Evaluation and differential diagnosis of keratoconjunctivitis sicca.

Patients with S ogren's syndrome (SS) have a high incidence of immune mediated ocular inflammation, making them more susceptible to infectious agents. However, the more common manifestation seen in patients with SS is immune mediated noninfectious inflammation of the lacrimal glands and ocular surface, resulting in decreased tear production and inflammatory changes on the ocular surface known as SS associated keratoconjunctivitis sicca (SS-KCS). Two categories of SS-KCS are recognized: aqueous deficient dry eye (decreased tear production by lacrimal glands) and evaporative dry eye (increased evaporative loss of tears from the ocular surface). There are a variety of tests for the differential diagnosis of SS-KCS, including the Schirmer test, with or without anesthetic; vital dye staining of the ocular surface for surface abnormalities; tear osmolarity; and lid margins evaluation. Current treatment of KCS involves artificial tears and punctal occlusion. New and emerging treatment options using androgens to suppress glandular inflammation and muscarinic M3 agonists, i.e., cevimeline and pilocarpine, show promise as treatment options for SS-KCS.

The 1998 Castroviejo Lecture. New strategies in the treatment of dry-eye states.

PURPOSE: To review developments in dry-eye research leading to new therapeutic possibilities and to suggest a prioritizing schema. METHODS: New development in our understanding of the pathogenesis, diagnoses, and treatment of dry-eye states have been reviewed along with the possible impact on new therapeutic approaches. RESULTS: A variety of approaches to the pathogenesis and degrees of dry-eye states have emerged, giving rise to significant new approaches to the treatment of these disorders. CONCLUSION: There are now new treatment possibilities. Ranking their development based on their fundamental reversal of disease mechanisms seems a reasonable approach with early therapeutic pay-off.

Omafilcon A (Proclear) soft contact lenses in a dry eye population.

PURPOSE: We conducted a 3-month, randomized, comparative cross-over study to evaluate the clinical performance of lenses manufactured from omafilcon A on subjects with signs and symptoms of dry eye. The subjects' own daily wear soft lenses were used as controls. METHODS: Seventy-six subjects with objective evidence of dry eye, as defined in the NEI/Industry Workshop Report 1995, were fit with either the omafilcon A lenses (Proclear) or new control lenses. Subjects wore the lenses for 6 weeks and then crossed over to bilateral wear of the other lenses for an additional 6 weeks. During each part of the study, we examined subjects at 1 week, 1 month, and 6 weeks. Signs and symptoms of dry eye were evaluated, and on-eye dehydration of the lens was assessed. RESULTS: When the subjects were wearing the omafilcon A lenses, there was a statistically significant improvement in a number of subjective parameters including comfort, dryness, frequency of eye irritation, and frequency of burning. We found significantly less on-eye dehydration of the lens and fluorescein corneal staining with the omafilcon A lenses. CONCLUSIONS: This study indicated that the daily wear of omafilcon A lenses provided better comfort, fewer symptoms, less on-eye dehydration, and less fluorescein corneal staining than other soft daily wear contact lenses in subjects with mild to moderate dry eye.

Sensitivity and specificity of a screening questionnaire for dry eye.

We developed a Dry Eye Screening Questionnaire for the Dry Eye Epidemiology Projects (DEEP), a proposed large epidemiologic study. All persons who screen positive and a small sample of those who screen negative are to be invited for a diagnostic examination. Containing 19 questions, of which only 14 were used in the analysis, the questionnaire takes only a few minutes to administer on the telephone. To construct a discriminator function and thus a ROC curve, we used stepwise multiple regression on screening responses from a clinic series of 77 cases and 79 controls. Stepwise regression may incorporate into the predictor equation variables whose relation to the predicted is only accidental. Further, misclassification rates are underestimated by the resubstitution method, in which the proportion misclassified is obtained from the same dataset in which the discriminator function was fitted. To counter these problems, we randomly divided the data in half. We chose as predictors only those variables (Dry and Irritated) selected by stepwise regression in both data halves. We estimated unbiased misclassification rates using the unbiased test set method, in which the discriminator is fitted in one data half, and misclassification rates are calculated in the other half. Comparison of ROC curves arising from resubstitution and test set estimates indicates that resubstitution bias in misclassification rate estimation is negligible in our data. A resubstitution estimate made on the entire data is thus preferred. The resulting sensitivity/specificity values are reasonably high (e.g., 60%/94%), suggesting that the questionnaire will be a useful screening tool in the DEEP study. A second discriminator using the sum of all 14 responses is similar in its misclassification characteristics to the first discriminator. A second potentially significant error, arising from applying results from a clinical series to a general population, will be investigated as survey results in DEEP become available.

Meibomian gland dysfunction.

Blepharitis is probably the most common disease entity seen in the general ophthalmologist's office. A significant proportion of these cases are secondary to meibomian gland disease. This review outlines our knowledge of the histopathology, lipid abnormalities and role of microorganisms in meibomian gland dysfunction. We will also review the physiology of meibomian gland secretion and present models of meibomian gland dysfunction which have enhanced our knowledge of this condition. The importance of diagnosing associated conditions such as aqueous tear deficiency, contact lens intolerance, rosacea, and seborrheic dermatitis is emphasized. Although this condition causes significant morbidity in the population, there are effective treatments available and these will be discussed.

Morphology and movement of corneal surface cells in humans.

We examined the morphology of the corneal surface epithelial cells in 13 eyes of 13 subjects using specular microscopy. We determined cell area, perimeter, and shape comparing the central cornea with the inferior and superior periphery. We found surface epithelial cells are significantly smaller in the central cornea. The cells measured 560 +/- 93 square microns in the central cornea, 850 +/- 135 square microns in the superior cornea and 777 +/- 176 square microns in the inferior cornea (p less than .005). Newly emerged surface cells are smaller and are thought to enlarge with time. We postulate that lid shearing forces are greater in the central cornea and contribute to epithelial cell exfoliation. We further postulate that preferential shearing of central corneal surface cells is an important factor driving the centripetal movement of corneal epithelial cells.

Morphologic effects of contact lens wear on the corneal surface.

We used specular microscopy of the corneal epithelium to examine 29 eyes of 29 patients each wearing one of five different types of contact lenses. We compared these with 24 eyes of 24 age-matched control patients. We found patients with aphakic extended wear soft contact lenses had significantly larger cells (818 +/- 186 microns2) than all other groups; and they were significantly larger than their age-matched control group (573 +/- 174 microns2) (P less than .002). The epithelial cells of extended wear soft contact lens patients (609 +/- 97 microns2) and daily wear rigid gas permeable contact lens patients (613 +/- 103 microns2) were larger than their control group of normal young patients (513 +/- 53 microns2). The cells of daily wear soft contact lens patients (484 +/- 111 microns2) and hard contact lens patients (517 +/- 46 microns2), however, were not different from controls. This study demonstrates a statistically significant shift in mean cell area of corneal epithelial cells in patients wearing some types of contact lenses.

Comparison of in vivo and ex vivo cellular structure in rabbit eyes detected by tandem scanning microscopy.

Using the tandem scanning microscope, in vivo confocal microscopic images of living eyes were compared to images obtained from ex vivo, freshly enucleated or fixed tissue in the rabbit. In the normal cornea, microscopic details of the superficial epithelium, basal lamina, stromal fibrocyte nuclei, nerves and endothelial cell borders were easily discernible. Removal of the eye from the intact animal resulted in loss of detail with distortion of the normal structural interrelationships within the corneal stroma whilst enhancing details of the corneal epithelium. Formalin fixation further enhanced details of the basal and suprabasal corneal epithelial cell nuclei and the stromal fibrocyte cell borders whilst inducing prominent brightly reflecting folds in the thickened stroma with concomitant enhancement of the edge contrast of the collagen lamellae. These changes appeared to be related, in part, to hydration of the cornea and artefactual pooling of water between structures that may enhance reflectivity by increasing the difference between the refractive index of the cellular and extracellular elements. We conclude that microscopic examination of ex vivo preparations of corneal tissue, although providing increased resolution similar to conventional light microscopic techniques, significantly altered the normal structural relationships and could lead to erroneous measurements of the physiological properties of the tissue as compared to in vivo microscopy of undisturbed, intact tissue.

Digital image acquisition in in vivo confocal microscopy.

A flexible system for the real-time acquisition of in vivo images has been developed. Images are generated using a tandem scanning confocal microscope interfaced to a low-light-level camera. The video signal from the camera is digitized and stored using a Gould image processing system with a real-time digital disk (RTDD). The RTDD can store up to 3200 512 x 512 pixel images at video rates (30 images s-1). Images can be input directly from the camera during the study, or off-line from a Super VHS video recorder. Once a segment of experimental interest is digitized onto the RTDD, the user can interactively step through the images, average stable sequences, and identify candidates for further processing and analysis. Examples of how this system can be used to study the physiology of various organ systems in vivo are presented.

Corneal steepening with final suture removal after penetrating keratoplasty.

We reviewed 53 patients after they underwent penetrating keratoplasty, comparing the change in average corneal curvature before and after final suture removal 15-18 months postsurgery. In 29 eyes with keratoconus, there was a significant increase in average curvature of 3.48 diopters +/- 3.76 (p less than 0.0005). In 24 eyes with other diagnoses, there was also a significant increase in the average curvature of 3.26 diopters +/- 3.98, (p less than 0.0005). The difference between these groups was not significant. The amount of steepening correlated negatively (-.6494) with the average corneal curvature before suture removal (p less than 0.005). We found no change in the average astigmatism after suture removal; however, large changes in astigmatism occurred unpredictably with some patients. This study shows that corneal curvature after penetrating keratoplasty steepens after suture removal, particularly in flat corneas, and astigmatism may shift unpredictably.

In vivo, real-time confocal imaging.

We have adapted a tandem scanning confocal microscope for real-time, non-invasive imaging of cells under in vivo conditions. This form of in vivo confocal imaging relies on the optical sectioning abilities of the confocal microscope to obtain en face, sequential, reflected light images of cells at various depths, up to 1 mm, within opaque organs in living animals. Of major consideration in the design of an in vivo confocal microscope is maximizing the real-time detection of signals reflected from low contrast structures which can be affected by the microscope design, objective, and image detector systems. Using an in vivo confocal microscope design with a 20 x BioOptics surface contact objective we have obtained live cellular images from selected tissues including cornea, kidney, liver, adrenal, thyroid, epididymis, and muscle and connective tissue of rabbits and rats. Images were captured, digitized, and processed using a DAGE Mti low light level SIT camera coupled to a Gould IP9527 image processor. In vivo images were also compared with conventional bright field light and scanning electron microscopic images of "dead," fixed tissues. Overall, in vivo confocal imaging can provide remarkable detail of living cells comparable to that of conventional microscopic images of "dead," fixed, and stained tissue. A more unique feature of in vivo confocal imaging is the ability to study cellular structure and function sequentially over time in the same organ or tissue and represents a fundamentally new paradigm in microscopy. With continued refinements in the microscope, objective and detection system designs and their consequent improvements in lateral and axial resolution, in vivo confocal microscopy will enable us as observers to see what no one has been able to see before.

Tight lens syndrome associated with a 24-hour disposable collagen lens: a case report.

Tight lens syndrome occurred 8 hours after a 24-hour Bio-Cor bandage collagen lens (Bausch & Lomb, Inc.) was placed on the eye of a 19 year old female patient with a history of Stevens-Johnson syndrome and recurrent corneal abrasions. Because collagen bandage contact lenses share some physical and fitting properties with hydrophilic lenses, they should be used with caution in patients at high risk for a tight lens.