Proper motions of the HH1 jet

We describe a new method for determining proper motions of extended objects, and a pipeline developed for the application of this method. We then apply this method to an analysis of four epochs of [S~II] HST images of the HH~1 jet (covering a period of $\sim 20$~yr). We determine the proper motions of the knots along the jet, and make a reconstruction of the past ejection velocity time-variability (assuming ballistic knot motions). This reconstruction shows an "acceleration" of the ejection velocities of the jet knots, with higher velocities at more recent times. This acceleration will result in an eventual merging of the knots in $\sim 450$~yr and at a distance of $\sim 80"$ from the outflow source, close to the present-day position of HH~1.Comment: 12 pages, 8 figure

Resultados da cirurgia de catarata em pacientes diabéticos : resultados do Pan-American Collaborative Retina Study Group

Purpose: This study was designed to evaluate the visual and anatomical outcomes after cataract surgery in diabetic patients with different intraoperative therapeutic strategies. Methods: The research design comprised of a multicentric, retrospective, interventional study conducted at 6 centers in Argentina, Brazil, Costa Rica, Puerto Rico, Spain, and Venezuela. We included 138 diabetic patients with at least 6-month follow-up following phacoemulsification and intraocular lens implantation. Best-corrected visual acuity (BCVA) and central subfield thickness were collected at baseline and at 1-, 2-, 3-, and 6-month follow-up. Of these, 42 cases were not treated with any intraoperative coadjuvant medication (Group 1), 59 patients received intraoperative bevacizumab (Group 2) and 37 patients received intraoperative triamcinolone (4 mg/0.1 ml) (Group 3). Results: The mean logMAR [± standard deviation (SD)] BCVA improved from 0.82 (± 0.43) at baseline, to 0.14 (± 0.23) at 6-month follow-up (p<0.001) in Group 1; from 0.80 (± 0.48) to 0.54 (± 0.45) (p<0.001) in Group 2; and from 1.0 (± 0.40) to 0.46 (± 0.34) (p<0.001) in Group 3. The mean central subfield thickness increased from 263.57 μm (± 35.7) at baseline to 274.57 μm (± 48.7) at 6-month follow-up (p=0.088) in Group 1; from 316.02 μm (± 100.4) to 339.56 μm (± 145.3) (p=0.184) in Group 2; and from 259.18 μm (± 97.9) to 282.21 μm (± 87.24) (p=0.044) in Group 3. Conclusions: Diabetic patients may significantly benefit from cataract surgery. This study provides evidence to support the use of intravitreal triamcinolone or bevacizumab at the time of cataract surgery in cases with pre-existent diabetic macular edema or moderate-severe non-proliferative diabetic retinopathy

Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials

Background: To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody. Methods: YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593). Findings: 3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference −0·2 ETDRS letters [−2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [−0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [−1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [−1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]). Interpretation: Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema. Funding: F Hoffmann-La Roche

Efficacy and safety of lampalizumab for geographic atrophy due to age-related macular degeneration: Chroma and Spectri phase 3 randomized clinical trials

IMPORTANCE: Geographic atrophy (GA) secondary to age-related macular degeneration is a leading cause of visual disability in older individuals. A phase 2 trial suggested that lampalizumab, a selective complement factor D inhibitor, reduced the rate of GA enlargement, warranting phase 3 trials.OBJECTIVE: To assess the safety and efficacy of lampalizumab vs sham procedure on enlargement of GA.DESIGN, SETTING, AND PARTICIPANTS: Two identically designed phase 3 double-masked, randomized, sham-controlled clinical trials, Chroma and Spectri, enrolled participants from August 28, 2014, to October 6, 2016, at 275 sites in 23 countries. Participants were aged 50 years or older, with bilateral GA and no prior or active choroidal neovascularization in either eye and GA lesions in the study eye measuring 2.54 to 17.78 mm(2) with diffuse or banded fundus autofluorescence patterns.INTERVENTIONS: Participants were randomized 2:1:2:1 to receive 10 mg of intravitreous lampalizumab every 4 weeks, sham procedure every 4 weeks, 10 mg of lampalizumab every 6 weeks, or sham procedure every 6 weeks, through 96 weeks.MAIN OUTCOMES AND MEASURES: Safety and efficacy assessed as mean change from baseline in GA lesion area at week 48 from centrally read fundus autofluorescence images of the lampalizumab arms vs pooled sham arms, in the intent-to-treat population and by complement factor I-profile genetic biomarker.RESULTS: A total of 906 participants (553 women and 353 men; mean [SD] age, 78.1 [8.1] years) were enrolled in Chroma and 975 participants (578 women and 397 men; mean [SD] age, 77.9 [8.1] years) were enrolled in Spectri; 1733 of the 1881 participants (92.1%) completed the studies through 48 weeks. The adjusted mean increases in GA lesion area from baseline at week 48 were 1.93 to 2.09 mm(2) across all groups in both studies. Differences in adjusted mean change in GA lesion area (lampalizumab minus sham) were -0.02 mm(2) (95% CI, -0.21 to 0.16 mm(2); P = .80) for lampalizumab every 4 weeks in Chroma, 0.16 mm(2) (95% CI, 0.00-0.31 mm(2); P = .048) for lampalizumab every 4 weeks in Spectri, 0.05 mm2 (95% CI, -0.13 to 0.24 mm(2); P = .59) for lampalizumab every 6 weeks in Chroma, and 0.09 mm(2) (95% CI, -0.07 to 0.24 mm(2); P = .27) for lampalizumab every 6 weeks in Spectri. No benefit of lampalizumab was observed across prespecified subgroups, including by complement factor I-profile biomarker. Endophthalmitis occurred after 5 of 12 447 injections (0.04%) or in 5 of 1252 treated participants (0.4%) through week 48.CONCLUSIONS AND RELEVANCE: In Chroma and Spectri, the largest studies of GA conducted to date, lampalizumab did not reduce GA enlargement vs sham during 48 weeks of treatment. Results highlight the substantial and consistent enlargement of GA, at a mean of approximately 2 mm(2) per year