Descemet Stripping Only: Long-Term Outcomes.

PURPOSE: Descemet stripping only (DSO) is a relatively novel treatment for Fuchs endothelial corneal dystrophy (FECD). In this procedure, a central area of Descemet membrane and endothelium is removed without the insertion of donor tissue. Evaluation of long-term outcomes (≥5 years) after DSO is imperative to establish the validity of this procedure and to determine its role in the management of Fuchs endothelial dystrophy. Published outcomes are limited but promising. This study evaluates the 5- and 6-year outcomes of patients who had DSO at a single institution. METHODS: This is a retrospective chart review of patients with FECD who underwent DSO in 2016 and 2017. RESULTS: Eleven patients and 13 eyes met the criteria. Twelve of 13 eyes achieved corneal clearance. Two eyes had corneal decompensation requiring subsequent endothelial keratoplasty (EK). Of the 10 eyes that maintained clear corneas, 9 had a best-corrected visual acuity (BCVA) of at least 20/30 (mean logarithm of the minimim angle of resolution [logMAR] visual acuity [VA] 0.18 ± 0.16) at 5 years post-operatively (POY5). At 6 years, 7 of 8 eyes had a VA better than 20/40 (mean logMAR VA 0.17 ± 0.04). One patient had decreased VA due to progression of macular degeneration. Patients who required EK achieved good vision and corneal clearance. CONCLUSIONS: This is the largest series of patients with long-term follow-up after DSO. Ten of the 13 eyes (77%) responded and maintained clear central corneas for at least 5 years. Patients with failed DSO can achieve corneal clearance and good vision with subsequent EK. These patient outcomes support the role of DSO in the management of patients with FECD.

Potent Tetrahydroquinolone Eliminates Apicomplexan Parasites.

Apicomplexan infections cause substantial morbidity and mortality, worldwide. New, improved therapies are needed. Herein, we create a next generation anti-apicomplexan lead compound, JAG21, a tetrahydroquinolone, with increased sp3-character to improve parasite selectivity. Relative to other cytochrome b inhibitors, JAG21 has improved solubility and ADMET properties, without need for pro-drug. JAG21 significantly reduces Toxoplasma gondii tachyzoites and encysted bradyzoites in vitro, and in primary and established chronic murine infections. Moreover, JAG21 treatment leads to 100% survival. Further, JAG21 is efficacious against drug-resistant Plasmodium falciparum in vitro. Causal prophylaxis and radical cure are achieved after P. berghei sporozoite infection with oral administration of a single dose (2.5 mg/kg) or 3 days treatment at reduced dose (0.625 mg/kg/day), eliminating parasitemia, and leading to 100% survival. Enzymatic, binding, and co-crystallography/pharmacophore studies demonstrate selectivity for apicomplexan relative to mammalian enzymes. JAG21 has significant promise as a pre-clinical candidate for prevention, treatment, and cure of toxoplasmosis and malaria.