Characterizing Flow and Structure of Diabetic Retinal Neovascularization after Intravitreal Anti-VEGF Using Optical Coherence Tomography Angiography: A Pilot Study

Background/Aims. This study evaluates changes of flow and structure of diabetic retinal neovascularization (NV) treated with intravitreal antivascular endothelial growth factor (VEGF) agents using optical coherence tomography angiography (OCTA). With OCTA, retinal blood vessels are visualized at high resolution to separately look at flow and structure information without the need for dye injection. We introduce a new measurement method including and combining information of flow and structure. Methods. Retrospective observational case series. Patients with proliferative diabetic retinopathy (PDR) were treated with intravitreal antiVEGF injections. Retinal NV were repeatedly imaged using swept-source OCTA (Zeiss PlexElite 9000) at baseline, after initial treatment block with 3-4 monthly injections, and during a follow-up period of up to 51 weeks. Change of size and flow density of the structural and angio area of NV was assessed. Results. Nine NV in eight eyes of five patients were analyzed with a median follow-up time of 45 weeks. After the initial treatment block, en face structural area regressed, 18.7% ± 39.0% (95% CI 44.2-6.8%, p=0.26), and en face angio area regressed, 51.9% ± 29.5% (95% CI 32.6 to 71.2%, p=0.007). Flow density within the en face structural area decreased by 33% ± 19.2% (95% CI 20.5-45.5%, p=0.0077). Flow density within the en face angio area decreased by mean 17.9% ± 25.2% (95% CI 1.4-34.4%, p=0.066). In two fellow eyes, NV recurrence could be observed before the onset of vitreous bleeding in one. Conclusion. Our study introduces a new quantitative measurement for NV in PDR, combining structure and flow measurement. The structure area remained after treatment, while its flow density and angio area regressed. We propose this measurement method as a more physiological and possibly more comparable metrics

Routine Clinical Practice Treatment Outcomes of Eplerenone in Acute and Chronic Central Serous Chorioretinopathy

Purpose: To evaluate efficacy of eplerenone therapy vs. observation on resolution of subretinal fluid (SRF) in patients with acute and chronic central serous chorioretinopathy (CSCR) in routine clinical practice. Methods: Retrospective comparative case series of eyes diagnosed with CSCR treated with eplerenone or observation. Primary outcome measure was maximum height of SRF at 12 months. Secondary outcome was percentage of eyes with complete resolution of SRF, percentage of eyes with reduction of SRF ≥50%, and best corrected visual acuity (VA) at 12 months. Separate analysis was conducted for eyes with acute and chronic CSCR. Results: Sixty-eight eyes of 60 patients (82% male) were included. Eleven of the 38 eyes with acute CSCR, and seven of the 30 eyes with chronic CSCR, received eplerenone. Subretinal fluid decreased from baseline to 12 months in acute (287 ± 221 to 31 ± 63 µm) and chronic (148 ± 134 to 40 ± 42 µm) CSCR. Kaplan-Meier curves were similar for treated and observed eyes and COX regression analysis did not show a significant difference in SRF resolution in treated vs. observed eyes (p = 0.6 for acute, p = 0.2 for chronic CSCR). Conclusion: This routine clinical practice outcome study did not show evidence of efficacy of eplerenone on resolution of SRF in acute nor chronic CSCR

Energy, SBS symptoms, and productivity in Swiss open-space offices: Economic evaluation of standard, actual, and optimum scenarios

The fundamental aspiration of new-generation high-performing buildings is to reduce energy use while securing indoor environmental quality conducive to human health and productivity. However, existing frameworks for identifying Key Performance Indicators (KPIs) of buildings are sporadic and limited to a few parameters. Based on two Swiss open-space buildings, this paper demonstrates an economic comparison combining three KPIs: health (represented by sick building syndrome (SBS) symptoms), occupants' productivity (based on the thermal environment and ventilation), and operational energy for heating (based on building simulations using measured inputs). Monetization translated various criteria into the same unit currency and compared them on equal terms. Three scenarios for human- and energy-related performance analysis were actual (considering measured data), standard (using parameters from the national standard), and optimal (maximized productivity). The actual environment in case studies measured in the Fall and Winter seasons was relatively warm, with poor ventilation in one of the two buildings as no mechanical ventilation was on. Therefore, there was some loss of productivity (0.11-0.4%) and SBS symptoms (e.g., dry eyes, fatigue) present in both buildings resulting in up to 2 times the difference between the energy and human costs. The minimum energy costs for the standard scenario indicated that standard settings prioritize energy objectives. Oppositely, energy costs were the highest (47.6-69.6%) in the optimal scenario minimizing the human-related costs but not the weekly SBS symptoms. The analysis presented highlights the conflicting goals when one parameter is prioritized over another one, thus demonstrating the importance of a multi-criteria approach

Photodynamische Therapie bei altersbedingter Makuladegeneration am schlechteren und besseren Auge

Zusammenfassung: Hintergrund: Die PDT ist die Standardbehandlung vieler Formen der exsudativen bzw. neovaskulären Makuladegeneration (AMD). Trotz Therapie fällt die Sehschärfe häufig in den Low-vision-Bereich ab. Die Kosteneffizienz der Therapie am schlechteren Auge wird daher kontrovers diskutiert. Patienten und Methoden: Retrospektive Fallkontrollstudie aller Patienten, welche zwischen September 1999 und November 2004 am Universitätsspital Zürich eine PDT erhalten haben. Die Situation bei Präsentation und der Verlauf unter Therapie wurden bei ersten (schlechteren) und zweiten (besseren) Augen verglichen. Ergebnisse: In 117/228Fällen (51,3%) war der Visus am behandelten Auge bei Präsentation besser (oder gleich) als der Visus am Partnerauge. Der Visus vor Behandlung betrug bei den besseren Augen im Mittel 0,58±0,27logMAR [Snellen: 0,26 (0,14-0,49)] und 0,69±0,4logMAR [Snellen 0,20 (0,08-0,51)] bei den schlechteren Augen (p=0,015). Nach Behandlung bestand zwischen den Gruppen weder bezüglich Visus bzw. Visusveränderung noch bezüglich Membrangröße bzw. Größenveränderung der Membran ein signifikanter Unterschied. Schlussfolgerung: Die Resultate nach PDT sind beim zweiten (bzw. besseren) Auge nicht signifikant besser als beim ersten (bzw. schlechteren) Aug

Vitamin A deficiency retinopathy related to medical interventions in a Swiss cohort: a case series

AIMS OF THE STUDY: Vitamin A deficiency retinopathy is a potentially blinding disease. In developed countries, vitamin A deficiency due to malnutrition is rare. However, vitamin A deficiency can be caused by malabsorption resulting from bowel resection or medication. In this retrospective study, we present five cases of vitamin A deficiency retinopathy related to malabsorption secondary to medical interventions. METHODS: Electronic charts over a ten-year period (2012–2022) were screened for vitamin A deficiency retinopathy. Only patients with vitamin A deficiency confirmed by laboratory tests were included. Symptoms, medical history, visual acuity, optical coherence tomography, fundus autofluorescence, electrophysiological examination, and vitamin A levels were reviewed. RESULTS: Five eligible cases were identified. Median age was 44.7 years (range 22.2–88.9), median duration of ocular symptoms prior to diagnosis was 14 months, and median visual acuity was 1.0 (range 0.5–1.0, Snellen, decimal). Three patients had a history of bariatric surgery, one patient had a small bowel resection and was on octreotide treatment, and one patient suffered from cystic fibrosis and had a history of small bowel resection and severe hepatopathy. Optical coherence tomography showed various abnormalities, including a reduced interdigitation zone, subretinal drusenoid deposits, and a thinned outer nuclear layer. Electroretinogram findings ranged from abnormal oscillatory potentials to non-recordable rod responses. CONCLUSIONS: Vitamin A deficiency retinopathy can occur following medical interventions associated with malabsorption. In cases of night blindness, vitamin A levels should be measured

Local and global modes of drug action in biochemical networks

It becomes increasingly accepted that a shift is needed from the traditional target-based approach of drug development to an integrated perspective of drug action in biochemical systems. We here present an integrative analysis of the interactions between drugs and metabolism based on the concept of drug scope. The drug scope represents the set of metabolic compounds and reactions that are potentially affected by a drug. We constructed and analyzed the scopes of all US approved drugs having metabolic targets. Our analysis shows that the distribution of drug scopes is highly uneven, and that drugs can be classified into several categories based on their scopes. Some of them have small scopes corresponding to localized action, while others have large scopes corresponding to potential large-scale systemic action. These groups are well conserved throughout different topologies of the underlying metabolic network. They can furthermore be associated to specific drug therapeutic properties

Structural Features of Patients with Drusen-like Deposits and Systemic Lupus Erythematosus

Background: The relevance of drusen-like deposits (DLD) in patients with systemic lupus erythematosus (SLE) is to a large extent uncertain. Their genesis is proposed to be correlated to immune-complex and complement depositions in the framework of SLE. The intention of this study was to determine potential morphological differences in the choroid and retina as well as potential microvascular changes comparing two cohorts of SLE patients divergent in the presence or absence of DLD using multimodal imaging. Methods: Both eyes of 16 SLE patients with DLD were compared to an age- and sex-matched control-group consisting of 16 SLE patients without detectable DLD. Both cohorts were treated with hydroxychloroquine (HCQ) and did not differ in the treatment duration or dosage. Using spectral-domain optical coherence tomography (SD-OCT) choroidal volume measures, choroidal vascularity indices (CVI) and retinal layer segmentation was performed and compared. In addition, by the exploitation of optical coherence tomography angiography vascular density, perfusion density of superficial and deep retinal capillary plexuses and the choriocapillaris were analyzed. For the choroidal OCT-scans, a subset of 51 healthy individuals served as a reference-group. Results: CVI measures revealed a significant reduction in eyes with DLD compared to healthy controls (0.56 (0.54–0.59) versus 0.58 (0.57–0.59) (p = 0.018) and 0.56 (0.54–0.58) versus 0.58 (0.57–0.60) (p < 0.001)). The photoreceptor cell layer presented significant thinning in both eyes of subjects with DLD compared to control subjects without DLD (68.8 ± 7.7 µm vs. 77.1 ± 7.3 µm for right eyes, p = 0.008, and 66.5 ± 10.5 µm vs. 76.1 ± 6.3 µm for left eyes, p = 0.011). OCTA scans revealed no significant changes, yet there could be observed numerically lower values in the capillary plexuses of the retina in eyes with DLD than in eyes without DLD. Conclusions: Our results illustrated significant alterations in the choroidal and retinal analyzes, suggesting a correlation between DLD and the progression of inflammatory processes in the course of SLE leading to retinal degeneration. For this reason, DLD could serve as a biomarker for a more active state of disease

Challenges in integrating Escherichia coli molecular biology data

One key challenge in Systems Biology is to provide mechanisms to collect and integrate the necessary data to be able to meet multiple analysis requirements. Typically, biological contents are scattered over multiple data sources and there is no easy way of comparing heterogeneous data contents. This work discusses ongoing standardisation and interoperability efforts and exposes integration challenges for the model organism Escherichia coli K-12. The goal is to analyse the major obstacles faced by integration processes, suggest ways to systematically identify them, and whenever possible, propose solutions or means to assistmanual curation. Integration of gene, protein and compound data was evaluated by performing comparisons over EcoCyc, KEGG, BRENDA, ChEBI, Entrez Gene and UniProt contents. Cross-links, a number of standard nomenclatures and name information supported the comparisons. Except for the gene integration scenario, in no other scenario an element of integration performed well enough to support the process by itself. Indeed, both the integration of enzyme and compound records imply considerable curation. Results evidenced that, even for a well-studied model organism, source contents are still far from being as standardized as it would be desired and metadata varies considerably from source to source. Before designing any data integration pipeline, researchers should decide on the sources that best fit the purpose of analysis and be aware of existing conflicts/inconsistencies to be able to intervene in their resolution. Moreover, they should be aware of the limits of automatic integration such that they can define the extent of necessary manual curation for each application.Portuguese FCT funded MIT-Portugal Program in Bioengineering (MIT-Pt/BS-BB/0082/2008); PhD grant from FCT (ref. SFRH/BD/22863/2005) to S.

Three-Year Outcomes of Neovascular Age-Related Macular Degeneration in Eyes That Do Not Develop Macular Atrophy or Subretinal Fibrosis

Purpose: To report the 36-month treatment outcomes of eyes with neovascular age-related macular degeneration (nAMD) receiving vascular endothelial growth factor (VEGF) inhibitors in daily practice who did not develop either subretinal fibrosis (SRFi) or macular atrophy (MA). Methods: This is a retrospective analysis of data from the Fight Retinal Blindness registry. Treatment-naïve eyes starting intravitreal injection of VEGF inhibitors for nAMD from January 1, 2010, to September 1, 2017, and did not have SRFI and MA at baseline were tracked. Results: We identified 2478 eligible eyes, of which 1712 eyes did not develop SRFi or MA, 291 developed extrafoveal SRFI or MA, and 475 developed subfoveal SRFi or MA over 36 months. The estimated visual acuity stabilized from 6 months to 36 months in eyes that did not develop SRFI or MA with a mean (95% confidence interval [CI]) change in VA of -1 (-2, 0) letters, whereas eyes that developed extrafoveal (-3 [-5, -2] letters) or subfoveal (-10 [-11, -8] letters) SRFi or MA declined in vision in the same period. Eyes with no or extrafoveal SRFi or MA over 36 months were more likely to maintain their visual improvement from six months to 36 months (odds ratio [OR; 95% CI] = 2.3 [1.5, 3.3] for absence vs. subfoveal SRFi or MA, P ≤ 0.01 and OR = 2.0 [1.2, 3.4] for extrafoveal vs. subfoveal MA or SRFi, P = 0.01). Conclusions: Treatment-naïve nAMD eyes receiving VEGF inhibitors maintain their initial six-month visual improvement over three years if they do not develop SRFI or MA. Translational relevance: The nAMD is still a major cause of blindness despite antiangiogenic treatments. We found that eyes that did not develop subretinal fibrosis or macular atrophy maintained their initial vision improvement for at least three years, suggesting that identifying treatments for these complications is the final barrier to achieving excellent outcomes in nAMD