Acute Red Eye Research Articles

AN EVALUATION OF MUCIN BALLS ASSOCIATED WITH HIGH Dk SILICONE HYDROGEL CONTACT LENS WEAR.

Conventional hydrogel contact lenses worn on an extended wear basis can cause many adverse responses,1-3 which can be described as non-significant, significant and sight-threatening. Non-significant findings, such as asymptomatic infiltrative keratitis (AIK), occur almost as frequently in spectacle wearers.4 Significant, specific symptomatic responses include contact lens acute red eye (CLARE), contact lens peripheral ulcer (CLPU), infiltrative keratitis (1K), superior epithelial arcuate lesion (SEAL) and contact lens papillary conjunctivitis (CLPC). The most serious and sight-threatening response is microbial keratitis (MK).3 A risk of developing MK exists for any contact lens wearer, but with conventional extended wear soft lenses, this risk increases 10-20 times when compared to rigid gas permeable lenses. The increased level of corneal hypoxia in the closed eye situation, in the presence of a soft contact lens, may play an important role in the development of MK.2.5The stressed superficial cells may desquamate prematurely, leaving microscopic gaps on the corneal surface and providing a route of entry for infection. 6.7 This is of particular concern in the case of continuous lens wear, in which the corneal epithelium may never fully recover from repeated hypoxia.

Decay-Accelerating Factor in Tears of Contact Lens Wearers and Patients with Contact Lens-Associated Complications

Complement activation fragments have been detected in the anterior segment during 1) eye closure, 2) contact lens wear, and 3) in some contact lens-associated pathologies. The decay-accelerating factor (DAF), a membrane-associated complement regulatory protein that inhibits the central C3 amplification convertases of the cascade, is present on both the ocular surface and in tears. In this study, we measured levels of tear DAF in asymptomatic contact lens patients and in patients who presented with contact lens-associated complications. Tears were collected from 55 patients using capillary pipettes. Subjects included normal non-contact lens wearing controls (N = 14), asymptomatic soft (N = 13) and rigid gas permeable (N = 5) wearers, and individuals with contact lens-induced acute red eye (CLARE) (N = 4), ulcerative keratitis (N = 3), giant papillary conjunctivitis (GPC) (N = 8), contact lens peripheral ulcers (N = 3), and infiltrative keratitis (N = 5). Levels of DAF were assessed using a two-site immunoradiometric assay using anti-DAF monoclonal antibodies. The mean concentration of DAF in normal controls was found to be 149+/-78 ng/ml, 117+/-59 ng/ml, and 111+/-86 ng/ml for noncontact lens patients, and asymptomatic soft and rigid gas permeable lens wearers, respectively. In the conditions of CLARE, infiltrative keratitis, and GPC, DAF concentrations were significantly reduced compared with normal noncontact lens controls. Compared with asymptomatic soft lens patients, the condition of infiltrative keratitis showed a significant reduction in tear DAF. This study documents a trend toward decreased levels of tear DAF in patients with the contact lens associated inflammatory conditions CLARE, GPC, and infiltrative keratitis. Tears of patients with infiltrates show the most significant reduction of tear DAF. The reductions may be associated with enhanced complement activation contributing to the pathogeneses of infiltrative keratitis and associated ocular surface diseases.

A Pseudomonas aeruginosa strain isolated from a Contact Lens-Induced Acute Red Eye (CLARE) is protease-deficient

A Pseudomonas aeruginosa strain isolated from a Contact Lens-Induced Acute Red Eye (CLARE) is protease-deficient

A Pseudomonas aeruginosa strain isolated from a Contact Lens-Induced Acute Red Eye (CLARE) is protease-deficient

Purpose. Pseudomonas aeruginosa proteases are thought to be important virulence factors in the pathogenesis of corneal disease. This study examined protease production from two strains of P. aeruginosa responsible for two very distinct clinical diseases: strain Paer1, isolated from a C ontact L ens-induced A cute R ed E ye (CLARE), and strain KEI 1025, isolated from a corneal ulcer. Strains were compared to a laboratory strain (ATCC 19660) known to produce severe keratitis in experimentally infected mice for protease production and for ocular virulence. Methods. Protease production was examined with colorimetric assays, gelatin zymography and western blots. Elastase A activity was quantitated with a staphylolytic assay. Ocular virulence was examined using a mouse scratch model of keratitis. Results. In contrast to strains KEI 1025 or ATCC 19660, Paer1 was unable to produce enzymatically active elastase A, elastase, and protease IV. All three strains produced active alkaline protease. Strains KEI 1025 and ATCC 19660 produced a fulminant keratitis in mice whereas Paer1 produced a mild transient infection. Restoration of elastase activity in Paer1 via genetic complementation did not result in a virulent phenotype. Co-infection of mouse eyes with strains Paer1 and ATCC 19660 resulted in the eventual loss of Paer1 from corneal tissue. Conclusions. These studies suggest that P. aeruginosa elastase A and/or protease IV, but not alkaline protease or elastase, contribute to the ocular virulence of this organism.

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.

Differences in the pathogenesis of bacteria isolated from contact-lens-induced infiltrative conditions.

The purpose of this study was to examine the ability of gram-negative bacteria isolated from the non-infectious condition contact-lens-induced acute red eye (CLARE) and infectious microbial keratitis (MK) to infect the eyes of mice. One cornea of BALB/c mice was scratched with a needle and 5 x 10(6) bacteria applied. Bacterial types used were Pseudomonas aeruginosa, Haemophilus influenzae, Serratia marcescens, Stenotrophomonas moltophilia and Aeromonas hydrophilia. The mice were killed after 1, 4 and 24 h and examined by slit lamp, histology and microbiology. CLARE strains were unable to infect the mouse corneas. The eyes inoculated with the CLARE strains had low levels of polymorphonuclear leucocytes (PMN) in the stroma. All eyes that had MK contained bacteria and large numbers of PMN after 24 h. The development of CLARE or MK is dependent on the type of bacteria with specific bacterial types being responsible for CLARE or MK.

Expression of interleukin-6 in the cornea in response to infection with different strains of Pseudomonas aeruginosa.

Strains of Pseudomonas aeruginosa causing keratitis can be either cytotoxic (6206) or invasive (6294), while a strain (Paer1) causing contact lens-induced acute red eye has been shown to be neither. In situ hybridization was used to examine the location and identity of cells expressing interleukin-6 (IL-6) mRNA in the murine cornea and changes in expression in response to infection with different strains of P. aeruginosa. The number of IL-6-positive cells was determined by image analysis. IL-6 protein levels were measured by an enzyme-linked immunosorbent assay. BALB/c mice were challenged by use of the wounded-cornea model with P. aeruginosa 6294, 6206, or Paer1 (2 x 10(6) CFU). At time intervals up to 24 h, postchallenge corneal tissue was probed for IL-6 mRNA. IL-6 mRNA expression was rapidly elevated in the epithelium in response to strains 6294 and 6206. At the conclusion of the experiments, infiltrating inflammatory cells also stained positively for IL-6 mRNA. In contrast, corneas challenged with strain Paer1 showed significant upregulation of IL-6 mRNA only at 4 h postchallenge. Three distinct patterns of IL-6 mRNA expression in the mouse cornea occur in response to these three ocular isolates of P. aeruginosa. The data obtained for mRNA expression in the cornea for all three strains of P. aeruginosa correlated well with IL-6 protein analysis of whole-eye homogenates. Differences in the cytokine responses to these strains correlate with differences in the pathology associated with each strain and may offer an opportunity to develop strategies for the improved management of ocular inflammation.

TNF-alpha production in the cornea in response to Pseudomonas aeruginosa challenge.

Pseudomonas aeruginosa can cause ulcerative bacterial keratitis or contact lens-induced acute red eye (CLARE) in humans. The present study used a mouse model of ocular infection and inflammation to examine the relationship between TNF-alpha and inflammation in the cornea in response to challenge with either a strain of P. aeruginosa causing keratitis or a CLARE strain. Constitutive TNF-alpha mRNA was detected in the epithelium, mainly towards the periphery. After infection with the keratitis-inducing strain (6294), TNF-alpha expression was elevated four-fold by 24 h post-challenge. No detectable induction of TNF-alpha mRNA was seen with CLARE strain (Paer1) challenge at any time point. The TNF-alpha protein production detected by ELISA showed a corresponding pattern to the mRNA expression, which also correlated with pathological changes. These results suggest that invasive strains of P. aeruginosa create greater pathological changes as a result of elevated TNF-alpha production, which contributes to inflammation during keratitis in vivo.

Diagnosis of the acute red eye

Diagnosis of the acute red eye

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.

Different strains of Pseudomonas aeruginosa isolated from ocular infections or inflammation display distinct corneal pathologies in an animal model

Purpose. The present investigation sought to define the responses of mouse eyes to challenge with three different strains of P. aeruginosa isolated from human corneas or contact lenses: two different strains produced an ulcerative keratitis, and one strain produced contact lens-induced acute red eye (CLARE).Methods. The corneas of BALB/c mice were inoculated with three different strains of P. aeruginosa. The strains were allowed to interact with the corneas for up to 24 h. In addition, strain Paerl, isolated from CLARE, was subjected to in vitro assays to measure its ability to invade corneal epithelial cells, or to produce cytotoxicity in these cells. Both these assays used cultured rabbit corneal epithelial cells.Results. Both MK isolates were able to infect the corneas of mice, but the CLARE isolate was non-infective. The predominant response to infection with the cytotoxic strain was severe corneal edema and infiltration of the corneal stroma with polymorphonuclear leukocytes (PMNs). The predominant response with the invasive MK isolate was corneal ulceration and infiltration with PMNs. The CLARE strain produced only low levels of PMN infiltration. In in vitro assays the CLARE strain was non-invasive and non-cytotoxic.Conclusions. This study has identified that P. aeruginosa produces at least three different types of corneal pathology and that not all strains are able to infect mouse corneas. Curr. Eye Res. 17:730–735, 1998.

Efficacy of oxymetazoline eye drops in non-infectious conjunctivitis, the most common cause of acute red eyes.

Oxymetazoline (OMZ) is an alpha-adrenergic agonist which causes potent vasoconstriction in various tissues. Thus, its effects on red eye conjunctivitis induced by histamine and arachidonic acid were tested in rabbit eyes. It was found that a brief conjunctivitis induced by 0.01% of histamine can be eliminated effectively by 0.001, 0.004, and 0.016% of OMZ. The long lasting conjunctivitis induced by 0.3% arachidonic acid can also be markedly reduced by 0.004, 0.008, and 0.016% of OMZ. These results indicate that OMZ is a potent, long acting decongestant for conjunctival red eye syndrome.

Acute red eye

PREVIEWAcute red eye is a common problem seen in primary care practice. Viral conjunctivitis, one of the most prevalent causes, often can be diagnosed and treated in this setting, although in some cases referral to an ophthalmologist is needed. This article discusses the presenting features of viral conjunctivitis, the key diagnostic criteria, differential diagnostic considerations, treatment regimens, and indications for referral.

Ten years of disposable contact lenses — a review of benefits and risks

The performance and benefits as well as the risks and complications of disposable soft lenses (single use disposable or re-used 2–4 weeks) are reviewed in relation to corneal physiology. Modern designs and advanced technology have resulted in disposable lenses providing excellent visual performance. Fewer subjective symptoms (e.g. dryness and grittiness), slit-lamp findings (such as injection and tarsal abnormalities), and inflammatory responses (papillary conjunctivitis; contact lens-induced acute red eye) have been reported with disposable lenses than with conventional soft lenses. The risk of contact lens-induced keratitis (CLIK) has been reported to be higher for daily wear of disposable lenses than for other lens types by UK investigators. Other studies have shown the risk of CLIK with disposable lenses to be equal to that with conventional soft lenses, and in two extensive Swedish studies, the incidence of severe keratitis was found to be significantly lower for daily wear (D W) of disposable lenses than for DW of conventional soft and rigid gas permeable lenses. Both the total complication rate and the number of unscheduled visits are found to be significantly lower for disposable lenses than for conventional soft lenses in several studies. Comfort has been reported to be significantly better and overall satisfaction significantly greater with disposable lenses than with conventional soft lenses according to many studies. These may be important reasons why the success rate for disposable lens wear is reported to be fairly high, generally 70–90%. The importance of appropriate care for ‘re-usable disposable lenses’ must be stressed. One day disposable lenses, if used as directed, will eliminate the risk factors of inadequate cleaning and disinfection as well as contaminated lens cases.

Lipopolysaccharide Induced Acute Red Eye and Corneal Ulcers

Using a new animal model, the aims of this study were to assess the role played by purified lipopolysaccharide (LPS) and neutrophils in the pathogenesis of acute red-eye reactions (ARE) and corneal ulcers. In addition, IL-1αwas assessed for its implications in the formation of corneal ulcers. Following corneal abrasion, eyes of rabbits underwent single or double exposures to various doses of LPS fromPseudomonas aeruginosaorSerratia marcescens.This protocol induced ARE symptoms, and their severity depended on the dosage, number of LPS exposures, and type of LPS used (LPS fromS. marcescensshowing highest virulence). Corneal ulcers were induced by delivering a high dose ofSerratiaLPS (100 μg) followed by a low dose (10 μg). Histopathological examination revealed that both ARE and corneal ulceration were associated with prominent neutrophil infiltration. In addition, many lymphocytes and other monocytic cells infiltrated ulcerated ocular tissue. Tear fluids obtained from ulcerated eyes contained high concentrations of a protein recognized by anti-rabbit IL-1αantibodies as demonstrated by immunoblotting studies. The results indicate that LPS can induce ARE and corneal ulceration in the absence of any live bacteria. Moreover, the findings implicate the accumulation of neutrophils and IL-1α-related proteins in the pathogenesis of ARE and corneal ulcers.

Haemophilus influenzae adherent to contact lenses associated with production of acute ocular inflammation.

Ten episodes of adverse responses to contact lens wear, including contact lens-induced acute red eye (CLARE), in which Haemophilus influenzae was isolated from contact lenses and/or from one of the external ocular sites at the time of the event, are described. All episodes occurred in patients wearing disposable hydrogel lenses on a 6-night extended-wear schedule. Two of the patients had recurrent episodes. H. influenzae was usually isolated in large numbers, and other bacteria or fungi colonizing the contact lens or the external ocular surface were usually present in low numbers. Those patients who were colonized with H. influenzae were more than 100 times as likely to have had a CLARE or infiltrative response than those subjects who were not colonized with this bacterium. H. influenzae colonization of the contact lens and eye may be subsequent to colonization of the nasopharynx because four of the seven patients presented with fever at the time of the event, with concurrent upper respiratory tract infection. Contact lens wearers should be made aware of the potential risk of CLARE associated with the wearing of contact lenses for extended periods during and subsequent to upper respiratory tract infection.

The role of serum calcium in the development of the acute red eye in chronic renal failure.

In patients with chronic renal failure treated by long-term dialysis, inflammatory reactions occasionally develop in the bulbar conjunctiva; the episcleral tissue is only rarely involved. Diffuse congestion of both the conjunctiva and episclera was present in 5.3% of our patients and was associated with a sudden, marked rise in serum calcium. Histopathological examination suggests that this form of hyperemia, clinically preceded by a marked shedding of calcific precipitates, is the result of a neurogenic-driven inflammatory reaction in which mast cell degranulation is mediated by the axon reflex. Focal hyperemia associated with elastosis ("pingueculitis") was present in 6.7% of the patients. This type of hyperemia was observed after an extended period of increasing levels of BUN and seemed independent of both serum calcium and phosphorus. Diffuse hyperemia of the conjunctiva, being clinically distinctly different from the combined diffuse conjunctival and episcleral hyperemia, was also observed in 6.7%. Diffuse conjunctival hyperemia seemed to be associated with low BUN. Here, again, there was no association with serum calcium and phosphorus levels.

Extended-wear of high oxygen-permeable quantum contact lenses

This study was performed to investigate the effects of extended-wear of rigid aspherical high gas-permeable contact lenses on the cornea. In the study 32 subjects (62 eyes) were followed over a period of 3 to 24 months. A high gas-permeable contact lens (Dk 92), made of fluoro-silicone-acrylate copolymer, was used. Vision remained constant during the studied period. The corneal thickness decreased significantly (p less than 0.05) during the first six months. Significant changes (p less than 0.05) were found after three months in the corneal curvature, especially in the vertical meridian. No further topographical changes were noted in the period between three and six months of extended-wear. Complications, like acute red eye syndrome and bacterial infections, which may be encountered in soft lens extended-wear, were not noticed. At the end of the study 20 subjects (38 eyes, 61%) were still on extended-wear, 9 subjects (18 eyes, 29%) changed to daily wear and 3 subjects (six eyes, 10%) became unavailable for follow-up. Extended-wear of rigid aspherical high gas-permeable contact lenses may be considered as an acceptable alternative for soft lens extended-wear.

Hydrogel contact lens cleaning with or without multi‐enzymes

In a group of 66 daily hydrogel contact lens wearers, all lenses were cleaned and disinfected daily using a regular daily cleaner and a 3% hydrogen peroxide system. In addition, one of the lenses for each subject was subjected to weekly enzymatic cleaning with a multi-enzyme pancreatin preparation. After 6 months there were highly significant differences (P less than 0.001) between the lenses, the enzymatically cleaned ones showing less deposits and longer break-up time (BUT) on the lens. Also, comfort was significantly (P less than 0.05) better for these latter lenses. No adverse reactions that could be attributed with certainty to the preparations used were observed. The effectiveness of the pancreatin preparation employed in this study is of interest, since it has been demonstrated that enzymatic removal of deposits from hydrogel lenses reduces complications such as acute red eye reaction, contact lens-induced papillary conjunctivitis, and presumably also corneal ulceration because of decreased bacterial adherence to the lenses.

Evaluation of current care and maintenance systems for hydrogel extended wear

The correct choice of an appropriate care maintenance system helps to minimise or avoid complications during extended hydrogel contact lens wear. A range of extended wear enses, of various watercontents, are currently available as are several care maintenance regimens. This paper describes a number of studies to determine the most appropriate care maintenance regimen in conjuction with regular lens replacement for both high and low water content contact lenses. The incidence of complications such as acute red eyes and papillary eyelid changes in a population of one hundred and thirty seven myopic extended wear patients will also be discussed.