James P. McCulley

The International Workshop on Meibomian Gland Dysfunction: Report of the Definition and Classification Subcommittee

Recommended definition of MGD: Meibomian gland dysfunction (MGD) is a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion. This may result in alteration of the tear film, symptoms of eye irritation, clinically apparent inflammation, and ocular surface disease. Previous definitions and criteria of MGD: There is no firmly established definition of MGD published in the literature. Most researchers have used a criterion-based approach to describe the condition, with combinations of objective findings and measurements. Anatomic changes of the lid margin, expressibility of meibomian lipids, gland dropout by meibography, evaporimetry, and meibometry are most commonly used (Table 1). Table 1. Criteria of Meibomian Gland Dysfunction Used in Previous Works

Clinical and diagnostic use of in vivo confocal microscopy in patients with corneal disease.

BACKGROUND The purpose of this article is to introduce the practicing ophthalmologist to the optical principles and images produced by a tandem scanning confocal microscope (recently approved by the Food and Drug Administration for general clinical use). The tandem scanning confocal microscope allows real-time viewing of structures in the living cornea at the cellular level in four dimensions (x, y, z, and time). METHODS Nine patients (2 males, 7 females), ranging in age from 7 to 52 years, were examined. Images were recorded on super VHS videotape, digitized and processed on a computer workstation, and photographed for presentation. RESULTS Two-dimensional (x, y) 400 x 400-microns images (9-microns z-axis thickness) are presented for normal corneal structures and for the clinical conditions of herpetic keratitis, wound healing after myopic excimer ablation, Acanthamoeba infection, corneal dystrophies (granular, Reis-Buckler), contact lens abrasion, and the irido-corneal endothelial syndrome. CONCLUSION Clinical confocal microscopy has the unique potential of providing noninvasive assessment of corneal injury and disease at the cellular level that is not available currently from other technologies.

Results of the Prospective Evaluation of Radial Keratotomy (PERK) Study One Year After Surgery

The Prospective Evaluation of Radial Keratotomy (PERK) study is a nine-center, self-controlled clinical trial of a standardized technique of radial keratotomy in 435 patients who had physiologic myopia with a preoperative refraction between -2.00 and -8.00 diopters. The surgical technique consisted of eight incisions using a diamond micrometer knife with blade length determined by intraoperative ultrasonic pachymetry and the diameter of central clear zone determined by preoperative refraction. At one year after surgery, myopia was reduced in all eyes; 60% were within +/- 1.00 diopter of emmetropia; 30% were undercorrected and 10% were overcorrected by more than 1.00 diopter (range of refraction, -4.25 to +3.38 D). Uncorrected visual acuity was 20/40 or better in 78% of eyes. The operation was most effective in eyes with a refraction between -2.00 and -4.25 diopters. Thirteen percent of patients lost one or two Snellen lines of best corrected visual acuity. However, all but three eyes could be corrected to 20/20. Ten percent of patients increased astigmatism more than 1.00 diopter. Disabling glare was not detected with a clinical glare tester, but three patients reduced their driving at night because of glare. Between six months and one year, the refraction changed by greater than 0.50 diopters in 19% of eyes.

Acanthamoeba keratitis associated with soft contact lenses.

Three patients (a 13-year-old girl, a 25-year-old man, and a 22-year-old woman) who used daily-wear soft contact lenses, sterilized with saline made from distilled water and salt tablets, developed Acanthamoeba keratitis. Acanthamoeba was cultured from the contact lens solution of one patient. This patient, in whom the diagnosis was made by corneal biopsy early in the clinical course, was successfully treated with topical neomycin-polymyxin, miconazole, and propamidine isethionate. The other two patients underwent penetrating keratoplasty. One of these patients, who received a graft early in the clinical course, developed a recurrence of disease in the graft, whereas the other, who received the graft 18 months after the initial symptoms, has maintained a clear corneal transplant with useful vision.

The pathogenesis of Acanthamoeba keratitis.

Free-living amoebae of the genus Acanthamoeba produce a progressive, blinding infection of the corneal surface. The pathogenesis of Acanthamoeba keratitis involves parasite-mediated cytolysis and phagocytosis of corneal epithelial cells and induction of programmed cell death. Acanthamoeba spp. elaborate a variety of proteases which may facilitate cytolysis of the corneal epithelium, invasion of the extracellular matrix, and dissolution of the corneal stromal matrix.

Meibomian Gland Function and the Tear Lipid Layer

The meibomian glands of the lid produce a lipid material whose synthesis is dependent on neuronal, hormonal, and vascular factors. This lipid material is fluid, spreads easily, is a surfactant as well as an aqueous barrier and must remain functional after a blink. To satisfy these requirements, the meibomian lipids have a specific composition. Even after delivery it may be modified by lipases produced by ocular bacteria, and modifications in the lipid components can lead to unique disease states. For example, bacteria may degrade lipids, producing an unstable tear film and irritating free fatty acids; and hormonal imbalances may alter lipid profiles to destabilize the tear film and produce evaporative dry eye.

Comparison of Ciprofloxacin Ophthalmic Solution 0.3% to Fortified Tobramycin-Cefazolin in Treating Bacterial Corneal Ulcers

PURPOSE The purpose of the study is to compare the clinical efficacy and safety of ciprofloxacin ophthalmic solution 0.3% (Ciloxan) with a standard therapy regimen (fortified tobramycin, 1.3%-cefazolin, 5.0%) for treating bacterial corneal ulcers. METHODS This randomized, parallel group, double-masked, multicenter study was conducted in 324 patients at 28 centers in the United States, Europe, and India. Patients were randomized into 2 treatment groups: 160 to ciprofloxacin and 164 to fortified tobramycin-cefazolin. Positive microbiologic cultures were obtained in 188 (58%) of 324 patients. Of these, 176 patients met protocol criteria and were evaluated for treatment efficacy: 82 in the ciprofloxacin group and 94 in the standard therapy group. The dosing schedule for both treatment groups was 1 to 2 drops of the first study medication (ciprofloxacin or fortified tobramycin) every 30 minutes for 6 hours, then hourly for the remainder of day 1; 1 to 2 drops every hour on days 2 and 3; 1 to 2 drops every 2 hours on days 4 and 5, followed by 1 to 2 drops every 4 hours on days 6 to 14. The second medication (ciprofloxacin or cefazolin) was instilled 5 to 15 minutes after the first drug, following the same dosing frequency. Physicians judgment of clinical success, cure rate, changes in ocular sings, and symptoms and the rate of treatment failures were the primary efficacy criteria. RESULTS Topical ciprofloxacin monotherapy is equivalent clinically and statistically to the standard therapy regimen of fortified antibiotics. No statistically significant treatment differences were found between ciprofloxacin (91.5%) and standard therapy (86.2%) in terms of overall clinical efficacy (P = 0.34). Similarly, no differences were noted in resolution of the clinical signs and symptoms (P > 0.08) or the time to cure (P = 0.55). The incidence of treatment failures was less in the ciprofloxacin group (8.5%) compared with the standard therapy group (13.8%). Significantly fewer patients treated with ciprofloxacin reported discomfort than did patients treated with the standard therapy regimen (P = 0.01). CONCLUSION Ciprofloxacin ophthalmic solution 0.3% monotherapy is equivalent clinically and statistically to standard therapy (fortified tobramycin-cefazolin) for the treatment of bacterial corneal ulcers and produces significantly less discomfort.

Acanthamoeba Keratitis: A Growing Problem in Soft and Hard Contact Lens Wearers

Eleven contact lens-wearing patients presented with Acanthamoeba keratitis. Eight cases were culture- and/or stain-positive for Acanthamoeba and three were presumed to have Acanthamoeba keratitis based on history and clinical findings. Six wore daily wear soft contact lenses, two wore extended-wear soft contact lenses, one wore a polymethylmethacrylate hard contact lens, one wore a gas-permeable hard contact lens, and one wore a Saturn lens (combined hard and soft lens). Four patients used distilled water and salt tablet saline, three used tap water and salt tablet saline, two used tap water rinse, two used well water rinse or storage, and one used intravenous (IV) saline. It is apparent that all contact lens wearers are at some risk for Acanthamoeba keratitis developing if proper contact lens care is not maintained. Of great concern is the inability of most current chemical sterilization methods to kill the organism if the lens becomes contaminated. Heat disinfection will kill Acanthamoeba trophozoites and cysts but the lens must not be placed into contaminated solutions afterward. Prevention is very important because medical and surgical treatment failures are frequent. Eye care practitioners who fit contact lenses are advised to use heat disinfection for low-water content stock soft contact lenses, and to use hydrogen peroxide without a catalyst for a minimum of 6 hours for all other stock lens fitting sets, to specifically inquire about contact lens care habits used by their patients, and to discourage the use of homemade saline solutions.

Polar lipids in human meibomian gland secretions.

Purpose. To determine the polar lipid composition of human meibomian gland secretions and their relationship to the preocular tear film. Methods. Meibomian secretions were collected from normals and patients with chronic blepharitis. These lipids (meibum) were first separated by thin layer chromatography. Polar lipids were then separated utilizing high-pressure liquid chromatography with ultraviolet detection. Individual peaks were identified by comparison with standards. Collected sample peaks were subjected to differential transmethylation with sodium methoxide-methanol and the resulting fatty acid methyl esters were analyzed by gas chromatography-mass spectroscopy. Results. Three phospholipids were identified as phosphatidylcholine, phosphatidylethanolamine and sphingomyelin; other unidentified phospholipids were also present. Also present in secretions were the sphingolipids ceramides and cerebrosides. Fatty acids present were 12-18 carbon chain length. All fatty acids were normal (not branched) saturated fatty acids except in sphingolipids, where hydroxy fatty acids were also present. Unsaturated normal fatty acids were present only in meibum from patients with meibomianitis. Conclusions. The composition of the polar lipids in meibomian gland secretions is more complex than previously thought. On the other hand, the type and carbon chain length of the polar lipid fatty acids appears strictly controlled. The relationship of these findings to the preocular tear film should be considered in terms of overall functionality. The polar lipid layer most likely is only one to three molecules thick and serves as a surfactant between aqueous tears and the thicker nonpolar lipid layer.

Comparative bacteriology of chronic blepharitis.

One hundred and fifteen patients with chronic blepharitis were compared with 47 normal controls. Six clinically distinct groups of blepharitis were observed: staphylococcal; seborrhoeic, alone, with associated staphylococcal superinfection, meibomian seborrhoea, or secondary inflammation of the meibomian glands; and meibomian keratoconjunctivitis (MKC). Staphylococcus aureus was isolated in appreciable frequency from the staphylococcal and the mixed staphylococcal/seborrhoeic groups in contrast to the normal and non-staphylococcal groups. Coagulase-negative Staphylococcus spp., Propionibacterium acnes, and cornyneform bacteria were the most commonly isolated bacteria from the lid for all groups. Cultures of material expressed from the meibomian glands yielded similar organisms but in reduced frequency. Testing of antibiotic susceptibility revealed Staph aureus to be usually sensitive to most commonly used ophthalmic antimicrobials except sulphonamides.