Experimental Calcification of HEMA-Based Hydrogels in the Presence of Albumin and a Comparison to the in Vivo Calcification

The precipitation patterns and characteristics of calcium phosphate (CaP) phases deposited on HEMA-based hydrogels upon incubation in simulated body fluid (SBF-2) containing a protein (human serum albumin) have been investigated in relation to the calcification in an organic-free medium (SBF-1) and to that occurring after subcutaneous implantation in rats. In SBF-2, the deposits occurred exclusively as a peripheral layer on the surface of the hydrogels and consisted mainly of precipitated hydroxyapatite, a species deficient in calcium and hydroxyl ions, similarly to the deposits formed on the implanted hydrogels, where the deposited layer was thicker. In SBF-1, the deposits were mainly of brushite type. There was no evidence that albumin penetrated the interstices of hydrogels. As the X-ray diffraction patterns of the CaP deposits generated in SBF-2 showed a similar nature with those formed on the implanted hydrogel, it was concluded that the calcification in SBF-2 can mimic to a reliable extent the calcification process taking place in a biological environment.

A method for profiling biometric changes during disaccommodation

PURPOSE: To demonstrate the application of low-coherence reflectometry to the study of biometric changes during disaccommodation responses in human eyes after cessation of a near task and to evaluate the effect of contact lenses on low-coherence reflectometry biometric measurements. METHODS: Ocular biometric parameters of crystalline lens thickness (LT) and anterior chamber depth (ACD) were measured with the LenStar device during and immediately after a 5 D accommodative task in 10 participants. In a separate trial, accommodation responses were recorded with a Shin-Nippon WAM-5500 optometer in a subset of two participants. Biometric data were interleaved to form a profile of post-task anterior segment changes. In a further experiment, the effect of soft contact lenses on LenStar measurements was evaluated in 15 participants. RESULTS: In 10 adult participants, increased LT and reduced ACD was seen during the 5 D task. Post-task, during fixation of a 0 D target, a profile of the change in LT and ACD against time was observed. In the two participants with accommodation data (one a sufferer of nearwork-induced transient myopia and other a non-sufferer), the post-task changes in refraction compared favorably with the interleaved LenStar biometry data. The insertion of soft contact lenses did not have a significant effect on LenStar measures of ACD or LT (mean change: -0.007 mm, p = 0.265 and + 0.001 mm, p = 0.875, respectively). CONCLUSIONS: With the addition of a relatively simple stimulus modification, the LenStar instrument can be used to produce a profile of post-task changes in LT and ACD. The spatial and temporal resolution of the system is sufficient for the investigation of nearwork-induced transient myopia from a biometric viewpoint. LenStar measurements of ACD and LT remain valid after the fitting of soft contact lenses.

Influence of accommodation and refractive status on the peripheral refractive profile

AIM: The aim of the study was to determine, objectively and non-invasively, whether changes in accommodative demand modify differentially the peripheral refraction in emmetropic and myopic human eyes. METHODS: Forty subjects (19 male, 21 female) aged 20-30 years (mean 22.7 (SD 2.8) years), 21 emmetropes (mean spherical equivalent refractive error (MSE) -0.13 (SD 0.29) D) and 19 myopes (MSE -2.95 (SD 1.76) D) participated in the study. Ametropia was corrected with soft contact lenses (etafilcon A, 58% water content). Subjects viewed monocularly a stationary, high contrast (85%) Maltese cross at 0.0, 1.0, 2.0 and 3.0 D of accommodative demand and at 0, 10, 20 and 30 degrees field angle (nasal and temporal) through a +3.0 D Badal optical system. Static recordings of the accommodation response were obtained for each accommodative level, at each field angle, with an objective, open-view, infrared optometer. RESULTS: Peripheral mean spherical equivalent (M) data showed that the emmetropic cohort exhibited relative myopic shifts into the periphery, while the myopic group showed hypermetropic shifts. Increasing accommodative demand did not alter the peripheral refractive profile in either the temporal (p = 0.25) or nasal (p = 0.07) periphery with no differential accommodative effect between refractive groups in either the temporal (p = 0.77) or nasal (p = 0.73) field. Significant shifts in the J(0) astigmatic component were seen in the temporal (p<0.0005) and nasal (p<0.0005) fields with increasing eccentricity. Interaction effects between eccentricity and accommodative demand illustrated that increasing accommodative demand significantly altered the peripheral refractive profile in the temporal J(0) astigmatic component (p<0.0005). The nasal periphery, however, failed to show such an effect (p = 0.65). CONCLUSIONS: Alterations in peripheral refraction augmented by changes in ocular accommodation are relatively unaffected by refractive error for young, healthy human eyes.

Ocular biomaterials and the anterior eye

Hydrogels, water swollen polymer matrices, have been utilised in many biomedical applications, as there is the potential to manipulate the properties for a given application by changing the chemical structure of the constituent monomers The eye provides an excellent site to examne the interaction between a synthetic material and a complex biological fluid without invasive surgery. There is a need for the development of new synthetic hydrogels for use in the anterior eye, Three applications of hydrogels in the eye were considered in this thesis. For some patients, the only hope of any visual improvement lies in the use of an artificial cornea, or keratoprosthesis, Preliminary investigations of a series of simple homogeneous hydrogel copolymers revealed that the mechanical properties required to withstand surgery and in eye stresses, were not achieved This lead to work on the development of semi-interpenetrating polymer networks based on the aforementioned copolymers, Manufacture of the device and cell response were also studied. Lasers have been employed in ocular surgery to correct refractive defects. If an irregular surface is ablated, an irregular surface is obtained. A hydrogel system was investigated that could be applied to the eye prior to ablation to create a smooth surface. Factors that may influence ablation rate were explored, Soft contact lenses can be used as a probe to study the interaction between synthetic materials and the biological constituents of tears. This has lead to the development of many sensitive analytical techniques for protein and lipid deposition, one of which is fluorescence spectrophotometry. Various commercially available soft contact lenses were worn for different periods of time and then analysed for protein and lipid deposition using fluorescence spectrophotometry, The influence of water content, degree of ionicity and the lens material on the level and type of deposition was investigated.

Synthetic analogues of protein-lipid complexes

Hypercoiling poly(styrene-alt-maleic anhydride) (PSMA) is known to undergo conformational transition in response to environmental stimuli. The association of PSMA with lipid 2-dilauryl-sn-glycero-3-phosphocholine (DLPC) produces polymer-lipid complex analogues to lipoprotein assemblies found in lung surfactant. These complexes represent a new bio-mimetic delivery vehicle with applications in the cosmetic and pharmaceutical industries. The primary aim of this study was to develop a better understanding of PSMA-DLPC association by using physical and spectroscopic techniques. Ternary phase diagrams were constructed to examine the effects of various factors, such as molecular weight, pH and temperature on PSMA-DLPC association. 31P-NMR spectroscopy was used to investigate the polymorphic changes of DLPC upon associating with PSMA. The Langmuir Trough technique and surface tension measurement were used to explore the association behaviour of PSMA both at the interface and in the bulk of solution, as well as its interaction with DLPC membranes. The ultimate aim of this study was to investigate the potential use of PSMA-DLPC complexes to improve the bioavailability and therapeutic efficacy of a range of drugs. Typical compounds of ophthalmic interest range from new drugs such as Pirenzepine, which has attracted clinical interest for the control of myopia progression, to the well-established family of non-steroid anti-inflammatory drugs. These drugs have widely differing structures, sizes, solubility profiles and pH-sensitivities. In order to understand the ways in which these characteristics influence incorporation and release behaviour, the marker molecules Rhodamine B and Oil Red O were chosen. PSMA-DLPC complexes, incorporated with marker molecules and Pirenzepine, were encapsulated in hydrogels of the types used for soft contact lenses. Release studies were conducted to examine if this smart drug delivery system can retain such compounds and deliver them at a slow rate over a prolonged period of time.

Protein deposition at polymer surfaces:the bulk and surface structure-property effects of hydrogels

The primary objective of this research has been to investigate the interfacial phenomenon of protein adsorption in relation to the bulk and surface structure-property effect s of hydrogel polymers. In order to achieve this it was first necessary to characterise the bulk and surface properties of the hydrogels, with regard to the structural chemistry of their component monomers. The bulk properties of the hydrogels were established using equilibrium water content measurements, together with water-binding studies by differential scanning calorimetry (D.S.C.). Hamilton and captive air bubble-contact angle techniques were employed to characterise the hydrogel-water interface and from which by a mathematical derivation, the interfacial free energy (ðsw) and the surface free energy components (ð psv, ðdsv, ðsv) were obtained. From the adsorption studies using the radio labelled iodinated (125I) proteins of human serum albumin (H.S.A.) and human fibrinogen (H.Fb.), it was Found that multi-layered adsorption was occurring and that the rate and type of this adsorption was dependent on the physico-chemical behaviour of the adsorbing protein (and its bulk concentration in solution), together with the surface energetics of the adsorbent polymer. A potential method for the invitro evaluation of a material's 'biocompatibility' was also investigated, based on an empirically observed relationship between the adsorption of albumin and fibrinogen and the 'biocompatibility' of polymeric materials. Furthermore, some consideration was also given to the biocompatibility problem of proteinaceous deposit formation on hydrophilic soft' contact lenses and in addition a number of potential continual wear contact lens formulations now undergoing clinical trials,were characterised by the above techniques.

Grading of corneal transparency

Aim: To examine the academic literature on the grading of corneal transparency and to assess the potential use of objective image analysis. Method: Reference databases of academic literature were searched and relevant manuscripts reviewed. Annunziato, Efron (Millennium Edition) and Vistakon-Synoptik corneal oedema grading scale images were analysed objectively for relative intensity, edges detected, variation in intensity and maximum intensity. In addition, corneal oedema was induced in one subject using a low oxygen transmissibility (Dk/t) hydrogel contact lens worn for 3 hours under a light eye patch. Recovery from oedema was monitored over time using ultrasound pachymetry, high and low contrast visual acuity measures, bulbar hyperaemia grading and transparency image analysis of the test and control eyes. Results: Several methods for assessing corneal transparency are described in the academic literature, but none have gained widespread in clinical practice. The change in objective image analysis with printed scale grade was best described by quadratic parametric or sigmoid 3-parameter functions. ‘Pupil image scales’ (Annunziato and Vistakon-Synoptik) were best correlated to average intensity; however, the corneal section scale (Efron) was strongly correlated to variations in intensity. As expected, patching an eye wearing a low Dk/t hydrogel contact lens caused a significant (F=119.2, P<0.001) 14.3% increase in corneal thickness, which gradually recovered under open eye conditions. Corneal section image analysis was the most affected parameter and intensity variation across the slit width, in isolation, was the strongest correlate, accounting for 85.8% of the variance with time following patching, and 88.7% of the variance with corneal thickness. Conclusion: Corneal oedema is best determined objectively by the intensity variation across the width of a corneal section. This can be easily measured using a slit-lamp camera connected to a computer. Oedema due to soft contact lens wear is not easily determined over the pupil area by sclerotic scatter illumination techniques.

International session at the BCLA conference

Full text: It seems a long time ago now since we were at the BCLA conference. The excellent FIFA World Cup in Brazil kept us occupied over the summer as well as Formula 1, Wimbledon, Tour de France, Commonwealth Games and of course exam paper marking! The BCLA conference this year was held in Birmingham at the International Convention Centre which again proved to be a great venue. The number of attendees overall was up on previous years, and at a record high of 1500 people. Amongst the highlights at this year's annual conference was the live surgery link where Professor Sunil Shah demonstrated the differences in technique between traditional phacoemulsification cataract surgery and femtosecond assisted phacoemulsification cataract surgery. Dr. Raquel Gil Cazorla, a research optometrist at Aston University, assisted in the procedure including calibrating the femtosecond laser. Another highlight for me was the session that I chaired, which was the international session organised by IACLE (International Association of CL Educators). There was a talk by Mirjam van Tilborg about dry eye prevalence in the Netherlands and how it was managed by medical general practitioners (GPs) or optometrists. It was interesting to know that there are only 2 schools of optometry there and currently under 1000 registered optometrists there. It also seems that GPs were more likely to blame CL as the cause for dry eye whereas optometrists who had a fuller range of tests were better at solving the issue. The next part of the session included the presentation of 5 selected posters from around the world. The posters were also displayed in the main poster area but were selected to be presented here as they had international relevance. The posters were: 1. Motivators and Barriers for Contact Lens Recommendation and Wear by Nilesh Thite (India) 2. Contact lens hygiene among Saudi wearers by Dr. Ali Masmaly (Saudi) 3. Trends of contact lens prescribing and patterns of contact lens practice in Jordan by Dr. Mera Haddad (Jordan) 4. Contact Lens Behaviour in Greece by Dr. Dimitra Makrynioti (Greece) 5. How practitioners inform ametropes about the benefits of contact lenses and overcome the potential barriers: an Italian survey, by Dr. Fabrizio Zeri (Italy) It was interesting to learn about CL practice in different parts, for example the CL wearing population ration in Saudi Arabia is around 1:2 Male:Female (similar to other parts of the world) and although the sale of CL is restricted to registered practitioners there are many unregistered outlets, like clothing stores, that flout the rules. In Jordan some older practitioners will still advise patients to use tap water or even saliva! But thankfully the newer generation of practitioners have been educated not to advise this. In Greece one of the concerns was that some practitioners may advise patients to use disposable lenses for longer than they should and again it seems to be the practitioners with inadequate education that would do this. In India it was found that cost was one barrier to using contact lenses but also some practitioners felt that they shouldn’t offer CLs due to cost too. In Italy sensitive eyes and CL care and maintenance were the barriers to CL wear but the motivators were vision and comfort and aesthetics. Finally the international session ended with the IACLE travel award and educator awards presented by IACLE president Shehzad Naroo and BCLA President Andrew Yorke. The travel award went to Wang Ling, Jinling Institute of Technology, Nanjing, China. There were 3 regional Contact Lens Educator of the Year Awards sponsored by Coopervision and presented by Dr. J.C. Aragorn of Coopervision. 1. Asia Pacific Region – Dr. Rajeswari Mahadevan of Sankara Nethralaya Medical Research Foundation, Chennai, India 2. Americas Region – Dr. Sergio Garcia of University of La Salle, Bogotá and the University Santo Tomás, Bucaramanga, Colombia 3. Europe/Africa – Middle East Region: Dr. Eef van der Worp, affiliated with the University of Maastricht, the Netherlands The posters above were just a small selection of those displayed at this year's BCLA conference. If you missed the BCLA conference then you can see the abstracts for all posters and talks in a virtual issue of CLAE very soon. The poster competition was kindly sponsored by Elsevier. The poster winner this year was: Joan Gispets – Corneal and Anterior Chamber Parameters in Keratoconus The 3 runners up were: Debby Yeung – Scleral Lens Central Corneal Clearance Assessment with Biomicroscopy Sarah L. Smith – Subjective Grading of Lid Margin Staining Heiko Pult – Impact of Soft Contact Lenses on Lid Parallel Conjunctival Folds My final two highlights are a little more personal. Firstly, I was awarded Honorary Life Fellowship of the BCLA for my work with the Journal, and I would like to thank the BCLA, Elsevier, the editorial board of CLAE, the reviewers and the authors for their support of my role. My final highlight from the BCLA conference this year was the final presentation of the conference – the BCLA Gold Medal award. The recipient this year was Professor Philip Morgan with his talk ‘Changing the world with contact lenses’. Phil was the person who advised me to go to my first BCLA conference in 1994 (funnily he didn’t attend himself as he was busy getting married!) and now 20 years later he was being honoured with the accolade of being the BCLA Gold Medallist. The date of his BCLA medal addressed was shared with his father's birthday so a double celebration for Phil. Well done to outgoing BCLA President Andy Yorke and his team at the BCLA (including Nick Rumney, Cheryl Donnelly, Sarah Greenwood and Amir Khan) on an excellent conference. And finally welcome to new President Susan Bowers. Copyright © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

The influence of simulated cataract on retinal vessel oximetry measurements

PURPOSE: To assess the impact of human crystalline lens opacification and yellowing, similar to that observed in patients with cataracts, on retinal vessel blood oxygen saturation measurements using custom manufactured soft contact lenses. METHODS: Ten healthy, non-smoking individuals were enrolled for this study. All subjects underwent digital blood pressure measurements, assessment of non-contact intra-ocular pressure, pupil dilation and retinal vessel oximetry using dual-wavelength photography (Oximetry Module, Imedos Systems). To simulate lens changes, three different contact lenses were inserted, one to simulate opacities followed by two more lenses to simulate different levels of lens yellowing (Cantor & Nissel). RESULTS: The measurements obtained showed an opposite change in arterial and venous oxygen saturation and optical density ratio across conditions, resulting in a statistically significant difference in arterial minus venous oxygen saturation value (p = 0.003). However, this difference was only significant for the 'opacity' condition but not for the 'yellowing' conditions. CONCLUSION: Lenticular changes such as cataracts can impact on spectrophotometric analysis in particular dual-wavelength retinal vessel oximetry. Hence, lenticular assessment and cataract grading should be considered when assessing elderly individuals and patient groups developing cataract earlier in life such as those suffering from diabetes mellitus.

Changes in Diadenosine Polyphosphates during Alignment-Fit and Orthokeratology Rigid Gas Permeable

Purpose.: To evaluate the levels of dinucleotides diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A) in tears of patients wearing rigid gas permeable (RGP) contact lenses on a daily wear basis and of patients wearing reverse-geometry RGP lenses overnight for orthokeratology treatment. Methods.: Twenty-two young volunteers (10 females, 12 males; 23.47 ± 4.49 years) were fitted with an alignment-fit RGP lens (paflufocon B) for a month, and after a 15-day washout period they were fitted with reverse-geometry RGP lenses for corneal reshaping (paflufocon D) for another month. During each period, tears were collected at baseline day 1, 7, 15, and 28. Ap4A and Ap5A were measured by high-pressure liquid chromatography (HPLC). Additionally, corneal staining, break-up time (BUT), Schirmer test, and dryness symptoms were evaluated. Results.: Ap4A concentrations increased significantly from baseline during the whole period of daily wear of RGP lenses (P < 0.001); concentration was also significantly higher than in the orthokeratology group, which remained at baseline levels during the study period except at day 1 (P < 0.001) and day 28 (P = 0.041). While BUT and Schirmer remained unchanged in both groups, discomfort and dryness were significantly increased during alignment-fit RGP daily wear but not during the orthokeratology period. Conclusions.: Daily wear of RGP lenses increased the levels of Ap4A due to mechanical stimulation by blinking of the corneal epithelium, and this is associated with discomfort. Also, orthokeratology did not produce symptoms or signs of ocular dryness, which could be a potential advantage over soft contact lenses in terms of contact lens-induced dryness.

Contact instabilities of anisotropic and inhomogeneous soft elastic films

Anisotropy plays important roles in various biological phenomena such as adhesion of geckos and grasshoppers enabled by the attachment pods having hierarchical structures like thin longitudinal setae connected with threads mimicked by anisotropic films. We study the contact instability of a transversely isotropic thin elastic film when it comes in contact proximity of another surface. In the present study we investigate the contact stability of a thin incompressible transversely isotropic film by performing linear stability analysis. Based on the linear stability analysis, we show that an approaching contactor renders the film unstable. The critical wavelength of the instability is a function of the total film thickness and the ratio of the Young's modulus in the longitudinal direction and the shear modulus in the plane containing the longitudinal axis. We also analyze the stability of a thin gradient film that is elastically inhomogeneous across its thickness. Compared to a homogeneous elastic film, it becomes unstable with a longer wavelength when the film becomes softer in going from the surface to the substrate.

Analysis of the peri-implant soft tissues in contact with zirconia abutments: an evidence-based literature review

The aim of this study is to evaluate through a literature review, the soft tissue response in contact with zirconia abutments, including case reports comparing prosthetics rehabilitations with zirconia and titanium abutments upto 3 years of follow-up as well as the factors that should be considered on implant's abutment selection. Metallic abutments can provide grayish color when in contact with thin soft tissues which may lead the implant prosthetic treatment to failure. In this context, the abutments of zirconia stand out because there is an excellent linking between esthetics and the health of peri-implant soft tissues. A consult of the published researches was made on the PubMed database from 2000 to September 2012. The including criteria were: literature reviews, clinical studies and case reports in English that focused on the response of the soft tissue in contact with zirconia implant abutments. The studies that were not in English and did not match the tackled issue were excluded. A total of 32 articles were found. According to the search strategy, just 16 articles were selected for this review. Three studies affirmed that zirconia abutments have an excellent soft tissue response; one study showed increased gingival recession with zirconia abutments and nine studies do not stand out any difference on biological behavior between titanium and zirconia abutments. Three studies affirmed that zirconia abutments provide natural gingival appearance, anatomic contour and greater esthetics. The use of zirconia abutments is recommended for anterior regions because of their greater optical properties and esthetic results and more studies should be performed and analyzed longitudinally regarding their biological response. The zirconia abutments have been established to be essential in order to achieve great esthetic results in cases of thin peri-implant soft tissues and in regions where the three-dimensional placement of implants is more superficial.

Comparison of fitting stability of the different soft toric contact lenses

Purpose: To compare lens orientation and rotational recovery of five currently available soft toric lenses. Methods: Twenty subjects were recruited and trialed with each of the study lenses in a random order. Study lenses were PureVision® Toric (B&L), Air Optix® for Astigmatism (Alcon), Biofinity® Toric (CooperVision), Acuvue® Advance for Astigmatism (Vistakon), and Proclear® Toric (CooperVision). Lens orientation in primary position to determine the lens rotation form the vertical position and rotational recovery to primary gaze orientation following a 45° manual misorientation for the different lenses was compared. Results: The Biofinity Toric showed the lowest rotation from the vertical position and the Proclear Toric the highest. Also, the highest and the lowest reorientation speed were related to the Biofinity Toric and the Acuvue Advance for Astigmatism, respectively. The Repeated Measures ANOVA showed a significant difference in the lens rotation (P=. 0.004) and rotational recovery (P<. 0.001) among different contact lenses and the performed multiple comparisons indicated differences in rotation and also in reorientation speed were only seen between the Biofinity Toric when compared to four other lenses (P<. 0.05). Conclusion: Although there was appropriate fitting, based upon lens orientation and reorientation speed, with each of the study lenses it would appear that the optimized ballast technique used in the design of the Biofinity Toric helps reduce lens rotation and improve rotational recovery compared to others.

Modelling the effects of bone fragment contact in fracture healing

The fracture healing process is modulated by the mechanical environment created by imposed loads and motion between the bone fragments. Contact between the fragments obviously results in a significantly different stress and strain environment to a uniform fracture gap containing only soft tissue (e.g. haematoma). The assumption of the latter in existing computational models of the healing process will hence exaggerate the inter-fragmentary strain in many clinically-relevant cases. To address this issue, we introduce the concept of a contact zone that represents a variable degree of contact between cortices by the relative proportions of bone and soft tissue present. This is introduced as an initial condition in a two-dimensional iterative finite element model of a healing tibial fracture, in which material properties are defined by the volume fractions of each tissue present. The algorithm governing the formation of cartilage and bone in the fracture callus uses fuzzy logic rules based on strain energy density resulting from axial compression. The model predicts that increasing the degree of initial bone contact reduces the amount of callus formed (periosteal callus thickness 3.1mm without contact, down to 0.5mm with 10% bone in contact zone). This is consistent with the greater effective stiffness in the contact zone and hence, a smaller inter-fragmentary strain. These results demonstrate that the contact zone strategy reasonably simulates the differences in the healing sequence resulting from the closeness of reduction.

Factors influencing the prescribing of hydrogel contact lenses

Despite the current market popularity of silicone hydrogel contact lenses, conventional hydrogel lenses still represent a significant proportion of the overall contact lens market. Data gathered from annual UK contact lens fitting surveys over the past 13 years indicate that 64% of hydrogel lenses prescribed during this period were of low/medium water content (<60% water). Whereas, in the past, practitioners would choose the water content of a hydrogel lens to meet specific clinical needs, this choice appears today to be largely governed by product availability.