Inflammatory Eye Disease

Question 1

What are 4 anti-inflammatory drugs commonly used in eyecare?

Answer 1

• Phenylephrine:
  o Sympathomimetic
  o In drop form it can be used in differential diagnosis of episcleritis versus scleritis
  o It is not used to treat these conditions
• Ibuprofen:
  o Oral systemic non-steroidal anti-inflammatory (NSAID) drug
  o Eye care practitioners may recommend that patients use systemic NSAIDS to manage mild to moderate pain (e.g. corneal abrasion)
• FML, Maxidex, Pred Forte:
  o These 3 drugs are e.g.s of topical ocular corticosteroids
  o They are often used to control eye inflammation in conditions such as scleritis, anterior uveitis and severe allergic conjunctivitis
• Ocufen:
  o Flurbiprofen is an e.g. of a topical ocular NSAID
  o This type of drug can be used to control inflammation in milder (less severe) cases such as corneal abrasion, episcleritis and post surgically
  o There is a reduced risk of systemic effects versus oral NSAIDS

Question 2

What are sympathomimetics useful for?

Answer 2

• Useful in differential diagnosis of episcleritis versus scleritis
• They are not used to treat inflammatory eye conditions

Question 3

What is the mechanism of action of sympathomimetics?

Answer 3

• Phenylephrine is a direct acting adrenergic alpha receptor agonist
• It does not reduce inflammation but is useful acting upon aplpha receptors that in turn target the walls of BVs, causing contraction of smooth muscle of conjunctival BV walls
  o This contraction results in vasoconstriction and a “white” conjunctiva, reducing conjunctival hyperaemia
• It does not however treat the underlying cause of this hyperaemia

Question 4

What are the clinical uses of sympathomimetics?

Answer 4

• As entry level practitioner, have access to phenylephrine 2.5% and 10%
• Hyperaemia associated with episcleritis will blanch with the instillation of this drop
• If hyperaemia is deeper, affecting scleral vessels (i.e. scleritis) the drops will not have any impact upon the hyperaemia
• There are other key signs & sxs to help with this differential diagnosis & sympathomimetics can aid decision making
• Phenylephrine, as a direct acting sympathomimetic, also has mydriatic properties, innervating iris dilator

Question 5

What are the contraindications of sympathomimetics?

Answer 5

• Contraindicated in a number of cases, primarily due to effect it may have on cardiovascular system if absorbed systemically
• Hypersensitivity
• Sytemic adrenergic effects mean these drugs should not be used in pxs with:
  o Cardiac disease, hypertension, aneurysms, tachycardia
  o Ashtma
  o Thyrotoxicosis
  o Long-standing insulin-dependent diabetes
  o Pxs on MAOIs, tricyclic antidepressants & antihypertensive agents
  o Pxs with closed-angle glaucoma or narrow angles

Question 6

What are the cautions and side-effects of sympathomimetics?

Answer 6

• Due to theoretical side effects upon vasculatures, there are groups who might be more at risk of systemic absorption
• 10% (stronger conc) should be used with caution in elderley and young children as they are at more risk of systemic absorption
• Common less serious side effects are mydriasis and resultant photophobia
• Due to effect on pupul dilator muscle, check anterior chamber angle for risk of angle closure before considering using the drops
  o However, as action solely on pupil dilator and not impacting pupil sphincter, the dilataion effect is weaker and pupil will constrict with light innervation
• If px has dry eye and corneal staining (incomplete epithelial layer), using 10% phenylephrine might result in clouding of cornea temporarily
  Image shows before and after of using phenylephrine 10%. Dramatic effect is temporary until drops are excreted from eye.

Question 7

Describe the inflammatory cascade?

Answer 7

• Cascade first initiated and triggered in response to cell membrane injury
• When cell membranes are altered, their phospholipid content is released and degraded by enzyme Phospholipase A2
• This results in formation of arachidonic acid
• Arachidonic acid is further broken down by cyclo-oxygenase enzyme (of which there are 2 sub-types of enzyme Cox 1 and Cox 2) into prostaglandins (that are all slightly different with varying roles)
  o Some of these prostaglandins can increase vascular permeability, some can attract leukocytes to the targeted/injured area, some can hypersensitise pain receptors to help in response to healing. Other prostaglandins can have opposing/inhibitory effect – this helps regulate & control the tight inflammatory response
• Arachidonic acid is further broken down by lipoxygenase enzyme – this forms a series of very potent chemical mediators known as leukotrienes
  o Different types of leukotrienes that can alter for e.g. permeability, capillary permeability, & this can then result in examples of tissue swelling of both conjunctiva and lids when talk about diseases/injuries occurring with eye

Question 8

Describe mechanism of action of NSAIDs?

Answer 8

• NSAIDs inhibit action of cyclo-oxygenase enzyme
• There are 2 sub-forms:
  o COX-1:
   Involved in normal processes in uninflamed tissues. It regulates stomach acid levels and helps protect the health of the GI tract
  o COX-2:
   Responsible for synthesis of prostaglandins in inflamed tissues
• Ideally an NSAID would be selective against COX-2 enzyme only
  o Unfortunately, many NSAIDs are non-selective
  o Inhibition of COX-1 has potential to cause gastro-intestinal side effects (e.g. nausea, stomach ulcers, peptic bleeding)
• NSAIDs mechanism of action is to inhibit action of cyclo-oxygenase enzyme
  o Even though cyclo-oxygenase enzyme is inhibited and therefore it inhibtis production of prostaglandins, it does NOT prevent formation of leukotrienes via the other pathway
  o Lipooxygenase enzyme is still produced, synthesised from arachidonic acid resulting in leukotrienes being produced and still have some degree of inflammatory mediators being produced

Question 9

What are the clinical uses of systemic NSAIDs?

Answer 9

• Wide range of indications of use of oral NSAIDs
• Eye care practitioners may recommend that pxs use systemic NSAIDs to manage mild to moderate pain (e.g. corneal abrasion)
• 3 major properties:
  o Anti-inflammatory (control inflammatory response)
  o Analgesic (relief from pain)
  o Anti-pyretic (control fever)
• Ibuprofen & aspirin are available as GSL & Pmeds
• Other oral NSAIDs such as naproxen and diclofenac are PoMs & not available for entry level practitioners

Question 10

What are the clinical uses of topical NSAIDs?

Answer 10

• As a more localised tx to affected area, there might be greater therapeutic effect on the area of the eye requiring tx, using NSAIDs in drop form
• Topical txs have advantage of reducing risk of systemic effects & topical NSAIDs have minimal ocular side effects
• Topical ocular NSAIDs are all licensed as PoMs & may be used to treat conditions such as:
  o Corneal abrasion
  o Seasonal allergic conjunctivitis
  o Episcleritis
  o Ocular procedures/surgery

Question 11

What are the contraindications, cautions and side-effects of oral and topical NSAIDs?

Answer 11

• Oral NSAIDs:
  o Not be used by pxs with allergy to aspirin/ibuprofen
  o Avoid in pxs with blood clotting disorders
  o Avoid in pxs with gastro-intestinal problems
  o May exacerbate asthma
  o Always check latest info & updates in BNF
• Topical Ocular NSAIDs:
  o Not to be used if there is a known hypersensitivity to any components in product
  o Use with caution with pxs with blood clotting disorders & with pxs with known hypersensitivity to oral NSAIDs
  o They can impair wound healing
  o Increased risk of keratitis & should be monitored regularly while on tx

Question 12

What are corticosteroids?

Answer 12

• Steroids are hormones which naturally occur within body
• They regulate innate responses (e.g. inflammation, allergy, immune system)
• Corticosteroids are both naturally occurring steroids & synthetic medications which are designed to mimic their action

Question 13

What is the mechanism of action of corticosteroids?

Answer 13

• Inhibit inflammatory response by inhibiting release of phospholipase A2 enzyme
• By doing so, this will inhibit the production of arachidonic acid
• In turn, this will reduce the prostaglandins via cyclo-oxygenase enzyme and the leukotrienes via lipoxygenase enzyme
  o Contrast to NSAIDs which will only inhibit cyclo-oxygenase enzyme & therefore formation of prostaglandins
  o Corticosteroids interrupt this cascade at a much earlier stage than NSAIDs will & therefore will have a much larger effect on the inflammatory response and increased therapeutic effect

Question 14

What are the clinical uses of corticosteroids?

Answer 14

• Corticosteroids have many uses in eye care to control ocular inflammation, reduce the sensation of pain & importantly plays a key role in reducing the risk of ocular tissue damage due to prolonged inflammatory reactions & scarring
• Some e.g.s of ocular conditions corticosteroids are used to treat:
  o Anterior uveitis
  o Severe allergic conjunctivitis
  o Scleritis
  o Cystoid macular oedema
• All corticosteroids used in eyecare are PoMs

Question 15

Describe the dosing & tapering of corticosteroids?

Answer 15

• Dosing strategy is different for corticosteroids versus NSAIDs
  o Initially intensive (e.g. 1 drop every 2hrs for 1st 48 hours) – if inflammation is significant (e.g. uveitis)
  o Reduce to normal therapeutic dose (e.g. QDS or BDS) – depending on severity of condition & depending on how px has responded to the tx
  o Abrupt cessation may cause rebound effect – communicate this to px
  o ‘Taper’ dose gradually over number of weeks – write on record card
   If px taking drops 8 times a day for week, then drop to 7 times a day for week, 6 a day for a week etc – can be on the steroids for long period of time until the eye is COMPLETELY quiet (wouldn’t stop the drops until have a completely white & quiet looking eye with no sxs)
   Balance of tapering versus risks associated with prolonged use
• Prolonged use of steroids increases risk of complications can occur
  o Particularly in pxs who have recurrent inflammation (recurrent uveitis – not taking drugs in one off scenario – may be taking drugs 3 or 4 times a year for extended period of time)
• Tapering is a slow reduction in dosing over time so there is no rebound effect

Question 16

What corticosteroid products are available?

Answer 16

• Steroids can be described by their potency & there are various products available in eye drop form with different potencies
• All steroids currently not available as PoM on exemption list as entry level optom – or part of px group directive where steroid is listed as one of the drugs available to treat certain inflammatory eye conditions
• Softer steroids, not as potent as other steroids – tend to be used for more superficial conditions (e.g. chronic dry eye where there is an inflammatory component that is causing the px severe discomfort/inflammation, Px with episcleritis, where non-pharmacological management options are not being effective, IP optom may use FML to reduce inflammatory response):
  o Fluoromethalone
  o Betamethasone
  o Loteprednol
• More potent steroids:
  o Prednisolone
  o Dexamethasone
   These drugs are usually used in conditions that are affecting tissue deeper in the eye like uvea such as uveitis
   Some can also be found in combination with antibiotics which can be used post-surgery – as a prophylactic anti-biotic effect as well as reducing the inflammation at same time

Question 17

What are the contraindications of corticosteroids?

Answer 17

• Steroids suppress immune system & reduce body’s ability to fight infection
• It is therefor important to be confident & sure about your diagnosis before commencing steroid tx
• If an acute infectious keratitis is present (bacterial or viral for e.g.) a steroid might exacerbate the condition v quickly
  o Initial use of steroids in these cases is contraindicated BUT delayed use (after acute stage treated with an anti-infective drug) may improve long-term prognosis & reduce scarring as result of corneal ulceration

Question 18

Describe adverse drug reactions (ADRs) of corticosteroids?

Answer 18

• Some serious side effects that can cause harm to ocular tissue is classed as ADRs here
• Corticosteroids are known to cause a number of long term effects to the eye
• Rise in IOP  sustained increased IOP can result in steroid glaucoma
  o Can occur in 18-36% of pxs who use steroids as part of their tx
  o Does not seem to be associated with the type of steroid that is used – but research suggests association with more potent steroids but can occur in softer steroids too
  o Much more likely to occur in prolonged dosing & higher frequency observed in glaucoma suspects
  o Mechanism of action that results in increased IOP is not fully understood – think steroid alters trab meshwork itself so outflow is reduced due to deposits of the drug in the matrix of the trab meshwork
• Significant rise in IOP in pxs are known as ‘steroid responders’ if they have this occur
  o Measure IOP at baseline and every 2-4 weeks
  o IOP typically returns to normal level 1-2 weeks after cessation of tx
   Problem occurs for pxs who need to continue the tx despite the rise in IOP
• In those pxs who have a chronic inflammatory condition that requires that steroid, they may also be put on IOP lowering drugs such as glaucoma drugs that will help keep the IOP at a safe level
• Steroid cataract (posterior sub-capsular cataract)
  o Not just eye drop form, can be inhaler or oral medication form
   Any absorption of steroid into body can result in steroid cataract
• Delayed corneal healing – enhanced immunosuppression
• Peripheral corneal thinning – if used over long period of time
• Central serous retinopathy (CSR) – problems at macula – fluid build up

Question 19

What is episcleritis - including signs and symptoms?

Answer 19

• Idiopathic inflammation of vascular connective tissue sheath between sclera & conjunctiva
• Can be subcategorised as diffuse & nodular
  o LEFT IMAGE- Diffuse: diffuse hyperaemia, conjunctiva appears flat with no evidence of a nodule present
  o RIGHT IMAGE- Nodular: central button of hyperaemia that appears raised. Nodular episcleritis is characterised by a discrete, elevated area of inflamed episcleral tissue
• Sxs:
  o Acute onset
  o Majority are unilateral
  o Painless
  o Mild irritation/ache/discomfort/tender
  o Can be recurrent
• Signs:
  o Hyperaemia; sectoral or diffuse
  o Nodule (~20%) within area of hyperaemia
  o VA unaffected in all types of episcleritis
  o No other signs of inflammation

Question 20

What is the management of episcleritis?

Answer 20

• Depends upon severity of initial presentation and length of time px has been experiencing sxs
• Vast majority of cases of episcleritis are self-limiting and don’t actually require pharmacological tx
• Would offer same advice if entry-level or IP:
  o Condition self-limiting 7-10days
  o Reassurance & advice to return if persists or worsens
   Cold compress to try and alleviate redness
   Offer artificial tear prn if discomfort – something more viscous like a gel where there is increased contact time, specifically if nodule present
• Wouldn’t normally require preservative free since condition is not chronic and only taking drops for short period of time – unless px has hypersensitivity
• If sxs persisting after 1 week, consider use of soft steroid
  o Steroids cannot be used or supplied by entry level optoms
  o Often optoms in community who are not IP qualified will liaise with GP to arrange an Rx for the soft steroid with agreement that you will follow px up appropriately
   Or if IP optom works in your practice can liaise with them
  o Usually 7-14 day course soft steroid
  o Soft steroids cannot penetrate further into the eye & used as they are least potent and decreasing risk of ADRs
• If sxs persisting after 1-2weeks:
  o Would want to refer px as if they may not have correct diagnosis, may require increased dosing and may want them investigated for systemic causes if recurring
• Only difference in the management is that the IP Optom can write the Rx for the 7-day course of steroids

Question 21

What are the top tips in prescribing steroids?

Answer 21

• 1. Check IOP before commencing tx
• 2. If tx is longer than 1 week, review IOP every 1-2 weeks
• 3. Consider tapering of the dose if the inflammation is severe or if a more potent steroid has been used
     There are other tx options for episcleritis outlined in the literature.
     Systemic NSAIDs may be beneficial and could be considered when steroids are contraindicated.
     Topical ocular NSAIDs – evidence is weak to support their use.

Question 22

What is scleritis and what are the types?

Answer 22

• Severe inflammatory disease of sclera
• Anterior scleritis represents around 90% of cases while much rarer posterior scleritis represents 10% of cases. They are however not mutually exclusive
• Aetiology can be idiopathic or linked to systemic inflammatory disease
• Distinct categories based on key clinical signs:
  o Anterior scleritis:
   Non-necrotising (75%)
• Diffuse (60%)
• Nodular (40%)
   Necrotising (15%)
• With inflammation
• Without inflammation
  o Posterior scleritis (10%)

Question 23

What are the symptoms of scleritis?

Answer 23

• Pain is key indicator of more severe inflammation involving deeper structures of eye
  o Pain described in scleritis tends to be around eye & forehead
  o Some pxs describe is as an ache type sensation on brow or even spreading to jaw
  o This pain can be intense despite no severe clinical signs matching the presenting sxs
  o Pain may be worse on eye movement
• Can be unilateral or bilateral
• Often gradual onset
• Eye will likely be red – but not always
• Px might described blurred vision in affected eye
• Photophobia might be present particularly if the anterior chamber is involved
• The px may well have a previous hx of episodes – take a detailed hx & call HES for info if required

Question 24

What are the signs of scleritis?

Answer 24

• Non-necrotising anterior scleritis may present as diffuse (without a module) or with a fixed nodule not moveable with manipulation
• Hyperaemia WILL NOT blanch with phenylephrine & will appear a richer & darker colour
• There may be anterior chamber activity present
• Necrotising anterior scleritis may present with OR without inflammation
  o There may be avascular dark blue-grey patches present (see lower image)
  o The patches may appear in absence of hyperaemia & pxs can be surprisingly asymptomatic in these cases initially
• If posterior pole involved there may be signs of inflammation in vitreous, retinal oedema or even detachment
• It is therefore critical to always assess the posterior segment

Question 25

What is the management of scleritis?

Answer 25

• Due to severe nature of scleritis, management is same regardless of prescribing qualifications
• Always ensure perform dilated fundus exam in both eyes and looked as you can in the posterior pole to check peripheral retina & vitreous to ensure there are no posterior complications from the anterior presentation
• Might suggest oral analgesic (e.g. aspirin, ibuprofen or paracetamol – taking into account cautions/contraindications) as 1st aid measure
• Call HES & arrange same day referral – letter in hand to px
  o Px requires topical & systemic anti-inflammatory tx (steroids often – to try & reduce risk of sight loss)
  o May also require immunosuppressants
  o Depending upon the recurrence and severity of condition & general health – they may be investigated for systemic associations such as rheumatoid arthritis

Question 26

What is uveitis and what are the three types?

Answer 26

• Inflammation of uvea & subdivided based upon structures affected; anterior, intermediate, posterior, panuveitis
  Anterior Uveitis:
• Inflammation of iris & anterior ciliary body
• Most common (75% of cases)
• Aetiology can be idiopathic, due to systemic disease or prior infection
  Intermediate Uveitis:
• Inflammation of posterior ciliary body, anterior vitreous & peripheral choroid/retina
  Posterior Uveitis:
• Inflammation of vitreous, choroid & retina

Question 27

What are the symptoms of anterior uveitis?

Answer 27

• Acute onset (less acute, more gradual with subsequent episodes)
• Unilateral (bilateral is less common = chronic)
• Pain – dull ache
• Photophobia
• Redness
• Blurred vision
• Lacrimation
  o In recurrent cases, there are less sxs (px does not always present with severe & acute sxs & they can be more subtle)

Question 28

What are the signs of anterior uveitis?

Answer 28

• Circumlimbal injection:
  o Perilimbal and episcleral injection associated with acute anterior uveitis
• Hypopyon:
  o Uncommon and mostly associated with very severe AC involvement where white blood cells collected and coalesced so much in AC that they have sunk to the bottom
• Posterior synechiae:
  o These adhesions occur between anterior lens surface and iris that can be seen (between 12 and 9 o’clock)
• Anterior chamber cells and flare:
  o Examination of AC is really important and critical for any acute red eye presentation – observe AC with high mag, while directing a very small beam of light obliquely into aqueous (conical beam technique)
  o The AC cells &/or flare are visible using the Tindal effect of the bright beam scattering the light
  o Useful to grade the number of cells and flare using the SUN grading scales
   Can help assess severity of anterior uveitis & assess the prognosis and progression over time when review the px
• Keratic Precipitates – Fine:
  o Deposited on corneal endothelium. Hallmark sign of non-granulomatous anterior uveitis are small discrete fine KPs scattered across the endothelium
• Keratic Precipitates – Mutton Fat:
  o Much larger KPs – much more suspicious of granulomatous uveitis – where there may be an underlying aetiology possibly autoimmune disease or systemic condition associated with this presentation
• Iris nodules – Koeppe:
  o Small nodules found around the margin between the pupil and the iris – suggestive of granulomatous uveitis
• Iris nodules – Bussacca:
  o Another type of nodule on surface of iris mid-peripherally – also suggests granulomatous uveitis

Question 29

What would make you suspicious that there was systemic involvement in anterior uveitis?

Answer 29

• Bilateral presentation
• Mutton fat KPs
• Retinal inflammation indicated on OCT scans
• Vitreous inflammation present
• Other general health problems
• Recurrent episodes

Question 30

What are the symptoms and signs of intermediate uveitis?

Answer 30

• Sxs:
  o Gradual (days) blurred vision
  o Floaters
  o Absence of pain & redness
• Signs:
  o Reduced VA – will not improve with Pinhole
  o Vitritis (cells in vitreous) – can be difficult to view retina (can become hazy)
  o Snowballs – inflammatory material in vitreous that looks white and fluffy – as these collect and coalesce with gravity they sink down and cause large coalesced plaques in the inferior vitreous which is known as snowbanking
  o Snowbanking – see above

Question 31

What are the symptoms and signs of posterior uveitis?

Answer 31

• Sxs:
  o Gradual (days) blurred vision
  o Floaters
  o Absence of pain & redness
• Signs:
  o Reduced VA
  o Vitritis
  o Snowballs
  o Snowbanking
  o Choroiditis – white or yellowy fuzzy deposits with indistinct edges (when disease is active) due to inflammation of choroid
  o Retinitis - white or yellowy fuzzy deposits with indistinct edges (when disease is active) due to inflammation of retina – inflammatory areas tend to be a bit more see through/translucent than those in choroid
  o Vasculitis – white fluffy margin around retinal arteries and veins in patches
  o CMO

Question 32

What is the management of anterior uveitis?

Answer 32

• Ensure you have performed a detailed examination
• When more severe inflammation is suspected & uveitis or scleritis are being strongly considered as your differential diagnosis, you should ensure you do following:
  o 1. Always assess BEs – bilateral disease (can be asymmetric) increases likelihood of systemic involvement
  o 2. Perform a dilated fundus exam BEs to exclude vitreous, choroid or retinal involvement
  o 3. Assess cornea in detail to exclude herpetic disease or infection – corticosteroids used in isolation may exacerbate these conditions very quickly
  o 4. Check IOP
  o 5. Immobilise iris & ciliary body – reduce pain & break synechiae (cycloplegic – cyclopentolate 1%)
• Offer advice to px:
  o 1. Explain diagnosis
  o 2. Advise sunglasses for photophobia
  o 3. Spectacles near addition for cycloplegia
  o 4. Warn pxs of possible recurrence & educate on early sxs of recurrence
   This convo tends to be save for during follow up appts (IP Optom more commonly)
• Entry Level Optoms:
  o If 1st ep, unilateral, no known systemic aetiology (hx & investigations), no posterior involvement – liaise with GP or IP Optom to manage in community
  Check IOP at baseline – before starting any therapy
  If the px returns after 2 days and there is rise in IOP or there is posterior synechiae or no improvement in sxs then refer emergency to HES
  Will get used to tapering & how long to leave px as see more pxs
  If at any point there are any red flags or start to get suspicious of any signs seen on SL, any posterior involvement – call HES for advice & probably arrange to get them seen that same day

Question 33

What is the management of anterior uveitis on 2nd or subsequent episode?

Answer 33

• If 1st ep resolved well with no complications and eye was quiet and no red flags
  o Then would refer as above – may be to IP optom
• May want to initiate tx but may want to consider referring them into HES for further investigation of underlying cause of their recurrent anterior uveitis
• Need to check the referral criteria for local health board surrounding anterior uveitis
  o In some health boards it may be 3 eps of uveitis before they want to follow them up with investigations – in others it may be 2 eps
• IOP should be monitored frequently during use

More complex cases should always be referred to HES