Deborah F. Sweeney

In vivo confocal microscopy of the human cornea

Aims: To describe the optics of in vivo confocal microscopy, its advantages over previous methods, and to summarise the literature that arose from its use for the observation of the human cornea. A critical review of the clinical usefulness of this new technology for the corneal examination is undertaken. Methods: Confocal microscopes obtain increased resolution by limiting the illumination and observation systems to a single point. Rapid scanning is used to reconstruct a full field of view and allows for “real time” viewing. Results: Coronal sections of the in situ epithelium, Bowman’s membrane, stroma, and endothelium can be visualised at a resolution of 1–2 μm. A backscattered light intensity curve allows objective measurements of sublayer thickness and corneal haze to be taken. In vivo confocal microscopy is therefore particularly useful in the areas of infective keratitis, corneal dystrophies, refractive surgery, and contact lens wear, where it aids in differential diagnosis and detection of subtle short and long term changes. Real time endothelial cell assessment can also be performed. Conclusion: Because of their ability to visualise living tissue at cellular levels, confocal microscopes have proved useful additions to the current clinical tools.

Tear film stability: A review

Tear film stability can be assessed via a number of tools designed for clinical as well as research purposes. These techniques can give us insights into the tear film, and allow assessment of conditions that can lead to dry eye symptoms, and in severe cases, to significant ocular surface damage and deterioration of vision. Understanding what drives tear film instability and its assessment is also crucial for evaluating existing and new therapies. This review examines various techniques that are used to assess tear film instability: evaluation of tear break-up time and non-invasive break-time; topographic and interferometric techniques; confocal microscopic methods; aberrometry; and visual function tests. It also describes possible contributions of different tear film components; namely meibomian lipids, ocular mucins and proteins, and factors such as age, contact lens wear, ocular surgery and environmental stimuli, that may influence tear film instability.

General and local contact lens induced papillary conjunctivitis (CLPC)

Contact lens induced papillary conjunctivitis (CLPC) is one of the most common reasons for discontinuation of contact lens wear. The hallmark signs are enlarged papillae accompanied by redness of the upper palpebral conjunctiva. Symptoms include discomfort, itching, mucous discharge, foreign body sensation, excessive lens movement and/or decentration and blurred vision caused by lens mislocation and/or lens depo~i t s .~-~ Management o p tions for CLPC include frequent cleaning and replacement of lenses to reduce deposits, a decrease in wear time, change in mode ofwear (from extended wear to daily wear) and changes in lens type or material.68 Although CLPC is associated with all lens types, the condition principally occurs during soft contact lens wear2 and appears to occur most frequently during extended wear.g It is thought that CLPC is an immunological response to denatured tear film protein that deposits onto the lens surface during wear;S.OJI however, the mechanisms for CLPC are poorly understood. Mechanical traurna,l2 meibomian gland dysfunction13-15 and types I and IV hypersensitivity all have been suggested as factors involved in the aetiology of CLPC. Our preliminary studies with extended wear soft contact lenses made from low and high oxygen permeable (Dk) materials indicate that there may be two distinct categories of CLPC: general and local.I8 CLPC involving enlarged papillae across the entire palpebral conjunctiva is classified as general (Figure 1) and papillae confined to one or two areas, generally in the central region nearest the lid margin, are termed local (Figure 2). This categorisation was based on prospective clinical trials of 1,584 eyes of 792 subjects wearing either low Dk disposable contact lenses on a six-night extended wear schedule or high Dk silicone contact lenses on a 30-night extended wear schedule. Of the 68 events of CLPC recorded, 53 per cent were classified as general and 47 per cent as local. We present two cases from an ongoing prospective study of high Dk soft contact lenses worn on a 30-night extended wear schedule to demonstrate the differences between these two presentations of CLPC. Clin Exp Optom 2002; 85: 3: 193-197

Clinical observations of biofouling on PEO coated silicone hydrogel contact lenses

Silicone hydrogel contact lenses, which have been a major advance in the field of vision correction, require surface modification or coatings for comfort and biocompatibility. While current coatings show adequate clinical performance, advanced coatings may improve the biocompatibility of contact lenses further by reducing biofouling and related adverse clinical events. Here, we have produced coatings on Lotrafilcon A contact lenses by deposition of a thin film of allylamine plasma polymer (ALAPP) as a reactive interlayer for the high density grafting of poly(ethylene oxide) dialdehyde (PEO(ALD)(2)), which had previously shown complete resistance to protein adsorption in vitro. The performance of these contact lenses was evaluated in a controlled clinical study over 6h using Focus Night and Day (also known as Air Optix Night & Day) contact lenses as control lenses. Surface modified lenses were characterised by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) before and after wear. Clinical data showed a high level of biocompatibility of the PEO coated lenses equivalent to control lenses. Surface analysis of worn contact lenses demonstrated that the high density PEO coating is effective in reducing biofouling in vivo compared to control lenses, however small amounts of protein deposits were still detected on all worn contact lenses. This study highlights that elimination of biofouling in vivo can be much more demanding than in vitro and discusses issues that are important for the analysis of worn contact lenses as well as the design of improved contact lenses.

Potential sources of bacteria that are isolated from contact lenses during wear.

Purpose The aim of this paper was to determine the possible contamination sources of contact lenses during wear. Methods Potential sources of the microbiota that colonized hydrogel contact lenses during wear were examined. The microorganisms that colonize contact lenses were grown, identified, and compared to those microorganisms that colonized the lower lid margins, upper bulbar conjunctiva, hands, and contact lens cases of contact lens wearers. In addition, the incidence of contamination of the domestic water supply in the Sydney area was obtained, and this was compared to the incidence of colonization of contact lenses by microorganisms in general and gram-negative bacteria in particular. Results There was a wide diversity of bacteria that were isolated from each site sampled. Coagulase-negative staphylococci and Propionibacterium spp. were the most common isolates from all ocular sites examined, and constituted the normal ocular microbiota. Other bacteria, including members of the families Enterobacteriaceae and Pseudomonadaceae, were isolated infrequently from all sites, but most frequently from contact lens cases. Statistical analysis revealed that there was a correlation between the isolation of bacteria from the contact lens and the lower lid margin (p < 0.001). Analysis of this correlation revealed that this was true for the normal microbiota. A correlation was also noted between the colonization of contact lenses by gram-negative bacteria and contamination of the domestic water supply. Discussion This study has demonstrated that the likely route for the normal ocular microbiota colonizing contact lenses is via the lid margins, whereas colonization by gram-negative bacteria, including potential agents of microbial keratitis, is likely to be from the domestic water supply.

Microbial contamination of hydrogel contact lenses

Bacterial contamination of contact lenses (CLs) may contribute to CL‐related corneal infection and inflammation. This study reports CL biota over time during daily and extended wear. Microbial contamination of a 58% water, ionic hydrogel CL and a 38% water, non‐ionic hydrogel CL was evaluated in an Australian and an Indian population. Fifty wearers were repeatedly sampled over 18 months. Overnight CL use did not alter the frequency of positive cultures, nor the spectrum of organisms compared with daily CL wear. There were no differences in type and frequency of CL contamination between the CL types. Positive cultures were more frequently recovered from the Indian population compared with the Australian population. Streptococcus spp. and Propionibacterium spp. were more frequently isolated from the Australian population. Fungi and Bacillus spp. were more frequently isolated from the Indian population. Normal CL biota alone cannot explain the increased rate of infection and inflammation in extended wear.

Two presentations of contact lens-induced papillary conjunctivitis (CLPC) in hydrogel lens wear: local and general.

Purpose. The purpose of this study was to confirm that two distinct clinical presentations of contact lens-induced papillary conjunctivitis (CLPC), local and general, occur in hydrogel lens wear. Methods. Retrospective analyses of 124 CLPC events were identified. The classification of CLPC was based on location and extent of papillae. CLPC was classified as local if papillae were present in one to two areas of the tarsal conjunctiva and general if papillae occurred in three or more areas. The CLPC events were compared with an asymptomatic control group in prospective clinical trials conducted from 1993 until 2003 at two clinical sites, Australia and India. Two hundred sixteen subjects from Australia and 914 subjects from India wore either high Dk silicone hydrogel or low Dk hydrogel lenses on a 6-night (6N) or 30-night extended-wear (EW) schedule. The physiological responses of the ocular surface, including tarsal conjunctiva redness and roughness, number of papillae present, lens fit and performance, and subjective patient symptoms, were measured during each visit at each site. These variables listed were compared between local CLPC groups and asymptomatic controls and general CLPC groups and asymptomatic controls. Results. Two types of CLPC in hydrogel lens wearers have been confirmed. Of the 124 CLPC events, there were 61 local and 63 general events. Local and general CLPC cases reported significantly greater frequency of symptoms compared with the asymptomatic controls, in particular itching, lens awareness, secretion, and blurred vision (p < 0.1). Conclusions. The classification of CLPC into two types, local and general, in hydrogel lens wear was confirmed based on presentations at both sites. This distribution of papillae between local and general CLPC may indicate separate etiologies involved in the pathogenesis of the condition.

Comparison of adverse events with daily disposable hydrogels and spectacle wear ☆: results from a 12-month prospective clinical trial

OBJECTIVEnTo evaluate the type and incidence of adverse events seen with daily disposable hydrogel contact lens wear compared with a control (spectacle) group over 12 months.nnnDESIGNnProspective, randomized, observer-masked, comparative clinical trial.nnnPARTICIPANTSnTwo hundred eighty-one myopes with no prior contact lens wear experience were enrolled from August to December 1996. Subjects were 16 to 35 years old and had refractive errors ranging from a -0.75-diopter (D) sphere to a -6.00-D sphere with a cylinder less than -1.00 D.nnnINTERVENTIONnEach subject was randomly assigned to wear either bilateral disposable hydrogels on a daily disposable wear schedule or spectacles.nnnMAIN OUTCOME MEASUREnType and incidence of adverse events from each group. Adverse events were categorized as serious, significant, and nonsignificant based on the potential to cause vision impairment, severity at event, and level of clinical concern.nnnRESULTSnAt baseline, 1.6% of eyes had asymptomatic infiltrates that were nonsignificant. During the study, asymptomatic infiltrates were seen in both contact lens and spectacle groups at 20.5 events versus 11.3 events per 100 eyes per year of wear. No significant events were seen with the spectacle group. With the contact lens group, the type and incidence of significant events per 100 eyes per year of lens wear were corneal peripheral ulcer, 2.5 events; infiltrative keratitis, 1.5 events; and papillary conjunctivitis, 1 event. The incidence of both significant and nonsignificant events was greater with the contact lens group (P<0.05). No serious events (i.e., microbial keratitis) were seen in either group. A greater number of subjects were lost to follow-up or permanently discontinued from the contact lens group relative to the spectacle group (33% vs. 17%, P = 0.002). Lens-related problems such as dryness, discomfort, and difficulty with insertion and removal accounted for 27% of discontinuations from the contact lens group. Poor compliance (40%) was the greatest reason for discontinuations from the spectacle group.nnnCONCLUSIONSnNo clinically serious events were seen with either group. Only a small percentage of contact lens-wearing eyes presented with significant events, which is promising for daily disposable lens wear. Far more contact lens subjects were lost to follow-up or discontinued. Small, asymptomatic, subepithelial corneal infiltrates of unknown significance were seen in both contact lens- and spectacle-wearing eyes.

Microbial keratitis in prospective studies of extended wear with disposable hydrogel Contact lenses

Purpose: To report the annualized incidence of microbial keratitis with extended wear of low oxygen transmissible (Dk/t) disposable soft contact lenses from prospective postmarket clinical trials. Methods: Seven hundred ninety subjects were enrolled at the L.V. Prasad Eye Institute (LVPEI), Hyderabad, India from March 1993 to March 2000, resulting in 1231 patient eye years, and 167 subjects were enrolled at the Cornea and the Contact Lens Research Unit (CCLRU), Sydney, Australia from July 1987 to December 1999, resulting in 842 patient eye years. Results: The annualized incidence of microbial keratitis per 10,000 eyes per year of lens wear was 32.5 (95% CI 8.9 to 83.2) for LVPEI, 23.8 (95% CI = 2.9 to 85.8) for CCLRU; when data are combined across both centers, the incidence was 28.9 (95% CI = 10.6 to 63) per 10,000 eyes per year of lens wear. This equates to 57.0 per 10,000 wearers or 1 in 173 wearers per year of lens wear. All events were rated as slight to moderate in severity and did not result in visual loss. Two events were described to highlight the challenges in diagnosis and treatment of microbial keratitis. Conclusions: The incidence of microbial keratitis with extended wear of low-Dk/t disposable lenses was higher in these prospective studies (1 in 210 wearers per year at CCLRU and 1 in 154 wearers per year at LVPEI) than that seen in retrospective population-based surveillance studies (1 in 500 wearers per year). Practitioners and patients should always be alert to signs and symptoms, and practitioners should adopt conservative strategies for diagnosis and management of contact lens-related adverse events.

Synthetic corneal inlays

This review is based on the activities of the Vision Cooperative Research Centre (previously Cooperative Research Centre for Eye Research and Technology) Corneal Implant team from 1991 to 2007. The development of a synthetic polymer of perfluoropolyether (PFPE), meeting essential physical and biological requirements, for use as a corneal inlay is presented. Each inlay was placed in a corneal flap created with a microkeratome and monitored over a two‐year period in a rabbit model. The results indicate that the PFPE implant shows excellent biocompatibility and biostability. As a result, a Phase 1 clinical trial is being conducted. Three years post‐implantation, the PFPE inlays are exhibiting continued excellent biocompatibility. Corneal inlays made from PFPE are biocompatible with corneal tissue in the long term and offer a safe and biologically‐acceptable alternative to other forms of refractive surgery.