The document provides information about ocular steroids. It begins with an introduction to steroids and their chemical structure. It then discusses the adrenal gland and its role in producing steroids. The anti-inflammatory effects of steroids are explained through their impact on the inflammatory response pathway. Common ophthalmic steroids are listed along with their formulations and concentrations. The indications, contraindications and side effects of steroid use are briefly covered.

1. OCULAR STEROID
Suraj Chhetri
B.Optometry
16th batch

2. PRESENTATION LAYOUT
 Introduction to steroids
 Introduction to adrenal gland
 Inflammatory response
 Pharmacologic principle of steroids
 Common ophthalmic steroids
 Indications, contraindications and side effects of steroids

3. 3
 “Steroid" is a chemical name for any substance
that has a characteristic chemical structure
consisting of multiple chemical rings of connected
atoms.
 Contains four cycloalkane rings
3 rings : cyclohexane
1 ring : cyclopentane
INTRODUCTION TO STEROID

4. cortisol dexamethasone
Some examples of natural steroids
Vitamin D
Cholesterol
Estrogen
Progesterone
Cortisol
Some examples of synthetic steroids
Prednisolone
Dexamethasone
Betamethasone
trimcinolone

5. ADRENAL GLAND
 Two in number, superior and
slight medial to kidneys
 Two parts: adrenal cortex (80%)
adrenal medulla (20%)
 Each weight about 4 grams

6. ADRENAL CORTEX
 Comprises 3 zones:
 Zona glomerulosa(15%)
 Zona fasciculata(75%)
 Zona reticularis(10%)

7.  ZONA GLOMERULOSA : Produce mineralocorticoids
i.e Aldosterone
 ZONA FASCICULATA : Produce glucocorticoids
e.g Cortisol , corticosterone , small amount of
adrenal androgens and estrogens
 ZONA RETICULARIS : Produce androgens
e.g Dehydroepiandrosterone ,small amount
of estrogen and some glucocorticoids

9. HYPOTHALAMO-PITUITARY-
ADRENAL AXIS

10.  Secretion of mineralocorticoids depend upon
extracellular fluid concentrations of angiotensin II and
potassium
 Secretion of glucocorticoids controlled by hypothalmic
–pituitary axis via ACTH(adrenocorticotropic
hormone)
Thus secretion pathway of mineralocorticoids and
glucocorticoids does not depend upon each other

11. FUNCTION OF MINERALOCORTICOIDS
 Aldosterone increases renal tubular reabsorption of
sodium and secretion of potassium
 Excess Aldosterone increases extracellular fluid
volume and arterial pressure but has only small effect
on plasma sodium concentration
 Excess aldosterone causes hypokalemia and muscles
weakness

12. FUNCTION OF GLUCOCORTICOIDS
1.Effect on carbohydrate metabolism i.e
stimulation of gluconeogenesis
 Decrease glucose utilization by the cells
 Elevate the blood glucose concentration and cause
Adrenal diabetes
Cortisol increases the enzyme required to convert the
amino acid into the glucose in liver cells
Cortisol causes mobilization of amino acids from the
extrahepatic tissue mainly from muscles

13. 2.Effect on protein metabolism
• Reduction of cellular protein
• Cortisol increases the liver and plasma protein
• Excess of cortisol may cause muscle so weak that
person can not rise from the squatting position
Reduction of protein stored in essentially all body cells
except those of liver cells
Decreases protein synthesis and increases catabolism of
protein already present

14. 3.Effect on fat metabolism
 Mobilization of fatty acids
 Excess cortisol causes obesity
It promotes mobilization of free fatty acids from adipose
tissue
Increases the concentration of free fatty acids in plasma ,
which increases there utilization for energy
Excess deposition of fat in chest and head regions of body
giving a buffalo like torso and rounded moon face

15. 4.Effect in resisting stress
 Almost all type of stress ( trauma , infections , intense
heat and cold , surgery ) cause immediate and marked
increase adrenocotical secretion of cortisol
Glucocorticoids cause rapid mobilization of amino acids and
fat from there cellular store , making them immediately
available both for energy and synthesis of other compounds

16. 5. Effect on immunity and blood
 Decreases activation and migration of leukocytes
 Lyse and destroy lymphocytes
Administration of large doses of the cortisol causes significant
atrophy of all lymphoid tissue through out the body
Cortisol increase the count of red blood cells , the cause of which
is unknown
Inhibit migration of neutrophils to extracellular space and
adherence to vascular endothelium

17. 6.Effect as strong anti-inflammatory agent
 To know about anti-inflammatory action , first
inflammation should be discussed
 “Inflammation is the entire complex tissue changes
due to noxious agents ”
 Five different stages of the inflammation
Inflammation

18. 1.Chemicals such as histamine , bradykinin , proteolytic
enzymes , prostaglandins and leukotrienes from
damage tissue cells activates the inflammation
2. Increases blood flow due to vasodilation called
erythema
3. Leakage of plasma out of capillaries into damaged area
because increase capillary permiability
4. Infiltration of area by leukocytes
5. After few days ingrowth of fibrous tissue that often
helps in the healing process

19. Membrane phospholipid
Arachidonic acid
Chemical
and
mechanical
stimuli
Phospholipase A
cyclooxygenase lipooxygenase
endoperoxidases leukotrienes
Prostacycli
n PGI2
PGE2 , PGD2 ,
PGF2a
Thromboxane A2
glucocorticoids
NSAIDs
Basis of inflammation

20. Basic steroidal activities towards inflammation
 Reduce histamine release from basophils induced by IgE
dependent stimulus
 Inhibit phospholipase A2 which prevents biosynthesis of
arachidonic acid and subsequent formation of prostacyclin,
prostaglandins and leukotrienes
 Decrease capillary permeability and fibroblast proliferation
and the quantity of collagen deposition thus influencing
tissue regeneration and repair
 The anti-inflammatory effects are nonspecific, occurring
whether the etiology is allergic, traumatic or infectious

21. Mode of action
 Every tissue has receptor for steroids
 Binds to glucocoticoid receptor in nucleus
Because cortisol is
lipid soluble it can
easily diffuse through
the cell membrane

22.  Transactivation : upregulates the expression of
anti-inflammatory proteins in
nucleus
 Transrepression : downregulates the expression
of proinflammatory proteins in
cytosol

23. It is better to understand “Increased concentration of
drug better than increased dozes”

24. Common Ophthalmic steroids
Corticosteroid Derivative Formulation Concentration
Prednisolone Acetate suspension 0.125% or 1%
Prednisolone Sodium
phosphate
solution 0.125% or 1%
Dexamethasone Alcohol Suspension 0.1
Dexamethasone Sodium
phosphate
Solution
Ointment
0.1
0.05
Flourometholo
ne
Alcohol Ointment
Suspension
0.1
0.1
Flourometholo
ne
Acetate Suspension
Suspension
0.25
0.1

25. Prednisolone
 A synthetic analogue of the major glucocorticoid i.e
cortisol or hydrocortisone
 Effective for external as well as intraocular inflammation
 Commercially formulated as acetate and phosphate ;
acetate derivative being more effective anti-inflammatory
agent
 Not available as an ophthalmic ointment.

26.  Available in concentration of 0.5% and 1% W/V
 Prednisolone acetate 1% is considered the standard,
by which all other topical ocular corticosteroids are
compared
As compared with other topical ocular steroids , 1% prednisolone
acetate is generally considered the most effective anti-inflammatory
agent for anterior segment ocular inflammation

27.  Has the greatest efficacy when compared to all other
available ophthalmic agents
 So,is more likely to elevate IOP and have greater side
effects than its weaker counterparts
Systemic prednisolone recommendation
•Tab. Prednisolone acetate 1 mg/kg of body weight *OD
•Tab. Ranitidine 150 mg *OD * AC
•Tab. Calcium * 500 mg * OD

28. Dexamethasone
 Structurally resemble cortisol
 Available as an alcohol or phosphate derivative
 0.1% ophthalmic suspension or solution
 Alcohol derivative more active than phosphate
 Resistant to metabolism after penetration into the
aqueous humor.

29.  Very effective in reducing ocular inflammation
 But has the propensity to increase IOP more than any
other topical ophthalmic corticosteroid
 Usually limited to shortcourse therapy
 Dexamethasone ointment is very useful for nighttime
coverage in cases of uveitis

30. Fluorometholone (FML)
 Structurally resemble progesterone
 Formulated both as an alcohol and acetate derivative
 Relatively weaker corticosteroid
 Decreased risk of unwanted complications, such as
IOP rise

31.  Treatment of choice in those patients with a history of
pressure rise due to corticosteroid therapy or
previously diagnosed glaucoma
 An effective agent in external ocular inflammations ,
like conjunctivitis, piguiculitis , scleritis and episleritis
 Available as 0.1% drop

32. Medrysone
 Like fluorometholone , a synthetic derivative of
progesterone
 Weakest of the available ophthalmic steroids
 Useful for superficial ocular inflammations , including
allergic and atopic conjunctivitis
 Generally do not respond to intraocular inflammatory
conditions
 Elevates IOP minimally or not at all

33. Betamethasone
 Available as 0.1% eyedrop or ointment
 Marked anti-inflammatory action
 Low dose is enough
 So, reduces the risk of side effects

34. Hydrocortisone
 1st corticosteroid used in medicine
 Available as 1% eyedrop and 0.5%, 1% or 3% ointment

35. Rimexolone
 Available as a 1% ophthalmic suspension (Vexol)
 Effective in suppressing cells, flare, keratin precipitates
and photophobia
 Main advantage - more of site-specific action than
other corticosteroids
 Less tendency to increase the IOP.

36. LOTEPREDNOL
 Available as 0.2% and 0.5% concentration
 Less potent steroid
 Indicated for temporary relief of the signs and
symptoms of seasonal allergic conjunctivitis

37. Dexamethasone
Prednisolone
Fluorometholon
Medrysone
A
N
T
I
N
F
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A
M
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A
T
O
R
Y
A
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T
I
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E
A
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E
I
N
I
O
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38. BIOAVAILABILITY OF TOPICAL STEROIDS
 Fraction of unchanged drug reaching the systemic
circulation
 Depends upon the ability to penetrate cornea
 The ideal steroid should be biphasic i.e solubility in
both the lipid (hydrophobic) layers of the epithelium
and endothelium and the aqueous (hydrophilic)
media of the stroma

39.  Acetate and alcohol derivatives more lipophilic i.e fat
soluble
 Sodium phosphate and hydrochloride more
hydrophilic i.e water soluble
 So, in intact epithelium , penetration of acetate
greater while in absence of epithelium penetration of
phosphate greater
Acetate and alcohol derivatives are more effective then the
phosphate derivatives in suppressing corneal
inflammation both in the presence and absence of
corneal epithelium

40. Preparations
 LOCAL : Eyedrops-suspension or solution
Ointments
Injection - subconjuctival , sub-tenon’s
capsule or retrobulbar
 SYSTEMIC : Tablets
Injections(intra venous)
-

41. Routes of administration
TOPICAL SYSTEMIC
Effective in anterior segment
diseases
Effective in posterior
segment diseases
Ease of application, relative
low cost
Difficult application,
relatively high cost
Dosage vary with severity of
disease
Generally single dose daily
Absence of systemic
complications
Systemic complications
present

42. Ocular indications
Topical Systemic
•Blepharitis
•Uveitis
•Allergic conjunctivitis
•Allergic keratitis
•Viral keratitis
•Pingueculitis
•Inflammation of pterygim
•Cystoid macular edema
•After ocular surgery
• posterior uveitis
•Systemic ophthalmia
•Papillitis
•Retrobulbar neuritis
•Scleritis
•Anterior ischemic optic
neuropathy
•Malignent exopthalmus
•Orbital pseudotumor

43. Alternate day therapy
 Single dose on alternate day systemic
administration of corticosteroids is as effective as
divided daily dose
 Permits metabolic recovery and prevents toxic side
effects from accumulating
Patients receives the entire total dose that would be given
over a 2-day period as a sing dose , every other morning
Alternate-day systemic therapy applies only to shorter
acting systemic steroids like prednisone, in case like
chronic uveitis

44. Double edged sword
It only inhibit the inflammatory
response not the cause of
inflammation
Magical drug

45. Why steroids dozes tapered ??
 Synthetic cortisone medication mimic cortisol,i.e
naturally occuring hormone produced by adrenal
gland
 Excess production of cortisol – negative feedback
mechanism (HPA axis)
 Using large dose for few days or smaller dose for more
than two weeks—prolonged decrease in HPA axis
function

47.  So tapering is required i.e continuing the therapy
for several days in reduced dose
 Gives time for adrenal glands to return their
normal patterns of secretion
 Also reduces the chance of recurrence of the
disease

48. Locally (in case of topical) ??
Corticosteroids reduce the leukocyte cells locally
White cells proliferate when therapy stops
Immature cells can produce large quantities of
antibodies to residual antigen in the ocular tissue
Massive polymorphonuclear leukocytic reaction
follows the resultant antigen- antibody reaction

49. This sequence of events , unless interrupted immediately ,
can lead to a recurring , serious necrotizing inflammation
Thus depending upon response and dozes used , topical
therapy should generally be tapered over several days to
weeks
Removal of corneal epithelium caused appearance of
leukocytes in tear fluid within 2-5 hrs which was greatly
reduced by 1% prednisolone and 0.01% flurbiprofen

51. Eyelids
 Allergic blepharitis
 Contact dermatitis
 Herpes zoster dermatoblepharitis
 Chemical burns
 Neonatal hemangioma

52. Conjunctiva
 Allergic conjunctivitis
 Vernal conjunctivitis
 Herpes zoster conjunctivitis
 Chemical burns
 Mucocutaneous conjunctival lesions

53. Cornea
 Immune reaction after keratoplasty
 Herpes zoster keratitis
 Disciform keratitis
 Marginal corneal infiltrates
 Superficial punctate keratitis
 Chemical burns
 Acne rosacea keratitis
 Interstitial keratitis

54. Uvea
Anterior uveitis
Posterior uveitis
Sympathetic ophthalmia

55. Sclera
Scleritis
Episcleritis

56. Retina
Retinal vasculitis
Optic nerve
Optic neuritis
Temporal arteritis
(arteretic anterior ischaemic optic
neuropathy)

57. Globe
Endophthalmitis
(except fungal endopthalmitis)
Hemorrhagic glaucoma
Orbit
Pseudotumor
Graves’ ophthalmopathy
Extraocular
muscles
Ocular myasthenia gravis

59. Generally contraindicated in:
 Peptic ulcer
 Osteoporosis
(an increased risk of fracture )
 psychoses

60. Should be used with caution in
 Diabetes mellitus
 Chronic renal failure
 Congestive heart failure
worsen the condition
 Systemic hypertension
 Infectious diseases
 glaucoma

61. Patients with prolonged systemic therapy, lack
sufficient adrenal reserve to respond to stress like
trauma and surgery , so require additional
corticosteroids to cover the stress.

63.  Adrenal insufficiency
 Cushing’s syndrome
 Peptic ulceration
 Osteoporosis
 Hypertension
 Muscle weakness or atrophy
 Inhibition of growth
 Diabetes
 Activation of infection
 Mood changes
 Delay in wound healing
SYSTEMIC SIDE EFFECTS

64. OCULAR SIDE EFFECTS
 Adverse event can occur with all routes of
administration & all preparations currently
available.
 Side effects more with long term high doses
therapy.

65.  Posterior subcapsular cataracts
 Ocular hypertension or glaucoma
 Secondary ocular infection
 Retardation of corneal epithelial healing
 Keratitis
 Corneal thinning or melting
 Scleral thinning
 Uveitis
 Mydriasis
 Ptosis
 Transient ocular discomfort
OCULAR SIDE EFFECT

66. Cataract
 Occurrence of PSCC
with all routes
 High incidence found in
long term systemic
therapy then the topical
therapy
Opacity associated with steroid administration resemble with
those produce by ionizing radiation and ocular disease such as
uveitis , retinitis pigmentosa and retinal detachment

67. Glucocorticoids enter lens fibres
reacts with lens crystallins
conformational change within cells
release of sulfhydryl groups
Form disulfide bonds protein aggregation
CATARACT
Mechanism

68. Mechanism
High blood glucose level
High level of sorbitol
Indrawing of water
Swelling of fibers and disruption of
cytoskeletal structures
cataract

69. mechanism
Corticosteroid induces the production of the new lens fibers
through equatorial region
Which goes and accumulate in posterior sub capsular region
Finally causes cataract

70. Ocular hypertension or glaucoma
 Reversible elevation of pressure with repeated use
of topical steroids.
 Steroid induced glaucoma ; a form of secondary
open-angel glaucoma
Recently developments in corticosteroids are aimed at
developing agents with less IOP effect and agents that
can be used intraocularly and periocularly

71. How steroids increase IOP…..?
GAGs present in the
trabecular meshwork
can not depolimerized
(stabilizing lysosomal
membrane)and they
retain water in
extracellular space
lead to narrowing of
trabecular meshwork
Suppress the
phagocytic activity of
endothelial cells of
trabecular meshwork
leading to collection
of deberies in
trabecular meshwork
Inhibit the
formation of PGE
and PGF leading
to decrease in
aqueous outflow
facility
Obstruction of aqueous outflow

72. IOP elevation in different steroid
 Dexamethasone 0.1% 22.0 +/- 2.9
 Prednisolone 1% 10.0 +/-1.7
 Fluoromethalone 0.1% 6.1 +/-1.4
 Hydrocortisone 0.5% 3.2 +/-1.0
 Tetrahydrotriamcenalone 0.25% 1.8 +/-1.3
 Medrysone 1% 1.0 +/-1.3
Preparation Avreage IOP rise in MM/Hg
Dexamethasone 0.005% 8.2+/-1.7

73.  Individuals differ in their responsiveness:
approximately 4% develop pressures higher than 31
mm Hg after 6 weeks of therapy with topical
dexamethasone
 Steroid- induce IOP elevation almost never occurs in
less than 5 days and rarely in less than 2 weeks
 Steroid-induce IOP rises are usually reversible by
discontinuance of therapy if the drug has not been
used for more than 1 year , but permanent elevations
of pressure are common if the therapy has continued
for 18 months or more 1
1 (armaly MF and becker b . Mills DW ARCH OPHTHALMOL 2003)

74. If IOP rises when we use the steroid ?
1) First stop steroid therapy and may use other anti-
infalmmatory agents like NSAIDs and cyclosporine
2) If IOP persist at higher level then IOP lowering agent
can be used like beta-blocker , carbonic acid
inhibitor but prostaglandin analogue are
contraindicated
3) If IOP remains at higher level then we can move to
other surgical procedure

75. Retardation of corneal epithelial healing
 Effect on collagen
synthesis and
fibroblastic activity
 Persistent epithelial
staining can be noted

76. Corticosteroid induce uveitis
 Pain, photophobia,
blurred vision, and
perilimbal (ciliary)
hyperemia; anterior
chamber cells and flare

77. Mydriasis
Increase in pupillary diameter
approximately 1 mm
Belharoptosis
Due to inhibition of sympathetic
innervation on mular muscle

78. Other ocular side effects
 Transient ocular discomfort
 Calcium deposits on cornea ; (Dry eye develop a
calcific band keratopathy)

79. SOME IMPORTANT FACTS
s Is not s
i.e cotricosteroids are not stored in adrenal gland, they
synthesized from cholesterol in the presence of stimulus
They promote growth of skeletal muscle (anabolic effect) and the
development of male sexual characteristics (androgenic effects)
Drugs used by athletes to boost strength and enhance physical
performance
Anabolic steroid ??

80.  PYRIMON
 BETNOR
 FML
 FML-NEO
 OCUPOL-D
 PRED-FORTE
 OXOP –D
Some topical steroid : Trade name and combination
(Dexamethasone 0.1% + Chloramphenicol 0.1% )
( Betamethasone 0.1% + Neomycin 0.5% )
(Fluromethalone 0.1%)
( Fluromethalone 0.1% + Neomycin 0.5%)
( Each gram contains : Dexamethasone 1 mg +
chloramphenicol 10 mg + polymyxin B sulphate 10000 IU)
(Prednisone acetate 1%)
(Ofloxacin 0.3% + Dexamithasone 0.1% )

81. REFRENCES