Claus Zehetner

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.

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

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).

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.

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.

White Centered Retinal Hemorrhages in Vitamin B12 Deficiency Anemia

Background: To report a case of severe vitamin B12 deficiency anemia presenting with white centered retinal hemorrhages. Methods: Interventional case report. Results: A 40-year-old man, general practitioner himself, presented with a 1-day history of diminished left visual acuity and a drop-shaped central scotoma. The corrected visual acuities were 20/20, OD and 20/100, OS. Ophthalmic examination revealed bilaterally pale tarsal conjunctiva, discretely icteric bulbar conjunctiva and disseminated white centered intraretinal hemorrhages with foveal involvement. OCT imaging through these lesions revealed a retinal thickening caused by a sub-ILM accumulation of hyperreflective and inhomogeneous deposits within the nerve fiber layer. Immediate laboratory work-up showed severe megaloblastic anemia caused by vitamin B12 deficiency requiring erythrocyte transfusions. Discussion: Most reports of white centered retinal hemorrhages have been described in patients with leukemic retinopathy and bacterial endocarditis. It is interesting that this case of vitamin B12 deficiency anemia retinopathy has a clinically indistinguishable fundus appearance. This is probably due to the common pathology of capillary disruption and subsequent hemostatic fibrin plug formation. In megaloblastic anemia, direct anoxia results in endothelial dysfunction. The loss of impermeability allows extrusion of whole blood and subsequent diffusion from the disrupted site throughout and above the nerve fiber layer. Therefore the biomicroscopic pattern of white centered hemorrhages observed in anemic retinopathy is most likely due to the clot formation as the reparative sequence after capillary rupture.

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)

[Comparison of IOL-Master 500 vs. Lenstar LS900 concerning the calculation of target refraction: A retrospective analysis].

BACKGROUND The choice of a suitable intraocular lens (IOL) and the calculation of postoperative refractive error is one of the most intriguing challenges of modern cataract surgery. This clinical trial compared the accuracy of two laser-assisted optical biometers, the IOL-Master 500 (Carl Zeiss Meditec, Jena, Germany) and the Lenstar LS900 (Haag-Streit, Bern, Switzerland) without taking the postoperative results into consideration. MATERIAL AND METHODS Artificial lenses (Alcon Pharma) for 114 eyes of 67 patients were measured using both biometric instruments. The deviation of the presumed refractive error from the desired preoperative refractive target was calculated with different formulae (i.e. SRK/T, HofferQ, Haigis and SRKII) based on the intraoperatively chosen IOL. The differences between both instruments were compared using Students t-test. RESULTS Using the SRKII formula a mean difference between the IOL-Master and the Lenstar of 0.07 D (p = 0.002) was calculated for 95 eyes, SRK/T used on 47 eyes showed a difference of 0.04 D (p = 0.27), HofferQ measured 0.09 D (p = 0.0001) between both instruments for 88 eyes and the Haigis formula also showed a mean difference of 0.09 D (p = 0.001) based on the calculations of 106 eyes. CONCLUSION Both instruments gave reproducible and accurate results with only a small deviation from the desired target refraction and can therefore be considered as comparable for the calculation of IOLs. Statistically significant differences in the results were found when using the SRKII, HofferQ and Haigis formulae but these were too low to have any influence on the choice of IOL to be implanted.

Clinical and Echographic Features of Retinochoroidal and Optic Nerve Colobomas

PURPOSE We reported the clinical and echographic features of colobomas, prevalence of retinal detachment, and associated visual acuity in these patients. METHODS The study is a nonrandomized consecutive case series of 140 colobomatous eyes in 98 patients (age range, 0-83 years). Coloboma depth, width, volume, and relative coloboma excavation (coloboma depth/axial length) were measured using standardized echographic images. The presence of structural and other ocular abnormalities was noted. The clinical and echographic findings present were correlated with visual acuity of the patient. In addition, these features were correlated with the presence or absence of retinal detachment. RESULTS Increased relative coloboma excavation was significantly associated with an increased risk of retinal detachment. A relative coloboma excavation (ratio of coloboma depth to axial length) greater than 0.15 was associated with an increased risk of retinal detachment (52%), compared to those with a relative coloboma excavation less than 0.15 (23%, P = 0.014). The presence of any structural abnormality and the presence of a retrobulbar cyst were associated with increased risk of retinal detachment and severe visual impairment (worse than 20/200). Increased coloboma depth, width, volume, and relative coloboma excavation were not associated with increased risk of severe visual impairment. CONCLUSIONS Clinical and echographic features of colobomas may be used in predicting the risk of retinal detachment. Measuring relative coloboma excavation upon presentation may alter follow-up and assist in the diagnosis of retinal detachment.

Vergleich IOL-Master 500 vs. Lenstar LS900 hinsichtlich der Berechnung der Zielrefraktion

BACKGROUND The choice of a suitable intraocular lens (IOL) and the calculation of postoperative refractive error is one of the most intriguing challenges of modern cataract surgery. This clinical trial compared the accuracy of two laser-assisted optical biometers, the IOL-Master 500 (Carl Zeiss Meditec, Jena, Germany) and the Lenstar LS900 (Haag-Streit, Bern, Switzerland) without taking the postoperative results into consideration. MATERIAL AND METHODS Artificial lenses (Alcon Pharma) for 114 eyes of 67 patients were measured using both biometric instruments. The deviation of the presumed refractive error from the desired preoperative refractive target was calculated with different formulae (i.e. SRK/T, HofferQ, Haigis and SRKII) based on the intraoperatively chosen IOL. The differences between both instruments were compared using Students t-test. RESULTS Using the SRKII formula a mean difference between the IOL-Master and the Lenstar of 0.07 D (p = 0.002) was calculated for 95 eyes, SRK/T used on 47 eyes showed a difference of 0.04 D (p = 0.27), HofferQ measured 0.09 D (p = 0.0001) between both instruments for 88 eyes and the Haigis formula also showed a mean difference of 0.09 D (p = 0.001) based on the calculations of 106 eyes. CONCLUSION Both instruments gave reproducible and accurate results with only a small deviation from the desired target refraction and can therefore be considered as comparable for the calculation of IOLs. Statistically significant differences in the results were found when using the SRKII, HofferQ and Haigis formulae but these were too low to have any influence on the choice of IOL to be implanted.

Unklarer Aderhauttumor mit Blutungen

Eine 65-jährige Patientin wird zur weiterenAbklärungbeibestehendemVerdacht auf ein Aderhautmelanom vom niedergelassenen Augenfacharzt vorgestellt. In der Anamnese beschreibt die Patientin eine zunehmendeVisusverschlechterung und Metamorphopsien am rechten Auge. Die Symptome sind vor 4 Wochen plötzlich aufgetreten.Vor 2 Jahrenwurde eine Kataraktoperation an beiden Augen durchgeführt, ansonsten sind die ophthalmologische und internistische Anamnese unauffällig.