Purpose: There is an urgent need for a more effective intervention to slow or prevent progression of agerelated macular degeneration (AMD) from its early stages to vision-threatening late complications. Subthreshold nanosecond laser (SNL) treatment has shown promise in preclinical studies and a pilot study in intermediate AMD (iAMD) as a potential treatment. We aimed to evaluate the safety of SNL treatment in iAMD and its efficacy for slowing progression to late AMD.Design: The Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study is a 36month, multicenter, randomized, sham-controlled trial.Participants: Two hundred ninety-two participants with bilateral large drusen and without OCT signs of atrophy. Methods: Participants were assigned randomly to receive Retinal Rejuvenation Therapy (2RT Ò ; Ellex Pty Ltd, Adelaide, Australia) SNL or sham treatment to the study eye at 6-monthly intervals.Main Outcome Measures: The primary efficacy outcome was the time to development of late AMD defined by multimodal imaging (MMI). Safety was assessed by adverse events.Results: Overall, progression to late AMD was not slowed significantly with SNL treatment compared with sham treatment (adjusted hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.33e1.14; P ¼ 0.122). However, a post hoc analysis showed evidence of effect modification based on the coexistence of reticular pseudodrusen (RPD; adjusted interaction P ¼ 0.002), where progression was slowed for the 222 participants (76.0%) without coexistent RPD at baseline (adjusted HR, 0.23; 95% CI, 0.09e0.59; P ¼ 0.002), whereas an increased progression rate (adjusted HR, 2.56; 95% CI, 0.80e8.18; P ¼ 0.112) was observed for the 70 participants (24.0%) with RPD with SNL treatment. Differences between the groups in serious adverse events were not significant.Conclusions: In participants with iAMD without MMI-detected signs of late AMD, no significant difference in the overall progression rate to late AMD between those receiving SNL and sham treatment were observed. However, SNL treatment may have a role in slowing progression for those without coexistent RPD and may be inappropriate in those with RPD, warranting caution when considering treatment in clinical phenotypes with RPD. Our findings provide compelling evidence for further trials of the 2RT Ò laser, but they should not be extrapolated to other short-pulse lasers.

Objective To evaluate the diagnostic accuracy of clinical decision rules and physician judgment for identifying clinically important traumatic brain injuries (TBIs) in children with minor head injuries presenting to the emergency department (ED). Methods We prospectively enrolled children <18 years of age with minor head injury (Glasgow Coma Scale 13 – 15) presenting within 24 hours of their injuries. We assessed the ability of 3 clinical decision rules (CATCH, CHALICE, PECARN) and 2 measures of physician judgment (estimated of <1% risk of TBI, actual CT ordering practice) to predict clinically important TBI, as defined by death from TBI, need for neurosurgery, intubation >24 hours for TBI, or hospital admission >2 nights for TBI. Results Among the 1,009 children, 21 (2%; 95% CI: 1% to 3%) had clinically important TBIs. Only physician practice and PECARN identified all clinically important TBIs, with ranked sensitivities as follows (95% CI): Physician practice and PECARN each 100% (84% to 100%), physician estimates 95% (76% to 100%), CATCH 91% (70% to 99%), and CHALICE 84% (60% to 97%). Ranked specificities were as follows: CHALICE 85% (82% to 87%), physician estimates 68% (65% to 71%), PECARN 62% (59% to 66%), physician practice 50% (47% to 53%), and CATCH 44% (41% to 47%). Conclusions Of the 5 modalities studied, only physician practice and PECARN identified all clinically important TBIs, with PECARN being slightly more specific. CHALICE was incompletely sensitive but the most specific of all rules. CATCH was incompletely sensitive and had the poorest specificity of all modalities.