It is created when the two arcuate
scotomas run in different arcs and meet to form a sharp right-angled
defect at the horizontal meridian.
6. Peripheral field defects. These appear sometimes at an early stage
and sometimes only late in the disease. The peripheral nasal step of
Roenne’s results from unequal contraction of the peripheral isopter.
7. Advanced glaucomatous field defects. The visual field loss gradually
spreads centrally as well as peripherally, and eventually only a small
island of central vision (tubular vision) and an accompanying temporal
island are left.
Investigations
1. Tonometry.
2. Central corneal thickness (CCT) measurement is essential in the
workup for glaucoma since a thinner cornea underestimates and a
thicker cornea overestimates the IOP on applanation tonometry.
3. Diurnal variation test.
4. Gonioscopy. It reveals a wide open angle of anterior chamber.
5. Documentation of optic disc changes.
6. Slit-lamp examination of anterior segment to rule out causes of
secondary open-angle glaucoma.
7. Perimetry to detect the visual field defects.
8. Nerve fibre layer analyzer (NFLA) is a recently introduced
device which helps in detecting the glaucomatous damage to the
retinal nerve fibres before the appearance of actual visual field
changes and/or optic disc changes.
Investigations of glaucoma
Diagnosis. Depending upon the level of intraocular pressure
(IOP), glaucomatous cupping of the optic disc and the visual field
changes the patients are assigned to one of the following
diagnostic entities:
1. Primary open-angle glaucoma (POAG).
Characteristically POAG is labelled when raised IOP (>21 mm of
Hg) is associated with definite glaucomatous optic disc cupping
and visual field changes.
2. Ocular hypertension. This term is used when a patient has
an IOP constantly more than 21 mm of Hg but no optic disc and
visual field changes.
3. Normal tension glaucoma (NTG) or low tension glaucoma
(LTG) is diagnosed when typical glaucomatous disc cupping with
or without visual field changes is associated with an intraocular
pressure constantly below 21 mm of Hg.
Therapeutic choices
■Medical therapy,
■Argon or diode laser trabeculoplasty, and
■Filteration surgery
Single drug therapy. Antiglaucoma drugs used are:
1. Prostaglandin analogues. These decrease the IOP by increasing the
uveo-scleral outflow of aqueous. Presently, a prostaglandin analogue is
being considered the drug of first choice for the treatment of POAG. The
available preparations include: Latanoprost (0.005%), Travoprost (0.004%),
Bimatoprost (0.03%).
2. Topical beta-blockers. These lower IOP by reducing the aqueous
secretion due to their effect on beta-2 receptors in the ciliary processes.
• Timolol maleate, a non-selective beta-blocker (0.25, 0.5%: 1–2 times/day),
is most popular as initial therapy. However, it should not be used in patients
having associated bronchial asthma and/ or heart blocks.
• Betaxolol (0.25%: 2 times/day). Being a selective beta-1 blocker it is
preferred as initial therapy in patients with asthma and other pulmonary
problems.
3. Adrenergic drugs. Brimonidine (0.2% : 2 times/day). It is a
selective alpha-2-adrenergic agonist and lowers IOP by decreasing
aqueous production and also by increasing uveo-scleral outflow.
Because of increased allergic reactions and tachyphylaxis rates it is
not considered the drug of first choice in POAG. It is used as second
drug of choice and also for combination therapy with other drugs.
4. Dorzolamide (2%: 2–3 times/day) or Brizolamide (1%, BD).
These are topical carbonic anhydrase inhibitors which lower IOP by
decreasing aqueous production by altering ion transport along the
ciliary process epithelium.
Combination topical therapy. If one drug is not effective, then a
combination of two drugs—one drug which decreases aqueous
production (timolol or other betablocker, or brimonidine or
dorzolamide) and other drug which increase aqueous outflow
(latanoprost or brimonidine or pilocarpine) may be used.
Role of oral carbonic anhydrase inhibitors in POAG.
Acetazolamide is not recommended for long-term use
because of their side-effects. However, acetazolamide 250
mg-tds may be added to control IOP for short term.
Hyperosmotic agents like mannitol 1–2 gm/kg body
weight may be used initially when patients present with
very high IOP ( >30 mm Hg).
Laser trabeculoplasty can be done using argon laser
(ALT), or diode laser (DLT) and selective laser
trabeculoplasty (SLT). It should be considered in patients
where IOP is uncontrolled despite maximal tolerated
medical therapy. It can also be considered as primary
therapy where there is non-compliance to medical therapy.
Surgical treatment of POAG primarily consists of a fistulizing
(filtration) surgery which provides a new channel for aqueous
outflow and successfully controls the IOP (below 21 mm of Hg).
Trabeculectomy is the most frequently performed filtration
surgery nowadays.
Indications
1. Uncontrolled glaucoma despite maximal medical
therapy and laser trabeculoplasty.
2. Noncompliance of medical therapy and
nonavailability of ALT/SLT.
3. Failure of medical therapy and unsuitable for
ALT either due to lack of cooperation or inability to
visualize the trabeculum.
4. Eyes with advanced disease, i.e., having very high
IOP, advanced cupping and advanced field loss
should be treated with filtration surgery as primary
line of management.
Primary angle closure disease, is characterised by apposition
of peripheral iris against the trabecular meshwork (TM) resulting
in obstruction of aqueous outflow by closure of an already narrow
angle of the anterior chamber. The condition is not associated
with any other ocular and systemic abnormalities.
Predisposing risk factors
1.Age. PACG with pupillary block occurs with greatest
frequency in 6th and 7th decades of life.
2.Gender. Male to Female ratio is 1:3.
3. Anatomical and ocular risk factors. Eyes anatomically
predisposed to develop primary angle-closure glaucoma
(PACG) include:
• Hypermetropic eyes with shallow anterior chamber and
short axial length.
• Eyes with narrow angle of anterior chamber, which may
be due to small eyeball, relatively large size of the lens and
smaller diameter of the cornea or bigger size of the ciliary
body or more anterior insertion of the iris on the ciliary
body.
Three pathomechanisms implicated in the causation of rise in IOP
of the eyes at risk of PACG are:
■Pupillary block mechanism,
■Plateau iris configuration and syndrome, and
■Phacomorphic mechanism.
1. Pupillary block mechanism. Mechanism of rise in IOP after
mydriasis. The probable sequence of events resulting in rise of IOP in
an anatomically predisposed eye is as follows: First of all due to the
effect of precipitating factors there occurs mid dilatation of the pupil
which increases the amount of apposition between iris and anteriorly
placed lens with a considerable pressure resulting in relative pupil
block. Consequently, the aqueous collects in the posterior chamber and
pushes the peripheral flaccid iris anteriorly (Iris bombe), resulting in
appositional angle closure due to iridocorneal contact. Eventually,
there occurs rise in IOP which is transient to begin with. But slowly the
appositional angle closure is converted into synechial angle closure
(due to formation of peripheral anterior synechiae) and an attack of
rise in IOP may last long. In some cases, a mechanical occlusion of the
angle by the iris is sufficient to block the drainage of aqueous. For this
reason, the instillation of atropine in an eye with a narrow angle is
dangerous, since it may precipitate an attack of raised IOP.
2. Plateau iris configuration and syndrome. Acute
angle closure glaucoma associated with plateau iris is
atypical in the patients that have normal central anterior
chamber depth, flat iris plane and minimal pupillary block.
The anterior chamber angle is closed by a pushing
mechanism because of the anterior positioned ciliary
processes displacing the peripheral iris anteriorly. Such a
situation is called plateau iris configuration and iridotomy
is sufficient to control IOP in such patients. Plateau iris
syndrome is labeled when acute angle closure glaucoma
occurs either spontaneously or after pharmacological
dilation, in spite of patent iridotomy. Such eyes are treated
with miotics and laser peripheral iridoplasty to produce
thinning of the peripheral iris.
3. Phacomorphic mechanism. The abnormal lens
may contribute by either causing pupillary block or by
pushing the peripheral iris forward into the angle
structures. Though the term phacomorphic glaucoma
refers to an acute secondary angle closure glaucoma
caused by the intumescent or other lens morphological
abnormalities; but now UBM and OCT studies have
shown that phacomorphic mechanism may be
responsible for initiating acute primary angle closure
glaucoma in predisposed patients (having occludable
angle). This also forms the base of lens extraction as a
treatment modality for acute primary angle closure
glaucoma.
Phacomorphic mechanism
Primary Angle-Closure Eyes with primary angle closure (PAC)
may be considered to comprise following entities of clinical
classification:
• Subacute primary angle closure
• Acute PAC
• Chronic PAC (asymptomatic).
Defining criteria for primary angle closure (PAC)
• Irido-trabecular contact noted on gonioscopy
• IOP elevated and/or peripheral anterior synechiae (PAS) present
• Optic disc: Normal, and
• Visual fields: Normal
Acute primary angle-closure. An attack of acute rise in IOP in
patients with primary angle closure (PAC) may occur due to pupillary
block causing sudden closure of the angle. It usually does not terminate
of its own and thus if not treated lasts for many days. It is a sight
threatening emergency.
Symptoms include:
■Pain. Typically acute attack is characterised by sudden onset of very
severe pain in the eye.
■Nausea, vomiting and prostrations are frequently associated with
pain.
■Rapidly progressive impairment of vision, redness, photophobia and
lacrimation develop in all cases.
Signs include:
• Cornea becomes oedematous and insensitive,
• Anterior chamber is very shallow,
• Angle of anterior chamber is completely closed as seen on gonioscopy,

• Iris may be discoloured,

• Pupil is semidilated, vertically oval and fixed. It is non-reactive to
both light and accommodation,
• IOP is markedly elevated, usually between 40 and 70 mm of Hg,
• Optic disc is oedematous and hyperaemic,
Acute angle closure is a serious ocular emergency and needs to be
managed aggressively as below:
• Immediate medical therapy to lower IOP,
• Definitive treatment,
• Prophylaxis of the fellow eye, and
• Long-term glaucoma surveillance and IOP management of both eyes.
A. Immediate medical therapy to lower IOP
1. Systemic hyperosmotic agents are required initially if IOP is
more than 40 mm Hg.
• Intravenous mannitol (1 gm/kg body weight).
• Oral hyperosmotics, e.g., glycerol 1 gm/kg body weight of 50% solution in
lemon juice.
2. Systemic carbonic anhydrase inhibitors, e.g., acetazolamide 500
mg IV stat followed by 250 mg tablet 3 times a day.
3. Topical antiglaucoma drugs to be instilled immediately
include:
• Beta-blocker, e.g., 0.5% timolol or 0.5% betaxolol
• Alpha adrenergic agonists, e.g., brimonidine 0.1–0.2%.
• Prostaglandin analogue, e.g., latanoprost 0.005%.
• Pilocarpine 2% QID should be started after 1 hour of the commencement
of the treatment, i.e., when IOP is lowered, as at higher IOP sphincter is
ischaemic and unresponsive to pilocarpine.
4. Topical steroid, e.g., prednisolone acetate 1% or dexamethasone eye
drops administered 3–4 times a day reduces the inflammation.
B. Definitive therapy
1. Laser peripheral iridotomy (LPI).
2. Filtration surgery, i.e., trabeculectomy.
3. Clear lens extraction by phacoemulsification with intraocular lens
implantation has recently been recommended by some workers,
especially in the presence of phacomorphic etiology (diagnosed on
UBM).
C. Prophylactic treatment in the normal fellow eye. Prophylactic
laser iridotomy (preferably) or surgical peripheral iridectomy should be
performed on the fellow asymptomatic eye (PACS).
D. Long-term glaucoma sur veillance and IOP management in
both eyes of a patient with acute PAC is must to ultimately prevent
glaucomatous blindness:
■Eyes treated with PI (both affected and fellow eye) may develop PACG
at any time.
■Filtration surgery may fail anytime during the course and hence need
to be repeated with antimetabolites.