Objectively-measured compliance to atropine penalization treatment in children with amblyopia: a pilot study

Background:To date,compliance to atropine penalization in amblyopic children has only been assessed through self-report.The goal of this pilot study is to measure compliance to atropine penalization objectively.Methods:Seven amblyopic children(3-8 years;20/40-20/125 in the amblyopic eye) were enrolled.None had been treated with atropine previously.Children were prescribed either a twice per week or daily atropine regimen by their physicians.Compliance was defined as the percentage of days in which the atropine eye drop was taken compared to the number of doses prescribed.We used medication event monitoring system(MEMS) caps to objectively measure compliance.The MEMS caps are designed to electronically record the time and date when the bottle is opened.The parents of the children were provided a calendar log to subjectively report compliance.Participants were scheduled for return visits at 4 and 12 weeks.Weekly compliance was analyzed.Results:At 4 weeks,objective compliance averaged 88%(range,57-100%),while subjective compliance was 98%(range,90-100%).The actual dose in grams and visual acuity(VA) response relationship(r=0.79,P=0.03) was significantly better than the relationship between regimen and response(r=0.41,P>0.05),or the relationship between actual dose in drops and response(r=0.52,P>0.05).Conclusions:Objective compliance to atropine penalization instructions can be monitored with MEMS,which may facilitate our understanding of the dose-response relationship.Objective compliance with atropine penalization decreases over time and varies with regimen.On average,subjective parental reporting of compliance is overestimated.

Neuroretinal hypoxic signaling in a new preclinical murine model for proliferative diabetic retinopathy

Diabetic retinopathy(DR)affects approximately one-third of diabetic patients and,if left untreated,progresses to proliferative DR(PDR)with associated vitreous hemorrhage,retinal detachment,iris neovascularization,glaucoma and irreversible blindness.In vitreous samples of human patients with PDR,we found elevated levels of hypoxia inducible factor 1 alpha(HIF1α).HIFs are transcription factors that promote hypoxia adaptation and have important functional roles in a wide range of ischemic and inflammatory diseases.To recreate the human PDR phenotype for a preclinical animal model,we generated a mouse with neuroretinal-specific loss of the von Hippel Lindau tumor suppressor protein,a protein that targets HIF1αfor ubiquitination.We found that the neuroretinal cells in these mice overexpressed HIF1αand developed severe,irreversible ischemic retinopathy that has features of human PDR.Rapid progression of retinopathy in these mutant mice should facilitate the evaluation of therapeutic agents for ischemic and inflammatory blinding disorders.In addition,this model system can be used to manipulate the modulation of the hypoxia signaling pathways,for the treatment of non-ocular ischemic and inflammatory disorders.