Perivascular macrophages in the neonatal macaque brain undergo massive necroptosis after simian immunodeficiency virus infection.

We previously showed that rhesus macaques neonatally infected with simian immunodeficiency virus (SIV) do not develop SIV encephalitis (SIVE) and maintain low brain viral loads despite having similar plasma viral loads compared to SIV-infected adults. We hypothesize that differences in myeloid cell populations that are the known target of SIV and HIV in the brain contribute to the lack of neonatal susceptibility to lentivirus-induced encephalitis. Using immunohistochemistry and immunofluorescence microscopy, we examined the frontal cortices from uninfected and SIV-infected infant and adult macaques (n = 8/ea) as well as adults with SIVE (n = 4) to determine differences in myeloid cell populations. The number of CD206+ brain perivascular macrophages (PVMs) was significantly greater in uninfected infants than in uninfected adults and was markedly lower in SIV-infected infants while microglia numbers were unchanged across groups. CD206+ PVMs, which proliferate after infection in SIV-infected adults, did not undergo proliferation in infants. While virtually all CD206+ cells in adults are also CD163+, infants have a distinct CD206 single-positive population in addition to the double-positive population commonly seen in adults. Notably, we found that more than 60% of these unique CD206+CD163- PVMs in SIV-infected infants were positive for cleaved caspase-3, an indicator of apoptosis, and that nearly 100% of this subset were concomitantly positive for the necroptosis marker receptor-interacting protein kinase-3 (RIP3). These findings show that distinct subpopulations of PVMs found in infants undergo programmed cell death instead of proliferation following SIV infection, which may lead to the absence of PVM-dependent SIVE and the limited size of the virus reservoir in the infant brain.

Updated Cost-Effectiveness of Intravitreal Ocriplasmin for Vitreomacular Adhesion and Macular Hole.

BACKGROUND AND OBJECTIVE: The purpose of this study is to provide an updated assessment of cost-efficacy of intravitreal ocriplasmin (IVO) for vitreomacular adhesion (VMA) and macular holes (MH). PATIENTS AND METHODS: This was a single-center, multiple-physician, institutional review board-approved, retrospective, 15-month cost-effectiveness analysis study (January 2015 to April 2016). Clinical charts and billing records of 247 patients with VMA and MH were reviewed. Patients were divided into group 1 (VMA and MH treated by pars plana vitrectomy [PPV]), group 2 (VMA and MH treated by IVO), and group 3 (VMA treated by IVO). Success rates of interventions in each group were compared, including cost-effectiveness, cost per line-year, and cost per quality-adjusted life-year (QALY). RESULTS: Success rates for initial intervention were 98% in group 1, 55.6% in group 2, and 67.7% in group 3. Cost of PPV at our institution was $6,538.00 and cost of IVO (2016) was $3,480.00. Using a cohort-based computer Markov model, the treatment decision tree demonstrated group 1 was less cost-effective, with cost per line of $2,654.39, cost per line-year saved of $185.62, and cost per QALY of $6,187.00. Group 2 was cost-effective with cost per line of $2,456.25, cost per line-year saved of $171.77, and cost per QALY of $5,726.00. The difference in cost-effectiveness showed IVO was more cost-effective than PPV, with a difference in cost per line of $198.14, cost per line-year saved of $13.85, and cost per QALY of $461.00. CONCLUSIONS: IVO is a more cost-effective intervention than vitrectomy for the treatment of VMA and MH in the setting of judicious use in appropriate patients. The success rate of IVO in our patient population was greater than currently published rates and most certainly impacted probability of cost-efficacy. Further research targeting optimizing IVO success rate is needed. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e240-e248.].