Growth Factor Treatment Research Articles

Patient Preferences with Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Multinational Discrete Choice Experiment Study.

New anti-vascular endothelial growth factor (VEGF) treatments are emerging for the treatment of diabetic macular edema (DME)/neovascular age-related macular degeneration (nAMD). This study aimed to explore the treatment attributes patients find important when deciding on treatment options. This noninterventional survey study assessed treatment preferences through a discrete choice experiment (DCE) among patients with DME/nAMD in the United States, Canada, France, Italy, Spain, and the United Kingdom. The DCE design was informed by a targeted literature review and qualitative interview research and included five treatment attributes: mode of administration, frequency of examinations, frequency of injections or refills, likely change in visual acuity, and eye-related side effects. Conditional logit models were used to analyze the choice data. Overall, 537 patients completed the DCE (DME, n = 173; nAMD, n = 364). Patients reported preferring "injection" over "implant surgery and refills" and better visual outcomes over "stabilization", which were also the most important attributes driving preference (35.1% and 31.5%, respectively). They also showed a preference for less-frequent treatment and examinations and for "mild-moderate, frequent" over "severe, rare" side effects. These findings were generally consistent across the two conditions, although significant differences were found depending on anti-VEGF treatment duration (nAMD, DME) and number of reported barriers (nAMD). Patient preferences for treatment are driven by several factors. Considering these is essential when designing/introducing new therapies. Individual treatment preferences should be identified and given key consideration when helping patients select from an expanding array of treatment options.

EXTH-04. COMBINATION OF BEVACIZUMAB ENHANCES THE ANTI-TUMOR EFFICACY OF AD-SGE-REIC FOR GLIOMA

Abstract Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor gene and its overexpression has been shown to exert anti-tumor effects as a therapeutic target gene in many human cancers. Recently, we revealed the anti-glioma effects of an adenoviral vector carrying REIC/Dkk-3 with the super gene expression system (Ad-SGE-REIC) and conducted the phase Ⅰ/Ⅱ a clinical trial for recurrent malignant glioma (jRCT2063190013). Anti-vascular endothelial growth factor treatments such as bevacizumab have demonstrated convincing therapeutic efficacy in patients with glioma. In this study, we examined the effects of Ad-SGE-REIC on glioma treated with bevacizumab in vitro and in vivo. Ad-SGE-REIC treatment resulted in a significant reduction in the number of invasion cells treated with bevacizumab. Western blot analyses revealed the increased expression of several endoplasmic reticulum stress markers in cells treated with both bevacizumab and Ad-SGE-REIC, as well as decreased β-catenin protein levels. In glioma-bearing mouse models, survival was extended in the combination therapy group. These results suggest that the combination therapy of Ad-SGE-REIC and bevacizumab showed anti-glioma effects by suppressing the angiogenesis and invasion of tumor cells. Combined Ad-SGE-REIC and bevacizumab might be a promising strategy for the treatment of malignant glioma.

Impact of metabolism-related markers on outcomes in ovarian cancer patients: Findings of the MITO16A/MaNGO-OV2 trial.

In ovarian cancer, expression of metabolism-related markers has been investigated in several studies focusing on individual markers; however, a parallel quantitative evaluation of markers mapping to distinct metabolic processes and their prognostic value in large patient cohorts is still lacking. Here, by using immunohistochemistry followed by digital pathology, we investigated the expression of several markers related to glycolysis including monocarboxylate transporter 1 and 4 (MCT1, MCT4), glutamine metabolism (glutaminase, GLS) and hypoxia/acidosis (carbonic anhydrase 9, CA IX) in tissue microarrays of > 300 patients recruited in the MITO16A clinical trial, which involved treatment of ovarian cancer patients with carboplatin/taxol plus bevacizumab. Regarding the prognostic impact of these markers, results indicate that GLS expression correlated with progression-free survival, but this effect disappeared when data were corrected for multiple testing. All other markers showed no correlation with clinical outcome. These results indicate marked heterogeneity of expression of metabolism-associated markers in ovarian cancer; however, there was a lack of association with clinical benefit after chemotherapy/anti-vascular endothelial growth factor treatment. Notwithstanding the lack of prognostic value, knowledge of the pattern of expression of these biomarkers in tumors can be useful for patient stratification purposes when new drugs targeting these metabolic pathways will be tested.

ROPRNet: Deep learning-assisted recurrence prediction for retinopathy of prematurity

Retinopathy of Prematurity (ROP) recurrence is significant for the prognosis of ROP treatment. In this paper, corrected gestational age at treatment is involved as an important risk factor for the assessment of ROP recurrence. To reveal the complementary information from fundus images and risk factors, a dual-modal deep learning framework with two feature extraction streams, termed as ROPRNet, is designed to assist recurrence prediction of ROP after anti-vascular endothelial growth factor (Anti-VEGF) treatment, involving a stacked autoencoder (SAE) stream for risk factors and a cascaded deep network (CDN) stream for fundus images. Here, the specifically-designed CDN stream involves several novel modules to effectively capture subtle structural changes of retina in the fundus images, involving enhancement head (EH), enhanced ConvNeXt (EnConvNeXt) and multi-dimensional multi-scale feature fusion (MMFF). Specifically, EH is designed to suppress the variations of color and contrast in fundus images, which can highlight the informative features in the images. To comprehensively reveal the inherent medical hints submerged in the fundus images, an adaptive triple-branch attention (ATBA) and a special ConvNeXt with a rare-class sample generator (RSG) were designed to compose the EnConvNeXt for effectively extracting features from fundus images. The MMFF is designed for feature aggregation to mitigate redundant features from several fundus images from different shooting angles, involving a designed multi-dimensional and multi-sale attention (MD-MSA). The designed ROPRNet is validated on a real clinical dataset, which indicate that it is superior to several existing ROP diagnostic models, in terms of 0.894 AUC, 0.818 accuracy, 0.828 sensitivity and 0.800 specificity.

Prognosis and factors related to anti-VEGF therapy in patients with retinal vein occlusion and concomitant carotid artery disease

To evaluate the prognosis and influencing factors of retinal vein occlusion (RVO) in patients with concomitant carotid artery disease receiving anti-vascular endothelial growth factor (VEGF) treatment. Patients diagnosed with RVO and receiving anti-VEGF treatment were included. Eye and clinical data were collected. The patients were divided into a group with concomitant carotid artery disease (Group A) and a group without concomitant carotid artery disease (Group B). The risk factors affecting the visual prognosis of RVO patients with concomitant carotid artery disease were analyzed. Among 177 eligible patients with RVO, 101 had concomitant carotid artery disease (Group A), while 76 did not (Group B). Group A had a significantly lower treatment effectiveness rate than Group B (P < 0.001). The age and platelet distribution width of Group A were significantly higher than Group B (P < 0.001). Multivariate logistic regression analysis showed that baseline best-corrected visual acuity (BCVA), disorganization of retinal inner layers (DRIL), external limiting membrane (ELM) disruption, and red blood cell distribution width (RDW) were significantly associated with the posttreatment visual prognosis of RVO patients with concomitant carotid artery disease(P < 0.05). RVO patients with concomitant carotid artery disease had a significantly lower treatment effectiveness rate than RVO patients without carotid artery disease. The poor baseline BCVA, DRIL, ELM disruption, and a greater RDW are risk factors for low anti-VEGF treatment efficacy among RVO patients with concomitant carotid artery disease.

Dexamethasone implant for refractory macular edema secondary to diabetic retinopathy and retinal vein occlusion.

To evaluate the efficacy, timing of retreatment and safety of dexamethasone (DEX) implant on macular edema (ME) secondary to diabetic retinopathy (DME) and retinal vein occlusion (RVO-ME) patients who were refractory to anti-vascular endothelial growth factor (VEGF) treatment. This retrospective study included 37 eyes received at least one DEX implant treatment for DME or RVO-ME between January 1, 2019, and January 1, 2023. These refractory DME and RVO-ME cases received at least 5 anti-VEGF injections and failure to gain more than 5 letters or a significant reduction in central retinal thickness (CRT). The best corrected visual acuity (BCVA) and CRT were measured at baseline, and at 1, 3, 4 and 6mo post-DEX implant injection. Adverse events such as elevated intraocular pressure (IOP) and cataract were recorded. For RVO cases (n=22), there was a significant increase in BCVA from 0.27±0.19 to 0.35±0.20 at 6mo post-DEX injection (P<0.05) and CRT decreased from 472.1±90.6 to 240.5±39.0 µm at 6mo (P<0.0001). DME cases (n=15) experienced an improvement in BCVA from 0.26±0.15 to 0.43±0.20 at 6mo post-DEX implant injection (P=0.0098), with CRT reducing from 445.7±55.7 to 271.7±34.1 µm at 6mo (P<0.0001). Elevated IOP occurred in 45.9% of patients but was well-controlled with topical medications. No cases of cataract or other adverse events were reported. DEX implants effectively improve BCVA and reduce CRT in refractory DME and RVO-ME. Further research with larger cohorts and longer follow-up periods is needed to confirm these findings and assess long-term outcomes.

Impact of Anti-Vascular Endothelial Growth Factor Treatment on Neovascular Age-Related Macular Degeneration with and without Retinal Pigment Epithelial Detachment: A Real-World Study.

This study evaluates the impact of anti-vascular endothelial growth factor (anti-VEGF) treatment on neovascular age-related macular degeneration (nAMD) with and without pigment epithelial detachment (PED) over a one-year period. Conducted at a tertiary referral center in Taiwan, this retrospective analysis included 88 eyes treated with intravitreal aflibercept injections. Patients were categorized into four groups based on the presence or absence of PED at baseline and 12 months post-treatment. Significant reductions in central macular thickness (CMT) and PED height were observed, although no statistical difference was found in best-corrected visual acuity (BCVA). The presence or type of PED did not negatively impact visual outcomes. Among nAMD patients with persistent PED throughout the first year of anti-VEGF treatment, linear regression analysis showed that mixed-type PED revealed poor final BCVA compared to those with serous PED. The analysis also identified older age and poorer initial BCVA as predictors of less favorable visual outcomes. This study highlights the effectiveness of anti-VEGF therapy in real-world settings and offers insights into factors influencing visual outcomes for nAMD patients with PED.

One-Year Real-World Outcomes of Intravitreal Faricimab for Previously Treated Neovascular Age-Related Macular Degeneration.

This study assessed the efficacy, durability, and safety of faricimab in patients with neovascular age-related macular degeneration (nAMD), previously treated with aflibercept or ranibizumab with unsatisfactory results. This was a single-center, prospective cohort study of all consecutive patients with nAMD switched to intravitreally administered faricimab from traditional anti-vascular endothelial growth factor (anti-VEGF) treatments between September 2022 and April 2023 because of unsatisfactory response (maximal fluid-free interval ≤ 8weeks). Faricimab was administered with a loading dose of four 4-weekly injections, followed by a treat-and-extend regimen. The primary outcome measures were maximum fluid-free interval after the switch and last assigned treatment interval. Secondary outcome measures included best-corrected visual acuity (BCVA) and structural optical coherence tomography parameters. Thirty-three eyes of 33 patients were included. Patients were followed for a median of 72weeks [interquartile range 61, 76]. Median maximum fluid-free treatment interval after switch to faricimab and the last assigned interval were significantly longer than before the switch (7 vs. 4weeks, p < 0.001 and 8 vs. 5weeks, p < 0.001, respectively). Significant improvements in central subfield thickness (353 vs. 281µm), macular volume (2.46 vs. 2.16mm3), and pigment epithelial detachment height (198 vs. 150µm) were observed (all p < 0.001). BCVA remained stable at 0.4 versus 0.3logMAR before switch (p = 0.190). One eye (3%) developed intraocular inflammation and one eye (3%) developed a retinal pigment epithelium tear. Faricimab improved anatomical outcomes and allowed longer treatment intervals in patients with nAMD previously treated with other anti-VEGF therapies with unsatisfactory response, reducing treatment burden. A favorable safety profile was observed.

Nomogram for predicting short-term response to anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration: An observational study.

Anti-vascular endothelial growth factor (anti-VEGF) therapy is critical for managing neovascular age-related macular degeneration (nAMD), but understanding factors influencing treatment efficacy is essential for optimizing patient outcomes. To identify the risk factors affecting anti-VEGF treatment efficacy in nAMD and develop a predictive model for short-term response. In this study, 65 eyes of exudative AMD patients after anti-VEGF treatment for ≥ 1 mo were observed using optical coherence tomography angiography. Patients were classified into non-responders (n = 22) and responders (n = 43). Logistic regression was used to determine independent risk factors for treatment response. A predictive model was created using the Akaike Information Criterion, and its performance was assessed with the area under the receiver operating characteristic curve, calibration curves, and decision curve analysis (DCA) with 500 bootstrap re-samples. Multivariable logistic regression analysis identified the number of junction voxels [odds ratio = 0.997, 95% confidence interval (CI): 0.993-0.999, P = 0.010] as an independent predictor of positive anti-VEGF treatment outcomes. The predictive model incorporating the fractal dimension, number of junction voxels, and longest shortest path, achieved an area under the curve of 0.753 (95%CI: 0.622-0.873). Calibration curves confirmed a high agreement between predicted and actual outcomes, and DCA validated the model's clinical utility. The predictive model effectively forecasts 1-mo therapeutic outcomes for nAMD patients undergoing anti-VEGF therapy, enhancing personalized treatment planning.

Quantitative Evaluation of Type 1 and Type 2 Choroidal Neovascularization Components Under Treatment With Projection-Resolved OCT Angiography.

To evaluate the response of type 1 and type 2 macular neovascularization (MNV) components under anti-vascular endothelial growth factor (VEGF) treatment in age-related macular degeneration (AMD) using projection-resolved optical coherence tomography angiography (PR-OCTA). This retrospective study included eyes with treatment-naïve exudative AMD treated with anti-VEGF injections under a pro re nata (PRN) protocol over 1 year. Two-dimensional MNV areas and three-dimensional MNV volumes were derived from macular PR-OCTA scans using an automated convolutional neural network. MNV was detected as flow signal within the outer retinal slab. Type 1 components and type 2 components were analyzed separately. Of 17 enrolled eyes, 12 eyes were pure type 1 MNV and five eyes were type 2 MNV. In eyes with pure type 1, the total (sum of type 1 and type 2 components) MNV area and volume did not change from baseline to 6 months or 12 months (P > 0.05). In eyes with type 2 MNV, the total MNV area significantly decreased from the baseline to 6 months (P = 0.0074) and 12 months (P = 0.014). The total type 2 MNV volume also decreased from baseline visit to visits at 6 months and at 12 months, nearing statistical signifiicance (P = 0.061 and P = 0.074). In eyes with type 2 MNV, the type 1 component increased from 0.093 mm2 to 0.30 mm2 (P = 0.058), and the type 2 component decreased from 0.37 mm2 at 6 months to 0 at 12 months (P = 0.0087). Type 1 and type 2 MNV may have different response under PRN anti-VEGF treatment over 1 year.

Factors Influencing Treatment Preference in Patients with Diabetic Macular Edema: A Study Using Conjoint Analysis.

Despite the wide range of treatment options available for diabetic macular edema (DME), adherence to treatment remains a barrier. Therefore, this study used conjoint analysis to examine the factors that patients with DME prioritize when choosing a course of treatment and investigated differences in quality of life and levels of disease self-management in patients with or without experience of anti-vascular endothelial growth factor (VEGF) treatment. A cross-sectional study was conducted through an online survey in Japan between May 31, 2022, and June 30, 2022. Questionnaires were sent to 27,236 individuals registered in the diabetes panels, with experience of treatment for DME within the last 10years. Conjoint analysis was employed to calculate the relative importance, i.e., degree of influence on patients' treatment choices, considering the trade-offs among five factors: cost per treatment, frequency of visits, anticipated post-treatment visual acuity, physician's explanation about disease and treatment, and frequency of treatment-related side effects. A total of 237 responses were used to assess the relative importance of cost per treatment, frequency of visits, anticipated post-treatment visual acuity, physician's explanation about the disease, treatment, and frequency of treatment-related side effects using conjoint analysis. The importance of each factor was anticipated post-treatment visual acuity at 30.0, frequency of treatment-related side effects at 25.5, treatment frequency at 17.7, cost per treatment at 16.5, and physician explanation about the disease and treatment at 10.4. The average EuroQoL 5 dimension 5 level index value in patients with and without anti-VEGF treatment experience was 0.785 and 0.825, respectively, with no major difference. Anticipated post-treatment visual acuity was identified as the most important factor in selecting a treatment regardless of the anti-vascular endothelial growth factor treatment experience demonstrating when patients with DME make treatment choices, anticipated post-treatment visual acuity is prioritized over treatment frequency and cost.

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION AND POOR VISUAL ACUITY.

To investigate the significance of intravitreal anti-vascular endothelial growth factor treatment in patients with neovascular age-related macular degeneration and poor visual acuity. Retrospective study of patients with neovascular age-related macular degeneration with baseline best-corrected visual acuity of ≤20/200. Patients were divided into regular treatment and scarce treatment groups according to whether they underwent consecutive intravitreal anti-vascular endothelial growth factor treatments at intervals of ≤4 months or not. A total of 131 eyes were included: 87 and 44 eyes in the regular treatment and scarce treatment groups, respectively. The regular treatment group showed significantly improved preservation of lesion size at both Years 1 and 2, with significantly fewer incidences of new subretinal hemorrhage. Improvements in visual acuity, reduction in central subfield macular thickness, and maximal height of choroidal neovascularization were significantly favorable in the regular treatment group at Year 1, and central subfield macular thickness was significantly decreased at Year 2. Survival analysis revealed that the regular treatment group had significantly greater preservation of visual acuity and lesion size than that in the scarce treatment group. Maintaining intravitreal anti-vascular endothelial growth factor treatment for patients with neovascular age-related macular degeneration and poor vision showed significant advantages in visual acuity and lesion size stability and reduced the incidence of new subretinal hemorrhage, which suggests preservation of paracentral vision.

MERLIN: Two-Year Results of Brolucizumab in Participants with Neovascular Age-Related Macular Degeneration and Persistent Retinal Fluid

PurposeTo report the safety and efficacy of brolucizumab (Beovu®) 6 mg vs. aflibercept (Eylea®) 2 mg administered every 4 weeks in participants with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid after the Week 52 primary endpoint analysis (from Week 52 up to Week 104, post-study termination). DesignMulticenter, randomized, double-masked Phase 3a study. ParticipantsParticipants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-vascular endothelial growth factor treatment). MethodsStudy eyes were randomized 2:1 to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks for 100 weeks, or until study termination. Main Outcome MeasuresAll available efficacy (analysis of noninferiority in mean best-corrected visual acuity [BCVA], central subfield thickness [CST], fluid-free status [no intraretinal fluid and no subretinal fluid]), and safety data up to study termination, including data up to Week 104 for those participants who completed the study prior to its termination. All P values after Week 52 were nominal and reflect observed data for the efficacy analyses. ResultsBrolucizumab 6 mg every 4 weeks was noninferior to aflibercept 2 mg in mean BCVA change from baseline to Week 104 (least squares mean difference, -0.4 Early Treatment Diabetic Retinopathy Study letters; 95% confidence interval [CI], -3.7 to 3.0; P = 0.0169). The proportion of eyes with ≥15-letter loss was 6.2% for brolucizumab and 4.7% for aflibercept. (P = 0.0014), and a greater proportion of eyes were fluid free at Week 104 (52.5% brolucizumab vs. 28.2% aflibercept; 95% CI, 11.9−37.3; P < 0.001) in eyes treated with brolucizumab vs. aflibercept. Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, was 11.5% (0.8% and 2.2%) for brolucizumab vs 6.1% (0% and 0.6%) for aflibercept, respectively. ConclusionsConsistent with 52-week results, brolucizumab 6 mg every 4 weeks was noninferior in mean BCVA change with anatomic outcomes superior to aflibercept 2 mg every 4 weeks from baseline to Week 104 or study termination. The incidence of IOI, including retinal vasculitis and retinal vascular occlusion, was higher with brolucizumab vs. aflibercept; therefore, brolucizumab should not be used more frequently than every 8 weeks following the loading regimen.

In silico modeling the potential clinical effect of growth factor treatment on the metabolism of human nucleus pulposus cells.

While growth factors have the potential to halt degeneration and decrease inflammation in animal models, the literature investigating the effect of dosage on human cells is lacking. Moreover, despite the completion of clinical trials using growth differentiation factor-5 (GDF-5), no results have been publicly released. The overall objective was to quantitatively assess the effect of three clinically relevant concentrations of GDF-5 (0.25, 1, and 2 mg) as a therapeutic for disc regeneration. Firstly, this work experimentally determined the effects of GDF-5 concentration on the metabolic and matrix synthesis rates of human nucleus pulposus (NP) cells. Secondly, in silico modeling was employed to predict the subsequent regenerative effect of different GDF-5 treatments (± cells). This study suggests a trend of increased matrix synthesis with 0.25 and 1 mg of GDF-5. However, 2 mg of GDF-5 significantly upregulates oxygen consumption. Despite this, in silico models highlight the potential of growth factors in promoting matrix synthesis compared to cell-only treatments, without significantly perturbing the nutrient microenvironment. This work elucidates the potential of GDF-5 on human NP cells. Although the results did not reveal statistical differences across all doses, the variability and response among donors is an interesting finding. It highlights the complexity of human response to biological treatments and reinforces the need for further human research and personalized approaches. Furthermore, this study raises a crucial question about whether these potential biologics are more regenerative in nature or better suited as prophylactic therapies for younger patient groups. Biological agents exhibit unique characteristics and features, demanding tailored development strategies and individualized assessments rather than a one-size-fits-all approach. Therefore, the journey to realizing the full potential of biological therapies is long and costly. Nonetheless, it holds the promise of revolutionizing spinal healthcare and improving the quality of life for patients suffering from discogenic back pain.

Topographical Quantification of Retinal Fluid in Type 3 MNV and Associations With Short-Term Visual Outcomes

PurposeThis study aims to quantify the volume of intraretinal fluid (IRF), subretinal fluid (SRF), and sub-retinal pigment epithelium (sub-RPE) fluid in treatment-naïve Type 3 macular neovascularization (MNV) eyes with age-related macular degeneration (AMD) and to investigate the correlation of these fluid volumes with visual acuity (VA) outcomes at baseline and following anti-vascular endothelial growth factor (VEGF) treatment. DesignRetrospective, clinical cohort study. MethodsIn this study, we analyzed patients diagnosed with exudative AMD and treatment-naïve Type 3 MNV undergoing a loading dose of anti-VEGF therapy. Using a validated deep-learning segmentation strategy, we processed optical coherence tomography (OCT) B-scans to segment and quantify IRF (i.e., both in the inner and outer retina), SRF, and sub-RPE fluid volumes at baseline. The study correlated baseline fluid volumes with baseline and short-term VA outcomes post-loading dose of anti-VEGF injections. ResultsForty-six eyes from 46 patients were included in this study. Visual acuity was 0.51±0.30 LogMAR at baseline and 0.33±0.20 LogMAR after the loading dose of anti-VEGF (p=0.001). Visual acuity at the follow-up visit was 0.40±0.17 LogMAR in patients with no complete resolution of retinal fluid and 0.31±0.20 LogMAR in eyes without retinal fluid after treatment (P=0.225). In the multivariable analysis, the IRF volume in the inner retina (P=0.032) and the distance of the MNV from the fovea (P=0.037) were predictors of visual acuity at baseline. The baseline IRF volume in the inner retina also predicted the visual acuity at follow-up (p=0.023). ConclusionThe present study highlights the fluid volume in the inner retina as a crucial predictor of short-term visual outcomes in Type 3 MNV, underscoring the detrimental effect of IRF on neuroretinal structures.

Efficacy of a Combination Treatment of Ablative Fractional Carbon Dioxide Laser Therapy and Recombinant Human Epidermal Growth Factor for Atrophic Acne Scars.

Atrophic acne scars (AAS) are disfiguring and permanent changes caused by inflammatory acne. Fractional carbon dioxide is a common ablative device used to treat this condition. However, issues such as unclear effectiveness, frequent treatments, and potential side effects exist. In recent years, recombinant human epidermal growth factor (rhEGF) has also been frequently reported for its application in the treatment of acne scars. To explore the potential synergistic effect of fractional carbon dioxide laser combined with rhEGF in AAS treatment. We enrolled 15 patients with AAS. They received fractional carbon dioxide laser treatment and were then randomly assigned to receive either rhEGF or a placebo on one side of the face. The procedure was repeated three times, and the results were evaluated using the échelle d'évaluation clinique des cicatrices d'acné (ECCA) score and analyzed using the CBS camera system, 3D analysis (3DMD). Reflectance confocal microscopy (RCM) examination was also conducted. Both sides exhibited significant improvement in the appearance of the acne scars after treatment, as confirmed by the ECCA score, 3DMD data, and CBS texture score. On the rhEGF-treated side, the pore number and epidermal pigment area significantly improved as compared to the control side, whereas no significant differences were observed in the other data. Under RCM, a significant increase in epidermal thickness and appearance of reticular collagen fibers in the dermal layer after treatment was observed. Compared to the sole use of laser, the combination of fractional carbon dioxide laser and rhEGF does not significantly enhance scar therapeutic effects. However, it does shorten the recovery period after laser treatment and improves the pore appearance.

Temporal regulation of BMP2 growth factor signaling in response to mechanical loading is linked to cytoskeletal and focal adhesion remodeling

Biophysical cues have the ability to enhance cellular signaling response to Bone Morphogenetic Proteins, an essential growth factor during bone development and regeneration. Yet, therapeutic application of Bone Morphogenetic Protein 2 (BMP2) is restricted due to uncontrolled side effects. An understanding of the temporal characteristics of mechanically regulated signaling events and underlying mechanism is lacking. Using a 3D bioreactor system in combination with a soft macroporous biomaterial substrate, we mimic the in vivo environment that BMP2 is acting in. We show that the intensity and duration of BMP2 signaling increases with increasing loading frequency in synchrony with the number and size of focal adhesions. Long-term mechanical stimulation increases the expression of BMP receptor type 1B, specific integrin subtypes and integrin clustering. Together, this triggered a short-lived mechanical echo that enhanced BMP2 signaling even when BMP2 is administered directly after mechanical stimulation, but not when it is applied after a resting period of ≥30 min. Interfering with cytoskeletal remodeling hinders focal adhesion remodeling verifying its critical role in shifting cells into a state of high BMP2 responsiveness. The design of biomaterials that exploit this potential locally at the site of injury will help to overcome current limitations of clinical growth factor treatment.

Caregiver Experience Survey of Anti-Vascular Endothelial Growth Factor Treatment for Diabetic Macular Edema and Neovascular Age-Related Macular Degeneration

Introduction: Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) require frequent anti-vascular endothelial growth factor (VEGF) treatment and monitoring visits. We aimed to understand the burden of treatment on caregivers. Methods: This multinational, noninterventional study used a cross-sectional survey of adult patients with DME or nAMD treated with anti-VEGF injections in the USA, Canada, France, Italy, Spain, and the UK. The survey assessed caregivers’ sociodemographic characteristics, patient relationships, patients’ clinical history and treatment experiences, caregivers’ experiences, and the Caregiver Reaction Assessment of caregiving burden. Results: Caregivers for patients with DME (n = 30) and nAMD (n = 95) completed surveys. Mean ± standard deviation (SD) age was 64.0 ± 13.4 years, and most were female (71.2%), white (70.4%), married (66.4%), and from Europe (67.2%). Most were caring for their mother/father or partner/spouse (85.6%). Mean ± SD length of time as a caregiver was 9.1 ± 10.0 years. Caregivers estimated they provided support for 4.2 ± 2.9 days/week and 6.0 ± 7.1 h/day on average. Nearly half of caregivers (45.6%) reported some impairment in daily activities, and more than two-thirds (70.5%) of working caregivers (n = 44) reported work absenteeism due to anti-VEGF treatment/monitoring appointments. At least one treatment barrier was reported by 66.7% and 50.5% of caregivers of patients with DME and nAMD, respectively, which were related to coronavirus disease 2019- (38.4%), clinic- (18.4%), social-/health- (13.6%), treatment- (10.4%), or financial-related factors (4.8%). Caregiver Reaction Assessment scores indicated mild-to-moderate burden, with higher caregiver schedule disruption scores associated with an increasing number of anti-VEGF treatment/monitoring visits among DME caregivers (r = 0.61). Conclusion: Caregivers devote substantial time to caregiving, leading to schedule disruptions and absenteeism for some working caregivers. Positive and negative impacts on caregiver mental health were reported.

The Short-Term Efficacy and Safety of Faricimab in Refractory Neovascular Age-Related Macular Degeneration: The Real-World Experience in Taiwan

Introduction: Anti-vascular endothelial growth factor (VEGF) treatment stands as the primary approach for neovascular age-related macular degeneration (nAMD). Faricimab has recently emerged as a novel anti-VEGF option for nAMD. This study aimed to assess the efficacy of faricimab in patients with refractory nAMD. Method: This retrospective study focused on refractory nAMD patients treated with faricimab at Taipei Veterans General Hospital from March 2023 to December 2023. Primary outcomes assessed the change in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) over the first 4 months. Secondary outcomes included the presence of subretinal and intraretinal fluid (SRF and IRF) and changes in pigment epithelial detachment (PED). Subgroup analysis for the successful and unsuccessful treatment groups was conducted to identify potential confounding factors influencing treatment response. Result: This study included 42 eyes with refractory nAMD treated with faricimab. During a 6-month follow-up, no significant improvement in BCVA was observed, while CRT significantly decreased at all time points, except during the 5-month follow-up. Height PED showed significant reduction up to 5 months. The prevalence of SRF decreased significantly, while IRF remained lower but not significant. According to the treatment criteria, 67.4% successfully met the treatment goals. Subgroup analysis between successful and unsuccessful groups showed no significant differences in baseline characteristics, except a higher predominantly serous PED percentage in the successful group. Conclusion: Faricimab showed favorable outcomes in refractory nAMD patients. Further investigations are needed to understand the factors contributing to its efficacy.

Factors Affecting Disease Stability After Intravitreal Brolucizumab Injection for Refractory Neovascular Age-Related Macular Degeneration.

The purpose of this study is to identify the factors affecting neovascular age-related macular degeneration (nAMD) disease stability after brolucizumab treatment. We retrospectively analyzed the medical records of 31 patients (31 eyes) with recalcitrant nAMD who were switched to brolucizumab after conventional anti-vascular endothelial growth factor (VEGF) treatment. We divided patients into two groups by treatment extension (TE) period: group 1 with TE < 12weeks (N = 16) and group 2 with TE ≥ 12weeks (N = 15). We compared outcomes between the groups at 2, 4, 8, and 12weeks, including morphological characteristics of choroidal neovascularization (CNV). Logistic regression analysis identified factors associated with TE ≥ 12weeks. Group 2 had a significantly greater proportion of patients with dry macula (subretinal and intraretinal fluids absent) than group 1 (60 vs. 12.5%) at 2weeks (P < 0.05). Best-corrected visual acuity (BCVA) and subfoveal choroidal thickness (SFCT) did not differ significantly between groups at all timepoints. Central subfield retinal thickness (CST) was significantly lower in group 2 at 2 (237.1 vs. 280.8μm; P < 0.05), 4 (224.0 vs. 262.9μm; P < 0.05), and 8weeks (216.8 vs. 331.1μm; P < 0.05). Group 2 had less vessel area (0.63 vs. 1.27 mm2; P < 0.05) and total vessel length (0.22 vs. 0.42mm; P < 0.05). Choriocapillaris flow deficit (CCFd) was significantly lower in group 2 (42.7 vs. 48.2%; P < 0.05). Dry macula at 2weeks (odds ratio [OR] = 8.3; P < 0.05) and a lower CCFd (OR = 0.73; P < 0.05) were associated with TE ≥ 12weeks. Early fluid-free status after switching to brolucizumab and choriocapillary function around CNV were prognostic factors for disease stability in nAMD refractory to anti-VEGF treatment.