Epimacular Brachytherapy for Previously Treated Neovascular Age-Related Macular Degeneration (MERLOT) A Phase 3 Randomized Controlled Trial Presented in part at: Retina Day, American Academy of Ophthalmology Annual Meeting, November 2015, Las Vegas, Nevada.

PurposeTo assess the safety and efficacy of epimacular brachytherapy (EMB) for patients with chronic, active, neovascular age-related macular degeneration (AMD).DesignPhase 3 randomized controlled trial.ParticipantsPatients (n = 363) with neovascular AMD already receiving intravitreal ranibizumab injections.InterventionEither pars plana vitrectomy with 24-gray EMB and ongoing pro re nata (PRN) ranibizumab (n = 224) or ongoing PRN ranibizumab monotherapy (n = 119).Main Outcome MeasuresThe coprimary outcomes, at 12 months, were the number of PRN ranibizumab injections and Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (VA). Secondary outcomes included the proportion of participants losing fewer than 15 ETDRS letters, angiographic total lesion size, choroidal neovascularization (CNV) size, and optical coherence tomography (OCT) foveal thickness. A predefined subgroup analysis tested the influence of baseline ocular characteristics on the response to EMB.ResultsThe mean number of PRN ranibizumab injections was 4.8 in the EMB arm and 4.1 in the ranibizumab monotherapy arm (P = 0.068). The mean VA change was −4.8 letters in the EMB arm and −0.9 letters in the ranibizumab arm (95% confidence interval of difference between groups, −6.6 to −1.8 letters). The proportion of participants losing fewer than 15 letters was 84% in the EMB arm and 92% in the ranibizumab arm (P = 0.007). In the EMB arm, the mean total lesion size increased by 1.2 mm2 versus 0.4 mm2 in the ranibizumab arm (P = 0.27). The CNV size decreased by 0.5 mm2 in the EMB arm and by 1.3 mm2 in the ranibizumab arm (P = 0.27). The OCT foveal thickness decreased by 1.0 μm in the EMB arm and by 15.7 μm in the ranibizumab arm (P = 0.43). Most subgroups favored ranibizumab monotherapy, some significantly so. One participant showed retinal vascular abnormality attributed to radiation, but otherwise safety was acceptable.ConclusionsThese results do not support the use of EMB for chronic, active, neovascular AMD. Safety is acceptable out to 12 months, but radiation retinopathy can occur later, so further follow-up is planned

Improved Outcomes with Heavy Silicone Oil in Complex Primary Retinal Detachment: A Large Multicenter Matched Cohort Study

\ua9 2023 American Academy of OphthalmologyPurpose: To establish whether Densiron 68, a heavier-than-water endotamponade agent, is an effective alternative to conventional light silicone oil in primary rhegmatogenous retinal detachment (RD) surgery for eyes with inferior breaks in the detached retina and severe proliferative vitreoretinopathy (PVR). Design: Cohort study of routinely collected data from the European Society of Retina Specialists and British and Eire Association of Vitreoretinal Surgeons vitreoretinal database between 2015 and 2022. Participants: All consecutive eyes that underwent primary rhegmatogenous RD surgery using Densiron 68 or light silicone oil as an internal tamponade agent. Methods: To minimize confounding bias, we undertook 2:1 nearest-neighbor matching on inferior breaks, large inferior rhegmatogenous RDs, PVR, and, for visual analyses, baseline visual acuity (VA) between treatment groups. We fit regression models including prognostically relevant covariates, treatment–covariate interactions, and matching weights. We used g-computation with cluster-robust methods to estimate marginal effects. For nonlinear models, we calculated confidence intervals (CIs) using bias-corrected cluster bootstrapping with 9999 replications. Main Outcome Measures: Presence of a fully attached retina and VA at least 2 months after oil removal. Results: Of 1061 eyes enrolled, 426 and 239 were included in our matched samples for anatomic and visual outcome analyses, respectively. The primary success rate was higher in the Densiron 68 group (113 of 142; 80%) compared with the light silicone oil group (180 of 284; 63%), with an adjusted odds ratio of 1.90 (95% CI, 1.63–2.23, P < 0.001). We also observed a significant improvement favoring Densiron 68 of –0.26 logarithm of the minimum angle of resolution (logMAR) in postoperative VA between the 2 groups (95% CI, –0.43 to –0.10, P = 0.002). The anatomic benefit of using Densiron 68 in eyes with inferior retinal breaks and large detachments was more pronounced among eyes with PVR grade C. We found no evidence of visual effect moderation by anatomic outcome or foveal attachment. Conclusions: Densiron achieved higher anatomic success rates and improved visual outcomes compared with conventional light silicone oil in eyes with inferior retinal pathology and severe PVR. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article

The effect of cataract on early stage glaucoma detection using spatial and temporal contrast sensitivity tests

Background: To investigate the effect of cataract on the ability of spatial and temporal contrast sensitivity tests used to detect early glaucoma. Methods: Twenty-seven glaucoma subjects with early cataract (mean age 60 ±10.2 years) which constituted the test group were recruited together with twenty-seven controls (cataract only) matched for age and cataract type from a primary eye care setting. Contrast sensitivity to flickering gratings at 20 Hz and stationary gratings with and without glare, were measured for 0.5, 1.5 and 3 cycles per degree (cpd) in central vision. Perimetry and structural measurements with the Heidelberg Retinal Tomograph (HRT) were also performed. Results: After considering the effect of cataract, contrast sensitivity to stationary gratings was reduced in the test group compared with controls with a statistically significant mean difference of 0.2 log units independent of spatial frequency. The flicker test showed a significant difference between test and control group at 1.5 and 3 cpd (p = 0.019 and p = 0.011 respectively). The percentage of glaucoma patients who could not see the temporal modulation was much higher compared with their cataract only counterparts. A significant correlation was found between the reduction of contrast sensitivity caused by glare and the Glaucoma Probability Score (GPS) as measured with the HRT (p<0.005). Conclusions: These findings indicate that both spatial and temporal contrast sensitivity tests are suitable for distinguishing between vision loss as a consequence of glaucoma and vision loss caused by cataract only. The correlation between glare factor and GPS suggests that there may be an increase in intraocular stray light in glaucoma

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Investigations in the initial build-up stages of polyelectrolyte multilayers by laser reflectometry and atomic force microscopy

This work aims to investigate the initial build-up stages of polyelectrolyte multilayers formed by the successive deposition of the weakly charged Poly(Allyl amine, HCl), PAH and the strong acid Poly(Styrene Sulfonate), PSS, on silica at pH = 9. Two complementary tools were used: laser reflectometry to determine the step-by-step deposited weight of each polymer and Atomic Force Microscopy (AFM) to characterize the topography and measure the thickness of the film. The experiments show that the deposited weight of PAH is the same at each step (around 0.5 mg.m− 2), whereas that of PSS increases more or less linearly along with the step number. Starting at the second polymer deposit (PSS), the structure of the film is very heterogeneous, with a thin polymer layer and bumps that are attributed to the presence of PSS/PAH hydrophobic complexes. The amount of bumps and their height were determined at each of the ten first polymer deposits. The film thickness between the bumps was evaluated by scratching small areas with an AFM tip. Our results support a former description of film growth, based on the electrostatic interactions between the two polymers and the substrate. They also reveal different the roles of the two polymers in the growth of the films: PAH is responsible for the progressive bi-dimensional coverage of the surface area and PSS for the increase in the thickness of the film

Surface morphology and thickness of a multilayer film composed of strong and weak polyelectrolytes: Effect of the number of adsorbed layers, concentration and type of salts

International audienceSelf-assembled multilayered films were prepared by alternate deposition of a strong cationic polyelectrolyte, poly(trimethylammonium ethyl methacrylate chloride) and a pH-dependant anionic polyelectrolyte, poly (acrylic acid). The layer-by-layer adsorption was followed in-situ by optical fixed-angle reflectometry and after drying by ellipsometry. A recently developed “substrate thickness method” was applied to calculate the adsorbed amount of polymer from the reflectometric signal. Surface film morphology was imaged before and after drying with atomic force microscopy (AFM). Influence of the number of adsorbed layers, concentration and type of salts on the multilayer growth was examined. The number of adsorbed layers produced a specific effect on the reflectometric signal which is linked to the refractive index of the film. Adjustment of the adsorbed amount of polyelectrolytes was done by changing sodium chloride salt concentration within a range of 10−3 to 10−1 M. AFM observations showed a significant evolution in surface morphology and a maximum of surface roughness for films built-up at 10−2 M. Experiments were then carried out at 10−3 M in either barium chloride or zinc chloride salts. In the presence of Ba2+ and Zn2+ ions, adsorption of 5 bilayers is completely modified and the surface morphology was smoother than the multilayers obtained using sodium chloride salt