anti-VEGF Therapy Research Articles

BNT162b2 vaccine booster dose did not influence the activity of the exudative form of age-related macular degeneration during anti-vascular endothelial growth factor therapy.

Due to safety concerns, patients were hesitant to receive a booster dose of COVID-19 vaccine. In this study, we investigated whether neovascular age-related macular degeneration activity deteriorated after receiving the booster dose of the BNT162b2 vaccine. Optical coherence tomography (OCT) of the macula, best-corrected visual acuity (BCVA), and slit-lamp examination data were collected from 89 patients. All these individuals were diagnosed with neovascular age-related macular degeneration (AMD) and treated with intravitreal injections of aflibercept or ranibizumab. During the process of treatment, patients received a booster dose of the BNT162b2 vaccine. Time points included two visits before (marked as "-2", "-1") and two visits after (marked as "1", "2") the uptake of the booster dose. There were significant differences in the average thickness and total volume of the macula during follow-up. Moreover, a decreased average thickness, total volume, total thickness of the macula, subretinal fluid thickness, and subretinal complex thickness was observed between the time points "-2" and "2", but only in the aflibercept group. There were no significant differences in the frequency of occurring intraretinal cysts, subretinal fluid, serous retinal pigment epithelial detachments retinal hemorrhage, subretinal hyperreflective material, complete RPE and outer retinal atrophy, and BCVA before and after the booster dose. These results demonstrate that the BNT162b2 vaccine booster dose did not deteriorate the course of neovascular AMD.

Efficacy and Safety of an Indian Bevacizumab BIOSimilar (BEVATAS) for Retinal Vein Occlusion (BIOS-RVO Study).

To evaluate the efficacy and safety of Bevatas®, an Indian bevacizumab biosimilar, in the management of both Central Retinal Vein Occlusion (CRVO) and Branch Retinal Vein Occlusion (BRVO) (BIOS-RVO). The BIOS-RVO study was a retrospective interventional study conducted at a single tertiary eye care facility in India. 154 treatment-naïve eyes with RVO (CRVO: 62 eyes; BRVO: 92 eyes) received intravitreal bevacizumab biosimilar (IVBb) therapy. Data on best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were collected at baseline and at 3, 6, and 12 months post-therapy. The average age of participants was approximately 55.99 (+12.56) years, with a nearly equal gender distribution (M:F = 49.4:50.6). Age differences between BRVO and CRVO groups were not significant (P=0.501), but gender distribution varied significantly (P=0.035), with more males in the CRVO group. Significant improvements in BCVA were observed in both CRVO and BRVO groups at 3 months, 6 months, and 1 year compared to baseline (P<0.001). Both groups showed significant reductions in CMT throughout the follow-up period (P<0.001). The mean number of injections was higher in the CRVO group (5.27[±1.45]) compared to the BRVO group (4.27 [±1.28]) (P<0.001). Significant IOP increases were observed at 1 month (P<0.001) and 6 months (P<0.001) in both BRVO and CRVO groups, although not clinically significant. Safety analysis revealed no additional ocular or systemic adverse events during the study period. The BIOS-RVO study demonstrates that Bevatas is an effective and safe treatment option for both CRVO and BRVO. These findings support the use of Bevatas as a cost-effective alternative to branded anti-VEGF agents, particularly in resource-limited settings.

Submacular Hemorrhage Rates Following Anti-Vascular Endothelial Growth Factor Injections for Exudative Age-Related Macular Degeneration

Objective: To examine rates of submacular hemorrhage in patients undergoing anti-VEGF injections, comparing rates between specific anti-VEGF agents. Design: Retrospective clinical cohort study. Participants: All patients in the database from January 2015-November 2023 with a diagnosis of neovascular age-related macular degeneration (nAMD) and accompanying submacular hemorrhage (SMH). Methods: SMH prevalence and associated anti-VEGF injection type were analyzed in 140,915 eyes (of which 9,107 had SMH) in a nationwide aggregated electronic health care database using chi-square test of proportion. Visual acuity (VA) data was assessed using 2-sample independent t-tests. The primary outcome was rate of SMH per injection type. Secondary datapoints examined were time between SMH diagnosis and last anti-VEGF injection, number of injections before SMH, treatment interval at time of SMH, VA before and at 12 months after SMH, eyes undergoing pars plana vitrectomy (PPV) within 30 days of SMH, and VA before PPV and at 12 months after PPV. Results: The last injection type in eyes with SMH was bevacizumab in 3,439 (37.8%) eyes, brolucizumab-dbII in 46 (0.51%) eyes, aflibercept in 3,221 (35.4%) eyes, ranibizumab in 2,246 (24.7%) eyes, and faricimab-svoa in 155 (1.7%) eyes. Rates of SMH were significantly higher (p≤0.001) for last injection with bevacizumab compared to every other injection type. Rates of SMH were significantly lower (p=0.0004) for last injection with faricimab-svoa compared to every other injection type. Patients receiving either faricimab-svoa or ranibizumab injections each had significantly shorter (mean and standard deviation (SD) 48.9 (27.9), p<0.02; mean and standard deviation (SD) 59.6 (38.2), p=0.003, respectively) mean time between SMH diagnosis and last injection than did patients undergoing any other injection. Mean VA before SMH and at 12 months after SMH did not significantly differ by injection type among all patients. The number of patients who underwent PPV were 52 (1.51%) for bevacizumab, 4 (8.7%) for brolucizumab-dbII, 58 (1.8%) for aflibercept, 41 (1.8%) for ranibizumab, and 3 (1.9%) for faricimab-svoa. Mean VA before SMH and at 12 months after SMH did not significantly differ by injection type in patients undergoing PPV. Conclusions: Faricimab may be more protective than other anti-VEGF injections against SMH in patients with nAMD.

TAS-102 (trifluridine/tipiracil) plus bevacizumab versus TAS-102 alone as salvage treatment options for metastatic colorectal cancer in routine clinical practice.

Both regimens of TAS-102 (trifluridine/tipiracil) with and without bevacizumab are considered standard options for salvage treatment in patients with refractory metastatic colorectal cancer. This analysis included patients with metastatic colorectal cancer who received either TAS-102 plus bevacizumab or TAS-102 alone between July 2022 and November 2023 at Samsung Medical Center. We evaluated the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety profile of both regimens. In total, 139 patients were included in this analysis. Median age was 60.8 years, and median number of previous lines of therapy was four (range: 2.45-6.55). More than half of the subjects (56.8%) had RAS mutations and 92.9% received previous anti-VEGF therapy. 83 (59.7%) patients received the combination of TAS-102 and bevacizumab and 56 (40.3%) received TAS-102 alone. The number of patients with prior regorafenib treatment was 14 in the TAS-102 with bevacizumab group and 5 in the TAS-102 alone group. The disease control rate was 51.8% in the combination group and 32.1% in the TAS-102 alone group. The median PFS was 3.3 months (95% CI, 2.7-6.6) in the combination group and 2.5 months (95% CI, 2.0-3.8) in the TAS-102 alone group (HR, 0.56; 95% CI, 0.38-0.82; p=0.003). The median OS in these two groups was 10.8 months (95% CI, 8.4-NA) and 6.0 months (95% CI, 4.8-9.8), respectively (HR, 0.62; 95% CI, 0.40-0.97, p=0.033). In the exploratory analysis of TAS-102 + Bev group, patients with the KRAS G12 mutation had inferior OS compared to those without the mutation (HR, 2.01, 95% CI, 1.04-3.90, p=0.035). Commonly observed adverse events were hematologic-related, including neutropenia, anemia, and thrombocytopenia, as well as nausea. While any grade neutropenia was observed at similar frequencies in the two groups (57.8% and 57.1%), grade 3 or higher neutropenia was more frequent in the combination group than the TAS-102 alone group (31.3% vs. 17.9%). Among patients who received subsequent anticancer therapy after treatment failure, 74.1% received regorafenib. The combination of TAS-102 and bevacizumab resulted in a better survival outcome than TAS-102 monotherapy, consistent with previous studies. This analysis supports the use of the combination of TAS-102 and bevacizumab as the best therapeutic option for patients with refractory metastatic colorectal cancer in clinical practice.

Translational Research and Therapies for Neuroprotection and Regeneration of the Optic Nerve and Retina: A Narrative Review

Most retinal and optic nerve diseases pose significant threats to vision, primarily due to irreversible retinal neuronal cell death, a permanent change, which is a critical factor in their pathogenesis. Conditions such as glaucoma, retinitis pigmentosa, diabetic retinopathy, and age-related macular degeneration are the top four leading causes of blindness among the elderly in Japan. While standard treatments—including reduction in intraocular pressure, anti-vascular endothelial growth factor therapies, and retinal photocoagulation—can partially delay disease progression, their therapeutic effects remain limited. To address these shortcomings, a range of neuroprotective and regenerative therapies, aimed at preventing retinal neuronal cell loss, have been extensively studied and increasingly integrated into clinical practice over the last two decades. Several of these neuroprotective therapies have achieved on-label usage worldwide. This narrative review introduces several neuroprotective and regenerative therapies for retinal and optic nerve diseases that have been successfully translated into clinical practice, providing foundational knowledge and success stories that serve as valuable references for researchers in the field.

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.

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.

Clinical characteristics and long-term treatment outcomes of polypoidal choroidal vasculopathy with classic type leakage

To investigate long-term treatment outcomes of polypoidal choroidal vasculopathy (PCV) with classic type leakage and to compare the outcomes with those of PCV without classic type leakage. This retrospective study included 153 patients diagnosed with PCV and treated with anti-vascular endothelial growth factor (VEGF). Patients showing classic type leakage on fluorescein angiography were included in the classic type leakage group (N = 40, 26.1%), and those without classic type leakage were included in the occult group (N = 113, 73.9%). The best-corrected visual acuity (BCVA) at baseline and 24 months, changes in BCVA, incidence of fibrosis, and lesion reactivation after initial loading injections were compared between the two groups. There was no significant difference in the baseline BCVA between the classic type leakage group (mean logarithm of minimal angle of resolution 0.67 ± 0.53[Snellen equivalents = 20/93]) and the occult group (0.55 ± 0.49[20/70])(P = 0.639). In addition, the BCVA at 24 months (0.44 ± 0.53[20/55] vs. 0.38 ± 0.41[20/47])(P = 1.000), changes in BCVA (0.22 ± 0.42 improvement[2.2 lines] vs. 0.16 ± 0.36 improvement[1.6 lines]) (P = 0.366), and lesion reactivation (P = 0.787) did not differ between the two groups. The incidence of fibrosis was higher in the classic type leakage group (37.5%) than in the occult group (14.2%) (P = 0.002). Although the incidence of fibrosis was higher in PCVs with classic type leakage, the overall treatments were not significantly different between PCVs with and without classic type leakage. In addition, substantial visual improvement was noted at 24 months, suggesting that PCVs with classic type leakage can be effectively treated with anti-VEGF therapy.

A cost-minimization analysis of anti-VEGFs for the treatment of neovascular age-related macular degeneration in the Netherlands.

Age-related macular degeneration (AMD) is the main cause of severe vision loss globally. Neovascular AMD (nAMD) is an advanced stage of AMD treated with anti-vascular endothelial growth factors (anti-VEGFs). Although anti-VEGF treatment is effective, the frequent intravitreal injections place a burden on patients, (in)formal caregivers, and clinics. This study assesses the health-economic impact of anti-VEGF agents with lower injection frequency that have the potential to reduce treatment burden and compares it to the standard of care. We developed a cost-minimization model to evaluate the direct medical costs associated with first-line unilateral anti-VEGF treatment across a 3-year time horizon in the Netherlands. The analysis compared aflibercept 8mg, aflibercept 2mg, bevacizumab, faricimab, and ranibizumab. Our model adopted a treat-and-extend (T&E) regimen for aflibercept 2mg, bevacizumab, and ranibizumab. For aflibercept 8mg, a flexible regimen that was extendable up to 24weeks was applied, while faricimab followed a flexible regimen that was extendable up to 16weeks. Additionally, since list prices may vary from net prices, we calculated the break-even price for each anti-VEGF in comparison to bevacizumab, which is the recommended first-line treatment due to its low medication price. Based on list prices, aflibercept 8mg led to the lowest treatment costs (€16,251 per patient over a 3-year time horizon), closely followed by bevacizumab (€17,616 per patient over a 3-year time horizon). Ranibizumab led to the highest per-patient costs (€31,746 over a 3-year time horizon). For bevacizumab, most costs were attributable to administration, while for the other anti-VEGFs, most were attributable to medication. Aflibercept 8mg is cost-saving compared to bevacizumab at their medication prices at the time of writing. Aflibercept 2mg, faricimab, and ranibizumab should be priced below €488, €591, and €75, respectively. To be cost-equal to bevacizumab with current list prices, anti-VEGFs should be administered with a maximum of 12.7 to 13.8 injections over a 3-year time horizon. According to the injection frequency observed in clinical trials, aflibercept 8mg would be the anti-VEGF that generates the lowest per-patient healthcare costs for the treatment of nAMD in the Netherlands after a treatment period of three years. Our study indicates that anti-VEGF drugs with a lower injection frequency might provide a cost-saving solution to the increasing burden of anti-VEGF treatment on the healthcare system.

Review of Guideline Recommendations for Optimal Anti-VEGF Therapy in Age-Related Macular Degeneration.

Neovascular age-related macular degeneration is a progressive, blinding macular disease that has become a burden both in healthcare systems and the global economy. The vascular endothelial growth factor (VEGF) is the main agent involved in the pathogenic process of the disease. The main goal of the age-related macular degeneration treatment is to maintain and improve visual acuity by injecting intravitreal anti-VEGF agents in either a reactive or proactive manner. Subretinal and intraretinal fluids are the main biomarkers that should be considered when managing the frequency of the therapy. This review discusses both functional and morphological treatment criteria according to current recommendations as opposed to real-life situations encountered during day-to-day clinical practice and highlights situations in which the benefits of continuing therapy are arguable in terms of improving patients' quality of life. Optimizing the treatment regimen represents an important aim of current clinical ophthalmological practice, as age-related macular degeneration patients usually have a long follow-up period.

Pneumatic displacement of submacular haemorrhage secondary to neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

To compare the visual and anatomical outcomes of pneumatic displacement (PD) combined with anti-vascular endothelial growth factor (VEGF) therapy versus anti-VEGF monotherapy in treatment-naive eyes with submacular haemorrhage (SMH) secondary to neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. In a retrospective comparative interventional study of 57 eyes, the changes in logMAR visual acuity (VA), and SMH height and area at baseline at months 1, 3 and 12 were compared between the PD and non-PD groups. There was no significant difference in mean VA in the PD versus non-PD group at month 12 (1.1 versus 0.7, p = 0.09). At baseline, the PD group, compared to the non-PD group, had significantly larger SMH area (35.9 versus 26.9 mm2, p = 0.04) and SMH height at the fovea (733.7 versus 503.6 µm, p < 0.01). The greatest reduction in SMH height and area occurred between baseline and month 1 in the PD group, which was faster than between month 1 and month 3 in the non-PD group, with similar findings in the matched pair analysis matched for SMH height and area. In the multivariable analysis, only baseline VA was associated with VA outcomes (month 1: β = -0.46, 95% [confidence interval] CI = -0.78 to -0.14, p = 0.006; month 3: β = -0.52, 95% CI = -0.86 to -0.18, p = 0.004; and month 12: β = -0.78, 95% CI = -1.16 to -0.39, p < 0.001). The visual outcome of SMH at month 12 in nAMD and PCV is poor regardless of whether PD is performed in addition to anti-VEGF therapy, although a more rapid resolution of SMH can be expected.

Intravitreal Dexamethasone Implant in Anti-Vascular Endothelial Growth Factor Pretreated Diabetic Macular Edema-A Swiss Cohort Study.

Diabetic macular edema (DME) is a significant cause of visual impairment, often treated with anti-vascular endothelial growth factor (anti-VEGF) agents. However, some patients do not respond adequately to this treatment. This study aims to evaluate the contribution of the intravitreal dexamethasone (DEX) implant as a second-line treatment in DME patients with insufficient response to anti-VEGF therapy or with high treatment burden. This retrospective multicenter cohort study was conducted across seven clinical sites in Switzerland. The study included eyes with active DME that had been pretreated with anti-VEGF for at least six months before receiving DEX therapy. Data were extracted from electronic patient records, focusing on best-corrected visual acuity (BCVA), central subfield thickness (CST), and injection frequency. A total of 95 eyes from 89 patients (38.8% females, mean age 65.6 ± 9.1 years, follow-up time 80.6 ± 38.5 [13.5-166.7] months) were analyzed. Prior to the first DEX implant, eyes had undergone an average of 16.0 ± 13.3 anti-VEGF injections over 32.5 ± 22.4 months. Post-DEX treatment, 22.1% of eyes received DEX monotherapy, 44.2% received a combination of DEX and anti-VEGF, 25.3% continued with anti-VEGF monotherapy, and 8.4% received no further treatment. The number of anti-VEGF injections decreased significantly from 6.4 ± 3.1 in the year before DEX to 1.6 ± 2.4 in the year after DEX (p < 0.001). BCVA remained stable (0.4 ± 0.3 logMAR at baseline, 0.4 ± 0.5 logMAR at 24 months, p = 0.2), while CST improved from 477.7 ± 141.0 to 320.4 ± 125.5 μm (p < 0.001), and the presence of retinal fluid decreased from 98.0% to 61.1% (p = 0.021). During follow-up, 26.3% of eyes required glaucoma medication, 4.2% underwent glaucoma surgery, and 1.1% needed cataract surgery. In real-world clinical settings, the addition of DEX to anti-VEGF therapy in DME patients significantly reduces treatment burden and retinal fluid while maintaining visual function. Treatment decisions should balance anatomical and functional outcomes, considering individual patient needs.

Attention-Enhanced Guided Multimodal and Semi-Supervised Networks for Visual Acuity (VA) Prediction after Anti-VEGF Therapy

The development of telemedicine technology has provided new avenues for the diagnosis and treatment of patients with DME, especially after anti-vascular endothelial growth factor (VEGF) therapy, and accurate prediction of patients’ visual acuity (VA) is important for optimizing follow-up treatment plans. However, current automated prediction methods often require human intervention and have poor interpretability, making it difficult to be widely applied in telemedicine scenarios. Therefore, an efficient, automated prediction model with good interpretability is urgently needed to improve the treatment outcomes of DME patients in telemedicine settings. In this study, we propose a multimodal algorithm based on a semi-supervised learning framework, which aims to combine optical coherence tomography (OCT) images and clinical data to automatically predict the VA values of patients after anti-VEGF treatment. Our approach first performs retinal segmentation of OCT images via a semi-supervised learning framework, which in turn extracts key biomarkers such as central retinal thickness (CST). Subsequently, these features are combined with the patient’s clinical data and fed into a multimodal learning algorithm for VA prediction. Our model performed well in the Asia Pacific Tele-Ophthalmology Society (APTOS) Big Data Competition, earning fifth place in the overall score and third place in VA prediction accuracy. Retinal segmentation achieved an accuracy of 99.03 ± 0.19% on the HZO dataset. This multimodal algorithmic framework is important in the context of telemedicine, especially for the treatment of DME patients.

A Nanogel Formulation of Anti-VEGF Peptide for Ocular Neovascularization Treatment.

Age-related macular degeneration (AMD) is an eye disorder that can lead to visual impairment in elder patients, and current treatments include repeated injections of monoclonal antibody-based antivascular endothelial growth factor (anti-VEGF) agents. This study investigates the potential of a nanoformulation of a peptide anti-VEGF molecule for neovascular AMD. Anti-VEGF peptide HRHTKQRHTALH (HRH), which has high affinity to VEGF-Fc receptor, was used as the bioactive agent to control neovascularization of the retina. The nanoformulation consisting of hyaluronic acid nanogel was generated by incorporating divinyl sulfone and cholesterol to increase the stability and control the size of the nanodrug. The encapsulation efficacy of nanogel was 65%, and drug release was 34.72% at the end of 192 h. Obtained nanogels were efficiently internalized in 15 min by human umbilical vascular endothelial cells (HUVECs) and ARPE-19 cells, and results indicate that nanoformulation is not toxic to ARPE-19 cells, whereas it inhibits HUVEC proliferation owing to anti-VEGF peptide in the nanogel structure. In the coculture experiment in which retinal penetration was modeled, it was observed that the nanogel reached HUVECs and negatively affected their proliferation without disturbing the monolayer of ARPE-19 cells. In vivo experiments with chick chorioallantoic membrane revealed that nanogel formulation has higher antiangiogenesis activity compared to free HRH. Additionally, in an oxygen-induced retinopathy model, the excessive growth of blood vessels was notably suppressed in mice treated with HRH-loaded nanogel. This research indicates that nanogels formulated in this study are promising candidates as a topical treatment for AMD.

Predictive Factors for Functional and Anatomical Outcomes After Anti-VEGF Treatment for Macular Edema in Patients with Branch Retinal Vein Occlusion.

This study aimed to identify predictive factors for the improvement of best-corrected visual acuity (BCVA) and reduction of central macular thickness (CMT) after treatment of macular edema (ME) due to branch retinal vein occlusion (BRVO) in a real-world setting. This retrospective study included patients with ME secondary to BRVO who were treated with intravitreal injection of bevacizumab as the first-line therapy and were followed up for 12 months. Demographic and clinical data, in addition to baseline spectral domain optical coherence tomography (SD-OCT) features, were considered as possible biomarkers of final BCVA and CMT. We also collected the data concerning the need for additional treatment including sectorial laser photocoagulation, change to another anti-VEGF agent, or intravitreal corticosteroid injection. A total of 161 eyes were analyzed. BCVA significantly improved from baseline to 12-month follow-up (0.6 and 0.4 logMAR, respectively; P 0.01). CMT decreased significantly during the follow-up period (from 498.0 to 325.0 m; P 0.01). Final BCVA correlated positively with baseline BCVA (P 0.01, r = 0.57). Older age at diagnosis and baseline SD-OCT findings including CMT, disruption of the retinal inner layers, retinal pigment epithelium (RPE) damage, and impairment of the ellipsoid zone and external limiting membrane negatively affected final BCVA (P 0.01). Multiple regression analysis identified age and BCVA at baseline as the only independent predictors of final BCVA (P = 0.001 and P 0.01, respectively). No association was found between clinical data, SD-OCT parameters, and final CMT. Various clinical and SD-OCT parameters are prognostically relevant for visual improvement in ME secondary to BRVO. Age at diagnosis and baseline BCVA were found to be independent predictors of visual outcome.

Comparing macular thickness and visual acuity responses retinal vein occlusion versus diabetic macular edema following anti vascular endothelial growth factor therapy: A retrospective analysis

: Vascular growth factor associates Retinal vein occlusion (RVO) and Diabetic Macular Edema (DME). A retrospective analysis using database from a tertiary hospital.: The study aims to evaluate effects of anti-vascular growth factor therapy on patients Diabetic Macular Edema with and retinal vein occlusion,: This study conducted between December 2022 and June 2023 where 30 patients diagnosed with Diabetic macular edema (DME, n=15) or Retinal vein occlusion (RVO, n=15) receiving anti-VEGF were examined. This focused on changes in best corrected visual acuity, central macular thickness and predictors over a period of three months.: Retinal Vein Occlusion (RVO) patients exhibited a more significant improvement in Best Corrected Visual Acuity (BCVA) compared to Diabetic Macular Edema (DME) (25 vs. 10 letters, p = 0.006) after three months. The change in Central Macular Thickness (CMT) also favored RVO (100µm) over DME (40µm, p = 0.012). Final BCVA median was 70 for DME and 65 for RVO (p = 0.461). Considering initial BCVA and CMT, RVO predicted better visual enhancement than DME.: RVO exhibited major BCVA improvement at three months with Anti-Vascular Endothelial Growth Factor. Final vision was indistinguishable for DME and RVO. Anti VEGF stabilizes DME vision. Despite the improvement, early RVO diagnosis and treatment may enhance final vision.

Multi-target and natural product-based multi-drug approach for anti-VEGF resistance in glioblastoma

Glioblastoma (GBM) remains a formidable challenge in neuro-oncology due to its aggressive nature and propensity for therapeutic resistance. Anti-vascular endothelial growth factor (VEGF) therapies, although promising, often encounter resistance that limits their clinical efficacy. A multi-target and multi-drug approach has emerged as compelling strategies to address this resistance to enhance the treatment outcomes. This review examines the complex environment of anti-VEGF resistant GBM and analyses a multi-target therapeutic approach using natural products.

Pharmacokinetics of intravitreal anti-VEGF drugs in vitrectomized eyes

Neovascular retinal diseases pose a significant burden, often resulting in visual impairment. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs serves as the primary therapeutic approach. Nonetheless, certain patients necessitate continued anti-VEGF treatment post-vitrectomy or other ocular surgeries. Emerging evidence suggests that variations in surgical techniques and postoperative vitreous cavity management may induce distinct intraocular pharmacokinetics (PK) of anti-VEGF agents following vitrectomy, prompting potential adjustments in therapeutic strategies. This review offers a thorough examination of the pharmacokinetic determinants impacting anti-VEGF drugs and their intraocular dynamics post-vitrectomy.

Optical coherence tomography angiography for microaneurysms in anti-vascular endothelial growth factor treated diabetic macular edema

BackgroundWe aimed to evaluate microaneurysms (MAs) after treatment with anti-vascular endothelial growth factor (anti-VEGF) therapy to understand causes of chronic edema and anti-VEGF resistance.MethodsPatients with non-proliferative diabetic retinopathy, with or without macular edema were recruited. Optical coherence tomography angiography (OCTA) MAs-related parameters were observed, including the maximum diameter of overall dimensions, material presence, and flow signal within the lumen. OCTA parameters also included central macular thickness (CMT), foveal avascular zone, superficial and deep capillary plexuses, and non-flow area measurements on the superficial retinal slab.ResultsOverall, 48 eyes from 43 patients were evaluated. CMT differed significantly between the diabetic macular edema (DME ) and non-DME (NDME) groups at 1st, 2nd, 3rd, and 6th months of follow-up (P < 0.001; <0.001; 0.003; <0.001, respectively). A total of 55 and 59 MAs were observed in the DME (mean = 99.40 ± 3.18 μm) and NDME (mean maximum diameter = 74.70 ± 2.86 μm) groups at baseline, respectively (significant between-group difference: P < 0.001). Blood flow signal was measurable for 46 (83.6%) and 34 (59.3%) eyes in the DME and NDME groups, respectively (significant between-group difference: P < 0.001).ConclusionsCompared to the NDME group, the DME group had larger MAs and a higher blood-flow signal ratio. Following anti-VEGF therapy, changes in the diameter of MAs were observed before changes in CMT thickness.Graphical

The Impact of ARMS2 (rs10490924), VEGFA (rs3024997), TNFRSF1B (rs1061622), TNFRSF1A (rs4149576), and IL1B1 (rs1143623) Polymorphisms and Serum Levels on Age-Related Macular Degeneration Development and Therapeutic Responses.

Age-related macular degeneration (AMD) is a major global health problem as it is the leading cause of irreversible loss of central vision in the aging population. Anti-vascular endothelial growth factor (anti-VEGF) therapies are effective but do not respond optimally in all patients. This study investigates the genetic factors associated with susceptibility to AMD and response to treatment, focusing on key polymorphisms in the ARMS2 (rs10490924), IL1B1 (rs1143623), TNFRSF1B (rs1061622), TNFRSF1A (rs4149576), VEGFA (rs3024997), ARMS2, IL1B1, TNFRSF1B, TNFRSF1A, and VEGFA serum levels in AMD development and treatment efficacy. This study examined the associations of specific genetic polymorphisms and serum protein levels with exudative and early AMD and the response to anti-VEGF treatment. The AA genotype of VEGFA (rs3024997) was significantly associated with a 20-fold reduction in the odds of exudative AMD compared to the GG + GA genotypes. Conversely, the TT genotype of ARMS2 (rs10490924) was linked to a 4.2-fold increase in the odds of exudative AMD compared to GG + GT genotypes. In females, each T allele of ARMS2 increased the odds by 2.3-fold, while in males, the TT genotype was associated with a 5-fold increase. Lower serum IL1B levels were observed in the exudative AMD group compared to the controls. Early AMD patients had higher serum TNFRSF1B levels than controls, particularly those with the GG genotype of TNFRSF1B rs1061622. Exudative AMD patients with the CC genotype of TNFRSF1A rs4149576 had lower serum TNFRSF1A levels compared to the controls. Visual acuity (VA) analysis showed that non-responders had better baseline VA than responders but experienced decreased VA after treatment, whereas responders showed improvement. Central retinal thickness (CRT) reduced significantly in responders after treatment and was lower in responders compared to non-responders after treatment. The T allele of TNFRSF1B rs1061622 was associated with a better response to anti-VEGF treatment under both dominant and additive genetic models. These findings highlight significant genetic and biochemical markers associated with AMD and treatment response. This study found that the VEGFA rs3024997 AA genotype reduces the odds of exudative AMD, while the ARMS2 rs10490924 TT genotype increases it. Lower serum IL1B levels and variations in TNFRSF1B and TNFRSF1A levels were linked to AMD. The TNFRSF1B rs1061622 T allele was associated with better anti-VEGF treatment response. These markers could potentially guide risk assessment and personalized treatment for AMD.