Publisher Correction: TGF-ß concentrations and activity are down-regulated in the aqueous humor of patients with neovascular age-related macular degeneration.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

TGF-ß concentrations and activity are down-regulated in the aqueous humor of patients with neovascular age-related macular degeneration.

Controversy still exists regarding the role of the TGF-ß in neovascular age-related macular degeneration (nAMD), a major cause of severe visual loss in the elderly in developed countries. Here, we measured the concentrations of active TGF-ß1, TGF-ß2, and TGF-ß3 by ELISA in the aqueous humor of 20 patients affected by nAMD, who received 3 consecutive monthly intravitreal injections of anti-VEGF-A antibody. Samples were collected at baseline (before the first injection), month 1 (before the second injection), and month 2 (before the third injection). The same samples were used in a luciferase-based reporter assay to test the TGF-ß pathway activation. Active TGF-ß1 concentrations in the aqueous humor were below the minimum detectable dose. Active TGF-ß2 concentrations were significantly lower at baseline and at month 1, compared to controls. No significant differences in active TGF-ß3 concentration were found among the sample groups. Moreover, TGF-ß pathway activation was significantly lower at baseline compared to controls. Our data corroborate an anti-angiogenic role for TGF-ß2 in nAMD. This should be considered from the perspective of a therapy using TGF-ß inhibitors.

HTRA1 and TGF-ß1 Concentrations in the Aqueous Humor of Patients With Neovascular Age-Related Macular Degeneration.

Purpose: The purpose of this study was to evaluate the expression of high-temperature requirement A serine peptidase 1 (HTRA1), TGF-ß1, bone morphogenetic protein 4 (BMP4), growth differentiation factor 6 (GDF6), and VEGFA proteins in the aqueous humor of patients with naïve choroidal neovascularization (nCNV) secondary to AMD. Methods: We measured by ELISA the concentrations of HTRA1, TGF-ß1, BMP4, GDF6, and VEGFA in the aqueous humor of 23 patients affected by nCNV who received three consecutive monthly intravitreal injections of 0.5 mg ranibizumab. Samples were collected at baseline (before the first injection), month 1 (before the second injection), and month 2 (before the third injection). Twenty-three age-matched cataract patients served as controls. Results: Bone morphogenetic protein 4 and GDF6 were not detectable in any samples. Baseline HTRA1 was higher than controls (P < 0.0001) and higher than both the month 1 (P < 0.0001) and the month 2 (P < 0.0001) values. Baseline VEGFA was higher than controls (P < 0.0001), not different from month 1 value (P = 0.0821), but higher than month 2 value (P < 0.0001). Baseline TGF-ß1 was higher than controls (P = 0.0015) and not different from month 1 (P = 0.129) and month 2 values (P = 0.5529). No correlation was found in naïve patients between concentrations of HTRA1 and TGF-ß1, HTRA 1 and VEGFA, or TGF-ß1 and VEGFA. Conclusions: In nCNV patients, HTRA1 and TGF-ß1 were significantly higher compared to controls. After treatment, TGF-ß1 was persistently elevated, while HTRA1 returned to control levels, suggesting the involvement of TGF-ß1 and HTRA1 in neovascular AMD and a VEGFA-independent role for TGF-ß1.

CD93 as a Potential Target in Neovascular Age-Related Macular Degeneration.

In patients with age-related macular degeneration (AMD), choroidal neovascularization is the major cause of severe visual loss. In these patients, the persistence of neovascular growth despite vascular endothelial growth factor-A blockage needs the discovery of new endothelial cell targets. The glycoprotein CD93, highly expressed in activated endothelial cells, has been recently involved in the regulation of the angiogenic process both as transmembrane and soluble protein. Choroidal neovascular membranes from patients affected by AMD were examined by immunofluorescence using anti-CD93 and anti-von Willebrand factor antibodies. Blood vessels within intraocular and extraocular neoplasias were used as controls for CD93 expression. All choroidal neovascular membranes displayed strong CD93 staining in the von Willebrand factor-positive endothelial cells, consistently with the analyses showing a high colocalization coefficient in the blood vessels. Intraocular and extraocular tumor vessels showed similar results, whereas the normal choroid displayed blood vessels with only faint CD93 staining. Additionally, the concentration of soluble CD93 was determined in the aqueous humor of patients affected by naïve neovascular AMD by enzyme-linked immunosorbent assays. Age-matched cataract patients served as controls. Soluble CD93 was significantly increased in the aqueous humor of naïve neovascular AMD patients and tended to decrease after treatment with an antiangiogenic drug. In conclusion, both transmembrane and soluble CD93 are overexpressed in patients with neovascular AMD, indicating that CD93 may represent a potential new antiangiogenic target in the treatment of choroidal neovascularization. J. Cell. Physiol. 232: 1767-1773, 2017. © 2016 Wiley Periodicals, Inc.

The Incidence of Rhegmatogenous Retinal Complications in Macular Surgery After Prophylactic Preoperative Laser Retinopexy: A Retrospective Study.

The aim of the study is to evaluate the clinical characteristics of intraoperative retinal breaks (RBs) and postoperative retinal detachment (RRD) in patients undergoing pars plana vitrectomy (PPV) for macular disorders, who were treated preoperatively with prophylactic peripheral laser retinopexy.This observational cohort study comprised of 254 patients who underwent macular surgery and were preoperatively subjected to prophylactic laser retinopexy anterior to the equator. The main outcome measures were the incidence and characteristics of intraoperative RBs and postoperative RRD.Intraoperative RBs occurred in 14 patients (5.5%). Ten patients presented a sclerotomy-related RB (3.9%) and 4 patients a nonsclerotomy-related RB (1.6%). Two patients showed postoperative RRD (0.7%). Neither of the 2 patients with postoperative RRD was macula-off at presentation: one of them was successfully operated on with scleral buckling and the other was managed by observation alone. A significantly increased risk for the intraoperative development of sclerotomy-related RB was found in 20-gauge PPV compared with 23/25-gauge PPV.Preoperative prophylactic peripheral laser retinopexy does not guarantee the prevention of intraopertaive RBs or postoperative RRD. However, it might prevent the involvement of the macula when RRD occurs postoperatively.

Forty-two-month outcome of intravitreal bevacizumab in myopic choroidal neovascularization.

PURPOSE: To evaluate the long-term efficacy of bevacizumab in the treatment of choroidal neovascularization (CNV) secondary to pathological myopia. METHODS: In this retrospective single-center non-comparative study the medical records of 29 eyes from 29 patients with naïve CNV secondary to high myopia and at least 42 months of follow up were reviewed. All eyes received a loading dose of one intravitreal injection per month for two consecutive months and were retreated on an as-needed basis during the course of follow up. The main outcome measures were post-treatment ETDRS best-corrected visual acuity (BCVA) and visual stabilization over time. Stepwise linear regression analysis was performed to identify prognostic factors for visual acuity gain and final visual acuity outcome at 42 months. RESULTS: At 42 months of follow-up bevacizumab was associated with the maintenance of significant benefits in visual acuity compared to baseline. No adverse ocular or systemic effects from treatment were encountered. No statistically significant correlations were found between BCVA change and any of the quantitative variables. However, when final BCVA was taken as a dependent variable and CNV size and pre-treatment VA were included as predictors, a bivariate model was identified by stepwise regression which gave a 75 % of explained variance. CONCLUSIONS: Bevacizumab treatment was found to be efficacious in the treatment of myopic CNV, resulting in stable gains in visual acuity lasting at least 42 months, without any adverse ocular or general events. Myopic CNV size was identified as a significant prognostic factor.

Treatment of macular edema because of occlusive vasculitis with bevacizumab (avastin): efficacy of three consecutive monthly injections.

PURPOSE: To report the efficacy of intravitreal bevacizumab, administered in a series of three monthly injections followed by a period of observation, in the treatment of cystoid macular edema because of occlusive vasculitis. METHODS: This is a retrospective review of 13 consecutive eyes of 13 patients with cystoid macular edema because of occlusive vasculitis, which had been unresponsive to other medications and were treated with intravitreal bevacizumab (1.25 mg). The evaluation consisted of a complete ophthalmologic examination, including best-corrected visual acuity measurement, ophthalmoscopy, fluorescein angiography, and optical coherence tomography. The eyes received a series of 3 monthly injections followed by a 3-month observation period. RESULTS: A significant improvement in foveal thickness and visual acuity was obtained after the first injection, which increased after the second and the third injections and was maintained for 1.5 months after the last injection. The 2 parameters returned to the baseline values 3 months after the last treatment. There were no ocular or systemic adverse effects. CONCLUSION: Intravitreal injection of bevacizumab seems to be well tolerated and is associated with short-term improvement of visual acuity and decreased retinal thickness in patients with cystoid macular edema because of vasculitis that is resistant to conventional therapy.

Rifabutin corneal deposits in a patient with acquired immunodeficiency syndrome: in vivo confocal microscopy investigation.

PURPOSE: To establish the real localization of rifabutin-related corneal deposits in a patient with human immunodeficiency virus (HIV) infection by in vivo HRT II confocal microscopy with related clinicopathologic implications. METHODS: Observational case report. After Siena University Institutional Review Board approval in May 2008 and specific informed consent, a 54-year-old patient with HIV infection under rifabutin treatment for acquired immunodeficiency syndrome-related Mycobacterium avium complex prevention who developed diffuse corneal deposits was examined at the Department of Ophthalmology of Siena University. He underwent a complete clinical eye examination, biomicroscopy, and digital slit lamp photographs, endothelial specular microscopy, ultrasound pachymetry, and confocal microscopy by HRT II system. RESULTS: Confocal scans revealed the presence of deep stromal and pre descemetic hyperreflective polymorphous deposits. In vivo confocal examination excluded the presence of rifabutin-related deposits at endothelial level. CONCLUSIONS: Confocal microscopy enables establishment of the real localization of rifabutin deposits at deep stromal level, providing a better qualitative analysis of all corneal layers compared to biomicroscopic examination, with clinical and physiopathologic implications.

Fractal analysis of fluoroangiographic patterns in anterior ischaemic optic neuropathy and optic neuritis: a pilot study.

BACKGROUND: To evaluate by means of fractal analysis the vascular pattern of the optic nerve head obtained by fluorescein angiogram, in non-arteritic anterior ischaemic optic neuropathy (NAION) and optic neuritis (ON). METHODS: Twenty-nine patients at the Department of Ophthalmology of the University of Siena, diagnosed as having either NAION or ON by clinical and instrumental criteria, were prospectively subjected to fractal analysis: 11 patients with NAION and 18 patients with ON. In the ON group, 12 patients showed optic disc oedema, whereas six patients showed no optic disc oedema. The unaffected eyes of six patients with NAION and of seven patients with ON associated with optic disc oedema served as controls. RESULTS: The mean fractal dimension D was 1.84 +/- 0.09 in the NAION group, 1.92 +/- 0.04 in the ON group with optic disc oedema, 1.86 +/- 0.04 in the ON group without optic disc oedema and 1.63 +/- 0.06 in the control group; all case groups showed significantly higher values than controls (P < 0.01). Among the case groups, the ON group with optic disc oedema showed a significantly higher mean fractal dimension value than the others (P < 0.01). CONCLUSIONS: Our data suggest that eyes with ON and NAION seem to have increased vascular complexity in the optic nerve head, manifested as an increase in fractal dimension.