Steroid implants for chronic uveitis not caused by infection

What is chronic non-infectious uveitis?

Uveitis is a group of eye diseases caused by inflammation (redness, swelling, pain, etc.) inside the eye, which can lead to vision loss. Uveitis can result from infections, or non-infectious causes. Non-infectious uveitis can result from a disease somewhere else in the body. The uvea (middle layer of the eye) has many blood vessels. If the immune system is fighting a problem in one area, the cells and chemicals it makes can travel through the bloodstream and enter the eye, leading to inflammation. Acute uveitis lasts less than three months; chronic uveitis lasts longer than three months.

How it is treated?

Chronic non-infectious uveitis is generally treated with steroids, applied near or inside the eye, or other medicines, taken either by mouth or injection, to control the inflammation. However, these medicines, including steroids, suppress the immune system and result in unwanted side effects.

What did we want to find out?

We assessed whether a steroid-containing implant (a small capsule that slowly releases steroids inside the eye) can reduce the return of uveitis, improve vision, or improve quality of life. We also evaluated whether these implants increased any unwanted side effects.

What we did

We searched for trials that randomly assigned children and adults with chronic non-infectious uveitis to receive either steroid-containing implants or another treatment; the other treatment could be a pretend (sham) procedure or other standard way of delivering care. We summarized the study findings, and assessed how confident we were in the findings.

What we found

We found two studies (282 participants) that compared surgically-placed implants that released fluocinolone acetonide into the eye with a sham procedure. The type and amount of medicine released was different in both studies. The steroid-containing implants appeared to reduce the risk of uveitis coming back, and lead to better vision and quality of life.

We found two studies (683 participants) that compared surgically-placed implants that released fluocinolone acetonide into the eye with standard treatment. Both studies used the same implant. The results did not show that the steroid-containing implants reduced the risk of uveitis coming back, or improved much vision, but the participants appeared to have a better quality of life.

Steroid-containing implants seemed to increase the risk for developing cataracts (clouding of the lens of the eye), and for increasing the pressure in the eye. All four studies included participants from multiple countries.

What are the limitations of the evidence?

We only included four studies. They did not enroll large numbers of participants, and had some flaws in their study design. Therefore, we have moderate to limited confidence in our findings.

How up to date is this evidence?

The evidence is current to November 2021.

Authors' conclusions: 

Our confidence is limited that local corticosteroid implants are superior to sham therapy or standard-of-care therapy in reducing the risk of uveitis recurrence. We demonstrated different effectiveness on BCVA relative to comparators in people with non-infectious uveitis. Nevertheless, the evidence suggests that these implants may increase the risk of cataract progression and IOP elevation, which will require interventions over time.

To better understand the efficacy and safety profiles of corticosteroid implants, we need future trials that examine implants of different doses, used for different durations. The trials should measure core standard outcomes that are universally defined, and measured at comparable follow-up time points.

Read the full abstract...
Background: 

Uveitis is a term used to describe a group of intraocular inflammatory diseases. Uveitis is the fifth most common cause of vision loss in high-income countries, with the highest incidence of disease in the working-age population. Corticosteroids are the mainstay of treatment for all subtypes of non-infectious uveitis. They can be administered orally, topically with drops, by periocular (around the eye) or intravitreal (inside the eye) injection, or by surgical implantation.

Objectives: 

To determine the efficacy and safety of steroid implants in people with chronic non-infectious posterior uveitis, intermediate uveitis, and panuveitis.

Search strategy: 

We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE Ovid, Embase, PubMed, LILACS, and three trials registries to November 2021.

Selection criteria: 

We included randomized controlled trials comparing either fluocinolone acetonide (FA) or dexamethasone (DEX) intravitreal implants with standard-of-care therapy or sham procedures, with at least six months of follow-up after treatment. We included studies that enrolled participants of all ages, who had chronic non-infectious posterior uveitis, intermediate uveitis, or panuveitis with vision that was better than hand-motion.

Data collection and analysis: 

We applied standard Cochrane methodology.

Main results: 

We included data from four trials (683 participants, 907 eyes) that compared corticosteroid implants with either sham or standard-of-care therapy.

Study characteristics and risk of bias
Of the two trials that compared corticosteroid implants with sham procedure, one examined a 0.18 mg FA implant, and the other, a 0.7 mg DEX implant. The other two trials compared a 0.59 mg FA implant with standard-of-care therapy, which included systemic corticosteroids and immunosuppressive medications, if needed. Considering improvement in visual acuity, we assessed the four trials to be at either low risk, or with some concerns of risk of bias across all domains.

Findings
Using sham procedure as control, combined results at the six-month primary time point suggested that corticosteroid implants may decrease the risk of uveitis recurrence by 60% (relative risk [RR] 0.40, 95% confidence interval [CI] 0.30 to 0.54; 2 trials, 282 participants; low-certainty evidence); and lead to a greater improvement in best-corrected visual acuity (BCVA; mean difference [MD] 0.15 logMAR, 95% CI 0.06 to 0.24; 1 trial, 153 participants; low-certainty evidence). Evidence based on a single-study report (146 participants) suggested that steroid implants may have no effects on visual functioning quality of life, measured on the National Eye Institute 25-Item Visual Function Questionnaire (MD 2.85, 95%CI -3.64 to 9.34; 1 trial, 146 participants; moderate-certainty evidence).

Using standard-of care therapy as control, combined estimates at the 24-month primary time point suggested that corticosteroid implants were likely to decrease the risk of recurrence of uveitis by 54% (RR 0.46, 95% CI 0.35 to 0.60; 2 trials, 619 eyes). Combined estimates at 24 months also suggested that steroid implants may have little to no effects on improving BCVA (MD 0.05 logMAR, 95% CI -0.02 to 0.12; 2 trials, 619 eyes; low-certainty evidence). Evidence based on a single-study report (232 participants) suggested that steroid implants may have minimal clinical effects on visual functioning (MD 4.64, 95% CI 0.13 to 9.15; 1 trial, 232 participants; moderate-certainty evidence); physical functioning (SF-36 physical subscale MD 2.95, 95% CI 0.55 to 5.35; 1 trial, 232 participants; moderate-certainty evidence); or mental health (SF-36 mental subscale MD 3.65, 95% CI 0.52 to 6.78; 1 trial, 232 participants; moderate-certainty evidence); but not on EuroQoL (MD 6.17, 95% CI 1.87 to 10.47; 1 trial, 232 participants; moderate-certainty evidence); or EuroQoL-5D scale (MD 0.02, 95% CI -0.04 to 0.08; 1 trial, 232 participants; moderate-certainty evidence).

Adverse effects
Compared with sham procedures, corticosteroid implants may slightly increase the risk of cataract formation (RR 2.69, 95% CI 1.17 to 6.18; 1 trial, 90 eyes; low-certainty evidence), but not the risk of cataract progression (RR 2.00, 95% CI 0.65 to 6.12; 1 trial, 117 eyes; low-certainty evidence); or the need for surgery (RR 2.98, 95% CI 0.82 to 10.81; 1 trial, 180 eyes; low-certainty evidence), during up to 12 months of follow-up. These implants may increase the risk of elevated intraocular pressure ([IOP] RR 2.81, 95% CI 1.42 to 5.56; 2 trials, 282 participants; moderate-certainty evidence); and the need for IOP-lowering eyedrops (RR 1.85, 95% CI 1.05 to 3.25; 2 trials, 282 participants; moderate-certainty evidence); but not the need for IOP-lowering surgery (RR 0.72, 95% CI 0.13 to 4.17; 2 trials, 282 participants; moderate-certainty evidence).

Evidence comparing the 0.59 mg FA implant with standard-of-care suggested that the implant may increase the risk of cataract progression (RR 2.71, 95% CI 2.06 to 3.56; 2 trials, 210 eyes; low-certainty evidence); and the need for surgery (RR 2.98, 95% CI 2.33 to 3.79; 2 trials, 371 eyes; low-certainty evidence); along with the risk of elevated IOP (RR 3.64, 95% CI 2.71 to 4.87; 2 trials, 605 eyes; moderate-certainty evidence); and the need for medical (RR 3.04, 95% CI 2.36 to 3.91; 2 trials, 544 eyes; moderate-certainty evidence); or surgical interventions (RR 5.43, 95% CI 3.12 to 9.45; 2 trials, 599 eyes; moderate-certainty evidence).

In either comparison, these implants did not increase the risk for endophthalmitis, retinal tear, or retinal detachment (moderate-certainty evidence).