Keratoconus and keratoectasia:advancements in diagnosis and treatment

Full text: Keratoconus (KC) and iatrogenic keratoectasia are receiving increasing attention, due to the improvements in diagnostic modalities and the availability of therapeutic options, which now include collagen cross-linking, intrastromal implants, intraocular lenses, microwave remodeling, and anterior lamellar keratoplasty. Limitations of surgical treatments of keratoconus are well known. Intrastromal implants, built in various shapes and now implanted more safely through femtosecond-laser-obtained stromal channels, still retain reduced predictability as for the refractive results and do not modify the structure of the diseased cornea. Anterior lamellar keratoplasty, even in its more advanced and technically difficult variant of deep anterior lamellar keratoplasty (DALK), cures the disease by the (almost) complete replacement of the ectatic stroma but, even when a regular and transparent interface is achieved, final refractive errors and higher-order aberrations may severely affect visual rehabilitation. The use of femtosecond laser in DALK to shape the donor and recipient margins has not significantly improved the picture yet. Parasurgical treatments of KC are therefore regarded as a temporary or definitive alternative to surgical interventions. Among the newest ideas, the promising use of microwave to heat and reshape the corneal apex shares the principle with previous modalities of thermal keratoplasty, which were characterized by regression and induction of irregular astigmatism. The long-term validity of microwave reshaping is, therefore, still being investigated. The use of collagen corneal cross-linking (CXL) with riboflavin and ultraviolet (UV) has rapidly expanded in the world and is currently regarded as the only recognized treatment to slow or arrest KC progression, obtaining in some cases a significant improvement of corneal curvature and regularity. However, as most new treatments, CXL is still far from being ideal. Riboflavin for CXL is unreasonably expensive; the treatment is long and tedious and is followed by postoperative pain and slow visual rehabilitation. Complications are not uncommon, including infections and scarring. The indications to the treatment are still debated as for age, KC stage, and corneal thickness. Alternative attempts to reduce the CXL operating time by increasing the irradiation energy or by avoiding epithelial removal have been made, but all deviations from the defined original protocol may reduce the efficacy of treatment, and therefore new treatment protocols are currently further investigated. In this special issue, various and new aspects of CXL are examined, rehabilitation with contact lenses of KC is reviewed, and the features of posterior KC at ultrasound biomicroscopy are evaluated. Patient selection for CXL is not completely codified, and age limits are conventionally established. For example, the Italian National Health Service limits CXL reimbursement for patients between 12 and 40 years, the lower limit being dictated by common sense and the upper limit by the presumption of spontaneous KC stabilization after 40. A. Caporossi and Mazzotta et al., leading experts of CXL, in their original study in this issue, compare KC stabilization, improvement of corneal curvature, visual acuity, and aberrations 48 months after CXL in different age groups, concluding that the highest benefits were obtained in younger eyes. CXL procedure was originally developed to stiffen the keratoconic cornea, but its indications have been recently extended to postrefractive surgery ectasia, to infectious keratitis (due to a powerful antimicrobial action), and to corneal edema, where CXL temporarily reduces the space for fluid accumulation. These new indications of CXL, as well as its physical and chemical background, biomechanical effects, and clinical results, are thoroughly reviewed in the paper by M. Hovakimyan et al., where the real possibilities of transepithelial CXL and of the new approach combining photorefractive keratectomy (PRK) and CXL are discussed. Several reports of infectious keratitis after CXL have recently raised the issue of CXL safety: it would appear that the risk of infection is considerably higher than after PRK. The length of the procedure or the slow epithelialization time could be the reasons for such increased infectious risk. In addition, the peculiar “demarcation” haze, regarded as a demonstration of the cross-linking effect, can sometimes turn into a significant, long-term scar. These complications and others are well reviewed in the paper by S. Dhawan et al. Fortunately, most patients with KC will never need to undergo any surgical or parasurgical procedure. Visual rehabilitation is sometimes possible with the sole help of spectacles, but the reduction of higher-order aberrations is only possible with contact lenses. The extended wear of contact lenses and the difficult adaptation in keratoconic eyes imply a thorough knowledge of various contact lens models available: this is the subject of the article by Ozkurt et al. The paper by B. Rejdak et al. is a case report of a rare, nonprogressive variant of KC, circumscribed posterior keratoconus. The correct diagnosis of this form of ectasia is only possible by modern three-dimensional imaging technique, and in this case ultrasound biomicroscopy and slit scanning topography were used to reveal the protrusion of the posterior corneal surface. In this historical period we are directly witnessing the rise (and fall) of many therapeutic modalities for KC, but we can nevertheless look with optimism at the future of a complex and multiform disease, characterized by individualised treatment and prognosis. We hope that this special issue will contribute to stimulating discussion

The Level-0 Muon Trigger for the LHCb Experiment

A very compact architecture has been developed for the first level Muon Trigger of the LHCb experiment that processes 40 millions of proton-proton collisions per second. For each collision, it receives 3.2 kBytes of data and it finds straight tracks within a 1.2 microseconds latency. The trigger implementation is massively parallel, pipelined and fully synchronous with the LHC clock. It relies on 248 high density Field Programable Gate arrays and on the massive use of multigigabit serial link transceivers embedded inside FPGAs.Comment: 33 pages, 16 figures, submitted to NIM

Neutrino Telescopes in the Mediterranean Sea

The observation of high energy extraterrestrial neutrinos can be an invaluable source of information about the most energetic phenomena in the Universe. Neutrinos can shed light on the processes that accelerate charge particles in an incredibly wide range of energies both within and outside our Galaxy. They can also help to investigate the nature of the dark matter that pervades the Universe. The unique properties of the neutrino make it peerless as a cosmic messenger, enabling the study of dense and distant astrophysical objects at high energy. The experimental challenge, however, is enormous. Due to the weakly interacting nature of neutrinos and the expected low fluxes very large detectors are required. In this paper we briefly review the neutrino telescopes under the Mediterranean Sea that are operating or in progress. The first line of the ANTARES telescope started to take data in March 2006 and the full 12-line detector was completed in May 2008. By January 2009 more than one thousand neutrino events had been reconstructed. Some of the results of ANTARES will be reviewed. The NESTOR and NEMO projects have made a lot of progress to demonstrate the feasibility of their proposed technological solutions. Finally, the project of a km3-scale telescope, KM3NeT, is rapidly progressing: a conceptual design report was published in 2008 and a technical design report is expected to be delivered by the end of 2009

Conception and Validation Software Tools for the Level 0 Muon Trigger of LHCb

The Level-0 muon trigger processor of the LHCb experiment looks for straight particules crossing muon detector and measures their transverse momentum. It processes 40×106 proton-proton collisions per second. The tracking uses a road algorithm relying on the projectivity of the muon detector. The architecture of the Level-0 muon trigger is complex with a dense network of data interconnections. The design and validation of such an intricate system has only been possible with intense use of software tools for the detector simulation, the modelling of the hardware components behaviour and the validation. A database describing the dataflow is the corner stone between the software and hardware components

Neutrino Mixing and Neutrino Telescopes

Measuring flux ratios of ultra-high energy neutrinos is an alternative method to determine the neutrino mixing angles and the CP phase delta. We conduct a systematic analysis of the neutrino mixing probabilities and of various flux ratios measurable at neutrino telescopes. The considered cases are neutrinos from pion, neutron and muon-damped sources. Explicit formulae in case of mu-tau symmetry and its special case tri-bimaximal mixing are obtained, and the leading corrections due to non-zero theta_{13} and non-maximal theta_{23} are given. The first order correction is universal as it appears in basically all ratios. We study in detail its dependence on theta_{13}, theta_{23} and the CP phase, finding that the dependence on theta_{23} is strongest. The flavor compositions for the considered neutrino sources are evaluated in terms of this correction. A measurement of a flux ratio is a clean measurement of the universal correction (and therefore of theta_{13}, theta_{23} and delta) if the zeroth order ratio does not depend on theta_{12}. This favors pion sources over the other cases, which in turn are good candidates to probe theta_{12}. The only situations in which the universal correction does not appear are certain ratios in case of a neutron and muon-damped source, which depend mainly on theta_{12} and receive only quadratic corrections from the other parameters. We further show that there are only two independent neutrino oscillation probabilities, give the allowed ranges of the considered flux ratios and of all probabilities, and show that none of the latter can be zero or one.Comment: 29 pages, 8 figures. Minor changes, to appear in JCA

The pd <--> pi+ t reaction around the Delta resonance

The pd pi+ t process has been calculated in the energy region around the Delta-resonance with elementary production/absorption mechanisms involving one and two nucleons. The isobar degrees of freedom have been explicitly included in the two-nucleon mechanism via pi-- and rho-exchange diagrams. No free parameters have been employed in the analysis since all the parameters have been fixed in previous studies on the simpler pp pi+ d process. The treatment of the few-nucleon dynamics entailed a Faddeev-based calculation of the reaction, with continuum calculations for the initial p-d state and accurate solutions of the three-nucleon bound-state equation. The integral cross-section was found to be quite sensitive to the NN interaction employed while the angular dependence showed less sensitivity. Approximately a 4% effect was found for the one-body mechanism, for the three-nucleon dynamics in the p-d channel, and for the inclusion of a large, possibly converged, number of three-body partial states, indicating that these different aspects are of comparable importance in the calculation of the spin-averaged observables.Comment: 40 Pages, RevTex, plus 5 PostScript figure

Test of CPT Symmetry and Quantum Mechanics with Experimental data from CPLEAR

We use fits to recent published CPLEAR data on neutral kaon decays to $\pi^+\pi^-$ and $\pi e\nu$ to constrain the CPT--violation parameters appearing in a formulation of the neutral kaon system as an open quantum-mechanical system. The obtained upper limits of the CPT--violation parameters are approaching the range suggested by certain ideas concerning quantum gravity.Comment: 9 pages of uuencoded postscript (includes 3 figures

Tests of the Equivalence Principle with Neutral Kaons

We test the Principle of Equivalence for particles and antiparticles, using CPLEAR data on tagged K0 and K0bar decays into pi^+ pi^-. For the first time, we search for possible annual, monthly and diurnal modulations of the observables |eta_{+-}| and phi_{+-}, that could be correlated with variations in astrophysical potentials. Within the accuracy of CPLEAR, the measured values of |eta_{+-}| and phi_{+-} are found not to be correlated with changes of the gravitational potential. We analyze data assuming effective scalar, vector and tensor interactions, and we conclude that the Principle of Equivalence between particles and antiparticles holds to a level of 6.5, 4.3 and 1.8 x 10^{-9}, respectively, for scalar, vector and tensor potentials originating from the Sun with a range much greater than the distance Earth-Sun. We also study energy-dependent effects that might arise from vector or tensor interactions. Finally, we compile upper limits on the gravitational coupling difference between K0 and K0bar as a function of the scalar, vector and tensor interaction range.Comment: 15 pages latex 2e, five figures, one style file (cernart.csl) incorporate

Background Light in Potential Sites for the ANTARES Undersea Neutrino Telescope

The ANTARES collaboration has performed a series of {\em in situ} measurements to study the background light for a planned undersea neutrino telescope. Such background can be caused by $^{40}$K decays or by biological activity. We report on measurements at two sites in the Mediterranean Sea at depths of 2400~m and 2700~m, respectively. Three photomultiplier tubes were used to measure single counting rates and coincidence rates for pairs of tubes at various distances. The background rate is seen to consist of three components: a constant rate due to $^{40}$K decays, a continuum rate that varies on a time scale of several hours simultaneously over distances up to at least 40~m, and random bursts a few seconds long that are only correlated in time over distances of the order of a meter. A trigger requiring coincidences between nearby photomultiplier tubes should reduce the trigger rate for a neutrino telescope to a manageable level with only a small loss in efficiency.Comment: 18 pages, 8 figures, accepted for publication in Astroparticle Physic