Abstract: Two trials (341 eyes of 238 children and adults) were included comparing efficacy and safety of laser photocoagulation to no therapy in people with proliferative sickle retinopathy. There were 121 males and 117 females with an age range from 13 to 67 years. The laser photocoagulation technique used was different in the two trials; one single-centre trial employed sectoral scatter laser photocoagulation using an argon laser; and the second, two-centre trial, employed feeder vessel coagulation using argon laser in one centre and xenon arc in the second centre. The follow-up period ranged from a mean of 21 to 32 months in one trial and 42 to 47 months in the second. Both trials were at risk of selection bias (random sequence generation) because of the randomisation method employed for participants with bilateral disease. One study was considered to be at risk of reporting bias. Using sectoral scatter laser photocoagulation, one trial (174 eyes) reported that complete regression of proliferative sickle retinopathy was seen in 30.2% in the laser group and 22.4% in the control group (no difference between groups). The same trial reported the development of new proliferative sickle retinopathy in 34.3% of laser-treated eyes and in 41.3% of eyes given no treatment; again, there was no difference between treatment groups. The second trial, using feeder vessel coagulation, did not present full data for either treatment group for these outcomes. There was evidence from both trials (341 eyes) that laser photocoagulation using scatter laser or feeder vessel coagulation may prevent the loss of vision in eyes with proliferative sickle retinopathy (at median follow up of 21 to 47 months). Data from both trials indicated that laser treatment prevented the occurrence of vitreous haemorrhage with both argon and xenon laser; with the protective effect being greater with feeder vessel laser treatment compared to scatter photocoagulation. Regarding adverse effects, the incidence of retinal tear was minimal, with only one event reported. Combined data from both trials were available for 341 eyes; there was no difference between the laser and control arms for retinal detachment. In relation to choroidal neovascularization, treatment with xenon arc was found to be associated with a significantly higher risk, but visual loss related to this complication is uncommon with long-term follow up of three years or more. Data regarding quality of life and other adverse effects were not reported in the included trials. Our conclusions are based on the data from two trials conducted over 20 years ago. In the absence of further evidence, laser treatment for sickle cell disease-related retinopathy should be considered as a one of therapeutic options for preventing visual loss and vitreous haemorrhage. However, it does not appear to have a significant different effect on other clinical outcomes such as regression of proliferative sickle retinopathy and development of new ones. No evidence is available assessing efficacy in relation to patient-important outcomes (such as quality of life or the loss of a driving licence). There is limited evidence on safety, overall, scatter argon laser photocoagulation is superior in terms of adverse effects, although feeder vessel coagulation has a better effect in preventing vitreous haemorrhage. Further research is needed to examine the safety of laser treatment compared to other interventions such as intravitreal injection of anti-vascular endothelial growth factors. In addition, patient-important outcomes as well as cost-effectiveness should be addressed.

Plain-language summary: We included two randomised trials with 341 eyes of 238 participants comparing laser treatment to no intervention. There were 121 males and 117 females with an age range from 13 to 67 years. The trials employed different types of laser treatment. One trial employed scatter laser treatment in which lasers were applied to the retina near the new blood vessels using argon laser. Another employed feeder vessel laser coagulation in which lasers were applied directly to feeding blood vessels using xenon arc as well as argon laser. Participants were followed up for an average of 21 to 47 months. There is mixed evidence on the benefits of using laser therapy in people with retinopathy related to sickle cell disease. For instance, the effect of laser therapy on stopping the progression of new blood vessels and the development of new lesions did not differ greatly between the groups. However, there is evidence that laser therapy may prevent loss of vision and sight-threatening complications. Patient-important outcome data, such as quality of life, were not reported. The safety of laser treatment is acceptable, particularly scatter laser treatment using an argon laser. Although xenon arc lasers are associated with a higher number of complications, a loss of vision is not common. However, given that there are few trials with relatively low quality evidence, results should be treated with caution. Further research is needed to examine the safety of laser treatment compared to other interventions. In addition, patient-important outcomes (such as quality of life and loss of driving licence) as well as cost-effectiveness should be addressed. Both trials were at risk of bias due to the way participants were selected for groups (especially since treatment may be required for both eyes). One study was considered to be at risk of reporting bias as some results were only presented for one of the two treatment groups.