How effective are the various techniques of laser photocoagulation in sickle cell disease-related proliferative retinopathy (development of sight-threatening complications due to excessive growth of blood vessels in the back of the eye)?
Sickle cell disease is a genetic disorder affecting many organs including the eyes. The back of the eye (retina) can develop problems due to sickle cell disease. A certain number of people with sickle cell disease develop sight-threatening complications due to excessive blood vessel growth in the retina which is known as proliferative sickle retinopathy. Laser therapy is used to control the growth of new blood vessels in affected eyes. There are different types and techniques of laser used in treatment. However, we do not know whether these various laser treatments offer advantages compared to no treatment or other interventions with regards to effectiveness and safety.
The evidence is current to: 26 June 2022.
We included three randomised trials (414 eyes, 399 participants), comparing laser treatment to no intervention. There were 160 males and 179 females ranging in age from 13 to 67 years. The trials used different types of laser treatment. One trial applied lasers to the retina near the new blood vessels (sectoral scatter laser treatment) using an argon laser. Another applied lasers directly to feeding blood vessels (feeder vessel laser coagulation) using either xenon arc or argon laser. The third trial used focal scatter laser photocoagulation with an argon laser. Participants were followed up for an average of 21 to 48 months.
There is low- to very low-certainty evidence on the effects of using laser therapy in people with retinopathy related to sickle cell disease. In one trial, 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 (very low-certainty evidence). From the evidence found, we are not sure if laser therapy can prevent loss of vision (very low-certainty evidence), but it may prevent sight-threatening complications (low-certainty evidence). The trials did not report on patient-important outcomes, such as quality of life.
Evidence from the three trials showed that the safety of laser treatment is acceptable (few adverse effects), particularly scatter laser treatment using an argon laser. Although xenon arc lasers are linked to a higher number of complications, a loss of vision is not common. However, given that there are few trials with relatively low-certainty evidence, results should be treated with caution. Further research is needed to examine the safety of laser treatment compared to other interventions. Trials should also measure patient-important outcomes (such as quality of life and loss of driving licence) as well as cost-effectiveness.
Certainty of the evidence
We thought there was a risk of bias due to the way participants were selected for groups in two trials, especially since treatment may be required for both eyes. We thought there was a risk of bias in one trial which only presented some results for one of the two treatment groups; and we thought a third trial had a risk of bias as it did not clearly state in the Methods section of the paper which outcomes they intended to report.
Our conclusions are based on the data from three trials (two of which were conducted over 30 years ago). Given the limited evidence available, which we assessed to be of low- or very low-certainty, we are uncertain whether laser therapy for sickle cell retinopathy improves the outcomes measured in this review. This treatment does not appear to have an effect on clinical outcomes such as regression of PSR and development of new incidences. No evidence is available assessing efficacy in relation to patient-important outcomes (such as quality of life or the loss of a driving licence). 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 (VEGFs) . Patient-important outcomes as well as cost-effectiveness should be addressed.
Sickle cell disease (SCD) includes a group of inherited haemoglobinopathies affecting multiple organs including the eyes. Some people with SCD develop ocular manifestations. Vision-threatening complications are mainly due to proliferative sickle retinopathy, which is characterised by proliferation of new blood vessels. Laser photocoagulation is widely applicable in proliferative retinopathies. It is important to evaluate the efficacy and safety of laser photocoagulation in the treatment of proliferative sickle retinopathy (PSR) to prevent sight-threatening complications.
To evaluate the effectiveness of various techniques of laser photocoagulation therapy in SCD-related proliferative retinopathy.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 4 July 2022.
We also searched the following resources (26 June 2022): Latin American and Caribbean Health Science Literature Database (LILACS); WHO International Clinical Trials Registry Platforms (ICTRP); and ClinicalTrials.gov.
Randomised controlled trials comparing laser photocoagulation to no treatment in children and adults with SCD.
Two review authors independently assessed eligibility and risk of bias of the included trials; we extracted and analysed data, contacting trial authors for additional information. We assessed the certainty of the evidence using the GRADE criteria.
We included three trials (414 eyes of 339 children and adults) comparing the efficacy and safety of laser photocoagulation to no therapy in people with PSR. There were 160 males and 179 females ranging in age from 13 to 67 years. The trials used different laser photocoagulation techniques; one single-centre trial employed sectoral scatter laser photocoagulation using an argon laser; a two-centre trial employed feeder vessel coagulation using argon laser in one centre and xenon arc in the second centre; while a third trial employed focal scatter laser photocoagulation using argon laser. The mean follow-up periods were 21 to 32 months in one trial, 42 to 47 months in a second, and 48 months in the third. Two trials had a high risk of allocation bias due to the randomisation method for participants with bilateral disease; the third trial had an unclear risk of selection bias. One trial was at risk of reporting bias. Given the unit of analysis is the eye rather than the individual, we chose to report the data narratively.
Using sectoral scatter laser photocoagulation, one trial (174 eyes) reported no difference between groups for complete regression of PSR: 30.2% in the laser group and 22.4% in the control group. The same trial also reported no difference between groups in the development of new PSR: 34.3% of lasered eyes and 41.3% of control eyes (very low-certainty evidence). The two-centre trial using feeder vessel coagulation, only presented data at follow-up for one centre (mean period of nine years) and reported the development of new sea fan in 48.0% in the treated and 45.0% in the control group; no statistical significance (P = 0.64). A third trial reported regression in 55% of the laser group versus 28.6% of controls and progression of PSR in 10.5% of treated versus 25.7% of control eyes. We graded the evidence for these two primary outcomes as very low-certainty evidence.
The sectoral scatter laser photocoagulation trial reported visual loss in 3.0% of treated eyes (mean follow-up 47 months) versus 12.0% of controlled eyes (mean follow-up 42 months) (P = 0.019). The feeder vessel coagulation trial reported visual loss in 1.14% of the laser group and 7.5% of the control group (mean follow-up 26 months at one site and 32 months in another) (P = 0.07). The focal scatter laser photocoagulation trial (mean follow-up of four years) reported that 72/73 eyes had the same visual acuity, while visual loss was seen in only one eye from the control group. We graded the certainty of the evidence as very low.
The sectoral scatter laser trial detected vitreous haemorrhage in 12.0% of the laser group and 25.3% of control with a mean follow-up of 42 (control) to 47 months (treated) (P ≤ 0.5). The two-centre feeder vessel coagulation trial observed vitreous haemorrhage in 3.4% treated eyes (mean follow-up 26 months) versus 27.5% control eyes (mean follow-up 32 months); one centre (mean follow-up nine years) reported vitreous haemorrhage in 1/25 eyes (4.0%) in the treatment group and 9/20 eyes (45.0%) in the control group (P = 0.002). The scatter laser photocoagulation trial reported that vitreous haemorrhage was not seen in the treated group compared to 6/35 (17.1%) eyes in the control group and appeared only in the grades B and (PSR) stage III) (P < 0.05). We graded evidence for this outcome as low-certainty.
Regarding adverse effects, only one occurrence of retinal tear was reported. All three trials reported on retinal detachment, with no significance across the treatment and control groups (low-certainty evidence). One trial reported on choroidal neovascularization, with treatment with xenon arc 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.
The included trials did not report on other adverse effects or quality of life.