Contexto Mundial y Nacional de la Salud Pública – Perú
I. LA SALUD PÚBLICA
1. EL CONTEXTO MUNDIAL Fin de la historia
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:
l laser machines
l 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
l 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
l metabolic control.
In this chapter we review some laser studies from more recent times. The 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 we 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.54
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.55
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.15
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.17This is a more restrictive approach than traditional PRP.
Methods
Inclusion and exclusion criteria forChapters 3and4
We used the same approach for laser trials (this chapter) and drug–laser combinations (seeChapter 4).
Inclusion criteria Type of studies
l For comparing effectiveness of different types of laser treatment and of the combination of lasers and anti-VEGF and steroid injections, we looked for RCTs.
l For assessing adverse events, we also included observational studies.
l Publication year 2000 or later, in order to reflect current practice.
l We included studies at any stage of retinopathy because of a dearth of laser studies at NPDR stage. For effectiveness in terms of visual state, we preferred a minimum duration of 6 months, but we included trials with follow-up of 3 months or more, because regression of neovascularisation can be seen 2–3 months after PRP. We also included non-trial studies of shorter duration for data on adverse effects.
Types of participants
l Patient groups–type 1 and type 2 diabetes, with NPDR or PDR, being treated with laser photocoagulation.
Follow-up
l For effectiveness, studies with a minimum follow-up period of 6 months were included.
l For safety, shorter duration trials were also included.
Outcomes
l Visual acuity; progression and regression of retinopathy; contrast sensitivity.
l Adverse effects in eye–pain, cataract, raised IOP, vitreous bleeds, need for vitrectomy.
l Number of treatments and hence visits required.
l We were not interested in outcomes not evident to patients such as retinal or central macular thickness (CMT), or angiogram results, which are more guides to treatment than outcomes.
Exclusion criteria
l Studies of treatment of DMO were excluded for assessing laser efficacy, as PRP is not used for DMO. However, they could be included for assessing the efficacy of drugs if they reported effects on DR (NPDR or PDR). Studies with fewer than 20 eyes were excluded.
Search strategy
The databases MEDLINE, EMBASE and The Cochrane Library were searched using the search strategies detailed inChapter 2andAppendix 2. The databases were searched from their inception until August 2013 and then auto-alerts were run until February 2014. However, for this section, only studies published since 2000 were included, as we were interested in recent laser methods and drug developments. In practice, this applied only to laser trials, as there were no drug-plus-laser studies before 2000.
Identification of studies
Titles and abstracts of the records retrieved were checked against the inclusion criteria by two independent reviewers (NW/PR). Any studies definitely or possibly fulfilling the inclusion criteria were retrieved in full and checked for final inclusion by two reviewers independently (NW/PR). There was no need for discussions with a third reviewer.
Data extraction strategy
Data were extracted into a predesigned data extraction form. Data were extracted by one reviewer (PR/DS/KF) and checked by a second reviewer (KF/DS/PA).
Quality assessment strategy
The risk of bias or quality of RCTs was assessed using the Cochrane risk of bias tool, including the following items:
l adequacy of sequence generation
l allocation concealment
l masking (patients, doctors, outcome assessors)
l adequacy of handling of incomplete outcome data
l selective reporting
l presence of other bias (e.g. lack of similarity at baseline, inadequate power)
l funding source and authors conflict of interest.
The quality assessment was done by one reviewer (DS/KF) and checked by a second reviewer (KF/DS/PA).
Results
Results of the searches
A total of 978 records were retrieved by the searches. The titles and abstracts were screened for inclusion and exclusion. Based on titles and abstracts, 102 were considered possible inclusions and full texts of these were obtained. Out of these, 38 were included inChapter 2, and 38 were excluded because of not meeting the inclusion criteria outlined above. Seventeen were excluded as they were published pre-2000; the reasons for exclusion of the remaining 21 studies are given inTable 15. For the sake of brevity the trials will simply be referred to by the name of the first author and publication year.
We included 12 RCTs (in 14 articles) published after 2000 to assess the efficacy and safety of new laser technologies in patients with DR, though most had PDR. These are reviewed in this chapter.
Also included were 11 RCTs (published in 12 articles) that used anti-VEGFs or injectable steroids on their own or in combination with laser and compared it against laser. These are reviewed inChapter 4.