Short-Term Clinical Outcomes of Patients with Diabetic Macular Edema Following a Therapy Switch to Faricimab.

Background: With this study, we investigate the short-term clinical outcomes of patients affected by diabetic macular edema (DME) after switching to intravitreal Faricimab (IVF) in a real-world setting. Methods: We conducted a retrospective chart review on all patients treated for DME with IVF who showed insufficient responses to prior anti-VEGF therapy. Data collected included baseline patient demographics, medical history, best-corrected visual acuity (BCVA), central retinal thickness (CRT) and central retinal volume (CRV). We analyzed functional and structural measures before and after IVF, compared baseline demographics and treatment factors between Faricimab-responders and reduced-responders and assessed influencing factors of the follow-up BCVA and CRT. Results: This study included 25 eyes from 16 patients. After switching to IVF, the mean BCVA showed no significant improvement, changing from 59.4 ± 13.4 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters at baseline to 61.4 ± 12.8 ETDRS letters at follow-up (p = 0.26). CRT significantly reduced from 414.4 ± 126.3 µm to 353.3 ± 131.1 µm (p < 0.011), and the 3 mm CRV significantly decreased from 2.8 ± 0.5 mm3 to 2.6 ± 0.6 mm3 (p < 0.012). Seven patients met the responder criteria, exhibiting an improvement of at least 5 ETDRS letters and a simultaneous CRT reduction of at least 30 µm. Further analysis showed that higher BCVA at baseline (p < 0.001) was associated with better BCVA following IVF, while higher baseline CRT (p < 0.003), a higher number of prior anti-VEGF agents (p < 0.034) and prior corticosteroid injections (p < 0.019) were associated with greater CRT at follow-up. Conclusions: Following the initial IVF injection series, we observed a clear improvement of anatomical measures. No functional improvement was observed, although visual acuity remained stable. Higher baseline BCVA was associated with better post-IVF BCVA, while higher baseline CRT, a greater number of prior anti-VEGF agents and prior corticosteroid injections were linked to higher CRT post-IVF.

Real-world insights and outcomes related to ciclosporin A 0.1% cationic emulsion for the long-term treatment of dry eye disease in Germany: Country-level sub-analysis of the PERSPECTIVE study.

PURPOSE: The PERSPECTIVE study was a real-world European, non-interventional, multicenter, observational study that evaluated the effectiveness, tolerability, and safety of ciclosporin A (CsA) 0.1% cationic emulsion (CE) in routine clinical practice as a treatment for adults with severe keratitis and dry eye disease (DED) that remained insufficiently controlled with artificial tears. This sub-analysis examined data from ophthalmology clinics in Germany to provide more precise insights into treatment patterns, outcomes, and clinical decision-making related to CsA 0.1% CE. METHODS: Study data were collected from adults starting CsA 0.1% CE (one drop in both eyes at bedtime) and followed up at Week 4, 12, and 24, and Month 12. The primary endpoint was mean change from baseline in corneal fluorescein staining (CFS) score (Oxford Grade Scale) at Month 12. Secondary endpoints examined the severity of ocular signs and symptoms, and adverse events (AEs). RESULTS: A total of 236 patients from 20 ophthalmology clinics in Germany participated in the PERSPECTIVE study (69.9% female; mean age 60.8 years). Following treatment with CsA 0.1% CE, patients experienced significant reductions in CFS score from Week 4, which were maintained through to Month 12 (P < 0.0001). From baseline, 81.6% of patients experienced an improvement in CFS score at Month 12. CsA 0.1% CE provided significant reductions in the severity of eyelid and conjunctival erythema at Month 12 compared with baseline (P < 0.001), as well as significant reductions in the severity of subjective ocular symptoms (all P ≤ 0.015). Safety data were consistent with the known safety profile of CsA 0.1% CE. Tolerability was rated as "satisfactory," "good," or "very good" by 97.2% of physicians and 95.7% of patients. CONCLUSION: Outcomes in Germany were similar to those reported for the overall European study population and are indicative of the treatment results that ophthalmologists may expect to see with CsA 0.1% CE treatment in real-life clinical practice. Treatment with CsA 0.1% CE provided long-term improvements over 12 months and was generally well tolerated.

Mid-term real world outcomes of the Hydrus® Microstent in open angle glaucoma.

PURPOSE: To evaluate the mid-term clinical results and the safety aspects of the Hydrus® Microstent (Ivantis, Inc, Irvine, CA) in a real-life setting. DESIGN: Retrospective case series. METHODS: Hydrus® Microstent was implanted in phakic eyes (88 eyes, 87.1%) and in pseudophakic eyes (13 eyes, 12.9%), respectively. Mean follow-up time was 16 ± 9 months with 27 eyes having a follow-up time of more than 24 months. MAIN OUTCOME MEASURES: The primary endpoint was reduction in IOP compared to baseline. Target IOP levels were set at ≤20 mmHg, ≤18 mmHg and ≤15 mmHg. Kaplan-Meier survival was defined as a reduction in IOP of ≥20% compared to baseline. Secondary endpoints were reduction in number of glaucoma medications and safety assessments addressing visual acuity, adverse events, re-surgery rate and identification of factors that made the implantation more difficult. RESULT: 101 eyes underwent Hydrus® implantation. The mean preoperative IOP was 21.60 mmHg (SD 6.6) on 2.18 (SD 1.3) medications. After a mean follow up time of 16 months, the mean IOP was reduced to 14.61 ± 3.7 mmHg on 1.12 (SD 1.1) medication classes (p < 0.001). Mean decrease in IOP was 26.7%. Analysis of the target IOP levels showed that in 29%, 34% and 35% of cases an IOP of ≤15 mmHg, ≤18 mmHg and ≤20 mmHg respectively could be achieved. BCVA improved from 0.56 ± 0.3 at baseline to 0.85 ± 0.3 more than 24 months after surgery (p < 0.001). The rate of re-operation was low at <3%. Adverse events occurred in 4 eyes (<4%). CONCLUSION: This study underlines the effectiveness and the safety of the Hydrus® Microstent in an elective setting, but it also demonstrates certain limits and risk factors of this procedure.

Structural insight into selectivity of amylin and calcitonin receptor agonists.

Amylin receptors (AMYRs), heterodimers of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins, are promising obesity targets. A hallmark of AMYR activation by Amy is the formation of a 'bypass' secondary structural motif (residues S19-P25). This study explored potential tuning of peptide selectivity through modification to residues 19-22, resulting in a selective AMYR agonist, San385, as well as nonselective dual amylin and calcitonin receptor agonists (DACRAs), with San45 being an exemplar. We determined the structure and dynamics of San385-bound AMY3R, and San45 bound to AMY3R or CTR. San45, via its conjugated lipid at position 21, was anchored at the edge of the receptor bundle, enabling a stable, alternative binding mode when bound to the CTR, in addition to the bypass mode of binding to AMY3R. Targeted lipid modification may provide a single intervention strategy for design of long-acting, nonselective, Amy-based DACRAs with potential anti-obesity effects.

Could oral hygiene prevent cases of at-home-acquired Legionnaires' disease? - Results of a comprehensive case-control study on infection sources, risk, and protective behaviors.

Introduction: The "LeTriWa study" on community-acquired cases of Legionnaires' disease (LD) found that most cases likely acquired their infection at home (AHALD). However, which sources confer the infection is largely unknown. We therefore analyzed the data set from the LeTriWa study to find out if individual sources were associated with AHALD and if specific behavioral habits may increase or lower the risk for AHALD. Methods: During the study we had used two comparison groups: (i) controls matched for age group and hospital ("controls"), (ii) household members of cases with AHALD ("AHALD-HHM"). We inquired about exposure to water sources, such as showering or wearing dentures, as well as behavioral factors and habits related to oral hygiene. We took standardized household bathroom water and biofilm samples of both cases with AHALD and controls, and in addition from households of cases with AHALD only samples from suspect residential (non-)drinking water sources. We first conducted bivariate analyses for infection sources and behaviors, followed by multivariable analyses. Results: There were 124 cases with AHALD, 217 controls and 59 AHALD-HHM. In bivariate analyses using controls for comparison, wearing dentures was the only variable significantly positively associated (odds ratio (OR) = 1.7, 95% confidence interval (CI) = 1.1-2.7, p-value = 0.02). Behavioral factors such as showering, letting water run before use and not being alcohol abstinent were significantly negatively associated, smoking was significantly positively associated. In a multivariable analysis, we identified good oral hygiene as a preventive factor for both denture wearers (OR = 0.33, 95% CI = 0.13-0.83, p-value = 0.02) and non-denture wearers (OR = 0.32, 95% CI = 0.10-1.04, p-value = 0.06). Analyses of comparisons with AHALD-HHM showed similar effects but lacked statistical power. We identified Legionella in 16 residential (non-)drinking water sources, one of which was a PCR-positive scratch sample of dentures. Discussion: Wearing (inadequately cleaned) dentures or poor oral hygiene might confer an increased risk for AHALD, and oral hygiene may prevent AHALD. The hypothesis that Legionella in oral biofilm or dental plaque may be the cause of cases with AHALD should be examined further. If confirmed this may open new and simple avenues for the prevention of LD.

Clinical benefits of systemic amoxicillin/metronidazole may depend on periodontitis stage and grade: An exploratory sub-analysis of the ABPARO trial.

AIM: Assessment of treatment response after systemic amoxicillin/metronidazole adjunctive to subgingival instrumentation (SI) according to stages and grades of the 2018 classification of periodontal diseases. MATERIALS AND METHODS: We carried out exploratory re-analysis of the placebo-controlled, multi-centre ABPARO trial (52; 45/60 years of age; 205 males, 114 active smokers). Patients were randomized to SI with systemic amoxicillin 500 mg/metronidazole 400 mg (three times a day for 7 days, n = 205; ANTI) or placebo (n = 200; PLAC) and maintenance therapy every 3 months. Patients were reclassified according to the 2018 classification (stage/extent/grade). Treatment effect was the percentage of sites per patient with new attachment loss ≥1.3 mm (PSAL ≥ 1.3 mm) at 27.5 months post-baseline/randomization. RESULTS: All patients were assigned according to the stage (n = 49 localized stage III, n = 206 generalized stage III, n = 150 stage IV). Because of missing radiographs, only 222 patients were assigned to grades (n = 73 B, n = 149 C). Treatment (PLAC/ANTI) resulted in PSAL ≥ 1.3 mm (median; lower/upper quartile) in localized stage III (PLAC: 5.7; 3.3/8.4% vs. ANTI: 4.9; 3.0/8.3%; p = .749), generalized stage III (8.0; 4.5/14.3% vs. 4.7; 2.4/9.0%; p < .001), stage IV (8.5; 5.1/14.4% vs. 5.7; 3.3/10.6%; p = .008), grade B (4.4; 2.4/6.7% vs. 3.6; 1.9/4.7%; p = .151) and grade C (9.4; 5.3/14.3% vs. 4.8; 2.5/9.4%; p < .001). CONCLUSIONS: In generalized periodontitis stage III/grade C, a clinically relevant lower percentage of disease progression after adjunctive systemic amoxicillin/metronidazole was observed compared to placebo (PLAC: 9.7; 5.8/14.3% vs. ANTI: 4.7; 2.4/9.0%; p < .001).

Long-term changes in the subgingival microbiota in patients with stage III-IV periodontitis treated by mechanical therapy and adjunctive systemic antibiotics: A secondary analysis of a randomized controlled trial.

AIM: To explore whether adjunctive antibiotics can relevantly influence long-term microbiota changes in stage III-IV periodontitis patients. MATERIALS AND METHODS: This is a secondary analysis of a randomized clinical trial on periodontal therapy with adjunctive 500 mg amoxicillin and 400 mg metronidazole or placebo thrice daily for 7 days. Subgingival plaque samples were taken before and 2, 8, 14 and 26 months after mechanical therapy. The V4-hypervariable region of the 16S rRNA gene was sequenced with Illumina MiSeq 250 base pair paired-end reads. Changes at the ribosomal sequence variant (RSV) level, diversity and subgingival-microbial dysbiosis index (SMDI) were explored with a negative binomial regression model and non-parametric tests. RESULTS: Overall, 50.2% of all raw reads summed up to 72 RSVs (3.0%) that were generated from 163 stage III-IV periodontitis patients. Of those, 16 RSVs, including Porphyromonas gingivalis, Tannerella forsythia and Aggregatibacter actinomycetemcomitans, changed significantly over 26 months because of adjunctive systemic antibiotics. SMDI decreased significantly more in the antibiotic group at all timepoints, whereas the 2-month differences in alpha and beta diversity between groups were not significant at 8 and 14 months, respectively. CONCLUSIONS: Mechanical periodontal therapy with adjunctive antibiotics induced a relevant and long-term sustainable change towards an oral microbiome more associated with oral health.

[Participation in a clinical trial-Is that something for me? : Video article]. / Teilnahme an einer klinischen Studie ­ Ist das etwas für mich? : Videobeitrag.

OBJECTIVE: The approval of new treatments in ophthalmology makes clinical studies essential. The recruitment of suitable study patients regularly poses a major challenge for the participating clinics. Many patients have fundamental reservations and fears about studies that prevent them from participating. As these concerns are similar across the country, a broadly applicable video aims to address them. For the first time, the aspects of study participation are conveyed purely from the patient's perspective. METHOD: The concept for the video was developed by the AG DOG Clinical Study Centers. Patients were sought for participation at several locations and two suitable protagonists were selected. Participation was voluntary and honorary. Filming took place in Q3 and Q4 2021 in Baden-Württemberg. The production was in the hands of the grasshopper creative agency in Tübingen. RESULTS: The two patients describe their own concerns before the study and how they experienced participating in the study themselves. Aspects such as voluntariness, the right to withdraw, fear of unpleasant examinations, the time burden and much more are discussed. The patients also address their personal motivation for participating. The video has an authentic effect, is in German and has subtitles for areas where it has to be presented without sound. These subtitles are also available in English to broaden the audience. CONCLUSION: With the video, an important tool for educating patients and recruiting clinical studies at eye clinics is available free of charge.

Serum Autoantibodies in Patients with Dry and Wet Age-Related Macular Degeneration.

BACKGROUND: To assess the serum autoantibody profile in patients with dry and exudative age-related macular degeneration compared with healthy volunteers to detect potential biomarkers, e.g., markers for progression of the disease. MATERIALS AND METHODS: IgG Immunoreactivities were compared in patients suffering from dry age-related macular degeneration (AMD) (n = 20), patients with treatment-naive exudative AMD (n = 29) and healthy volunteers (n = 21). Serum was analysed by customized antigen microarrays containing 61 antigens. The statistical analysis was performed by univariate and multivariate analysis of variance, predictive data-mining methods and artificial neuronal networks were used to detect specific autoantibody patterns. RESULTS: The immunoreactivities of dry and wet AMD patients were significantly different from each other and from controls. One of the most prominently changed reactivity was against alpha-synuclein (p ≤ 0.0034), which is known from other neurodegenerative diseases. Furthermore, reactivities against glyceraldehyde-3-phosphat-dehydrogenase (p ≤ 0.031) and Annexin V (p ≤ 0.034), which performs a major role in apoptotic processes, were significantly changed. Some immunoreacitvities were antithetic regulated in wet and dry-AMD, such as Vesicle transport-related protein (VTI-B). CONCLUSIONS: Comparison of autoantibody profiles in patients with dry and wet AMD revealed significantly altered immunoreactivities against proteins particularly found in immunological diseases, further neurodegenerative, apoptotic and autoimmune markers could be observed. A validation study has to explore if these antibody pattern can help to understand the underlying differences in pathogenesis, evaluate their prognostic value and if those could be possibly useful as additional therapeutic targets.

LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration.

INTRODUCTION: Photobiomodulation (PBM) represents a potential treatment for non-exudative age-related macular degeneration (AMD). PBM uses wavelengths of light to target components of the mitochondrial respiratory chain to improve cellular bioenergetic outputs. The aim of this study was to further investigate the effects of PBM on clinical, quality of life (QoL) and anatomical outcomes in subjects with intermediate stage non-exudative AMD. METHODS: The multicenter LIGHTSITE II study was a randomized clinical trial evaluating safety and efficacy of PBM in intermediate non-exudative AMD. The LumiThera Valeda® Light Delivery System delivered multiwavelength PBM (590, 660 and 850 nm) or sham treatment 3 × per week over 3-4 weeks (9 treatments per series) with repeated treatments at baseline (BL), 4 and 8 months. Subjects were enrolled with 20/32 to 20/100 best-corrected visual acuity (BCVA) and no central geographic atrophy (GA) within the central fovea (500 µm). RESULTS: LIGHTSITE II enrolled 44 non-exudative AMD subjects (53 eyes). PBM-treated eyes showed statistically significant improvement in BCVA at 9 months (n = 32 eyes, p = 0.02) with a 4-letter gain in the PBM-treated group versus a 0.5-letter gain in the sham-treated group (ns, p < 0.1) for patients that received all 27 PBM treatments (n = 29 eyes). Approximately 35.3% of PBM-treated eyes showed ≥ 5-letter improvement at 9 months. Macular drusen volume was not increased over time in the PBM-treated group but did show increases in the sham-treated group. While PBM and sham groups both showed GA lesion growth in the trial period, there was 20% less growth in the PBM group over 10 months, suggesting potential disease-modifying effects. No safety concerns or signs of phototoxicity were observed. CONCLUSION: These results confirm previous clinical testing of multiwavelength PBM and support treatment with Valeda as a novel therapy with a unique mechanism of action as a potential treatment for non-exudative AMD. TRIAL REGISTRATION: Clinicaltrial.Gov Registration Identifier: NCT03878420.