Sajad Hussain and Normal Litvin¹

¹Bradford Royal Infirmary and Teaching Trust

Introduction

Uveitis is an umbrella term that refers to inflammation of the uveal tract and adjacent structures of the eye, which can be infectious or non-infectious in aetiology (1). Uveitis can be classified as anterior, intermediate, posterior, or panuveitis based on the anatomical location of the inflammation in the eye (2).  Anterior uveitis is inflammation of the iris and ciliary body and is the most common form of uveitis (3). Intermediate uveitis is defined as inflammatory cells in the vitreous humour. Posterior uveitis is defined as inflammation of the retina/choroid (choroiditis, chorioretinitis, retinitis) and panuveitis is inflammation of all three parts of the uvea, i.e. the anterior chamber, vitreous humour, and choroid or retina (4).

The prevalence of the various types of uveitis depends upon multiple factors such as age, sex, race, geographic distribution, environmental influence, genetics, and social habits (2). Approximately 10% to 15% of preventable blindness in Western countries is caused by uveitis and associated complications (5-6). Although less common than anterior uveitis, non-infectious intermediate uveitis, posterior uveitis, or panuveitis (NIIPPU) typically either is idiopathic and comprises many well-defined uveitic ocular conditions or is associated with systemic underlying autoimmune disorders, both of which present with varying degrees of ocular comorbidities; these complications account for most uveitis- related visual complications in these patients (1).

Sight-threatening complications such as macula oedema, cataracts, glaucoma and retinopathy can occur with NIIPU (7-8). If panuveitis is left untreated, this can lead to irreversible loss of sight. The mainstay of treatment for these conditions includes reducing inflammation using corticosteroids and other immunosuppressive agents. Long-term corticosteroid use for the treatment of uveitis can lead to the development of conditions such as glaucoma and cataracts, to which significant ocular morbidity can be attributed however when balanced with the morbidity caused by the effects of uveitis, it is deemed to be significantly less burden on healthcare systems (1).

Case Report

A 29-year-old female was referred to this outpatient eye clinic in March 2023 from a neighbouring eye clinic for suspected panuveitis. The patient initially presented at the other eye casualty in October 2022 after she woke up with a red, painful and sore right eye. She was started on topical corticosteroid, oral prednisolone and omeprazole. Investigations for systemic association had been done and no link was identified. She was initially commenced on 60mg oral steroids and slowly tapered down, but when reviewed in Jan 2023, she was down to 40mg once daily, it was noted her uveitis was not controlled, so the dose was once again increased to 60mg and tapered slowly again. Her history noted she had a stroke in 2021 and left lateral medullary syndrome with a suspected seizure. She reported no skin changes, joint pain, cough or chest pain.

On slit lamp examination it was noted she had features of panuveitis in her right eye which included snowballs opacities in the anterior vitreous, central lens opacity and central macula oedema.  Her VA was noted to be reduced to 6/9 in the affected eye. The intraocular pressures (IOPs) were noted to be 22mmhg in her right eye and 25mmhg in her left eye.

In the initial visit, the plan was made for her to re-start oral prednisolone at 60mg and taper down to 7.5mg over several weeks, start mycophenolate 1g twice daily for 2 weeks, have a monitoring blood test done and then increase to 1.5mg twice daily. A further blood test was scheduled for two weeks. She was told to remain on that dose with a blood test to be done again 4 weeks later. She was booked to be reviewed again in a clinic 3 months later. 

3 months later, she was reviewed in the clinic after having fluorescein angiography (FFA) done 1 week previously. It was noted her IOPs were stable, but FFA noted she had some active leaking in both eyes at the macula. Her VA remained stable at 6/9 best corrected. She was advised to continue the mycophenolate 1.5 mg twice daily and to reduce the oral prednisolone by 2.5mg weekly until she reached 10mg, whereby she would maintain that dose. She was scheduled for a 2-week review, and it was agreed to commence Ozurdex in both eyes. This was implanted in July 2023 in her left eye and in August 2023 in her RE. A further review done in November 2023 noted her macula oedema was improving but her IOPs were increasing slowly.  She was booked to be reviewed again in Jan 2024.

In Jan 2024 review it was noted her IOP had increased significantly in each eye due to steroid use. Her right IOP was 39 mmhg and left 45mmhg. She was commenced on Latanaprost with Timolol (Xalacom) and later visits commenced on Brinzolamide with Brimonidine (Simbrinza). It was however noted her IOPs remained very high. A discussion was had regarding the Ozurdex, explaining the benefits of keeping the Ozurdex implant and the risks associated with the risk of IOP increase. It was agreed to maintain the Implant as the benefits outweighed the risks and a new implant was inserted in March 2024.

In April 2024, due to persistent elevated IOPs, she was commenced on oral acetazolamide 250mg three times a day for 4 weeks. In May 2024 IOPs were reviewed and remained elevated despite being on maximal topical therapy. Her IOPs remained elevated with notable Left corneal oedema. She was continued on maximal topical therapy and remained on oral acetazolamide 250mg three times a day. In June 2024, her IOPS reduced to R: 23mmhg and Left 29mmhg and left cornea oedema had settled. It was discussed regarding the long-term IOP plan as nerve fibres indicated some inferior temporal damage in her left eye. Various options were discussed including Preserflo implant and trabeculectomy. The risks and benefits of each were discussed and agreed to proceed with Preserflo in the left eye first.

Discussion

Steroids in certain individuals can lead to a clinical presentation like primary open-angle glaucoma. It is reported around five percent of the population are high steroid responders and develop an intraocular pressure (IOP) elevation of more than 15 mm Hg above baseline (9).  IOP elevation can occur anywhere between day 1 to as late as 12 weeks after intravitreal triamcinolone in 20–65% of patients. On average, 75% of eyes with steroid implants require IOP-lowering therapy at some point within 3 years of follow-up (9).

Systemic Steroids

Although there has been an association of increased IOP and increased steroid production in the body, several studies have examined the link and stated the likelihood of IOP elevation with systemic steroids is less than the topical route. However, they noted the groups of patients being treated with long-term systemic steroids showed higher mean IOPs, as well as an increased number of individuals with higher pressures than are present in the normal population (10).

Intravitreal sustained-release steroid implant

Intravitreal steroid implants are designed for controlling intraocular inflammation due to non-infectious posterior-segment uveitis or macular oedema due to vascular accidents (9). A study by Bollinger et al. (2009), involving patients with implants noted 75% of eyes receiving the fluocinolone acetonide implant required IOP-lowering therapy at some point within the course of the 3-year study. They noted more than one-third of the eyes (36.6%) required IOP-lowering surgery. The most common surgery employed was trabeculectomy (76.2%) and 20.6% received glaucoma drainage devices as first-line treatment (11).

Management

The most effective method in reducing IOPs in cases of steroid response would be to cease the steroid. In cases where the steroid needs to continue, it is recommended for regular IOP monitoring. In many cases, medical management is the first line as it is the easiest to cease after steroids have stopped. In all cases, the medical management is the same as primary open angle glaucoma. A study done by Sihota et al (12) in a cohort of 34 patients, found 73.5% of patients had their IOPs controlled adequately with medical management. A further study by Gillies et al (13) found a single medication was sufficient in 85.7% of patients, whereas the other 14.3% required 2 medications to control IOP.

If a patient’s IOP remains persistently high after medical management, then surgical intervention should be considered. Although most patients can be treated medically, around 5% must still undergo surgical interventions (9). The most common surgery in patients with healthy conjunctiva is trabeculectomy; otherwise, shunt implantation or cyclodestructive procedures may be considered. Pietris et al (14) looked at the use of Preserflo to reduce IOP and found a significant mean reduction in IOP of 9.07mmHg.

Conclusion

This case highlights the importance of balancing clinical treatments and their adverse side effects. It highlights, that starting clinical treatments sometimes requires extra precautions as the side effects can lead to visual loss. In this case, the treatment of the CMO with steroids resulted in elevated IOPs, however without the steroid treatment the patient would have had vision loss due to continued CMO. This highlights the tiered treatment process from medical management to more invasive surgical treatment.

References

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