Abstract
Introduction
Anterior uveitis is rare, with an annual incidence of 12/100,000 population, although it is more common in Finland (annual incidence of 23/100,000), probably because of genetic factors, such as high frequency of HLA–B27 in the population. It is often self-limiting, but can, in some cases, lead to complications such as posterior synechiae, cataract, glaucoma, and chronic uveitis.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of anti-inflammatory eye drops on acute anterior uveitis? We searched: Medline, Embase, The Cochrane Library and other important databases up to November 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found six systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: corticosteroids, mydriatics, and non-steroidal anti-inflammatory drug eye drops.
Key Points
Anterior uveitis is inflammation of the uveal tract, and includes iritis (inflammation of the iris) and iridocyclitis (inflammation of both iris and ciliary body).
It is usually rare, with an annual incidence of 12/100,000 population, although it is more common in Finland (annual incidence of 23/100,000), probably because of genetic factors, such as high frequency of HLA–B27 in the population.
It is often self-limiting, but can in some cases lead to complications such as posterior synechiae, cataract, glaucoma, and chronic uveitis.
Corticosteroid eye drops have been the standard treatment for uveitis since the early 1950s, although the evidence supporting their effectiveness is somewhat sparse.
Widely known adverse effects of topical corticosteroid eye drops include local irritation, hyperaemia, oedema, and blurred vision.
The studies examining the effects of NSAID eye drops or mydriatics were either too small or of insufficient quality to allow us to judge their effectiveness in treating uveitis.
Clinical context
About this condition
Definition
Anterior uveitis is inflammation of the uveal tract, and includes iritis and iridocyclitis. It can be classified according to its clinical course into acute or chronic anterior uveitis, or according to its clinical appearance into granulomatous or non-granulomatous anterior uveitis. Acute anterior uveitis is characterised by an extremely painful red eye, often associated with photophobia, and occasionally with decreased visual acuity. Chronic anterior uveitis is defined as inflammation lasting over 6 weeks. It is usually asymptomatic, but many people have mild symptoms during exacerbations.
Incidence/ Prevalence
Acute anterior uveitis is rare, with an annual incidence of 12/100,000 population. It is particularly common in Finland (annual incidence 22.6/100,000 population, prevalence 68.7/100,000 population), probably because of genetic factors such as the high frequency of HLA–B27 in the Finnish population. It is equally common in men and women, and more than 90% of cases occur in people older than 20 years of age.
Aetiology/ Risk factors
No cause is identified in 60–80% of people with acute anterior uveitis. Systemic disorders that may be associated with acute anterior uveitis include ankylosing spondylitis, Reiter's syndrome, Kawasaki's disease, infectious uveitis, Behçet's syndrome, inflammatory bowel disease, interstitial nephritis, sarcoidosis, Vogt–Koyanagi–Harada syndrome, and masquerade syndromes. Acute anterior uveitis also occurs in association with HLA–B27 expression not linked to any systemic disease. Acute anterior uveitis may occur after surgery, or as an adverse drug or hypersensitivity reaction.
Prognosis
Acute anterior uveitis is often self limiting, but we found no evidence about how often it resolves spontaneously, in which people, or over what length of time. Complications include posterior synechiae, cataract, glaucoma, and chronic uveitis. In a study of 154 people (232 eyes) with acute anterior uveitis (119 people HLA–B27 positive), visual acuity was better than 20/60 in 209/232 eyes (90%), and 20/60 or worse in 23/232 (10%) eyes, including worse than 20/200 (classified as legally blind) in 11/232 (5%) eyes.
Aims of intervention
To reduce inflammation; to relieve pain; and to prevent complications and loss of visual acuity, with minimal adverse effects.
Outcomes
Degree of inflammation using scores that register a range of different variables as markers of disease severity: number of anterior chamber cells per examination field, flare in the anterior chamber, keratic precipitates, ciliary flush, clinical cure, and severity of symptoms (photophobia and pain), quality of life, and adverse effects of treatment.
Methods
Clinical Evidence search and appraisal November 2009. The following databases were used to identify studies for this systematic review: Medline 1966 to November 2009, Embase 1980 to November 2009, and The Cochrane Database of Systematic Reviews 2009, Issue 4 (1966 to date of issue). An additional search within The Cochrane Library was carried out for the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews of RCTs and RCTs in any language, at least single blinded, and containing more than 20 individuals of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. We included systematic reviews of RCTs and RCTs where harms of an included intervention were studied applying the same study design criteria for inclusion as we did for benefits. In addition we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ). The categorisation of the quality of the evidence (into high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table 1.
GRADE evaluation of interventions for acute anterior uveitis
| Important outcomes | Disease severity, adverse effects | ||||||||
| Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of anti-inflammatory eye drops on acute anterior uveitis? | |||||||||
| 1 (60) | Disease severity | Corticosteroid eye drops v placebo eye drops | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data, incomplete reporting of results, poor follow-up, and no intention-to-treat analysis |
| 4 in 2 reports (516) | Disease severity | Corticosteroid eye drops v each other | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for no intention to treat analysis in 2 RCTs (people excluded from analysis) and only reporting results for subgroup of people enrolled in 1 RCT |
| 1 (64) | Disease severity | NSAID eye drops v placebo eye drops | 4 | –2 | 0 | –2 | 0 | Very low | Quality points deducted for sparse data and no intention-to-treat analysis. Directness points deducted for unclear outcome (clinical cure) and co-intervention (atropine) |
| 3 (173) | Disease severity | NSAID eye drops v corticosteroid eye drops | 4 | –2 | 0 | –2 | 0 | Very low | Quality points deducted for sparse data and no intention-to-treat analysis. Directness point deducted for unclear outcome (clinical cure) and co-intervention (atropine) |
Type of evidence: 4 = RCT. Consistency: similarity of results across studies Directness: generalisability of population or outcomes Effect size: based on relative risk or odds ratio
Glossary
- Iridocyclitis
Inflammation of both iris and ciliary body. Cells are present in the anterior chamber and in the vitreous.
- Iritis
Inflammation of the iris. Cells are seen in the anterior chamber but not in the vitreous.
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Masquerade syndromes
Comprise a group of disorders that occur with intraocular inflammation and are often misdiagnosed as a chronic idiopathic uveitis.
- Posterior synechiae
Adhesions between the iris and the lens capsule.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
Contributor Information
Niaz Islam, Queens Hospital, Romford, UK.
Carlos Pavesio, Moorfields Eye Hospital, London, UK.
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