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HomemieyecareManaging Chronic Uveitis in a Steroid Responder

Managing Chronic Uveitis in a Steroid Responder

Key Learning Points

  1. Patients with uveitis who are at higher risk of developing CMO should be monitored more frequently. Risk factors include diabetes, vitreomacular pathology (e.g., ERM), previous uveitis, previous retinal vein occlusion, and complicated cataract surgery.
  2. Additional ocular manifestations at the posterior segment include ERM, choroidal neovascular membrane (CNVM), retinal vasculitis, vitritis, and glaucoma.
  3. Exclude a specific cause of uveitis by conducting a thorough history with targeted uveitis systems review, physical exam for systemic features, and investigations including OCT, intraocular and periocular signs and possibly FFA.
  4. Performing an OCT is crucial in identifying and monitoring uveitic CMO.
  5. Most cases of uveitic CMO respond well with time. Use a stepwise treatment approach to management and carefully monitor symptoms, IOP, VA, OCT and possibly FFA. Document signs of uveitis (e.g., AC cells, flare, keratic precipitates, hypopyon, vitritis, CMO, vasculitis).
  6. Start with conservative management (intense topical steroid and NSAID medication). If the IOP is elevated or the patient is a steroid responder, prescribe a non-inflammatory IOP-lowering agent such as Timoptol-XE. Surgery to lower the IOP might be required (e.g., trabeculectomy).

Topical steroids are the accepted first-line treatment for uveitis with a non-infectious aetiology.1 But what happens when your patient is a known steroid responder, whereby a rise in intraocular pressure (IOP) presents an additional therapeutic challenge?  The following case study highlights the need for careful consideration during the management pathway.

Peter,* a 59-year-old Caucasian male with a 20-year history of chronic anterior uveitis in his right eye, was referred by his GP with worsening right visual acuity (VA). The referral notes indicated he was positive for human leukocyte antigen B27 (HLA-B27), had a systemic diagnosis of ankylosing spondylitis, was a known steroid responder and had undergone right phacoemulsification and monofocal IOL implantation in 2005.

In 2007, he attended the Royal Victorian Eye and Ear Hospital (RVEEH), where he was diagnosed with acute anterior uveitis and associated cystoid macular oedema (CMO). Oral prednisolone and topical Prednefrin Forte were prescribed for exacerbations, with a careful monitoring plan due to the history of steroid response that included topical IOP lowering agents. According to the referral letter, he was later discharged from the RVEEH with no regular follow-up by an ophthalmologist.


Peter presented with deteriorating VA in his right eye. On examination, the right bestcorrected visual acuity (BCVA) was 6/15 and the left BCVA was 6/5. IOPs were 9mmHg in the right eye and 13mmHg in the left. The right pupil was poorly reactive to light with an irregular shape, while the left was responsive to light and accommodation. No relative afferent pupillary defect was observed.

Slit lamp examination revealed signs of mild anterior uveitis in the right eye, with fine keratic precipitates, posterior synechiae and trace cells in the anterior chamber (AC). The right IOL also showed mild posterior capsular opacification (PCO). OCT scan of the right macula showed a trace epiretinal membrane (ERM), along with mild CMO that was mostly non-central (Figure 1).

OCT scans are crucial for diagnosing and monitoring uveitic CMO.

At this point, the differential diagnoses included:

  1. Infectious uveitis
  2. HLA-B27+ uveitis
  3. non-HLA-B27+ uveitis
  4. Masquerade syndromes including neoplastic causes, such as intraocular lymphomas.

Evaluation of patients with uveitis requires a systematic approach with targeted historytaking, including uveitis systems review, ocular examination with relevant ocular scans (OCT and possible fundus fluorescein angiography (FFA)) and systemic testing (e.g., blood tests for inflammatory markers and infectious serology).


After exclusion of other causes, Peter’s diagnosis was right-sided acute, recurrent anterior uveitis secondary to HLA-B27 positivity, and subsequent uveitic CMO. The degree of CMO may have been exacerbated by the presence of the ERM. HLA-B27+ anterior uveitis is one of the most common causes of uveitic CMO.2 Steroids are the mainstay of treatment when the cause is non-infectious. However, using steroids in a steroid responder is a red flag for IOP spikes and the potential for raised IOP, glaucoma and cataract development. So, how do we proceed?

A careful, stepwise approach is prudent. First, evaluation of optic nerve function and possible glaucoma is important before commencing any steroid treatment. Steroid response is more likely in those with established glaucoma and those with a family history of glaucoma. Although the IOP in Peter’s right eye was normal at baseline, an OCT scan of the right optic disc, including retinal nerve fibre layer assessment, was performed and was unremarkable. Another consideration is the risk of steroid-induced cataract development; however, our patient is a pseudophake, which rules this out.

The patient was commenced on four-hourly topical steroids (dexamethasone/Maxidex 0.1%) and a non-steroidal anti-inflammatory drop (ketorolac/Acular 0.5%, four times daily). To mitigate the possibility of future IOP spikes, Peter was also started on a oncedaily beta-blocker (Timolol/Timoptol-XE 0.5%) after careful exclusion of any contraindications to its use (in particular, cardiorespiratory diseases). Prostaglandin analogues (e.g., latanoprost/Xalatan) and alpha agonists (e.g., brimonidine/Alphagan) can be proinflammatory and could increase the risk of uveitis/uveitic CMO. As such, they should only be used with caution in this setting.3

HLA-B27 positivity has systemic associations with other diseases (e.g., psoriasis, ankylosing spondylitis, inflammatory bowel disease and reactive arthritis).4 Referral and comanagement with a rheumatologist should be considered, especially if biological/ immunosuppressive therapy is warranted. This may be the case when the uveitis is responding poorly to local treatment alone, and a steroid-sparing immunosuppressive agent and/or biological agent might be necessary. Peter has previously been diagnosed with ankylosing spondylitis and is already under the care of a rheumatologist.

Although not the case here, pars plana vitrectomy may be indicated in patients with uveitis where there is a vision-threatening ERM and/or presence of dense vitreous opacities. Analysis of the vitreous can also be helpful in determining the uveitis aetiology (e.g., microbiological diagnosis for some infectious cases, immunological testing for some conditions such as lymphoma).

Prostaglandin analogues (e.g. latanoprost) and alpha agonists (e.g. brimonidine) can be pro-inflammatory and increase the risk of uveitis. They should only be used with caution in this setting.

Six-Week Review

Peter was monitored every one to two weeks. The topical steroid (Maxidex) was increased to one to two-hourly, but no improvement was made in his right VA and severity of CMO. On examination at the six-week mark, his right BCVA had reduced to 6/24 with an IOP of 9mmHg. His left BCVA remained stable at 6/5. The repeat OCT scan confirmed that the CMO had worsened despite the topical anti-inflammatory drops (Figure 2).

Given Peter’s previous uveitis and ERM, local/ intravitreal treatment is the preferred next step. Ozurdex, a slow-release dexamethasone implant, is listed on the PBS for treatment of non-infectious posterior uveitis for three to six months.5 A systematic review conducted by Saincher and Gottlieb (2020), along with several small prospective studies, found that Ozurdex is safe and effective in reducing retinal thickness and improving vision in patients with uveitic CMO.6,7 Potential side-effects include a spike in IOP, cataract development and endophthalmitis (which is a risk for all intravitreal injections).

Peter had no contra-indications to its use, namely a right IOP within the normal range, no signs of glaucoma and previous cataract surgery. The implant was administered following subconjunctival anaesthesia and Peter was instructed to continue daily prophylactic treatment with Timoptol-XE.

10-Week Review

At the next follow-up, Peter reported noticeable visual improvement in his right eye. His right BCVA had improved from 6/24 to 6/12. His IOP was controlled at 12mmHg. Slit lamp examination showed a white eye and no AC cells or chorioretinitis present. The IOL also appeared central and stable. The post-Ozurdex OCT scans showed a reduction in CMO with a stable ERM (Figure 3).

Peter was instructed to continue Timoptol- XE once daily to control his IOP and return in eight weeks for a review and possibly a second Ozurdex injection to maintain treatment response.

Four-Month Review

Peter reported stable vision in the right eye and is still using Timoptol-XE daily. The right BCVA was 6/12 with an IOP of 9mmHg. There was no recurrence of uveitic CMO in the right eye, indicating a good response to Ozurdex. No AC cells or posterior segment uveitis were visible on slit lamp examination.

A repeat Ozurdex injection was not indicated, given the effectiveness of the first dose and stability of the response. Peter will continue daily Timoptol-XE and return for a review in three months.

Most cases of uveitic CMO respond well with time.

* Patient name changed for anonymity.

Dr Justin Sherwin is an experienced ophthalmologist, with special interests in cataract and refractive surgery, glaucoma, and retinal conditions. He completed his clinical ophthalmology training at the Royal Victorian Eye and Ear Hospital, where he currently holds a public appointment, and sub-specialist training in glaucoma and cataract surgery at Oxford Eye Hospital, UK. Dr Sherwin holds postgraduate degrees (MPhil, MChir, PhD) in epidemiology and eye research from the University of Cambridge, UK.

Dr Sherwin consults at Vision Eye Institute Footscray.

Annie Huang is an orthoptist at Vision Eye Institute Footscray. She completed her Bachelor of Biomedicine at the University of Melbourne and Masters of Orthoptics at La Trobe University. She works alongside Dr Sherwin and assists him with cataract assessments and minor procedures. Ms Huang has special interests in retinal conditions, cataracts and intraocular lenses.


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  7. Khurana R.N., Porco T.C., Efficacy and safety of dexamethasone intravitreal implant for persistent uveitic cystoid macular edema. Retina 2015;35(8):1640–1646.