[Meibomian glands : part III. Dysfunction - argument for a discrete disease entity and as an important cause of dry eye]. / Meibom-Drüsen : Teil III: Dysfunktion (MGD) - Plädoyer für ein eigenständiges Krankheitsbild und wichtige Ursache für das trockene Auge.

Meibomian gland dysfunction (MGD), mainly synonymous with posterior blepharitis but typically without prominent inflammatory alterations of the lid margin, is a discrete disease entity and a frequent cause of wetting deficiencies of the ocular surface leading to dry eye disease that deserves increased recognition by clinicians. The history, classification, pathology, influencing factors, diagnostics and therapy are explained and discussed. MGD is mainly based on an obstructive mechanism caused by hyperkeratinization of the excretory duct and/or increased viscosity of the secretion (meibum) with subsequent deficiency of the tear film lipid layer. MGD is influenced by the hormonal status and by chemical and mechanical noxes as well as genetic defects and it occurs more frequently in women and generally increases with age. It results in stasis of meibum inside the glands, dilatation of the ductal system and eventually in atrophy and loss of glandular tissue (gland dropout). Careful investigation of the eyelids and lid margins with eversion, if necessary, should therefore be performed in every case of a wetting defect, notably before fitting contact lenses. Particularly important is the inspection of the meibomian orifices and diagnostic expression by mild mechanical compression of the lid.

[Blepharitis]. / Blepharitis.

Blepharitis is characterized by a great variety of clinical manifestations, which often include alterations of the ocular surface. This as well as its tendency to be therapy-resistant and recurrent explains why blepharitis marks a challenge for all ophthalmologists. Occasionally dermatologic diseases represent one of the causes of the disease, thus calling for an interdisciplinary approach. The present article describes the state of the art with regard to pathogenesis and therapy of blepharitis.

[Dry eye disease as a complex dysregulation of the functional anatomy of the ocular surface. New concepts for understanding dry eye disease]. / Das trockene Auge als komplexe Fehlregulation der funktionellen Anatomie der Augenoberfläche. Neue Impulse zum Verständnis des trockenen Auges.

INTRODUCTION: Dry eye disease is a disorder of the tear film that results in epithelial damage and in a disruption of the normal homeostasis at the ocular surface. It is widespread and causes symptoms ranging from discomfort to blindness. METHODS: A review of the existing literature was used to compare different past and recent concepts for the understanding of dry eye disease with a focus on aspects of the integrating functional anatomy of the ocular surface. RESULTS: The understanding of the pathogenesis of dry eye disease has proceeded from the mere recognition of a lack of tears to a consideration of their quality and to the concept of wetting of the ocular surface. However, several other aspects as epithelial differentiation, innervation, hormonal status or immune protection contribute to the intact functional anatomy of the ocular surface. Recently it has been recognized that immunologically regulated mechanisms of inflammation represent a primary or secondary pathogenetic factor for dry eye disease. This is conceivably regulated by the cells of the physiological mucosal immune defence system, the eye-associated lymphoid tissue (EALT). Androgens represent an important trophic factor for the ocular surface and their deficiency predisposes to inflammation. CONCLUSION: Dry eye disease represents a complex dysregulation of the functional anatomy of the ocular surface that can start from different alterations (e.g. insufficient secretion, defects in wetting or innervation). Immune-based inflammation is able to interconnect and negatively reinforce these different pathomechanisms, resulting in a vicious circle.

Dry eye disease: the scale of the problem.

Dry eye disease, or keratoconjunctivitis sicca, is among the most frequently established diagnoses in ophthalmology; in Germany, one in four patients consulting an ophthalmologist complains of the symptoms of dry eye. Although epidemiological studies investigating the prevalence of dry eye disease are rare, published studies indicate that up to 20% of adults aged 45 years or more experience dry eye symptoms. Recent studies have shown that immunologic changes play a role in the pathogenesis of dry eye, not only in Sjögren's syndrome, but also in postinfectious and age-related conditions. Despite increasing understanding of the pathogenic factors involved in dry eye disease, there has been a lack of consensus on diagnostic criteria, classification of disease states, and the aims and interpretation of specific diagnostic tests. There is a need, therefore, for standardization of disease terminology and diagnostic tests in order to improve the usefulness of epidemiological and clinical investigation of this important ocular disorder.

[Vision disorders in the elderly]. / Sehstörungen im Alter.

BACKGROUND: British trials from the 60's reveal that older patients tend to underreport their health problems. They misjudge them as non specific or being caused by old age. In this study we investigate whether standard preventive assessment facilitates the detection and early intervention of ophthalmological problems in old age. METHODOLOGY: For the first time a representative screening trial for older patients visiting their general practitioner was carried out in Germany, 1994. The surgeries as well as the 466 participating patients over 69 years were randomly selected. GPs were asked to examine the visual problems of the participants per standardized questionnaire and visual accuracy test. GPs had to report uncovered problems and planned interventions. RESULTS: Altogether, 75% of the participating patients had some need for a further ophthalmological diagnostic or therapeutic intervention. Every fourth patient had not seen an ophthalmologist within the last two years. 40% of the participants complained of eye problems. 22% had symptoms of a glaucoma. Visual accuracy was low in 17% of the older patients. General practitioners had only been aware of 50% of all visual problems requiring further intervention. About half of the patients with a low visual accuracy and 70% with an indication of glaucoma had been unknown before. For about half of the patients requiring ophthalmological investigation (excluding problems with glasses) an intervention was planned. For every fifth, the general practitioners initiated referrals. CONCLUSION: The standard preventive facilitated to detect a high rate of visual problems in old age. Close cooperation with ophthalmologists is necessary for patients who do not take up the specialists' eye check ups (especially those at risk). Patients with severe eye problems in some cases in spite of specialists' care also require interdisciplinary treatment.

[Contact lenses. 2: Contact lens associated infections]. / Kontaktlinsen. Teil 2: Kontaktlinsenassoziierte Infektionen.

Contact lens wearers, especially those who wear soft or extended wear contact lenses, are at increased risk of suffering from keratitis. Among the causes of corneal infections, an inadequate hygiene or overextended wear play an important role. An insufficient cleaning and disinfection leads to contamination with pathological germs. Sites of entry for these germs are corneal microlesions, caused by the setting and removal of contact lenses, and epithelial defects, as a result of the wearing of old or defective contact lenses. Primary eye diseases of patients who wear contact lenses can be altered by their wearing, and vice-versa. Even more, miscellaneous infections may lead to infectious corneal ulcerations. Having an adequate hygiene, a proper patient orientation during the medical visit, and a regular control are therefore of great importance for the reduction in the frequency of such infections by patients who wear contact lenses.

[Contact lenses. 1: Contact lens associated complications]. / Kontaktlinsen. Teil 1: Kontaktlinsenassoziierte Komplikationen.

The contactology as frontier between ophthalmology and eye optics requires special attention by part of ophthalmologists. Contact lenses influence the anatomy, the physiology and the immunological responses of the external eye. The corneal metabolic disorders of contact lens wearers are among others, the result of a diminished oxygen supply to the cornea. These disorders are influenced by contact lens deposits, tear film dysfunction and intrinsical characteristics of contact lenses. Sensibilisation and allergic reactions are result of the wearing of contact lenses. Even toxic reactions, as a result of the disinfection systems used, may be observed Ophthalmologists must be able to recognize the contact lens induced diseases and to advice their patients properly. Therefore, regular ophthalmological control examinations are indispensable.

[Contact lenses. Infections and hygiene]. / Kontaktlinsen. Infektionen und Hygiene.

BACKGROUND: Contact lens wearers are subject to increased risk of infection, and an attempt was made to determine which factors cause the overproportional risk of infection? PATIENTS: The aim of this paper is to explain with appropriate bibliographic support why people who wear contact lenses are at risk of infection. RESULTS: The relative risk of keratitis is a function of the lens material and the wearing time of the contact lenses. Extended wear of hydrogel lenses is associated with an overproportional risk of infection. According to the literature, the frequency of complications in contact lens wearers generally is the result of poor hygiene in 66% of the cases. The general lack of hygiene among contact lens wearers must, therefore, be regarded as one cause among pathophysiological mechanisms of the eye. The microbial spectrum favors gram-negative bacteria living in a wet environment such as Pseudomonas, Serratia and parasites like Acanthamoeba. CONCLUSION: The specific spectrum of pathogens and new problem organisms not only challenge the fitter but also the manufacturers to adapt hygiene (sanitary) measures and products to the new development. Disposable contact lens systems are the first step, but they do not solve all the problems of contact lens wearers. Therefore, the importance of contact lens hygiene must be especially emphasized when the ophthalmologist is giving instructions to the patient. On the other hand, hygiene should also not be neglected by the contact lens fitters since it is part of the whole problem.

How can the bioavailability of timolol be enhanced? A pharmacokinetic pilot study of novel hydrogels.

BACKGROUND: Carbomerbased hydrogels with timolol maleate (T-Gel) were chosen to study the vehicle effect on ocular bioavailability. Pharmacokinetic profiles of T-Gel 0.05% (0.05% timolol), T-Gel 0.025% (0.025% timolol) and commercial timolol ophthalmic solution (TOS 0.1%; 0.1% timolol) were determined and compared. METHODS: A single dose was administered to rabbits' eyes. Timolol was determined by HPLC in aqueous humour, blood samples and washings of the ocular surface (as a measure of residence time). Sampling times were 0.5 h, 1 h and 4 h after instillation. RESULTS: Concentration versus time curves (AUC) of timolol in aqueous humour demonstrate no significant differences between TOS 0.1% and T-Gel 0.025% (P = 0.19), whereas the difference between T-Gel 0.05% and TOS 0.1% is significant (P = 0.006); the AUC ratio of T-Gel 0.05%:TOS 0.1%:T-Gel 0.025% was 2.14:1:0.87. Timolol blood levels were highest with TOS 0.1% at every time point. Peak levels occurred after 0.5 h with all test products; the ratio of peak levels (Cmax) for T-Gel 0.05%:TOS 0.1%:T-Gel 0.025% was 0.55:1:0.17. Timolol was detected in the washings up to 1 h after instillation of test products; the highest levels were observed after T-Gel 0.05%. CONCLUSION: The new vehicle obviously improves the bioavailability of topically applied timolol.

[Changes in corneal topography after using tear substitutes]. / Veränderungen der Hornhaut-Topographien nach Anwendung von Tränenersatzmitteln.

BACKGROUND: Computer-controlled video keratoscopy is being employed ever more frequently and for various indications. PATIENTS: We have studied the effects of high-viscosity and low-viscosity tear substitutes on the corneal topography, one and five minutes after application to 14 normal eyes of 7 subjects, and compared the results. RESULTS: In contrast to low-viscosity preparations, high-viscosity preparations cause an appreciable increase in astigmatism and an alteration of the axis shortly after application. The variations caused by low-viscosity tear substitutes lie within the normal range of variation between several measurements. CONCLUSIONS: At least in the case of the normal eye, gels should not be applied immediately before keratometry. In the case of patients who have undergone keratoplasty, however, it can be helpful before fitting contact lenses. In addition keratometry can be helpful to determine the residence time of ophthalmic preparations being different in viscosity.

[Hydroxyethyl starch for reversing edema in short-term culture media for donor corneas]. / Hydroxyäthylstärke als Entquellungssubstanz in Kurzzeitkulturmedien für Spenderhornhäute.

PURPOSE: To investigate the feasibility to use hydroxyethylstarch as an alternative deswelling additive in short-term preservation media. MATERIALS AND METHODS: Corneoscleral discs were prepared from pairs of eye balls of freshly slaughtered pigs. Corneas were stored in MEM-medium containing either 10% or 20% hydroxyethylstarch 450 000 at 4 degrees C in a refrigerator. Subsequently, the tissue was stored for 24 hours in organ culture at 37 degrees C in MEM-medium containing 10% fetal calf serum to detect latent endothelial cell damage. Mate corneas were treated the same except for being stored in Optisol GS during 4 degrees C storage. We determined corneal endothelial cell density, stromal thickness, and glucose concentration in the medium directly after preparation, after short-term storage at 4 degrees C, and after subsequent organ culture at 37 degrees C. Scanning electron microscopy of corneal endothelium was performed at each step during the experimental course. RESULTS: We did not observe any significant differences in endothelial-cell density between experimental groups and control groups. No decrease in endothelial-cell density was observed during the course of experiments. No increase in stromal thickness was determined in any group after short-term storage at 4 degrees C. Corneas stored in medium containing 20% hydroxyethylstarch showed a decrease in stromal thickness after short-term storage. After subsequent organ culture all corneas displayed a uniform stromal swelling. Glucose concentrations in the media decreased in all groups during the experiment. In scanning-electron microscopy we observed a reversible degeneration of cell borders after storage at 4 degrees C. Additionally, corneas stored in Optisol GS showed a reversible cobblestone appearance at this stage of the experiments. CONCLUSION: Hydroxyethylstarch appears to be an alternative to the use of dextran and chondroitin sulfate as a deswelling additive in corneal preservation media.

[Changes in visual function caused by work at a data display terminal]. / Veränderungen von Sehfunktionen durch Arbeit am Datensichtgerät.

Working at video display terminals (VDTs) is particularly demanding in terms of orthopaedic and visual functions. This study was initiated to examine whether, and if so how, VDT work can influence the visual system. It was designed as a 5-year-prospective study based on the matched-pairs technique. The subjects were examined at the beginning and after 5 years of VDT work. The study group consisted of 102 people working at VDTs, and these were paired with 102 other office workers who did not use VDTs. The legally prescribed screening examinations of visual acuity (distance and near vision, phorias, stereopsis, and colour vision) were carried out. We also checked the anterior segments by examination with the slit-lamp and the fundus by ophthalmoscopy. Break-up time, Schirmer-I test, perimetry and tonometry were included in our range of examinations. We found a significant difference in asthenopia and daily hours of VDT work between VDT workers working less than 6 h daily and those working more than 6 h daily. In the study group pre-existing exophoria seemed to increase, but no statistical significance was found on testing. Nor was there any significant difference between the study group and the control group in the parameters examined in the course of the screening examination. In our investigation of monocular VDT workers (n = 3) we could not find any visual problems.

Induction of conjunctival epithelial alterations by contact lens wearing. A prospective study.

In a prospective clinical study, contact lenses were applied to 14 wearers of glasses with clinically and cytologically normal conjunctiva. The alterations of conjunctival cytology after the start of contact lens wearing were recorded with the technique of impression cytology over a period of 6 months. Within the first few weeks after application of the contact lenses, the patients developed a rapidly increasing alteration of cell size and nuclear morphology. Enlargement of the cell diameter with flattening of the cell body was seen together with numerous different nuclear alterations, in particular snakes (condensations of the nuclear chromatin into a sticklike or snakelike shape, centrally arranged in the nucleus). After this very rapid onset, the alterations increased more slowly towards a possible saturation point (and it seemed that the ultimate changes might possibly not be reached within the investigated period). At about 3-6 months, the patients reached a degree of cytological alteration which was seen in long-time contact lens wearers in our previous study and before this, except for the lack of keratinization, only observed in diseases of the ocular surface. There was a distinct squamous metaplasia of major parts of the conjunctival epithelium which normally is columnar and a decrease of goblet cell density. Squamous metaplasia and nuclear alterations increased with the length of time which had elapsed since the application of contact lenses and with extending the daily wearing time but were always restricted to the contact lens excursion zone on the eye and disappeared after contact lens omission, as seen before. Even patients with major cytological alterations remained free of symptoms, and the conjunctiva was still clinically normal.

Conjunctival cytology in asymptomatic wearers of soft contact lenses.

Conjunctival epithelium was systematically investigated with impression cytology in clinically asymptomatic wearers of soft contact lenses who had been using their lenses for several years. Severe abnormalities were observed, which had so far only been seen in diseases of the ocular surface mainly in dry eye syndromes. All patients showed evidence of squamous metaplasia with distinctly enlarged, flattened cells without evidence of keratinization. They also showed frequent nuclear abnormalities, primarily a high percentage of snakelike-appearing condensations of nuclear chromatin (snakes). The goblet cell density observed was relatively low. Snakes were for the first time detected outside the known localization (upper bulbar conjunctiva, 12 o'clock position) and could be demonstrated throughout the whole bulbar conjunctival epithelium. It is suggested that the changes observed are due to chronic mechanical irritation by the contact lens, as indicated by their topographical distribution and as proven by their reversibility after omission of contact lens wear.

[Clinical study of the effectiveness of a preservative-free tear substitute]. / Klinische Studie zur Wirksamkeit eines nicht konservierten Tränenersatzmittels.

57 patients with dry eye syndrome of various etiology were treated with a preservative-free hydrogel in an open clinical trial. All patients enrolled in the 12 weeks study had a history of pretreatment with usual commercial tear substitutes which was either insufficient for relief of complaints or caused hypersensitivity. Detailed analysis of patients self assessment of their condition (by means of a linear scale), tear film break-up time, Schirmer Test, and physician's assessment of therapeutical results revealed that in about 90% of cases existing patient complaints and findings related to dry eye syndrome were significantly improved by symptomatic therapy with this preservative-free gel.

[Scanning electron microscopic study on local cornea tolerance of beta-blocker eye drops with and without preservatives]. / Rasterelektronenmikroskopische Untersuchungen zur lokalen Hornhautverträglichkeit von Betablockeraugentropfen mit und ohne Konservierungsstoffe.

The influence of beta-blockers in short- and long-term application on the epithelium of the cornea was studied in rabbits with intact tear film, concentrating not on the completeness of the drug group but on general differences. The new unpreserved beta-blocker timolol was compared on an exemplary level with the following beta-blocker formulas: (1) beta-blocker eye drops with 0.01% of the preservative benzalkonium chloride; (2) beta-blocker eye drops with 0.005% of the preservative benzalkonium chloride, and (3) beta-blocker eye drops with 0.004% of the preservative benzalkonium chloride and the tear substitute polyvinyl alcohol. Exposure time in the short-term test was 30 min, in long-term tests the time was 24 weeks. Any cell damages observed were of only minor importance and rarely of clinical relevance; however, it could be shown that micromorphological cell reactions differed as a function of the preservative concentration. Complete absence of preservatives causes no difference in micromorphologically relevant changes in comparison with the control group. Drugs without preservatives are thus a meaningful alternative for patients with allergies, sensitive eyes or existing impairment of the precorneal film.

[Tear substitutes. Experimental and clinical observations]. / Tränenersatzmittel. Experimentelle und klinische Beobachtungen.

Dry-eye conditions do not represent an etiologically homogeneous clinical picture, and therapy is therefore difficult. Tear substitution by means of artificial tears of various viscosities has been common practice, and the use of highly viscous artificial tears is considered appropriate therapy in many cases of dry eye because of their prolonged contact time on the ocular surface. A clinical study with a gel made of cross-linked polymers of acrylic acid with a high molecular weight (Thilo-Tears) showed that both the subjective and objective effects were good. Clinical parameters and data describing the differences in contact times of the highly viscous preparations and a low-viscosity solution (2% PVP), Schirmer's test, Jones's test, and BUT are described and assessed in detail. Furthermore, an attempt is made to supplement and corroborate the clinical findings and the rationale of using highly viscous solutions by presenting experimental results on the preocular film. In particular, considerations pertaining to the relevance and the formation of the glycocalyx from vesicles of corneal epithelial cells are discussed, and the interaction of the epithelial cell membranes with the preocular film is emphasized.