Rodolfo Mastropasqua

Reproducibility and repeatability of foveal avascular zone measurements in healthy subjects by optical coherence tomography angiography

Background/aims To assess the reproducibility and repeatability of foveal avascular zone (FAZ) area measurements using optical coherence tomography angiography (OCT-A) in healthy subjects. Methods Sixty healthy volunteers (60 eyes) were subjected to FAZ area measurements by means of high speed and high resolution spectral-domain OCT (SD-OCT) XR Avanti with the split-spectrum amplitude decorrelation angiography algorithm by two experienced examiners in two different sessions. Results The mean±SD age of the subjects was 28.9±7.6 years. Overall FAZ areas measured by the first and second observer were 0.251±0.096 mm2 and 0.252±0.096 mm2, respectively. Within subjects, the coefficients of variations were 1.83% (95% CI 1.51% to 2.20%) and 1.86% (95% CI 1.33% to 2.43%) for the first and second observers, respectively. The coefficient of repeatability average measurements of FAZ area were 0.015 mm2 and 0.013 mm2 for the first and second observers, respectively. The intraclass correlation coefficient values were 0.997 (95% CI 0.995 to 0.998) and 0.998 (95% CI 0.996 to 0.999) for the first and second observers, respectively. Inter- and intraobserver concordance correlation coefficients ranged from 0.994 (95% CI 0.990 to 0.977) to 0.999 (95% CI 0.997 to 0.999) and from 0.997 (95% CI 0.995 to 0.998) to 0.996 (95% CI 0.994 to 0.998), respectively. Conclusions FAZ area measurements by means of OCT-A showed excellent reproducibility and repeatability in healthy eyes. OCT-A is a non-invasive diagnostic method, and its reliability makes it an interesting potential diagnostic tool for disease detection and follow-up in retinal pathologies involving foveal microcirculation.

Corneal cross-linking: intrastromal riboflavin concentration in iontophoresis-assisted imbibition versus traditional and transepithelial techniques.

PURPOSE To determine differences in riboflavin concentration in the anterior, intermediate, and posterior stroma after 3 corneal cross-linking imbibition techniques (standard epithelial [epi]-off, epi-on, and iontophoresis-assisted administration) of 0.1% riboflavin. DESIGN Experimental laboratory investigation of human cadaver corneas not suitable for transplantation. METHODS Ten corneas underwent imbibition with epi-on (n = 3), epi-off (n = 3), iontophoresis (n = 3), and saline exposure (control; n = 1). Femtosecond laser was used to produce 3 8-mm discs of the superficial (0-150 μm), intermediate (150-300 μm), and deep stroma (>300 μm). Riboflavin concentration was measured with high-performance liquid chromatography. The main outcome measure was riboflavin concentration at the 3 evaluated depths. RESULTS The overall stromal concentration of riboflavin was 34.1 ± 7.1 μg/g in epi-off, 7.2 ± 3.7 μg/g in epi-on, and 15.0 ± 5.1 μg/g in iontophoresis. The mean riboflavin content in the superficial slice in the epi-off group was about 2-fold greater than that of the iontophoresis group (50.5 ± 5.3 μg/g and 23.6 ± 2.5 μg/g, respectively) and 4-fold greater than that of the epi-on group (11.7 ± 3.3 μg/g). Similar differences among the 3 groups were observed for the intermediate and posterior stromal slices, presenting an evident reduction of riboflavin concentration with increasing depth in all groups. Slice depth-dependent decrease in riboflavin concentration was statistically significant (general linear model (GLM); F1,6 = 62.265, P < .001), as was the group-dependent variation (GLM; F2,6 = 20.268, P = .002) and the slice depth group interaction (GLM; F2,6 = 18.004, P = .002). CONCLUSIONS Corneal cross-linking transepithelial iontophoresis imbibition yielded greater and deeper riboflavin saturation with respect to conventional epi-on, while maintaining the advantages of avoiding epithelial removal and shorter procedure time, but did not reach concentrations obtained with standard epi-off.

Optical Coherence Tomography Angiography in Retinal Vascular Diseases and Choroidal Neovascularization

Purpose. To assess the ability of optical coherence tomography-angiography (OCT-A) to show and analyze retinal vascular patterns and the choroidal neovascularization (CNV) in retinal vascular diseases. Methods. Seven eyes of seven consecutive patients with retinal vascular diseases were examined. Two healthy subjects served as controls. All eyes were scanned with the SD-OCT XR Avanti (Optovue Inc, Fremont CA, USA). Split spectrum amplitude decorrelation angiography algorithm was used to identify the blood flow within the tissue. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) with Spectralis HRA + OCT (Heidelberg Engineering GmbH) were performed. Results. In healthy subjects OCT-A visualized major macular vessels and detailed capillary networks around the foveal avascular zone. Patients were affected with myopic CNV (2 eyes), age-related macular degeneration related (2), branch retinal vein occlusion (BRVO) (2), and branch retinal artery occlusion (BRAO) (1). OCT-A images provided distinct vascular patterns, distinguishing perfused and nonperfused areas in BRVO and BRAO and recognizing the presence, location, and size of CNV. Conclusions. OCT-A provides detailed images of retinal vascular plexuses and quantitative data of pathologic structures. Further studies are warranted to define the role of OCT-A in the assessment of retinovascular diseases, with respect to conventional FA and ICG-A.

Femtosecond laser versus manual clear corneal incision in cataract surgery.

PURPOSE To compare functional and morphological outcomes of femtosecond laser clear corneal incision (CCI) versus manual CCI during cataract surgery. METHODS Sixty eyes of 60 patients who underwent CCI during cataract surgery were randomized into two groups: femtosecond laser CCI (30 eyes) and manual CCI (30 eyes). RESULTS There were no significant between-group differences in uncorrected distance visual acuity, corrected distance visual acuity, surgically induced astigmatism, and corneal aberrations. Keratometric astigmatism was significantly lower in the femtosecond laser CCI group compared to the manual CCI group at 30 and 180 days (P < .05). Central endothelial cell count was significantly higher in the femtosecond laser CCI group compared to the manual CCI group at 7 and 30 days postoperatively (P < .05). A lower increase of corneal thickness at the incision site was observed at 30 and 180 days postoperatively in the femtosecond laser CCI group compared to the manual CCI group (P < .05). In addition, femtosecond laser CCI showed a better morphology (lower percentage of endothelial and epithelial gaping and endothelial misalignment) compared to manual CCI at different time points. Total phacoemulsification time was significantly lower in the femtosecond laser CCI group (P < .05). CONCLUSIONS The femtosecond laser procedure was safe, efficient, and less damaging, as evidenced by lower central endothelial cell loss, lower increase of corneal thickness at the incision site, and better tunnel morphology compared to the manual technique.

Circadian intraocular pressure patterns in healthy subjects, primary open angle and normal tension glaucoma patients with a contact lens sensor

To examine the circadian intraocular pressure (IOP) patterns in healthy subjects, in primary open angle and normal tension glaucoma (POAG; NTG) using a contact lens sensor (CLS; Sensimed Triggerfish, Lausanne, Switzerland).

Role of microRNAs in the modulation of diabetic retinopathy

Diabetic retinopathy (DR) is the leading cause of vision loss in the working-age adults. It affects a third of diabetics. Diabetic macular edema, an advanced complication of DR, develops in nearly 7% of diabetic patients. MicroRNAs (miRNAs) are a novel group of non-coding small RNAs that post-transcriptionally control gene expression by promoting either degradation or translational repression of target messenger RNA. They are implicated in a large variety of physiological and pathophysiological processes, including glucose homeostasis, angiogenesis and modulation of inflammatory response. MiRNAs also play a critical role in the pathogenesis of diabetes and the related micro- and macrovascular complications. The purpose of this review is to describe the potential role of miRNAs in diabetes and evaluate their implication in DR. MiRNAs involved in the modulation of glucose metabolism (insulin secretion and sensitivity) and MiRNAs playing a role in the pathogenesis of DR with their potential target genes are reviewed. Understanding MiRNAs implication in DR could be helpful for developing new gain- or loss- of -function strategies in order to establish effective treatments and reduce the rate of visual disability due to progression of retinopathy.

Systemic thromboembolic adverse events in patients treated with intravitreal anti-VEGF drugs for neovascular age-related macular degeneration

Introduction: The consistent association between choroid neovascularization (CNV) and increased VEGF-A expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of neovascular age-related macular degeneration (AMD). The authors report the systemic side effects secondary to intravitreal administration of these compounds, that is, the main cardiovascular effects, as well as the less frequent cerebrovascular accidents, myocardial infarction, transient ischemic attacks, deep vein thrombosis, pulmonary embolism and thromboflebitis. Areas covered: The authors reviewed major Clinical Trials and publications concerning systemic adverse events of anti-VEGF drugs in order to identify the main thromboembolic events related to the use of these agents and their occurrence. Anti-VEGF efficacy, safety and tolerability are also discussed. Expert opinion: Three compounds (pegaptanib, ranibizumab and aflibercept) have been approved for the treatment of AMD; a fourth agent, bevacizumab, is used off-label. Anti-VEGF therapy has not shown the ability to fully eradicate the CNV, so that recurrences are common when the intravitreal injections are suspended. Although no evident rise in anti-VEGF-induced thromboembolic side effects was reported, more data are required to evaluate hemodynamic and pharmacokinetics of these compounds. Since only few studies have focused on these aspects, further researches are mandatory to determine distribution, effects and duration of these substances.

Morphological modification of the cornea after standard and transepithelial corneal cross-linking as imaged by anterior segment optical coherence tomography and laser scanning in vivo confocal microscopy.

Purpose: In vivo analysis of corneal modifications after traditional and transepithelial corneal cross-linking (CXL). Methods: Forty eyes of 35 patients underwent traditional or transepithelial CXL; there was randomization of 20 eyes to each group. By means of in vivo confocal microscopy and anterior segment ocular coherence tomography, we evaluated corneal alterations at 1 week, 1 month, and 3, 6, and 12 months after the treatment. Results: During follow-up, in vivo confocal microscopy showed a significant decrease in anterior keratocyte density (P = 0.001) and more evident stromal edema and keratocyte activation (P = 0.001) in the traditional group, whereas in the transepithelial group, no significant changes were observed (P > 0.05). Anterior segment ocular coherence tomography indicated the presence of hyperreflective stromal line significantly deeper and more persistent in the traditional group (P < 0.001). Conclusions: The preliminary results suggest that traditional CXL induced marked corneal modifications, which were poorly evident in the transepithelial group.

Conjunctival goblet cells density and preservative-free tafluprost therapy for glaucoma: an in vivo confocal microscopy and impression cytology study

Purpose:  To evaluate the density of conjunctival goblet cells (GCs) in glaucomatous patients treated with preservative‐free (PF) tafluprost, using laser scanning confocal microscopy (LSCM) and impression cytology (IC).

Structural modifications and tissue response after standard epi-off and iontophoretic corneal crosslinking with different irradiation procedures.

PURPOSE The aim of this study is to investigate modifications in human cadaver corneas after different crosslinking procedures, including standard epi-off treatment, iontophoresis imbibition, and different exposure to ultraviolet A (UVA) sources (30 minutes at 3 mW and 9 minutes at 10 mW). METHODS A total of 12 human cadaver corneas was examined and divided as follows: 3 served as control (group 1), 3 were treated with a standard epi-off procedure (group 2), 6 underwent iontophoresis imbibition for 5 minutes, and then 3 were irradiated for 30 minutes with 3 mW UVA (group 3), and 3 for 9 minutes at 10 mW UVA (group 4). Deformation amplitude index was measured before and after the corneas underwent treatment. After treatment, corneas were prepared for hematoxylin-eosin and immunohistochemistry evaluation. The expression of TUNEL, matrix metalloproteinase-1 (MMP-1), collagen type I, and CD34 was investigate in all samples. RESULTS The deformation amplitude index decreased in all groups, in particular in group 4, indicating an improvement of corneal biomechanical properties. Immunohistochemical staining showed a significant stromal alteration in group 2, mild damage in group 3, and no modifications in corneal morphology in group 4. The TUNEL (P < 0.001) and MMP-1 (P = 0.002) positivity was more evident in group 4. Collagen type I positivity significantly increased in groups 3 (P = 0.002) and 4 (P = 0.002). The CD34 expression was more evident in groups 2 (P = 0.003) and 3 (P = 0.003). CONCLUSIONS Iontophoresis imbibition followed by UVA irradiation for 9 minutes at 10 mW determined less tissue damage and better stromal remodeling.