Laser photocoagulation for proliferative diabetic retinopathy (Review)

Methodological quality of the review: High confidence

Author: Evans JR, Michelessi M, Virgili G

Region: United States of America (USA), United Kingdom (UK) and Japan

Sector: Diabetic retinopathy

Sub-sector: Laser photocoagulation

Equity focus:  None specified

Review type: Other review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background:
Diabetic retinopathy is a complication of diabetes in which high blood sugar levels damage the blood vessels in the retina. Sometimes new blood vessels grow in the retina, and these can have harmful effects; this is known as proliferative diabetic retinopathy. Laser photocoagulation is an intervention that is commonly used to treat diabetic retinopathy, in which light energy is applied to the retina with the aim of stopping the growth and development of new blood vessels, and thereby preserving vision.

Objectives:
To assess the effects of laser photocoagulation for diabetic retinopathy compared to no treatment or deferred treatment.

Main findings:
Authors included a total of five randomized controlled trials (RCTs) in the review. Three studies were conducted in the USA, one study in the UK and one study in Japan. A total of 4,786 people (9,503 eyes) were included in these studies. The majority of participants in four of these trials were people with proliferative diabetic retinopathy; one trial recruited mainly people with non-proliferative retinopathy. Four of the studies evaluated panretinal photocoagulation with argon laser and one study investigated selective photocoagulation of non-perfusion areas. Three studies compared laser treatment to no treatment and two studies compared laser treatment to deferred laser treatment. All studies were at risk of performance bias because the treatment and control were different and no study attempted to produce a sham treatment. Three studies were considered to be at risk of attrition bias.

At 12 months, authors noted that, there was little difference between eyes that received laser photocoagulation and those allocated to no treatment (or deferred treatment), in terms of loss of 15 or more letters of visual acuity (risk ratio (RR) 0.99, 95%  confidence interval (CI) 0.89 to 1.11; 8,926 eyes; 2 RCTs, low-quality evidence). Authors reported that longer term follow-up did not show a consistent pattern, but one study found a 20% reduction in risk of loss of 15 or more letters of visual acuity at five years with laser treatment. Treatment with laser reduced the risk of severe visual loss by over 50% at 12 months (RR 0.46, 95% CI 0.24 to 0.86; 9,276 eyes; 4 RCTs, moderate quality evidence). Authors saw a beneficial effect on progression of diabetic retinopathy with treated eyes experiencing a 50% reduction in risk of progression of diabetic retinopathy (RR 0.49, 95% CI 0.37 to 0.64; 8,331 eyes; 4 RCTs, low quality evidence) and a similar reduction in risk of vitreous haemorrhage (RR 0.56, 95% CI 0.37 to 0.85; 224 eyes; 2 RCTs, low quality evidence).

Authors found that none of the studies reported near visual acuity or patient-relevant outcomes such as quality of life, pain, loss of driving licence or adverse effects such as retinal detachment.

Authors did not plan any subgroup analyses, but it was noted that there was a difference in baseline risk in participants with non-proliferative retinopathy compared to those with proliferative retinopathy. With the small number of included studies, authors could not do a formal subgroup analysis comparing effect in proliferative and non-proliferative retinopathy.

Authors concluded that this review provides evidence that laser photocoagulation is beneficial in treating proliferative diabetic retinopathy. In addition, they noted that future Cochrane Reviews on variations in the laser treatment protocol are planned. Future research on laser photocoagulation should investigate the combination of laser photocoagulation with newer treatments such as anti-vascular endothelial growth factors (anti-VEGFs).

Methodology: 

Inclusion criteria consisted of RCTs where people (or eyes) with diabetic retinopathy were randomly allocated to laser photocoagulation or no treatment or deferred treatment. Primary outcome was the proportion of people who lost 15 or more letters (3 lines) of best-corrected visual acuity (BCVA) as measured on a logMAR chart at 12 months. Authors also looked at longer-term follow-up of the primary outcome at two to three years. Secondary outcomes included mean best corrected distance visual acuity, severe visual loss, mean near visual acuity, progression of diabetic retinopathy, quality of life, pain, loss of driving licence, vitreous haemorrhage and retinal detachment.

Authors searched CENTRAL, Ovid MEDLINE resources, EMBASE, the metaRegister of Controlled Trials, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. Authors did not use any date or language restrictions in the electronic searches for trials. The searches were last conducted on 3 June 2014. Two authors independently screened studies for inclusion and extracted data of included studies. Risk of bias was assessed using the Cochrane Collaboration’s tool for assessing the risk of bias as described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions.

Authors calculated the risk ratio (RR) for all dichotomous variables and for continuous variables authors calculated the mean difference. All measures of effect were reported with 95%confidence intervals (CIs). Authors assessed heterogeneity by visual inspection of the forest plots and by calculating the I² value.

Authors pooled data using a random-effects model, unless there were three or fewer trials, in which case we used a fixed-effect model. There was considerable heterogeneity, and for many analyses the I² statistic was over 50%. In most analyses all effect estimates were in the same direction and authors report a pooled value.

Applicability/external validity:

Authors note that overall, the evidence is applicable to people presenting with moderate to severe pre-proliferative and PDR.

Geographic focus:

Authors noted that included studies were all conducted some time ago in high-income countries, leaving a lack of evidence for lower- and middle-income countries and different parts of the world. However, authors state having no reason to suppose that the effectiveness of these treatments would be different in lower-income countries.

Summary of quality assessment:

Overall, there is high confidence in the conclusions of this study. Authors used rigorous methods to screen studies for inclusion and extract data of included studies, avoiding biases. Authors used appropriate methods to pool data of included studies and assess risk of bias.