The intraocular lens: challenges in the prevention and therapy of infectious endophthalmitis and posterior capsular opacification

Cataract is the leading cause of visual impairment worldwide. In the UK, some 30% of the population over 65 years of age have visually impairing cataract. Importantly, 88% of those with treatable visual impairment from cataract are not in contact with any ocular healthcare service, representing a major potential healthcare need [1]. In the USA, it has been estimated that 17.2% of the population (approximately 20.5 million) over 40 years of age have cataract in either eye and by 2020, this number is expected to rise to 30.1 million. Currently, cataract is responsible for 60% of Medicare costs associated with vision [2]. Furthermore, as the populations of industrialized countries such as the UK and the USA continue to age, the costs associated with treatment of cataract can only be expected to increase. Consequently, the development of the intraocular lens to replace the cataractous lens and the advances in intraocular lens design and implantation represent a major development in cataract treatment. However, despite such advances, cataract surgery is not without complications, such as postoperative infectious endophthalmitis, a rare but potentially devastating condition, and posterior capsular opacification, a less serious but much more common problem. This review will examine the epidemiology of cataracts, the polymeric construction of intraocular lenses implanted during cataract surgery and the complications of postoperative infectious endophthalmitis and posterior capsular opacification with regard to therapeutic interventions and prophylactic strategies. Advances in biomaterial design and function will be discussed as novel approaches to prevent such postoperative complications.

Light emission from scanning tunnelling microscope on polycrystalline Au films - what is happening at the single-grain level?

When operated with a metallic tip and sample the scanning tunnelling microscope constitutes a nanoscale, plasmonic light source yielding broadband emission up to a photon energy determined by the applied bias. The emission is due to tunnelling electron excitation and subsequent radiative decay of localized plasmon modes, which can be on the lateral scale of a single metal grain (similar to 25 nm) or less. For a Au-tip/Au-polycrystalline sample under ambient conditions it is found that the intensity and spectral content of the emitted light are not dependent on the lateral grain dimension, but are predominantly determined by the tip geometry. However, the intensity increases strongly with increasing film thickness (grain depth) up to 20-25 nm or approximately the skin depth of the Au film. Photon maps can show less emissive grains and two classes of this occurrence are distinguished. The first is geometrical in origin - a double-tip structure in this case - while the second is due to a contamination-induced lowering of the local work function that causes the tunnel gap to increase. It is suggested that differences in work-function lowering between grains presenting different crystalline facets, combined with an exponential decay in emitted light intensity with tip - sample distance, leads to grain contrast. These results are relevant to tip-enhanced Raman scattering and the fabrication of micro/nano-scale planar, light-emitting tunnel devices.

Novel Porphyrin-Incorporated Hydrogels for Photoactive Intraocular Lens Biomaterials

Novel surface-modified hydrogel materials have been prepared by binding charged porphyrins TMPyP (tetrakis-(4-N-methylpyridyl)porphyrin) and TPPS (tetrakis(4-sulfonatophenyl)porphyrin) to copolymers of HEMA (2-hydroxyethyl methacrylate) with either MAA (methacrylic acid) or DEAEMA (2-(diethylamino)ethylmethacrylate). The charged hydrogels display strong electrostatic interactions with the appropriate cationic or anionic porphyrins to give materials which are intended to be used to generate cytotoxic singlet oxygen (1O2) on photoexcitation and can therefore be used to reduce postoperative infection of the intraocular hydrogel-based replacement lenses that are used in cataract surgery. The UV/vis spectra of TMPyP in MAA:HEMA copolymers showed a small shift in the Soret band and a change from single exponential (161 ���­s) triplet decay lifetime in solution to a decay that could be fitted to a biexponential fit with two approximately equal components with ���´ ) 350 and 1300 ���­s. O2 bubbling reduced the decay to a dominant (90%) component with a much reduced lifetime of 3 ���­s and a minor, longer lived (20 ���­s) component. With D2O solvent the 1O2 lifetime was measured by 1270 nm fluorescence as 35 ���­s in MAA:HEMA, compared to 67 ���­s in solution, although absorbance-matched samples showed similar yield of 1O2 in the polymers and in aqueous solution. In contrast to the minor perturbation in photophysical properties caused by binding TMPyP to MAA:HEMA, TPPS binding to DEAEMA:HEMA copolymers profoundly changed the 1O2 generating ability of the TPPS. In N2-bubbled samples, the polymer-bound TPPS behaved in a similar manner to TMPyP in its copolymer host; however, O2 bubbling had only a very small effect on the triplet lifetime and no 1O2 generation could be detected. The difference in behavior may be linked to differences in binding in the two systems. With TMPyP in MAA:HEMA, confocal fluorescence microscopy showed significant penetration of the porphyrin into the core of the polymer film samples (>150 ���­m). However, for TPPS in DEAEMA:HEMA copolymers, although the porphyrin bound much more readily to the polymer, it remained localized in the first 20 ���­m, even in heavily loaded samples. It is possible that the resulting high concentration of TPPS may have cross-linked the hydrogels to such an extent that it significantly reduced the solubility and/or diffusion rate of oxygen into the doped polymers. This effect is significant since it demonstrates that even simple electrostatic binding of charged porphyrins to hydrogels can have an unexpectedly large effect on the properties of the system as a whole. In this case it makes the apparently promising TPPS/DEAEMA:HEMA system a poor candidate for clinical application as a postoperative antibacterial treatment for intraocular lenses while the apparently equivalent cationic system TMPyP/MAA:HEMA displays all the required properties.

Thomson scattering system at the Tokyo electron beam ion trap

A Thomson scattering system has been installed at the Tokyo electron beam ion trap for probing characteristics of the electron beam. A YVO4 green laser beam was injected antiparallel to the electron beam. The image of the Thomson scattering light from the electron beam has been observed using a charged-coupled device camera. By using a combination of interference filters, the spectral distribution of the Thomson scattering light has been measured. The Doppler shift observed for the scattered light is consistent with the beam energy. The beam radius dependence was investigated as a function of the beam energy, the beam current, and the magnetic field at the trap region. The variation of the measured beam radius against the beam current and the magnetic field were similar to those in Herrmann's prediction. The beam radius as a function of the beam energy was also similar to Herrmann's prediction but seemed to become larger at low energy. (C) 2002 American Institute of Physics.

Cataract surgery induces retinal pro-inflammatory gene expression and protein secretion

To investigate the effect(s) of cataract surgery on the expression of pro-inflammatory genes and proteins in the retina using an experimental rodent model. An extracapsular lens extraction was performed in one eye of C57BL/6 mice (n=24); the contralateral unoperated eyes (n =24) as well as eyes from unoperated animals (n = 9) served as controls. The neurosensory retina and retinal pigment epithelium (RPE)/choroid were collected postoperatively. Expression of genes involved in the acute inflammatory/ injury response, including IL-1ß, fibroblast growth factor, transforming growth factor ß, chemokine CCL2, SDF-1, and complements C3, C4, and factor B (CFB), were examined by real-time PCR and, selectively, by immunohistochemistry. The expression of IL-1 ß and CCL2 genes was markedly upregulated (>0-fold, P >0.01) in the neurosensory retina 30 minutes postoperatively and maintained for the 2-week postoperative period of observation; IL-1 ß expression was also upregulated in RPE/choroid. The expression of complement C3 (>-fold) and CFB (>0-fold) genes in the neurosensory retina was also significantly upregulated (P

Increased levels of advanced glycation endproducts in the lenses and blood vessels of cigarette smokers.

BACKGROUND: Advanced glycation endproducts (AGEs) arise from the spontaneous reaction of reducing sugars with the amino groups of macromolecules. AGEs accumulate in tissue as a consequence of diabetes and aging and have been causally implicated in the pathogenesis of several of the end-organ complications of diabetes and aging, including cataract, atherosclerosis, and renal insufficiency. It has been recently proposed that components in mainstream cigarette smoke can react with plasma and extracellular matrix proteins to form covalent adducts with many of the properties of AGEs. We wished to ascertain whether AGEs or immunochemically related molecules are present at higher levels in the tissues of smokers.

MATERIALS AND METHODS: Lens and coronary artery specimens from nondiabetic smokers and nondiabetic nonsmokers were examined by immunohistochemistry, immunoelectron microscopy, and ELISA employing several distinct anti-AGE antibodies. In addition, lenticular extracts were tested for AGE-associated fluorescence by fluorescence spectroscopy.

RESULTS: Immunoreactive AGEs were present at significantly higher levels in the lenses and lenticular extracts of nondiabetic smokers (p < 0.003). Anti-AGE immunogold staining was diffusely distributed throughout lens fiber cells. AGE-associated fluorescence was significantly increased in the lenticular extracts of nondiabetic smokers (p = 0.005). AGE-immunoreactivity was significantly elevated in coronary arteries from nondiabetic smokers compared with nondiabetic nonsmokers (p = 0.015).

CONCLUSIONS: AGEs or immunochemically related molecules are present at higher levels in the tissues of smokers than in nonsmokers, irrespective of diabetes. In view of previous reports implicating AGEs in a causal association with numerous pathologies, these findings have significant ramifications for understanding the etiopathology of diseases associated with smoking, the single greatest preventable cause of morbidity and mortality in the United States.

Far field subwavelength source resolution using Phase Conjugating Lens Assisted With Evanescent-to-Propagating Spectrum Conversion

The imaging properties of a phase conjugating lens operating in the far field zone of the imaged source and augmented with scatterers positioned in the source near field region are theoretically studied in this paper. The phase conjugating lens consists of a double sided 2D assembly of straight wire elements, individually interconnected through phase conjugation operators. The scattering elements are straight wire segments which are loaded with lumped impedance loads at their centers. We analytically and numerically analyze all stages of the imaging process; i) evanescent-to-propagating spectrum conversion; ii) focusing properties of infinite or finite sized phase conjugating lens; iii) source reconstruction upon propagating-to-evanescent spectrum conversion. We show that the resolution that can be achieved depends critically on the separation distance between the imaged source and scattering arrangement, as well as on the topology of the scatterers used. Imaged focal widths of up to one-seventh wavelength are demonstrated. The results obtained indicate the possibility of such an arrangement as a potential practical means for realising using conventional materials devices for fine feature extraction by electromagnetic lensing at distances remotely located from the source objects under investigation

Mutation altering the miR-184 seed region causes keratoconus with cataract

MicroRNAs (miRNAs) bind to complementary sequences within the 3? untranslated region (UTR) of mRNAs from hundreds of target genes, leading either to mRNA degradation or suppression of translation. We found that a mutation in the seed region of miR-184 (MIR184) is responsible for familial severe keratoconus combined with early-onset anterior polar cataract, by deep sequencing of a linkage region known to contain the mutation. The mutant form fails to compete with miR-205 (MIR205) for overlapping target sites on the 3? UTRs of INPPL1 and ITGB4. Although these target genes and miR-205 are expressed widely, the phenotype is restricted to the cornea and lens because of the very high expression of miR-184 in these tissues. Our finding highlights the tissue-specificity of a gene network regulated by a miRNA. Awareness of the important function of miRNAs may aid identification of susceptibility genes and new therapeutic targets for treatment of both rare and common diseases.

Characterization of novel Ag on TiO2 films for surface-enhanced Raman scattering

Novel Ag on TiO₂ films are generated by semiconductor photocatalysis and characterized by ultraviolet-visible (UV/Vis) spectroscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM), as well as assessed for surface-enhanced Raman scattering (SERS) activity. The nature and thickness of the photodeposited Ag, and thus the degree of SERS activity, is controlled by the time of exposure of the TiO₂ film to UV light. All such films exhibit the optical characteristics (λ_max ≅ 390 nm) of small (<20 nm) Ag particles, although this feature becomes less prominent as the film becomes thicker. The films comprise quite large (>40 nm) Ag islands that grow and merge with increasing levels of Ag photodeposition. Tested with a benzotriazole dye probe, the films are SERS active, exhibiting activity similar to that of 6-nm-thick vapordeposited films. The Ag/TiO₂ films exhibit a lower residual standard deviation (∼25%) compared with Ag vapor-deposited films (∼45%), which is, however, still unacceptable for quantitative work. The sample-to-sample variance could be reduced significantly (<7%) by spinning the film during the SERS measurement. The Ag/TiO₂ films are mechanically robust and resistant to removal and damage by scratching, unlike the Ag vapor-deposited films. The Ag/TiO₂ films also exhibit no obvious loss of SERS activity when stored in the dark under otherwise ambient conditions. The possible extension of this simple, effective method of producing Ag films for SERS, to metals other than Ag and to semiconductors other than TiO₂, is briefly discussed. 

Scattering theory of cooling and heating in optomechanical systems

We present a one-dimensional scattering theory which enables us to describe a wealth of effects arising from the coupling of the motional degree of freedom of scatterers to the electromagnetic field. Multiple scattering to all orders is taken into account. The theory is applied to describe the scheme of a Fabry-Perot resonator with one of its mirrors moving. The friction force, as well as the diffusion, acting on the moving mirror is derived. In the limit of a small reflection coefficient, the same model provides for the description of the mechanical effect of light on an atom moving in front of a mirror.

Scattering theory of multilevel atoms interacting with arbitrary radiation fields

We present a generic transfer matrix approach for the description of the interaction of atoms possessing multiple ground state and excited state sublevels with light fields. This model allows us to treat multi-level atoms as classical scatterers in light fields modified by, in principle, arbitrarily complex optical components such as mirrors, resonators, dispersive or dichroic elements, or filters. We verify our formalism for two prototypical sub-Doppler cooling mechanisms and show that it agrees with the standard literature.

Metal Oxide Nanoparticle Mediated Enhanced Raman Scattering and Its Use in Direct Monitoring of Interfacial Chemical Reactions

Metal oxide nanoparticles (MONPs) have widespread usage across many disciplines, but monitoring molecular processes at their surfaces in situ has not been possible. Here we demonstrate that MONPs give highly enhanced (X10(4)) Raman scattering signals from molecules at the interface permitting direct monitoring of their reactions, when placed on top of flat metallic surfaces. Experiments with different metal oxide materials and molecules indicate that the enhancement is generic and operates at the single nanoparticle level. Simulations confirm that the amplification is principally electromagnetic and is a result of optical modulation of the underlying plasmonic metallic surface by MONPs, which act as scattering antennae and couple light into the confined region sandwiched by the underlying surface. Because of additional functionalities of metal oxides as magnetic, photoelectrochemical and catalytic materials, enhanced Raman scattering mediated by MONPs opens up significant opportunities in fundamental science, allowing direct tracking and understanding of application-specific transformations at such interfaces. We show a first example by monitoring the MONP-assisted photocatalytic decomposition reaction of an organic dye by individual nanoparticles.

Electric currents and lens regeneration in the rat

We studied the process of lens regeneration in the rat following an extracapsular lens extraction preserving the anterior lens capsule and anterior lens epithelium. We assessed clinically the clarity of the newly regenerated lens, evaluated changes in the lens electrical currents following surgery and during the regeneration process and correlated these changes with findings on light microscopy. Protein analysis of the regenerated lens was also undertaken. Experiments were performed in 41 Sprague-Dawley rats, sacrificed at 0, 2, 4 and 8 weeks postoperatively. Our results showed that complete lens regeneration occurred 8 weeks postoperatively only if the anterior epithelium was preserved and the lens capsule was closed surgically. Lens electrical currents, altered following surgery, recovered in parallel with the process of regeneration of the lens. The newly regenerated lens was optically clear and biochemical analysis revealed a pattern of protein expression resembling that observed during lens development. In conclusion, complete lens regeneration occurs in the rat and it is possible that lens electrical signals, together with other cues, may play an important role in this process. © 2009 Elsevier Ltd.

A new model of posterior capsule opacification in rodents

PURPOSE. To describe a new model of posterior capsule opacification (PCO) in rodents METHODS. An extracapsular lens extraction (ECLE), by continuous curvilinear capsulorrhexis and hydrodissection, was performed in 42 consecutive Brown Norway rats. Animals were killed at 0, 6, and 24 hours and 3, 7, and 14 days after surgery. Eyes were enucleated and processed for light microscopy and immunohistochemistry. RESULTS. In 34 (81%) of the animals the operated eye appeared well healed before death, with a clear cornea and a well-formed anterior chamber. In eight (19%) there was no view of anterior segment structures because of hyphema, fibrin, or corneal opacification. PCO was clinically evident 3 days after ECLE and was present in all animals at 2 weeks. Immediately after ECLE, lens epithelial cells (LECs) were present in the inner surface of the anterior capsule and lens bow. Twenty-four hours after surgery, LECs started to migrate toward the center of the posterior capsule. At 3 days, multilayered LECs, some spindle shaped, were present throughout the lens capsule. Capsular wrinkling was apparent. Lens fibers and Soemmering's ring were observed in all animals 14 days after surgery, indicating some degree of cellular differentiation. Activated macrophages were present in greater numbers at 3 and 14 days after surgery (P <0.05), when proliferation and migration of LECs appeared to be greatest, and lens fiber differentiation was evident, respectively. CONCLUSIONS. In rodents PCO occurs after ECLE and is associated with low-grade inflammation, mostly of mononuclear macrophages. Although no intraocular lens implantation was performed, this model appears to be valuable for studying the sequence of events that leads to PCO after cataract surgery and the extracellular matrix cues that promote lens fiber differentiation.

Clinicopathological correlation of epiretinal membranes and posterior lens opacification following perfluorohexyloctane tamponade

Background/aims - Epiretinal and retrolental proliferation may occur during prolonged use of the novel tamponade agent perfluorohexyloctane (F H ). This study aims to determine whether there is any histological evidence that F H has a role in the formation of these membranes. Methods - Eight epiretinal membranes and three opaque posterior lens capsules were excised from patients in whom F H had been used as a long term retinal tamponade agent. The membranes and capsules were examined employing light microscopic methods, including immunohistochemistry. Results - The epiretinal membranes showed histological features typical of proliferative vitreoretinopathy (PVR) epiretinal membranes, but they also exhibited a dense macrophagic infiltration. In addition, three of the membranes contained multinucleated cells. Macrophages represented up to 30% of the cells present and appeared to contain large intracytoplasmic vacuoles. Similar cells were seen on the back of the posterior lens capsule in one specimen and all three capsules had posterior migration of lens epithelium. Conclusion - The pathological findings are not simply those of PVR. The macrophage infiltration suggests that there may be a biological reaction to F H which could reflect its surmised propensity to emulsify. Further investigations concerning the cellular response to this promising tamponade agent are warranted.