Correction to: pH of anti-VEGF agents in the human vitreous: low impact of very different formulations

Abstract After the publication of this article [1], we were made aware that the osmolarity of aflibercept (Eylea) was incorrect and should have been 286 mOsm and not 1000 mOsm. The correct version of Table 1 is shown in this correction

Overexpression of Neuregulin-1 Type III Has Impact on Visual Function in Mice

Schizophrenia is associated with several brain deficits, including abnormalities in visual processes. Neuregulin-1 (Nrg1) is a family of trophic factors containing an epidermal growth factor (EGF)-like domain. It is thought to play a role in neural development and has been linked to neuropsychiatric disorders. Abnormal Nrg1 expression has been observed in schizophrenia in clinical studies. Moreover, in schizophrenia, there is more and more evidence found about pathological changes of the retina regarding structural, neurochemical and physiological parameters. However, mechanisms of these changes are not well known. To investigate this, we analysed the function of the visual system using electroretinography (ERG) and the measurement of visual evoked potentials (VEP) in transgenic mice overexpressing Nrg1 type III of three different ages (12 weeks, 24 weeks and 55 weeks). ERG amplitudes tended to be higher in transgenic mice than in control mice in 12-week old mice, whereas the amplitudes were almost similar in older mice. VEP amplitudes were larger in transgenic mice at all ages, with significant differences at 12 and 55 weeks (p values between 0.003 and 0.036). Latencies in ERG and VEP measurements did not differ considerably between control mice and transgenic mice at any age. Our data show for the first time that overexpression of Nrg1 type III changed visual function in transgenic mice. Overall, this investigation of visual function in transgenic mice may be helpful to understand corresponding changes that occur in schizophrenia, as they may find use as biomarkers for psychiatric disorders as well as a potential tool for diagnosis in psychiatry

pH of anti-VEGF agents in the human vitreous: low impact of very different formulations

Abstract Background The aim of the study was to measure pH changes of the human vitreous caused by the intravitreal drugs bevacizumab, ranibizumab, aflibercept, and ziv-aflibercept. Methods Fresh human vitreous samples were obtained during core vitrectomy (23-gauge) from patients with epiretinal gliosis. Aliquots of bevacizumab, ranibizumab, aflibercept or ziv-aflibercept (2 µl) were added consecutively to 200 µl of vitreous samples or 0.9% NaCl saline. The pH was measured using a pH-sensitive microelectrode. Rituximab, in off-label use against intraocular lymphoma, was tested as an IgG1 antibody. Results The pH of the administered drugs was 5.91 for bevacizumab (95% CI 5.63–6.19), 5.32 for ranibizumab (95% CI 5.0–5.63), 6.05 for aflibercept (95% CI 5.78–6.31), ziv-aflibercept 6.1 (95% CI 6.05–6.15), and 6.29 for rituximab (95% CI 5.97–6.61). While the fresh and undiluted vitreous fluid showed pH values of 7.0–7.4, pH values increased if saline or rituximab were added. In contrast, the pH decreased slightly if aflibercept, bevacizumab, ranibizumab or ziv-aflibercept were supplemented. The observed pH decreases were not significant after ranibizumab was added. Significant changes were only notable with higher-than-normal amounts of bevacizumab (26–40 µl). The vitreous showed the most robust buffering capacity towards ranibizumab and rituximab. Conclusions The pH changes in vitreous samples elicited by the usual intravitreal anti-VEGF drugs differed clearly, but only by much higher concentrations than used in the clinical routine. Although the ingredient solution of ranibizumab showed the lowest pH, it caused only moderate changes of vitreal pH compared to bevacizumab, aflibercept or ziv-aflibercept

Distribution of macular ganglion cell layer thickness in foveal hypoplasia: A new diagnostic criterion for ocular albinism.

Background/aimsTo analyse the distribution of macular ganglion cell layer thickness (GCLT) in patients with foveal hypoplasia (FH) with or without albinism to obtain new insights into visual pathway anomalies in albinos.MethodsPatients with FH who presented at our institution between 2013 and 2018 were retrospectively drawn for analysis. Mean GCLT was calculated after automated segmentation of spectral domain-optical coherence tomography (SD-OCT) scans. Patients with FH due to albinism (n = 13, termed 'albinism FH') or other kinds (n = 10, termed 'non-albinism FH') were compared with control subjects (n = 15). The areas: fovea (central), parafovea (nasal I, temporal I) and perifovea (nasal II, temporal II) along the horizontal meridian were of particular interest. Primary endpoints of this study were the ratios (GCLT-I- and GCLT-II-Quotient) between the GCLT measured in the temporal I or II and nasal I or II areas.ResultsThere was a significant difference between the GCLT-I-Quotient of healthy controls and albinism FH (pConclusionMacular GCLT-distribution showed a characteristic temporal to central shift in patients with FH due to albinism. Calculation of the GCLT-II-Quotient at a cut-off of <0.7169 presents a new diagnostic criterion for identification of ocular albinism

Expression of purinergic receptors on microglia in the animal model of choroidal neovascularisation

Abstract To investigate the effect of P2 receptor on microglia and its inhibitor PPADS on choroidal neovascularization. Forty CX3CR1GFP/+ mice were randomly divided into 8 groups. In addition to the normal group, the rest of groups were receiving laser treatment. The retina and choroid from the second, third, fourth and fifth group of mice were taken in the 1, 4, 7, 14 days after laser treatment. The mice in the sixth and seventh group received intravitreal injection of 2 µl PPADS or PBS respectively immediately after laser treatment. The mice in the eighth group received topical application of PPADS once per day of three days. The mice in sixth, seventh and eighth group received AF and FFA examination on the fourth day after laser treatment. Immunofluorescence histochemical staining and real-time quantitative PCR were used to evaluate P2 expression and its effect on choroidal neovascularization. After laser treatment, activated microglia can express P2 receptors (P2X4, P2X7, P2Y2 and P2Y12). The expression of P2 increased on the first day after laser damage, peaked on the fourth day (tP2X4 = 6.05, tP2X7 = 2.95, tP2Y2 = 3.67, tP2Y12 = 5.98, all P < 0.01), and then decreased. After PPADS inhibition, compared with the PBS injection group, the mRNA of P2X4, P2X7, P2Y2 and P2Y12 were decreased significantly in the PPADS injection group (tP2X4 = 5.54, tP2X7 = 9.82, tP2Y2 = 3.86, tP2Y12 = 7.91, all P < 0.01) and the PPADS topical application group (tP2X4 = 3.24, tP2X7 = 5.89, tP2Y2 = 6.75, tP2Y12 = 4.97, all P < 0.01). Compared with the PBS injection group, not only the activity of microglia cells but also the leakage of CNV decreased significantly (P < 0.01) in the PPADS injection group and the PPADS topical application group. But between two PPADS groups, the leakage of CNV had no difference (P = 0.864). After laser induced CNV, activated microglia can express P2 receptors. The P2 receptor inhibitor, PPADS, can significantly affect the function of microglia and inhibit the formation of choroidal neovascularization

Dexamethasone-Loaded Pseudo-Protein Nanoparticles for Ocular Drug Delivery: Evaluation of Drug Encapsulation Efficiency and Drug Release

Ophthalmic drug delivery for treating various eye diseases still remains a challenge in ophthalmology. One perspective way of overcoming this problem is to use nanoscale biodegradable drug carriers that are able to safely deliver pharmaceuticals directly to the locus of disease and maintain a therapeutic concentration of drug for a long time. The goal of the present study was the preparation of drug- (dexamethasone-, DEX-) loaded pseudo-protein nanoparticles (NPs) and investigation of drug encapsulation efficiency and drug release kinetics. DEX-loaded pseudo-protein NPs (DEX-NPs) were successfully prepared by the nanoprecipitation method. DEX-NPs were characterized by size (average diameter, AD), size distribution (polydispersity index, PDI), and surface charge (zeta-potential, ZP) using the dynamic light scattering technique. DEX encapsulation characteristics were determined using the UV-spectrophotometric method, and kinetics of DEX release from DEX-NPs was studied according to the dialysis method in PBS at 37°C. The obtained results showed that size of DEX-NPs varies within 143.6–164.1 nm depending on DEX content during the preparation. DEX incorporation characteristics were determined—encapsulation efficiency (EE) and actual drug loading (DL) were high enough and reached 55.1 and 10.2%, respectively. The kinetics of DEX release from DEX-NPs showed a typical biphasic release pattern—an initial rapid (burst) release and further much more continuous slow release. Based on the obtained data, we can conclude that the elaborated DEX-NPs have potential for the application in ophthalmology as ocular drug delivery nanocarriers