Dysregulated complement is thought to play a central role in AMD pathogenesis, but the specific mechanisms have yet to be determined. In maculas of AMD specimens, we found that the complement regulatory protein, CD59, was increased in regions of uninvolved retinal pigmented epithelium (RPE) of early AMD, but decreased in the RPE overlying drusen and in geographic atrophy, an advanced form of AMD. While CD46 immunostaining was basolaterally distributed in the RPE of unaffected controls, it was decreased in diseased areas of early AMD samples. Since oxidized low density lipoproteins (oxLDL) collect in drusen of AMD and are a known complement trigger, we treated ARPE-19 cells with oxLDL and found that cellular CD46 and CD59 proteins were decreased by 2.9-fold and 9-fold (p<0.01), respectively. OxLDLs increased complement factor B mRNA and Bb protein, but not factor D, I, or H. OxLDLs increased C3b, but not C3a, C5 or C5b-9. C5b-9 was increased by 27% (p<0.01) when medium was supplemented with human serum, which was sufficient to induce poly (ADP-ribose) polymerase cleavage, a marker of apoptosis. The decreased levels of CD46 and CD59 were in part, explained by their release in exosomal and apoptotic membranous particles. In addition, CD59 was partially degraded through activation of IRE1α. Collectively, these results suggest that a combination of impaired complement regulators results in inadequately controlled complement by the RPE in AMD that induces RPE damage.

Our finding that 0% of parents correctly defined fever is both surprising and unsettling, and it should inform future discussions of fever between parents and clinicians.

This study was designed to validate a grading scheme for lateral nasal wall insufficiency with interrater and intrarater reliability measures. Representative endoscopic videos depicting varied degrees of lateral nasal wall insufficiency were collated into a 30-clip video (15 clips in duplicate). This was rated by five reviewers for a total of 150 observations. Interrater and intrarater reliability were determined using Fleiss kappa and intraclass correlation coefficient (ICC) statistics, respectively. Good agreement was established between reviewers (interrater reliability), with a Fleiss kappa of 0.7733 (p < 0.01). Analysis of intrarater variability with the ICC revealed a very strong agreement (ICC = 0.88; p < 0.01). The proposed grading system is shown to have good interrater and intrarater reliability. It provides a reliable instrument for assessing lateral wall insufficiency.

The SUNDROP initiative demonstrated a high degree of diagnostic reliability and was able to capture all infants with TW-ROP. Telemedicine offers a cost-effective, reliable and accurate screening methodology for identifying infants with TW-ROP without sacrificing quality of care.

Telemedicine demonstrates high diagnostic accuracy for detection of TW-ROP and can complement ROP screening.