Non-surgical treatment of stage 4A retinopathy of prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is a major cause of visual impairment in premature infants, often requiring surgical interventions in advanced stages. This retrospective case series study investigates non-surgical management for Stage 4A ROP, specifically the use of combined laser therapy and intravitreal anti-vascular endothelial growth factor (VEGF) injections. METHODS: Ten eyes from five infants with Stage 4A ROP were treated with a combined laser and anti-VEGF approach. Comprehensive follow-up examinations were conducted to evaluate the treatment outcomes. RESULTS: The study demonstrated successful retinal attachment without complications, showcasing the efficacy and safety of this non-surgical method. A comparison with surgical interventions highlighted the potential benefits in terms of reduced adverse effects. DISCUSSION: This combined treatment emerges as a promising first-choice option for Stage 4A ROP, offering rapid regression without surgical intervention, particularly in early stages. However, larger randomized clinical trials are necessary to validate these findings and establish definitive guidelines for managing this complex condition. CONCLUSION: Combined laser and anti-VEGF therapy proved to be an effective and safe non-surgical approach for Stage 4A ROP, with the potential to reduce the need for surgery, especially in its early presentation. Further research is required to confirm these findings and provide comprehensive recommendations for clinical practice.

Status of alternative angiogenic pathways in glioblastoma resected under and after bevacizumab treatment.

Glioblastoma multiforme (GBM) acquires resistance to bevacizumab (Bev) treatment. Bev affects angiogenic factors other than vascular endothelial growth factor (VEGF), which are poorly understood. We investigated changes in angiogenic factors under and after Bev therapy, including angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), placental growth factor (PLGF), fibroblast growth factor 2, and ephrin A2 (EphA2). Fifty-four GBM tissues, including 28 specimens from 14 cases as paired specimens from the same patient obtained in three settings: initial tumor resection (naïve Bev), tumors resected following Bev therapy (effective Bev), and recurrent tumors after Bev therapy (refractory Bev). Immunohistochemistry assessed their expressions in tumor vessels and its correlation with recurrent MRI patterns. PLGF expression was higher in the effective Bev group than in the naïve Bev group (p = 0.024) and remained high in the refractory Bev group. ANGPT2 and EphA2 expressions were higher in the refractory Bev group than in the naïve Bev group (p = 0.047 and 0.028, respectively). PLGF expression was higher in the refractory Bev group compared with the naïve Bev group for paired specimens (p = 0.036). PLGF was more abundant in T2 diffuse/circumscribe patterns (p = 0.046). This is the first study to evaluate angiogenic factors other than VEGF during effective and refractory Bev therapy in patient-derived specimens.

Switching to the aflibercept (3 mg) therapy for treatment-resistant wet age-related macular degeneration: 1-year outcomes.

This study aimed to elucidate 1-year outcomes following switching to the aflibercept (3 mg) therapy for treatment-resistant wet age-related macular degeneration (wAMD). In this prospective, open-label, non-controlled clinical trial, 18 patients with wAMD who had multiple recurrences or persistent exudation despite intravitreal injections of anti-vascular endothelial growth factor agents (except aflibercept) received a 3-mg intravitreal aflibercept injection every 4 weeks. Each patient received 3 to 8 injections. The central retinal thickness and fibrovascular pigment epithelial detachment height decreased significantly at 1 month after initiation of the aflibercept injection, and the values were 146 and 163.2 µm, respectively, at the final visit. The morphological improvement was sustained. The intraretinal and subretinal fluid was completely absorbed at the end of the follow-up. The logMAR vision increased from baseline 0.68 to 0.59 (P < .05). No ocular or systemic adverse events occurred. The intravitreal injection of 3-mg aflibercept seems to be feasible in the treatment of wAMD unresponsive to other anti-vascular endothelial growth factor agents.

Impact of Anti-angiogenic Drugs on Severity of COVID-19 in Patients with Non-Small Cell Lung Cancer.

Introduction: The 2019 coronavirus disease (COVID-19) pandemic has reshaped oncology practice, but the impact of anti-angiogenic drugs on the severity of COVID-19 in patients with non-small cell lung cancer (NSCLC) remains unclear. Patients and Methods: We carried out a retrospective study involving 166 consecutive patients with NSCLC who were positive for COVID-19, aiming to determine the effects of anti-angiogenic drugs on disease severity, as defined by severe/critical symptoms, intensive care unit (ICU) admission/intubation, and mortality outcomes. Risk factors were identified using univariate and multivariate logistic regression models. Results: Of the participants, 73 had been administered anti-angiogenic drugs (termed the anti-angiogenic therapy (AT) group), while 93 had not (non-AT group). Comparative analyses showed no significant disparity in the rates of severe/critical symptoms (21.9% vs 35.5%, P = 0.057), ICU admission/intubation (6.8% vs 7.5%, P = 0.867), or death (11.0% vs 9.7%, P = 0.787) between these two groups. However, elevated risk factors for worse outcomes included age ≥ 60 (odds ratio (OR): 2.52, 95% confidence interval (CI): 1.07-5.92), Eastern Cooperative Oncology Group performance status of 2 or higher (OR: 21.29, 95% CI: 4.98-91.01), chronic obstructive pulmonary disease (OR: 7.25, 95% CI: 1.65-31.81), hypertension (OR: 2.98, 95% CI: 1.20-7.39), and use of immunoglobulin (OR: 5.26, 95% CI: 1.06-26.25). Conclusion: Our data suggests that the use of anti-angiogenic drugs may not exacerbate COVID-19 severity in NSCLC patients, indicating their potential safe application even during the pandemic period.

ID1high/activin Ahigh glioblastoma cells contribute to resistance to anti-angiogenesis therapy through malformed vasculature.

Although bevacizumab (BVZ), a representative drug for anti-angiogenesis therapy (AAT), is used as a first-line treatment for patients with glioblastoma (GBM), its efficacy is notably limited. Whereas several mechanisms have been proposed to explain the acquisition of AAT resistance, the specific underlying mechanisms have yet to be sufficiently ascertained. Here, we established that inhibitor of differentiation 1 (ID1)high/activin Ahigh glioblastoma cell confers resistance to BVZ. The bipotent effect of activin A during its active phase was demonstrated to reduce vasculature dependence in tumorigenesis. In response to a temporary exposure to activin A, this cytokine was found to induce endothelial-to-mesenchymal transition via the Smad3/Slug axis, whereas prolonged exposure led to endothelial apoptosis. ID1 tumors showing resistance to BVZ were established to be characterized by a hypovascular structure, hyperpermeability, and scattered hypoxic regions. Using a GBM mouse model, we demonstrated that AAT resistance can be overcome by administering therapy based on a combination of BVZ and SB431542, a Smad2/3 inhibitor, which contributed to enhancing survival. These findings offer valuable insights that could contribute to the development of new strategies for treating AAT-resistant GBM.

Short Term Effect of Pre-Operative Anti-VEGF on Angiogenic and Fibrotic Profile of Fibrovascular Membranes of Proliferative Diabetic Retinopathy.

Purpose: Adjuvant, pre-operative intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have been used to reduce peri-operative bleeding in eyes undergoing pars-plana vitrectomy for complications of proliferative diabetic retinopathy (PDR). To address the concern over their potential off-target effects of progressive fibrous contraction, we sought to dissect the transcriptional changes in the surgically extracted fibrovascular membranes (FVMs). Methods: We analyzed surgically extracted FVMs from 10 eyes: 4 eyes pretreated with intravitreal bevacizumab (IVB) and 6 untreated eyes. FVMs were digested into single cells, mRNA was extracted from endothelial cell-enriched (microbead selection with CD31) and non-endothelial cell compartments, followed by RT-qPCR quantification. We then compared the relative expression of genes involved in angiogenesis, endothelial cell integrity, and myofibroblastic processes between treated and untreated FVMs. Results: Endothelial cells from IVB pretreated FVMs showed significant reduction of VEGFA, VEGF receptors (FLT1 and KDR), and angiopoietin 2 expression as well as increased vascular endothelial cadherin and endothelin, suggesting reduced angiogenesis and enhanced vascular integrity. The non-endothelial cell fraction showed decreased expression of VEGFA and fibronectin, without significant difference in the expression of other profibrotic factors. Conclusions: Our findings confirm that adjuvant pre-operative IVB decreased fibronectin and increase endothelin-1 expression without affecting other profibrotic gene expression, uncovering an important interaction between IVB and endothelin-1 that deserves further study.

Brolucizumab in recalcitrant neovascular age-related macular degeneration-real-world data in Chinese population.

This retrospective study aimed to determine the short-term efficacy and safety of brolucizumab treatment for recalcitrant neovascular age-related macular degeneration (nAMD) in a real-world setting in Taiwan. Recalcitrant nAMD patients who were treated with brolucizumab from November 2021 to August 2022 at Taipei Veterans General Hospital were included. Patients were followed for 3 months after switching to brolucizumab. The primary outcomes were changes in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to the third month. The secondary outcomes included the incidence of intraocular inflammation (IOI), proportion of patients with subretinal and intraretinal fluid (SRF and IRF), and change in pigment epithelial detachment (PED) height from baseline to the third month. The significance level was considered as p < .05 in all tests. A total of 38 patients (40 eyes) with a mean (±SD) age of 76.3 (±10.84) years were included. The baseline BCVA was 0.92±0.64 logMAR, and the CRT and PED height were 329.0±171.18 and 189.8±114.94 um, respectively. The patients had a significant reduction in CRT and resolution of IRF and SRF from baseline to the third month. There were numerical improvements in mean BCVA and PED height, but they were not significant. The percentages of achieving at least 0.1, 0.2, and 0.3 logMAR (equivalent to 5, 10, 15 ETDRS letters) visual gain were 50%, 37.5%, and 30%, respectively, during the first 3 months of follow-up. No IOI occurred in these patients. This study demonstrated that brolucizumab had good short-term structural and functional efficacy in recalcitrant nAMD patients.

Exploring the Impact of Saccharin on Neovascular Age-Related Macular Degeneration: A Comprehensive Study in Patients and Mice.

Purpose: We aimed to determine the impact of artificial sweeteners (AS), especially saccharin, on the progression and treatment efficacy of patients with neovascular age-related macular degeneration (nAMD) under anti-vascular endothelial growth factor (anti-VEGF-A) treatment. Methods: In a cross-sectional study involving 46 patients with nAMD undergoing intravitreal anti-VEGF therapy, 6 AS metabolites were detected in peripheral blood using liquid chromatography - tandem mass spectrometry (LC-MS/MS). Disease features were statistically tested against these metabolite levels. Additionally, a murine choroidal neovascularization (CNV) model, induced by laser, was used to evaluate the effects of orally administered saccharin, assessing both imaging outcomes and gene expression patterns. Polymerase chain reaction (PCR) methods were used to evaluate functional expression of sweet taste receptors in a retinal pigment epithelium (RPE) cell line. Results: Saccharin levels in blood were significantly higher in patients with well-controlled CNV activity (P = 0.004) and those without subretinal hyper-reflective material (P = 0.015). In the murine model, saccharin-treated mice exhibited fewer leaking laser scars, lesser occurrence of bleeding, smaller fibrotic areas (P < 0.05), and a 40% decrease in mononuclear phagocyte accumulation (P = 0.06). Gene analysis indicated downregulation of inflammatory and VEGFR-1 response genes in the treated animals. Human RPE cells expressed taste receptor type 1 member 3 (TAS1R3) mRNA and reacted to saccharin stimulation with changes in mRNA expression. Conclusions: Saccharin appears to play a protective role in patients with nAMD undergoing intravitreal anti-VEGF treatment, aiding in better pathological lesion control and scar reduction. The murine study supports this observation, proposing saccharin's potential in mitigating pathological VEGFR-1-induced immune responses potentially via the RPE sensing saccharin in the blood stream.

Osimertinib in combination with anti-angiogenesis therapy presents a promising option for osimertinib-resistant non-small cell lung cancer.

BACKGROUND: Osimertinib has become standard care for epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) patients whereas drug resistance remains inevitable. Now we recognize that the interactions between the tumor and the tumor microenvironment (TME) also account for drug resistance. Therefore, we provide a new sight into post-osimertinib management, focusing on the alteration of TME. METHODS: We conducted a retrospective study on the prognosis of different treatments after osimertinib resistance. Next, we carried out in vivo experiment to validate our findings using a humanized mouse model. Furthermore, we performed single-cell transcriptome sequencing (scRNA-seq) of tumor tissue from the above treatment groups to explore the mechanisms of TME changes. RESULTS: Totally 111 advanced NSCLC patients have been enrolled in the retrospective study. The median PFS was 9.84 months (95% CI 7.0-12.6 months) in the osimertinib plus anti-angiogenesis group, significantly longer than chemotherapy (P = 0.012) and osimertinib (P = 0.003). The median OS was 16.79 months (95% CI 14.97-18.61 months) in the osimertinib plus anti-angiogenesis group, significantly better than chemotherapy (P = 0.026), the chemotherapy plus osimertinib (P = 0.021), and the chemotherapy plus immunotherapy (P = 0.006). The efficacy of osimertinib plus anlotinib in the osimertinib-resistant engraft tumors (R-O+A) group was significantly more potent than the osimertinib (R-O) group (P<0.05) in vitro. The combinational therapy could significantly increase the infiltration of CD4+ T cells (P<0.05), CD25+CD4+ T cells (P<0.001), and PD-1+CD8+ T cells (P<0.05) compared to osimertinib. ScRNA-seq demonstrated that the number of CD8+ T and proliferation T cells increased, and TAM.mo was downregulated in the R-O+A group compared to the R-O group. Subtype study of T cells explained that the changes caused by combination treatment were mainly related to cytotoxic T cells. Subtype study of macrophages showed that proportion and functional changes in IL-1ß.mo and CCL18.mo might be responsible for rescue osimertinib resistance by combination therapy. CONCLUSIONS: In conclusion, osimertinib plus anlotinib could improve the prognosis of patients with a progressed disease on second-line osimertinib treatment, which may ascribe to increased T cell infiltration and TAM remodeling via VEGF-VEGFR blockage.

Off-label use of intravitreal bevacizumab: A global conundrum.

Bevacizumab is a monoclonal, humanized, full-length antibody targeting vascular endothelial growth factor(VEGF-A), known for its anti-angiogenic properties. The off-label use of bevacizumab has stirred legal, financial, industrial, and ethical complexities. With its potential to treat diverse ocular conditions, this commentary delves into the multifaceted dimensions of bevacizumab's off-label utilization, encompassing clinical trials, regulatory frameworks, safety considerations, comparative effectiveness, and economic implications.

Machine learning and optical coherence tomography-derived radiomics analysis to predict persistent diabetic macular edema in patients undergoing anti-VEGF intravitreal therapy.

BACKGROUND: Diabetic macular edema (DME) is a leading cause of vision loss in patients with diabetes. This study aimed to develop and evaluate an OCT-omics prediction model for assessing anti-vascular endothelial growth factor (VEGF) treatment response in patients with DME. METHODS: A retrospective analysis of 113 eyes from 82 patients with DME was conducted. Comprehensive feature engineering was applied to clinical and optical coherence tomography (OCT) data. Logistic regression, support vector machine (SVM), and backpropagation neural network (BPNN) classifiers were trained using a training set of 79 eyes, and evaluated on a test set of 34 eyes. Clinical implications of the OCT-omics prediction model were assessed by decision curve analysis. Performance metrics (sensitivity, specificity, F1 score, and AUC) were calculated. RESULTS: The logistic, SVM, and BPNN classifiers demonstrated robust discriminative abilities in both the training and test sets. In the training set, the logistic classifier achieved a sensitivity of 0.904, specificity of 0.741, F1 score of 0.887, and AUC of 0.910. The SVM classifier showed a sensitivity of 0.923, specificity of 0.667, F1 score of 0.881, and AUC of 0.897. The BPNN classifier exhibited a sensitivity of 0.962, specificity of 0.926, F1 score of 0.962, and AUC of 0.982. Similar discriminative capabilities were maintained in the test set. The OCT-omics scores were significantly higher in the non-persistent DME group than in the persistent DME group (p < 0.001). OCT-omics scores were also positively correlated with the rate of decline in central subfield thickness after treatment (Pearson's R = 0.44, p < 0.001). CONCLUSION: The developed OCT-omics model accurately assesses anti-VEGF treatment response in DME patients. The model's robust performance and clinical implications highlight its utility as a non-invasive tool for personalized treatment prediction and retinal pathology assessment.

Emerging therapies targeting growth factors in hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a primary liver cancer that commonly arises in the background of chronic liver inflammation and/or cirrhosis. Chronic liver inflammation results in the production of different growth factors, remodeling of the microenvironment architecture into fibrosis, and eventually carcinogenesis. Overexpression of some growth factors has been associated with worse prognosis in patients with HCC. Targeted therapies against growth factors may disrupt cell signaling and the mechanisms that allow for cell survival (e.g. angiogenesis, proliferation, metastases). AREAS COVERED: We herein review potential growth factor targets of HCC and the limited research that exists regarding targeted therapy of these ligands and their receptors. We performed an extensive literature search to investigate preclinical studies, clinical research, and clinical trials. EXPERT OPINION: Systemic therapy for patients with HCC is continuing to evolve. Anti-angiogenic therapy holds the most promise among targeted therapy for growth factors among patients with HCC. Improving our understanding of growth factors in HCC will hopefully lead to the development of new targeted therapies and strategies for combination therapies with immune checkpoint inhibitors.

Central subfield thickness of diabetic macular edema: Correlation with the aqueous humor proteome.

Purpose: Diabetic macular edema (DME) is a sight-threatening complication of diabetes. Consequently, studying the proteome of DME may provide novel insights into underlying molecular mechanisms. Methods: In this study, aqueous humor samples from eyes with treatment-naïve clinically significant DME (n = 13) and age-matched controls (n = 11) were compared with label-free liquid chromatography-tandem mass spectrometry. Additional aqueous humor samples from eyes with treatment-naïve DME (n = 15) and controls (n = 8) were obtained for validation by enzyme-linked immunosorbent assay (ELISA). Best-corrected visual acuity (BCVA) was evaluated, and the severity of DME was measured as central subfield thickness (CST) employing optical coherence tomography. Control samples were obtained before cataract surgery. Significantly changed proteins were identified using a permutation-based calculation, with a false discovery rate of 0.05. A human donor eye with DME and a control eye were used for immunofluorescence. Results: A total of 101 proteins were differentially expressed in the DME. Regulated proteins were involved in complement activation, glycolysis, extracellular matrix interaction, and cholesterol metabolism. The highest-fold change was observed for the fibrinogen alpha chain (fold change = 17.8). Complement components C2, C5, and C8, fibronectin, and hepatocyte growth factor-like protein were increased in DME and correlated with best-corrected visual acuity (BCVA). Ceruloplasmin and complement component C8 correlated with central subfield thickness (CST). Hemopexin, plasma kallikrein, monocyte differentiation antigen CD14 (CD14), and lipopolysaccharide-binding protein (LBP) were upregulated in the DME. LBP was correlated with vascular endothelial growth factor. The increased level of LBP in DME was confirmed using ELISA. The proteins involved in desmosomal integrity, including desmocollin-1 and desmoglein-1, were downregulated in DME and correlated negatively with CST. Immunofluorescence confirmed the extravasation of fibrinogen at the retinal level in the DME. Conclusion: Elevated levels of pro-inflammatory proteins, including the complement components LBP and CD14, were observed in DME. DME was associated with the loss of basal membrane proteins, compromised desmosomal integrity, and perturbation of glycolysis.

Flavonoids with Anti-Angiogenesis Function in Cancer.

The formation of new blood vessels, known as angiogenesis, significantly impacts the development of multiple types of cancer. Consequently, researchers have focused on targeting this process to prevent and treat numerous disorders. However, most existing anti-angiogenic treatments rely on synthetic compounds and humanized monoclonal antibodies, often expensive or toxic, restricting patient access to these therapies. Hence, the pursuit of discovering new, affordable, less toxic, and efficient anti-angiogenic compounds is imperative. Numerous studies propose that natural plant-derived products exhibit these sought-after characteristics. The objective of this review is to delve into the anti-angiogenic properties exhibited by naturally derived flavonoids from plants, along with their underlying molecular mechanisms of action. Additionally, we summarize the structure, classification, and the relationship between flavonoids with their signaling pathways in plants as anti-angiogenic agents, including main HIF-1α/VEGF/VEGFR2/PI3K/AKT, Wnt/ß-catenin, JNK1/STAT3, and MAPK/AP-1 pathways. Nonetheless, further research and innovative approaches are required to enhance their bioavailability for clinical application.

[Challenges and strategies in the treatment of neovascular age-related macular degeneration].

Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness in the elderly, and anti-vascular endothelial growth factor (VEGF) therapy is currently the primary treatment approach. However, the real-world effectiveness of nAMD treatment is not always satisfactory and faces various challenges. Frequent administration and follow-up burdens can lead to decreased patient compliance during long-term treatment, resulting in suboptimal outcomes. Some lesions exhibit poor or no response to anti-VEGF treatment, leading to difficulties in maintaining or even declining visual acuity. Factors such as lesion fibrosis and tissue atrophy can contribute to visual deterioration. Therefore, standardizing and individualizing treatment plans, along with enhancing comprehensive monitoring and management throughout the disease course, are crucial improvement measures. The evidence-based guidelines for diagnosis and treatment of age-related macular degeneration in China, released in 2023, provide guidance for standardized clinical diagnosis and treatment. Meanwhile, research and development of new drugs and administration methods are anticipated for the future.

Aflibercept 5+PRN with retinal laser photocoagulation is more effective than retinal laser photocoagulation alone and aflibercept 3+PRN with retinal laser photocoagulation in patients with high-risk proliferative diabetic retinopathy and diabetic macular edema: a 12-month clinical trial.

Objective: This study aimed to investigate and compare the efficacy and safety of retinal laser photocoagulation (PRP) alone, PRP with aflibercept 3+PRN, and PRP with aflibercept 5+PRN in patients with both high-risk proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). Methods: Overall, 170 patients with high-risk PDR and DME (170 eyes from 170 patients) who visited our ophthalmology clinic from December 2018 to December 2020 were divided into the PRP (n=58), aflibercept 5+PRN with PRP (n=53), and aflibercept 3+PRN with PRP (n= 59) groups. General information, such as age, sex, and eye category, was obtained. Moreover, best-corrected visual acuity (BCVA), baseline central macular foveal thickness (CFT), microaneurysm (MA), area of neovascularization (NV), area of hard exudate (HE), and cytokine levels in atrial fluid before and after treatment, were assessed. The χ2 test was used for comparison between groups for statistical data. Analysis of variance was used for the statistical description of measurement data, independent samples were analyzed using Student's t-test, and Student-Newman-Keuls test was used for group comparisons. Differences were considered statistically significant at P < 0.05. Results: After treatment, no significant improvement in the BCVA (logMAR) of patients in the PRP group was observed. The BCVA (log MAR) decreased from 0.72 ± 0.17 and 0.74 ± 0.17 to 0.50 ± 0.13 and 0.53 ± 0.17 in PRP with aflibercept 5+PRN and PRP with aflibercept 3+PRN groups, respectively, with a statistically significant difference compared to those in the PRP group (P<0.05 in all cases). However, no statistically significant difference was observed between the combined treatment groups (P>0.05). The CFT in the PRP-only group decreased slightly from 361.80 ± 36.70 µm to 353.86 ± 40.88 µm, with no statistically significant difference (P>0.05), whereas the CFT in the aflibercept 5+PRN with PRP and aflibercept 3+PRN with PRP groups decreased from 356.57 ± 37.57 µm and 358.17 ± 44.66 µm to 284.87 ± 31.52 µm and 303.19 ± 37.00 µm, respectively, with statistically significant differences before and after treatment (P<0.05 for both groups). Statistically significant differences were observed in CFT between the three groups after treatment (P<0.05 in all cases). The number of MA (pcs) in the PRP, aflibercept 5+PRN with PRP, and aflibercept 3+PRN with PRP groups decreased from 118.34 ± 27.96, 118.60 ± 33.34, and 116.59 ± 28.95 to 92.95 ± 29.04, 44.60 ± 20.73, and 54.26 ± 25.43, respectively. The two-way comparison of the three groups revealed statistically significant differences in MA (P<0.05 in all cases). In the three groups, NV decreased from 1.00 ± 0.21 mm², 1.01 ± 0.18 mm², and 0.98 ± 0.20 mm² before treatment to 0.49 ± 0.17 mm², 0.31 ± 0.16 mm², and 0.38 ± 0.14 mm², respectively, with statistically significant differences (P<0.05 in all cases). After 12 months of treatment, 13, 18, and 18 patients had reduced HE area in the PRP-only, aflibercept 5+PRN with PRP, and aflibercept 3+PRN with PRP groups, respectively, with statistically significant differences (P<0.05 in all cases). After 12 months of treatment, vascular endothelial growth factor, monocyte chemoattractant protein-1, and glial fibrilliary acidic protein levels (pg/mL) in the aqueous humor decreased in both combined treatment groups compared with that at baseline, with statistically significant differences; however, no significant difference was observed between the two combined treatment groups (P>0.05). Conclusion: Aflibercept 5+PRN combined with PRP was safe and effective in treating patients with high-risk PDR and DME, and was more effective than PRP-only and aflibercept 3+PRN with PRP in improving CFT and MA.

Prediction of neovascular age-related macular degeneration recurrence using optical coherence tomography images with a deep neural network.

Neovascular age-related macular degeneration (nAMD) can result in blindness if left untreated, and patients often require repeated anti-vascular endothelial growth factor injections. Although, the treat-and-extend method is becoming popular to reduce vision loss attributed to recurrence, it may pose a risk of overtreatment. This study aimed to develop a deep learning model based on DenseNet201 to predict nAMD recurrence within 3 months after confirming dry-up 1 month following three loading injections in treatment-naïve patients. A dataset of 1076 spectral domain optical coherence tomography (OCT) images from 269 patients diagnosed with nAMD was used. The performance of the model was compared with that of 6 ophthalmologists, using 100 randomly selected samples. The DenseNet201-based model achieved 53.0% accuracy in predicting nAMD recurrence using a single pre-injection image and 60.2% accuracy after viewing all the images immediately after the 1st, 2nd, and 3rd injections. The model outperformed experienced ophthalmologists, with an average accuracy of 52.17% using a single pre-injection image and 53.3% after examining four images before and after three loading injections. In conclusion, the artificial intelligence model demonstrated a promising ability to predict nAMD recurrence using OCT images and outperformed experienced ophthalmologists. These findings suggest that deep learning models can assist in nAMD recurrence prediction, thus improving patient outcomes and optimizing treatment strategies.

Relative yield of retinal imaging versus clinical exam in following neovascular exudative age related macular degeneration.

PURPOSE: To compare therapeutic decisions between 3 diagnostic protocols and to assess the need for in-person physical doctor-patient encounter in follow up and treatment of neovascular exudative age-related macular degeneration (AMD). METHODS: Analysis of 88 eyes of 88 unique patients with neovascular AMD who were routinely followed at our medical retina clinic. A retinal specialist reviewed all images in advance and wrote his decisions. He later attended an in-person encounters with all patients and documented his decisions. Masking was done by not exposing any identifying information to the specialist and by randomizing patient's images order before the in-person encounter. Therapeutic decisions regarding intravitreal injections intervals and agent selection were made based on three protocols: (1) optic coherence tomography (OCT); (2) OCT/Ultra-widefield (UWF) color image; (3) OCT/UWF/full clinical exam. Visual acuity (VA) was incorporated into all protocols. RESULTS: We found an agreement of 93% between those protocols regarding the intervals of injections, and of 100% regarding injection agent selection. When comparing OCT, OCT/UWF and OCT/UWF/clinical exam guided decision making, there were no discrepancies between OCT and OCT/UWF. There were 6 out of 88 discrepancies (7%) between OCT/UWF and OCT/UWF/clinical exam. Of those 6 discrepancies, all were regarding intervals (Bland-Altman bias = - 0.2386). All discrepancies between OCT/UWF and OCT/UWF/Clinical exam were due to patients' preferences, socioeconomic issues and fellow eye considerations, addressed during the face-to-face encounter with patients. Physical examination itself did not affect decision making. CONCLUSIONS: Neovascular exudative AMD follow up and treatment decisions can be guided by VA and OCT, with UWF adding important information regarding macula and peripheral retina, but rarely affecting decision making. However, decision making may also be driven by patients' preferences and other considerations that are being made only during the face-to-face visit and discussion. Thus, every approach supporting imaging only decision making, must take these factors into account.

Evidence-Based Use of Bevacizumab in the Management of Neovascular Age-Related Macular Degeneration.

Indicated for colorectal cancer for decades, bevacizumab has been widely used off label to treat retinal diseases, and the benefits of its use, specifically in neovascular age-related macular degeneration, have been demonstrated in multiple clinical trials. The intravitreal delivery of bevacizumab requires it to be aseptically repackaged into individual syringes by compounding pharmacies for use in the eye. Although the repackaging process is permitted by the US Food and Drug Administration, the resultant product does not meet the specific standards of products approved for use as ophthalmic injectables nor is the parenteral innovator solution compliant with ophthalmic standards. Studies have also demonstrated variability in the quality and quantity of repackaged bevacizumab. This narrative review summarizes the evidence and discusses the role of off-label bevacizumab in the treatment and management of retinal diseases, its mechanism of action, current challenges and provides a critical appraisal of current evidence, clinical implications, and future directions. [Ophthalmic Surg Lasers Imaging Retina 2024;55:155-162.].