Normobaric oxygen therapy.

The article by Sharifipour et al, covers an extremely important area of unmet medical need in ophthalmology.1 Severe ischemia of the sclera, leading to necrotizing disease and possible scleral melt, is one of the veritable emergencies among anterior segment disorders. Causes of necrotizing scleral disease are myriad and include autoimmune disease, especially vasculitides (e.g. Wegener’s granulomatosis, also called granulomatosis with polyangiitis) and rheumatoid arthritis among others, infections, surgery, and thermal or chemical injuries. The therapeutic approach to treatment of necrotizing scleritis is complex and significantly determined by (i) the etiology of scleritis (infectious, immune mediated, toxic, etc.) and (ii) patient-specific factors such as age and comorbidities such as renal insufficiency, hypertension and liver disease. Nevertheless, response to therapy is highly variable even in the best circumstances. As such, development and validation of novel adjunctive strategies that can assist scleral healing is of high relevance and an area of unmet needs. Hyperbaric oxygen has been shown to induce vascularization in certain ischemic pathologies including ischemic scleral disease. The precise mechanisms by which oxygen can induce vascularity remain incompletely understood and may involve enhanced fibroblast growth factor expression which can induce de novo collagen synthesis. Moreover, since necrotizing disease and severe ischemia are often associated (given the deleterious effect of severe inflammation on the integrity and survival of vascular endothelial cells), hyperbaric oxygen may promote tissue healing by suppressing cell death and tissue breakdown. In contrast to hyperbaric oxygen, much less is understood about the potential therapeutic benefits of normobaric oxygen, which has shown some efficacy for treatment of certain chemical and thermal injuries. In the cited study by Sharifipour et al, nine eyes of eight patients with scleral ischemia or melt which were inadequately responsive to conventional medical and surgical therapy received normobaric oxygen at a flow of 10L/min for 1 hour twice daily and showed a therapeutic response which began within several days after commencing therapy. As such, this small case series provides additional evidence suggesting that normobaric oxygen can provide therapeutic benefit as an adjunctive measure to standard therapy for scleral necrosis. There are several limitations to this study, which the authors openly acknowledge. The most significant is that this small case series did not have any controls. The heterogeneous etiologies of the scleritis cases listed would not necessarily pose a major problem in this regard; for example, it would be possible to apply a face-mask to a control group with much lower flow of oxygen to determine whether the observed therapeutic benefit is indeed due to the amount of oxygen delivered to the patients. One important consideration is that there are very few downsides to oxygen therapy, except for perhaps lengthened hospital stay, although this may be circumvented by prescribing oxygen at patients’ home. Notwithstanding the important suggestions made by this study, significant scientific questions remain: what is the relationship between normobaric versus hyperbaric oxygen and VEGF regulation? Is there a linear relationship between the amount of oxygen delivered and leukocyte function, or collagen synthesis? Is there a direct effect from oxygen administration on in situ expression of inflammatory cytokines? These are critical questions, since theoretically normobaric oxygen has several distinct advantages over hyperbaric therapy; normobaric therapy is safer and has very few, if any, contraindications in the vast majority of patients, it is readily available and much less costly. In summary, Sharifipour et al1 are to be congratulated for studying the difficult area of novel therapies for scleral necrosis. This study adds to the evidence being accumulated suggesting that oxygen therapy can provide a useful adjunct for managing difficult-to-treat wounds and necrotic tissue complications, including in scleritis.