What is dry eye?
Dry eye is a common condition that occurs when a person's tears cannot lubricate their eyes sufficiently. Tears can be inadequate and unstable for many reasons. For example, dry eye may occur when tear production is reduced or when the tear quality is poor. This tear instability leads to inflammation and damage of the eye's surface. Dry eye is uncomfortable. People with dry eye often feel stinging or burning and sometimes experience blurred vision.
How is it treated?
Many treatment options are available for dry eye. For dry eye caused by the relative lack of the water layer in tears, treatments may include artificial tears, tear stimulants, serum eye drops, and punctal plugs. For dry eye caused by the blocked secretion of the lipid layer in tears, treatment options may include topical antibiotics, warm compresses, and anti-inflammatory agents, such as corticosteroids and cyclosporine A. Corticosteroids eye drops aim to reduce the inflammatory process and provide symptom relief with short-term use. High eye pressure and cataract formation are common concerns with longer-term use of corticosteroids.
What did we want to find out?
We evaluated whether corticosteroids eye drops, alone or in combination with other medications, can improve dry eye symptoms or test results used to diagnose or monitor dry eye. We also examined whether corticosteroids eye drops cause any unwanted effects on the eyes.
What we did
We conducted a systematic review. We searched for studies that compared corticosteroids eye drops with lubricating controls, other active treatment, or no treatment. We summarized these study findings and rated the evidence based on numbers of study participants and methods used in the studies.
What we found
We identified 22 clinical trials that enrolled a total of 4169 participants with dry eye. Most trials involved adults with a mean age between 50 and 67 years, except for one trial that exclusively involved children aged 3 to 14 years. Treatment duration ranged between 7 days and 3 months. When compared with lubricants, such as artificial tears, or with cyclosporine A, corticosteroids eye drops were probably effective in improving patient-reported symptoms and clinical tests, such as corneal staining. Clinicians may use corneal staining as a test for cornea damage. However, corticosteroids eye drops may result in little to no difference in tear quality or quantity. At the same time, it is uncertain whether steroid use may increase or decrease the chance of increased eye pressure, new cataract formation, or worsening of an existing cataract.
What are the limitations of the evidence?
More than half of the included trials had flawed study methods or did not report their results fully. These deficiencies led to concerns about the study findings and decreased our confidence in the evidence generated in this systematic review.
How up-to-date is this evidence?
The evidence is up-to-date as of August 2021.
Overall, the evidence for the specified review outcomes was of moderate to very low certainty, mostly due to high risk of bias associated with selective results reporting. For dry eye patients whose symptoms require anti-inflammatory control, topical corticosteroids probably provide small to moderate degrees of symptom relief beyond lubricants, and may provide small to moderate degrees of symptom relief beyond CsA. However, the current evidence is less certain about the effects of steroids on improved tear film quality or quantity. The available evidence is also very uncertain regarding the adverse effects of topical corticosteroids on IOP elevation or cataract formation or progression. Future trials should generate high certainty evidence to inform physicians and patients of the optimal treatment strategies with topical corticosteroids in terms of regimen (types, formulations, dosages), duration, and its time-dependent adverse profile.
Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such as ocular dryness, burning, itching, pain, and visual impairment. Given their well-established anti-inflammatory effects, topical steroid preparations have been widely used as a short-term treatment option for DED. Because of potential risks of ocular hypertension, cataracts, and infections associated with the long-term use of topical steroids, published trials comparing the efficacy and safety of topical steroids (versus placebo) have mostly been of short duration (three to eight weeks).
To evaluate the effectiveness and safety of topical corticosteroids compared with no treatment, placebo, other steroidal or non-steroidal therapies, or a combination of therapies for DED.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 8); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), without restriction on language or year of publication. The date of the last search was 20 August 2021.
We included randomized controlled trials (RCTs) in which topical corticosteroids, alone or in combination with tobramycin, were compared with no treatment, artificial tears (AT), vehicles, AT plus tobramycin, or cyclosporine A (CsA).
We applied standard Cochrane methodology.
We identified 22 RCTs conducted in the USA, Italy, Spain, China, South Korea, and India. These RCTs reported outcome data from a total of 4169 participants with DED.
Study characteristics and risk of bias
All trials recruited adults aged 18 years or older, except one trial that enrolled children and adolescents aged between 3 and 14 years. Half of these trials involved predominantly female participants (median 79%, interquartile range [IQR] 76% to 80%). On average, each trial enrolled 86 participants (IQR 40 to 158). The treatment duration of topical steroids ranged between one week and three months; trial duration lasted between one week and six months. Eight trials were sponsored exclusively by industry, and four trials were co-sponsored by industry and institutional or governmental funds. We assessed the risk of bias of both subjective and objective outcomes using RoB 2, finding nearly half of the trials to be at high risk of bias associated with selective outcome reporting.
Findings
Of the 22 trials, 16 evaluated effects of topical steroids, alone or in combination with tobramycin, as compared with lubricants (AT, vehicle), AT plus tobramycin, or no treatment. Corticosteroids probably have a small to moderate effect on improving patient-reported symptoms by 0.29 standardized mean difference (SMD) (95% confidence interval [CI] 0.16 to 0.42) as compared with lubricants (moderate certainty evidence). Topical steroids also likely have a small to moderate effect on lowering corneal staining scores by 0.4 SMDs (95% CI 0.18 to 0.62) (moderate certainty evidence). However, steroids may increase tear film break-up time (TBUT) slightly (mean difference [MD] 0.70 s, 95% CI 0.06 to 1.34; low certainty evidence) but not tear osmolarity (MD 1.60 mOsm/kg, 95% CI −10.47 to 13.67; very low certainty evidence).
Six trials examined topical steroids, either alone or in combination with CsA, against CsA alone. Low certainty evidence indicates that steroid-based interventions may have a small to moderate effect on improving participants' symptoms (SMD −0.33, 95% CI −0.51 to −0.15), but little to no effect on corneal staining scores (SMD 0.05, 95% CI −0.25 to 0.35) as compared with CsA. The effect of topical steroids compared to CsA alone on TBUT (MD 0.37 s, 95% CI −0.13 to 0.87) or tear osmolarity (MD 5.80 mOsm/kg, 95% CI −0.94 to 12.54; loteprednol etabonate alone) is uncertain because the certainty of the evidence is low or very low. None of the included trials reported on quality of life scores.
Adverse effects
The evidence for adverse ocular effects of topical corticosteroids is very uncertain. Topical corticosteroids may increase participants' risk of intraocular pressure (IOP) elevation (risk ratio [RR] 5.96, 95% CI 1.30 to 27.38) as compared with lubricants. However, when compared with CsA, steroids alone or combined with CsA may decrease or increase IOP elevation (RR 1.45, 95% CI 0.25 to 8.33). It is also uncertain whether topical steroids may increase risk of cataract formation when compared with lubricants (RR 0.34, 95% CI 0.01 to 8.22), given the short-term use and study duration (four weeks or less) to observe longer-term adverse effects.