Grid laser photocoagulation for macular oedema after branch retinal vein occlusion (BRVO)

Review question: We assessed the role of macular grid laser (laser performed in a grid pattern) compared to other new treatments.

Background
When a vein is blocked ('occluded') in the retina at the back of the eye, swelling of the macula (the central retina) can occur, which reduces vision. The options are to wait to see whether the swelling clears up on its own, or to treat the swelling by applying laser to the macula, injecting the eye with steroids or injecting the eye with anti-vascular endothelial growth factor (anti-VEGF). Laser has been an established mode of treatment ever since a landmark study, (the Branch Vein Occlusion Study in 1984) showed the advantage of laser compared to no treatment. However, over the last 10 years laser technology has evolved, and new injection treatments have become available.

Search date
The electronic databases were searched on 21 August 2014.

Study characteristics
We include five studies with a total of 715 participants. Three studies were from Italy and two were from the USA.

Key results
We looked primarily at the proportion of participants gaining or losing significant vision. The trial comparing grid laser to no laser showed a clear benefit for grid laser. The result of the trial comparing early grid laser to delayed grid laser for macular BRVO (a subgroup of BRVO in which the occlusion is limited to a small vessel draining a sector of the macular region) was uncertain, and the quality of the evidence was low. We could not be certain that bevacizumab injections were better than grid laser treatment, because the effect was imprecise and the quality of the evidence was low. We could not be certain if subthreshold diode laser treatment was better than threshold laser treatment because the results were imprecise. The trial comparing grid laser treatment to triamcinolone (steroid) injection was imprecise, but there was a suggestion of a benefit for grid laser over 1 mg triamcinolone at 36 months and a benefit for grid laser over 4 mg triamcinolone at 24 months. Two of the five studies were at risk of bias, meaning that there were problems with the design and execution of two of the five studies which raised questions about the validity of these two studies.

Four of the five studies reported on adverse outcomes. Grid laser was well tolerated within these studies. One participant had an apparent perforation of Bruch's membrane (a membrane under the macula) following laser but this did not affect their vision. Bevacizumab injection was also well tolerated with only minor local side effects (transient red eye and superficial bleeding). Participants receiving triamcinolone injection were at risk of developing a raised eye pressure that required medication or surgery, at risk of developing a cataract, and at risk of developing a serious eye infection (endophthalmitis).

Quality of the evidence
Good-quality evidence was available from one trial to support macular grid laser treatment for macular swelling following a blocked vein. There is insufficient evidence to recommend early grid laser, subthreshold laser, bevacizumab injections or triamcinolone injections over grid laser. Anti-VEGF and steroid treatments are becoming increasingly popular for treating eye conditions. However, more studies are needed to assess the longer-term outcome of these treatments against grid laser treatment in the management of macular oedema after branch retinal vein occlusions.

Authors' conclusions: 

Moderate-quality evidence from one RCT supports the use of grid laser photocoagulation to treat macular oedema following BRVO. There was insufficient evidence to support the use of early grid laser or subthreshold laser. There was insufficient evidence to show a benefit of intravitreal triamcinolone or anti-vascular endothelial growth factor (VEGF) over macular grid laser photocoagulation in BRVO. With recent interest in the use of intravitreal anti-VEGF or steroid therapy, assessment of treatment efficacy (change in visual acuity and foveal or central macular thickness using optical coherence tomography (OCT)) and the number of treatments needed for maintenance and long-term safety will be important for future studies.

Read the full abstract...
Background: 

Branch retinal vein occlusion (BRVO) is the second most common cause of retinal vascular abnormality after diabetic retinopathy. Persistent macular oedema develops in 60% of eyes with a BRVO. Untreated, only 14% of eyes with chronic macular oedema will have a visual acuity (VA) of 20/40 or better. Macular grid laser photocoagulation is used for chronic non-ischaemic macular oedema following BRVO and has been the mainstay of treatment for over 20 years. New treatments are available and a systematic review is necessary to ensure that the most up-to-date evidence is considered objectively.

Objectives: 

To examine the effects of macular grid laser photocoagulation in the treatment of macular oedema following BRVO.

Search strategy: 

We searched CENTRAL, Ovid MEDLINE, EMBASE, Web of Science Conference Proceedings Citation Index, the metaRegister of Controlled Trials (mRCT), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 August 2014.

Selection criteria: 

We included randomised controlled trials (RCTs) comparing macular grid laser photocoagulation treatment to another treatment, sham treatment or no treatment.

Data collection and analysis: 

We used standard methodological procedures expected by Cochrane.

Main results: 

We included five studies conducted in Europe and North America. Four separate trials compared grid laser to no treatment, sham treatment, intravitreal bevacizumab and intravitreal triamcinolone. One further trial compared subthreshold to threshold laser. Two of these trials were judged to be at high risk of bias in one or more domains.

In one trial of grid laser versus observation, people receiving grid laser were more likely to gain visual acuity (VA) (10 or more ETDRS letters) at 36 months (RR 1.75, 95% confidence interval (CI) 1.08 to 2.84, 78 participants, moderate-quality evidence). The effect of grid laser on loss of VA (10 or more letters) was uncertain as the results were imprecise (RR 0.68, 95% CI 0.23 to 2.04, 78 participants, moderate-quality evidence). On average, people receiving grid laser had better improvement in VA (mean difference (MD) 0.11 logMAR, 95% CI 0.05 to 0.17, high-quality evidence). In a trial of early and delayed grid laser treatment versus sham laser (n = 108, data available for 99 participants), no participant gained or lost VA (15 or more ETDRS letters). At 12 months, there was no evidence for a difference in change in VA (from baseline) between early grid laser and sham laser (MD -0.03 logMAR, 95% confidence interval (CI) -0.07 to 0.01, 68 participants, low-quality evidence) or between delayed grid laser and sham laser (MD 0.00, 95% CI -0.04 to 0.04, 66 participants, low-quality evidence).

The relative effects of subthreshold and threshold laser were uncertain. In one trial, the RR for gain of VA (15 or more letters) at 12 months was 1.68 (95% CI 0.57 to 4.95, 36 participants, moderate-quality evidence); the RR for loss of VA (15 or more letters) was 0.56 (95% CI 0.06 to 5.63, moderate-quality evidence); and at 24 months the change in VA from baseline was MD 0.07 (95% CI -0.10 to 0.24, moderate-quality evidence).

The relative effects of macular grid laser and intravitreal bevacizumab were uncertain. In one trial, the RR for gain of 15 or more letters at 12 months was 0.67 (95% CI 0.39 to 1.14, 30 participants, low-quality evidence). Loss of 15 or more letters was not reported. Change in VA at 12 months was MD 0.11 logMAR (95% CI -0.36 to 0.14, low-quality evidence).

The relative effects of grid laser and 1mg triamcinolone were uncertain at 12 months. RR for gain of VA (15 or more letters) was 1.13 (95% CI 0.75 to 1.71, 1 RCT, 242 participants, moderate-quality evidence); RR for loss of VA (15 or more letters) was 1.20 (95% CI 0.63 to 2.27, moderate-quality evidence); MD for change in VA was -0.03 letters (95% CI -0.12 to 0.06, moderate-quality evidence). Similar results were seen for the comparison with 4mg triamcinolone. Beyond 12 months, the visual outcomes were in favour of grid laser at 24 months and 36 months with people in the macular grid group gaining more VA.

Four studies reported on adverse effects. Laser photocoagulation appeared to be well tolerated in the studies. One participant (out of 71) suffered a perforation of Bruch's membrane, but this did not affect visual acuity.

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