Different lasers and techniques for proliferative diabetic retinopathy (Review)

Methodological quality of the review: High confidence

Author: Moutray T, Evans JR, Lois N, Armstrong DJ, Peto T, Azuara-Blanco A

Region: Europe, Asia, Middle East and USA

Sector: Diabetic retinopathy

Sub-sector: Treatment

Equity focus: None specified

Review type: Other review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background:

Diabetic retinopathy (DR) is a chronic progressive disease of the retinal microvasculature associated with prolonged hyperglycaemia. Proliferative DR (PDR) is a sight-threatening complication of DR and is characterized by the development of abnormal new vessels in the retina, optic nerve head or anterior segment of the eye. Argon laser photocoagulation has been the gold standard for the treatment of PDR for many years, using regimens evaluated by the Early Treatment of Diabetic Retinopathy Study (ETDRS). Over the years, there have been modifications of the technique and introduction of new laser technologies.

Objectives: To assess the effects of different types of laser, other than argon laser, and different laser protocols, other than those established by the ETDRS, for the treatment of PDR. We compared different wavelengths; power and pulse duration; pattern, number and location of burns versus standard argon laser undertaken as specified by the ETDRS.

Main findings:

Authors identified 11 studies from Europe (6), the USA (2), the Middle East (1) and Asia (2). Five studies compared different types of laser to argon: Nd:YAG (2 studies) or diode (3 studies). Other studies compared modifications to the standard argon laser PRP technique. Authors judged all studies to be at high risk of bias in at least one domain. The sample size varied from 20 to 270 eyes but the majority included 50 participants or fewer.

Nd:YAG versus argon laser (2 studies): very low-certainty evidence on vision loss, vision gain, progression and regression of PDR, pain during laser treatment and adverse effects.

Diode versus argon laser (3 studies): very-low certainty evidence on vision loss, vision gain, progression and regression of PDR and adverse effects; authors noted moderate certainty evidence that diode laser was more painful (risk ratio (RR) troublesome pain during laser treatment (RR 3.12, 95% confidence interval  CI) 2.16 to 4.51; eyes = 202; studies = 3; I2 = 0%).

0.5 second versus 0.1 second exposure (1 study): authors found low-certainty evidence of lower chance of vision loss with 0.5 second compared with 0.1 second exposure, but estimates were imprecise and compatible with no difference or an increased chance of vision loss (RR 0.42, 95% CI 0.08 to 2.04, 44 eyes, 1 RCT);  authors also reported low-certainty evidence that people treated with 0.5 second exposure were more likely to gain vision (RR 2.22, 95% CI 0.68 to 7.28, 44 eyes, 1 RCT) but again authors noted the estimates were imprecise. Findings from the review shown that people given 0.5 second exposure were more likely to have regression of PDR compared with 0.1 second laser PRP again with imprecise estimate (RR 1.17, 95% CI 0.92 to 1.48, 32 eyes, 1 RCT). Authors reported that there was very low-certainty evidence on progression of PDR and adverse effects.

Based on intensity, authors reported that ‘light intensity’ PRP versus classic PRP (1 study): vision loss or gain was not reported but the mean difference in logMAR acuity at 1 year was −0.09 logMAR (95% CI −0.22 to 0.04, 65 eyes, 1 RCT); and low-certainty evidence that fewer patients had pain during light PRP compared with classic PRP with an imprecise estimate compatible with increased or decreased pain (RR 0.23, 95% CI 0.03 to 1.93, 65 eyes, 1 RCT).

‘Mild scatter’ (laser pattern limited to 400 to 600 laser burns in one sitting) PRP versus standard ‘full’ scatter PRP (1 study): very low certainty evidence on vision and visual field loss.

‘Central’ (a more central PRP in addition to mid-peripheral PRP) versus ‘peripheral’ standard PRP (1 study): low-certainty evidence that people treated with central PRP were more likely to lose 15 or more letters of best corrected visual acuity (BCVA) compared with peripheral laser PRP (RR 3.00, 95% CI 0.67 to 13.46, 50 eyes, 1 RCT); and less likely to gain 15 or more letters (RR 0.25, 95% CI 0.03 to 2.08) with imprecise estimates compatible with increased or decreased risk.

‘Centre sparing’ PRP (argon laser distribution limited to 3 disc diameters from the upper temporal and lower margin of the fovea) versus standard ‘full scatter’ PRP (1 study): low-certainty evidence that people treated with ‘centre sparing’ PRP were less likely to lose 15 or more ETDRS letters of BCVA compared with ‘full scatter’ PRP (RR 0.67, 95% CI 0.30 to 1.50, 53 eyes). Low-certainty evidence of similar risk of regression of PDR between groups (RR 0.96, 95% CI 0.73 to 1.27, 53 eyes). Adverse events were not reported.

‘Extended targeted’ PRP (to include the equator and any capillary non-perfusion areas between the vascular arcades) versus standard PRP (1 study): low-certainty evidence that people in the extended group had similar or slightly reduced chance of loss of 15 or more letters of BCVA compared with the standard PRP group (RR 0.94, 95%CI 0.70 to 1.28, 270 eyes). Low-certainty evidence that people in the extended group had a similar or slightly increased chance of regression of PDR compared with the standard PRP group (RR 1.11, 95% CI 0.95 to 1.31, 270 eyes). Very low-certainty information on adverse effects.

In terms of conclusions, authors noted that modern laser techniques and modalities have been developed to treat PDR. However, there is limited evidence available with respect to the efficacy and safety of alternative laser systems or strategies compared with the standard argon laser as described in ETDRS.

Methodology: 

Authors included randomized controlled trials (RCTs) of pan-retinal photocoagulation (PRP) using standard argon laser for treatment of PDR compared with any other laser modality. Excluded studies included those of lasers that are not in common use, such as the xenon arc, ruby or Krypton laser. Authors searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 5); OvidMEDLINE; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov and the ICTRP. The date of the search was 8 June 2017 and no language restrictions were applied. Reference lists of potentially includable studies were searched to identify any additional trials.

Applicability/external validity:

Authors noted that there was no difference in the population included in these studies. All studies looked at both male and female adults with a clinical diagnosis of Type 1 or Type 2 diabetes mellitus, between the age of 18 to 79 years of age. One or both eyes of each participant were required to have high risk PDR.

Geographic focus:

Authors did not discuss the applicability of findings to low- and middle-income countries.

Summary of quality assessment:

High confidence was attributed in the conclusions about the effects of this study. Authors used rigorous methods to identify and screen studies for inclusion, extract data and assess the risk of bias of included studies. Appropriate methods were used to analyze the findings of included studies.