Aflibercept Off-Target Effects in Diabetic Macular Edema: An In Silico Modeling Approach.

Intravitreal aflibercept injection (IAI) is a treatment for diabetic macular edema (DME), but its mechanism of action (MoA) has not been completely elucidated. Here, we aimed to explore IAI's MoA and its multi-target nature in DME pathophysiology with an in silico (computer simulation) disease model. We used the Therapeutic Performance Mapping System (Anaxomics Biotech property) to generate mathematical models based on the available scientific knowledge at the time of the study, describing the relationship between the modulation of vascular endothelial growth factor receptors (VEGFRs) by IAI and DME pathophysiological processes. We also undertook an enrichment analysis to explore the processes modulated by IAI, visualized the effectors' predicted protein activity, and specifically evaluated the role of VEGFR1 pathway inhibition on DME treatment. The models simulated the potential pathophysiology of DME and the likely IAI's MoA by inhibiting VEGFR1 and VEGFR2 signaling. The action of IAI through both signaling pathways modulated the identified pathophysiological processes associated with DME, with the strongest effects in angiogenesis, blood-retinal barrier alteration and permeability, and inflammation. VEGFR1 inhibition was essential to modulate inflammatory protein effectors. Given the role of VEGFR1 signaling on the modulation of inflammatory-related pathways, IAI may offer therapeutic advantages for DME through sustained VEGFR1 pathway inhibition.

Assessment of quality of life, psychosocial, and epidemiological aspects in patients diagnosed with tuberculous uveitis.

PURPOSE: To assess the quality of life in patients diagnosed as having tuberculous uveitis and its association with sociodemographic, clinical, and psychosocial aspects. METHOD: By conducting standardized interviews, clinical and demographic data were collected using a measure developed in this study. This measure was applied in addition to other measures, namely SF-12, Hospital Anxiety and Depression Scale, and NEI-VFQ-39, which were used to assess health-related quality of life, anxiety and depression symptoms, and visual functioning. RESULTS: The study included 34 patients [mean age: 46.5 ± 15.1 years, female patients: 21 (61.8%)]. The mean of the VFQ-39 score was 74.5 ± 16.6 and that of SF-12 physical and mental component scores were 45.8 ± 10.1 and 51.6 ± 7.5, respectively, for the health-related quality of life. Anxiety symptoms were the most prevalent compared with depression symptoms and were found in 35.3% of the participants. CONCLUSION: Tuberculous uveitis affects several scales of quality of life, thereby affecting a population economically active with a social, psychological, and economic burden.

Progression of Retinal Ganglion Cell and Nerve Fiber Layer Loss in Spinocerebellar Ataxia 3 Patients.

Spectral domain optical coherence tomography (SD-OCT) allows noninvasive measurements of retinal neuron layers. Here, we evaluate the relationship between clinical features and anatomical SD-OCT measurements in patients with spinocerebellar ataxia type 3 (SCA3) and how they change with time. A retrospective review was conducted on SCA3 patients. Clinical variables such as disease duration, number of CAG repeats, and the Scale for the Assessment and Rating of Ataxia (SARA) score were correlated with SD-OCT measurements, including retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, macular volume (MV), and central macular thickness (CMT). Seventeen SCA3 patients with an average follow-up of 44.9 months were recruited. Clinical features with significant baseline correlations with SD-OCT measurements included disease duration (CMT r = - 0.590; GCC r = - 0.585), SARA score (CMT r = - 0.560; RNFL r = - 0.390), and number of CAG repeats (MV r = - 0.552; RNFL r = - 0.503; GCC r = - 0.493). The annual rate of change of the SARA score during follow-up was associated with that of both the MV (r = - 0.494; p = 0.005) and GCC thickness (r = - 0.454; p = 0.012). High disability (stages 2 and 3) was independently inversely associated with the annual change in MV (ß coefficient - 17.09; p = 0.025). This study provides evidence of an association between clinical features and objective anatomical measurements obtained by SD-OCT in SCA3 patients. MV and GCC thickness could serve as potential biomarkers of disease severity, as their rates of decrease seem to be related to a worsening in the SARA score. These findings highlight the potential of SD-OCT as a noninvasive tool for assessing disease severity and progression in SCA3 patients.

Serum Vitamin D Levels as Biomarkers in Patients with Autoimmune Uveitis and their Possible Correlation with Disease Activity.

This study investigated the correlation between serum vitamin D levels and intraocular inflammation in patients with autoimmune uveitis (AIU). We evaluated 67 patients with active and inactive AIU and measured their serum 25-hydroxyvitamin D [25(OH)D] concentration, sun exposure habits, number of relapses, and complications. Of the patients evaluated, 85% had significantly lower vitamin D levels, and patients with active uveitis had lower 25(OH)D levels than those with inactive uveitis. The odds of developing active uveitis decreased by 6% with each 1-unit increase in 25(OH)D. Patients with recurrent active AIU had significantly lower 25(OH)D serum levels than inactive forms, indicating that low vitamin D levels may alter the clinical course of intraocular inflammation in AIU. Additionally, the study found that a higher mean BMI increased the chances of an individual having active uveitis by 14%. These results suggest that serum vitamin D concentration could be a prognostic clinical biomarker in AIU.

A Framework for Human Corneal Endothelial Cell Culture and Preliminary Wound Model Experiments with a New Cell Tracking Approach.

Cell injection therapy is emerging as an alternative to treat corneal endothelial dysfunction (CED) and to avoid corneal scarring due to bullous keratopathy. However, establishing a standardized culture procedure that provides appropriate cell yield while retaining functional features remains a challenge. Here, we describe a detailed framework obtained from in vitro culture of human corneal endothelial cells (HCECs) and comparative in vivo experimental models for CED treatment with a new cell tracking approach. Two digestion methods were compared regarding HCEC morphology and adhesion. The effect of Y-27632 (ROCKi) supplementation on final cell yield was also assessed. Cell adhesion efficacy with two cell delivery systems (superparamagnetic embedding and cell suspension) was evaluated in an ex vivo human cornea model and in an in vivo rabbit CED model. The injection of supplemented culture medium or balanced salt solution (BSS) was used for the positive and negative controls, respectively. HCEC isolation with collagenase resulted in better morphology and adhesion of cultured HCEC when compared to EDTA. Y-27632 supplementation resulted in a 2.6-fold increase in final cell yield compared to the control. Ex vivo and in vivo adhesion with both cell delivery systems was confirmed by cell tracker fluorescence detection. Corneal edema and opacity improved in both animal groups treated with cultured HCEC. The corneas in the control groups remained opaque. Both HCEC delivery systems seemed comparable as treatments for CED and for the prevention of corneal scarring.

A Comparative Study Using Fluorescent Confocal Microscopy and Flow Cytometry to Evaluate Chondrocyte Viability in Human Osteochondral Allografts.

The preservation conditions of fresh osteochondral allografts for clinical applications are critical due their objective: to transplant mature hyaline cartilage containing viable chondrocytes, maintaining their metabolic activity and also preserving the structural and functional characteristics of the extracellular matrix. The aim of the present study was to compare fluorescence confocal microscopy and flow cytometry techniques to evaluate the viability of the chondrocytes present in the osteochondral tissue, in order to determine their effectiveness and thus ensure reproducibility and robustness of the analysis. To this end, osteochondral allografts from human cadaveric donors were preserved at 4 °C for 3 weeks in a preservation medium supplemented with antibiotic and antifungal agents. Cell viability of chondrocytes was determined by monitoring the cartilage for 3 weeks of preservation by confocal fluorescence microscopy and flow cytometry, obtaining cell viabilities of 83.7 ± 2.6% and 55.8 ± 7.8% for week three, respectively. The confocal fluorescence microscopy approach is more advantageous and accurate, as it correlates better with actual cell viability values for monitoring osteochondral graft preservation, detecting only the cells that died a natural death associated with the preservation method.

Postoperative treatment compliance rate and complications with two different protocols after pterygium excision and conjunctival autografting.

AIM: To evaluate compliance rate to pterygium postoperative treatment with two different protocols. METHODS: Review of clinical data of patients submitted to pterygium excision and conjunctival autografting in a single centre (and a single surgeon) in Barcelona between March 2014 and December 2017. Initial postoperative protocol (protocol 1) consisted of 4 months of topical steroids in a tapering fashion. Protocol 2 consisted of topical steroids tapered over 5 weeks. Compliance rate, complications and clinical outcomes were evaluated, and statistical comparisons were made. RESULTS: 120 surgeries were performed in 99 patients. Protocol 1 was applied in 63 cases and the next 57 followed protocol 2. Compliance with protocol 1 (57.6%) was lower than with protocol 2 (84.9%) (p = 0.002). Intraoperative complications (graft tear, corneal thinning, corneal perforation and bleeding) were found in 10 cases of protocol 1 and three cases of protocol 2, p = 0.08. Postoperative complications (graft dislocation, graft haematoma, ocular hypertension and recurrence) were found in 31 cases of protocol 1 (46.2%) and eight cases of protocol 2 (14%), p = 0.001. Six weeks after surgery, ocular hypertension was detected in eight cases corresponding to protocol 1 (13.6%) and two cases of protocol 2 (3.8%), p = 0.099. Recurrence rate during first year was higher in protocol 1 (26.3%) compared to protocol 2 (7.6%), p = 0.011. No cases of visual acuity worsening or infection were registered. CONCLUSION: Protocol 2 has shown to have higher compliance rate than protocol 1 and less postoperative complications, proving to be a safe and effective postoperative treatment after pterygium surgery.

In vitro biofilm distribution on the intraocular lens surface of different biomaterials.

PURPOSE: To study the disposition of bacterial adhesion to intraocular lens (IOL) biomaterials depending on the material and region of the optic IOL surface: center or peripheral edge. SETTING: School of Medicine, University of Barcelona, Barcelona, Spain. DESIGN: Experimental study. METHODS: For the in vivo study, IOLs were explanted from donor ocular globes without clinical symptoms of endophthalmitis. Biofilm formation was qualitatively studied by scanning electron microscopy (SEM). For the in vitro study, 5 IOL biomaterials (hydrophilic acrylic, hydrophobic acrylic, poly[methyl methacrylate] [PMMA], heparinized PMMA, and silicone) were contaminated with a biofilm-producing strain of Staphylococcus epidermidis. Bacterial densities were quantitatively (colony-forming units per area) compared by SEM and direct counting of viable adherent bacteria, according to the biomaterial, region of the IOL optic surface, and time of incubation. For SEM, bacterial adhesion was also qualitatively classified according to the characteristics of biofilm observed: structure, cocci per cluster, homogeneity of cluster distribution, and extracellular matrix production. RESULTS: At 3 hours of incubation, bacterial counts for hydrophilic acrylic and PMMA IOLs were significantly lower, but at 72 hours there were no statistically significant differences among biomaterials. A higher density of bacteria was observed at the periphery of the IOL's optic of assayed biomaterials for in vitro and in vivo studies. Biofilm formation and the presence of extracellular matrix were predominantly restricted to the edges of IOL optic surface. CONCLUSION: Bacterial adhesion and biofilm development on the IOL optic surface depended on the region and biomaterial of the IOL. FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in any material or method mentioned.

Resultados de la queratoplastía penetrante en la queratopatía climática en gotas / Results of penetrating keratoplasty in climatic droplet keratopathy

Estudio retrospectivo de 14 ojos sometidos a queratoplastía penetrante óptico-refractiva, cuyo diagnóstico histopatológico fue de queratopatía climática en gotas, con seguimiento oftalmológico mínimo de cinco años. Se analizaron las agudezas visuales inicial y final, la integridad del injerto a largo plazo, así como los hallazgos epidemiológicos e histopatológicos más comunes. Hubo relación directa significativa (p = 0,004) entre la gravedad clínica de la alteración inicial en la córnea y la presencia de recidiva u opacificación del injerto. Los mejores resultados visuales fueron significativos (p = 0,02) en el grupo de queratoplastías donde se usaron injertos de 7.5 mm de diámetro o menos. Los hallazgos histopatológicos más característicos fueron la degeneración elastótica con depósitos en el estroma (93 por ciento), las alteraciones en la membrana de Bowman (85 por ciento), la cicatrización estromal (85 por ciento), seguido de las irregularidades del epitelio corneal (65 por ciento). La evolución crónica de la alteración en la córnea, la asociación a enfermedades inflamatorias conjuntivales recidivantes, y una distribución geográfica característica, fueron condiciones comunes para esta serie de pacientes.