PURPOSE:This study evaluated the validity and diagnostic efficacy of a modified Schein dry eye questionnaire and compared it to the Ocular Surface Disease Index (OSDI). METHODS:The original Schein survey was modified to allow numerical scoring on a 0 to 24 scale and evaluated in prospective studies in normal and dry eye subjects. Receiver operating characteristic (ROC) analysis for test efficacy in aqueous deficient dry eye (ADDE) and evaporative dry eye (EDE) related to meibomian gland dysfunction was determined. RESULTS:Dry eye subtype, age and gender were statistically significant in explaining variation in modified Schein scores (n = 377; general linear model; all P values < 0.006) whereas for Ocular Surface Disease Index (OSDI) only age and gender were significant, but not dry eye subtype. The modified Schein ROC curve had an area under the curve (AUC) of 0.693 (95% confidence interval [CI], 0.635-0.753), with cutpoint of 7.5 (sensitivity of 0.75, specificity of 0.55). Similarly, the OSDI had an AUC of 0.685 (95% CI, 0.610-0.760), at a cutpoint of 10.4 (sensitivity of 0.75, specificity of 0.55). Modified Schein and OSDI correlated well (Pearson r = 0.81; P < 0.001). Symptom change for the modified Schein with artificial tear treatment was significant in EDE subjects (Dunnet's tests, P value < 0.001). CONCLUSIONS:The modified Schein questionnaire is rapid to administer and score and compares well with the OSDI for test efficacy. Moreover, it differentiates normals from ADDE and EDE subtypes and is responsive to dry eye treatment. These attributes make the modified Schein survey an attractive dry eye symptom characterization instrument. TRANSLATIONAL RELEVANCE:The modified Schein symptom survey, validated against clinical diagnosis and an existing survey, provides a new, efficacious diagnostic and treatment monitoring instrument in dry eye disease.

Objectives: The aim of this study was to develop and evaluate, using psychometric approaches, a meibomian gland dysfunction (MGD)-specific questionnaire in noncontact lens wearers. Methods: The MGD subjects were recruited and classified as the MGD dry eye subtype based on accepted tests (e.g., Schein symptom survey, tear breakup time, corneal and conjunctival staining, abnormal meibum or meibomian gland atrophy, and a normal Schirmer test). The MGD questionnaire items were drawn from published and anecdotal sources. The preliminary instrument contained 24 items targeting the frequency and intensity of 12 symptoms. Rasch analysis was used for psychometric evaluation of the survey items. Results: Sixty nine MGD subjects completed the survey and clinical testing. Sample severity levels were as follows: none subclinical, 10 minimal, 43 mild, 16 moderate, and none severe. Three iterations of analysis, eliminating INFIT and OUTFIT scores <, and >3.0, and using subject responses reduced the final questionnaire to seven question pairs. Final analysis for the remaining 14 items demonstrated an excellent fit to the Rasch model (e.g., for persons, INFIT MNSQ=0.97; ZSTD=−0.2; OUTFIT MNSQ=0.96; ZSTD=−0.2; item fit statistics were similar). Construct validity also seems good (e.g., correlation to Schein and change with treatment). Conclusions: The MGD-specific instrument is a valid quantitative measure of the symptoms stemming from MGD sufferers. Further research is necessary to determine whether diagnostic efficacy is sufficient to differentiate the MGD dry eye subtype in an independent sample of normals and both major dry eye subtypes exhibiting a broad severity range.

As the number of digital retinal fundus images taken each year grows at an increasing rate, there exists a similarly increasing need for automatic eye disease detection through image-based analysis. A new method has been developed for classifying standard color fundus photographs into both healthy and diseased categories. This classification was based on the calculated network fluid conductance, a function of the geometry and connectivity of the vascular segments. To evaluate the network resistance, the retinal vasculature was first manually separated from the background to ensure an accurate representation of the geometry and connectivity. The arterial and venous networks were then semi-automatically separated into two separate binary images. The connectivity of the arterial network was then determined through a series of morphological image operations. The network comprised of segments of vasculature and points of bifurcation, with each segment having a characteristic geometric and fluid properties. Based on the connectivity and fluid resistance of each vascular segment, an arterial network flow conductance was calculated, which described the ease with which blood can pass through a vascular system. In this work, 27 eyes (13 healthy and 14 diabetic) from patients roughly 65 years in age were evaluated using this methodology. Healthy arterial networks exhibited an average fluid conductance of 419 ± 89 μm3/mPa-s while the average network fluid conductance of the diabetic set was 165 ± 87 μm3/mPa-s (p < 0.001). The results of this new image-based software demonstrated an ability to automatically, quantitatively and efficiently screen diseased eyes from color fundus imagery.

Purpose.: To study melting characteristics and the morphology of human and mouse meibum. Methods.: Hot stage cross-polarized light microscopy (HSPM) and immunohistochemical approaches were used. Results.: Isolated human meibum, and meibum of mice (either isolated or within the meibomian ducts of mice), were found to be in liquid-crystal state at physiological temperatures. Melting of both types of meibum started at approximately 10°C and was completed at approximately 40°C. Melting curves of isolated meibum and meibum inside the meibomian ducts were multiphasic with at least two or three clearly defined phase transition temperatures, typically at approximately 12 ± 2°C (minor transition), 21 ± 3°C, and 32 ± 3°C, regardless the source of meibum. Melting was highly cooperative in nature. Samples of abnormal human meibum collected from dry eye patients with meibomian gland dysfunction often showed an increased presence of nonlipid, nonmelting, nonbirefringent, chloroform-insoluble inclusions of a protein nature. The inclusions were positively stained for cytokeratins. The presence of these inclusions was semiquantitatively characterized using a newly proposed 0 to 4 scale. In the presence of large amounts of these inclusions, melting characteristics of meibum and its structural integrity were altered. Conclusions.: HSPM is an effective tool that is suitable for biophysical and morphological evaluation of meibum. Morphological properties and melting characteristics of human meibum were found to be similar to those of mice. Abnormal meibum of many dry eye patients contained large quantities of nonlipid, protein-like inclusions, which were routinely absent in meibum of normal controls.

Visual acuity, a forced-choice psychophysical measure of visual spatial resolution, is the sine qua non of clinical visual impairment testing in ophthalmology and optometry patients with visual system disorders ranging from refractive error to retinal, optic nerve, or central visual system pathology. Visual acuity measures are standardized against a norm, but it is well known that visual acuity depends on a variety of stimulus parameters, including contrast and exposure duration. This paper asks if it is possible to estimate a single global visual state measure from visual acuity measures as a function of stimulus parameters that can represent the patient's overall visual health state with a single variable. Psychophysical theory (at the sensory level) and psychometric theory (at the decision level) are merged to identify the conditions that must be satisfied to derive a global visual state measure from parameterised visual acuity measures. A global visual state measurement model is developed and tested with forced-choice visual acuity measures from 116 subjects with no visual impairments and 560 subjects with uncorrected refractive error. The results are in agreement with the expectations of the model.

PurposeTo quantify changes in contact lens parameters induced by lens wear and determine whether these changes are associated with contact lens-induced conjunctival staining (CLICS).MethodsIn vitro: Lens diameter, sag, edge shape, base curve of six contact lens brands (balafilcon, comfilcon, etafilcon, lotrafilcon B, omafilcon and senofilcon) measured at 21°C and 35°C (eye temperature). Ex vivo: Diameter of lenses collected from a prospective, randomised, contra-lateral, cross-over clinical trial from 36 subjects wearing all lens types for 1 week daily wear, measured in 35°C PBS after removal. Ocular surface was examined for lens-induced conjunctival staining by masked examiner.ResultsIn vitro: Changes in diameter and base curve outside ISO tolerance were found with etafilcon A and omafilcon A. Ex vivo: Comfilcon A and etafilcon A had greatest shrinkage in diameter (0.18mm) and base curve (0.11mm steeper) with temperature increase from 21°C to 35°C. Senofilcon A, lotrafilcon B and balafilcon A maintained most stable parameters between 21°C and 35°C. Changes in diameter and base curve from lens wear were not correlated with CLICS (p>0.49). Multivariate analysis showed significantly greater levels of lens induced staining were associated with lens modulus (p<0.001) and knife (p<0.001) and chisel (p<0.001) edge shapes.ConclusionsParameter changes induced by lens wear were associated with increasing temperature, but these changes in lens diameter and base curve did not induce CLICS. Modulus and edge shape were associated with increased CLICS. The susceptibility of etafilcon A and omafilcon A lenses to parameter changes might be related to their high water content.

Meibum is the primary component of the tear film lipid layer. Thought to play a role in tear film stabilization, understanding the physical properties of meibum and how they change with disease will be valuable in identifying dry eye treatment targets. Grazing incidence X-ray diffraction and X-ray reflectivity were applied to meibum films at an air-water interface to identify molecular organization. At room temperature, interfacial meibum films formed two coexisting scattering phases with rectangular lattices and next-nearest neighbor tilts, similar to the Ov phase previously identified in fatty acids. The intensity of the diffraction peaks increased with compression, although the lattice spacing and molecular tilt angle remained constant. Reflectivity measurements at surface pressures of 18 mN/m and above revealed multilayers with d-spacings of 50 Å, suggesting that vertical organization rather than lateral was predominantly affected by meibum-film compression.

Reported are adsorption isotherms for guar and hydroxypropyl guar (HPG), with and without the presence of borate ions, onto surfactant free anionic polystyrene latex. Guar and HPG formed adsorbed monolayers on the hydrophobic latex. The presence of borate ions converted the nonionic guar and HPG into an anionic polyelectrolyte. However, there was no measurable influence of bound borate ions on the adsorption of guar or HPG onto anionic, hydrophobic latex. To underscore the unusual behavior of HPG–borate, a sample of HPG was oxidized to introduce carboxyl groups, and the adsorption of the carboxylated HPG onto anionic polystyrene was measured. Unlike HPG–borate, oxidized HPG did not adsorb onto negative polystyrene latex at neutral pH because of electrostatic repulsion. To explain the adsorption of negative HPG–borate onto negative latex, we proposed that as HPG–borate segments approach the latex surface, the negative electrostatic potential near the latex surface induces the detachment of the labile borate groups from HPG.

The influence of hydroxypropyl guar (HPG), with and without boric acid, on dodecyltrimethyl ammonium bromide (DTAB) micellization was characterized by surface tension measurements, isothermal titration calorimetry, and small-angle neutron scattering. Although HPG is a nonionic water-soluble polymer, borate ions form weak bonds with HPG, transforming it into an anionic polyelectrolyte, HPG-borate. Surprisingly, the three independent measurements showed that HPG-borate does not promote DTAB micellization or phase separation normally seen when mixing oppositely charged polyelectrolytes and surfactants. However, the neutron scattering results suggested that HPG-borate binds to and flocculates existing DTAB micelles. The unusual behavior of HPG-borate with DTAB was underscored by showing that carboxymethyl guar (CMG) formed precipitates with DTAB.