Uveitis is characterised by inflammation of the uveal tract, which comprises the iris, ciliary body and choroid.1,2 It can be classified based on the predominant anatomical site of inflammation into variously anterior, intermediate, posterior or panuveitis.1,3,4 A prevalence of 115 uveitis cases per 100,000 persons has been reported.5
Anterior uveitis (AU) accounts for 60-90 per cent of reported uveitis episodes, making it the most common type.6 Highlighting the potential severity of the disease is the fact that uveitis accounts for 10-15 per cent of visual disability in working-age persons.7
AU can be acute (sudden onset and limited), chronic (relapse in less than three months of treatment) or recurrent (repeated episodes; inactive periods on or after three months of treatment).3 Of these, acute anterior uveitis (AAU) is the most common form.6 AAU is a frequent cause of a unilateral red eye with presenting symptoms of photophobia, lacrimation, possible blurring of vision and a dull ocular pain enriched by accommodative effort.1,2,6,8,9 Signs vary depending on the degree of inflammation and are listed in Table 1.
Table 1. Acute anterior uveitis clinical signs
AU aetiology may be infectious, autoimmune, malignant, traumatic or idiopathic.1,2,4,6 Approximately 50 per cent of AU cases have an idiopathic mechanism, which forms the most common aetiology.5,6 The propensity for AAU to have an immune origin is reflected in the high occurrence of systemic conditions among AAU sufferers.10,11
Both genetic predisposition and environmental factors are thought to be involved in AAU pathogenesis.12
The goals of AAU treatment are to provide symptomatic relief, promptly eliminate inflammation and prevent the development of sight-threatening ocular sequelae.6,9 This is typically achieved by use of a topical corticosteroid and cycloplegic/mydriatic agent;6,12 however, it is imperative to rule out an infectious or neoplastic cause, as corticosteroid therapy may have deleterious effects in such cases.12
A 56-year-old Caucasian male presented to a rural optometry practice with a five-day history of an irritated, sore and red left eye. He had no significant ocular history, no general health issues and was not taking any systemic medications. The patient denied back pain, joint pain or bowel issues and was unaware of his HLA-B27 status.
INITIAL PRESENTATION DAY 1
The patient’s BCVA was OD 6/6, OS 6/9.5. His intraocular pressure (IOP) at 1:00 pm was OD 21 mmHg and OS 16 mmHg. A slitlamp examination of his left eye revealed moderate circumlimbal injection and moderate to severe diffuse bulbar conjunctival hyperaemia (Efron Grading Scale), Grade 4+ anterior chamber cells and 1+ anterior chamber flare, as per SUN grading.3
The pupil margin was irregular and demonstrated posterior synechiae at 2-3 and 7-10 o’clock. A few non-granulomatous keratic precipitates were present. The anterior chamber angles were open on Van Herick OU and no corneal NaFl staining was present. No discharge, hypopyon, iris nodules or iris trans-illumination defects were noted. Slitlamp examination of the right eye was unremarkable. No posterior involvement was observed on dilated fundus examination.
Given the presentation of an acute, unilateral, sore and red left eye and clinical findings of anterior chamber cells and flare, circumlimbal injection, posterior synechiae and reduced OS IOP, a diagnosis of OS AAU was provided. Because the patient had no systemic symptoms (back or joint pain, bowel issues, skin rashes), no known systemic conditions, his HLA-B27 status was unknown, and he reported no history or signs suggestive of an infectious cause, an idiopathic mechanism was presumed.
The patient was prescribed Prednefrin Forte eye-drops (prednisolone acetate 1%, phenylephrine 0.12% suspension); loading dose every 20 minutes for one hour, then every 30 minutes for four hours, then every hour during waking hours. As well, he was prescribed Isopto Homatropine 2% every 30 minutes for first hour, then four times a day and one drop phenylephrine 2.5%.
After one hour of therapy, the 7-10 o’clock posterior synechiae had broken (Figure 1). The patient’s condition was scheduled to be reviewed on the following day.
Figure 1. OS anterior eye, demonstrating circumlimbal injection, posterior synechiae at 2-3 o’clock and resolved posterior synechiae at 7-10 o’clock
• AAU of infectious origin, such as herpetic uveitis (herpes simplex virus or varicella zoster virus. However, IOP was not raised, iris transillumination defects were absent, there was no previous history of an ocular infection and no skin rashes or vesicles were present. Reconsider if worsening with therapy.
• HLA-B27-associated AAU, given that the patient was male and the AAU demonstrated significant anterior chamber cells and flare. However, HLA-B27 status was unknown, there was no known underling seronegative spondyloarthropathy, no symptoms suggestive of back or joint pain, or skin rashes or plaques, and no history of a previous AAU attack.
• Microbial keratitis, due to the unilateral red eye and anterior chamber reaction. However, no epithelial defect or corneal ulcer, infiltrate, hypopyon or mucopurulent discharge was present and there was no associated contact lens wear or other predisposing factor(s).
• Acute angle closure, given the acute unilateral red eye, circumlimbal injection and posterior synechiae. However, IOP in the affected eye was reduced.
• Scleritis, due to the symptom of ocular pain, vascular congestion and the anterior chamber reaction. However, the vascular injection was superficial and lacked a violaceous hue, IOP was reduced and there was no history or symptoms suggestive of a systemic connective tissue disease.
OS REVIEW, DAY 2
The patient reported symptomatic improvement. His IOP was OD 20 mmHg and OS 23 mmHg. The patient had a slight reduction in OS circumlimbal injection and bulbar conjunctival hyperaemia, resolution of the 2-3 o’clock posterior synechiae, reduction in anterior chamber cells to Grade 3+ and resolution of the fibrin (Grade 0) (SUN grading).3 There was no posterior involvement.
The patient was prescribed Prednefrin Forte 1% every hour until the end of day, then reduced to every two hours as well as Homatropine 2% four times a day. The patient was scheduled for review in two days.
OS REVIEW, DAY 4
On the four-day follow-up, the patient’s IOP was: OD 20 mmHg and OS 27 mmHg. There was a resolution of OS ciliary injection and bulbar conjunctival hyperaemia, Grade 1+ anterior chamber cells, Grade 0 fibrin (SUN grading).3 There was no posterior involvement.
The patient was prescribed Prednefrin Forte 1% every three hours, Homatropine 2% four times a day until end of day, then cease. If IOP reached 30 mmHg, add a topical ocular hypotensive agent. The patient was scheduled for review in two days.
OS REVIEW, DAY 6
On the six-day follow-up, the patient’s BCVA: was OD 6/6; OS 6/7.5; IOP was: OD 19 mmHg; OS 20 mmHg (non-contact tonometer) and OS grade 0.5+ anterior chamber cells, Grade 0 fibrin (SUN grading).3
The patient was prescribed Prednefrin Forte 1% four times a day, and scheduled for review in one week.
Corticosteroids in AAU treatment
As AAU is an inflammatory process for which the mainstay of treatment is topical corticosteroids.6,13,15 Corticosteroids increase the synthesis of lipocortins, which inhibit phospholipase A2. This prevents the production of arachidonic acid from phospholipids. Consequently, there is inhibition of both the cyclo-oxygenase and the lipoxygenase pathways and ultimately, the inflammatory cascade.9,16
Corticosteroid efficacy in AAU is based on its corneal penetration and anterior chamber potency.6 This depends on the chemical composition of the corticosteroid and the dosing frequency.6 The corneal epithelium is lipoidal and provides the greatest barrier to drug penetration.15,17 Therefore, hydrophilic derivatives (prednisolone phosphate) are significantly retarded in comparison to lipophilic derivatives (dexmethasnone alcohol and prednisolone acetate).18
Essentially, all data relating to corticosteroid efficacy in anterior segment inflammation are extrapolated from its corneal effects.14 It can be seen in Table 2 that among the topical corticosteroids available to Australian optometrists with a scheduled medicines endorsement, prednisolone acetate 1% yields the greatest corneal anti-inflammatory effect.
Table 2. Reduction in corneal inflammation and comparison of human aqueous humour concentration of corticosteroids following topical application
Both prednisolone acetate and dexamethasone alcohol demonstrate sufficient aqueous penetration and therefore are appropriate agents to be used for AAU treatment (Table 2).15 It can be seen that prednisolone acetate 1% achieves the highest concentration in the anterior chamber.15 This is attributable to its high corneal penetration. Indeed, prednisolone acetate is from 3.5 to six times more potent than dexamethasone in the anterior chamber.14 Furthermore, Prednefrin Forte also contains 0.12% phenylephrine, which is an alpha adrenoreceptor agonist.20 Therefore, it can cause vasoconstriction by stimulating alpha adrenoreceptors on the conjunctival blood vessels, thereby blanching these vessels to improve cosmesis in AAU.
The frequency of corticosteroid administration depends on the degree of inflammation, with higher drop instillation frequency demonstrating greater anti-inflammatory activity. A ‘loading dose’ was implemented in the reported case to achieve a therapeutic concentration quicker. This is sometimes recommended;21 however, more frequent dosing can increase the rate of significant IOP increase.22-25
The patient’s OS IOP spiked to 27 mmHg at the second review. This IOP spike could be a result of the inflammation or it could be corticosteroid-induced (see ‘AAU sequelae’ below). Corticosteroids can raise IOP by increasing aqueous outflow resistance and consequently, can lead to secondary OAG.13,15,26 However, corticosteroid-induced IOP rise typically occurs after two to eight weeks of steroid use.19 Given the spike occurred after only three days of corticosteroid use, in addition to the fact that IOP subsequently reduced at the following review, an inflammatory mechanism was most likely (see ‘AAU ocular sequelae’ below).
Cycloplegic/mydriatic agents in AAU
Cycloplegic/mydriatic agents are cholinergic antagonists. The goals of cycloplegic/mydriatic use are to provide symptomatic relief and photophobia by immobilising the inflamed iris and ciliary body.6,12,29 They are also used to break previously-formed posterior synechiae, prevent future posterior synechiae from forming and to stabilise the blood aqueous barrier.6,12,19 Potential agents include atropine, homatropine, cyclopentolate and tropicamide.9,12,28
Phenylephrine is an alpha 1-adrenergic agonist that binds alpha 1-adrenergic receptors on the iris dilator muscle to cause mydriasis.20 It may be used in the acute phase to exert a synergistic effect with an anti-cholinergic agent to cause maximal pupillary dilation in order to break existing posterior synechiae.9
It is thought that to reduce the risk of synechiae formation in the fixed dilated pupil position, a shorter-acting anti-cholinergic agent is preferred to allow a degree of pupil mobility.2,29 Homatropine encompasses the most desirable effects. It has a duration of mydriasis and cycloplegia from five hours to four days, and from 10 hours to two days, respectively.19,28 Recently, homatropine was discontinued. This calls for use of an alternative agent. Cyclopentolate has been reported to induce a chemokinetic neutrophil response and therefore is not recommended in active inflammatory processes.6,30 Given this, along with its short duration of action (mydriasis: one day, cycloplegia: six to 24 hours), atropine appears to be the next best candidate for future AAU management.28
Cycloplegic agents may be withdrawn when flare is absent, minimal cellular reaction is present, and a low risk of synechiae forming exists.6,9 This is documented to be typically within two weeks; however, the reported case showed a much shorter duration.6
AAU ocular sequelae
With appropriate treatment, the prognosis of AAU is favourable.6
The most common sequelae are posterior synechiae, secondary cataract, cystoid macular oedema (CMO), peripheral anterior synechiae (PAS), ocular hypertension, secondary glaucoma, band keratopathy, epiretinal membrane formation, hypotony and most devastatingly, phthisis bulbi.1,2,6,7
Many mechanisms exist for inducing ocular hypertension in AAU. These include trabeculitis, trabeculosclerosis, inflammatory cellular/debris accumulation in the trabecular meshwork, PAS, posterior synechiae, or corticosteroids.
It is important to monitor and treat any significantly elevated IOP. The risk of glaucomatous damage and other complications, such as retinal vein occlusion, increases at higher IOPs.3,32,33 Practitioners in the SUN working group suggest an IOP above 30 mmHg warrants initiation of hypotensive therapy.3 Topical hypotensive agents aiming to reduce aqueous production are typically used.6 Beta-adrenoreceptor antagonists, alpha 2-adrenoreceptor agonists and topical carbonic anhydrase inhibitors are alternative options.6 Prostaglandin analogues pose a theoretical risk of amplifying inflammation and therefore, should typically be avoided.6 Likewise, miotics should be used with caution as they may exacerbate blood-aqueous barrier breakdown and increase the risk of inducing posterior synechiae in the miosed position.6,19
HLA-B27 typing in AAU
HLA-B27 is present in approximately 50 per cent of AAU patients.1,33,34 It also significantly increases the chance of developing a seronegative spondyloarthropathy.34 It has been suggested that an undiagnosed spondyloarthropathy could be overlooked in about 40 per cent of patients if only recurrent AAU cases are provided onward referral.33 Therefore, key questioning regarding HLA-B27 typing, back or joint pain, and skin rashes was appropriate to determine if onward referral was required.
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