Elisabetta Nuti

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).

HTRA1 and TGF-β1 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-β1, 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-β1, 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-β1 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-β1, HTRA 1 and VEGFA, or TGF-β1 and VEGFA. Conclusions In nCNV patients, HTRA1 and TGF-β1 were significantly higher compared to controls. After treatment, TGF-β1 was persistently elevated, while HTRA1 returned to control levels, suggesting the involvement of TGF-β1 and HTRA1 in neovascular AMD and a VEGFA-independent role for TGF-β1.

Unilateral corneal endothelial dystrophy and anterior keratoconus

Purpose. To describe a case of keratoconus and Fuchs’ corneal endothelial dystrophy in the left eye with no corneal disease in the right eye. Methods. A 64-year-old woman presented with visual impairment in her left eye; computer-assisted topographic analysis and specular microscopy were performed in both eyes and left cornea was histopathologically examined. Results. Keratoconus was diagnosed by slit-lamp examination, keratometry, and computer-assisted topographic analysis. Corneal endothelial dystrophy was diagnosed on the basis of clinical examination and specular microscopy. Histopathologic examination revealed a stromal degeneration typical of keratoconus and a non-guttae form of endothelial dystrophy. Conclusions. This is a rare case of unilateral corneal endothelial dystrophy and keratoconus.

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.

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.

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

AbstractThe 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.

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.

TGF-β 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-β 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-β1, TGF-β2, and TGF-β3 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-β pathway activation. Active TGF-β1 concentrations in the aqueous humor were below the minimum detectable dose. Active TGF-β2 concentrations were significantly lower at baseline and at month 1, compared to controls. No significant differences in active TGF-β3 concentration were found among the sample groups. Moreover, TGF-β pathway activation was significantly lower at baseline compared to controls. Our data corroborate an anti-angiogenic role for TGF-β2 in nAMD. This should be considered from the perspective of a therapy using TGF-β inhibitors.

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

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Response to the letter to the editor entitled "Forty-two-month outcome of intravitreal bevacizumab in myopic choroidal neovascularization"

Dear Editor, We thank Chew and Tan for their interest in our recent article in Graefes Archive for Clinical and Experimental Ophthalmology [1]. With regard to extrafoveal myopic choroidal neovascularization (mCNV), we agree with Chew and Tan about a continuing role for photodynamic therapy in this patient category [2]. Our population was composed of subfoveal and juxtafoveal mCNV. In our opinion, for such mCNV locations the treatment of choice is anti-VEGF therapy. However, anti-VEGF therapy should be offered paying close attention to the ocular and systemic side-effects, bearing in mind that the clinical trials for anti-VEGF were not focused primarily on safety [3]. A limitation of our study was the lack of evaluation of any OCTchanges [1].We agree with Chew and Tan that important additional information could have been provided by such an evaluation. For this reason, in successive patients we decided, as suggested by Chew and Tan, to perform the analysis of CMT differences after adding 60 μm to the CMT values measured by the Stratus OCT [4]. Swept-source OCT could certainly add to our Banatomical knowledge^ [5]. Acknowledgments None of the authors have a proprietary interest.