Polymeric hydrogels for novel contact lens-based ophthalmic drug delivery systems: a review.

Only about 5% of drugs administrated by eye drops are bioavailable, and currently eye drops account for more than 90% of all ophthalmic formulations. The bioavailability of ophthalmic drugs can be improved by a soft contact lens-based ophthalmic drug delivery system. Several polymeric hydrogels have been investigated for soft contact lens-based ophthalmic drug delivery systems: (i) polymeric hydrogels for conventional contact lens to absorb and release ophthalmic drugs; (ii) polymeric hydrogels for piggyback contact lens combining with a drug plate or drug solution; (iii) surface-modified polymeric hydrogels to immobilize drugs on the surface of contact lenses; (iv) polymeric hydrogels for inclusion of drugs in a colloidal structure dispersed in the lens; (v) ion ligand-containing polymeric hydrogels; (vi) molecularly imprinted polymeric hydrogels which provide the contact lens with a high affinity and selectivity for a given drug. Polymeric hydrogels for these contact lens-based ophthalmic drug delivery systems, their advantages and drawbacks are critically analyzed in this review.     

Surface morphology of contact lenses probed with microscopy techniques.

The present study is bringing a comparison of surface morphology for various types of contact lenses. A novel method--scanning electron microscopy under aqueous conditions (cryo-SEM)--was tested for visualization of lenses at magnifications up to 2000x. For imaging lens surface on nanometre scale, we employed atomic force microscopy (AFM) in aqueous media. Various materials of lenses, based on silicone hydrogels or conventional hydrogels, were investigated. Total, 10 types of contact lenses from five manufacturers were selected and probed. We found that different methods of lens manufacture (lathe-cutting, cast-moulding, and spin casting) led to different values of surface roughness. In the swollen state, roughness values of lens surfaces lie between 4 and 140 nm. Lenses manufactured by lathe-cutting exhibit notable higher values, so that they could be easily distinguished from others. In cast-moulded lenses, the surface roughness decreased with increasing water content. Moreover, additional treatments of lenses introduced unique structural motifs onto surface. For instance, porous structure was found on lens surface finalized with plasma oxidation.     

In-eye performance of soft contact lenses made from different materials.

The in-eye performance of soft contact lenses may be affected by the material from which they are fabricated and may alter during wear. This study describes clinical and laboratory experiments that were conducted in order to examine the in-eye performance of eight soft contact lenses manufactured from different materials; these materials (and nominal water contents) were: HEMA/VP 40%, HEMA/VP 55%, HEMA/VP 70%, VP/MMA 55%, VP/MMA 70%, HEMA 40%, HEMA/MAA 55% and HEMA/MAA 70% (HEMA: 2-hydroxy-ethyl methacrylate, VP: vinyl pyrrolidone, MMA: methyl methacrylate, MAA: methacrylic acid). Two lenses from each of the eight soft contact lens groups were used in experiments concerning their parameter stability. Six subjects were fitted with lenses for 1 day. Verification of back optic zone radius, total diameter, back vertex power, centre thickness and water content was undertaken at 20 degrees C. In vitro measurements of total diameter were taken at 35 degrees C before lens fitting and after 6 h of lens wear. In vivo measurements of lens centration, up-gaze lag, post-blink movement, total diameter and subjective assessment of comfort were taken (a) immediately after lens insertion (1 min), (b) 20 min later and (c) 6 h later (same day). The majority of differences of the in vivo parameters between lens types (with respect to lens centration, lag, movement on blink, lens total diameter and comfort) were not found to be statistically significant throughout the 6 h wearing period. It was also found that lenses increase in diameter when first placed on the eye and decrease in diameter when they were removed from the eye. The information generated in study concerning the in-eye performance of soft contact lens materials may assist the contact lens industry and contact lens practitioners in developing and prescribing soft lenses with optimal performance characteristics.     

Calculated tear oxygen tension under contact lenses offering resistance in series: piggyback and scleral lenses.

BACKGROUND: Models of oxygen delivery to the cornea with contact lens wear have considered the customary situation of one lens being worn on the cornea. However, two lenses, such as a rigid lens piggybacked on a soft lens, may be worn by patients with special ocular and visual needs. This paper extends existing single lens models to circumstances where two lenses offer resistance to oxygen in series. METHODS: Theoretical oxygen tensions are calculated for tear layers trapped beneath piggyback contact lens systems (and scleral lenses) and the anterior corneal surface with a simple single chamber corneal model using a personal computer software spreadsheet. RESULTS: Acceptable values are anticipated for contact lens materials of modern oxygen permeability values of approximately 60-100 Fatt Dk units under open eye conditions. CONCLUSIONS: The results of this spreadsheet model of oxygen supply to the anterior corneal surface offer a useful guide to clinicians concerned about providing their patients with physiologically acceptable piggyback lens systems.     

The effect of contact lens wear on dynamic ocular surface temperature.

AIM: To determine the dynamic emitted temperature changes of the anterior eye during and immediately after wearing different materials and modalities of soft contact lenses. METHOD: A dynamic, non-contact infrared camera (Thermo-Tracer TH7102MX, NEC San-ei) was used to record the ocular surface temperature (OST) in 48 subjects (mean age 21.7 +/- 1.9 years) wearing: lotrafilcon-A contact lenses on a daily wear (LDW; n=8) or continuous wear (LCW; n=8) basis; balafilcon-A contact lenses on a daily wear (BDW; n=8) or continuous wear (BCW; n=8) basis; etafilcon-A contact lenses on a daily disposable regimen (EDW; n=8); and no lenses (controls; n=8). OST was measured continuously five times, for 8s after a blink, following a minimum of 2h wear and immediately following lens removal. Absolute temperature, changes in temperature post-blink and the dynamics of temperature changes were calculated. RESULTS: OST immediately following contact lens wear was significantly greater compared to non-lens wearers (37.1 +/- 1.7 degrees C versus 35.0 +/- 1.1 degrees C; p < 0.005), predominantly in the LCW group (38.6 +/- 1.0 degrees C; p < 0.0001). Lens surface temperature was highly correlated (r=0.97) to, but lower than OST (by -0.62 +/- 0.3 degrees C). There was no difference with modality of wear (DW 37.5 +/- 1.6 degrees C versus CW 37.8+/-1.9 degrees C; p=0.63), but significant differences were found between etafilcon A and silicone hydrogel lens materials (35.3 +/- 1.1 degrees C versus 37.5 +/- 1.5 degrees C; p < 0.0005). Ocular surface cooling following a blink was not significantly affected by contact lens wear with (p=0.07) or without (p=0.47) lenses in situ. CONCLUSIONS: Ocular surface temperature is greater with hydrogel and greater still with silicone hydrogel contact lenses in situ, regardless of modality of wear. The effect is likely to be due to the thermal transmission properties of a contact lens.     

Clinical evaluation of a custom-made toric soft lens.

PURPOSE: The fitting of toric soft contact lenses is often complicated by interference between the toric optics and the geometry need to stabilise the lens on the eye. The use of a spherical trial lens to determine the parameters of a toric soft contact lens can lead to unintended positioning and movement of the lens ordered. The purpose of this study was to evaluate clinically the success. PURPOSE: The fitting of toric soft contact lenses is often complicated by interference between the toric optics and the geometry needed. METHOD: The design of the lenses used was such that optical correction and stabilisation were separated. The lenses had a back tonic surface limited to the central optical zone and base down prism stabilisation in the periphery. The empirical system used corneal radii, spectacle refraction and horizontal visible iris diameter as lens design parameters. RESULTS: This multi-centre trial, comprised of 105 patients (193 eyes), revealed an overall success rate of 86%. The total number of lenses ordered to achieve success was 1.46 per eye in new patients and 1.69 per eye in patients who were failures with other toric soft lenses. In 14% of the cases success could not be achieved despite ordering several lenses (up to 4 lenses/eye). Many of these patients (60%) were also failures with other toric soft lenses. CONCLUSION: It is concluded that in new patients successful toric soft contact lens fitting can be achieved with an empirically based method. When refitting former toric soft lens failures, we recommend discontinuation after two further unsuccessful fittings.     

Silicone hydrogel daily disposable benefits: The evidence

Daily disposable (DD) contact lenses first came to the market approximately 25 years ago and eye care professionals (ECPs) started prescribing silicone hydrogel (SiH) contact lenses, primarily for extended or continuous wear, approximately 20 years ago. It has now been over ten years since SiH DD contact lenses have been available, and while SiH materials are routinely prescribed by ECPs for reusable daily wear, hydrogel materials are still frequently selected for the DD modality of contact lens wear. This article reviews the evidence to support the benefits of both a DD modality and SiH materials and how patients’ needs may be met with SiH DD contact lenses, with respect to clinical performance, health outcomes, satisfaction, compliance and convenience. Factors which may enable or constrain ECPs from prescribing SiH DD contact lenses, as opposed to hydrogel DD and reusable contact lenses, for more of their patients are discussed with the objective of providing ECPs with a greater understanding of the advantages that can be afforded by prescribing SiH DD contact lenses to both their new and existing contact lens wearers.     

Corneal epithelial bullae after short-term wear of small diameter scleral lenses

Complications of scleral lens wear are not well documented or understood. While multiple studies focus on oxygen transmission during scleral lens wear and associated corneal swelling, little is known about the effects of varying scleral lens fitting relationships, especially when there is corneal interaction. Scleral lenses, by convention, are designed to completely clear the corneal surface and rest on the conjunctival and scleral tissue. However, some designs maximize oxygen transmission by reducing the lens diameter, thickness, and recommended corneal clearance.While the modifications increase oxygen transmission in any scleral lens design, they also distribute the lens mass closer to the limbus and make visualization of corneal clearance, especially narrow in the limbal region, more difficult. The sequelae from mechanical interaction between scleral lenses and the ocular surface, in particular the cornea, remain uncertain.This case series will describe corneal epithelial bullae, molding, and epithelial erosions as unintended scleral lens complications. These corneal changes corresponded to areas of contact lens-corneal bearing confirmed utilizing a combined scanning laser ophthalmoscopy (SLO) and anterior segment OCT. This case series will discuss epithelial bullae detection, their etiology, and suggestions for application of this information into scleral lens fitting protocols.     

Refractive index of rigid contact lens materials.

A simple hand-held refractometer was used to measure the refractive index of 27 rigid gas permeable contact lens materials. As a general rule, lenses with refractive indices lower than 1.458 are made from fluorosilicone acrylates; lenses with refractive indices in the range of 1.458 to 1.469 are made from either fluorosilicone acrylates or silicone acrylates; and lenses with refractive indices greater than 1.469 are made from silicone acrylates. It is demonstrated how refractometry can be used by contact lens practitioners for the identification and verification of rigid contact lenses.     

Flexure of thin rigid contact lenses.

The flexure of spherical rigid contact lenses was measured on the eyes of 10 young subjects using a videokeratoscope. Five subjects had little or no with-the-rule astigmatism (<0.75 D) andfive had moderate levels of with-the-rule astigmatism (1.00-2.00 D). Two lens materials (polymethylmethacrylate [PMMA] and Boston XO) in three centre thicknesses (0.05, 0.10 and 0.15 mm) were used in the study. No significant difference in the amount of flexure was found between the two materials tested. The degree of regular astigmatism on the lens front surface was found to increase as the centre thickness of the contact lens decreased. For the astigmatic group, the lenses with centre thicknesses of 0.05 mm had levels of front surface astigmatism similar to those of the underlying cornea. On spherical corneas the level of regular astigmatism can exceed that of the cornea for thinner lenses. When sphero-cylinder variations are accounted for, residual higher order aberration (root mean square) levels were found to approach those of the cornea when the lens thickness was reduced to 0.05 mm.     

BCLA CLEAR - Effect of contact lens materials and designs on the anatomy and physiology of the eye

This paper outlines changes to the ocular surface caused by contact lenses and their degree of clinical significance. Substantial research and development to improve oxygen permeability of rigid and soft contact lenses has meant that in many countries the issues caused by hypoxia to the ocular surface have largely been negated. The ability of contact lenses to change the axial growth characteristics of the globe is being utilised to help reduce the myopia pandemic and several studies and meta-analyses have shown that wearing orthokeratology lenses or soft multifocal contact lenses can reduce axial length growth (and hence myopia).However, effects on blinking, ptosis, the function of Meibomian glands, fluorescein and lissamine green staining of the conjunctiva and cornea, production of lid-parallel conjunctival folds and lid wiper epitheliopathy have received less research attention. Contact lens wear produces a subclinical inflammatory response manifested by increases in the number of dendritiform cells in the conjunctiva, cornea and limbus. Papillary conjunctivitis is also a complication of all types of contact lenses. Changes to wear schedule (daily disposable from overnight wear) or lens materials (hydrogel from SiHy) can reduce papillary conjunctivitis, but the effect of such changes on dendritic cell migration needs further study. These changes may be associated with decreased comfort but confirmatory studies are needed. Contact lenses can affect the sensitivity of the ocular surface to mechanical stimulation, but whether these changes affect comfort requires further investigation.In conclusion, there have been changes to lens materials, design and wear schedules over the past 20+ years that have improved their safety and seen the development of lenses that can reduce the myopia development. However, several changes to the ocular surface still occur and warrant further research effort in order to optimise the lens wearing experience.     

Acanthamoeba keratitis associated with misuse of daily disposable contact lenses.

PURPOSE: To report a case of Acanthamoeba keratitis that occurred in a daily disposable contact lens wearer. METHOD: Case report. RESULTS: A 70-year-old gentleman presented to eye casualty with a red left eye with reduced vision and corneal epithelial changes. Acanthamoeba keratitis was not suspected initially as he was a daily disposable contact lens wearer. This led to a delay of 17 days in initiating treatment. He responded well to topical polyhexamethylene biguanide and propamidine and made a full recovery. CONCLUSION: Acanthamoeba keratitis can occur in patients who reuse daily disposable contact lenses. A diagnosis of Acanthamoeba keratitis can be difficult to make and should be considered in all patients who wear contact lenses, including daily disposable lenses. All patients who wear daily disposable contact lenses should be reminded that the benefits of this modality of contact lens are only possible if the lenses are worn once and thrown away.     

Contact lenses and the rate of evaporation measured in vitro; the influence of wear,squalene and wax

Accelerated evaporation of tears may contribute to dry eye symptoms. It is not clear whether contact lenses decrease or increase the rate of evaporation of tears. In this study, the rates of evaporation through contact lenses (ERTCL) were measured in vitro to gain insight to this question. Contact lenses were equilibrated with various solutions to determine if they influenced ERTCL in vitro. ERTCL was measured gravimetrically. ERTCL measured in vitro for used contact lenses was about 20% faster than for buffer alone suggesting that natural tear components bound to the lenses changed the ERTCL. One natural tear component that binds to contact lenses is waxes. Equilibration of contact lenses with wax increased the ERTCL by about 30% suggesting that waxes might potentially increase ERTCL in vivo. Squalene, found in sebum and possibly meibum was infused into the contact lenses as a step toward decreasing the ERTCL. Squalene decreased ERTCL by over 60% in vitro. Soaking a contact lens in DuraSite^® with benzalkonium chloride (BAK) did not alter the ERTCL. ERTCL were about 40% higher than the evaporation rate of DuraSite^® alone or without BAK.In addition to lowering the ERTCL, the squalene in contact lenses could be a source of terpenoids to replace the terpenoids deficient in patients with MGD. If the ERTCL could be minimized in vivo, contact lenses could potentially be used to relieve dry eye symptoms in patients with evaporative dry eye.     

Effects of lysosomal deposition on the friction coefficient of hydrogel contact lenses

When a contact lens is in contact with the eyelid and the cornea, tear proteins start to be accumulated on the lens and may subsequently undergo conformational changes. Protein adsorption or conformational changes on the lens may lead to discomfort, red eye, or even inflammatory reactions. Although measuring the friction coefficient of contact lens has been linked to comfort degree in vivo, there is not much research about the effects of tear protein deposition on the friction coefficient of the contact lens. Therefore, we investigated the friction coefficient of three distinct materials of contact lenses in two different lysosomal concentrations. We also studied lysozyme deposition on the lens without the influence of friction. The results demonstrated that although the amount of lysozyme deposition was high on all the materials we tested, it was not corresponded to higher friction coefficient. In addition, we investigated the effect of the contact lens care solution we developed on friction coefficient and lysozyme deposition of three different materials of contact lenses. The results showed that the care solution could reduce the increased friction coefficient caused by high lysosomal concentration. Therefore, we proposed a potential mechanism of why lysosomal deposition may result in high friction coefficient for certain types of hydrogel contact lenses.     

Exploring contact lens opportunities for patients above the age of 40 years

PurposeContact lenses offer a good option for patients with presbyopia, especially with improved optical designs available in modern multifocal contact lenses. Due to the ageing population there is good opportunity to increase contact lens penetration by managing these patients better. However, multifocal contact lenses achieve low penetration in the market.MethodsA questionnaire was administered to people aged above 40 years, to investigate their perceptions of contact lenses for presbyopia. Only people, with presbyopia, who were existing contact lens wearers or willing to try contact lenses were included. Participants were recruited from United Kingdom (UK), United States of America (USA), Netherlands, Germany, France, Spain and Italy.ResultsData from 1540 participants above the age of 40 years was collected, 57.9% were females and 42.1% males. Overall, 50.8% of the participants wore contact lenses, but contact lens wear was less common amongst older participants. Some data supported earlier studies, such as 6.1% wore gas permeable lenses. However, only 25% of the contact lens wearers used multifocal contact lenses. The reasons the participants wanted to wear contact lenses were similar to younger patient such as sports or cosmesis reasons. Reasons why participants had dropped out of contact lenses included discomfort and dry eye related issues. Poor visual performance with contact lenses was a reason to dropout of contact lenses for the older participants.ConclusionsThe study highlights some failings by eye care practitioners in the management of patients with presbyopia. It seems that patients of this age group are seeking suggestions and recommendations from their eye care practitioner including upgrading contact lenses and dual wear options. The day-to-day problems encountered by the contact lens wearers in this study seem to be, in the main, things that could be easily tackled by additional counselling and instruction from the eye care practitioners.     

Contact lens wear and diabetes mellitus.

An estimated 30,000 diabetic patients in the United Kingdom currently wear contact lenses. Anecdotal clinical experience indicates that such patients have an increased risk of developing potentially sight-threatening ocular complications such as ulcerative keratitis. The corneal complications associated with diabetes, for example structural changes in the epithelial and endothelial cells, have led to some controversy regarding the suitability of contact lenses for diabetic patients. There have been few published studies documenting the ocular response of the diabetic eye to current generation contact lens materials. The purpose of this paper is to review the anterior eye manifestations of diabetes and to discuss how such changes could influence contact lens wear.     

Water properties of soft contact lens materials.

The properties of water in soft contact lenses such as the water content, free-to-bound water ratio, and the extent to which soft lenses dehydrate during wear, are key determinants of their in eye performance and oxygen transmissibility characteristics. This study describes clinical and laboratory experiments that were conducted in order to examine the state of water in eight soft contact lenses manufactured from different materials. Specifically, lenses made from the following eight materials (and nominal water contents) were used: HEMA/VP 40%, HEMA/VP 55%, HEMA/VP 70%, VP/MMA 55%, VP/MMA 70%, HEMA 40%, HEMA/MAA 55% and HEMA/MAA 70% [HEMA = 2-hydroxy-ethyl methacrylate, VP = vinyl pyrrolidone, MMA = methyl methacrylate, MAA = methacrylic acid]. Differential scanning calorimetry (DSC) was used for measuring the free water content in the materials listed above. Some noticeable differences in water properties among soft contact lens materials having approximately the same water contents were revealed. Low water content materials exhibited a simple endotherm and all water melted around 0 degrees C. On the other hand, medium and high water content materials exhibited multiple melting endotherms, representing a broad range of interactions between water and the polymer. Low water content soft contact lenses have approximately the same amount of bound water as those with much higher water contents. Six subjects were then fitted with the same lenses for one day. In vitro measurements of water content and oxygen transmissibility were taken at 35 degrees C, both before lens fitting and after 6 h of lens wear. Water content and oxygen transmissibility were correlated with the water properties of the soft contact lens materials. The relative change in lens water content (%deltaWC) and relative change in lens oxygen transmissibility (%deltaDk/t) were calculated and correlated with the water properties of the eight soft contact lens materials. It was concluded that (a) oxygen transmissibility, free water content and free-to-bound water ratio are increased when the water content of a contact lens is increased and (b) water content, free water content and free-to-bound water ratio cannot be used for the prediction of soft contact lens dehydration in vivo.     

Retention of conditioning agent hyaluronan on hydrogel contact lenses

Hyaluronan, a member of the glycosaminoglycan family of biological polysaccharides, is a high-molecular-weight disaccharide polymer found throughout the human body, particularly in the eye. Bausch + Lomb Biotrue? multi-purpose solution contains hyaluronan as a lens conditioning agent. The retention of hyaluronan from Biotrue multi-purpose solution to a variety of hydrogel contact lenses was evaluated over time. Fluorescein-tagged hyaluronan was allowed to adhere to lenses, which were then rinsed with balanced salt solution at a rate comparable to human tear secretion. Results demonstrated that hyaluronan was released slowly throughout the rinse period. The chemistry of the lens materials appeared to contribute to the hyaluronan retention capacity for each lens type. The results suggest that a multi-purpose solution containing hyaluronan has the potential to provide lens conditioning regardless of the hydrogel contact lens used.     

BCLA CLEAR - Contact lens wettability,cleaning, disinfection and interactions with tears

Contact lens materials have undergone significant changes over the past 20 years, particularly with respect to the introduction of silicone hydrogel materials. Whilst this development addressed hypoxic issues, other important areas relating to contact lens success, notably comfort, require further research.Contact lens wettability remains a crucially important part of biocompatibility. Contact lenses can be made more wettable by incorporation of surfactants into blister packs, internal wetting agents, surface treatments or care solutions. However, there remains no clear association between contact lens wettability and comfort, making it challenging to determine the potential for these approaches to be of significant clinical benefit. Most contact lenses are used on a daily wear, reusable basis, which requires them to be disinfected when not worn. The ideal disinfecting solution would also improve comfort during wear. However, balancing these requirements with other factors, including biocompatibility, remains a challenge. Soft lens materials invariably take up and subsequently release certain components of disinfecting solutions onto the ocular surface. This may affect tear film stability and the normal ocular microbiome, and further research is needed in this area to determine whether this has any affect on comfort. Finally, contact lens materials sorb components of the tear film, and these interactions are complex and may change the biochemistry of the tear film, which in turn may affect their comfort.In conclusion, the interaction between lens materials, tear film and disinfection solution plays an important role in the biocompatibility of lenses. However, the exact role and whether this can be altered to improve biocompatibility and comfort during wear remains debatable. This report summarises the best available evidence to examine this complex relationship and the opportunities for practitioners to enhance in-eye comfort of contemporary lenses, along with providing suggestions for areas of study that may provide further information on this topic.