Contact Lens-induced Peripheral Ulcer Research Articles

POLY (2-METHYL-2-OXAZOLINE) (PMOXA) AND ANTIMICROBIAL PEPTIDE GKH17 AS POTENTIAL ANTIMICROBIAL COATINGS FOR CONTACT LENSES

Microbial contamination on contact lens surfaces can occur during handling, storage, and even cleaning with contaminated solutions. Several severe consequences of this event include microbial keratitis, contact lens-induced peripheral ulcer, and inflitrative keratitis. In this study we used SiO2 as a model substrate for silicon-based contact lenses. The antimicrobial activities of two polymers, poly(2-methyl-2-oxazoline) (PMOXA) and antimicrobial peptide GKHKNKGKKNGKHNGWK (GKH17), on surfaces, were tested against two types of bacteria, Gram-positive Staphlyococcus sp. and Gram-negative Neisseria sp., isolated from used contact lenses. The inhibition activity of the polymers was first tested using the Kirby-Bauer method, and the properties of the polymers immobilized on SiO2 surface were investigated by means of viable plate count and DNA absorbance measurements. Our results show that both types of bacteria are susceptible to both PMOXA and GKH17, however with a different degree of susceptibility. Both polymers are thus potential antimicrobial coatings for contact lenses.

Corneal Inflammatory Events with Daily Silicone Hydrogel Lens Wear

This study aimed to determine the probability and risk factors for developing a corneal inflammatory event (CIE) during daily wear of lotrafilcon A silicone hydrogel contact lenses. Eligible participants (n = 218) were fit with lotrafilcon A lenses for daily wear and followed up for 12 months. Participants were randomized to either a polyhexamethylene biguanide-preserved multipurpose solution or a one-step peroxide disinfection system. The main exposures of interest were bacterial contamination of lenses, cases, lid margins, and ocular surface. Kaplan-Meier (KM) plots were used to estimate the cumulative unadjusted probability of remaining free from a CIE, and multivariate Cox proportional hazards regression was used to model the hazard of experiencing a CIE. The KM unadjusted cumulative probability of remaining free from a CIE for both lens care groups combined was 92.3% (95% confidence interval [CI], 88.1 to 96.5%). There was one participant with microbial keratitis, five participants with asymptomatic infiltrates, and seven participants with contact lens peripheral ulcers, providing KM survival estimates of 92.8% (95% CI, 88.6 to 96.9%) and 98.1% (95% CI, 95.8 to 100.0%) for remaining free from noninfectious and symptomatic CIEs, respectively. The presence of substantial (>100 colony-forming units) coagulase-negative staphylococci bioburden on lid margins was associated with about a five-fold increased risk for the development of a CIE (p = 0.04). The probability of experiencing a CIE during daily wear of lotrafilcon A contact lenses is low, and symptomatic CIEs are rare. Patient factors, such as high levels of bacterial bioburden on lid margins, contribute to the development of noninfectious CIEs during daily wear of silicone hydrogel lenses.

Ocular complications of soft contact lens wearers in a tertiary eye care centre of Nepal

To determine the prevalence and the major types of ocular complications related with soft contact lenses (CL) in a tertiary eye care centre of Nepal. Medical files of 4064 soft CL wearers who started wearing CL between January 2003 and December 2010 in BP Koirala Lions Centre for Ophthalmic Studies (BPKLCOS) Kathmandu, Nepal, were retrospectively reviewed. Records of patients who visited the hospital with complications were analyzed. Patients with ocular complications non-related with CL wear were excluded. Complications were found in 4.9% of the total soft CL wearers. Contact lens induced papillary conjunctivitis (CLPC) was the most common complication, comprising 36.9% of the total patients with complications. The other commonly found complications were superior punctuate keratitis (SPK) in 16.2%, conjunctivitis in 18.2%, meibomian gland dysfunction (MGD) in 8.6%, contact lens induced peripheral ulcer (CLPU) in 4%, corneal vascularization in 3.5% and microbial keratitis in 3%. The average time of first occurrence of complications after starting of contact lens wear was 14.3±11.4 months. CLPC, conjunctivitis and SPK were the most common types of soft CL related complications found in Nepal. Vision threatening complications like microbial keratitis was also found in some patients. Patient education in CL hygiene, after care schedule and frequent follow up examinations may help to minimize CL related complications.

External Ocular Surface and Lens Microbiota in Contact Lens Wearers With Corneal Infiltrates During Extended Wear of Hydrogel Lenses

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. 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. 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. Bacterial carriage on contact lenses during EW predisposes the wearer to the development of corneal inflammatory events including CLARE, CLPU, and AI.

In Vivo Performance of Melimine as an Antimicrobial Coating for Contact Lenses in Models of CLARE and CLPU

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. 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. 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). 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.

Are Inflammatory Events a Marker for an Increased Risk of Microbial Keratitis?

To consider whether inflammatory events, such as contact lens-induced peripheral ulcers, contact lens-induced acute red eye, and infiltrative keratitis are a marker for an increased risk for the occurrence of microbial keratitis. A review of relevant studies was undertaken with the view to answering two questions: 1) Do inflammatory events associated with contact lens wear progress to infection or microbial keratitis; and 2) Do episodes of inflammatory events predispose a patient to having an event of microbial keratitis? The large body of laboratory work, along with the epidemiologic data on incidence rates and clinical data with regard to differences between the nature of inflammatory events and infection, supports the supposition that inflammatory events are not a marker for increased risk of microbial keratitis. Inflammatory events are not a marker for increased risk of microbial keratitis, nor will they progress to infection because they are separate disease entities.

Can Subtypes of Contact Lens-Associated Corneal Infiltrative Events Be Clinically Differentiated?

A schema has recently been described for clinical differentiation among 4 symptomatic subtypes of contact lens-associated corneal infiltrative events (CIEs): microbial keratitis (MK), contact lens-induced peripheral ulcer (CLPU), contact lens-induced acute red eye (CLARE), and infiltrative keratitis (IK). The clinical utility of this schema has been challenged in the literature. The aim of this study is to determine whether it is possible to clinically differentiate among these conditions. Criteria for MK, CLPU, CLARE, and IK were applied to a data set of 111 contact lens-associated CIEs, spanning a wide range of clinical severities, presenting consecutively to a hospital clinic. A Venn diagram analysis was used to determine the extent to which these conditions can be clinically differentiated. Of the 111 CIEs, 20% could be classified unambiguously as MK, CLPU, CLARE, or IK, 56% could be classified as 1 of 2 conditions, 13% could be classified as 1 of 3 conditions, and 0% could be classified as 1 of 4 conditions. Eleven percent of CIEs could not be classified as any of the 4 conditions. Although the etiology of CIEs is multifactorial, the considerable overlap between the clinical presentation of MK, CLPU, CLARE, and IK is such that it is not possible to clinically differentiate between them with any degree of certainty. A preferred approach might be to consider CIEs as part of a disease continuum whereby these events can manifest in various degrees of severity, depending as well on the point at which the condition is observed in the course of the natural history of the disease.

Clinical characterization of corneal infiltrative events observed with soft contact lens wear.

Corneal infiltrates are commonly observed during adverse reactions associated with contact lens wear. Broad ranges of presentations are encountered, and there is no well-established classification system. The aim of this paper is to categorize corneal infiltrates associated with soft lens wear and present the typical clinical characteristics associated with each type of event. All events of corneal infiltrates occurring in soft contact lens clinical trials over 10 years (9 years retrospective and 1 year prospective) and conducted at two contact lens research centers were reviewed by a panel of experts comprising ophthalmologists, optometrists, and other biologic scientists. Classification of each event was based on assessment of a range of signs and symptoms by the review panel. A classification scheme was devised to distinguish infiltrative events that were serious and symptomatic (microbial keratitis), clinically significant and symptomatic (contact lens-induced peripheral ulcer, contact lens-induced acute red eye, infiltrative keratitis), and clinically nonsignificant and asymptomatic (asymptomatic infiltrative keratitis and asymptomatic infiltrates). Corneal infiltrates can be classified into six distinct categories. This classification scheme, based on clinical characteristics, should aid diagnosis, management, and treatment of corneal infiltrates as well as assisting investigations into the etiology of each of these conditions.

Differential Diagnosis of Microbial Keratitis and Contact Lens-Induced Peripheral Ulcer

Differentiating a contact lens-induced peripheral ulcer (CLPU) from early stage microbial keratitis (MK) is primarily based on clinical judgment rather than on microbiologic or histopathologic investigations. For this reason, tests do not provide valuable information at the early stages in the clinical course of MK. Whereas in gross terms, the clinical picture of MK is more acute and severe than CLPU, clinical features of the two can overlap, sometimes resulting in errors of judgment and mismanagement. This article provides clinical clues that help distinguish the two conditions. In addition, a scoring system has been devised for MK and CLPU. Microbial keratitis (MK) is a dreaded complication for contact lens wearers. Although the risk is small, the large population of contact lens (CL) users have made CL wear a major predisposing factor for corneal infection. The reported incidence of MK among CL wearers may be inaccurate because it can be easily confused with its sterile counter part, contact lens-induced peripheral ulcer (CLPU). An accurate initial clinical impression is critical in avoiding mismanagement of these conditions. Clinical differentiation between infected and sterile corneal infiltrates in CL wearers has been addressed in the literature. We suggest a scheme for distinguishing early stage MK from CLPU.

The causes of and cures for contact lens-induced peripheral ulcer.

Contact lens-induced peripheral ulceration (CLPU) is a relatively common adverse response associated with wearing hydrogel lenses, especially on an extended wear schedule. Bacteriologic examination of lenses at the time of an event has demonstrated an association with Staphylococci spp. We sought to investigate the causes of CLPU in a rabbit model of contact lens wear. Rabbits wore contact lenses for a period of 24 hr in the presence or absence of bacteria or in presence or absence of epithelial scratches made in the periphery of the cornea before lens wear. Bacteria tested were a strain of Staphylococcus aureus or a strain of Staphylococcus epidermidis isolated from human CLPUs. Rabbits were also challenged with S. aureus in the presence of an epithelial defect and in the absence of a contact lens. Corneas were monitored by slitlamp, histology, and microbial culture after 24 hr. No CLPU-like lesions were detected under the following conditions: corneal scratch plus lens wear with no bacteria; corneal scratch plus S. epidermidis colonized lenses; corneal scratch without lens wear and with S. aureus applied to eyes; no scratch plus S. aureus colonized lenses; and corneal scratch plus contact lenses colonized by dead S. aureus. CLPU-like lesions were found only when the corneas were scratched and contact lenses colonized by viable S. aureus were applied to the eye. The histology of the lesions demonstrated a frank epithelial break with underlying stromal infiltration. Only low numbers of bacteria could be cultivated from the corneas with CLPU-like lesions. The CLPU-like lesions shared many similarities with CLPU in humans. CLPU-like lesions were only produced by S. aureus and not S. epidermidis in the presence of an epithelial abrasion and contact lens. Thus, we hypothesize that to reduce the incidence of CLPU, contact lenses designed to reduce corneal interaction and repel microbial colonization should be produced.

Contact lenses and tear film interactions.

Contact lenses are a successful form of vision correction. However, under certain circumstances adverse inflammatory responses can occur during lens wear. These inflammatory responses can be divided into those that involve the cornea and conjunctiva, and those that are primarily conjunctival. The former category includes microbial keratitis, contact lens-induced acute red eye, contact lens-induced peripheral ulcers, infiltrative keratitis, asymptomatic infiltrative keratitis and asymptomatic infiltrates. These conditions have recently been described in detail, and many are produced by bacterial contamination of contact lenses.1-4 The major contact lens-related inflammatory conditions primarily associated with the conjunctiva are contact lens-induced papillary conjunctivitis (CLPC), and the more severe form of this disease, giant papillary conjunctivitis (GPC). However, the etiology of these conditions is poorly understood. The aim of the current study is to examine the effect of contact lens wear on tear proteins and determine which and how much specific tear proteins are adsorbed to the contact lens during wear.

Varicella-Zoster Virus Eye Disease

To review the epidemiology, biology, systemic and ocular features, and treatment options for varicella zoster disease, including postherpetic neuralgia. Literature search and review of author's experience with patients with varicella and herpes zoster ophthalmicus. In recent years there has been an increase in the knowledge about the biology, latency, and epidemiology of the varicella-zoster virus. The clinical features are correlated with the pathologic changes. The pathophysiologic mechanisms and treatment of postherpetic neuralgia are reviewed. Treatment options with antiviral therapy and corticosteroids are offered. Initial experience with the varicella vaccine is encouraging. The laboratory and clinical studies have enhanced our knowledge of the varicella-zoster virus and increased our ability to treat this infection and the aftermath. We are still far short of providing adequate therapy for patients who experience the severe forms of the disease.

Adverse events with extended wear of disposable hydrogels: Results for the first 13 months of lens wear

Objective To determine the type and incidence of adverse events seen in the first 13 months of extended wear from a prospective clinical trial involving the use of disposable hydrogels on a 6-night extended wear and replacement schedule. Design A prospective, noncomparative clinical trial. Participants Three hundred thirty subjects were enrolled in the study from March 1993 to August 1996 and commenced in extended wear. The subjects were new contact lens users with ages ranging from 16 to 39 years and refractive errors from −1.00 to −6.50-diopter (D) sphere with cylindrical component less than 1.0 D. Intervention Disposable hydrogel lenses on a 6-night extended wear and replacement schedule. Main outcome measures To determine the incidence of adverse events in the first 13 months of lens wear with the use of disposable hydrogels on an extended wear schedule. In addition, corneal infiltrative events observed with lens wear were classified based on their presenting signs and symptoms. Results A total of 137 adverse events were seen in 102 subjects in the first 13 months of extended wear. The type of adverse events and the incidence per 100 patients per year of lens wear were as follows: corneal infiltrative events (44.4 events), contact lens papillary conjunctivitis (6.4 events), neovascularization and corneal wrinkling (1.7 events each), corneal striae and superior epithelial arcuate lesions (1.3 events each), and blepharokeratoconjunctivitis (0.4 event). Viral keratoconjunctivitis was also observed (0.8 event). The corneal infiltrative events were further subclassified as follows: contact lens-induced peripheral ulcers (13.6 events), contact lens-induced acute red eyes (12.3 events), infiltrative keratitis (9.7 events), and asymptomatic infiltrative events (8.9 events). There were no events of infectious keratitis. Except for all events of contact lens-induced peripheral ulcers and two isolated events of infiltrative keratitis that resulted in scarring, all of the corneal infiltrative events resolved without sequelae. None of the events caused any loss of best-corrected visual acuity. Conclusions Based on the observations from the first 13 months of extended wear in the trial, the majority of the complications associated with extended wear of disposable hydrogels are corneal infiltrative events. No events of microbial keratitis were seen in the first 13 months of extended wear. None of the events were associated with loss in best-corrected visual acuity. Clearly, frequent and regular disposing of lenses does not eliminate adverse effects, and better materials and designs are required for extended wear to be a successful method.

Contact Lens-Induced Peripheral Ulcers with Extended Wear of Disposable Hydrogel Lenses

Contact lens-induced peripheral ulcer (CLPU), a sudden-onset adverse event observed with extended wear of hydrogel lenses, is characterized by a single, small, circular, focal anterior stromal infiltrate in the corneal periphery or midperiphery. The condition is always associated with a significant overlying epithelial loss and resolves in a scar. The aim was to determine, by using histopathologic techniques, the nature and type of the corneal infiltrate of these events. Three CLPUs observed in three patients using disposable hydrogel lenses on an extended-wear schedule were examined. The eye was topically anesthetized, and a corneal section including all of the infiltrate was taken. A small triangular piece of conjunctiva immediately adjacent to the infiltrate was sectioned. The tissue was immediately fixed, processed, stained using hematoxylin and eosin and periodic acid-Schiff stains, and examined by using light microscopy. The diameter of these three corneal infiltrates varied from 0.3 to 0.6 mm. Histopathology of the corneal sections revealed a focal epithelial loss corresponding to the infiltrated stroma in all three patients. The adjacent epithelium was thinned. Bowman's layer was intact in two patients and had a localized area of loss in the remaining patient. The anterior stroma was densely infiltrated with polymorphonuclear leukocytes and had focal areas of necrosis. The infiltration was most dense in the region immediately underlying Bowman's layer. No other infiltrative cell type was seen in any of the sections. Histopathology of the conjunctiva revealed features consistent with normal conjunctival tissue. On histopathology of CLPU, distinctive features (i.e., focal corneal epithelial loss, an intact Bowman's membrane, and a localized infiltration of the anterior stroma with polymorphonuclear leukocytes) were seen. These features suggest that the event is an acute inflammatory process and probably noninfective in nature.

Detection of staphylococcal superantigens from contact-lens-induced inflammatory diseases.

We investigated the correlation between the production of superantigens in Staphylococcus-aureus-induced ulcer and contact-lens-induced peripheral ulcer (CLPU) and infiltrative keratitis (IK). Twenty-five S. aureus strains used in the study were isolated either from CLPU cases (six), or IK events (13) or asymptomatic eyes (six). A polymerase chain reaction (PCR) was employed to detect genes for superantigenic staphylococcal enterotoxins A-D, toxic shock syndrome toxin-1 and exfoliative toxins A and B. Reversed passive latex aggregation, enzyme-linked immunosorbent assay (ELISA) and immunoblot were used to examine the production of staphylococcal enterotoxins A-D and toxic shock syndrome toxin-1. The frequency of the superantigenic genes was not significantly different among the clinical isolates when asymptomatic isolates were compared with the strains isolated from CLPU and IK events. ELISA and immunoblot showed non-specific protein cross-reactions. The results suggest that detection of superantigenic toxin genes in ocular strains of S. aureus by PCR is a specific, sensitive, rapid and inexpensive alternative to traditional immunological assays. The role, if any, of the S. aureus superantigens in the production of CLPU/IK remains uncertain.

Cytokine and Lipid Inflammatory Mediator Profile of Human Tears During Contact Lens Associated Inflammatory Diseases

Contact lens induced acute red eye (CLARE) and contact lens induced peripheral ulcer (CLPU) are among the most common contact lens induced inflammatory reactions. Both CLARE and CLPU are characterized by corneal infiltration which indicates the presence of chemoattractants and other inflammatory mediators. The aim of this study was to characterize the cytokine and chemotactic lipid inflammatory mediator profile in the tears of people experiencing CLARE or CLPU. Cytokines IL-1β, IL-6, IL-8, GM-CSF and LTB4in tears were measured by antibody sandwich and competition inhibition enzyme-linked immunosorbent assays (ELISA). Platelet activating factor-like activity was measured by a degranulation assay by measuring the release of labelled serotonin from platelets. The functional role GM-CSF and chemoattractants were determined by flow cytometry and chemotaxis. Increased levels of cytokines and chemoattractants were detected in both CLARE and CLPU tears. CLPU tears showed increased levels of LTB4(P=0.002) and PAF-like activity (P=0.047)whereas CLARE tears showed increased levels of GM-CSF (P=0.002), IL-8 (P<0.05), LTB4(P=0.002) and PAF-like activity (P=0.047) compared to>control tears. Flow cytometric analysis revealed that incubation of PMN with CLARE tears increased the number of IgA receptors indicating that the GM-CSF in CLARE tears was active. Combinations of suboptimal concentrations (which were found in CLARE and CLPU tears) of IL-8 with either LTB4or PAF significantly (P<0.0001) enhanced the chemotactic activity for PMN compared to their individual effects. Our data highlight the possible pathophysiological roles of these inflammatory mediators in leukocyte recruitment and activation during ocular inflammatory responses. The results suggests that GM-CSF, IL-8 and LTB4are active during corneal pathology and LTB4or IL-8 may maintain the contact lens induced PMN response in vivo.