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Savak Teymoorian,1 E Randy Craven,2 Lannhi Nguyen,1 Erica Werts2 1Harvard Eye Associates, Laguna Hills, CA, USA; 2Allergan, an AbbVie company, Irvine, CA, USACorrespondence: Savak Teymoorian, Harvard Eye Associates, 23961 Calle de la Magdalena, Suite 300, Laguna Hills, CA, 92653, USA, Tel +1 (949) 951-2020, Email sev@powerupdoc.comPurpose: A sustained-release, biodegradable, intracameral 10-μg bimatoprost implant (Durysta) is approved for single administration per eye to lower intraocular pressure (IOP) in open-angle glaucoma (OAG) and ocular hypertension (OHT). The purpose of this study was to evaluate the IOP-lowering effectiveness and safety of a single implant administration per eye in patients with OAG or OHT in a real-world clinical setting.Methods: This was a retrospective, single-site study involving 105 consecutive adult patients with OAG or OHT treated with the bimatoprost implant in 1 or both eyes in routine clinical practice. Available medical records of the patients for 12 months or longer after the initial implant administration were reviewed, and data including IOP, IOP-lowering medication and procedure use, and safety outcomes were collected and analyzed. The analysis used ranges of follow-up because of the real-world setting.Results: The study included 197 eyes (85.3% diagnosed with OAG, 94.9% pseudophakic, and 83.8% with angle grade 4). IOP reduction was observed through 1 year after the bimatoprost implant administration. Mean IOP was 16.6 mmHg at baseline and 13.3 mmHg at 11– 13 months, with the mean number of topical IOP-lowering medications used reduced from 1.4 at baseline to 0.2 at 11– 13 months. IOP and IOP-lowering medication use were similarly reduced in eyes treated with both selective laser trabeculoplasty (SLT) and bimatoprost implant (including 66 eyes with their last SLT before implant administration and 28 eyes with their last SLT after implant administration). There were no cases of treatment-emergent corneal edema after bimatoprost implant administration, and no eye required implant removal.Conclusion: A single bimatoprost implant administration safely and effectively reduced IOP for up to 1 year and decreased the need for topical IOP-lowering medications in eyes with OAG or OHT with or without previous or subsequent SLT.Keywords: biodegradable implant, drug delivery system, intraocular injection, prostaglandin analog

Introduction: This study evaluated the intraocular pressure (IOP)-lowering efficacy and safety of a single intracameral administration of bimatoprost implant 10 µg in adults with open-angle glaucoma or ocular hypertension., Methods: Two identically designed, randomized, 20-month, parallel-group, phase 3 clinical trials (one study eye/patient) compared three administrations of 10- or 15-µg bimatoprost implant (day 1, weeks 16 and 32) with twice-daily topical timolol maleate 0.5%. An open-label, 24-month, phase 1/2 clinical trial compared one or two implants administered in the study eye with once-daily topical bimatoprost 0.03% in the fellow eye. Separate analyses of the pooled phase 3 and phase 1/2 study datasets evaluated outcomes in the 10-µg bimatoprost implant and comparator treatment arms after a single implant administration, up to the time of implant re-administration or rescue with IOP-lowering medication., Results: In the phase 3 studies, 10-µg bimatoprost implant single administration demonstrated IOP reductions (hour 0) of 4.9-7.0 mmHg through week 15 from a mean (standard deviation, SD) baseline IOP of 24.5 (2.6) mmHg (n = 374); IOP in the topical timolol BID group was reduced by 6.0-6.3 mmHg from a mean (SD) baseline IOP of 24.5 (2.6) mmHg (n = 373). In the phase 1/2 study (n = 21), median time to use of additional IOP-lowering treatment (Kaplan-Meier analysis) was 273 days (approximately 9 months), and 5 of 21 enrolled patients (23.8%) required no additional IOP-lowering treatment up to 24 months after single administration. In each study, after a single implant administration there were no reports of corneal edema, corneal endothelial cell loss, or corneal touch, and no patients had 20% or greater loss in corneal endothelial cell density., Conclusions: Bimatoprost implant single administration lowers IOP and has a favorable safety profile. Additional studies are needed to further evaluate the duration of effect and factors predicting long-term IOP lowering after a single implant administration., Trial Registration Numbers: ClinicalTrials.gov NCT02247804, NCT02250651, and NCT01157364., (© 2022. The Author(s).)

Background: The 0.2 µg/day fluocinolone acetonide (FAc) implant delivers continuous, low-dose, intravitreal corticosteroid for the treatment of diabetic macular oedema (DMO). This ongoing, 3-year, observational clinical trial provides long-term, 'real-world' safety results for the FAc implant in DMO., Methods: This 24-month interim analysis of a prospective, observational study investigated patients with DMO receiving the commercially available intravitreal 0.2 µg/day FAc implant. The primary outcome was incidence of intraocular pressure (IOP)-lowering procedures. Other IOP-related signals and their relationship to previous corticosteroid exposure, best-corrected visual acuity, central subfield thickness (CST), ocular adverse events and frequency of other treatments were also measured., Results: Data were collected from 95 previously steroid-challenged patients (115 study eyes) for up to 36 months pre-FAc and 24 months post-FAc implant. Mean IOP for the overall population remained stable post-FAc compared with pre-FAc implant. IOP-related procedures remained infrequent (two IOP-lowering surgeries pre-FAc; two trabeculoplasties and four IOP-lowering surgeries post-FAc). Mean visual acuity was stable post-FAc (mean improvement of 1-3 letters) and fewer DMO treatments were required per year following FAc implant. Mean CST was significantly reduced at 24 months post-FAc implant (p<0.001) and the percentage of patients with CST ≤300 µm was significantly increased (p=0.041)., Conclusion: Few IOP-related procedures were reported during the 24 months post-FAc implant. Positive efficacy outcomes were noted after treatment, with stabilisation of vision and reduction in inflammation, demonstrated by CST. The FAc implant has a favourable benefit-risk profile in the management of DMO, especially when administered after a prior steroid challenge., Trial Registration Number: NCT02424019., Competing Interests: Competing interests: SEM has received clinical trial research funds from Alimera Sciences, Chengdu Kanghong Biotechnology, Clearside Biomedical and Genentech. DFK has received research support from Adverum, Alimera Sciences, Allergan, EyePoint and Graybug Pharmaceuticals, received consultant fees from Adverum, Alimera Sciences, Allergan, BVI, EyePoint, Genentech, Mallinckrodt, Notal Vision, Novartis, Physician Recommended Neutriceuticals and Regeneron, and participated in speakers bureau for Alimera Sciences, Allergan, EyePoint, Genentech, Mallinckrodt, Notal Vision, Physician Recommended Neutriceuticals, Regeneron and Spark Therapeutics. DBR has received personal fees from Alimera Sciences, Allergan and Genentech. DE has received personal fees from Alimera Sciences, Allergan, Clearside, EyePoint, Genentech, Gyroscope, Kodiak, Network Eye, Notal Vision, Novartis and Regeneron, received research support from Alimera Sciences, Allergan, Chengdu, Clearside, DORC, Genentech, Gyroscope, Kodiak NGM, Mylan, Network Eye, Novartis, Ophthotech, Ophthea and Recens Medical and received equity from Boston Image Reading Center, Hemera Biopharmaceuticals and US Retina. NMH has received research support from Gemini, Gyroscope, Roche and Genentech, received consultant fees from Acucela, Alimera Sciences, Allegro, Allergan, Clearside, Genentech, Katalyst, Lineage Cell Therapeutics, Notal Vision, Novartis, Regeneron, and Spark, and has patents and stock ownership with Katalyst. SK and EW are employees of Alimera Sciences., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Ablation of neoplastic disease by freezing has found increasing utility as a potential therapeutic modality. To assess the effect of cooling temperatures on cellular radiation response, an established human cervical carcinoma cell line (HTB35) was subjected to holding temperatures of 0, 5, or 15 degrees C for up to 24 h before irradiation. Survival was measured by in vitro clonogenic assay of colonies containing at least 50 cells. Cooling for up to 12 h did not significantly decrease survival, but after 24 h survival fell to 75% of control cultures grown at 37 degrees C. X-irradiation immediately after cooling for 24 h resulted in 1.6-fold enhanced radiosensitivity. However, the radiosensitizing effect decayed rapidly if the cooled cells were returned to normal growth temperature for 6 h or longer before irradiation and subculture. Both temperature and cooling duration influenced the radiation response. With 0, 5, or 15 degrees C, radiosensitivity increased after 3, 6, or 12 h, respectively, and progressively rose with up to 24 h of cooling. By flow cytometric analysis, no statistically significant difference was observed in the S-phase fraction between control cells and those cooled to 0 degree C for 24 h. These data demonstrate cooling-enhanced in vitro radiation sensitivity which is dependent upon cooling temperature, duration, and rewarming interval before irradiation. While cell cycle redistribution does not appear to be a factor in the increased radiosensitivity, differences in the radiation survival curves between cooled versus normothermic cells suggest that diminished capacity for sublethal damage repair may be a significant influence on the changes which were observed.