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Jason Bacharach,1 Cathleen McCabe,2 Mitchell Jackson,3 Sanjay Rao,4 I Paul Singh,5 Sebastian Heersink,6 Nathan Radcliffe,7 Robert Weinstock,8 Dario Paggiarino,9 Keyur Patel9 1North Bay Eye Associates Petaluma, Petaluma, CA, USA; 2The Eye Associates, Bradenton, FL, USA; 3Jacksoneye Ophthalmology, Lake Villa, IL, USA; 4DeKalb Eye Consultants - Hauser-Ross Eye Institute, Sycamore, IL, USA; 5The Eye Centers of Racine & Kenosha, Racine, WI, USA; 6Eye Center South, Dothan, AL, USA; 7New York Eye Surgery Center, Bronx, NY, USA; 8The Eye Institute of West Florida, Largo, FL, USA; 9EyePoint Pharmaceuticals, Watertown, MA, USACorrespondence: Jason Bacharach, North Bay Eye Associates, 104 Lynch Creek Way, Suite 15, Petaluma, CA, 94954, USA, Email jbacharach@northbayeye.comPurpose: To evaluate dexamethasone intraocular suspension 9% (intraocular DXM) in real-world clinical use to manage inflammation associated with cataract surgery.Setting: Patients who underwent cataract surgery and received intraocular DXM at 22 outpatient eye surgery centers in the US.Design: Retrospective, observational chart review.Methods: Records of all patients who received intraocular DXM from March to December 2019 at participating centers were reviewed.Main Outcome Measures: Outcomes included anterior chamber cell (ACC) grades, anterior chamber flare (ACF) grades, and visual acuity, as well as intraocular pressure (IOP) and adverse events (AEs) at postoperative days (PODs) 1, 8, 14, 30. Descriptive statistics were generated.Results: The study population included 527 patients (641 eyes), with glaucoma history in 66 patients (80 eyes). Among eyes with recorded ACC grades, the percentage with grade 0 increased from 40% at POD 1 to 89.7% at POD 30, with similar results in eyes with glaucoma history. Among eyes with recorded ACF grades, the percentage with grade 0 increased from 78.4% at POD 1 to 97.1% at POD 30. At POD 30, 96.6% eyes with recorded results achieved target acuity. Mean IOP was 18.6 mmHg at POD 1 but declined to ≤ 15.2 mmHg thereafter. Investigators reported 22 AEs in 20 patients, all reported mild or moderate, the most common: IOP increase (7 events).Conclusion: Patients undergoing cataract surgery and treated with intraocular DXM showed favorable inflammatory and visual outcomes, without unanticipated safety problems, consistent with results of previous controlled clinical trials.Keywords: cataract surgery, corticosteroids, dexamethasone, inflammation, intraocular suspension, ocular drug delivery systems more...

BackgroundTo evaluate the safety, tolerability, pharmacokinetics, and dose-limiting toxicities of a single intravitreal (IVT) injection of PF-04523655, a 19-nucleotide, O-methyl stabilized, double-stranded small interfering ribonucleic acid targeting the RTP801 gene in patients with neovascular age-related macular degeneration (AMD).MethodsProspective, phase 1, clinical multicentre trial, enrolled 27 patients with neovascular AMD unresponsive to prior treatment and best corrected visual acuity (BCVA) ≤20/200 in the study eye in stratum 1: (dose-escalating, open-label: 50 to 3000 μg of PF-04523655) and 27 patients who had potential to benefit from therapy and BCVA of ≤20/100 and ≥20/800 in stratum 2 (parallel, masked study of 1000, 1500, 2250, and 3000 μg of PF-04523655). The primary outcome was safety and tolerability assessment as well as pharmacokinetic profiling following a single IVT injection of PF-04523655.ResultsDoses of PF-04523655 ≥400 μg were generally detectable in the plasma at 1, 4, and 24 h post-injection. And all doses were below the lowest level of quantification by day 14. A single IVT injection of 50 to 3000 μg of PF-045237655 was generally safe and well tolerated over 24 months. There were no dose-limiting toxicities.ConclusionA single IVT injection of PF-0523655 ≤3000 μg seems safe and well tolerated in eyes with neovascular AMD. [ABSTRACT FROM AUTHOR] more...

Background and Objective: Characterize timing of intraocular pressure (IOP) elevation in patients treated with fluocinolone acetonide insert (FAi) for uveitis., Patients and Methods: A post-hoc subset analysis of data from a randomized, prospective, double-masked, sham-controlled, 3-year, phase 3 clinical trial with 129 participants with noninfectious posterior uveitis randomly assigned to receive 0.18-mg fluocinolone acetonide insert or sham injection. The number of eyes with IOP of 30 mm Hg or greater at different time points were recorded., Results: The incidence of FAi eyes that reached IOP 30 mm Hg or greater was 17.2%. The mean number of days to first IOP response was 241. IOP elevations were divided into four time periods: under 1 month (33%), 3 to 6 months (33%), 6 to 18 months (26.7%), and greater than 18 months (6.7%). Ten cases of elevated IOP were managed medically and five required surgical management. Visual field analysis revealed no significant change in mean deviation compared to patients' own, untreated eyes ( P > .05)., Conclusions: IOP elevations occurred in 15 out of 87 patients treated with the FAi. The onset of elevated IOP was fairly evenly distributed across the 36-month trial. Patients should be regularly evaluated for increased IOP, which can be successfully managed by traditional means. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:387-390.] . more...

Purpose: To characterize intraocular pressure (IOP) response after treatment with dexamethasone intraocular suspension 9% vs placebo (vehicle) injection or topical prednisolone acetate 1% and to identify factors associated with increased IOP after cataract surgery., Setting: Data were pooled from two multicenter phase 3 clinical trials of patients undergoing routine cataract surgery., Design: Randomized, double-blind study and open-label study., Methods: Subjects were randomized to treatment with dexamethasone intraocular suspension or placebo in the double-blind study 1 and to dexamethasone intraocular suspension or topical prednisolone acetate in the open-label study 2. Subjects who experienced 10 mm Hg or greater, 15 mm Hg or greater, or 20 mm Hg or greater postoperative IOP increase from baseline were stratified by baseline IOP. Univariate and multivariate logistic regression models of patient variables were applied to identify independent risk factors predictive of IOP elevation of 10 mm Hg or greater or 15 mm Hg or greater., Results: The study comprised 414 subjects. Dexamethasone intraocular suspension was associated with a slightly higher mean IOP at the first postoperative visit vs prednisolone (P < .05); however, mean IOP was not statistically different between the 2 groups by postoperative day 8 (P = .5006) or thereafter. Univariate analysis showed that both prednisolone and dexamethasone intraocular suspension increased risk for postoperative IOP elevation compared with placebo; however, there was no statistically significant increased risk with dexamethasone intraocular suspension vs prednisolone. Aside from antiinflammatory treatment, risk factors for postoperative IOP elevation by univariate and multivariate analyses were higher baseline IOP, high myopia, and, when defining IOP increase as 15 mm Hg or greater from baseline, male sex., Conclusions: Dexamethasone intraocular suspension was associated with IOP elevation patterns comparable with topical prednisolone. High myopia, higher baseline IOP, and male sex were significant predictors of postoperative IOP elevation in this cohort., (Copyright © 2020 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.) more...

Dapiprazole HCL is currently available in the United States for reversal of diagnostic mydriasis. The recommended dosage for this indication is 2 drops followed 5 minutes later by 2 drops. We studied the dose-response profile and tolerance of three different treatment regimens: 1 drop alone, 1 drop followed by 1 additional drop 5 minutes later, and 2 drops followed by 2 additional drops 5 minutes later. Sixty normal male and female volunteers between 18 and 40 years of age were recruited for a double-masked, placebo-controlled, crossover study in which each eye of each subject was dilated with 2.5% phenylephrine. After one hour, one eye was treated with 0.5% dapiprazole, and the contralateral eye was treated with placebo. Each subject was treated with each of the three dapiprazole regimens in three different study sessions separated by at least 5 days (drug half-life in the eye is 5 hours). Analysis of AUC demonstrated no significant difference (P = 0.620) between the 1 drop regimen and the 2 + 2 regimen. A single drop of dapiprazole has a clinical effect equivalent to the 2 + 2 drop regimen in eyes dilated with 2.5% phenylephrine, which should improve the cost-effectiveness of this mydriolytic agent. more...

Purpose: By means of a multicenter, prospective randomized, placebo-controlled study, to assess the impact of adding the radiation-enhancing agent lonidamine to standard "curative-intent" radiation therapy upon overall survival, progression-free survival, and local progression-free survival of patients with clinically localized but nonresectable nonsmall cell lung cancer., Methods and Materials: Lonidamine, or the lonidamine-placebo, was administered at a dose of 265 mg/m2 in three divided daily doses. Drug therapy began 2 days prior to the initiation of radiation therapy and continued until progression of disease mandated a change in therapy. The radiation therapy dose was 55-60 Gy, at a daily dose of 1.8 Gy and five treatments per week. Patients with clinical Stage II or III nonsmall cell lung cancer were stratified within the treatment center, and within two histologic strata: epidermoid vs. other nonsmall cell cancers., Results: A total of 310 patients were enlisted on study, 152 on the placebo arm and 158 on the lonidamine arm. The median survival durations were 326 days and 392 days for the placebo and lonidamine-treated groups respectively, p = 0.41 for a comparison of the survival curves. Median progression-free survival and median local progression-free survival durations were 197 days and 341 days for placebo + radiation therapy vs. 230 days and 300 days for lonidamine + radiation therapy; p-values for the respective curves were 0.75 and 0.42. Although there were proportionately more lonidamine-treated patients than placebo-treated patients demonstrating continued local control in excess of 12 months, the numbers of patients still at risk after 24 months were too small for meaningful statistical analysis., Conclusion: This multicenter Phase III study failed to demonstrate a significant advantage in the lonidamine-treated population in overally patient survival, in progression-free survival, or in the median duration of local control. more...

The time-response effect of two currently used mydriatics, phenylephrine and tropicamide, were evaluated in 524 eyes. Four different types of dilating regimens were used: 2.5% phenylephrine, 10% phenylephrine, 0.5% tropicamide, and the combination of 2.5% phenylephrine and 0.5% tropicamide. The analysis indicated that the recovery from mydriasis occurs between 5.5 and 7.0 hours with 2.5% phenylephrine and at more than 7 hours with 10% phenylephrine. The 0.5% tropicamide induced rapid dilation, whereas the combined treatment, 2.5% phenylephrine plus 0.5% tropicamide, produced the largest maximum pupillary diameter. Tropicamide, alone or in combination, also produced a longer mydriatic effect, lasting more than 7.0 hours. The recovery from the cycloplegic effect of the mydriatics occurred between five and seven hours in the majority of patients, with tropicamide alone or in combination with phenylephrine requiring the most time to revert to normal ranges of accommodation. The findings in this study indicate that, in normal subjects, the recovery from the effect of mydriatic agents is longer than what is generally reported in the literature. more...

Lonidamine (LNM) has been employed in the treatment of advanced head and neck cancer (H & N) primarily with radiotherapy. It has been proposed that LNM potentiates the effects of radiation by inhibiting repair of potentially lethal damage by interfering with the mitochondrial associated repair processes. In addition, LNM appears to be more effective with fractionated doses of radiotherapy, which in light of the current emphasis on hyper/accelerated fractionation schemes may make it more efficacious. Initial H & N studies comparing LNM treated patients to historical controls report a complete response (CR) rate of 65% versus 45% respectively. All major H & N sites were included. Subsequent nonrandomized Phase II studies, although containing small numbers of patients, showed LNM to be ineffective as a single agent in patients previously treated with chemotherapy and not significantly different when radiotherapy was given with conventional dose rates. In a randomized Phase III study in which patients received an accelerated radiotherapy schedule (150 cGy bid) with either lonidamine or placebo, the CR rate was not significantly different, however, the local regional control rate was 48% versus 25% in favor of the LNM group. In addition, the 3 and 5 year duration of resonse (44% and 42% versus 26% and 17%) was improved in the LNM group. However, the 3-year actuarial survival rate was not different (49% v 43%). In summary the role of LNM as a radiopotentiator in advanced head and neck cancer appears to improve the local control rate, although survival was not significantly changed. However, future studies employing hyperfractionation schemes may show that the improved local control rate will translate into improved survival. more...

The effects of central and peripheral duct occlusion on the pancreas of the pig were investigated. The occlusion was obtained by injecting into the distal part of the pancreatic duct an ether diluted delicron or a fluid silicone solution. The pancreatic duct was then interrupted. At different intervals, gross morphology of the residual pancreas was studied and specimens were obtained for histology, immunocytochemistry and electronmicroscopy. A rapid progression of sclerotic modifications, with gradual destruction of exocrine gland, substantially concluded after 60 days, was demonstrated. However Langerhans' islets appeared preserved. These findings permit to suggest the application of this valid experimental model of chronic pancreatitis to the conservative treatment of human chronic pancreatitis. more...