Downregulation of CYP17A1 by 20-hydroxyecdysone: plasma progesterone and its vasodilatory properties.

Aim: To investigate the effect of 20-hydroxyecdysone on steroidogenic pathway genes and plasma progesterone, and its potential impact on vascular functions. Methods: Chimeric mice with humanized liver were treated with 20-hydroxyecdysone for 3 days, and hepatic steroidogenic pathway genes and plasma progesterone were measured by transcriptomics and GC-MS/MS, respectively. Direct effects on muscle and mesenteric arterioles were assessed by myography. Results: CYP17A1 was downregulated in 20-hydroxyecdysone-treated mice compared with untreated group (p = 0.04), with an insignificant increase in plasma progesterone. Progesterone caused vasorelaxation which was blocked by 60 mM KCl, but unaffected by nitric oxide synthase inhibition. Conclusion: In the short term, 20-hydroxyecdysone mediates CYP17A1 downregulation without a significant increase in plasma progesterone, which has a vasodilatory effect involving inhibition of voltage-dependent calcium channels, and the potential to enhance 20-hydroxyecdysone vasorelaxation.

MONTHLY INTRAVITREAL INFLIXIMAB IN BEHÇET'S DISEASE ACTIVE POSTERIOR UVEITIS: A Long-Term Safety Study.

PURPOSE: To study the safety of extended monthly intravitreal infliximab injections in patients with active posterior uveitis in Behcet's disease. METHODS: This is a prospective, interventional, noncomparative, open-label, pilot study of 9 monthly intravitreal infliximab injections (1 mg/0.05 mL) for 22 eyes of 16 patients with active posterior uveitis in Behcet's disease. Control of inflammation and visual outcomes were assessed, and ocular complications were monitored during the study period. RESULTS: Successful treatment was achieved in 7 eyes (35%), and failure was encountered in 13 eyes (65%). Only seven eyes of six patients (35%) had completed the study and achieved complete resolution of inflammation with improved best-corrected visual acuity and no complications. Failure was either because of inability to control the inflammation in nine eyes (45%) or development of exacerbation of inflammation in four eyes (20%). Four eyes developed severe immunological reaction from the drug after first (n = 1), second (n = 2), and third (n = 1) injections and had to discontinue the injections. Kaplan-Meier survival analysis showed that the mean estimated time to failure was 3.3 ± 0.2 months, and all failed eyes required revision of their systemic immunotherapy to control the ocular inflammation. CONCLUSION: Intravitreal infliximab for active posterior uveitis in Behcet's disease was associated with a high complication rate and failure to control inflammation in most eyes. It should not be considered a substitute to systemic therapy.

Change in Ophthalmology Practice during COVID-19 Pandemic: Egyptian Perspective.

PURPOSE: To assess the impact of the COVID-19 pandemic on ophthalmology practice in the Cairo metropolitan area. METHODS: This is a cross-sectional observational analytic study among ophthalmologists practicing in different hospitals in the Cairo metropolitan area. The data were collected through a self-administered questionnaire covering general measures taken during practice. RESULTS: The questionnaire was sent to 250 ophthalmologists, with an 82% response rate. Most of the participants were concerned about the economic impact of the pandemic, as there is a 60-80% reduction in the flow of patients with a consequent 80-100% reduction in surgical cases. Most of the participants have access to personal protective equipment, and the safety protocols are followed, especially by the older ophthalmologists. Thus, the surgeons are willing to perform elective surgeries, adhering to strict safety protocols (70.8, 42.6, and 18.8% of the refractive surgeons, corneal surgeons, and retinal surgeons, respectively; p = 0.00). Furthermore, 63.9% of the participants, especially the young ophthalmologists, are willing to see COVID-19 patients and operate on them if needed. CONCLUSIONS: The COVID-19 pandemic could go on for months or even years with a significant impact on ophthalmology practice. Trying to keep a balance between safety and economic burden, the majority of ophthalmologists are willing to see elective patients and urgently operate on a COVID-19 patient, under adherence to the safety protocols.

INTRAVITREAL INFLIXIMAB IN REFRACTORY UVEITIS IN BEHCET'S DISEASE: A Safety and Efficacy Clinical Study.

PURPOSE: To assess the safety and efficacy of intravitreal infliximab (1 mg/0.05 mL) in patients with refractory posterior uveitis in Behcet's disease. METHODS: Twenty patients were included in this study. Best corrected visual acuity (BCVA), vitreous haze (graded 0-4), vasculitis, retinitis, and papillopathy (presence or absence) were assessed at baseline, Day 1 and Week 2, 4, 6, 8, 12, and 18. Optical coherence tomography (OCT) central foveal thickness, fluorescein angiography, and flash electroretinogram were done at baseline and 4, 12, and 18 weeks. RESULTS: Mean baseline logMAR BCVA was 0.94 (20/160), had improved significantly by Week 2 to 0.6 (20/80) (P < 0.0001), and reached 0.36 (20/40) by Weeks 18 with three injections (P < 0.0001). Mean central foveal thickness OCT decreased significantly from baseline 361 µm to 180 µm at the end of follow-up (P < 0.0001). Profound decrease in mean vitreous haze gradings from two to 0.2 by the end follow-up (P < 0.05). There was a significant reduction in the number of patients with vasculitis (15 at baseline to 1 weeks at 18 weeks), retinitis (nine at baseline to none at 4 weeks), and papillitis (two at baseline to none at 4 weeks) (P < 0.05). No significant electrophysiological changes or ocular adverse inflammatory reactions were observed during the study period. CONCLUSION: Intravitreal infliximab appeared to be safe and effective in treating uveitis in Behcet's disease and should be considered as an alternative to systemic therapies.