Adverse events during 2 years of daily wear of silicone hydrogels in children.

PURPOSE: Type and incidence of adverse events and rate of discontinuations for 2 years of daily wear with silicone hydrogel contact lenses in Chinese children with myopia. METHODS: Two hundred forty children aged 7 to 14 years were enrolled in a prospective randomized clinical trial from November 2008 to April 2009. Children with myopia of up to -3.50 diopters (D) spherical equivalent with astigmatism less than or equal to -0.75 D were randomized to one commercial and three experimental lens designs of Lotrafilcon B silicone hydrogel lenses (four groups) used bilaterally on a daily wear, monthly replacement schedule. The main outcome measures were incidence per 100 patient-years (incidence, in percentage) of adverse events and rate of discontinuations. RESULTS: There were no events of microbial keratitis. Fifty-five adverse events (incidence, 14.2%) were seen. There were also 12 recurrent events. The type and incidence percentage were contact lens papillary conjunctivitis (16 events, 4.1%), superior epithelial arcuate lesions (SEALs, six events, 1.5%), corneal erosions (eight events, 2.1%), infiltrative keratitis (five events, 1.3%), asymptomatic infiltrative keratitis (seven events, 1.8%), and asymptomatic infiltrates (13 events, 3.42%). There were differences in the incidence of SEALs between groups (p = 0.023), with the incidence of SEALs being greater with one of the experimental designs. No event resulted in any vision loss. Seventy participants (29.2%) discontinued, with one-third (26 participants, 10.8%) occurring in the first month of lens wear. Discomfort and non-lens-related reasons such as safety concern and disinterest were frequently cited reasons for discontinuations. CONCLUSIONS: Adverse events with daily wear of silicone hydrogels in children were mainly mechanical in nature, and significant infiltrative events were few. The large number of dropouts in the early days of lens wear and their reasons for discontinuation suggest that adaptation and patient motivation are critical for survival in lens wear.

The future of silicone hydrogels.

Significant advances during the past decade in silicone hydrogel lenses have made them the primary mode for new contact lens wear. Their dominance in the market place is driven largely by the elimination of structural and physiological changes induced by contact lens-induced hypoxia, as exemplified especially by the reduction in limbal redness. However, end-of-day dryness and discomfort still drives many to discontinue lens wear. Evidence also indicates that the rate of serious adverse events, such as microbial keratitis, have not been impacted with the use of silicone hydrogel lenses. Moreover, there are additional challenges relating to 'corneal staining' and corneal infiltrates associated with the incompatibility of lens care product with contact lens polymers. On the other hand, technological advances enabled by the high oxygen platform present opportunities for expanding the use of contact lenses in areas that have exhibited limited uptake in the past such as astigmatism, presbyopia, and importantly myopia control. The challenges and opportunities facing the field will be discussed.

External ocular surface and lens microbiota in contact lens wearers with corneal infiltrates during extended wear of hydrogel lenses.

OBJECTIVES: To determine whether carriage of microbes on the contact lens or ocular surfaces during extended wear (EW) with soft hydroxyethyl methacrylate (HEMA)-based contact lenses predisposes the wearer to adverse events. METHODS: Participants (non-contact lens wearers) were enrolled in a clinical study involving wear of HEMA-based hydrogel lenses on a six night EW basis with weekly replacement. Type and number of bacteria colonizing the lower lid margins, upper bulbar conjunctiva, and contact lenses during EW after one night, 1 week, 1 month, and thereafter every 3 months for 3.5 years were determined. The association of bacteria with adverse responses was compared between carriers (defined as having significant microbes cultured from two or more samples with 1 year) and noncarriers, and the strength of the association was estimated using multivariate logistic regression. RESULTS: Carriers of gram-positive bacteria on lenses (particularly coagulase negative staphylococci or Corynebacterium spp.) were approximately three and eight times more likely to develop contact lens-induced peripheral ulcers (CLPUs) and asymptomatic infiltrates (AIs), respectively. Staphylococcus aureus was most frequently isolated from lenses during CLPU. Carriers of gram-negative bacteria on lenses were five times more likely to develop contact lens-induced acute red eye (CLARE). Haemophilus influenzae was isolated most frequently from lenses during CLARE and AI events. CONCLUSIONS: Bacterial carriage on contact lenses during EW predisposes the wearer to the development of corneal inflammatory events including CLARE, CLPU, and AI.

Risk factors for corneal inflammatory and mechanical events with extended wear silicone hydrogel contact lenses.

PURPOSE: To identify risk factors for contact lens-related corneal inflammatory events and mechanical events in wearers of silicone hydrogel lenses on a 30-night extended wear (EW) schedule in India. METHODS: An interventional study with 188 subjects wearing silicone hydrogel lenses bilaterally on a 30-night EW schedule. Subjects were dispensed with lenses and reviewed at scheduled visits up to 6 months of EW. Multivariate logistic regression, after adjusting for within subject correlation, was used to develop the statistical model. RESULTS: Occupations in non-ideal environments were found to predispose a lens wearer to inflammatory events (p = 0.003). Wearers in the non-ideal group, who had varying degrees of exposure to ocular irritants in their work environment had highest incidence of inflammatory events (19.2%). Wearers in a controlled, ideal environment had lowest levels of events (3.3%). Students occupied a position between the two groups (9.3%). Inflammatory rate was higher among wearers with increased microbial contamination of lenses (p = 0.002). Wearers with an inflammatory event had mean colony forming unit of 1.97 log compared with mean colony forming unit of 1.45 log in group with no inflammatory event. Corneal vascularization was associated with the development of inflammatory events (p = 0.001) with 50% of wearers with vascularization experiencing events compared with 7.6% of subjects with no vascularization. Reduced lens movement was associated with inflammatory events with subjects more likely to develop inflammatory events compared with those wearers with optimal lens movement (p = 0.027). CONCLUSIONS: A multitude of factors, including environmental influences, lens contamination, ocular characteristics, and lens fit, contributes to the development of inflammatory events, information that is of clinical relevance to practitioners worldwide. Occupational environment was also a contributory factor, confirming that a duty of clinicians is to ascertain the nature of the work environment of lens wearers (and potential wearers) and to balance the needs of the wearer with the potential risks.

In vivo performance of melimine as an antimicrobial coating for contact lenses in models of CLARE and CLPU.

PURPOSE: One strategy to minimize bacteria-associated adverse responses such as microbial keratitis, contact lens-induced acute red eye (CLARE), and contact lens induced peripheral ulcers (CLPUs) that occur with contact lens wear is the development of an antimicrobial or antiadhesive contact lens. Cationic peptides represent a novel approach for the development of antimicrobial lenses. METHODS: A novel cationic peptide, melimine, was covalently incorporated into silicone hydrogel lenses. Confirmation tests to determine the presence of peptide and anti-microbial activity were performed. Cationic lenses were then tested for their ability to prevent CLPU in the Staphylococcus aureus rabbit model and CLARE in the Pseudomonas aeruginosa guinea pig model. RESULTS: In the rabbit model of CLPU, melimine-coated lenses resulted in significant reductions in ocular symptom scores and in the extent of corneal infiltration (P < 0.05). Evaluation of the performance of melimine lenses in the CLARE model showed significant improvement in all ocular response parameters measured, including the percentage of eyes with corneal infiltrates, compared with those observed in the eyes fitted with the control lens (P < or = 0.05). CONCLUSIONS: Cationic coating of contact lenses with the peptide melimine may represent a novel method of prevention of bacterial growth on contact lenses and consequently result in reduction of the incidence and severity of adverse responses due to Gram-positive and -negative bacteria during lens wear.

Guinea pig models of acute keratitis responses.

PURPOSE: Contact lens acute red eye (CLARE) and infiltrative keratitis (IK) are inflammatory responses of the eye associated with extended wear of soft contact lenses and are associated with bacterial colonization of contact lenses. Development of animal models to study these conditions is of importance in confirming risk factors and developing preventative strategies. METHODS: Silicone hydrogel contact lenses contaminated with a human CLARE isolate of Pseudomonas aeruginosa at inocula ranging from 1 x 10 to 6 x 10 colony-forming units (CFUs) for 15 minutes, 1 hour, or 24 hours were worn by guinea pigs for times up to 48 hours in 3 models designed to simulate contamination during wear and contact lens care regimens. Eyes were examined by slit-lamp biomicroscopy and histology to evaluate ocular responses and inflammation. RESULTS: Three different models for the effects of bacterial contamination on the etiology of CLARE/IK were developed and tested in the guinea pig eye. Bacterial contamination of contact lenses was confirmed to be a major risk factor for the development of CLARE/IK and a dose response shown. The pathological features of CLARE/IK in the guinea pig were virtually identical to those observed in human eyes. CONCLUSION: The models characterized here provide a useful tool for development of interventional and therapeutic strategies for these important ocular inflammatory conditions.

IgE antibody on worn highly oxygen-permeable silicone hydrogel contact lenses from patients with contact lens-induced papillary conjunctivitis (CLPC).

PURPOSE: To investigate whether the level of IgE is increased in the eyes of patients during general contact lens-induced papillary conjunctivitis (CLPC) events, which involve enlarged papillae across the entire palpebral conjunctiva, or local CLPC events, in which papillae are confined to one or two parts of the area. METHODS: Worn contact lenses were collected and soaked in phosphate-buffered saline. The levels of eluted IgE and IgE retained on contact lenses were detected by enzyme-linked immunosorbent assay. RESULTS: IgE was detected in 6 of 12 cases of general CLPC, 8 of 21 cases of local CLPC, and none of 14 control contact lenses. The average level of eluted IgE was 0.54 +/- 1.06 IU/contact lens, 0.28 +/- 0.54 IU/contact lens, and 0.04 +/- 0.06 IU/contact lens for general CLPC, local CLPC, and the control group, respectively. The incidences of positive IgE were significantly higher in patients with CLPC (general and local) than in control subjects, but no statistical difference was found between general and local CLPC. Generally higher amounts of retained IgE were detected on contact lenses that had increased levels of eluted IgE. Contact lenses that were collected before or after a CLPC event did not show increased levels of IgE. CONCLUSIONS: The level of IgE is increased in the eyes of some patients during an acute event of CLPC. The similar incidence of IgE-positive cases and levels of IgE from general and local CLPC contact lenses suggest that the conditions may share similar causal pathways.

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.

OBJECTIVE: To 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. DESIGN: Prospective, randomized, observer-masked, comparative clinical trial. PARTICIPANTS: Two 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. INTERVENTION: Each subject was randomly assigned to wear either bilateral disposable hydrogels on a daily disposable wear schedule or spectacles. MAIN OUTCOME MEASURE: Type 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. RESULTS: At 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. CONCLUSIONS: No 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.