Cytidine 5'-Diphosphocholine (Citicoline): Evidence for a Neuroprotective Role in Glaucoma

Glaucoma, a heterogeneous set of progressively degenerative optic neuropathies characterized by a loss of retinal ganglion cells (RGCs) and typical visual field deficits that can progress to blindness, is a neurodegenerative disease involving both ocular and visual brain structures. Although elevated intraocular pressure (IOP) remains the most important modifiable risk factor of primary open-angle glaucoma (POAG) and is the main therapeutic target in treating glaucoma, other factors that influence the disease course are involved and reaching the optimal IOP target does not stop the progression of glaucoma, as the visual field continues to narrow. In addition to a managed IOP, neuroprotection may be beneficial by slowing the progression of glaucoma and improving the visual defects. Citicoline (cytidine 5'-diphosphocholine) is a naturally occurring endogenous compound that has been investigated as a novel therapeutic agent for the management of glaucoma. Citicoline has demonstrated activity in a range of central neurodegenerative diseases, and experimental evidence suggests a it performs a neuromodulator and neuroprotective role on neuronal cells, including RGCs, associated with improvement in visual function, extension of the visual field and central benefits for the patient. This review aims to critically summarize the current evidence for the neuroprotective properties of citicoline in glaucoma

Long-term Results of Riboflavin Ultraviolet A CornealCollagen Cross-linking for Keratoconus in Italy:The Siena Eye Cross Study

● PURPOSE: To report the long-term results of 44 keratoconic eyes treated by combined riboflavin ultraviolet A collagen cross-linking in the first Italian open, nonrandomized phase II clinical trial, the Siena Eye Cross Study. ● DESIGN: Perspective, nonrandomized, open trial. ● METHODS: After Siena University Institutional Review Board approval, from September 2004 through September 2008, 363 eyes with progressive keratoconus were treated with riboflavin ultraviolet A collagen crosslinking. Forty-four eyes with a minimum follow-up of 48 months (mean, 52.4 months; range, 48 to 60 months) were evaluated before and after surgery. Examinations comprised uncorrected visual acuity, best spectacle-corrected visual acuity, spherical spectacle-corrected visual acuity, endothelial cells count (I Konan, Non Con Robo; Konan Medical, Inc., Hyogo, Japan), optical (Visante OCT; Zeiss, Jena, Germany) and ultrasound (DGH; Pachette, Exton, Pennsylvania, USA) pachymetry, corneal topography and surface aberrometry (CSO EyeTop, Florence, Italy), tomography (Orbscan IIz; Bausch & Lomb Inc., Rochester, New York, USA), posterior segment optical coherence tomography (Stratus OCT; Zeiss, Jena, Germany), and in vivo confocal microscopy (HRT II; Heidelberg Engineering, Rostock, Germany). ● RESULTS: Keratoconus stability was detected in 44 eyes after 48 months of minimum follow-up; fellow eyes showed a mean progression of 1.5 diopters in more than 65% after 24 months, then were treated. The mean K value was reduced by a mean of 2 diopters, and coma aberration reduction with corneal symmetry improvement was observed in more than 85%. The mean best spectacle-corrected visual acuity improved by 1.9 Snellen lines, and the uncorrected visual acuity improved by 2.7 Snellen lines. ● CONCLUSIONS: The results of the Siena Eye Cross Study showed a long-term stability of keratoconus after cross-linking without relevant side effects. The uncorrected visual acuity and best spectacle-corrected visual acuity improvements were supported by clinical, topographic, and wavefront modifications induced by the treatment

Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena eye cross study

PURPOSE: To report the long-term results of 44 keratoconic eyes treated by combined riboflavin ultraviolet A collagen cross-linking in the first Italian open, nonrandomized phase II clinical trial, the Siena Eye Cross Study. DESIGN: Perspective, nonrandomized, open trial. METHODS: After Siena University Institutional Review Board approval, from September 2004 through September 2008, 363 eyes with progressive keratoconus were treated with riboflavin ultraviolet A collagen cross-linking. Forty-four eyes with a minimum follow-up of 48 months (mean, 52.4 months; range, 48 to 60 months) were evaluated before and after surgery. Examinations comprised uncorrected visual acuity, best spectacle-corrected visual acuity, spherical spectacle-corrected visual acuity, endothelial cells count (I Konan, Non Con Robo; Konan Medical, Inc., Hyogo, Japan), optical (Visante OCT; Zeiss, Jena, Germany) and ultrasound (DGH; Pachette, Exton, Pennsylvania, USA) pachymetry, corneal topography and surface aberrometry (CSO EyeTop, Florence, Italy), tomography (Orbscan IIz; Bausch & Lomb Inc., Rochester, New York, USA), posterior segment optical coherence tomography (Stratus OCT; Zeiss, Jena, Germany), and in vivo confocal microscopy (HRT II; Heidelberg Engineering, Rostock, Germany). RESULTS: Keratoconus stability was detected in 44 eyes after 48 months of minimum follow-up; fellow eyes showed a mean progression of 1.5 diopters in more than 65% after 24 months, then were treated. The mean K value was reduced by a mean of 2 diopters, and coma aberration reduction with corneal symmetry improvement was observed in more than 85%. The mean best spectacle-corrected visual acuity improved by 1.9 Snellen lines, and the uncorrected visual acuity improved by 2.7 Snellen lines. CONCLUSIONS: The results of the Siena Eye Cross Study showed a long-term stability of keratoconus after cross-linking without relevant side effects. The uncorrected visual acuity and best spectacle-corrected visual acuity improvements were supported by clinical, topographic, and wavefront modifications induced by the treatment

Corneal Collagen Cross-Linking With Riboflavin and Ultraviolet A Light for Pediatric Keratoconus: Ten-Year Results

PURPOSE: To assess the 10-year follow-up efficacy and safety of riboflavin ultraviolet A-induced cross-linking (CXL) in a population of pediatric patients aged 18 years and younger with progressive keratoconus (KC).METHODS: The prospective longitudinal cohort study included 62 eyes of 47 keratoconic patients undergoing epithelium-off CXL who completed 10-year follow-up. The surgical procedure was performed in all patients according to the Siena (Dresden modified) protocol. Evaluation included uncorrected distance visual acuity, corrected distance visual acuity, Scheimpflug corneal tomography, and optical coherence tomography demarcation line measurement. Follow-up measurements taken up to 10 years after treatment were compared with baseline values, and statistical analysis was performed using a 2-tailed paired sample Student t test.RESULTS: Uncorrected distance visual acuity and corrected distance visual acuity improved from 0.45 to 0.23 logarithm of the minimum angle resolution (P = 0.0001) and from 0.14 to 0.1 logarithm of the minimum angle resolution (P = 0.019). KC stability was recorded after 10 years of follow-up in nearly 80% of the patients. The overall 10-year follow-up progression rate was 24% including 13 eyes of 9 patients with Kmax progression over 1 diopter and 2 eyes of 2 patients who underwent corneal grafting.CONCLUSIONS: The study demonstrates the ability of CXL to slow down KC progression in pediatric patients, improving functional performance. Long-term stability may be correlated with CXL-induced delay in corneal collagen turnover and with spontaneous age-related KC stabilization. A 24% regression rate could be contemplated in the patients who were aged 15 years and younger at the time of inclusion in the treatment protocol

Age-Related Long-Term Functional Results after Riboflavin UV A Corneal Cross-Linking

Purpose. To report a comparative prospective long-term functional analysis after Riboflavin UV A corneal cross-linking (CXL) in three different age groups of patients affected by progressive keratoconus (KC). Methods. Functional analysis comprised paediatric patients ( 6418 years) included 152 eyes (29.5%); intermediate group (19-26 years) 286 eyes (55.4%), and adults ( 6527 years) 78 eyes (15.1%). CXL was performed according to the Siena protocol by using the Vega CBM (Caporossi-Baiocchi-Mazzotta) X linker (CSO, Florence, Italy) at Siena University by the same authors. Pre- and post-op examinations included UCVA, BSCVA, corneal topography, and surface aberrometry (CSO Eye Top, Florence, Italy), at 48 months followup. Results. At 48 months followup paediatrics, intermediate, and adult patients showed a mean gain in UCVA of +0.2, +0.14 and +0.12 Snellen lines. BSCVA gained by a mean of +0.21, +0.2, and +0.1 Snellen lines. K(max) was reduced by a mean value of -0.9\u2009D, -0.6\u2009D, and -0.5\u2009D, respectively. Coma values improved by a mean of -0.45\u2009\u3bcm, -0.91\u2009\u3bcm, and -0.19\u2009\u3bcm, respectively. Treatment ensured a long-term keratoconus stabilization in over 90% of treated patients. Conclusion. According to our long-term comparative results, epithelium-off Riboflavin UV A cross-linking should be the first choice therapy of progressive KC, particularly in paediatric age and patients under 26 years

Parasurgical therapy for keratoconus by riboflavin-ultraviolet type A rays induced cross-linking of corneal collagen: preliminary refractive results in an Italian study

PURPOSE: To assess the effectiveness of riboflavin-ultraviolet type A rays induced cross-linking of corneal collagen in reducing progression of keratoconus and in improving visual acuity in patients with progressive keratoconus. SETTING: Department of Ophthalmology, Siena University, Siena, Italy. METHODS: This was a second-phase prospective nonrandomized open study. Starting in September 2004, 10 eyes of 10 patients (mean age 31.4 years) with bilateral keratoconus were treated by combined riboflavin-ultraviolet type A rays (UVA) collagen cross-linking. Radiant energy was 3 mW/cm2 or 5.4 joule/cm2 for a 30-minute exposure at 1 cm from the corneal apex. A complete ophthalmologic examination (uncorrected visual acuity [UCVA], sphere spectacles corrected visual acuity (SSCVA), best spectacle-corrected visual acuity [BSCVA]) was performed. Patients had corneal computerized topographic examination, linear scan optical tomography, endothelial cell count, ultrasound pachometry, intraocular pressure (IOP) evaluation, and HRT II system confocal microscopy at 1, 2, 3, and 6 months. After treatment, eyes were medicated and dressed with a soft contact lens. RESULTS: Comparative preoperative and postoperative results showed increases of 3.6 lines for UCVA (P = .0000112), 1.85 lines for SSCVA (P = .00065), and 1.66 lines for BSCVA (P = .00071). Topographic analysis showed a mean K reduction of 2.1 +/- 0.13 diopters (D) in the central 3.0 mm. Statistical analysis of IOP and endothelial cell count did not show significant differences. Topo-aberrometric analysis findings of corneal symmetry showed a trend toward increasing corneal symmetry with a major reduction in asymmetry between vertical hemimeridians. CONCLUSIONS: Refractive results showed a reduction of about 2.5 D in the mean spherical equivalent, topographically confirmed by the reduction in mean K. Results of surface aberrometric analysis showed improvement in morphologic symmetry with a significant reduction in comatic aberrations

Corneal crosslinking: riboflavin concentration in corneal stroma exposed with and without epithelium

PURPOSE: To evaluate intrastromal concentrations of riboflavin with and without epithelium to ensure the efficacy and safety of corneal crosslinking (CXL) by the standard and transepithelial procedures. SETTING: Department of Ophthalmology and Department of Pharmacology G. Segre, Siena University, Siena, Italy. METHODS: This study comprised keratoconic patients enrolled for penetrating keratoplasty (PKP) and warm-stored sclerocorneal rings unsuitable for transplantation. Half the PKP specimens were debrided, and half were left with the epithelium in situ. One of the latter and 1 debrided sample were not exposed to riboflavin (controls). Samples in both groups were soaked with 0.1% riboflavin-dextran 20% solution instilled every 2 minutes for 5, 15, and 30 minutes. Riboflavin concentrations were determined by high-performance liquid chromatography (HPLC). RESULTS: The study evaluated 14 PKP specimens and 16 sclerocorneal rings. Control samples did not show a riboflavin emission peak. In exposed samples with epithelium, the mean riboflavin concentration was 91.88 ng/g after 5 minutes of exposure, 95.60 ng/g after 15 minutes, and 94.92 ng/g after 30 minutes. In the debrided samples, the mean riboflavin concentration was 14.42 microg/g, 20.92 microg/g, and 24.06 microg/g, respectively. No differences were seen between the in vivo samples and the ex vivo samples. CONCLUSIONS: The HPLC quantitative study showed that stromal concentrations of riboflavin increased with exposure time only if the epithelium was removed. A theoretically safe and effective riboflavin concentration of 15 microg/g was obtained for ultraviolet A-induced CXL only after the epithelium was removed and after at least 10 minutes of riboflavin application every 2 minutes

Performance evaluation of TTEthernet-based architectures for the VEGA launcher

The objective of the paper is to propose and evaluate the performance of a TTEthernet network architecture applied in small launchers in order to interconnect the terminals (on-board computer, telemetry apparatus, Inertial Reference System,...) performing the Guide, Navigation and Control (GNC) operations and producing/receiving telemetry traffic. The work described in the paper was been funded by Italian Space Agency (ASI) within the research agreement titled 'Advanced Avionic Architecture (AAA)'. Time-Triggered Ethernet (TTEthernet) improved the performance of Avionic Full Duplex Ethernet in terms of delay determinism by introducing time-triggered mechanism and by introducing a static allocation of the network capacity for the messages needing hard delay constraints. The strongest points of the TTEthernet solution applied to small launcher with respect to the classical one based on 1553B technology can be summarized as follows: i) the connections between flight stages can be limited to switch to switch connections and this reduces greatly the connectors and harness in the launcher with the consequence to reduce single points of failure, weight and complexity of assembly and integration activities during production; ii) the compatibility with Ethernet technology allows for the use of standard mass devices (PC) to perform checks and tests in standard ground operations during launch campaign; iii) the possibility to interconnect critical and non-critical equipment on the same network without the need for a physical segregation allows for cost reduction; iv) the increase in available bandwidth allows for the support of additional functional and telemetry data We propose a TTEthernet-based architecture ad hoc for small launchers and compare it to a benchmark TTEthernet architecture in which all of the traffic (GNC and telemetry) is classified as Time-Triggered. Conversely the proposed architecture operates a traffic classification in which only GNC messages with hard delay requirements are classified as Time Triggered. The remaining telemetry messages are classified as rate constrained so as to guarantee a maximum delay only. We show how the proposed traffic classification allows for advantages in terms of bandwidth efficiency and routing computational complexity. The comparison is performed when the compared communication networks handle messages extrapolated by the message set of VEGA, a small launcher jointly designed by Italian Space Agency and European Space Agency. The type and characteristic of the messages considered allows for achieving realistic results and for evaluating the effectiveness of the TTEthernet solution applied to small launchers. The results are provided in the case of star network topology with two redundant channels. We show how the adoption of a TTEthernet as launcher network allows to satisfy all of the delay requirements of GNC messages. The achieved results show how the proposed architecture allows for a 75% bandwidth saving in the most critical network link and a 50% routing table complexity reduction with respect to the benchmark architecture

Feature article: Definition and performance evaluation of an advanced avionic TTEthernet architecture for the support of launcher networks

Standard Ethernet has been well established and widely used in office and home networks known as Local Area Networks (LAN). In the recent decade, standard Ethernet has been widely adopted into other network domains such as industrial automation, automotive, railway, and aerospace domains [1], [2]. One of the main attractions of Ethernet is its high bandwidth, a bandwidth that is much higher than in other communication networks. Another one is that the prices of commercial-off-the-shelf standard Ethernet components are relatively low [3], [4]. Since standard Ethernet was not originally designed to be capable of providing temporal guarantees for real-time communication, there have been many protocol designs adapting standard Ethernet to being capable of providing such temporal guarantees. Some examples are: EtherCAT, Ethernet/ IP, PROFINET [5], Avionic Full Duplex Ethernet, and Time- Triggered (TT) Ethernet (TTEthernet) [6]