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.

Escape times for rigid Brownian rotators in a bistable potential from the time evolution of the Green function and the characteristic time of the probability evolution

The greatest relaxation time for an assembly of three- dimensional rigid rotators in an axially symmetric bistable potential is obtained exactly in terms of continued fractions as a sum of the zero frequency decay functions (averages of the Legendre polynomials) of the system. This is accomplished by studying the entire time evolution of the Green function (transition probability) by expanding the time dependent distribution as a Fourier series and proceeding to the zero frequency limit of the Laplace transform of that distribution. The procedure is entirely analogous to the calculation of the characteristic time of the probability evolution (the integral of the configuration space probability density function with respect to the position co-ordinate) for a particle undergoing translational diffusion in a potential; a concept originally used by Malakhov and Pankratov (Physica A 229 (1996) 109). This procedure allowed them to obtain exact solutions of the Kramers one-dimensional translational escape rate problem for piecewise parabolic potentials. The solution was accomplished by posing the problem in terms of the appropriate Sturm-Liouville equation which could be solved in terms of the parabolic cylinder functions. The method (as applied to rotational problems and posed in terms of recurrence relations for the decay functions, i.e., the Brinkman approach c.f. Blomberg, Physica A 86 (1977) 49, as opposed to the Sturm-Liouville one) demonstrates clearly that the greatest relaxation time unlike the integral relaxation time which is governed by a single decay function (albeit coupled to all the others in non-linear fashion via the underlying recurrence relation) is governed by a sum of decay functions. The method is easily generalized to multidimensional state spaces by matrix continued fraction methods allowing one to treat non-axially symmetric potentials, where the distribution function is governed by two state variables. (C) 2001 Elsevier Science B.V. All rights reserved.

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.

Anti-infective photodynamic biomaterials for the prevention of intraocular lens-associated infectious endophthalmitis

Bacterial attachment onto intraocular lenses (IOLs) during cataract extraction and IOL implantation is a prominent aetiological factor in the pathogenesis of infectious endophthalmitis. Photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) have shown that photosensitizers are effective treatments for cancer, and in the photoinactivation of bacteria, viruses, fungi and parasites, in the presence of light. To date, no method of localizing the photocytotoxic effect of a photosensitizer at a biomaterial surface has been demonstrated. Here we show a method for concentrating this effect at a material surface to prevent bacterial colonization by attaching a porphyrin photosensitizer at, or near to, that surface, and demonstrate the principle using IOL biomaterials. Anionic hydrogel copolymers were shown to permanently bind a cationic porphyrin through electrostatic interactions as a thin surface layer. The mechanical and thermal properties of the materials showed that the porphyrin acts as a surface cross-linking agent, and renders surfaces more hydrophilic. Importantly, Staphylococcus epidermidis adherence was reduced by up to 99.0 ± 0.42% relative to the control in intense light conditions and 91.7± 5.99% in the dark. The ability to concentrate the photocytotoxic effect at a surface, together with a significant dark effect, provides a platform for a range of light-activated anti-infective biomaterial technologies.

Key biological issues in contact lens development

A contact lens is a medical device widely used as an alternative to spectacles in order to correct refractive vision problems. The evolution of polymeric biomaterials has heralded a continuous development in the materials used to produce contact lenses and maximize patient comfort and limit adverse events. Microbial keratitis (MK) is a relatively rare but potentially devastating condition associated with contact lens use, particularly with the extended wear of hydrogel lenses. It is the principal complication related to contact lens wear and the large population at risk make it a public health concern. Bacterial binding to the contact lens material is a precursor to the development of MK and is influenced by properties of the material and the bacteria. In order for bacteria to infiltrate the cornea there must be some degree of corneal damage, usually caused by trauma or hypoxia. The most recent materials available aim to allow the continuous wear of lenses while limiting corneal hypoxia, thus helping to prevent the development of MK. Limitations to the treatment of MK require that novel approaches may be necessary in order to limit bacterial adhesion to contact lens materials.

Curl antenna lens as angle of arrival sensor

A lens antenna consisting of a double-sided 3 x 3 array of curl antennas that can convert an incident LH/RHCP signal into a transmitted LH/RHCP signal is shown to have an additional property that allows the angle of incidence of an incoming linear or circularly polarised signal to be determined. Here the angle of arrival information is obtained via a simple boresight power measurement made at the lens receive side. It is shown that an unambiguous angle of arrival information for signals arriving at up to +/- 45 degrees can be obtained.

Rigid tetracatenar liquid crystals derived from 1,10-phenanthroline

Tetracatenar liquid crystals were obtained by substituting the 1,10-phenanthroline central core unit at the 3- and 8-positions by extended, rigid acetylene moieties, equipped at the termini with two alkoxy chains of various lengths (n = 6, 8, 10, 12, 14). The liquid crystals exhibit a rich mesomorphism including smectic C, cubic, hexagonal and rectangular columnar phases, depending on the alkoxy chain length. The corresponding rhenium(I) complexes containing the bulky [ReBr(CO)₃] fragment are not liquid-crystalline. The ligands and rhenium(I) complexes were investigated by scanning tunneling microscopy (STM). Both the ligands and the rhenium(I) complexes can be self-assembled into monolayers at the TCB–graphite and octanoic acid–graphite interfaces. The ligands and rhenium(I) complexes are luminescent.