The evidence from ETDRS suggests that treatment of severe NPDR and early PDR was more effective in reducing future visual loss than waiting to treat at HR-PDR stage, but there are weaknesses in the evidence. Only SVLV reached statistical significance. ETDRS did not provide results separately for severe NPDR and early PDR. The primary end point was SVL which was uncommon in all groups, and as defined was very severe. The reduction in the development of HRC-PDR in eyes treated with PRP earlier might have been expected to lead to further reductions in visual loss with longer follow-up.
So one question for policy-makers is whether the evidence is deemed sufficient to recommend PRP at NPDR and early PDR stage, or whether further research is necessary, which might include separating NPDR and early PDR.
However, the balance of risk and harm, and costs, may have changed since the advent of new laser technologies and treatment regimes. These may be as effective but have fewer adverse effects. So recommendation for treatment or for further research would need to take account of changes in:
- laser machines
- more modern regimens. It is necessary to consider both type of laser and the ways in which they are used – number of burns, number of sessions, selective versus PRP
- more accurate diagnosis aided by imaging devices such as OCT and wide-angle cameras, that were not available at the time of the DRS and ETDRS *metabolic control.
In this chapter from NCBI Bookshelf. (A service of the National Library of Medicine, National Institutes of Health.) by Royle P, Mistry H, Auguste P, et al. Pan-retinal photocoagulation and other forms of laser treatment and drug therapies for non-proliferative diabetic retinopathy: systematic review and economic evaluation. Southampton (UK): NIHR Journals Library; 2015 Jul. (Health Technology Assessment, No. 19.51.)
they have provided review of some laser studies from more recent times. Their main aim is to identify which machines and regimens would be used now, either in treatment or research. Preliminary searches showed that none of the newer trials addressed our primary question of the optimum timing of PRP, and they therefore decided to use studies of laser photocoagulation at later stages and see what could be extrapolated from these.
A feature of trends in laser photocoagulation is that it tended to use less intense laser burns, and may be more targeted, for example treating only areas of peripheral ischaemia detected using wide-angle FA, with fewer adverse effects. One question which then arises is whether it has become less effective.
Modified ETDRS (mETDRS) direct/grid photocoagulation as used for DMO was described by the DRCRN (DRCRnet) as being targeted only at areas of thickened retina, areas of retinal non-perfusion and leaking microaneurysms using a smaller laser spot (50 µm) and less intense burn end point (grey) in order to balance therapeutic effect and adverse effects.
Most people now use pattern lasers for PRP, rather than the argon laser, because they are faster and less painful, but there is still sparse use of argon.
The sub-threshold diode laser is less destructive than the argon laser, depending on how it is applied. If at sub-threshold level then it would be expected to cause less damage than argon applied at threshold levels. If the diode was applied with a micropulse mode (reducing the temperature of the tissue – less thermal effect so less damage. Photocoagulation with the diode laser is reported to damage only the outer retinal layers and the choroid, whereas the argon laser damages both inner and outer retina and choroid.
The sub-threshold diode laser has been introduced in the treatment of DMO, but has not spread much into use, possibly because for PRP, it requires more sessions and more burns.
We also note that in Japan, a more selective approach to laser therapy is used, with targeting based on FA, so that only ischaemic areas are lasered. This is a more restrictive approach than traditional PRP.
Here is detailed publication