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Purpose This analysis of the pivotal phase 3 HAWK and HARRIER trials aimed to provide insights on the timing of presentation, management, and outcomes of intraocular inflammation (IOI)-related adverse events (AEs), as reported by investigators in these trials. Design Post hoc analysis of investigator-reported IOI-related AEs in HAWK and HARRIER. Participants Of 1088 brolucizumab-treated eyes (3 or 6 mg), 49 eyes demonstrated at least 1 IOI-related AE and were included in this analysis. Methods Reports of IOI-related AEs were analyzed and descriptive statistics were provided for outcome measures. Main Outcome Measures Incidence and description of eyes with IOI-related AEs, timing of presentation, management, clinical outcomes, and brolucizumab treatment after the first IOI-related AE. Results Seventy IOI-related AEs were reported in 49 eyes. Before the onset of first IOI-related AE, eyes received a mean ± standard deviation (SD) of 3.9 ± 2.2 brolucizumab injections. Median time to first IOI-related AE from the last administered brolucizumab injection was 18.0 days (interquartile range, 4.0–29.0 days). Of the 70 AEs, 61 (87.1%) were treated, most with topical corticosteroids; systemic and intraocular corticosteroids were used for 3 AEs each. Overall, inflammation resolved completely in 39 eyes (79.6%), resolved with sequelae in 5 eyes (10.2%), and did not resolve in 5 eyes (10.2%) by end-of-study (EOS). Overall, the mean ± SD best-corrected visual acuity (BCVA) change from baseline to EOS, before AE to the lowest BCVA in 3 months after AE, and from before AE to EOS were −0.84 ± 20.6 , −16.31 ± 17.6, and −0.22 ± 18.9 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, respectively. Of the 36 eyes (73.5%) that continued with brolucizumab therapy after the first IOI-related AE, 24 completed the trials and 12 discontinued; mean ± SD BCVA change in these eyes was 2.6 ± 17.6, 7.8 ± 13.2, and −7.7 ± 21.3 ETDRS letters, respectively, from baseline to EOS. The remaining 13 eyes (26.5%) were not treated with brolucizumab after first IOI-related AE and showed a mean ± SD BCVA change of −10.4 ± 25.5 ETDRS letters from baseline to EOS. Conclusions Findings of this analysis highlight the need for continued vigilance and monitoring for any signs of IOI-related events in patients receiving brolucizumab.

Purpose Recent reports have described a spectrum of uncommon findings of intraocular inflammation (IOI), retinal vasculitis, or retinal vascular occlusion in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal injection (IVI) of brolucizumab. We present guidance on the clinical presentation of this spectrum and propose recommendations for management of these events. Design PubMed literature review and expert opinion panel. Participants A working group of international medical experts and Novartis medical personnel. Methods The working group deliberated on the clinical presentations and used a 3-pronged approach to develop management recommendations based on (1) critical appraisal of scientific literature; (2) clinical insights from the HAWK and HARRIER trials, postmarketing reports, and assessments from an independent Safety Review Committee (SRC); and (3) their clinical experience. Main Outcome Measures Management recommendations for a spectrum of ocular inflammatory events after treatment with brolucizumab or other anti–vascular endothelial growth factors (VEGFs). Results Based on insights gained from the available information and the expertise of the contributors, recommendations were proposed for ocular examinations, imaging modalities, and treatment strategies for management of this spectrum of events. Patients should be educated to promptly report any relevant or persistent symptoms after IVI to facilitate timely intervention. Patients diagnosed with IOI should be evaluated for concomitant retinal vasculitis or retinal vascular occlusive events. Clinical examination can be augmented with multimodal imaging techniques, including widefield imaging, fluorescein angiography (with peripheral sweeps), and OCT. Once confirmed, the ongoing brolucizumab treatment should be suspended and intensive treatment with potent corticosteroids (topical, subtenon, intravitreal, or systemic) is recommended, which may be supplemented with other treatment strategies depending on the severity. Based on the clinical outcome of these events, individualized treatment with locally available standard of care should be considered for the underlying nAMD. Conclusions These recommendations emphasize the need for early diagnosis, prompt and timely intervention, intensive treatment, and frequent monitoring to minimize the risk of progression of these events. The proposed recommendations may facilitate a consistent management approach of this spectrum of ocular inflammatory events should they arise in nAMD after treatment with brolucizumab or other anti-VEGFs.

Health care is rapidly changing, and a key focus of this evolution is preventative medicine, as opposed to treatment and curative options once disease has been established. This focus on prevention is aimed at reducing the overall health-care burden through better education, improved lifestyle choices and, in some cases, specific therapy to avoid disease. Natural supplements have been used in various forms for centuries, and increasingly they are undergoing vigorous scientific research in order to explore their various associated claims. Of these, probiotics are some of the most extensively investigated, and they potentially represent a safe and viable option for the prevention of certain conditions. The volume of research into probiotics has increased in parallel with the search for alternative, natural therapies with fewer side effects and clinical implications. This is reflected by the development of medicinal probiotics with extensive pre-clinical and clinical research to support their use. This review article will introduce some of the basic concepts related to probiotics, the human bacterial population (microbiome) and some of the evidence available to support their use in preventing disease.

The last few decades have seen the search for alternative therapies increase immeasurably as the general and scientific population look for more natural treatments for many diseases, with fewer side effects and clinical implications. This review article looks at some of the evidence behind the use of probiotic supplements within the hospital setting with specific clinical applications. The evidence for their use is growing and compelling in certain therapeutic situations. With the increase in volume and quality of clinical evidence, the use of probiotics should become more widespread in the future.