Anti-inflammatory Eye Preparations

There are four broad categories of ophthalmic anti-inflammatory preparations:

• Corticosteroids
• Anti-histamines
• Mast cell stabilisers
• Non-steroidal anti-inflammatories (NSAIDs)

In the primary care setting, topical agents are most commonly used, with the marked exception of suspected giant cell arteritis (GCA) where systemic steroids may need to be initiated promptly prior to urgent specialist review. Common conditions warranting anti-inflammatory treatment include allergic conjunctivitis and hypersensitivity reactions. These drugs are also very commonly used in specialist units to treat a very wide range of conditions. These include uveitis, cystoid macular oedema, scleritis and episcleritis, certain cases of herpes simplex keratitis, during and after surgical procedures and in the early stages of thyroid eye disease.¹

Overview¹

• Examples - betamethasone, dexamethasone, fluoromethalone, hydrocortisone acetate, prednisolone, rimexolone
• Use - short term treatment of local inflammation
• Action² - decrease number and function of inflammatory cells, increase vascular permeability and inhibit chemical mediators of inflammation
• Contraindications - undiagnosed red eye
• Caution - prescription and monitoring needs to be done in a specialist unit
• Administration - largely depends on the condition: may be as frequent as every 30 minutes in severe inflammatory states. There is then a gradual reduction over time (again, depends on condition) according to symptoms and clinical findings. Period of reduction may be weeks or even months, with a small minority of patients being kept on very low doses of weak steroids for extended periods of time (years) to prevent recurrence.
• Ocular side-effects - rise in intraocular pressure (may be insidious or rapid: "steroid responders"), cataract formation in long-term use, corneal thinning, delay in corneal healing, increased susceptibility to microbial infections and a paradoxical uveitis.
• Systemic side-effects - theoretical but be aware of susceptible individuals (pregnancy, peptic ulcer disease, tuberculosis, active infection, psychosis).
• Additional information - a number of topical corticosteroid drops are available in combination with anti-microbials but such prescriptions are not recommended in the primary care setting. In severe inflammatory states, a local injection of steroids around the globe can be performed by ophthalmologists.

Corticosteroids available in ointment form

• Examples - betnesol and hydrocortisone acetate
• Use - atopic conditions involving the peri-ocular skin, can be used as a substitute for night time steroid drop application in some cases and where there is difficulty in applying drops (e.g. due to arthritic hands).

Corticosteroids available in minims®

Dexamethasone comes in this form and is used where there is preservative toxicity.

• It is unusual to treat ocular conditions with systemic steroids but there are some exceptions such the case of rheumatoid arthritis related corneal melt (where the cornea thins to the point of perforation) and that of GCA. Primary care practitioners will normally only be involved in initial management of the latter.
• A patient aged less than 55 years is extremely unlikely to have GCA; risk factors are outlined below:

• All GCA suspects need urgent ESR/plasma viscosity and CRP: a normal CRP virtually excludes GCA, even in the presence of an elevated ESR or plasma viscosity.
• Prednisolone is the standard steroid of choice for the treatment of GCA.
• Contraindications include peptic ulcer disease, tuberculosis, active infection, psychosis and pregnancy (unusual in this age category): liaise urgently with the ophthalmology / rheumatology teams if these conditions are present.
• Prior to commencing, check full blood count, urea and electrolytes, glucose, pregnancy test and chest X ray.
• Side-effects include: hyperglycaemia, hypokalaemia, hypertension, peptic ulcer, mental state change, osteoporosis, decreased wound healing, pseudotumour cerebri as well as a number of other effects.
• Treatment should be initiated as follows with referral to ophthalmologists (in the presence of visual symptoms) or vascular surgeons / rheumatologists (in the absence of visual symptoms):

• Starting steroid therapy does not affect the likelihood of a positive biopsy if the biopsy is performed within 10 days.
• Tapering of steroids should be guided by inflammatory markers rather than by clinical symptoms / signs.

• Examples - antazoline sulphate, azelastine hydrochloride, emedastine, epinastine hydrochloride, ketotifen, levocabastine (withdrawn)
• Use⁴ - allergic conjunctivitis, seasonal and perennial conjunctivitis
• Action - they inhibit histamine-mediated inflammatory responses
• Caution - some agents are not licensed for young children, there can be rebound vasodilation after prolonged use,⁵ severe renal impairment, pregnancy and breast-feeding
• Administration - most preparations twice daily until cessation of symptoms
• Ocular side-effects - local irritation and stinging possible, visual disturbances, keratitis, oedema, photophobia, pruritis
• Systemic side-effects - (rare): headache, drowsiness and dry mouth reported
• Additional information⁴ - these drugs act quickly but consider oral anti-histamines if symptoms severe or not limited to the eye. May be used concurrently with mast cell stabiliser (ketotifen has mast cell stabilizing properties too). Anatazoline preparations are available over the counter.⁶

• Examples - lodoxamide, nedocromil sodium, olopatadine, sodium cromoglicate (cromoglycate)
• Use⁴ - allergic, seasonal and vernal conjunctivitis
• Action² - stabilise mast cell membranes, therefore these drugs have a more prophylactic role as they are administered before mast cell priming with IgE and allergens.
• Caution - some agents not licensed for young children, pregnancy and breast-feeding
• Contra-indication - soft contact lens wear⁷
• Administration - most preparations are applied four times daily for a maximum of 12-16 weeks
• Ocular side-effects - transient local irritation and stinging possible, dry eye and localised oedema
• Systemic side-effects - headache, dizziness and taste disturbance
• Additional information - may be used concurrently with anti-histamines. Sodium cromoglicate preparations are available over the counter.⁶

• Examples - diclofenac, ketorolac, flurbiprofen
• Use - post operative inflammation in cataract surgery, pain after accidental or surgical corneal trauma. Diclofenac also has a role in seasonal allergic conjunctivitis.
• Action² - inhibit the synthesis of eicosanoids (prostaglandins, thromboxanes and leukotrienes)
• Caution - some agents not licensed for young children, rebound vasodilation after prolonged use,⁵ pregnancy and breast-feeding
• Administration - most preparations twice daily until cessation of symptoms
• Ocular side-effects - local irritation and stinging possible
• Systemic side-effects - none reported for topical drugs

• Rule out worrying causes of a red eye
• Prescribe mast cell stabiliser for prophylaxis
• Prescribe anti-histamine drops for acute relief of symptoms (possibly systemic anti-histamines if nose and sinuses affected too).
• Cool compresses over the eyes can also help with symptom relief
• Advise to return to the surgery should symptoms not respond or worsen