Andrew Loc Nguyen

Precorneal residence time of artificial tears measured in dry eye subjects.

Purpose. The purpose of this investigation was to measure the precorneal residence time of saline and five marketed artificial tears in dry eye subjects using fluorometry. Methods. FITC-dextran, 70 kDa molecular weight, was admixed under sterile conditions (0.1% wt/vol) into buffered saline and the marketed artificial tear formulations of varying viscosity. Precorneal residence time (RT) was measured directly in 16 mild to moderate dry eye subjects, classified by sub-type, in a six-way cross-over, masked and randomized study. FITC-dextran tracer decay with a scanning fluorometer was used to estimate the gross RT (i.e., the time in minutes for the signal to return to baseline). Results. All subjects were classified as having non-inflammatory meibomian gland dysfunction except one, who had a mixture of aqueous deficiency and meibomian gland dysfunction. In two separate determinations, the saline RTs were 19.1 ± 7.4 and 17.6 ± 8.2 min. The RTs for the formulations varied to some degree by viscosity, with two higher viscosity formulations demonstrating the longest RTs of 36 to 41 min, approximately twice that of saline (p < 0.001 for both 0.4% polyethylene glycol/0.3% propylene glycol, and 1.0% carboxymethylcellulose). An oil emulsion, low viscosity carboxymethylcellulose and moderate viscosity hydroxypropylmethylcellulose-containing formulation were not statistically different from saline (RTs of 18, 22 and 24 min, p values = 0.983, 0.818 and 0.099, respectively). Conclusions. More than two-fold RT differences were found for the higher viscosity, more muco-adhesive formulations compared to saline. However, other formulations provided RTs close to saline, suggesting that RT is influenced by factors other than simple viscosity. Future studies should examine the interplay of spreading characteristics, pseudoplasticity and muco-adhesion relative to RT to determine the individual and cumulative effects on formulation retention.

Contrast Sensitivity and Tear Layer Aberrometry in Dry Eye Patients

Purpose. Dry eye disease is a common condition that affects millions of people world wide. The common findings of dry eye disease are blurred vision and tear film instability. The purpose of this study was to determine if long-term use of artificial tears altered visual disturbances and tear film instability of dry eye patients. Methods. Contrast sensitivity and optical aberrations were measured in 22 dry eye and 10 normal patients before and after daily use of artificial tears. The contrast sensitivity and optical aberrations were measured in response to the administration of a single drop of artificial tear placed in the eye. Results. The short-term effect (i.e., a few minutes) of a single drop of artificial tear placed in the eye was a decrease in contrast sensitivity and an increase in optical aberrations. Long-term daily use of the artificial tears (i.e., up to 2 weeks) resulted in less of a short-term effect in dry eye patients. No long-term effect was observed for normal subjects. Both contrast sensitivity loss and optical aberrations decreased by 35% per week of artificial tear use for the dry eye patients suggesting that the changes in contrast sensitivity were the result of optical aberrations. Conclusions. The results suggest that the changes in contrast sensitivity with artificial tear administration were the result of optical aberrations. It appears that long-term use of artificial tears may normalize the tear layer of dry eye disease patients.

Retention and retention of effect of topical formulations in dry eye subjects.

Purpose. It was the purpose of this investigation to examine both retention time (RT) and retention of effect of two ophthalmic formulations in the same dry eye subjects. Methods. This was a randomized, subject-masked cross-over study. Dry eye subjects, characterized by sub-type, were recruited. For direct RT measurement, fluorescein isothiocyanate (FITC)-dextran, 70 kDa molecular weight, was admixed at 0.1% wt/vol concentration into buffered saline (active control) and a viscous marketed artificial tear formulations (test formulation). RT in minutes was estimated directly as the return to baseline intrinsic fluorescence with an objective scanning fluorometer. Retention of effect was measured with a xeroscope as non-invasive breakup time (NIBUT) and by use of a numerical rating scale for comfort. Results. Eleven subjects, with most being classified as having non-inflammatory meibomian gland dysfunction, completed the study. The RTs averaged 17.7 (±10.0) and 26.8 (±16.5) minutes for the saline and test formulations, respectively. The averages for NIBUT were 8.73 (±6.1) and 19.5 (±4.9) minutes, for saline and the test formulations, respectively. Return to baseline for the numerical rating scale comfort averages were 9.91 (±4.1) and 20.21 (±6.4) minutes for the saline and test formulations, respectively. When residence time was subtracted from the retention of effect measures, no statistical significance was found for the polymeric solution (vs. comfort, p = 0.153; vs. NIBUT, p = 0.109). However, statistical differences were found for direct retention compared against comfort (p = 0.01) and NIBUT (p = 0.004) for buffered saline. Conclusions. It seems that these two retention of effect measures are much shorter than RT measured directly. Future work should aim to confirm these findings in additional dry eye sub-types and in those with more severe disease manifestations.

Determinants and standardization of mesopic visual acuity.

Purpose It is well established that visual acuity (VA) decreases with luminance but the specific factors that are responsible remain unclear. The purpose of this study was to quantify the contributions of accommodative error, pupil size, and higher-order aberrations to the decrease in VA when transitioning from photopic to mesopic light levels. Additionally, repeatability of VA at photopic and mesopic levels was measured to derive a luminance recommendation for mesopic VA testing, which can provide the standardization needed for future translational clinical studies and the widespread adoption of mesopic VA testing. Methods Monocular VAs were assessed at one photopic and three mesopic light levels: 94, 3, 0.75, and 0.38 cd/m2, with an E-ETDRS testing system in 43 normal subjects. Accommodative error, pupil size, and higher-order aberrations were obtained. Twenty subjects were retested at another visit to assess VA repeatability. Results The mean (±SD) logMAR (logarithm of the minimum angle of resolution) VA was −0.08 (±0.06) at 94 cd/m2, 0.05 (±0.07) at 3 cd/m2, 0.16 (±0.06) at 0.75 cd/m2, and 0.27 (±0.09) at 0.38 cd/m2. Light level and accommodative error were significantly associated with VA, and light level explained 75% of the variance. The mean differences in VAs between two visits were not significantly different from zero (p > 0.05). The coefficients of repeatability for 94, 3, 0.75, and 0.38 cd/m2 were 0.08, 0.11, 0.14, and 0.14 logMAR, respectively. Conclusions Light level, among all other factors studied, contributes the most to the reduction in VA tested under mesopic conditions. Testing mesopic VA at 0.75 cd/m2, or about 2.0 log units less than photopic testing, provides a significant and repeatable decrease in VA similar to standardized low-contrast VA testing, and therefore this level is recommended.

Evaluation of the Waggoner Computerized Color Vision Test

Purpose Clinical color vision evaluation has been based primarily on the same set of tests for the past several decades. Recently, computer-based color vision tests have been devised, and these have several advantages but are still not widely used. In this study, we evaluated the Waggoner Computerized Color Vision Test (CCVT), which was developed for widespread use with common computer systems. Methods A sample of subjects with (n = 59) and without (n = 361) color vision deficiency (CVD) were tested on the CCVT, the anomaloscope, the Richmond HRR (Hardy-Rand-Rittler) (4th edition), and the Ishihara test. The CCVT was administered in two ways: (1) on a computer monitor using its default settings and (2) on one standardized to a correlated color temperature (CCT) of 6500 K. Twenty-four subjects with CVD performed the CCVT both ways. Sensitivity, specificity, and correct classification rates were determined. Results The screening performance of the CCVT was good (95% sensitivity, 100% specificity). The CCVT classified subjects as deutan or protan in agreement with anomaloscopy 89% of the time. It generally classified subjects as having a more severe defect compared with other tests. Results from 18 of the 24 subjects with CVD tested under both default and calibrated CCT conditions were the same, whereas the results from 6 subjects had better agreement with other test results when the CCT was set. Conclusions The Waggoner CCVT is an adequate color vision screening test with several advantages and appears to provide a fairly accurate diagnosis of deficiency type. Used in conjunction with other color vision tests, it may be a useful addition to a color vision test battery.

Characterization of expressed human meibum using hyperspectral stimulated Raman scattering microscopy

PURPOSEnThis study examined whether hyperspectral stimulated Raman scattering (hsSRS) microscopy can detect differences in meibum lipid to protein composition of normal and evaporative dry eye subjects with meibomian gland dysfunction.nnnMETHODSnSubjects were evaluated for tear breakup time (TBUT), staining, meibum expression and gland dropout. Expressed meibum was analyzed using SRS vibrational signatures in the CH stretching region (2800-3050u202fcm-1). Vertex component analysis and K-means clustering were used to group the spectral signatures into four fractions containing high lipid (G1) to high protein (G4).nnnRESULTSnThirty-three subjects could be statistically analyzed using pooled meibum (13 with stable tear films (TBUTsu202f>u202f10u202fs) and 20 with unstable tear films (TBUTsu202f≤u202f10u202fs). Significant differences in meibum from subjects with unstable vs. stable TBUTs were found for the G1 fraction (medians 0.164 and 0.020, respectively; pu202f=u202f0.012) and the G2 fraction (medians 0.244 and 0.272, respectively; pu202f=u202f0.045). No differences were observed for the G3 and G4 fractions. Single orifice samples were not significantly different vs. pooled samples from the fellow eye, and eyelid sector samples (nasal, central and temporal) G2:G3 fractional components were not significantly different (pu202f=u202f0.449). Spearman analysis suggested a significant inverse correlation between G1 fraction and TBUT (Ru202f=u202f-0.351; pu202f=u202f0.045).nnnCONCLUSIONSnhsSRS microscopy allows compositional analysis of expressed meibum from humans which correlated to changes in TBUT. These findings support the hypothesis that hsSRS may be useful in classifying meibum quality and evaluating the effects of therapy.

Development of a Meibomian Gland Dysfunction-specific Symptom Questionnaire.

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.