Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 6 appraisals
European journal of pediatrics
Efficacy and safety of procedural sedation-analgesia during laser photocoagulation for retinopathy of prematurity: a systematic review
UNLABELLED: Laser photocoagulation for retinopathy of prematurity (ROP) in preterm infants causes significant procedural pain. Although general anaesthesia (GA) is the standard of care, many settings frequently rely on inadequate sedation-analgesia or topical anaesthesia alone, exposing neonates to considerable pain and clinical instability. This systematic review aimed to evaluate the efficacy and safety of procedural sedation-analgesia during laser photocoagulation for ROP. We searched MEDLINE, Embase, and Cochrane CENTRAL for trials investigating sedation-analgesic agents during laser photocoagulation. Primary outcome was analgesic efficacy (pain score reduction, rescue analgesics required). Additional outcomes included adverse effects (e.g., apnea, oxygen requirement). Two reviewers extracted relevant information and assessed risk-of-bias using ROB2 and evidence certainty using GRADE methodology. Of 540 articles screened, four relevant RCTs were identified (n = 265). These RCTs compared varying combinations of agents (oral dextrose vs. no dextrose, fentanyl vs. oral sucrose, fentanyl vs. ketamine, ketamine-propofol vs. GA). Three RCTs evaluating pain-related outcomes (PIPP-R score and intra-procedural crying duration) suggested that the investigated non-general anaesthetic regimens may provide inadequate procedural analgesia (low to very low-certainty evidence). The evidence is very uncertain about the effect of ketamine-propofol on post-procedure ventilation requirement compared with general anaesthesia. Apnea was the commonest adverse effect (three studies), especially with high-dose fentanyl (30%). Three studies had a low risk-of-bias, while one had some concerns (randomisation, outcome measurement). CONCLUSION: Overall, the included studies were small RCTs evaluating varying combinations of interventions, precluding concrete conclusions about the superiority of any analgesic regimen during laser photocoagulation. Further high-quality studies are needed to identify safe and effective analgesia for settings where GA is unavailable. REVIEW REGISTRATION: Prospectively registered on PROSPERO (CRD420251070146). WHAT IS KNOWN: • Laser photocoagulation procedure for retinopathy of prematurity is immensely painful. • Despite general anaesthesia being the standard, most neonates undergo the procedure under inadequate analgesia, particularly in high-burden settings. Optimal analgesic regimen for the laser procedure, in settings where general anaesthesia is unavailable, is unknown. WHAT IS NEW: • This systematic review of trials investigating analgesic agents for laser procedure for ROP found four RCTs with significant heterogeneity in intervention agents. • Low- to very low-certainty evidence suggests that none of the evaluated sedo-analgesic regimens consistently achieved optimal analgesia, and most infants continued to experience moderate-to-severe procedural pain.
13 July 2026
Read appraisal →The New England journal of medicine
Subretinal Gene Therapy for X-Linked Retinoschisis
BACKGROUND: X-linked retinoschisis is a recessive disease characterized by progressive macular degeneration and vision loss due to pathogenic variation in RS1. METHODS: We administered a single subretinal injection of an AAV8 vector containing human RS1 complementary DNA (scAAV8-hRS1) into one eye of patients 5 to 18 years of age who had X-linked retinoschisis. The primary end point was safety during the 52-week period after injection. Secondary end points included the change from baseline to week 52 in the best corrected visual acuity (BCVA), retinal structure (assessed with swept-source optical coherence tomography; SS-OCT), the function of photoreceptor and bipolar cells (assessed with full-field electroretinography), and macular sensitivity to light (assessed with microperimetry). RESULTS: A total of 12 patients were enrolled. The dose-escalation phase included two cohorts of 3 patients each who received scAAV8-hRS1 at a dose of 7.5×1010 or 1×1011 vector genomes. In the dose-expansion phase, 3 additional patients were enrolled in each cohort. Overall, 56 adverse events were reported during the 52 weeks after surgery. No patient was reported to have an adverse event of grade 3 or higher or ocular inflammation. A macular hole in the treated eye was observed at week 1 in 1 patient. The mean increase at week 52 in the BCVA was 10.8 letters among the treated eyes and 2.4 letters among the untreated eyes. SS-OCT imaging showed closure of the macular schisis cavity by week 13 in the treated eye in all 12 patients. The mean change at week 52 in central retinal thickness was -437.7 μm among the treated eyes and -17.2 μm among the untreated eyes; the outer retinal layers in the treated eyes of 9 patients were continuous at week 52. No clinically meaningful changes in the function of photoreceptor and bipolar cells or macular retinal sensitivity were observed in the treated eyes. CONCLUSIONS: In this study of subretinal gene therapy with scAAV8-hRS1 in 12 patients with X-linked retinoschisis, there were no reports of adverse events of grade 3 or higher or ocular inflammation. Further clinical testing of scAAV8-hRS1 is warranted. (Funded by the National Natural Science Foundation of China and others; Chinese Clinical Trial Registry number, ChiCTR2300076682.).
13 June 2026
Read appraisal →The British journal of ophthalmology
Ethnic and dose-dependent differences in atropine efficacy for myopia control: a systematic review and meta-analysis
BACKGROUND/AIM: Clinical uncertainty remains regarding optimal atropine concentration, treatment duration and potential differences in efficacy for myopia control between Asian and non-Asian children. This systematic review and meta-analysis evaluated the efficacy of different concentrations of atropine for myopia control, comparing outcomes among East Asian, South Asian and white European children. METHODS: Five databases were searched for randomised controlled trials (RCTs) including children ≤16 years with myopia who received atropine treatment. Thirty-four RCTs with ≥12 months of follow-up were included. Weighted mean differences (WMD) in spherical equivalent refraction (SER) progression and axial length (AL) elongation were pooled by atropine concentration and ethnicity. RESULTS: Compared with controls, atropine significantly reduced myopia progression across all concentrations: <0.1% (WMD in SER: 0.44 (95% CI 0.35 to 0.52) dioptres (D)/year; AL: -0.20 (95% CI -0.24 to -0.16) mm/year), 0.1% to <0.5% (0.81 (95% CI 0.50 to 1.13) D/year) and ≥0.5% (1.06 (95% CI 0.88 to 1.24) D/year; -0.36 (95% CI -0.40 to -0.33) mm/year). The pooled effect on SER and AL progression across all concentrations was greater in East Asians (0.63 (95% CI 0.50 to 0.76) D/year; -0.26 (95% CI -0.31 to -0.20) mm/year) than in South Asians (0.40 (95% CI 0.11 to 0.70) D/year; -0.13 (95% CI -0.21 to -0.05) mm/year) or white Europeans (0.18 (95% CI 0.11 to 0.25) D/year; -0.11 (95% CI -0.16 to -0.05) mm/year). CONCLUSION: Atropine slows myopia progression in a dose-dependent manner in studies with 1-5 years of follow-up. Efficacy appears greater in Asian children, particularly East Asians, who also exhibit greater photopic pupil dilation. These findings support the role of atropine in myopia control and highlight the importance of ethnicity-specific considerations when prescribing and tailoring treatment strategies. PROSPERO REGISTRATION NUMBER: CRD42023454104.
26 Apr 2026
Read appraisal →The British journal of ophthalmology
Two-year outcomes of repeated red light therapy in premyopic children: sustained efficacy and rebound effects
BACKGROUND: To evaluate the long-term prevention effectiveness and rebound effect of repeated red light therapy (RRLT) in children with premyopia over 2 years. METHODS: A total of 108 premyopic children (cycloplegia spherical equivalent refraction (SER): -0.50 to +0.75 D) were enrolled and followed for 24 months. Participants were randomly assigned to the RRLT or control groups. The RRLT was administered two times per day for 3 min per session, with at least 4-hour interval. At the beginning of the second year, participants receiving RRLT were further randomised into continued treatment and washout subgroups. Axial length (AL), SER and subfoveal choroidal thickness (SChT) were measured. RESULTS: Over 2 years, the RRLT group showed significantly smaller AL elongation (0.26 mm; 95% CI 0.18 to 0.35 mm) and SER progression (-0.21 D; 95% CI -0.35 to -0.08 D) compared with the controls (AL: 0.43 mm; 95% CI 0.36 to 0.49 mm; SER: -0.66 D; 95% CI -0.79 to -0.52 D). The RRLT group also demonstrated significantly less SChT thinning (-2.44 µm; 95% CI -16.11 to 11.23 µm) than the controls (-44.12 µm; 95% CI -53.05 to -35.19 µm). After RRLT cessation in the second year, the washout subgroup exhibited significantly faster AL elongation and more SChT thinning than the controls, with no significant difference in SER progression. CONCLUSIONS: The 2-year RRLT intervention effectively retarded AL elongation and SER progression in premyopic children by 0.17 mm and -0.45 D, respectively. Notably, a significant rebound effect was observed in AL growth following 1-year RRLT cessation.
25 Apr 2026
Read appraisal →European journal of pediatrics
The impact of growth hormone therapy on ocular structural parameters in idiopathic short stature: a systematic review and meta-analysis
This study aimed to conduct a systematic review and meta-analysis of the effects of growth hormone (GH) therapy on ocular structures and biometric parameters in children with idiopathic short stature (ISS), synthesizing existing evidence for future research. We systematically searched PubMed, EMBASE, the Cochrane Library, CNKI, Wanfang, and VIP databases from inception to September 2025. Randomized controlled trials and observational studies comparing the effects of GH therapy versus control on ocular biometric and refractive outcomes in children with ISS were included. Study quality was assessed using the Cochrane Risk of Bias Tool (RoB 2) and the NOS. Meta-analysis was performed using R software version 4.3.2, with effect sizes expressed as MD or SMD and 95% CI. Nine studies were included (4 RCTs, 5 cohort studies). Meta-analysis showed no significant association of GH therapy with corneal curvature (SMD = 0.13, 95% CI: -0.34 to 0.61). For axial length, the random-effects model showed no significant difference (MD = 0.72, 95% CI: -0.36 to 1.81), with high heterogeneity (I2 = 91.7%). Similarly, no significant association was found for intraocular pressure (MD = 1.38, 95% CI: -0.66 to 3.43; I2 = 95.9%). However, a significant association was observed for refractive status (MD = 0.53, 95% CI: 0.20 to 0.86; I2 = 0.0%). Sensitivity analysis showed robust results for corneal curvature and refractive outcomes, while axial length and intraocular pressure results were influenced by individual studies. Funnel plots and Egger's test indicated no significant publication bias.Conclusion: The associations between GH therapy and ocular biometric parameters in children with ISS remain uncertain. Current evidence suggests a possible link with refractive changes but shows no significant associations with axial length or intraocular pressure when accounting for high heterogeneity. The findings are inconsistent and should be regarded as hypothesis-generating, insufficient to recommend changes in clinical monitoring practice. Future large-sample, long-term studies are required.
17 Apr 2026
Read appraisal →The Cochrane database of systematic reviews
Insulin-like growth factor-1 for the prevention or treatment of retinopathy of prematurity
RATIONALE: Retinopathy of prematurity (ROP) is a disorder of the developing retina in which abnormal proliferation of retinal blood vessels may lead to severe visual compromise or retinal detachment in infants born preterm. Insulin-like growth factor-1 (IGF-1) promotes normal retinal vessel growth in utero; however, IGF-1 levels fall substantially following preterm birth. By returning IGF-1 to in utero levels, postnatal treatment with IGF-1 may interrupt ROP pathogenesis, preventing disease or reducing its severity. OBJECTIVES: To compare treatment with IGF-1 to standard care or placebo for the prevention of retinopathy of prematurity or treatment of early retinopathy of prematurity. SEARCH METHODS: We used CENTRAL, MEDLINE, Embase, Cochrane Database of Systematic Reviews, Issue 3, 2025, in the Cochrane Library, CINAHL Plus with Full Text (EBSCOhost), Epistemonikos, clinical trials registries (US National Library of Medicine Clinicaltrials.gov, World Health Organization's International Trials Registry Platform, and ISRCTN Registry), together with reference checking and citation searching to identify studies that are included in this review. The latest search date was 10 March 2025. ELIGIBILITY CRITERIA: We considered all randomized controlled trials (RCTs), cluster-RCTs, and quasi-RCTs comparing IGF-1 with standard care or placebo for the prevention of ROP or treatment of early ROP in preterm infants. We planned to exclude cross-over randomized trials. OUTCOMES: Our outcomes of interest were: • Development of Type 1 ROP, defined as ROP requiring treatment at any time during the birth hospitalization or outpatient follow-up • Development of ROP ≥ stage 3 at any time during the birth hospitalization or outpatient follow-up • Development of ROP of any severity at any time during the birth hospitalization or outpatient follow-up • Occurrence of one or more serious adverse events (SAEs) at any time during the birth hospitalization • Mortality during the birth hospitalization • Hypoglycemia during the birth hospitalization RISK OF BIAS: We used the original Cochrane Risk of Bias 1 tool (RoB 1) to assess possible bias in the included studies. SYNTHESIS METHODS: Dichotomous data were reported using risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CIs). Where possible, we synthesized results for each outcome using meta-analysis with fixed-effect models. We used GRADE to assess the certainty of evidence for each outcome. INCLUDED STUDIES: We included two studies totaling 140 participants. Both included studies were parallel-group RCTs performed between 2011 and 2016 enrolling extremely preterm infants in well-resourced settings in Europe and North America. The two published primary study references describe a two-center RCT (n = 19) and a 20-center RCT (n = 121) comparing treatment starting on the first day of life with intravenous IGF-1 (as mecasermin rinfabate) to standard care for prevention of ROP in newborn infants at 23 weeks' to 27 weeks plus six days' gestational age with follow-up through 40 weeks' postmenstrual age. SYNTHESIS OF RESULTS: Type 1 ROP/ROP requiring treatment Evidence is very uncertain regarding the effect of treatment with IGF-1 as compared to standard care/placebo for preventing development of Type 1 ROP/ROP requiring treatment (RR 0.94, 95% CI 0.38 to 2.35; P = 0.90; I2 = 0%; 2 RCTs, 116 infants; very low-certainty evidence). ROP ≥ stage 3 Evidence is very uncertain regarding the effect of treatment with IGF-1 as compared to standard care/placebo for preventing development of severe ROP (RR 1.27, 95% CI 0.61 to 2.65; P = 0.52; I2 = 0%; 2 RCTs, 116 infants; very low-certainty evidence). ROP of any severity Evidence is very uncertain regarding the effect of treatment with IGF-1 as compared to standard care/placebo for preventing development of ROP of any severity (RR 1.30, 95% CI 0.94 to 1.80; P = 0.12; I2 = 0%; 2 RCTs, 116 infants; very low-certainty evidence). SAEs during the birth hospitalization Evidence is very uncertain regarding the safety of treatment with IGF-1 as compared to standard care/placebo as reflected by the occurrence of one or more SAEs during the birth hospitalization in preterm infants (RR 1.18, 95% CI 0.94 to 1.47; P = 0.15; I2 = 65%; 2 studies, 140 infants; very low-certainty evidence). Post-hoc sensitivity analysis including only the larger RCT demonstrated an increased risk of experiencing one or more SAEs with IGF-1 compared to controls (RR 1.28, 95% CI 1.01 to 1.62, P = 0.05; RD 0.17, 95% CI 0.01 to 0.33, P = 0.04; number needed to treat for an additional harmful outcome (NNTH) 5.9; I2 = not applicable; 1 RCT, 121 infants; very low-certainty evidence). All-cause mortality during the birth hospitalization Evidence is very uncertain regarding the effect of treatment with IGF-1 as compared to standard care/placebo on all-cause mortality during the birth hospitalization in preterm infants (RR 1.69, 95% CI 0.71 to 3.99; P = 0.23; I2 = not applicable; 1 RCT, 121 infants; very low-certainty evidence). Hypoglycemia during the birth hospitalization Evidence is very uncertain regarding the safety of treatment with IGF-1 as compared to standard care/placebo as reflected by the incidence of hypoglycemia in preterm infants during the birth hospitalization (RR 1.00, 95% CI 0.62 to 1.63; P = 0.99; I2 = 0%; 2 RCTs, 140 infants; very low-certainty evidence). We assessed all results to be of very low certainty due to small total enrollment and substantial risk of bias. Both included studies had a high risk of bias in two domains. In addition, both were funded by industry. AUTHORS' CONCLUSIONS: The available data are of very low certainty, and so we are not able to draw conclusions about the effects of treatment with IGF-1 in preterm infants for preventing or treating ROP, or about its effects on risk of serious adverse events, mortality, or hypoglycemia in this population. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol available via DOI: 10.1002/14651858.CD013216.
16 Apr 2026
Read appraisal →