Hydroxychloroquine and COVID-19: a Rheumatologist's Take on the Lessons Learned.

PURPOSE OF REVIEW: Told from the viewpoint of rheumatologists, this review tells the story of hydroxychloroquine and its swift ascent to become a household name as a therapeutic strategy against the novel SARS-CoV-2 virus. This review describes the history, mechanisms, pharmacokinetics, therapeutic applications, and safety profile of hydroxychloroquine as an immunomodulatory and antiviral agent. It also summarizes the major studies that launched and assessed the use of hydroxychloroquine against COVID-19 infection. RECENT FINDINGS: More recent literature calls into question the long-held dogma that endolysosomal alkalinization is the primary mode of action of hydroxychloroquine. Ongoing uncertainty about the multiple potential mechanisms contributing to the therapeutic effect of hydroxychloroquine in rheumatic and viral disease led to a natural avenue for exploration in the treatment of COVID-19. Taken as a whole, the literature does not support utilizing hydroxychloroquine to treat or prevent infection from the SARS-CoV-2 virus. This is, at least in part, due to the wide variability in hydroxychloroquine pharmacokinetics between patients and difficulty achieving adequate target tissue concentrations of hydroxychloroquine without encountering unacceptable toxicities. Hydroxychloroquine continues to be a routinely prescribed, well-tolerated, effective, and low-cost treatment for rheumatic disease. Its therapeutic versatility has led to frequent repurposing for other conditions, most recently as an investigative treatment against the SARS-CoV-2 virus. Despite overall negative findings, the intense study of hydroxychloroquine against COVID-19 infection has enhanced our overall understanding of how hydroxychloroquine operates in autoimmune disease and beyond.

A medieval fallacy: the crystalline lens in the center of the eye.

OBJECTIVE: To determine whether, as most modern historians have written, ancient Greco-Roman authors believed the crystalline lens is positioned in the center of the eye. BACKGROUND: Historians have written that statements about cataract couching by Celsus, or perhaps Galen of Pergamon, suggested a centrally located lens. Celsus specifically wrote that a couching needle placed intermediate between the corneal limbus and the lateral canthus enters an empty space, presumed to represent the posterior chamber. METHODS: Ancient ophthalmic literature was analyzed to understand where these authors believed the crystalline lens was positioned. In order to estimate where Celsus proposed entering the eye during couching, we prospectively measured the distance from the temporal corneal limbus to the lateral canthus in 30 healthy adults. RESULTS: Rufus of Ephesus and Galen wrote that the lens is anterior enough to contact the iris. Galen wrote that the lens equator joins other ocular structures at the corneoscleral junction. In 30 subjects, half the distance from the temporal corneal limbus to the lateral canthus was a mean of 4.5 mm (range: 3.3-5.3 mm). Descriptions of couching by Celsus and others are consistent with pars plana entry of the couching needle. Anterior angulation of the needle would permit contact of the needle with the lens. CONCLUSION: Ancient descriptions of anatomy and couching do not establish the microanatomic relationships of the ciliary region with any modern degree of accuracy. Nonetheless, ancient authors, such as Galen and Rufus, clearly understood that the lens is located anteriorly. There is little reason to believe that Celsus or other ancient authors held a variant understanding of the anatomy of a healthy eye. The notion of the central location of the lens seems to have arisen with Arabic authors in 9th century Mesopotamia, and lasted for over 7 centuries.