Pharmacotherapy of Glaucoma

Dr.Suryaprakash Dhaneria
M.D. (Pharmacology),
D.M.(Clinical Pharmacology),
D.N.B.(Clinical Pharmacology & Therapeutics)
M.Sc.(Bio chemistry), LL.B.(Hons.)
MNAMS
Dean (Academics)
Professor & Head
Department of Pharmacology
All India Institute of Medical Sciences
(AIIMS) Raipur (C.G.)
 GLAUCOMA
 Aqueous humour is secreted by ciliary process.
 GLAUCOMA
 Raised Intra Ocular Tension (IOT) is due to
imbalance between drainage of Aqueous humour
and production of Aqueous humour.
 Ocular hypertension is a condition where IOT is
>21mm of Hg.
 Glaucoma is an ocular condition characterized
by raised IOT leading to cupping of optic
disc/progressive damage to optic nerve
resulting in gradual but irreversible loss of
vision.
 Optic nerve damage occurs when IOT is
persistently > 30 mm of Hg.
 GLAUCOMA
Congenital Glaucoma
Treatment is surgery

Secondary Glaucoma
Some pre-existing cause is responsible
for raised IOT. Like – disease or trauma or
drugs

Treatment of pre-existing cause

reduces IOT.
 Chronic simple
Acute congestive glaucoma
glaucoma

Pathology –
Here angle of anterior
Acute congestive glaucoma chamber is wide, but
it is due to narrowing of increase in intraocular
angle of anterior chamber pressure is due to
which blocks the drainage of pathology in trabecular
aqueous humor. Therefore it meshwork leading to
is also known as narrow impaired drainage of
angle glaucoma. aqueous humor.
 Acute congestive Chronic simple
glaucoma glaucoma
Precipitating factor –

Anything which causes Not significant.

dilatation of pupil Onset of disease is gradual.
precipitates the acute
congestive glaucoma – Risk factors are -
Old age
a) Anticholinergic Diabetes mellitus
medication. Myopia
b) Emotional stress due to Family history of glaucoma
adrenaline release.
c) Watching movie in dark
theater.
It usually occurs in
hypermetropia
 Acute congestive Chronic simple
glaucoma glaucoma

Clinical manifestations –
Acute congestive glaucoma is a It is usually bilateral.
medial emergency. If left
untreated then may result in There is constriction of
blindness in 2-5 days. peripheral vision, which
may lead to tunnel vision.
It is usually unilateral.
Central vision remains good
Patient complains of - until late in disease.
Severe ocular pain, headache,
nausea, vomiting, abdominal
cramps and sweating.
Initially blurring of vision with
halos around light, but later on
marked impairment in vision.
 Acute congestive Chronic simple
glaucoma glaucoma

Ocular examination reveals–

Eye is red and hard to touch, Cupping and pallor of optic

Cornea is hazzy.
Pupil is moderately dilated and
non reactive to light.
disc.
IOP (Intraocular pressure) is
usually > 21mm of Hg.

IOP (Intraocular pressure) is

usually > 50mm of Hg
 AIM OF THERAPY
 Aim of therapy in glaucoma is to prevent
further loss of vision.
 Loss of nerve cells and vision in glaucoma
is irreversible.
 Lowering of IOT will not restore the lost
vision but prevent the further loss of
vision.
 In case of visual impairment and neuronal
damage IOT is usually kept < 16 mm of Hg.
 DRUGS REDUCE INTRAOCULAR TENSION BY :
I. Drugs which reduce production of Aqueous Humour.

i. Β-blockers

ii. Carbonic anhydrase inhibitors

iii. α2 agonists

iv. Osmotic diuretics.

v. Sympathomimetics
 DRUGS REDUCE INTRAOCULAR TENSION BY :
II. Drugs which facilitate the drainage of
Aqueous Humour.
i. 80 - 90% of aqueous humour is drained through
trabecular meshwork. This is conventional outflow
pathway. Drugs increasing drainage by this pathway are –
Miotics
Rho kinase inhibitors

ii. 10 - 20% of aqueous humour is drained through

uveoscleral pathway. This is secondary outflow pathway.
Drugs increasing drainage by this pathway are –
Prostaglandin analogues.
No YES
 Acute congestive glaucoma- management

 Miotics are ineffective when IOT is > 60

mm. of Hg. because of paralysis of iris
sphincter due to ischemia. Response of iris
is restored when IOT is < 60 mm. of Hg.

 In fellow eye, low dose miotic is instilled

and prophylactic iridotomy or iridectomy is
also done.
 Drugs reducing production of Aqueous Humour
β blockers
• Reduce intra-ocular tension by decreasing the production of
Aqueous humour.
• These are used in open angle glaucoma (Chronic simple
glaucoma) as eye drop.
• These drugs offer following advantages over Miotics:
o Do not cause constriction of pupil so no diminution of
vision in dim light and preferred in cataract.
o Long acting – used once or twice a day.
o No induced myopia, so better tolerated by young patients.
o No headache and browache.
o No fluctuation in intra-ocular tension.
o Timolol, Metipranolol and Betaxolol offer protection to
retinal neurons.
 β blockers in Glaucoma
Drugs Dose
Non-selective β blockers
Timolol 0.25 – 0.5 % one drop twice a day or
0.5% gel once a day.
Levobunolol 0.25 – 0.5 % one drop twice a day.
Metipranolol 0.3 – 0.6 % one drop twice a day.
Carteolol 1% one drop twice a day.
Selective β1 blockers
Betaxolol 0.25 – 0.5 % one drop twice a day.
Use of non-selective β blocker in some patients may precipitate
bronchospasm due to blockade of β2 receptors. In this situation,
the selective β1 blocker is preferred. However, the efficacy of
selective β1 blocker is less than non-selective β blocker in
Glaucoma because β2 blockade is necessary for reducing the
production of aqueous humour.
Drugs reducing production of Aqueous Humor
Carbonic Anhydrase Inhibitors
Sysemically used drugs
Drugs Doses
Acetazolamide 500 mg. I/V and then 250
mg. orally 3 - 4 times a day
Dichlorhenamide 50 mg. 1 – 3 times a day
Methazolamide 50 – 100 mg. 2 times a day

Topically used drugs

Dorzolamide 2 % three times a day
Brinzolamide 1 % three times a day
Systemically used drugs may cause renal stones, acidosis,
paresthesia, fatique and bone marrow depression.
Topical CA inhibitors are preferred when topical β-blockers
are contraindicated or ineffective.
 Drugs reducing production of Aqueous Humor
α2 - Agonists
 These drugs reduce production of Aqueous
Humour by stimulating post synaptic α2 receptors

Topically used drugs

Brimonidine 0.2 % twice a day
Apraclonidine 0.5 - 1 % three times a day

 Apraclonidine is used to manage acute rises in

IOP in resitant cases and after laser therapy.

 Tachyphylaxis limits the long term use of

Apraclonidine.
 Drugs reducing production of Aqueous Humor
Sympathomimetics
 These drugs reduce production of Aqueous
Humour by causing vasoconstriction of ciliary
process. Dipivefrine may increase aqueous
humour outflow.

Topically used drugs

Adrenaline 1 % twice a day
Dipivefrine 0.1 % twice a day

 Dipivefrine is a prodrug and converted to

adrenaline in eyes.
 Because of availability of better drugs, these
are not used now a days in Glaucoma.
Drugs reducing production of Aqueous Humor

Osmotic Diuretics
 These drugs reduce production of Aqueous
Humour by increasing the Osmolality of plasma,
which draws the fluid from ciliary process.

 Drug used I/V is Mannitol – in the dose 1-2 gm/kg

Bw in 30-60 minutes.

 Drugs used orally are – Glycerol and Isosorbide

 These drugs are mainly used in acute congestive

glaucoma.
 Drugs facilitating the drainage of
Aqueous Humour

Prostaglandin analogues
 These drugs facilitate drainage of aqueous humor
mainly through uveoscleral outflow which accounts
for 10-20 % drainage. This drainage becomes
important when trabecular meshwork is damaged.

 These drugs may release metalloprotease enzyme

which digests extracelluar matrix material and clear
trabecular outflow tract.

 These drugs are preferred because of effectiveness,

once a day administration and no significant systemic
toxicity.
 Prostaglandin analogues
Topically used drugs
Latanoprost 0.005 % one drop daily at night
Trovoprost 0.004 % one drop daily at night
Bimatoprost 0.03 % one drop daily at night
Unoprostone 0.15 % one drop twice a day
Tafluprost 0.0015 % one drop daily at night

 These are prodrugs, activated by corneal esterase.

 These drugs are administered at night to achieve

peak effect when attack of glaucoma is more likely to
occur i.e. in night due to wide pupillary dilatation.
 Prostaglandin analogues
Adverse effects
 Darkening of iris colour after prolonged use due to
increased production of melanin by melanocytes in iris.
Pure brown eyes and pure blue eyes are not affected.
Mixed coloured eyes like blue-brown, yellow-brown,
gray-brown, green-brown, hazel eyes are more likely to
be affected.

 Eye lashes changes - increased number, length, thickness

and pigmentation which may be regarded as benefit by
most patients.

 Risk of macular oedema in patients with aphakia.

 May cause reactivation of herpes simplex keratitis.

Pigmentation of Iris by Latanoprost
 Drugs facilitating the drainage of
Aqueous Humour
Miotics
 These drugs facilitate drainage of aqueous humour
through canal of schlemm and trabecular meshwork
by causing miosis.
Topically used drugs
Drugs Doses
Pilocarpine 2% four times a day
Pilocarpine ocusert Placed in cul-de-sac at bed time
and effective for 7 days
Physostigmine 0.25 – 0.5 % four times a day
Echothiophate 0.125 – 0.25 % twice a day
Demecarium 0.125 – 0.25 % twice a week
 Miotics
Adverse effects
 Difficulty in dark adaptation.

 Headache, browache and ocular pain.

 Decrease in vision in cataract but preferred in
aphakia and psudophakia.

 Because of induced myopia, not tolerated by young

patients.

 Prolonged use may cause sub-capsular cataract

formation (specially with long acting drugs).

 Systemic absorption may cause stuffy

nose, sweating, increased salivation and occasional
vomiting and diarrhoea.
 Drugs facilitating the drainage of
Aqueous Humour

Rho kinase inhibitors

 These drugs facilitate drainage of aqueous humor
mainly through trabecular meshwork.

Topically used drugs

Drugs Doses
Netarsudil 0.02 % once a day

Ripasudil 0.4 % twice a day

 FDCs - in Glaucoma

 β – blockers + Topical carbonic anhydrase inhibitor

 β – blockers + Brimonidine

 β – blockers + Prostaglandin analogues

Lifelong treatment is needed in Chronic simple glaucoma

FDCs improve compliance of patient as number of eye

drops to be used are reduced.
Cupping of Optic Disc in Chronic simple glaucoma
 Surgery in Chronic Simple Glaucoma

 Laser trabeculoplasty

 Surgical trabeculectomy

 Viscocanalostomy and deep sclerectomy

with collagen implant

 Trabectome
T han k You