The relationship between imaging features, therapeutic response, and overall survival in pediatric diffuse intrinsic pontine glioma.

We aimed to evaluate the relationship between imaging features, therapeutic responses (comparative cross-product and volumetric measurements), and overall survival (OS) in pediatric diffuse intrinsic pontine glioma (DIPG). A total of 134 patients (≤ 18 years) diagnosed with DIPG were included. Univariate and multivariate analyses were performed to evaluate correlations of clinical and imaging features and therapeutic responses with OS. The correlation between cross-product (CP) and volume thresholds in partial response (PR) was evaluated by linear regression. The log-rank test was used to compare OS patients with discordant therapeutic response classifications and those with concordant classifications. In univariate analysis, characteristics related to worse OS included lower Karnofsky, larger extrapontine extension, ring-enhancement, necrosis, non-PR, and increased ring enhancement post-radiotherapy. In the multivariate analysis, Karnofsky, necrosis, extrapontine extension, and therapeutic response can predict OS. A 25% CP reduction (PR) correlated with a 32% volume reduction (R2 = 0.888). Eight patients had discordant therapeutic response classifications according to CP (25%) and volume (32%). This eight patients' median survival time was 13.0 months, significantly higher than that in the non-PR group (8.9 months), in which responses were consistently classified as non-PR based on CP (25%) and volume (32%). We identified correlations between imaging features, therapeutic responses, and OS; this information is crucial for future clinical trials. Tumor volume may represent the DIPG growth pattern more accurately than CP measurement and can be used to evaluate therapeutic response.

Personalized therapy guided by longitudinal liquid biopsies for treatment of leptomeningeal disease from lung adenocarcinoma: A case report.

Molecular-based targeted therapies have significantly benefited certain patients with cancer; however, those with leptomeningeal disease (LMD) persistently exhibit a poor prognosis and are often excluded from clinical trials. Tumor-derived cell-free (cf)DNA, found in the cerebrospinal fluid (CSF) of patients with LMD, can assist in diagnosis and tracking of disease progression. However, the utilization of CSF to direct targeted cancer therapy has yet to be extensively explored. The present study reported the case of a patient with lung adenocarcinoma and LMD who was monitored by performing a series of liquid biopsies of CSF and blood. Targeted sequencing was performed on cfDNA from the CSF and plasma, and the variant allele frequencies (VAFs) of BRAF and NRAS mutations were assessed and analyzed in conjunction with the clinical presentation of the patient. The patient then underwent serial chemotherapy, radiation therapy, immunotherapy and targeted treatment based on the results of the liquid biopsies. Upon the LMD diagnosis, a BRAF p.V600E mutation was detected in plasma cfDNA. Consequently, the patient was treated with vemurafenib and responded favorably to this consolidation treatment for 13 months. After a relapse in July 2018, both BRAF p.V600E and NRAS p.Q61K mutations were detected in CSF supernatant and sediment cell samples, suggesting drug resistance. Therefore, the treatment strategy for the patient changed to cobimetnib plus vemurafenib. Notably, the changes of VAF in the CSF supernatant samples were associated with the clinical status of the patient. The patient survived for 33 months post-LMD diagnosis. The present case report highlights the potential use of liquid biopsy in personalized therapy, as it was instrumental in informing the combinational treatment plan of the patient, which ultimately proved beneficial.

Different genetic profiles contribute to worse overall survival in patients with leptomeningeal metastases of non-small-cell lung cancer.

BACKGROUND: To assess the genetic characteristics of central nervous system (CNS) metastases from non-small-cell lung cancer (NSCLC), we gathered the genetic profiles of brain metastases (BM) and leptomeningeal metastases (LM). Our objective was to identify genetic factors contributing to poorer overall survival (OS) in NSCLC patients with LM. METHODS: This study included 25 consecutive patients with BM and 52 patients with LM from Guangdong Sanjiu Brain Hospital. All participants underwent 168-target panel sequencing. RESULTS: Among the 25 patients with BM, TP53 was the most frequently mutated gene (44%), followed by driver genes such as EGFR and BRAF (40% and 20%, respectively). In patients with BM, EGFR_amp and CDK4 were also frequently mutated, with rates of 20% and 16%, respectively. The genetic landscape of patients with LM differed, with the top mutated genes being EGFR, TP53, EGFR_amp, CDKN2A, CCNE1, CDK4, PMS2, and PIK3CA, with mutation rates of 77%, 69%, 31%, 29%, 13%, 13%, 13%, and 12%, respectively. In our study, patients with LM exhibited significantly worse OS compared to those with BM (p = 0.029). The mutation rates of TP53, EGFR_amp, and CDKN2A varied between patients with LM and those with BM, at 69.23% vs. 44%, 30.77% vs. 20%, and 28.85% vs. 12%, respectively. Further exploration revealed that patients with BM with TP53 mutations had a shorter OS than patients without TP53 mutations (p = 0.014). Similarly, patients with LM and TP53 mutations presented with worse OS than those without TP53 mutations (p = 0.0067). LM patients with CDKN2A deletions had worse OS than those without CDKN2A deletions (p = 0.037). Additionally, patients with EGFR_amp had a shorter OS than those without EGFR_amp (p = 0.044). CONCLUSIONS: Patients with LM exhibited significantly worse OS than those with BM. Gene signatures, such as TP53, EGFR_amp, and CDKN2A, may account for shorter outcomes in patients with LM.

PD-1-induced encephalopathy: a report of 2 cases on neurological toxicities with immune checkpoint inhibitors.

Background: Immune-related adverse effects (irAEs) often occur during immune checkpoint inhibitor (ICI) therapy. In the nervous system, the incidence of irAEs ranges from 0.1-12%, with 80% occurring within the first 4 months of ICI application. For complications of the nervous system, adequate diagnosis is made by signs, symptoms, imaging and cerebrospinal fluid. If severe irAEs occur, ICIs should be discontinued and patients should be treated with high-dose glucocorticoids, immunoglobulins, or immunosorbent therapy with systemic support. Patients who develop severe neurologic irAEs have a poorer prognosis. Case Description: In this article, we report 2 cases of encephalopathy induced by anti-programmed cell death protein 1 (PD-1) monoclonal antibodies at the initial diagnoses. Our findings may help clinicians to differentiate between encephalopathy caused by immunotherapy and other neurological disorders. Case 1 was a 24-year-old male patient who had undergone PD-1 immunotherapy to treat olfactory neuroblastoma. After the 6th course of therapy, he began to develop persistent epilepsy, which decreased significantly after high doses of glucocorticoid and immunosorbent therapy were administered. Based on his medical history and laboratory examination results, PD-1-induced encephalopathy was the most likely diagnosis. Case 2 was a 67-year-old female patient who had been treated with PD-1/programmed death ligand-1 therapy for lung adenocarcinoma. She began to have headaches after 1 cycle of treatment, and her cognitive function gradually decreased with the continuation of immunotherapy. Conclusions: These case reports show the difficulty in distinguishing PD-1-induced encephalopathy from other neurological disorders, especially paraneoplastic neurological syndromes. If not treated properly, patients' lives may be endangered. Thus, early identification and early treatment are very important.

Gastrointestinal signet ring cell malignancy: current advancement and future prospects.

Globally, gastrointestinal cancer is the most widespread neoplastic disease and the primary contributor to cancer-associated fatalities. Gastrointestinal signet ring cell carcinoma (SRCC) exhibits unique distinguishing features in several aspects when compared to adenocarcinomas (ACs). The scarcity of signet ring cell carcinoma has resulted in a heightened significance of related clinical and molecular investigations. However, a comprehensive and systematic review of the clinical, molecular, therapeutic, and research aspects of this disease is currently absent. This review provides an overview of the latest developments in our understanding of the clinical and molecular features of gastrointestinal signet ring cell carcinoma (SRCC). Additionally, we have compiled a list of potential therapeutic targets or biomarkers, as well as an examination of the current treatment options and the possible mechanisms of formation.

Efficacy and safety of osimertinib for leptomeningeal metastases from EGFR-mutant non-small cell lung cancer: a pooled analysis.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of osimertinib for the treatment of leptomeningeal metastases (LM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). METHODS: We conducted a systematic review and meta-analysis to aggregate the clinical outcomes of patients with LM from EGFR-mutant NSCLC treated with osimertinib. A comprehensive literature search for published and unpublished studies was implemented in April 2021 of PubMed, EMBASE, the Cochrane Library, and several international conference databases, in accordance with the PRISMA guidelines. Meta-analysis of proportions was conducted to calculate the pooled rate of overall response rate (ORR), disease control rate (DCR), one-year overall survival (OS), and adverse events (AEs). RESULTS: A total of eleven studies (five prospective and six retrospective) including 353 patients were included. The majority of patients (346/353, 98.0%) received osimertinib as ≥ 2nd-line treatment for LM, either at a dosage of 80 mg (161/353, 45.6%) or 160 mg (191/353, 54.1%). The pooled rates of ORR and DCR were 42% (95% CI 24% to 59%) and 93% (95% CI 88% to 97%), respectively. The pooled one-year OS rate was 59% (95% CI 53% to 65%) in 233 patients from five studies. The highest incidence of AEs of all grades was rash (53%), followed by diarrhea (45%), paronychia (35%), decreased appetite (35%), and dry skin (27%), based on data from four studies. CONCLUSIONS: Our study highlighted and confirmed the meaningful efficacy and a manageable safety profile of osimertinib for the treatment of LM from EGFR-mutant advanced NSCLC.

Lorlatinib for ALK-fused, infant-type hemispheric glioma with lung metastasis: a case report.

Infant-type hemispheric glioma, a new subtype of pediatric high-grade glioma, arises in the cerebral hemispheres. Despite better survival outcomes, the treatment of infant-type hemispheric glioma is still facing challenges. Here, we reported a case of QKI-ALK fusion, infant-type hemispheric glioma with lung metastasis who achieved a complete clinical response after lorlatinib treatment. This typical case demonstrated the importance of appropriate molecularly targeted treatments in ALK-fused tumors, and lorlatinib may serve as an effective complement to conventional chemotherapy and radiotherapy in primary glioma harboring ALK fusions and its metastasis.

The PTEN-associated immune prognostic signature reveals the landscape of the tumor microenvironment in glioblastoma.

Glioblastoma (GBM) is a common brain tumor with a complex and diverse tumor microenvironment (TME). As PTEN mutation is the most common mutation in GBM, we aimed to investigate how PTEN mutation regulates the immune response in GBM TME and thus affects the prognosis of GBM patients. In this study, we conducted a comprehensive analysis of multiple levels of data, including whole-exome sequencing (WES), transcriptome RNA sequencing, patient survival and immune signatures, to study the relationship between PTEN mutation and TME in GBM. We developed an immune-related prognostic signature (IPS) based on the PTEN-associated immune-related genes (IRGs), and the IPS exhibited a powerful prognosis prediction capacity in different GBM cohorts. A scoring nomogram based on the IPS was also established for clinical application. In addition, the correlations of the IPS with tumor immune cell infiltration and immune checkpoints were systematically analyzed. This study illustrates the influence of PTEN mutation on the immune microenvironment of GBM. Our IPS, which is sensitive to PTEN mutation status, can enhance the prognosis prediction ability for GBM patients and provides potential targets for immunotherapy.

Radiomics features based on MRI predict BRAF V600E mutation in pediatric low-grade gliomas: A non-invasive method for molecular diagnosis.

OBJECTIVE: To investigate the clinical application value of radiomics features based on preoperative magnetic resonance imaging for predicting B-Raf proto-oncogene serine/threonine-protein (BRAF) V600E mutation in pediatric low-grade gliomas. MATERIALS AND METHODS: The clinical, imaging, and pathological data from 113 pediatric patients with low-grade gliomas patients were retrospectively analyzed. Using open-source software, three-dimensional imaging features were extracted on the basis of FLAIR sequences, and the radiomics process was analyzed to dichotomize BRAFV600E mutant and wild type. All cases were randomly divided into the training and test sets according to a 7:3 training and test group ratio, and a 5-fold cross-validation was performed on the training set. The optimal hyperparameters were selected to build the prediction model, and the test set was used for external validation to assess the diagnostic value of the model using the receiver operating characteristic curve. RESULTS: The training set comprised 79 patients (47 males, 32 females, mean age 9.86 ± 5.20) and the test set comprised 34 patients (20 males, 14 females, mean age 10.97 ± 5.14). Sex, age, and brain side were not significant predictors of BRAF, and tumor location on the supratentorial region was a BRAF predictor (p < 0.05). The radiomics model constructed by principal component analysis for dimensionality reduction, Kruskal-Wallis for filtering of features, and random forest as a classifier performed best. In the training set, the mean area under the curve (AUC) with a five-fold cross-validation was 0.72 ( ± 0.057; 95 % confidence interval (CI), 0.602-0.831) and AUC of the test set was 0.875 ( ± 0.062; 95 % CI, 0.731-0.983). CONCLUSION: The use of a radiomics model based on FLAIR sequences can help predict BRAF V600E mutations in pediatric low-grade gliomas.

Analysis on the Correlation Between Long-term Refractive Regression and Visual Quality after FS-LASIK.

PURPOSE: To record the long-term visual quality after FS-LASIK and analyze the effect of long-term refractive regression after corneal laser surgery on visual quality. METHODS: Seventy-eight patients (153 eyes) who had undergone FS-LASIK more than 5 years before and had undergone follow-ups between November 2020 and March 2021. We collected data on the patients' age of surgery, postoperative period, and preoperative diopters (corrected to LogMAR 0.0 by mydriatic optometry). We obtained the measurements of ARC, PRC, THP by Pentacam, and extracted values for UCVA(LogMAR), CTRmsTotal, CTRmsHO, RmsTotal, RmsHO, MTFTotal, MTFHO, PSFTotal, PSFHO, Coma-T, Coma-CT, SA-T, SA-CT, Trefoil-T, and Trefoil-CT measured with OPD Scan III. We allocated the patients into emmetropia group (SE≤ -0.5 D) 40 patients (78 eyes) and regression group (SE > -0.5D) 38 patients (75 eyes) based on their postoperative diopters. RESULTS: The values for postoperative periods, preoperative diopters, CTRmsTotal, CTRmsHO, and RmsTotal, Coma-CT, CTSA-CT in the emmetropia group were significantly lower than those in the regression group. The age of surgery, UCVA, MTFTotaL, MTFHO, PSFTotal, and CTPSF values in the emmetropia group were significantly higher than those in the regression group. The ARC, PRC, THP, RmsHO, Coma-T, SA-T, Trefoil-T, and Trefoil-CT values were similar in both groups. There was no significant difference in preoperative sphere, spherical equivalent and BCVA between the two groups. There were significant differences in postoperative parameters at 1 year, 3 years, and 5 years. The postoperative diopter value was significantly correlated with age of surgery, postoperative period, THP, MTFTotal, PSFTotal, Coma-T, and SA-CT. CONCLUSION: After FS-LASIK, young patients with relatively thin cornea are susceptible to refractive regression. With the extension of postoperative period, refractive regression may aggravate. There was no significant correlation between postoperative refractive regression and higher order aberrations.

Survival outcomes, hematologic complications and growth impairment after sequential chemoradiotherapy in intracranial NGGCTs: a retrospective study.

PURPOSE: This study aimed to evaluate the clinical features, prognostic factors, and survival outcomes for patients with intracranial nongerminomatous germ cell tumors (NGGCTs), with a particular focus on treatment toxicity for long-term survivors. METHODS: Intracranial NGGCTs treated with platinum-based chemotherapy and craniospinal irradiation (CSI) in our institution were retrospectively analyzed. Hematological complications following sequential chemoradiotherapy as well as height and weight in childhood survivors were evaluated. Plasma growth hormone (GH) concentrations prior to and after radiotherapy were obtained for the comparisons. RESULTS: A total of 111 intracranial NGGCTs were included. The 3­year overall survival (OS) and event-free survival (EFS) rates were 83.5% ± 3.9% and 71.0% ± 4.8%, respectively. A combined treatment modality consisting of ≥ 4 cycles of platinum-based chemotherapy and CSI was associated with an improved OS (P = 0.003) and EFS (P < 0.001). Thrombocytopenia of any grade occurred in 35.4% (34/96) of patients, and the threshold age for an increased risk of thrombocytopenia was 14 years (area under the curve AUC = 0.752, P < 0.0001) as derived from receiver operating characteristic (ROC) analysis. Growth impediment was found in 8 of 56 (14%) patients. The age for receiving radiotherapy was found to inversely correlate with height development, revealing a cut-off age of 11.5 years for risking growth impairment (AUC = 0.806, P = 0.004). Consistently, a significant decline in plasma growth hormone after radiotherapy was observed in patients ≤ 11.5 years (P < 0.01) but not patients > 11.5 years. (P > 0.05). CONCLUSION: Our study suggested that a combined treatment modality with at least four cycles of chemotherapy and CSI was safe and effective for patients with intracranial NGGCTs. Radiotherapy should be used with caution for patients < 11.5 years due to growth impairment.

A Novel Six Autophagy-Related Genes Signature Associated With Outcomes and Immune Microenvironment in Lower-Grade Glioma.

Since autophagy and the immune microenvironment are deeply involved in the tumor development and progression of Lower-grade gliomas (LGG), our study aimed to construct an autophagy-related risk model for prognosis prediction and investigate the relationship between the immune microenvironment and risk signature in LGG. Therefore, we identified six autophagy-related genes (BAG1, PTK6, EEF2, PEA15, ITGA6, and MAP1LC3C) to build in the training cohort (n = 305 patients) and verify the prognostic model in the validation cohort (n = 128) and the whole cohort (n = 433), based on the data from The Cancer Genome Atlas (TCGA). The six-gene risk signature could divide LGG patients into high- and low-risk groups with distinct overall survival in multiple cohorts (all p < 0.001). The prognostic effect was assessed by area under the time-dependent ROC (t-ROC) analysis in the training, validation, and whole cohorts, in which the AUC value at the survival time of 5 years was 0.837, 0.755, and 0.803, respectively. Cox regression analysis demonstrated that the risk model was an independent risk predictor of OS (HR > 1, p < 0.05). A nomogram including the traditional clinical parameters and risk signature was constructed, and t-ROC, C-index, and calibration curves confirmed its robust predictive capacity. KM analysis revealed a significant difference in the subgroup analyses' survival. Functional enrichment analysis revealed that these autophagy-related signatures were mainly involved in the phagosome and immune-related pathways. Besides, we also found significant differences in immune cell infiltration and immunotherapy targets between risk groups. In conclusion, we built a powerful predictive signature and explored immune components (including immune cells and emerging immunotherapy targets) in LGG.

Stereotactic radiosurgery for treatment of large cerebellum metastases from lung cancer.

BACKGROUND: Stereotactic radiosurgery (SRS) is an important treatment option. This report evaluated the efficacy and safety of SRS in patients with large cerebellum metastases from lung cancer. METHODS: Between September 2016 and January 2020, a total of 44 patients with large cerebellum metastases >2 cm from lung cancer were evaluated. A median dose of 20 Gy (range, 8-24 Gy) was delivered in 1 to 3 fractions for SRS treatment. The survival rate was analyzed with SPSS software 21.0 and compared by log-rank test using the Kaplan-Meier method. RESULTS: The median overall survival (OS) and neurological progression-free survival (PFS) were 10.5 months (range, 1-32 months) and 9.0 months (range, 1-32 months), respectively. The median diameter and volume of the metastases were 3.5 cm (range, 2.1-5.7 cm) and 12.5 cc (range, 1.8-39.7 cc), respectively. The median volume of peritumoral edema was 36.3 cc (range, 3.7-100.3 cc). The median ratio of tumor volume to cerebellum volume was 8.7% (range, 1.3-27.0%). The median ratio of peritumoral edema volume to cerebellum volume was 25.0% (range, 2.5-68.6%). Neurological symptoms were present in 97.7% (43/44) of patients. After SRS treatment, symptoms improved in 83.7% (36/44) patients, stabilized in 11.6% (5/44) patients, whilst two patients experienced symptomatic progression. Of the latter, one patient accepted emergency surgery and the other accepted palliative care. CONCLUSIONS: Large cerebellum metastases are amongst the most severe forms of brain tumors. Increased tumor volume and peritumoral edema volume correlate with the most severe symptoms. SRS may be an effective alternative treatment for large cerebellum metastases from lung cancer and may preserve neurological function.

Bevacizumab as a treatment for radiation necrosis following stereotactic radiosurgery for brain metastases: clinical and radiation dosimetric impacts.

BACKGROUND: Brain necrosis (RN) is a common radiotherapy sequela for brain metastases. Bevacizumab is identified as a therapeutic strategy for RN. This study aimed to study the clinical and radiobiological impacts on the efficacy of Bevacizumab in treating RN following stereotactic radiosurgery (SRS) for brain metastases. METHODS: From April 2011 to November 2019, 40 patients diagnosed with RN after SRS for brain metastases were retrospectively analyzed. Patients were treated with Bevacizumab for RN and follow-up for 6 months using MR imaging at different timepoints. Linear regression was performed to evaluate the relationship between these variables. RESULTS: The median time course from the end of radiotherapy to the onset of RN was 11 months (range, 7-35 months). No significant difference was found in the edema volume between the chemotherapy group and non-chemotherapy group (P>0.05). Patients received with SRS + WBRT exhibited relatively larger edema volumes post radiotherapy than those without WBRT (P<0.05). Interestingly, the ratio of BED/GTV (Gy/cm3 ) correlated positively with the severity (time for half-reduction dose of corticosteroids) (r2 =0.13, P<0.05), and negatively with the latency period (time course for development of radiation-induced brain necrosis) (r2 =0.21, P<0.01). A new radiation doses volume index, BED × GTV (Gy·cm3 ), was proposed to facilitate the risk stratifications of patients for radiation-induced brain necrosis. Furthermore, no significant difference was found in alleviating brain edema between different regimens of Bevacizumab, i.e., 5 vs. 10 mg/kg, 2 vs. >2 cycles (both P>0.05). CONCLUSIONS: Bevacizumab is a feasible and favorable salvage treatment of BN after SRS for patients with BM. The efficacy is mainly manifested in radiological improvement and symptoms alleviation. The development of RN was found to be largely associated with radiation dose and gross tumor volume, and thus we proposed two new indexes, i.e., BED/GTV (Gy/cm3 ) for quantitative assessment of the severity and latency time, and BED × GTV (Gy·cm3 ) for risk stratifications for BN. A low dose with two cycles of Bevacizumab is recommended.

[Clinicopathological features for epithelioid glioblastoma: A newly defined tumor by the 2016 World Health Organization Classification of Tumors of the Central Nervous System].

OBJECTIVE: To retrospectively summarize the clinicopathological features of epithelioid glioblastoma (Ep-GBM) and to explore new treatment for Ep-GBM.
 Methods: The clinical data of 13 patients with Ep-GBM, who were treated in our department from March 2016 to July 2017, were retrospectively analyzed. The clinicopathological features were summarized and the efficacy was evaluated.
 Results: The positive rate of BRAFV600E mutant and INI-1 was 76.9% (10/13) and 80% (8/10), respectively, while the median Ki-67 index was 30%. Meningeal metastases occurred in 9 cases (69.7%) during the course. The median follow-up time was 12 (6-25) months, and the median progression-free time was 8.6 (2.2-16.5) months. Three patients died and the 1-year overall survival rate was 54%.
 Conclusion: Ep-GBM has a high degree of malignancy and is prone to spread to leptomeninges. INI-1 expression and BRAFV600E mutation are common for Ep-GBM. BRAF inhibitor might be a potential therapeutic drug for it.

Intravitreal vascular endothelial growth factor concentration and axial length.

BACKGROUND: To examine the intravitreal concentration of vascular endothelial growth factor (VEGF) in dependence of the axial length in eyes without intraocular neovascularization. METHODS: The concentrations of VEGF in vitreous samples and blood samples of patients undergoing pars plana vitrectomy for treatment of idiopathic macular holes or epiretinal membranes were examined using enzyme-linked immunosorbent assay. Axial length was determined by biometry. RESULTS: The study included 34 patients with macular holes (n = 21) or epiretinal membranes (n = 13) with a mean age of 62.4 ± 10.5 years (range: 35-76 years) and a mean axial length of 24.1 ± 1.8 mm (range: 21.0-29.1 mm). The intravitreal VEGF concentration (mean: 71.0 ± 63.2 pg/mL) was significantly (P < 0.001) lower than the VEGF concentration in the blood (830 ± 585 pg/mL). Both parameters were significantly associated with each other (P = 0.04; correlation coefficient r = 0.35). The intravitreal VEGF concentration was not significantly associated with gender (P = 0.25) or age (P = 0.48). A higher intravitreal VEGF concentration was significantly associated with a shorter axial length (P = 0.025; r = -0.39) or a higher hyperopic refractive error (P = 0.04; r = 0.35). Neither plasma concentration of VEGF nor the ratio of plasma VEGF concentrations to intravitreal VEGF concentration was significantly associated with axial length (P = 0.89 and P = 0.22, respectively) or with refractive error (P = 0.89 and P = 0.26, respectively). CONCLUSION: Intravitreal VEGF concentration decreased with increasing axial length. It suggests a diluting effect in eyes with larger intraocular volume and/or a faster turnover rate of VEGF in axially myopic eyes with vitreous liquefaction.