The Impact of the COVID-19 Pandemic on the Quality of Care of Treatment-Naïve Patients with Neovascular Age-Related Macular Degeneration Receiving Intravitreal Aflibercept. / Die Auswirkungen der COVID-19-Pandemie auf die Versorgungsqualität von therapienaiven PatientInnen mit neovaskulärer altersbedingter Makuladegeneration unter intravitrealer Aflibercept-Therapie.

OBJECTIVE: The aim of this study was to compare the quality of care received by treatment-naïve patients with neovascular age-related macular degeneration (nAMD) who received intravitreal aflibercept therapy before the coronavirus disease 2019 (COVID-19) pandemic with patients who received the same therapy during the pandemic. METHODS: Data, including best corrected visual acuity (BCVA) as the logarithm of the minimum angle of resolution (logMAR) and anatomical outcomes at diagnosis and at each follow-up, was collected on 297 treatment-naïve patients who received intravitreal aflibercept. Therapy-naïve patients who started therapy at least 24 months prior to the first pandemic-related lockdown and were thus treated exclusively prior to the pandemic (n = 123) were compared with patients who started therapy within 12 months prior to the first lockdown and were thus treated during the pandemic (n = 174). Both groups were followed over a two-year period. RESULTS: In patients treated before the COVID-19 pandemic, VA remained stable (0.58 ± 0.41 logMAR) compared to baseline (0.54 ± 0.34 logMAR; p = 0.228) until the end of the observation period. In patients treated during the COVID-19 pandemic, BCVA dropped below the baseline (0.56 ± 0.35 logMAR) within 24-month of follow-up (0.79 ± 0.43 logMAR; p = 0.010). Compared to the patients treated prior to the COVID-19 pandemic, the latter group showed a significantly worse VA at the 6-month (p = 0.041), 12-month (p = 0.040), 18-month (p = 0.024), 21-month (p = 0.035), and 24-month (p = 0.004) follow-up. Additionally, the group treated during the COVID-19 pandemic received significantly fewer aflibercept injections (3,94 ± 1,9 vs. 3,30 ± 1,6; p = 0,007) and fewer follow-up examinations (2,71 ± 1,2 vs. 2,16 ± 0,9; p < 0,001) in the second year compared to the group that was treated before the COVID-19 pandemic. CONCLUSION: We confirmed significantly worse VA outcomes in the group of nAMD patients treated during the COVID-19 pandemic. Impeded access to care could be attributed to the restrictions imposed owing to the COVID-19 pandemic.

Long-term persistence with aflibercept therapy among treatment-naïve patients with exudative age-related macular degeneration in a universal health care system: a retrospective study.

BACKGROUND: This study aimed to analyse the persistence rates of treatment-naïve patients with neovascular age-related macular degeneration (nAMD) who received intravitreal aflibercept therapy in a universal health care system. METHODS: In this single-centre retrospective cohort study, we audited data of 918 treatment-naïve patients who received exclusively intravitreal aflibercept therapy for nAMD between September 2015 and May 2021. The primary outcome measures were the rates of treatment nonpersistence (gap in ophthalmological care > 6 months) and long-term nonpersistence (> 12 months). RESULTS: The rates of nonpersistence and long-term nonpersistence were 12.3% and 3.4% after one year; 22.4% and 9.5% after two years; and 38.3% and 19.3% after five years, respectively. Logistic regression analysis revealed that older age (p = 0.045), male sex (p = 0.039), requirement for caretakers or ambulance (p = 0.001), and low visual acuity of the study eye (p = 0.010) or fellow eye (p = 0.029) were independent risk factors for long-term nonpersistence. Patients aged > 80 and > 85 years (p = 0.013 and p = 0.022, respectively) had more than twice the risk for being nonpersistent to therapy within two years of follow-up compared with younger patients. Male patients (p = 0.033), patients requiring a caretaker (p = 0.038), and patients living > 60 km from the clinic (p = 0.029) had a 2 × higher risk of being persistently nonpersistent to therapy. CONCLUSIONS: Patients with nAMD who were treated with aflibercept had lower nonpersistence rates than those reported in current literature. Multiple independent risk factors were correlated with long-term nonpersistence, early nonpersistence, or complete loss to follow-up. Considering the possible consequences of reduced compliance, further strategies are urgently needed for patients at risk of nonpersistence to therapy.

Intravitreal Aflibercept Therapy and Treatment Outcomes of Eyes with Neovascular Age-Related Macular Degeneration in a Real-Life Setting: A Five-Year Follow-Up Investigation.

INTRODUCTION: We aimed to evaluate visual and anatomical outcomes among eyes with neovascular age-related macular degeneration (nAMD) that were persistent to intravitreal aflibercept therapy compared to those that were nonpersistent to therapy. METHODS: We audited 648 treatment-naïve eyes of 559 patients regarding visual acuity (VA) given as the logarithm of the minimum angle of resolution (logMAR) and anatomic outcomes at baseline and at each subsequent follow-up visit for up to 5 years. Nonpersistence was defined as a visit-free interval of > 6 months. RESULTS: Among the enrolled eyes, 405 were persistent to the therapy and 243 (37%) were nonpersistent, of which 161 (66%) eyes returned for further therapy after a gap of clinical care. In the nonpersistent group, we observed a decline from 0.58 ± 0.35 to 0.92 ± 0.57 logMAR (p = 0.01) after 60 months. Compared with the persistent group, the nonpersistent group had worse visual outcomes at their 33-month (p = 0.03), 42-month (p = 0.01), 51-month (p = 0.001) and 60-month (p = 0.01) visits. Additionally, 5/405 (1.2%) eyes in the persistent group and 8/161 (5.0%) eyes in the nonpersistent group developed an end-stage disease with a subfoveal fibrosis during the observational period (p = 0.013). CONCLUSION: We found that eyes with nAMD that were nonpersistent to intravitreal aflibercept therapy experienced statistically significantly worse VA compared to eyes persistent to therapy within 3 years. Moreover, eyes in the nonpersistent group had a four-fold higher risk of developing a fovea-involving fibrosis. Considering the potential irreversible deterioration with respect to best-corrected VA within nAMD, strategies need to be developed for patients at risk of nonpersistence to therapy.

Two Cases of Acute Macular Neuroretinopathy Associated with the Adenovirus-based COVID-19 Vaccine Vaxzevria (Astrazeneca).

PURPOSE: To report two cases of acute macular neuroretinopathy (AMN) in young female patients following the administration of the adenovirus-based coronavirus disease 2019 (COVID-19) vaccine Vaxzevria (AstraZeneca). METHODS: Spectral-domain optical coherence tomography and infrared imaging were used to confirm the diagnosis of AMN. RESULTS: Both patients showed a parafoveal hyperreflective band in the outer nuclear layer, disruption of the ellipsoid and interdigitation zones of the photoreceptor layers, and correlating hyporeflective areas on the near-infrared images. Both patients presented with flu-like fever and sudden onset of fortifications within 48 hours of vaccination. One patient showed altered flow in the deep capillary plexus and highly elevated thrombotic parameters. CONCLUSION: We report a possible association between immune-mediated AMN and the administration of adenovirus-based COVID-19 vaccine Vaxzevria.

CHANGES IN SYSTEMIC LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR AFTER INTRAVITREAL INJECTION OF AFLIBERCEPT OR BROLUCIZUMAB FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To analyze and compare the effects of intravitreal brolucizumab versus aflibercept on systemic vascular endothelial growth factor (VEGF)-A levels in patients with neovascular age-related macular degeneration. METHODS: In this prospective interventional case series study, brolucizumab (6.0 mg/50 µL) or aflibercept (2.0 mg/50 µL) was injected intravitreally in 30 patients each. Blood samples were drawn at baseline and 7 days and 28 days after the first injection. Systemic VEGF-A levels were measured using enzyme-linked immunosorbent assay. Thirty healthy individuals served as controls. RESULTS: The median baseline systemic VEGF-A levels in the brolucizumab, aflibercept, and control groups were 10.8 (8.0-13.2), 12.0 (8.0-18.5), and 10.0 (8.0-15.1) pg/mL, respectively (P = 0.315). In the brolucizumab group, VEGF-A levels significantly decreased to 8.0 (8.0-11.5) pg/mL on Day 7 (P = 0.0254) and to 8.0 (8.0-8.0) pg/mL on Day 28 (P < 0.001). In the aflibercept group, VEGF-A levels significantly decreased to 8.0 (8.0-8.0) pg/mL on Day 7 (P < 0.001) but returned to the baseline level, 12.5 (8.5-14.6) pg/mL, on Day 28 (P = 0.120). Vascular endothelial growth factor-A levels were significantly different between the treatment groups after 28 days (P < 0.001). CONCLUSION: Intravitreal brolucizumab resulted in a sustained reduction of systemic VEGF-A levels until 28 days posttreatment, which raises concerns regarding its safety and long-term effects.

Efficiency benchmarks in the surgical management of primary rhegmatogenous retinal detachment: a monocentric register cohort study of operating room time metrics and influential factors.

OBJECTIVES: To investigate the effect of clinical, methodological and logistic factors on operating room (OR) efficiency in the surgical management of primary rhegmatogenous retinal detachment (RRD). DESIGN: Monocentric retrospective register cohort study. SETTING: Single tertiary centre in the western region of Austria. PARTICIPANTS: We audited patients diagnosed with primary RRD who were treated between January 2014 and August 2019. In total, 783 eyes of 776 consecutive patients were included in this study. Various risk factors affecting OR time efficiency and anatomical success after pars plana vitrectomy (PPV) procedures and scleral buckle (SB) surgery were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: OR efficiency was the primary outcome measure. Secondary outcome measures were the primary success rate after PPV procedures and SB surgery. RESULTS: PPV was performed in 641 (81.9%) eyes and SB surgery in 142 (18.1%) eyes. Mean surgical times in PPV and SB under retrobulbar anaesthesia (RA) were 74.0 (±32.6) min and 62.1 (±24.6) min (p<0.001), respectively, while under general anaesthesia (GA), these values were 112.0 (±52.0) min and 76.0 (±22.5) min (p<0.001), respectively. A regression analysis revealed the following main risk factors for prolonged OR time for the surgical management of RRD with PPV (all p<0.001): presence of a giant tear (ß=24.01; 32%), proliferative vitreoretinopathy (PVR)-C (ß=16.43; 22%), surgery postponed for 72 hours after diagnosis (ß=21.40; 29%), GA (ß=23.64; 32%) or surgery performed by a trainee (ß=17.35; 23%). PVR (p=0.022) in PPV cases, after-hours settings (p=0.006) and surgeon experience (p=0.030) in SB cases were independent risk factors for reduced success rates. CONCLUSIONS: OR coordinators should consider various independent clinical (giant tear, PVR-C, advanced detachment), methodological (PPV vs SB) and logistic (GA vs RA, after-hours setting and surgeon experience) factors to improve the success rate and surgical management planning of RRD accurately while optimising OR resources and staff efficiency.

Effects of Intravitreal Aflibercept on the Systemic Insulin-like Growth Factor-I and Vascular Endothelial Growth Factor-A in Patients with Diabetic Retinopathy and Age-Related Macular Degeneration.

PURPOSE: To analyze the effect of intravitreal aflibercept injections on systemic levels of insulin-like growth factor-1 and vascular endothelial growth factor-A in patients with diabetic retinopathy and age-related macular degeneration. METHODS: Vascular endothelial growth factor-A and insulin-like growth factor-1 levels were determined before and one week and four weeks after intravitreal injection of aflibercept (2.0 mg/50 µl) for 19 patients with age-related macular degeneration (mean age, 76 ± 11 years) and 18 patients with diabetic retinopathy (mean age, 64 ± 14 years). Twenty-two healthy individuals were enrolled as controls. RESULTS: A significant decline in systemic vascular endothelial growth factor-A level, from 43 (30-57) pg/ml at baseline to 8 (8-8) pg/ml (p < 0.001) at week one and 17 (8-25) pg/ml (p=0.0054) at week four, was observed in the age-related macular degeneration group. In the diabetic retinopathy group, vascular endothelial growth factor-A levels declined from 53 (35-117) pg/ml to 2 (1-5) pg/ml (p < 0.0001) one week after injection and 16 (13-22) pg/ml four weeks after injection (p=0.0327). At baseline, systemic insulin-like growth factor-1 concentration was higher in the diabetic retinopathy group (57 [37-99] pg/ml) than in the age-related macular degeneration group (35 [24-51] pg/ml) (p=0.0056). A subgroup analysis showed that patients in the proliferative diabetic retinopathy subgroup had significantly higher systemic insulin-like growth factor-1 concentrations (71 [44.7-243] pg/ml) than those in the nonproliferative diabetic retinopathy subgroup (43 [29-66] pg/ml) (p=0.0048). CONCLUSIONS: The difference between the baseline systemic insulin-like growth factor-1 levels of the age-related macular degeneration and diabetic retinopathy groups and the higher insulin-like growth factor-1 levels in the proliferative diabetic retinopathy subgroup one week after aflibercept therapy suggest that insulin-like growth factor-1 may play a role in the pathomechanism of diabetic retinopathy.

Systemic counterregulatory response of angiopoietin-2 after aflibercept therapy for nAMD: a potential escape mechanism.

PURPOSE: To analyse the effect of intravitreal aflibercept injections on systemic angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF)-A levels in patients with neovascular age-related macular degeneration (nAMD). METHODS: In a prospective, randomized study, aflibercept (2.0 mg/50 µl) or ranibizumab (0.5 mg/50 µl) was administered intravitreally to 38 treatment-naive patients. Blood samples were taken before, 7 days after, and 28 days after the first intravitreal therapy. Cytokine levels were measured by enzyme-linked immunosorbent assay. Twenty-two age- and sex-matched individuals served as controls. RESULTS: At baseline, there were no significant differences of systemic Ang2 and VEGF-A levels among the treatment and control groups. After intravitreal aflibercept administration, median (interquartile range: IQR) systemic Ang2 was significantly upregulated from 1819 pg/ml (1262-3099) to 2123 pg/ml (1441-3769; p = 0.011) 7 days after the drug injection and remained non-significantly elevated at 1944 pg/ml (1431-2546 pg/ml; p = 0.653) 28 days after the drug injection. Median (IQR) systemic VEGF-A levels were significantly reduced from 43 pg/ml (30-57) to 8 pg/ml (8-8; p < 0.0001) 7 days and 16 pg/ml (8-26; p = 0.001) 28 days after the injection in the aflibercept group. There were no significant effects on systemic VEGF-A and Ang2 levels in the ranibizumab group at any time point following the first injection. CONCLUSION: In this study, we report significant systemic upregulation of Ang2 after intravitreal aflibercept administration. This counterregulatory response may represent a potential escape mechanism from antiangiogenic therapy.

[Patient Mobility and Journey Distance as Risk Factors for Severe Visual Impairment: Real-Life Data Analysis of Treatment-naïve Patients with nAMD under Intravitreal Aflibercept Therapy]. / PatientInnen-Mobilität und Anreisedistanz als Risiko für höhergradige Sehbehinderung: Real-Life-Daten therapienaiver AMD-PatientInnen unter intravitrealer Aflibercept-Therapie.

OBJECTIVE: The aim of this study is to describe the effectiveness of aflibercept in treatment-naive patients with neovascular age related macular degeneration (nAMD) and the impact of patients' residential distance to the clinic and patients' mobility on therapy in a pro re nata regime. METHODS: A retrospective dataset analysis of 483 treatment-naive patients with nAMD was performed. The main outcomes were best corrected visual acuity (BCVA), central foveal thickness (CFT), bilateral visual impairment, distance and type of transport to the clinic. Secondary outcomes were injection rate, numbers and reasons of loss to follow-up. RESULTS: Patients received 4.91 ± 1.9 injections in their first year and 7.06 ± 3.6 after the period of 25 months (m). Initially the BCVA improved significantly after a loading dose from 0.72 logMAR (± 0.44) to 0.63 logMAR (± 0.45; p = 0.03). However, the BCVA significantly decreased after 2 years to 0.82 (± 0.48; p < 0.001). The proportion of patients with higher visual impairment and patients needing assistance with transport increased with the distance of their residence to the clinic (both p < 0.001). The LTFU rate was 3% and showed a correlation with greater age (p = 0.019). CONCLUSION: The presented data show that aflibercept is effective for the treatment of nAMD. Although a good increase in visual acuity is initially achieved in the majority of patients, the initial success of treatment is not maintained throughout the course of the disease. Compared to controlled clinical studies, the presented data show reduced therapeutic success and lower injection frequencies. The rising demand for patient transport aid and increased visual impairment with increased distance indicate potential problems within the healthcare system.

[Diagnosis, treatment and monitoring of diabetic eye disease (Update 2019)]. / Diagnose, Therapie und Verlaufskontrolle der diabetischen Augenerkrankung (Update 2019).

Diabetes mellitus can cause diabetic retinopathy, diabetic macular edema, optic neuropathy, cataract or dysfunction of the eye muscles. The incidence of these defects correlates with disease duration and quality of metabolic control. Recommendations of the Austrian Diabetes Association for diagnosis, therapeutic procedures and requirements for adequate follow-up depending on stage of diabetic eye disease are summarized.

Triamcinolone in small-gauge vitrectomy for epiretinal membrane peeling.

OBJECTIVE: We compared visual and macular morphological outcomes after epiretinal membrane (ERM) peeling, with and without IVTA treatment. DESIGN: Interventional, retrospective, consecutive case-control study. PARTICIPANTS: Forty-one eyes of 41 participants (17 men, 24 women) were included. Twenty-one were treated by standard vitrectomy and peeling (controls) and 20 patients received intravitreal triamcinolone after vitrectomy and peeling. METHODS: Pre-and postoperative letter score and central foveal thickness (CFT) through the foveal centre were compared between both groups. Best-corrected visual acuity (BCVA) was measured using Snellen charts and converted to logMAR for statistical analyses. RESULTS: CFT and BCVA had improved by the 6-month follow-up from baseline. In the control group, the mean logMAR BCVA improved from 0.57 (SD: 0.22) to 0.21 (0.17) (p < 0.01), and the mean CFT reduced from 462.5 (98.6) µm to 329.8 (82.7) µm (p < 0.01). The mean logMAR BCVA of the IVTA group improved from 0.73 (0.17) to 0.36 (0.31) (p < 0.01), and the mean CFT reduced from 561.45 (131.0) µm to 339.25 (72.6) µm (p < 0.01). Visual improvement and CFT did not differ significantly at follow up (p = 0.583; p= 0.85). Significant reduction of CFT is seen in the IVTA group (p = 0.048). CONCLUSIONS: Visual acuity and macular morphology improved after ERM peeling, with or without IVTA. Although conjunctive IVTA did not significantly influence visual outcome at 6 months, a significant decrease in CFT was observed after IVTA administration.

Effects of Intravitreal Aflibercept on Galectin-1 and Vascular Endothelial Growth Factor-A Plasma Levels in Patients with Diabetic Retinopathy.

PURPOSE: To analyze the interaction between aflibercept and galectin-1 and evaluate the plasma levels of galectin-1 and vascular endothelial growth factor (VEGF)-A after intravitreal injection of aflibercept in patients with diabetic retinopathy (DR). METHODS: Interaction of galectin-1 with aflibercept was determined via immunoprecipitation. Seventeen patients with type 2 diabetes and diabetic macular edema (DME) were each treated with a single intravitreal injection of aflibercept (2.0 mg, 50 µL) monthly for three consecutive months. Plasma galectin-1 and VEGF-A levels were measured just before an injection was administered, 1 week after the first injection, and 2 months after the last injection. Nineteen age- and sex-matched healthy participants served as controls. RESULTS: Irrespective of the tested galectin-1 concentration, 24% of added galectin-1 was precipitated by aflibercept. Baseline plasma concentrations of galectin-1 were 22.0 and 23.0 ng/mL in the control and aflibercept-treated groups, respectively. Systemic galectin-1 levels increased to 27.0 and 24.0 ng/mL at 7 days and 4 weeks, respectively, after treatment. At week 8, plasma galectin-1 levels significantly increased to 36.0 ng/mL. This level persisted for 20 weeks. Systemic VEGF-A levels significantly reduced to below the minimum detectable dose in 16 DME patients at 7 days after treatment. This level persisted for 4 weeks. Plasma VEGF-A levels were reduced at weeks 8 (p = 0.099) and 20 (p = 0.023). Decreased plasma VEGF-A levels were observed in all patients after treatment. CONCLUSION: We confirmed that physiological aflibercept levels precipitate galectin-1 in in vitro assays. Additionally, systemic upregulation of galectin-1 might be induced by intravitreal aflibercept, which may be relevant in the clinical outcomes of DR treatment.

[Diagnosis, treatment and monitoring of diabetic eye control]. / Diagnose, Therapie und Verlaufskontrolle der diabetischen Augenerkrankung.

Diabetes mellitus can cause diabetic retinopathy, diabetic macular edema, optic neuropathy, cataract or dysfunction of the eye muscles. The incidence of these defects correlates with disease duration and quality of metabolic control. Recommendations of the Austrian Diabetes Association for diagnosis, therapeutic procedures and requirements for adequate follow up depending on stage of diabetic eye disease are summarized.

Systemic counterregulatory response of placental growth factor levels to intravitreal aflibercept therapy.

PURPOSE: Placental growth factor (PlGF) has been implicated as a contributor to resistance against anti-VEGF therapy. The purpose of the present study was to analyze the systemic levels of PlGF, VEGF-A, and VEGF-B in patients with neovascular age-related macular degeneration (AMD) after treatment with aflibercept, ranibizumab, or bevacizumab. METHODS: Totals of 19 patients were treated with intravitreal aflibercept, 19 with ranibizumab, and 18 with bevacizumab. The cytokine levels were measured by ELISA just before the injection, and 7 days and 1 month thereafter. Age- and sex-matched participants (n = 22) served as controls. RESULTS: The median PlGF plasma concentration at baseline was <12.0 pg/mL in the control group as well as in all three anti-VEGF treatment cohorts. After intravitreal aflibercept injection, a significant upregulation of systemic PlGF could be observed in all treated patients (38.0 [31.0-44.0] pg/mL after 1 week [P < 0.001] and 16.0 [0.0-19.0] pg/mL [P = 0.005] after 4 weeks). No significant effects on plasma PlGF concentrations could be detected in those treated with ranibizumab and bevacizumab. The systemic VEGF-A levels were significantly reduced 1 and 4 weeks after intravitreal aflibercept (P < 0.001, P < 0.001) and bevacizumab (P < 0.001, P < 0.01) injections. No significant effects on plasma cytokine concentrations could be observed in the ranibizumab cohort. No significant effects on systemic VEGF-B could be observed in any of the treatment groups. CONCLUSIONS: In this study, we report a significant systemic upregulation of the proangiogenic cytokine PlGF after intravitreal administration of aflibercept. This might represent a counter-regulatory response to antiangiogenic therapy.

Systemic levels of vascular endothelial growth factor before and after intravitreal injection of aflibercept or ranibizumab in patients with age-related macular degeneration: a randomised, prospective trial.

PURPOSE: To evaluate the changes of vascular endothelial growth factor (VEGF) plasma levels after intravitreal injections of aflibercept or ranibizumab in patients with exudative age-related macular degeneration (AMD). METHODS: Thirty-eight patients with exudative AMD were included in this randomised, prospective study. Nineteen patients were randomised to treatment with intravitreal aflibercept (2.0 mg) and 19 to intravitreal ranibizumab (0.5 mg). The concentration of VEGF was measured by ELISA just before the injection, after 7 days and 1 month. Twenty-two age- and sex-matched healthy patients without chorioretinal diseases served as control. RESULTS: The median baseline plasma VEGF concentration was 61.0 pg/ml in the control group, 43.0 pg/ml in the aflibercept group and 59.0 pg/ml in the ranibizumab group (p=0.127). Seven days after intravitreal injection of aflibercept plasma levels were significantly reduced to values below the minimum detectable dose (MDD) in 17 of 19 patients (89.5%) resulting in a median VEGF concentration of <9 pg/ml (p<0.001). The reduction persisted throughout 1 month with values below the MDD in 5 of 19 patients (26.3%) and a median measurement of 17.0 pg/ml (p<0.001). In patients treated with ranibizumab no significant effects could be observed with a baseline VEGF of 59.0 pg/ml, 54.0 pg/ml at 7 days (p=0.776) and 58.5 pg/ml at 4 weeks of follow-up (p=0.670). CONCLUSION: After intravitreal aflibercept injection, the systemic VEGF levels were significantly reduced throughout the observational period of 4 weeks. No significant systemic effects of intravitreal ranibizumab on plasma VEGF were observed.

Systemic upregulation of PDGF-B in patients with neovascular AMD.

PURPOSE: To determine the plasma levels of platelet-derived growth factor-B (PDGF-B), VEGF, and TNF-α in patients with neovascular AMD and in patients with diabetic macular edema (DME). METHODS: Thirty patients with neovascular AMD, 30 patients with DME, and 12 healthy controls were included in this prospective study. The concentrations of PDGF-B, VEGF, and TNF-α were measured by ELISA. RESULTS: The PDGF-B concentration in the plasma of controls was (median [25th-75th percentile]) 263.5 (162.0-513.3) pg/mL and in patients with DME 219.0 (122.8-604.8) pg/mL. In patients with neovascular AMD, PDGF-B levels were significantly higher with a median plasma concentration of 783.5 (289.3-1183.5) pg/mL (P = 0.003). The VEGF concentrations in patients with DME 33.0 (21.8-73.0) pg/mL and in patients with neovascular AMD 55.0 (37.0-116.3) pg/mL showed no significant differences (P = 0.159). A positive correlation of PDGF-B and VEGF plasma levels was found in patients with neovascular AMD and in patients with DME (r = 0.683, P < 0.001, and r = 0.612, P < 0.001, respectively). No significant differences of systemic TNF-α levels could be found between the three study groups. CONCLUSIONS: Patients with neovascular AMD have significantly higher plasma PDGF-B levels compared with patients with DME and healthy controls. Our study data indicate that PDGF-B may be involved in the pathogenesis of neovascular AMD. (https://eudract.ema.europa.eu number, EudraCT 2010-024654-11)

Reduced-fluence photodynamic therapy combined with ranibizumab for nonproliferative macular telangiectasia type 2.

PURPOSE: To report the efficacy of reduced-fluence photodynamic therapy (PDT) combined with intravitreal ranibizumab for the treatment of nonproliferative macular telangiectasia (MacTel) type 2. METHODS: Noncomparative, interventional, retrospective case series; 5 eyes of 4 patients were studied. Patients were treated with reduced-fluence PDT and intravitreal ranibizumab within 24 h. After initial treatment, follow-up was at least 12 months in all patients. RESULTS: At baseline median logMAR (logarithm of the minimal angle of resolution) best-corrected visual acuity (BCVA) was 1.0 (range, 1.0-0.3). At 3 months of follow-up vision increased in 3 out of 5 eyes and median BCVA was 0.4 (range, 1.0-0.2). The gain of BCVA ranged from 6 lines to 1 line. Visual acuity remained stable in the other 2 study eyes. No eyes lost vision at 3 months of follow-up. At 12 months of follow-up median logMAR BCVA was 0.7 (range, 1.3-0.3). Two eyes had maintained their gain in BCVA compared to baseline. Two eyes lost vision compared to baseline and 1 eye showed unchanged visual acuity at 12 months of follow-up. CONCLUSION: A combination therapy with reduced-fluence PDT and intravitreal ranibizumab might be a valuable treatment option for eyes with progressive vision loss due to nonproliferative MacTel type 2.

Correlation of vascular endothelial growth factor plasma levels and glycemic control in patients with diabetic retinopathy.

PURPOSE: To determine whether glycemic control of patients with diabetic retinopathy (DR) due to type 2 diabetes was related to VEGF plasma levels. METHODS: The prospective study included 30 patients with DR due to type 2 diabetes. Retinopathy was classified according to the international clinical DR disease severity scale. The concentrations of VEGF in the blood plasma were measured by ELISA. Glycosylated hemoglobin (HbA1c) was assessed all patients. Results were reported as DCCT/NGSP-HbA1c (%) values. RESULTS: The median plasma level of VEGF was 34.5 (range 15-217) pg/ml. Median HbA1c was 7.5 (range 5.3-10.6). The highest individual plasma VEGF measurements were found in patients with severe non-proliferative DR. HbA1c levels revealed a significant correlation with plasma VEGF concentrations (r = 0.573, p = 0.001). Age (r = 0.097, p = 0.611), gender (r = -0.315, p = 0.09) and severity of DR (r = 0.256, p = 0.172) were with no significant relationship to the VEGF measurements. CONCLUSION: Poor glycemic control is positively correlated with increased levels of plasma VEGF in patients with type 2 diabetes. As normalization of HbA1c is one of the most effective ways to prevent progression of DR and VEGF has been to shown to be clearly implicated in the development of DR, it affirms the importance of glycemic control in patients with DR.

Plasma levels of vascular endothelial growth factor before and after intravitreal injection of bevacizumab, ranibizumab and pegaptanib in patients with age-related macular degeneration, and in patients with diabetic macular oedema.

AIMS: To determine the level of vascular endothelial growth factor (VEGF) in the plasma of patients with diabetic macular edema (DME) and of patients with exudative age-related macular degeneration (ARMD) before and after intravitreal injection of bevacizumab, ranibizumab or pegaptanib. METHODS: 30 patients with DME and 30 patients with ARMD were included in this randomized controlled study. Patients were randomized to treatment with ranibizumab (0.5 mg), bevacizumab (1.25 mg) or pegaptanib (0.3 mg). 10 patients with DME received bevacizumab, 10 ranibizumab and 10 pegaptanib. The same randomized treatment allocation applied to the 30 patients with ARMD. The concentrations of VEGF were measured by ELISA just before the injection, after 7 days and 1 month. RESULTS: Plasma VEGF in patients with exudative ARMD before the injection of bevacizumab was 89.7 pg/ml. It was significantly reduced to 25.1 pg/ml after 7 days (p=0.01), and to 22.8 pg/ml after 1 month (p=0.008). In patients with DME the same systemic reduction by bevacizumab was observed with a significant decrease of baseline VEGF level from 72.2 pg/ml to 13.7 pg/ml after 7 days (p=0.008) and 17.1 pg/ml at 4 weeks with (p=0.012). No significant reductions of plasma VEGF levels were observed in patients receiving ranibizumab or pegaptanib during follow-up. CONCLUSIONS: Bevacizumab significantly reduces the level of VEGF in the blood plasma for up to one month in patients with DME as well as in those with ARMD. No significant systemic effects of intravitreal ranibizumab or pegaptanib on plasma VEGF could be observed.