Ocular Manifestations of Corticosteroids
Corticosteroids are indicated for management and recovery in many disease processes. From systemic autoimmune diseases to local skin reactions, corticosteroids provide systemic relief by lowering the body’s immune system and inducing anti-inflammatory mediators. However, while corticosteroids provide many benefits, they also can cause some undesirable side effects. Short term use of corticosteroids can induce hypertension, hyperglycemia, pancreatitis, hematologic, immunologic, and neuropsychological effects. The effects of long-term use of corticosteroids are associated with more serious complications such as osteoporosis, aseptic joint necrosis, adrenal insufficiency, gastrointestinal, hyperlipidemia, growth suppression, possible congenital malformation, and ophthalmologic effects. 
In ophthalmology, steroids have a history of being used for the treatment of inflammatory conditions. Topical steroids are generally used to treat anterior segment conditions while posterior segment conditions generally require periocular, intravitreal, or systemic administration for penetration.  Low levels of intraocular inflammation can induce damage to the eye. Classic clinical symptoms of ocular inflammation are erythema, edema, pain, photophobia, and an itchy sensation.  Corticosteroids have become a staple in management of conditions that induce inflammation because if ocular inflammation is left untreated, there is high risk of temporary or permanent vision loss may occur. 
Mechanism of Action
There are two main groups of steroids: corticosteroids (glucocorticoids and mineralocorticoids) and gonadocorticoids (androgen, estrogen and progesterone). In ophthalmology, the majority of steroids are glucocorticoids.  Glucocorticoids mediate anti-inflammatory effects through binding to the glucocorticoid receptor (GR) located in the cytoplasm. Once bound to the GR, the corticosteroid-GR complex travels to the nucleus to modulate the genomic expression of proteins. The corticosteroid-GR complex induces an increase in the expression of anti-inflammatory mediators while also repressing the transcription of proinflammatory proteins. The GR is thought to influence more than 5000 genes which can have profound effects on the body. 
Some of the effects that the corticosteroid-GR complex influence include: suppression of cellular infiltration, capillary dilation, proliferation of fibroblasts, collagen deposition, scar formation, stabilization of intra and extracellular membranes, and increased synthesis of lipocortin. Elevated concentration of lipocortin is particularly important because lipocortin inhibits phospholipase A2 and inhibits histamine synthesis in mast cells. Phospholipase A2 inhibition prevents the conversion of phospholipids to arachidonic acid which is a crucial step in the inflammatory pathway. 
Indications and Uses
Use of corticosteroids in ophthalmology includes but is not limited to:
- Allergic and hypersensitivity reactions
- Scleritis and episcleritis
- Uveal tract inflammation
- Giant-cell arteritis
- Herpes zoster ophthalmicus
- Post-operative medication (glaucoma and cataract surgery)
- Systemic fungal infections
- Intrathecal administration
- Cerebral malaria
- Concomitant live or live attenuated virus vaccination (if using glucocorticoids in immunosuppressive doses)
- Idiopathic thrombocytopenic purpura (IM administration)
- Use in premature infants (formulations containing benzyl alcohol)
- Dermatologic: bacterial, viral, or fungal infection of the mouth or throat (triamcinolone)
- Acute untreated purulent ocular infections, fungal or mycobacterial ocular infections, viral conjunctivitis, or keratitis
Systemic Complications of Corticosteroid Use
- Hematological complications
- Suppressed immunity
- Neuropsychological complications
- Aseptic joint necrosis
- Adrenal insufficiency
- Growth suppression
- Possible congenital malformations
- Ophthalmologic complications
Ophthalmologic Complications of Corticosteroid Use
In glaucoma, there is damage to the optic nerve typically related to an increase in intraocular pressure (IOP). It has been shown that corticosteroids can increase IOP by decreasing the outflow of aqueous humor in the anterior chamber. The decrease in the outflow of aqueous humor is thought to be through the involvement of trabecular meshwork cells and myocilin gene expression. Corticosteroids inhibit the degradation and/or enhance the deposition of extracellular matrix material trabecular meshwork, causing a decrease in aqueous outflow.  Myocilin is a 55-kDa protein that is induced when trabecular meshwork cells are exposed to corticosteroids and has also been linked to decreased outflow of aqueous humor and steroid-induced IOP.  Currently, the risk factors for steroid induced glaucoma are pre-existing primary open angle glaucoma, a history or increased IOP with previous steroid administration, Type 1 diabetes, very young and very old patients. 
Cataract formation is a widely recognized potential complication of corticosteroid use. While the mechanism behind steroid induced cataracts is elusive, the most plausible hypothesis involves non-enzymatic formation of Schiff base intermediates. The Schiff base intermediates are formed between the steroid C-20 ketone group and nucleophilic groups. After the formation of Schiff base intermediates, Heyns rearrangement of the adjacent C-21 hydroxyl group occurs which results in stable anime-substituted adducts.  This hypothesis is popular because the adducts have only been observed in steroid-induced cataracts and not in other subtypes of cataracts.  The type of cataract that is typically steroid-induced is a posterior subcapsular cataract, which is formed in the back of the lens. 
Enhancement of Infectious Disease
Corticosteroids cause a depression in the patient's immune system and inhibit growth factors that are crucial to wound healing. Depression of the patient's immune system can mask the progression of infecting agents. Fungus infections are particularly prone to enhancement when the patient is under steroid-induced immune suppression. The most clinically important and most disastrous effect of steroid-induced immune suppression is the patient's susceptibility to herpetic epithelial keratitis.  Awareness of patients' increased susceptibility to infection should be taken into consideration when administering corticosteroids for patients at risk.
The aim of therapy and treatment with corticosteroids should be to control and/or cure whatever disorder a patient may present. Corticosteroids play an important role in medical practice so it is important physicians are aware of the signs and symptoms of overuse. Since corticosteroids can cause systemic and ocular complications, attempts should be made to find the lowest effective dose.
Patients who are prescribed to long-term steroid use should be referred to an ophthalmologist to monitor any ocular complications. 
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