Retinal Blood Vessel Formation in the Macula Following Intravitreal Ranibizumab Injection for Aggressive Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Recently, anti-vascular endothelial growth factor (VEGF) drugs have been widely used for ROP to inhibit abnormal retinal angiogenesis. However, there is a concern that such drugs potentially also affect normal retinal vascular development. We report a case of blood vessel growth across the macula after anti-VEGF treatment for zone I aggressive ROP. A 25-week-old female infant was administered 0.2 mg of ranibizumab for bilateral aggressive ROP in both eyes at 33 weeks of postmenstrual age. Under normal development, retinal blood vessels do not grow into the center of the future macular region. After five weeks, however, a horizontal blood vessel sprouted from the optic disc and extended across the macula in the right eye. The blood vessel ran straight to the vascular-avascular juncture by 41 weeks of postmenstrual age during the follow-up period. While the focus has been on arresting retinal vascular development through VEGF inhibition, anti-VEGF treatment may induce vascular abnormalities in patients with severe ROP. Infants with retinal vascular abnormalities should be carefully monitored for their visual prognosis.

Volumetric fluid analysis of fixed monthly anti-VEGF treatment in patients with neovascular age-related macular degeneration.

AIM: To evaluate visual outcomes and changes in fluid after administering monthly anti-vascular endothelial growth factor (VEGF) injections to treat neovascular age-related macular degeneration (nAMD) with subretinal fluid (SRF) and pigment epithelial detachment (PED). METHODS: This prospective study included eyes with nAMD previously treated with as-needed anti-VEGF injections. The patients were treated with six monthly intravitreal injections of ranibizumab. Quantitative volumetric segmentation analyses of the SRF and PED were performed. The main outcome measures included best-corrected visual acuity (BCVA), and SRF and PED volumes. RESULTS: Twenty eyes of 20 patients were included in this study. At the 6-month follow-up, BCVA and PED volume did not change significantly (P=0.110 and 0.999, respectively) but the mean SRF volume decreased from 0.53±0.82 mm3 at baseline to 0.08±0.23 mm3 (P=0.002). The absorption rate of the SRF volume was negatively correlated with the duration of previous anti-VEGF treatment (P=0.029). Seven of the 20 eyes (35%) showed a fluid-free macula and significant improvement in BCVA (P=0.036) by month 6. CONCLUSION: Quantifying the SRF can precisely determine the patient's responsiveness to anti-VEGF treatment of nAMD.

Functional and Anatomical Outcomes of Anti-Vascular Endothelial Growth Factor Treatment for Exudative Age-Related Macular Degeneration with or without Obstructive Sleep Apnea.

(1) To investigate the functional and anatomical outcomes of anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with exudative age-related macular degeneration (AMD) with or without obstructive sleep apnea (OSA); (2) In total, 65 patients with AMD with or without OSA who received three consecutive doses of intravitreal anti-VEGF injections were enrolled. The primary outcomes-best-corrected visual acuity (BCVA) and central macular thickness (CMT)-were assessed at 1 and 3 months. Moreover, morphological changes observed through optical coherence tomography were analyzed; (3) In total, 15 of the 65 patients had OSA and were included in the OSA group; the remaining 50 patients were included in the non-OSA (control) group. At 1 and 3 months after treatment, BCVA and CMT had improved but did not differ significantly between the groups. More patients in the OSA group demonstrated subretinal fluid (SRF) resorption at 3 months after treatment than in the non-OSA group (p = 0.009). Changes in other imaging biomarkers, such as intraretinal cysts, retinal pigment epithelium detachment, hyperreflective dots, and ellipsoid zone disruptions, did not differ significantly between the groups; (4) Our results suggest that the BCVA and CMT outcomes 3 months after anti-VEGF treatment are similar between patients with and without OSA. Moreover, patients with OSA may exhibit superior SRF resorption. A large-scale prospective study is mandatory to evaluate the association between SRF resorption and visual outcomes in AMD patients with OSA.

Advances in the diagnosis and treatment of retinal artery macroaneurysms / 国际眼科杂志(Guoji Yanke Zazhi)

Retinal arterial macroaneurysm(RAM)is a kind of acquired retinal vascular disorder. The pathogenesis of RAM is not yet clear, and it is associated with some systemic conditions, including hypertension, arteriosclerosis and hyperlipidemia. RAM is prone to exudation or bleeding, leading to some other complications in the condition of hypertension due to the weak tube wall, and its clinical manifestations are complex and diverse, which makes it difficult to diagnose. RAM itself has a tendency of self-degeneration, and the prognosis of visual acuity is good if the lesion doesn't involve the macular area. However, when the macula is affected by exudation and/or bleeding, the vision is severely affected and some feasible treatments are needed. Understanding the typical imaging manifestations of RAM is helpful to make a definite diagnosis and give corresponding treatment measures. In this paper, the manifestations of RAM by various examination methods are reviewed and the corresponding treatments of different types of RAM are summarized, aiming to provide reference for the early diagnosis and treatment of RAM in the future.

Impact of Treating Age-Related Macular Degeneration before Visual Function Is Impaired.

Visual outcomes of age-related macular degeneration (AMD) have substantially improved via anti-vascular endothelial growth factor (anti-VEGF) therapy. However, the treatment effects vary among individuals. Medical charts of 104 eyes (104 patients) with AMD, treated with anti-VEGF drugs and followed up for 12−36 months, were retrospectively analyzed. Logistic regression analyses adjusted for age showed that eyes with an initial best-corrected visual acuity (BCVA) < 0.3 in the logarithm of the minimum angle of resolution (logMAR) were a positive predictor (odds ratio = 3.172; 95% confidence interval [CI] = 1.029−9.783; p = 0.045), and the presence of initial fibrovascular pigment epithelial detachment (PED) was a negative predictor (0.222; 0.078−0.637; p = 0.005) of maintained or improved BCVA at the final visit. Kaplan−Meier survival analysis showed that eyes with an initial BCVA < 0.3 (Cox hazard ratio = 2.947; 95% CI = 1.047−8.289; p = 0.041) had a better survival rate after adjusting for age when failure was defined as a BCVA reduction ≥ 0.2 of logMAR. Eyes with an initial BCVA < 0.3 belonged to younger patients; more frequently had subretinal fluid as an exudative change; and less frequently had intraretinal fluid, submacular hemorrhage, and fibrovascular PED. Initiating anti-VEGF treatment before BCVA declines and advanced lesions develop would afford better visual outcomes for AMD eyes in the real-world clinic, although further analyses are required.

Anti-Vascular Endothelial Growth Factor Treatment for Macular Edema in Eyes with Branch Retinal Vein Occlusion with vs Without Glaucoma - Does Glaucoma Affect Visual Outcome in Eyes with BRVO-ME After antiVEGF Injections?

Purpose: To compare the therapeutic effects of anti-vascular endothelial growth factor (anti-VEGF) agents in eyes with macular edema associated with branch retinal vein occlusion (BRVO-ME) with glaucoma to those without glaucoma. Patients and Methods: This retrospective study was conducted using the medical records of Mie University Hospital from 2013 to 2017. Patients were recruited if they had received anti-VEGF agents for BRVO-ME treatment and included 30 patients (30 eyes) without glaucoma (G[-] group) and 27 patients (27 eyes) with glaucoma (G[+] group). The central retinal thickness (CRT) and best-corrected visual acuity (BCVA) at 3 months after a single injection of anti-VEGF agents were compared between the two groups. Results: Before treatment, the mean±standard deviation of the CRT was 514.2±117.3 µm for the G[-] group, which was not significantly different from that for the G[+] group (533.4±171.4 µm). The CRT in the G[-] and G[+] groups significantly reduced to 321.1±114.6 µm and 347.8±134.7 µm, respectively, at 1 month after the injection and to 360.4±159.5 µm and 352.4±151.9 µm, respectively, at 3 months after the injection (P<0.01 for each group). The difference in the degree of CRT reduction between the two groups was not significant. Before treatment, the BCVA was 0.42±0.32 logMAR units in the G[-] group and 0.57±0.33 logMAR units in the G[+] group, showing no significant difference. The BCVA in the G[-] and G[+] groups improved significantly to 0.27±0.26 logMAR units and 0.34±0.42 logMAR units, respectively, at 1 month, and to 0.18±0.20 logMAR units and 0.39±0.34 logMAR units, respectively, at 3 months (P<0.01). The BCVA in the G[-] group was significantly better than that in the G[+] group at 3 months (P=0.02). Conclusion: The therapeutic response of anti-VEGF agents for BRVO-ME is affected by the presence of glaucoma.

Intravitreal aflibercept for diabetic macular edema in real-world clinical practice in Japan: 24-month outcomes.

PURPOSE: To report the safety and effectiveness of intravitreal aflibercept (IVT-AFL) for diabetic macular edema (DME) in the real-world clinical practice setting in Japan. METHODS: In this prospective, multicenter, observational, post-marketing surveillance, patients with DME newly receiving IVT-AFL were enrolled. During a 24-month follow-up, the primary outcome was the occurrence of safety events. Other pre-specified endpoints were effectiveness indicators, such as best-corrected visual acuity (BCVA), central retinal thickness, and injection frequency. RESULTS: In total, 646 patients administered at least one IVT-AFL injection were included in the safety analysis. During the follow-up period, adverse events occurred in 42 patients (6.50%), whereas adverse drug reactions occurred in 12 (1.86%). In the 12 patients who had adverse drug reactions, seven events occurred in seven patients within the first month of the most recent injection. In addition, 622 patients were included in the effectiveness analysis set. The number of injections over 24 months was 3.6 ± 3.0 (mean ± standard deviation [SD]). BCVA (logarithm of the minimum angle of resolution) was 0.437 ± 0.362 (mean ± SD) (n = 622) at baseline and 0.321 ± 0.348 (n = 177) after 24 months of treatment with IVT-AFL. Central retinal thickness was 440.8 ± 134.2 µm (mean ± SD) (n = 444) at baseline and 355.5 ± 126.4 µm (n = 140) at 24 months. CONCLUSION: Routine administration of IVT-AFL for DME was not associated with new safety concerns, and BCVA outcomes were maintained over 24 months in the real-world setting. Nonetheless, patients in this real-world setting received fewer injections than those in clinical trials, suggesting that a margin for improvement exists in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02425501.

Real-World Data on Intravitreal Aflibercept for Macular Edema Secondary to Central Retinal Vein Occlusion: 24-Month Outcomes.

Purpose: To report on the safety and effectiveness of intravitreal aflibercept (IVT-AFL) for macular edema secondary to central retinal vein occlusion (CRVO) in clinical practice in Japan. Patients and Methods: This prospective, noninterventional, multicenter post-authorization safety study enrolled patients who were treated with IVT-AFL for macular edema secondary to CRVO and followed up for 24 months. The primary outcome was the occurrence of safety events. Other pre-specified outcomes were indicators of effectiveness, including best corrected visual acuity (BCVA), central retinal thickness (CRT), and frequency of injections. Results: The safety analysis included 377 patients who received at least one IVT-AFL. Adverse events (AEs) occurred in 22 patients (5.84%) and adverse drug reactions occurred in 5 (1.33%) over 24 months. Of the 22 patients with AEs, 72.7% experienced their first AEs by the third injection. The effectiveness analysis set comprised 360 patients for whom data on each outcome could be collected. The number of injections over 24 months was 3.4 ± 2.4 (mean ± standard deviation [SD]). BCVA (logarithm of the minimum angle of resolution) was 0.709 ± 0.535 (mean ± SD) (n = 357) at baseline and 0.543 ± 0.559 (n = 97) after 24 months of treatment with IVT-AFL. CRT was 552.6 ± 211.3 µm (mean ± SD) (n = 214) at baseline and 331.5 ± 144.0 µm (n = 54) at 24 months. Conclusion: There were no new safety issues concerning routine administration of IVT-AFL for macular edema secondary to CRVO. BCVA recovered during 24 months of IVT-AFL treatment in the real-world setting. However, there was a trend toward less improvement compared with the results of randomized controlled trials, likely due in part to undertreatment.

The second Japanese family with Malattia Leventinese/Doyne honeycomb retinal dystrophy.

PURPOSE: To describe the clinical and genetic findings of patients in the second Japanese family with Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD). METHODS: Two patients (a 41-year-old male proband and his third son) underwent comprehensive ophthalmic examinations, including full-field and multifocal electroretinography (ERG). Sanger sequencing was performed to detect an EFEMP1 gene variant (p.Arg345Trp), which was identified as the only causative pathogenic variant. RESULTS: Genetic analysis revealed that both patients carried the heterozygous variant, but the other unaffected family members did not. Although the proband exhibited innumerable radially distributed drusen in both the posterior poles and good visual acuity at initial presentation, bilateral choroidal neovascularization (CNV) developed during the 15-year follow-up. The proband received 15 intravitreal anti-vascular endothelial growth factor (VEGF) injections in the left eye (LE) and two injections in the right eye (RE). At 56 years of age, his decimal best-corrected visual acuity was 0.1 and 1.2 in the LE and RE, respectively. Full-field ERG showed that while the rod and combined responses were within normal amplitudes, the cone and 30-Hz flicker responses had slightly decreased amplitudes. Multifocal ERG revealed attenuated central responses in the LE and decreased temporal responses in the RE. In the 20-year-old son, multifocal ERG showed normal responses in both eyes. CONCLUSION: This is the first report of ML/DHRD in a patient who developed bilateral CNV and received anti-VEGF treatment in both eyes. Although multifocal ERG exhibited worsening of macular function, the generalized photoreceptor function was preserved until middle age.

Replacement of polyps with type 1 macular neovascularization in polypoidal choroidal vasculopathy imaged with swept source OCT angiography.

PURPOSE: To investigate the morphological changes of polyps in eyes with polypoidal choroidal vasculopathy (PCV) after treatment with vascular endothelial growth factor (VEGF) inhibitors using swept source optical coherence tomography angiography (SS-OCTA). OBSERVATIONS: Following anti-VEGF therapy, polyps were found to evolve into typical type 1 macular neovascularization (MNV) in five eyes. In all of these five eyes, a polypoidal lesion was detected adjacent to a serous or hemorrhagic retinal pigment epithelial detachment (PED). CONCLUSIONS AND IMPORTANCE: Polypoidal lesions in PCV can evolve into typical type 1 MNV. This morphological evolution suggests that these polyps are clusters of tangled vessels that can proliferate into a more typical neovascular pattern, and this evolution may be facilitated by being adjacent to a PED. Since this morphological appearance could be associated with a better prognosis, SS-OCTA might be helpful in identifying cases of transformed polyps that may be associated with a decreased risk for vision loss.

Interpretation of Clinical Guideline for Anti-vascular Endothelial Growth Factor Therapy of Retinopathy of Prematurity by Japanese Ophthalmological Society / 中华实验眼科杂志

Retinopathy of prematurity (ROP) is the leading cause of blindness in children worldwide.Intravitreal injection of anti-vascular endothelial growth factor (VEGF) has become a widely used first-line treatment for ROP in recent decade, but the anti-VEGF treatment of ROP is off-label in China, and the injection method and dosage are different from adults.In December 2020, the Clinical Guideline for Anti-vascular Endothelial Growth Factor Therapy of Retinopathy of Prematurity was released by the Japanese Ophthalmological Society, which is by far the only guideline for anti-VEGF treatment of ROP.Due to the ethnic similarity between Japanese and Chinese, this guideline is of high reference value to Chinese ROP clinical practice.This article introduced and interpreted the main information in the guideline to provide Chinese ophthalmologists references for the understanding, diagnosis and treatment of ROP.

The Role of Serum Inflammation-Based Factors in Anti-Vascular Endothelial Growth Factor Treatment for Macular Edema Secondary to Retinal Vein Occlusion and Its Subtypes.

OBJECTIVE: The aim of this work was to evaluate the association between pretreatment inflammation-based factors and outcomes in patients with macular edema (ME) secondary to retinal vein occlusion (RVO) and its subtypes after intravitreal ranibizumab or conbercept implant. METHODS: This retrospective observational study included patients who were diagnosed with ME secondary to RVO at the First Affiliated Hospital of Nanchang University between January 2017 and January 2019, and who subsequently received intravitreal anti-vascular endothelial growth factor (VEGF) treatment. Blood-based parameters were measured before treatment, and correlations between best-corrected visual acuity (BCVA) and each of 3 parameters - neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) - were analyzed to identify predictors of effective intravitreal injection treatment outcomes. RESULTS: A total of 315 treatment-naïve eyes treated with anti-VEGF drugs for RVO-ME were retrospectively analyzed in this study. The mean PLR value was significantly different in the effective and ineffective group for RVO-ME (138.03 ± 48.61 vs. 106.79 ± 27.28), branch RVO (BRVO)-ME (216.47 ± 53.04 vs. 185.94 ± 51.47), and central RVO (CRVO)-ME (231.07 ± 66.05 vs. 196.20 ± 60.44). The cutoff value of the PLR was 97.92, the area under the curve was 0.70, and the sensitivity and specificity were 81.5 and 44.3%, respectively. The mean NLR value was significantly different in the effective and ineffective groups for RVO-ME (2.20 ± 1.40 vs. 1.92 ± 0.89), and BRVO-ME (2.01 ± 0.80 vs. 1.82 ± 0.84), but not in patients with CRVO-ME (2.51 ± 2.02 vs. 2.12 ± 0.95). There are no significant differences between BRVO-ME and its subtype groups in MLR values. But the mean MLR value was significantly higher in the conbercept group than in the ranibizu-mab group among patients in the effective group (0.27 ± 0.11 vs. 0.25 ± 0.14). CONCLUSION: Higher pretreatment PLR was associated with BCVA in patients with RVO-ME and its subtypes who were treated with anti-VEGF drugs. The PLR may be used as a predictive and prognostic tool for effective intravitreal injection treatment outcomes.

Patient Preferences for Anti-Vascular Endothelial Growth Factor Treatment for Wet Age-Related Macular Degeneration in Japan: A Discrete Choice Experiment.

BACKGROUND: In Japan, intravitreal anti-vascular endothelial growth factor (anti-VEGF) dosing regimens for wet age-related macular degeneration (wAMD) include pro re nata, every 2 months, and treat-and-extend, resulting in different outcomes and patient burden. Although reflecting patient preferences in treatment decision-making is desirable, few studies have examined this in Japan. This study assessed the patients willingness to trade-off between different dosing regimens. PATIENTS AND METHODS: Patients with wAMD were recruited from four Japanese university hospitals to complete a face-to-face cross-sectional survey. In a discrete choice experiment, patients were asked to choose their preferred option from two anti-VEGF treatment profiles shown side-by-side across a series of choice tasks. The profiles varied on four attributes: number of injections in 12 months, number of physician consultations in 12 months, chance of 1-year visual acuity (VA) improvement, and chance of 2-year VA maintenance. Preference weights were estimated using hierarchical Bayes' models. RESULTS: Overall, 120 patients (30 treatment naïve and 90 anti-VEGF experienced) completed the survey. Patients were willing to accept an increase from three to approximately eight injections in 12 months to increase the chance of 1-year VA improvement from 25% to 40%. They would be willing to accept 11 injections in 12 months if the chance of 2-year VA maintenance increased from 80% to 96%. The most valued attributes were increasing the chance of 2-year VA maintenance and reducing the number of injections in 12 months, which were each about twice as important as decreasing physician consultations in 12 months and increasing the chance of 1-year VA improvement (p<0.001). Among the dosing regimens, patients most preferred treat-and-extend because of its higher chance of 2-year VA maintenance. CONCLUSION: Informing patients with wAMD about the likelihood of long-term VA maintenance when selecting treatment may increase the acceptance of an optimal treatment regimen and number of injections.

Clinical course of acute zonal occult outer retinopathy complicated by choroidal neovascularization.

PURPOSE: To report the clinical course and multimodal imaging features of acute zonal occult outer retinopathy (AZOOR) complicated by choroidal neovascularization (CNV) treated with anti-vascular endothelial growth factor (VEGF) treatment or photodynamic therapy (PDT). METHODS: Observational case series. Retrospective analysis of patients presenting to different institutions with evidence of AZOOR and neovascular lesions. Diagnosis of AZOOR was made on the basis of clinical presentation and multimodal imaging. All patients underwent a comprehensive ophthalmic evaluation and multimodal retinal imaging, including color fundus photos, fundus autofluorescence, fundus fluorescein angiography and spectral-domain optical coherence tomography. RESULTS: Four patients (three males, mean age 53.5 years) were included in the study. Mean follow-up was 5.1 years. Presentation of AZOOR was unilateral in two patients and bilateral in the remainder two patients. One of the patients presenting with unilateral AZOOR developed zonal lesions in the fellow eye during follow-up. All patients presented with unilateral type 2 (subretinal) CNV. Three patients underwent intravitreal anti-VEGF injections and one patient underwent a single PDT. Multimodal retinal imaging showed zonal or multizonal progression during treatment. After treatment, visual acuity and CNV stabilization was observed in all patients. CONCLUSIONS: The presence of CNV expands the clinical spectrum of AZOOR. CNV complicating AZOOR may be effectively treated with intravitreal injections of anti-VEGF, despite progression of the zonal lesions. Further studies are required to define the role of treatment in the progression of the zonal lesions.

Disorganization of the Retinal Inner Layers after Anti-VEGF Treatment for Macular Edema due to Branch Retinal Vein Occlusion.

PURPOSE: To evaluate the association between disorganization of the retinal inner layers (DRIL) and visual acuity (VA) after anti-VEGF treatment for macular edema (ME) due to branch retinal vein occlusion (BRVO). METHODS: Sixty eyes of 60 patients were retrospectively investigated. Baseline characteristics and factors analyzed on optical coherence tomography (OCT) examination at the final visit were evaluated in association with VA at the final visit. RESULTS: DRIL was detected in 39 eyes at the final visit. The central subfield thickness was significantly higher in the eyes with DRIL. While DRIL length at the final visit showed a significant association with final VA on univariable analysis, only age and ellipsoid zone disruption on OCT at the final visit were found to be significantly associated with VA on multivariable analysis. CONCLUSIONS: DRIL had only a minor role in determining VA after anti-VEGF treatment for ME due to BRVO.

Diabetic macular oedema treated with intravitreal anti-vascular endothelial growth factor - 2-4 years follow-up of visual acuity and retinal thickness in 566 patients following Danish national guidelines.

PURPOSE: To investigate long-term functional and anatomical outcomes, discontinuation patterns, drug switching and rates of nonimprovement in patients treated with ranibizumab pro re nata (PRN) regimen for diabetic macular oedema (DME) according to the Danish national guidelines. METHODS: Retrospective cohort study of 566 eyes in 566 patients with centre-involved DME who started intravitreal treatment with ranibizumab between January 2011 and December 2013 in the Greater Copenhagen region. Data were retrieved from a database and patient records between January 2011 and March 2016 and analysed using mixed-model statistics. RESULTS: At the conclusion of follow-up, 24.6% were in active ranibizumab follow-up, 25.4% had switched to other intravitreal pharmacotherapy, 31.6% had been discontinued because of disease stability, 13.8% had been lost to follow-up, 1.4% had been discontinued because of low visual acuity (VA), and 3.2% had died. At baseline, mean best-corrected visual acuity (BCVA) and mean central subfield thickness (CST) were 64.9 (±15.0) letters and 400.2 (±120.3) µm. Mean change in BCVA and mean change in CST from baseline to 3, 12, 24, 36 and 48 months of follow-up were +3.9, +3.5, +2.7, +1.8, +2.3 letters and -97.4, -102.6, -106.9, -105.9, -131.6 µm, respectively. Mean number of injections was 6.1 in year 1 and 1.8 in year 4. In 93 patients, drug switching to aflibercept showed no difference between the two drugs on BCVA or CST. In 79 patients, CST decreased <10% compared to baseline during the first year. CONCLUSION: In a single-centre clinical setting, 566 patients treated for DME with ranibizumab according to the Danish national guidelines were followed for up to 4 years. Best-corrected visual acuity (BCVA) outcomes are in the low end of clinical studies, but studied on a wider population and achieved with fewer injections.

Recruitment of CD11b+Ly6C+ monocytes in non-small cell lung cancer xenografts challenged by anti-VEGF antibody.

A series of antibodies against vascular endothelial growth factor (VEGF) have been developed for the treatment of various types of cancer, including non-small cell lung cancer (NSCLC) in recent years. However, tumors frequently demonstrate resistance to these strategies of VEGF inhibition. Efforts to better understand the mechanism underlying the acquired resistance to anti-VEGF antibodies are warranted. In the present study, in order to develop a xenograft model of acquired resistance to anti-VEGF antibody, xenografts of human adenocarcinoma A549 cells were generated through the successive inoculation of tumor tissue explants into first (F1), second (F2) and third (F3) generations of mice treated with the anti-VEGF antibody B20. Tumor growth rate and vessel-forming ability, assessed via cluster of differentiation (CD) 31 staining, were significantly lower in the F1, F2 and F3 groups compared with in the F0 control group (P<0.01), suggesting that drug resistance was not successfully acquired. The percentages of CD11b+ myeloid-derived suppressor cells and lymphocyte antigen 6C (Ly6C)+ subsets were significantly smaller in F1, F2 and F3 groups compared with in F0 (P<0.01). However, the ratio of Ly6C+ to CD11b+ cells was significantly higher in the F3 group compared with in F0 and F1 groups (P<0.01), indicating increasing recruitment of the Ly6C+ subset with successive challenges with the anti-VEGF antibody. In conclusion, the recruitment of CD11b+Ly6C+ monocytes increased with successive generations of NSCLC-xenografted mice challenged by B20, an anti-VEGF agent.

Long-Term Follow-Up of Choroidal Neovascularization due to Angioid Streaks with pro re nata Intravitreal Anti-VEGF Treatment.

PURPOSE: To evaluate the long-term outcomes of intravitreal anti-vascular endothelial growth factor (VEGF) drugs with a pro re nata (PRN) regimen for the treatment of choroidal neovascularization (CNV) secondary to angioid streaks (AS). METHODS: This is a retrospective, multicenter, noncomparative case series of consecutive AS eyes affected by treatment-naïve CNV. A complete ophthalmologic examination was performed every 30-45 days after the loading phase, including fluorescein angiography and/or optical coherence tomography. RESULTS: In all, 52 eyes of 39 patients were treated with intravitreal bevacizumab and/or ranibizumab and followed up for a mean of 33.8 months. The best corrected visual acuity at baseline was 20/40, and it deteriorated by an average of 6.8 ETDRS letters per year (p < 0.001). We performed an average of 5.1, 6.5, and 6.8 injections at the 1-, 2-, and 3-year follow-up, respectively. CONCLUSIONS: Intravitreal anti-VEGF drugs in a PRN regimen with close monitoring appear to slow the progression of CNV in AS, but they do not prevent the affected eyes from progressive visual loss.

Spontaneous or secondary to intravitreal injections of anti-angiogenic agents retinal pigment epithelial tears in age-related macular degeneration.

AIM: To evaluate the visual function evolution of retinal pigment epithelial (RPE) tears in patients with age-related macular degeneration (AMD) according to type of occurrence [spontaneous or secondary to anti-vascular endothelial growth factor (anti-VEGF) injection] and the topographic location of the tear after a two-year follow-up period. METHODS: A total of 15 eyes of 14 patients with RPE tears in exudative AMD were analyzed retrospectively at the University Eye Clinic of Trieste. Inclusion criteria were: patient age of 50 or older with AMD and RPE tears both spontaneous occurring or post anti-VEGF treatment. Screening included: careful medical history, complete ophthalmological examination, fluorescein angiography (FA), indocyanine green angiography (ICG), autofluorescence and infrared imaging and optical coherence tomography (OCT). Patients were evaluated every month for visual acuity (VA), fundus examination and OCT. Other data reported were: presence of PED, number of injections before the tear, location of the lesion. RESULTS: Mean follow-up was 24wk (SD±4wk). A total of 15 eyes were studied for RPE tear. In 6 cases (40%), the RPE tears occurred within two years of anti-VEGF injections the others occurred spontaneously. In 13 cases (86.6%), the RPE tear was associated with pigment epithelial detachment (PED). In 7 cases (46.6%), the RPE tear occurred in the central area of the retina and involved the fovea. Two lesions were found in the parafoveal region, six in the extra-macular area. In all cases visual acuity decreased at the end of the follow-up period (P<0.01) independently of the type or the topographical location of the lesion. CONCLUSION: RPE tear occurs in exudative AMD as a spontaneous complication or in relation to anti-VEGF injections. Visual acuity decreased significantly and gradually in the follow-up period in all cases. No correlation was found between visual loss and the type of onset or the topographic location of the tears.

Choroidal excavation with polypoidal choroidal vasculopathy: a case report.

PURPOSE: This is a report of a case of choroidal excavation accompanied by polypoidal choroidal vasculopathy (PCV) and retinal pigment epithelium detachment (PED). METHODS: A 57-year-old Japanese woman who had begun complaining of metamorphopsia in her left eye 7 months earlier underwent spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and indocyanine green angiography (IA), as well as a routine ophthalmological examination. RESULTS: The patient's intraocular pressure, visual acuity, and visual field were within normal range. Ophthalmoscopy revealed a serous macular detachment, soft drusen, exudates, and a reddish-orange elevated lesion in the macula of the left eye. The right eye was normal. SD-OCT revealed two lesions in the left eye. One was a PED accompanied by a notch sign, and the other was a choroidal excavation. Additionally, FA revealed a window defect in the PED, and IA showed typical PCV. Three monthly injections of antivascular endothelial growth factor preserved visual acuity, but failed to have any visible effect on the lesion during the 6-month follow up period. CONCLUSIONS: This is the first report of choroidal excavation accompanied by PED and PCV. The data suggest that choroidal excavation may be associated with various changes that have not been previously reported. Careful observation of such cases may therefore be necessary.