Objectives: To investigate prospectively whether the presence of pre-plus disease predicts progression to severe retinopathy of prematurity (ROP) requiring laser treatment. Methods: Posterior retinal video recordings were obtained during 710 indirect ophthalmoscopy examinations of 214 premature infants over a period of 5 years. Two masked experts reviewed short video recordings and determined whether there was plus disease, pre-plus disease, or neither. The primary analysis included results of one examination of the right eye at 33 to 34 weeks' postmenstrual age. The primary outcome was a comparison of the proportion of eyes subsequently requiring laser treatment between the group graded as having pre-plus disease vs the group graded as having neither plus disease nor pre-plus disease. Results: Of 10 eyes with pre-plus disease at 33 to 34 weeks' postmenstrual age, 7 (70%) subsequently required laser treatment; of 154 eyes without pre-plus disease or plus disease at 33 to 34 weeks' postmenstrual age, 14 (9%) subsequently required laser treatment (risk ratio, 7.7; 95% confidence interval, 4.1-14.8; P < .001). The mean time between the examination diagnosing preplus disease and laser treatment was 1.6 weeks (range, 1.0-2.4 weeks). When adjusting for birth weight, gestational age, ROP location (zone), and ROP severity (stage), the presence of pre-plus disease at 33 to 34 weeks' postmenstrual age independently predicted the need for laser treatment (adjusted odds ratio, 7.6; 95% confidence interval, 1.4-42.3; P = .02). Conclusions: Pre-plus disease observed early during the course of ROP is strongly associated with the development of severe ROP requiring laser treatment. The diagnosis of pre-plus disease has prognostic value beyond that already provided by birth weight, gestational age, ROP zone, and ROP stage. Eyes with pre-plus disease should be closely observed to allow optimal timing of intervention.
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