Corticosteroids are secreted by the adrenal cortex. Adrenocorticotrophic hormone(ACTH) stimulates the adrenal cortex to produce corticosteroids. Types of adrenal cortex-related steroids are glucocorticoids and mineralocorticoids. Corticosteroids have anti-inflammatory and immunosuppressive effects

1. Ocular
steroids
Dr Gauri Sr Shrestha
IOM, TU

2. Background
•Corticosteroids are secreted by
the adrenal cortex.
• Adrenocorticotrophic
hormone(ACTH) stimulates the
adrenal cortex to produce
corticosteroids.
• Types of adrenal cortex-related
steroids
• Glucocorticoids
• Mineralocorticoids
•Have anti-inflammatory and
immunosuppressive effects

3. Hypothalamus-
pituitary-Adrenal
(HPA) axis
CRH = Corticotropin-releasing
hormone
ACTH = Adrenocorticotrophic
hormone

4. Therapeutic
and Adverse
effects of
Glucocorticoids
CNS = central nervous system
Hypothalamus-pituitary-Adrenal
(HPA) axis
Desired therapeutic and adverse effects of glucocorticoids
Desired
therapeutic
effect
Adverse
effect

5. Adverse effects of Glucocorticoids
(additional reading)
• Carbohydrate and Protein Metabolism
• Hyperglycaemia, insulin resistance, protein degradation, loss of
osteoid, thinning of the skin, and lympholysis, Hyperosmolar non-
ketotic coma
• Fat metabolism
• Lipolysis, fat deposit in tissues, moon face, fish mouth, buffalo hump
• hyperlipidemia, centripetal obesity, Cushing’s syndrome
• Calcium metabolism
• Inhibit intestinal absorption, increase renal excretion, and spongy
bones

6. Adverse effects of Glucocorticoids
(additional reading)
• Musculo-Skeletal system
• Muscle wasting, hypo- or hyper-corticism-related weakness, Myopathy,
osteoporosis, vertebral compression fracture
• Central nervous system
• Euphoria, insomnia, anxiety or depression, increased motor activity, psychosis
• Gastrointestinal
• Secretion of gastric acid and pepsin,
• Peptic ulcer, gastric hemorrhage, intestinal perforation, pancreatitis
• Cardiovascular and Renal
• Restrict capillary permeability, and myocardial contractility, maintain the tone
of arterioles
• Na and water retention, hypertension, edema

7. Adverse effects of Glucocorticoids
(additional reading)
• Endocrinal
• Suppression of hypothalamic, pituitary, and adrenal system,
growth failure, secondary amenorrhea
• Inhibition of fibroplasia
• Impaired wound healing, subcutaneous tissue atrophy
• Suppression of immune system
• Secondary bacteria and fungal infection
• Lymphoid tissues
• Enhanced destruction of lymphoid cells

8. Effects of
Mineralocorticoids
(additional reading)
• Enhance Na+
reabsorption in the
distal convoluted
tubules in the kidney
• Causes fluid
retention and
hyperkalemia
Comparison of mineralocorticoids and glucocorticoids

9. Pharmacodynamics
(self-reading)
• Steroids in the blood
• Binds with CBG (corticosteroid binding globulin)
• enters the cell as a free molecule
• intracellular receptor bound to stabilizing protein
• the steroid- receptor complex can enter the nucleus and bind to
glucocorticoid response element-regulate transcription by RNA polymerase
II and associated transcription factors (they are peptides).
• The resulting mRNA is edited and exported to the cytoplasm for the
production of proteins that bring the final hormone response.

10. Pharmacokinetics
(self-reading)
• Absorbs topically, orally, and parenterally.
• Metabolizes in the liver
• Excretes through urine

11. Contraindication (in general)
• Peptic ulcer
• Diabetes mellitus
• Hypertension
• Pregnancy
• Tuberculosis and other infection
• Osteoporosis
• Herpes simplex keratitis
• Psychosis
• Epilepsy
• Congestive heart failure
• Renal failure
• Viral, bacterial and fungal
infections

12. Ocular steroids with commonly used topical
preparations
• Dexamethasone
alcohol (0.1%
solution, 0.05%
eye ointment)
• Betamethasone
0.1%

13. Ocular steroids with commonly used topical
preparations
• Prednisolone acetate
(1% solution)
• Flurometholone HCL
(0.1% solution, least
potent for IOP rise)

14. Arachidonic
acid pathway

15. Anti-inflammatory response of
steroids
• Vasoconstriction and decrease
vascular permeability
• Lysosomal membrane
stabilization
• Decrease degranulation of PMN
cells
• Prevent PMN cell adherence to
vascular endothelium

16. Anti-inflammatory response of steroids
• Suppress lymphocyte
proliferation
• Suppress fibroplasia
• Inhibit macrophage
recruitment and
migration
• Inhibit phospholipase
A2

17. Immunological and antiallergic responses
•Stabilise mast cells and
basophils
•Decrease circulating
eosinophils and monocytes
•Suppress the recruitment of
leukocytes by antigens
•Decrease cell-mediated
immunity
• Inhibit IL-1 and IL-2 formation
• Suppress natural killer cells
• Decrease lymphocyte
production
• Suppress bactericidal activity
of macrophage and monocyte

18. Application of ocular steroids
• Blepharitis, Atopic Dermatitis, Chalazion.
Eyelids
• Allergic conjunctivitis (e.g., hay fever, vernal and atopic),
Viral conjunctivitis (EKC-guarded), Chemical burn,
Cicatricial pemphigoid, Mucocutaneous inflammation
Conjunctiva
• ??? Herpes simplex keratitis, Interstitial keratitis,
Herpes zoster keratitis
Cornea
• Episcleritis, scleritis
Sclera

19. Application of ocular steroids
• Iridocyclitis, posterior uveitis, sympathetic
ophthalmia, pars planitis, endophthalmitis, Vogt-
Koyangi-Harada syndrome
Uvea
• Vasculitis, choroiditis, retinitis, cystoid macular
edema, acute retinal necrosis
Retina
• Optic neuritis, temporal arteritis
Optic Nerve
• Graves orbitopathy, pseudotumor, myositis,
myasthenia gravis
Orbit

20. Application of ocular steroids
• Rheumatoid arthritis with ocular manifestation,
ocular sarcoidosis, Wegener’s granulomatosis,
polyarteritis nodosa, corneal graft rejection
Immune infiltrates
• Highly recommended
Post-operative
inflammation-corneal or
intraocular surgery
• Juvenile xanthogranuloma,
haemangioma
Neoplasm

21. Ocular Adverse effect (summary)
• Cataract (mostly posterior subcapsular)
• Secondary open-angle glaucoma (increase IOP)
• Decrease facility of outflow and changes in ocular rigidity
• Secondary infection (fungal, bacterial and viral)
• Delayed conjunctival and corneal wound healing
• Mydriasis
• Ptosis
• Pseudotumor cerebri ( idiopathic intracranial hypertensin)
• Calcium deposit on the cornea
• Transient ocular discomfort

22. Important Ophthalmic Effects (additional
reading)
• Fibroblast collagen effects:
• Impair fibroblastic and keratocyte activity
• This slows the replacement of collagen and corneal wound healing
• Also slows scar formation
• Disadvantageous during healing of surgical wounds
• Lymphocytic response
• Corticosteroids lyse and destroy lymphocytes
• Never suddenly discontinue corticosteroid as this may induce massive
necrotizing rebound invasion of leukocytes

23. Important Ophthalmic Effects (additional self
reading)
• Neural response
• Increase neural response e.g., retinal sensitivity increases with steroid use
causing supernormal ERG
• Inhibit neovascularisation
• Corneal healing with inhibited vascularisation (non-specific)

24. Thank you