Pulsed Light Accelerated Crosslinking versus Continuous Light Accelerated Crosslinking: One-Year Results

Purpose. To compare functional results in two cohorts of patients undergoing epithelium-off pulsed (pl-ACXL) and continuous light accelerated corneal collagen crosslinking (cl-ACXL) with dextran-free riboflavin solution and high-fluence ultraviolet A irradiation. Design. It is a prospective, comparative, and interventional clinical study. Methods. 20 patients affected by progressive keratoconus were enrolled in the study. 10 eyes of 10 patients underwent an epithelium-off pl-ACXL by the KXL UV-A source (Avedro Inc., Waltham, MS, USA) with 8 minutes (1 sec. on/1 sec. off) of UV-A exposure at 30 mW/cm2 and energy dose of 7.2 J/cm2; 10 eyes of 10 patients underwent an epithelium-off cl-ACXL at 30 mW/cm2 for 4 minutes. Riboflavin 0.1% dextran-free solution was used for a 10-minutes corneal soaking. Patients underwent clinical examination of uncorrected distance visual acuity and corrected distance visual acuity (UDVA and CDVA), corneal topography and aberrometry (CSO EyeTop, Florence, Italy), corneal OCT optical pachymetry (Cirrus OCT, Zeiss Meditec, Jena, Germany), endothelial cells count (I-Conan Non Co Robot), and in vivo scanning laser confocal microscopy (Heidelberg, Germany) at 1, 3, 6, and 12 months of follow-up. Results. Functional results one year after cl-ACXL and pl-ACXL demonstrated keratoconus stability in both groups. Functional outcomes were found to be better in epithelium-off pulsed light accelerated treatment together with showing a deeper stromal penetration. No endothelial damage was recorded during the follow-up in both groups. Conclusions. The study confirmed that oxygen represents the main driver of collagen crosslinking reaction. Pulsed light treatment optimized intraoperative oxygen availability improving postoperative functional outcomes compared with continuous light treatment

Accelerated Corneal Collagen Cross-Linking Using Topography-Guided UV-A Energy Emission: Preliminary Clinical and Morphological Outcomes

Purpose. To assess the clinical and morphological outcomes of topography-guided accelerated corneal cross-linking. Design. Retrospective case series. Methods. 21 eyes of 20 patients with progressive keratoconus were enrolled. All patients underwent accelerated cross-linking using an ultraviolet-A (UVA) exposure with an energy release varying from 7.2 J/cm2 up to 15 J/cm2, according to the topographic corneal curvature. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, topography, in vivo confocal microscopy (IVCM), and anterior segment optic coherence tomography (AS-OCT) were evaluated preoperatively and at the 1, 3, 6, and 12 months postoperatively. Results. 12 months after surgery UDVA and CDVA did not significantly vary from preoperative values. The average topographic astigmatism decreased from -4.61±0.74 diopters (D) to -3.20±0.81 D and coma aberration improved from 0.95 ± 0.03 μm to 0.88 ± 0.04 μm after surgery. AS-OCT and IVCM documented differential effects on the treated areas using different energies doses. The depths of demarcation line and keratocyte apoptosis were assessed. Conclusions. Preliminary results show correspondence between the energy dose applied and the microstructural stromal changes induced by the cross-linking at various depths in different areas of treated cornea. One year after surgery a significant reduction in the topographic astigmatism and comatic aberration was detected. None of the patients developed significant complications

HTRA1 and TGF-β1 concentrations in the aqueous humor of patients with neovascular age-related macular degeneration

PURPOSE: To evaluate the expression of high-temperature requirement A serine peptidase 1 (HTRA1), transforming growth factor beta 1 (TGF-β1), bone morphogenetic protein 4 (BMP4), growth differentiation factor 6 (GDF6), and vascular endothelial growth factor A (VEGFA) proteins in the aqueous humor of patients with naïve choroidal neovascularization (nCNV) secondary to age-related macular degeneration. 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 3 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). 23 age-matched cataract patients served as controls. RESULTS: BMP4 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 nAMD and a VEGFA-independent role for TGF-β1

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

Barbe Bleue

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library

Barbe Bleue

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library

Fractal Analysis in Neuro-ophthalmology

Fractal analysis has been proven useful in diagnosis and prognosis of the patient in several neuro-ophthalmological disorders. In our experience, entropy was able to differentiate optic neuritis and nonarteritic anterior ischemic optic neuropathy and geometric complexity to objectively quantize the alteration of corneal innervation in Sjogren’s syndrome patients

Mass Dimension Evaluation of the Optic Nerve Head Microvascularity in Non-Glaucomatous Optic Neuropathies

In several diseases, fractal analysis has been proven useful to give contribution in diagnosis and prognosis of the patient and to improve treatments. In the present work we have evaluated the mass dimension of the vascular pattern of optic nerve head in non-glaucomatous optic neuropathic patients and healthy controls. Static fluorescein angiogram was performed and the images of the early venous phase were saved. A manual outline of the trajectories of the two-dimensional vascular network was performed down to vessels of 20 um diameter, processed to threshold the vessel network without background interference and converted into an outline of single pixels and then the fractal analysis was performed-Mass dimension evaluation of the optic nerve head microvascularity was able to differentiate health condition vs. non-glaucomatous neuropathies (p&lt;0.01), as well optic neuritis vs. nonarteritic anterior ischemic optic neuropathy (p&lt;0.01), with high sensitivity and specificity (p&lt;0.0001; p&lt;0.0001). Mass dimension index shows a significantly increased vascular complexity of the optic nerve head in cases compared with controls, also permitting to distinguish between patients affected by optic neuritis vs. nonarteritic anterior ischemic optic neuropathy. This new, fast, unexpensive, methodology may be used in helping the clinician to perform the differential diagnosis between the pathologies and to study the effect of therapies during the follow up of the patient.</p

Decreased Geometric Complexity of Corneal Nerve Fibers Distribution in Sjogren’s syndrome Patients

Objective: Dry eye affects many individuals worldwide and a significant portion of patient with dry eye present the Sjogren’s syndrome (SS), a progressive, autoimmune condition. In order to choose and follow the best therapy it’s necessary to have noninvasive quantitative methods able to characterize the status of the corneal nerve fibers of the patients. Methods: Local fractal dimension by box-counting (evaluation of geometric complexity) of the nerve corneal fibers distribution observed by confocal microscopy was performed in patients with primary SS (n=36: 6 males, 30 females, 21- 81 years), diagnosed by biopsy of salivary gland and blood tests and in sex- age-matched healthy subjects (n=12). In selected patients salivary glands atrophy degree was also evaluated. Results: Fractal analysis reveals that the nerve corneal distribution is fractal. In healthy subjects the fractal dimension of the corneal nerve distribution is close to the value of the Diffusion Limited Aggregation Process, a typical value of geometric complexity in normal individuals. Geometric complexity statistically distinguishes between Sjogren’s syndrome patients and healthy subjects: patients present a lower value of geometric complexity of the corneal nerve fibers distribution than healthy individuals (p<0.001). The percentage of grouped cases classified by geometric complexity (D cut-off =1.40) according to the subjects (SS patients vs healthy) showed a 100% ratio between the number of correctly classified cases and all cases, p<0.001. The nonlinear index correlates with salivary glands atrophy degree (p<0.01). Conclusions: Fractal analysis of the cornea observed by a laser confocal microscopy appears able to quantitatively and nonivasively characterize the SS patient in relation to the recognition of an impairment of the ocular surface. The analysis is inexpensive and not time-consuming, of relevance in order to choose the best therapy