Laser treatment of drusen to prevent progression to advanced age-related macular degeneration

Review question
We reviewed the evidence about the effect of laser treatment of the centre of the retina in people with macular drusen to prevent the occurrence of the more advanced type of age-related macular degeneration (AMD).

Background
Drusen are yellowish deposits that can be seen in the macula (the centre of the retina) in a larger proportion of people as they get older. People with drusen, particularly extensive large drusen, are at higher risk of developing AMD. The most common complications in AMD are the growth of new blood vessels in the centre of the macula (called choroidal neovascularisation (CNV), also known as 'wet AMD') and loss of retinal cells or photoreceptors in the macula (called geographic atrophy). It has been observed clinically that making very small burns around the macula with laser light (laser photocoagulation) makes drusen disappear. Laser photocoagulation of drusen has thus been proposed as a way to prevent the development of CNV and geographic atrophy. More recently, subthreshold photocoagulation has been used to cause invisible laser burns and achieve drusen reduction with less damage to the retinal structure.

Search date
The evidence is current to 3 August 2015.

Study characteristics
This review included data from 11 trials conducted in Australia, Europe and North America. The studies followed up 2159 participants with drusen (3580 eyes) to two years, of which six studies (1454 participants) included people with one eye randomised to treatment and one to control. Four studies (850 eyes) used subthreshold photocoagulation.

Study funding sources
Three out of four studies using laser subthreshold photocoagulation were sponsored by the laser producer.

Key results
These studies showed that laser photocoagulation of drusen leads to their disappearance. However, laser photocoagulation of drusen did not reduce the risk of developing CNV, which was about 10% at three years in untreated participants. A smaller number of studies reported on the development of geographic atrophy, that is, atrophy in the centre of the macula, but these studies were inconclusive and the effect of laser treatment of drusen on the development of geographic atrophy was uncertain. The risk of visual loss was similar in treated and untreated groups. There was no suggestion that a benefit may exist with subthreshold photocoagulation.

Quality of the evidence
The overall quality of the evidence was high regarding failure to prevent CNV, but it was low for prevention of atrophy due to the small number of participants for whom this outcome was assessed.

Authors' conclusions: 

The trials included in this review confirm the clinical observation that laser photocoagulation of drusen leads to their disappearance. However, treatment does not result in a reduction in the risk of developing CNV, and was not shown to limit the occurrence of geographic atrophy or visual acuity loss.

Ongoing studies are being conducted to assess whether the use of extremely short laser pulses (i.e. nanosecond laser treatment) cannot only lead to drusen regression but also prevent neovascular AMD.

Read the full abstract...
Background: 

Drusen are amorphous yellowish deposits beneath the sensory retina. People with drusen, particularly large drusen, are at higher risk of developing age-related macular degeneration (AMD). The most common complication in AMD is choroidal neovascularisation (CNV), the growth of new blood vessels in the centre of the macula. The risk of CNV is higher among people who are already affected by CNV in one eye.

It has been observed clinically that laser photocoagulation of drusen leads to their disappearance and may prevent the occurrence of advanced disease (CNV or geographic atrophy) associated with visual loss.

Objectives: 

To examine the effectiveness and adverse effects of laser photocoagulation of drusen in AMD.

Search strategy: 

We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2015), EMBASE (January 1980 to August 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 3 August 2015.

Selection criteria: 

Randomised controlled trials (RCTs) of laser treatment of drusen in AMD in which laser treatment had been compared with no intervention or sham treatment. Two types of trials were included. Some trials studied one eye of each participant (unilateral studies); other studies recruited participants with bilateral drusen and randomised one eye to photocoagulation or control and the fellow eye to the other group.

Data collection and analysis: 

Two review authors independently selected studies and extracted data. We pooled data from unilateral and bilateral studies using a random-effects model. For the bilateral studies, we estimated the within-person correlation coefficient from one study and assumed it was valid for the others.

Main results: 

The update of this review found two additional studies, totaling 11 studies that randomised 2159 participants (3580 eyes) and followed them up to two years, of which six studies (1454 participants) included people with one eye randomised to treatment and one to control. Studies were conducted in Australia, Europe and North America.

Overall, the risk of bias in the included studies was low, particularly for the larger studies and for the primary outcome development of CNV. Photocoagulation did not reduce the development of CNV at two years' follow-up (odds ratio (OR) 1.07, 95% confidence interval (CI) 0.79 to 1.46, 11 studies, 2159 participants (3580 eyes), high quality evidence). This estimate means that, given an overall occurrence of CNV of 8.3% in the control group, we estimated an absolute risk reduction by no more than 1.4% in the laser group, according to the lower CI limit. Only two studies investigated the effect on the development of geographic atrophy and could not show a difference, but estimates were imprecise (OR 1.30, 95% CI 0.38 to 4.51, two studies, 148 participants (148 eyes), low quality evidence).

Among secondary outcomes, photocoagulation led to drusen reduction (OR 9.16, 95% CI 6.28 to 13.4, three studies, 570 participants (944 eyes), high quality evidence) but was not shown to limit loss of 3 or more lines of visual acuity (OR 0.99, 95% CI 0.81 to 1.22, nine studies, 2002 participants (2386 eyes), moderate quality evidence).

In a subgroup analysis, no difference could be shown for conventional visible (eight studies) versus subthreshold invisible (four studies) photocoagulation for the primary outcomes (P value = 0.29). The effect in the subthreshold group did not suggest a relevant benefit (OR 1.27, 95% CI 0.82 to 1.98). No study used micropulse subthreshold photocoagulation.

No other adverse effects (apart from development of CNV, geographic atrophy or visual loss) were reported.

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