Adhesion molecules and relationship to leukocyte levels in allergic eye disease.

PURPOSE: To evaluate the conjunctival expression of leukocyte cell adhesion molecules (CAMs) and their relationship to leukocyte patterns on the microvasculature in the different clinical subtypes of allergic eye disease. METHODS: Immunohistochemical analysis, using appropriate monoclonal antibodies, was applied to glycolmethacrylate-embedded biopsies of bulbar and tarsal conjunctival tissue. The proportion of total blood vessels expressing a particular CAM was derived and related to individual cell types identified by cell-specific markers, such as mast cells, eosinophils, neutrophils, T cells, and macrophages. Statistical analysis was used to correlate adhesion molecule expression and, ultimately, cell type. RESULTS: There was a basal expression of intercellular adhesion molecule-1 (ICAM-1) (21% bulbar, 18% tarsal), E-selectin (15% bulbar, 21% tarsal), and vascular cell adhesion molecule-1 (VCAM-1) (13% bulbar and tarsal) in normal controls. In seasonal and perennial (bulbar and tarsal conjunctival) allergic tissue, ICAM-1 and E-selectin were expressed in 40% to 78% of vessels; in chronic disease, they were expressed in 45% to 80% of vessels; and in vernal giant papillae, they were expressed in as many as 90% of vessels. There was also increased expression of endothelial VCAM-1 in all forms of allergic eye disease; the greatest values were found in vernal giant papillae (64%). Biopsies taken in winter from seasonal sufferers demonstrated a marked reduction in levels of all three CAMs compared with those taken in the pollen season. This is almost consistent with values found in normal conjunctiva. Positive correlations were found between the levels of ICAM-1 and E-selectin expression and the degree of granulocyte and lymphocyte infiltration, although VCAM-1 expression correlated most closely with eosinophil numbers. CONCLUSIONS: Increased levels of cell adhesion molecules on the microvasculature and the factors that regulate them are likely to be responsible for the infiltration of cells bearing their ligands and may perpetuate inflammation in the chronic forms of allergic eye disease.

Perfluorocarbon heavy liquids in the management of posterior dislocation of the lens nucleus during phakoemulsification.

We report a case in which the lens nucleus dislocated into the vitreous cavity through a posterior capsular rupture during phakoemulsification. We performed a vitrectomy and removed the lens nucleus using the perfluorocarbon heavy liquid perfluoro-1,3-dimethylcyclohexane. The management of posterior dislocation of the lens nucleus during cataract surgery is discussed.

Silicone rubber contact lenses for the compromised cornea.

Silicone rubber contact lenses (SRCLs) are infrequently used because of the risk of developing unpredictable lens tightening, their poor availability, and their expense. However, their high oxygen transmissibility and nonabsorption of water make them valuable as therapeutic lenses. SRCLs are routinely used in our management of severely dry eyes, decompensated or vascularised corneas, and conditions where the corneal shape is flat or irregular. The records of 48 consecutive patients fitted with SRCLs between January 1989 and June 1990 were studied. The clinical history, indications, complications, success, and duration of SRCL wear were analysed. Therapeutic goals, which included epithelial healing, sealing of corneal perforations, and improved comfort and vision, were achieved in 53 of 62 eyes. The best corrected acuity was attained using SRCLs in 58 of 62 eyes. Failure of lens wear was due to lens tightening (four eyes), spoilation (two), discomfort, fornix shortening, handling problems, and decentration (one each). Infective keratitis complicated one case, but SRCL wear was resumed after successful treatment. With adequate follow-up, SRCLs have a low complication rate and are well tolerated even in severely compromised eyes, for which conventional lenses may be contraindicated. Their continued use as therapeutic lenses is advocated in carefully selected cases.

Risk factors for acanthamoeba keratitis in contact lens users: a case-control study.

OBJECTIVE: To investigate reasons for an increase in cases of Acanthamoeba keratitis related to contact lenses. DESIGN: Case-control study. Cases were contact lens related acanthamoeba keratitis patients treated between 1 September 1989 and 31 August 1992. Controls were lens users without lens related disease who presented as new patients to the casualty department from 1 March 1992 to 31 August 1992. All subjects completed a questionnaire detailing lens use and hygiene practices. SETTING: Eye hospital. SUBJECTS: 35 cases with acanthamoeba keratitis and 378 controls. MAIN OUTCOME MEASURES: Relative risks comparing different contact lens types, socioeconomic classification, age, sex, lens use, lens wearing experience, hygiene compliance, and hygiene systems. RESULTS: The crude relative risk for developing acanthamoeba keratitis with the use of daily wear disposable lenses was 49.45 (95% confidence interval 6.53 to 2227; P < 0.001) compared with conventional soft lenses (the referent). Multivariable analysis showed that this increased risk could be largely attributed to lack of disinfection (relative risk 55.86 (10 to 302); P < 0.001) and use of chlorine based disinfection (14.63 (2.8 to 76); P = 0.001) compared with other chemical systems (the referent). None of the other outcome measures showed a significant association. CONCLUSIONS: Both failure to disinfect daily wear soft contact lenses and the use of chlorine release lens disinfection systems, which have little protective effect against the organism, are major risk factors for acanthamoeba keratitis. These risks have been particularly common in disposable lens use. Over 80% of acanthamoeba keratitis could be avoided by the use of lens disinfection systems that are effective against the organism.

Spontaneous foreign body extrusion following perforating eye injury.

A structured approach to the management of a perforating ballistic eye injury is illustrated in this case, where initial treatment was limited to simple corneal wound closure and antibiotic prophylaxis. A pellet had passed completely through the globe but the retina remained attached, and it was decided to manage the case conservatively. Two retained foreign bodies were extruded spontaneously some months after the injury when suture removal and delayed cataract surgery led to a virtually perfect visual outcome. The patient has had no further complications at least three years after initial injury. The management of this civilian case illustrates some basic concepts in treating ballistic eye injuries that may be applicable in a military setting.

The superior peripheral iridectomy: prevention of pupil block due to silicone oil.

Superior peripheral iridectomy has been performed in 40 patients who have undergone silicone oil surgery for retinal detachment and who are aphakic. Only two developed raised intraocular pressure due to pupil block by liquid silicone and in each case the iridectomies seemed to be closed by proliferative membrane rather than the silicone meniscus. This type of iridectomy is particularly suitable in patients requiring intracapsular cataract extraction after previous vitrectomy and silicone oil surgery.

Acanthamoeba keratitis. The value of early diagnosis.

BACKGROUND: The treatment of Acanthamoeba keratitis has been increasingly successful as diagnoses are made earlier. The authors investigated features of the disease and prognosis in a consecutive series of 15 patients who were treated within 1 month of initial symptoms. METHODS: A database of patients with Acanthamoeba infection presenting between March 1984 and March 1992 was analyzed. The recognition, presenting features, culture methods, results, and treatment of the early cases were reviewed to determine the reasons for a good outcome. RESULTS: Recognition depended on perineural infiltrates (11/15), uveitis (10/15), limbitis (14/15), and infiltrated epithelium; 6 of 15 patients had epithelial defects, but only 3 of 15 had ring infiltrates or ulcers. Epithelial biopsy was culture-positive in 12 of 15 patients. Most (11/15) patients needed only two anti-amebal drugs. One patient only required penetrating keratoplasty for uncontrolled disease. The final visual acuity was at least 6/12 in all patients who had been treated within 1 month of first symptoms, whereas only 17 (53%) of 32 eyes of patients who presented after 1 month achieved a visual acuity of 6/12. CONCLUSIONS: Subtle diagnostic signs, supported by comprehensive microbiologic investigation, justify the immediate instigation of specific antiamebal therapy. Treatment within 1 month of onset results in a lower morbidity and a good visual outcome.

Combined extracapsular cataract extraction and trabeculectomy using a separated corneal section.

A retrospective study of 35 cases of extracapsular cataract extraction with posterior chamber lens implant combined with trabeculectomy was undertaken. The cataract extractions were performed through a corneal section to separate the cataract wound from the trabeculectomy. Control of intraocular pressure was achieved without medication in 77% of cases. Median improvement in visual acuity was 3.5 lines at one year. This technique provided improved trabeculectomy drainage compared with previous reports for corneoscleral incisions. Improvement in visual acuity was poorer for a group of patients with severe preoperative field loss.

Phenotypic characterization of T cells infiltrating the conjunctiva in chronic allergic eye disease.

BACKGROUND: Chronic allergic conjunctivitis comprises a spectrum of diseases including atopic keratoconjunctivitis, atopic blepharoconjunctivitis, vernal keratoconjunctivitis, and contact lens-associated giant pupillary conjunctivitis. Each condition is characterized by a complex immunopathology with a mixed cellular infiltrate. Treatment with conventional mast cell stabilizers is often unsatisfactory, and therapy depends heavily on topical corticosteroids. OBJECTIVE: Recent evidence suggests that T lymphocytes play an important role in mediating the immunopathology seen in the chronic allergic response in the skin and the lungs. METHODS: We have therefore investigated the prevalence of T cells and their subsets in the different chronic allergic eye conditions by means of immunohistochemistry. RESULTS: We found significantly increased numbers of CD4+, CD45RO+, and HLA-DR+ T cells in the conjunctiva of patients with atopic and vernal keratoconjunctivitis and giant papillary conjunctivitis, with a corresponding upregulation of markers present on antigen presenting cells. CONCLUSIONS: These findings suggest that like allergic conditions in the skin and lungs, CD4+ memory T cells are involved in the regulation of the immunopathology of chronic allergic eye responses. Further characterization of these T cells will provide the information necessary for future immunotherapeutic interventions.

Mast cell distribution and neutral protease expression in acute and chronic allergic conjunctivitis.

Allergic eye disease has a variety of clinical manifestations including seasonal atopic conjunctivitis (SAC), perennial atopic conjunctivitis (PAC), atopic keratoconjunctivitis (AKC), and atopic blepharoconjunctivitis (ABC). We have investigated the number, distribution and protease expression of mast cells in normal and diseased conjunctiva with the use of immunohistochemistry in water-miscible resin sections. The median mast cell densities in normal subjects were 17 mm-2 in the bulbar substantia propria and 9 mm-2 in tarsal substantia propria. Mast cells were absent from the normal conjunctival epithelium at both sites. Mast cell densities were increased in the bulbar substantia propria in SAC, AKC and ABC. Tarsal substantia propria showed a significant increase in mast cells in ABC and AKC disease states. Mast cells express a range of proteases which varies according to their anatomic site. Mast cells in connective tissue are described to contain tryptase, chymase, cathepsin-G and carboxypeptidase-A, whereas mucosal mast cells contain only tryptase. In the diseased conjunctiva there was a marked reduction in proteases other than tryptase in the intraepithelial mast cells. There were also significant reductions in protease expression other than tryptase in the bulbar substantia propria in AKC and ABC. There appear to be specific alterations in the distribution of mast cells in the sub-categories of allergic eye disease. The distinction between mucosal and connective tissue mast cell phenotypes is not clear-cut and may depend on the functional state of the mast cells in relation to the microenvironment.

Infective endophthalmitis following vitreoretinal surgery.

Eleven cases of endophthalmitis occurring after vitreoretinal surgery are described. At Moorfields Hospital, London, from 1986 to 1990 the incidence of endophthalmitis after explant surgery with or without drain was 0.19% and after vitrectomy was 0.15%. We conclude that the parity may be due to the intraocular instrumentation of most conventional retinal detachment repair procedures. The best indicator of poor prognosis was speed of onset of symptoms, those with rapid evolution having the worst outcome; 2 of these cases were enucleated. Those presenting at 2-3 days had the best outcome, consistent with infection due to a less virulent organism. Delays in diagnosis were in part due to the posterior location of signs of infection. Potential risk factors amenable to prophylactic strategy were identified in 10 of the 11 patients. Supplementary prophylaxis using ciprofloxacin or imipenem is proposed for cases with an identifiable risk factor. After systemic administration these antibiotics achieve vitreous levels that exceed the MIC90 of the commonest causative pathogens.

A review of 72 consecutive cases of Acanthamoeba keratitis, 1984-1992.

A review of consecutive cases of Acanthamoeba keratitis presenting since 1984 was undertaken in order to assess prognostic factors, the success of culture procedures and the outcome of medical and surgical management, with reference to current clinical practice. Seventy-two consecutive cases (77 eyes) of Acanthamoeba keratitis have been managed. Sixty-four patients were contact lens wearers, 28 of these wearing disposable lenses. Superficial corneal involvement and perineural infiltrates were common in those diagnosed less than a month after first symptoms, designated 'early' presentation. Ring infiltrates and ulceration with stromal lysis characterised those presenting at 1-2 months ('intermediate') or after 2 months ('late'); these groups also progressed more frequently to hypopyon, scleritis, glaucoma and cataract formation. Positive corneal cultures were obtained in 10 of 14 (71%) intermediate and 17 of 23 (74%) late cases; early cases underwent epithelial biopsy but formal trephine biopsy was not usually justified (1 of 35 cases) and only 19 of 35 (54%) were tissue-positive. Microbial co-isolates were obtained from 20 corneas. Thirty-four penetrating keratoplasties were performed in 23 eyes, 21 whilst inflamed and 13 when quiet. Of 13 failures in inflamed eyes, 9 were due to recurrence of Acanthamoeba infection. Medical cure is known to have been achieved in 64 of 73 (88%) eyes, 4 of the original 77 having been lost to follow-up abroad. Fifty-eight of 73 eyes (79%) achieved a final visual acuity of 6/12, and of the culture-positive cases, 32 of 46 (70%) achieved 6/12.(ABSTRACT TRUNCATED AT 250 WORDS)

The origin of keratopathy in chronic allergic eye disease: a histopathological study.

Although the clinical features of atopic keratoconjunctivitis have been well described, it is recognised that some adults with severe chronic allergic conjunctivitis do not develop a keratopathy despite having marked disease of their lid margins and conjunctiva. The aetiology of the keratopathy of chronic allergic eye disease is not known but may result from the release of toxic mediators from mast cells, eosinophils and neutrophils in the inflamed conjunctiva. To examine this theory we have counted these cells in tarsal and bulbar conjunctival biopsies from patients with severe allergic conjunctivitis and compared the numbers in samples from patients with or without keratopathy. Our results indicate that patients with chronic allergic conjunctivitis with keratopathy have higher cell numbers in their conjunctiva than patients with no keratopathy, especially those staining for eosinophil cationic protein in the tarsal epithelium. A statistically significant difference between disease groups could only be demonstrated, however, when the combined totals of mast cells, eosinophils and neutrophils were compared.

Seasonal allergic conjunctivitis is accompanied by increased mast cell numbers in the absence of leucocyte infiltration.

BACKGROUND: Seasonal allergic conjunctivitis (SAC) is the most common allergic disease to affect the eye, occurring alone or in association with allergic rhinitis. Infiltration with mast cells and eosinophils is characteristic of the chronic forms of allergic conjunctivitis such as vernal and atopic keratoconjunctivitis, and these cell types also contribute significantly to allergic inflammation in the skin. Indirect evidence for a similar pattern of cellular events in SAC comes from studies which demonstrate raised eosinophil and neutrophil numbers in conjunctival scrapings and elevated levels of mast cell tryptase in tears following allergen challenge. OBJECTIVE: To directly characterize the inflammatory cell infiltrate in SAC and to determine its clinical relevance. METHODS: We employed specific immunohistochemical staining to count mast cells, eosinophils and neutrophils in the conjunctival epithelium and lamina propria of eight atopic patients with SAC in, and 12 SAC patients out of the hay fever season. Sixteen patients with no history of ocular allergy were used as control subjects. RESULTS: Mast cells were absent from normal epithelium. During the pollen season median mast cell numbers in the lamina propria were found to be increased by 61% in patients with SAC compared with normals (P=0.012). Eosinophils were found in the lamina propria in less than half of the symptomatic patients with SAC and in only three patients were eosinophils present in the epithelium. The neutrophil numbers in the lamina propria of patients with SAC tended to be higher than normals but these changes did not reach statistical significance. CONCLUSION: These data based on the direct assessment of conjunctival tissue provide evidence that symptoms occur in SAC in the absence of detectable recruitment of eosinophils or neutrophils. This suggests that this disorder is related to mast cell-mediated changes.

Tear and conjunctival changes during the allergen-induced early- and late-phase responses.

BACKGROUND: Allergic eye disease is common, but little is known about the underlying disease mechanisms. Conjunctival allergen challenge causes symptoms similar to those of seasonal allergic conjunctivitis and is a useful model to study. OBJECTIVE: We have used allergen challenge to investigate the course of the ocular response, tear inflammatory mediators, tissue adhesion protein expression, and cellular infiltration. METHODS: Eighteen atopic patients and 4 nonatopic control subjects were challenged with extracted mixed grass or Dermatophagoides pteronyssinus in one eye and control vehicle in the other. The clinical response was recorded, and tears were collected over a 6-hour period. Conjunctival biopsy specimens were taken from the challenged eye at 6 or 24 hours. RESULTS: An early-phase response (maximal at 20 minutes) showed a significant increase in tear histamine and tryptase levels, reducing to control levels again by 40 minutes. At 6 hours, a late-phase response occurred with increased symptoms, a second peak of tear histamine and eosinophil cationic protein but not tryptase, upregulation of the adhesion molecules E-selectin and intercellular adhesion molecule, and a cellular infiltrate of mast cells, neutrophils, eosinophils, macrophages, and basophils, with T cells increased only in bulbar biopsy specimens. CONCLUSIONS: The early peaks of tear histamine plus tryptase indicate that the mast cell is responsible for the early-phase response, but basophils may be involved in the late-phase response. Both tear and biopsy findings underline the significance of the late-phase response as the transition between a type I response and clinical disease.