Adam Keech

Variability of the analysis of the tear meniscus height by optical coherence tomography.

Purpose. Tear meniscus height (TMH) is an established parameter indicative of tear film volume and has recently been determined using an optical coherence tomographer (OCT). The purpose of this study was to evaluate the inter and intra observer variability in TMH assessment using OCT. Methods. Ten subjects (6 M, 4 F; aged 32.5 ± 6.4 years) had 10 consecutive scans taken of their inferior central tear meniscus (5 scans originating at 90° and 5 origination at 270°) using the OCT2 (Humphrey-Zeiss). Images were analyzed by two observers using custom software on three separate occasions. Following a training session among observers, the images were reevaluated to assess differences in variability. Data were analyzed for differences within and across examiners, for the effect of examiner training and between scan directions. Results. The mean TMH and tear volume collapsed across subjects were between 0.24 and 0.25 mm and 25 to 27 nL/mm, respectively. No difference was noted within observers. An interobserver mean volume difference (p = 0.044) was present but was eliminated post training (p = 0.167). Variability was less with scans originating at 90°. Conclusions. The values of the TMH and tear volume are similar to those reported in the literature. Due to the interobserver differences observed, a training session between examiners may prove to be valuable, especially in a large or multicenter study.

Impact of Time Between Collection and Collection Method on Human Tear Fluid Osmolarity

Abstract Aim: To generate data on the variability of tear osmolarity in a control (normal, non-dry eye) and symptomatic dry eye population (Ocular Surface Disease Index: OSDI ≥20). A secondary outcome is the determination of the effect that tear collection technique has on the osmolarity of the sample. Materials and methods: This was a two-phase study that recruited 20 subjects (n = 10 normal, n = 10 dry eye) to evaluate the influence of time between measurements (Phase I) and 30 subjects (n = 15 normal, n = 15 dry eye) to evaluate the influence of collection technique (Phase II). As part of Phase I, serial tear osmolarity measurements were performed on each eye; four separated by 15 min followed by four separated by 1 min, at each of three visits. Phase II compared the consecutive measurement of four in vivo tear samples to four in vitro measurements on tears collected and dispensed from a glass capillary tube. Results: During Phase I, the dry eye group had a significantly higher maximum osmolarity (334.2 ± 25.6 mOsm/L) compared to the normal group (304.0 ± 8.4 mOsm/L, p = 0.002). No significant differences were observed whether collections were performed at 15 or 1 min intervals. During Phase II, the in vivo osmolarity was equivalent to in vitro measurements from glass capillary tube samples for both the dry eye group (323.0 ± 16.7 mOsm/L versus 317.7 ± 24.8, p = 0.496), and for the normal subjects (301.2 ± 7.2 mOsm/L versus 301.9 ± 16.0 mOsm/L, p = 0.884). Conclusion: Symptomatic dry eye subjects exhibited a significantly higher tear osmolarity and variation over time than observed in normal subjects, reflecting the inherent tear film instability of dry eye disease. There was no change in the distribution of tear osmolarity measurements whether tears were collected in rapid succession or given time to equilibrate, and collection method had no impact on tear osmolarity.

Conformational and Quantitative Characterization of Lysozyme Extracted from Galyfilcon and Senofilcon Silicone Hydrogel Contact Lenses

Purpose: To compare two solvents for retrieval of lysozyme deposited on a silicone hydrogel (SH) contact lens material galyfilcon A (GA; Acuvue Advance). Methods: Two buffers used were 50:50 acetonitrile/0.02% trifluoroacetic acid (buffer 1) and 50:50 acetonitrile/50 mM NaOH (buffer 2). Results: Extraction efficiency from GA lenses was 74% (buffer 1) and 83% (buffer 2). Buffer 2 decreased lysozyme activity > buffer 1. Ex vivo GA lenses showed total protein deposition of 2–16 μ g/lens with total lysozyme deposition of 0.3–3.9 μg/lens. Conclusions: We have developed a low acid strength extraction buffer that can be used to efficiently extract active lysozyme protein from novel siloxane-based contact lens materials.

Tear Meniscus Height Determination Using the OCT2 and the RTVue-100

Purpose. To compare anterior segment spectral-domain optical coherence tomography (SOCT) tear meniscus height (TMH) measures with those from the more commonly used time-domain OCT (TOCT). Methods. The right eye of 50 healthy subjects had images of their TMH captured with TOCT (OCT2) and SOCT (RTVue-100). Data were acquired using two different anterior segment lenses, the cornea/anterior module-short (CAM-S) and long (CAM-L), on the SOCT. Images were then analyzed for differences in their derived TMH. Results. The average TMH for TOCT was 0.280 ± 0.139 mm, whereas the mean TMH measured using the SOCT was 0.354 ± 0.163 mm and 0.345 ± 0.167 mm for the CAM-S and CAM-L, respectively. There was a significant difference (p < 0.001) when comparing TOCT with either of the SOCT lenses. There was no statistically significant difference between the CAM-L and CAM-S (p = 1.0). Bland-Altman analysis showed poor agreement between TOCT and SOCT (95% limits of agreement −0.138 to + 0.285 mm for the CAM-S and −0.185 to +0.315 mm for the CAM-L). Conclusions. The RTVue-100 produces TMH measurements that are significantly higher than OCT2 in a normal patient population. However, the RTVue-100 showed a number of other advantages over the OCT2 in the measurement and analysis of images. Future work needs to determine the causative factors behind the observed differences.

Repeatability of pachymetry and thinnest point localization using a fourier-domain optical coherence tomographer.

Purpose. To evaluate the repeatability of pachymetry measures at six distinct locations using a Fourier-domain optical coherence tomographer. The location of the thinnest point was also described using vector analysis, and repeatability of the localization of the thinnest point was calculated. Methods. The right eye of 25 healthy subjects had 3 images of their right cornea captured using the pachymetry protocol and anterior segment lens of a commercially available Fourier-domain optical coherence tomographer (RTVue-100, Optovue, Fremont, CA). The first two images were used to quantify repeatability in the central (2 mm) and paracentral (2–5 mm) cornea. Cartesian coordinates representing the location of the thinnest point were used to determine the mean location in relation to the central cornea. Results. Mean central thickness was 536.8 ± 31.1 &mgr;m, and the mean minimum thickness was 526.4 ± 33.1 &mgr;m. The thickest paracentral zone was the superior cornea and the thinnest was the temporal cornea. Intraclass correlation values ranged between 0.969 and 0.996, and the mean coefficient of repeatability was 1.74% across all locations evaluated. The thinnest point was located in the inferior temporal region in 80% of eyes and was an average distance of 1.01 mm from the corneal apex, subtending an angle of 26.7° from the horizontal. Conclusions. The RTVue-100 provides a highly repeatable measure of corneal thickness at various locations. The instrument is capable of describing and consistently duplicating the location of the thinnest point of the cornea; however, further comparative work with other clinical imaging modalities is required.

Subjective and objective variation of the tear film pre- and post-sleep.

Purpose. To date, few studies have correlated the overnight effects of the preocular tear film (POTF) with subjective symptoms. This study investigates the POTF volume and stability, bulbar hyperemia (BH), tear ferning (TF) and the participants subjective symptoms, pre- and post-sleep. Methods. Thirty subjects were recruited, consisting of two evenly distributed groups who were symptomatic of dry eye (DE) and those that were asymptomatic dry eye, determined using the McMonnies questionnaire. Subjects were evaluated at 10 p.m. (baseline), on waking at 7 a.m., and then hourly until 10 a.m. At each visit, tear meniscus height (TMH), various subjective factors, BH and POTF stability by non-invasive break-up time (NIBUT) were assessed. Tear collection was performed at 10 p.m, 7 and 10 a.m. for TF analysis. Results. With the exception of burning, all other symptoms (comfort, dryness, clarity of vision, and grittiness) revealed an overnight change (p < 0.05) within each group, but not between the two groups (p > 0.05). Both the tear meniscus height and BH were elevated upon waking and differed significantly between test times for each group (p < 0.05), but not between groups (p > 0.05). NIBUT was lower for the DE group (p < 0.001). The non-dry eye (NDE) group did not significantly alter over time (p > 0.05), but the DE group did (p = 0.004), with a longer NIBUT in the morning. TF demonstrated a degraded pattern upon waking for both groups (p < 0.05). Most of the changes returned to baseline within an hour after waking. Conclusions. The properties of the POTF undergo a change during extended periods of eye closure and the human POTF is different upon waking to that present immediately before sleep. Most of the parameters determined rapidly revert to baseline levels once the POTF is allowed to refresh.

Tear osmolarity changes after use of hydroxypropyl-guar-based lubricating eye drops

Purpose To evaluate tear osmolarity after using a hydroxypropyl-guar (HP-guar)-based lubricating eye drop four times daily (QID) for 3 weeks. Methods Thirty-one participants with dry eye disease (Ocular Surface Disease Index [OSDI] score ≥20 and tear osmolarity ≥300 mOsm/L in at least one eye) were enrolled in this prospective, dispensing, non-randomized study involving a baseline visit and 3-week follow-up. Tear osmolarity, non-invasive tear break up time (NITBUT), conjunctival hyperemia, corneal and conjunctival staining were determined at baseline. Participants were instructed to instill one drop of a HP-guar-based drop QID in each eye for 3 weeks. At the follow-up visit, the symptoms and ocular surface parameters were reassessed. At this visit, one HP-guar drop was instilled into each eye and osmolarity was measured after 15 minutes, to examine short-term changes in osmolarity. Results Twenty-eight participants completed the study (5M, 23F; median age 54 yrs, range 25–83 yrs). At baseline, mean OSDI score was 44.9±15.2 and mean osmolarities were 314.63±11.9/306.6±10.1 mOsm/L (worst eye [WE]/better eye [BE]). After 3 weeks, mean osmolarity reduced to 307.7±15.7/303.9±11.3 mOsm/L (WE/BE; p<0.05 and p=0.228, respectively) and mean OSDI scores reduced to 28.3±17.0 (p<0.01). A significant reduction in osmolarity was observed 15 minutes after instilling the lubricating drop (p<0.05 WE, p=0.09 BE). Significant improvements in central corneal staining (p<0.05 OU) and NITBUT (p<0.05 WE only) were observed. Reductions in conjunctival staining and hyperemia were observed, but were not significant (p>0.05). Conclusions A significant reduction in tear osmolarity and improvements in dry eye symptoms, corneal staining, and NITBUT were observed after 3 weeks of QID use of a HP-guar-based lubricant drop. A decrease in osmolarity was also demonstrated 15 minutes after drop instillation.

Self versus examiner administration of the Ocular Surface Disease Index(

Purpose To compare the difference in Ocular Surface Disease Index© (OSDI) scores when participants were given the OSDI to complete on their own (self-guided, SG), versus under the guidance of the examiner (examiner-guided, EG). Methods 100 participants enrolled in this prospective two-visit study (fifty under-45 years old, 38F/12M; and fifty 45 years-and-older, 42F/8M). Participants who scored ≥1 on the Subjective Evaluation of Symptoms of Dryness (SESoD) were included in this study. Participants completed the OSDI SG during the first visit. Participants returned the next day and repeated the OSDI, but with EG (with standardized instructions). Participants were under deception and believed that they were comparing the OSDI to the SESoD. Results The mean OSDI score of the SG and EG administration was 32.0 ± 17.3 and 33.8 ± 19.6 respectively (p > 0.05) with 95% limits of agreement between −20.6 and +24.2. The correlation between SG and EG administration was Spearmans r = 0.81, p < 0.01. The mean difference between SG and EG was not significant (p > 0.05) for both the under-45 group, and 45-and-older group. The 95% limits of agreement for the under-45 group were smaller than the 45-and-older group (under-45: [−15.5, +13.1,], 45-and-older: [−23.3, +32.2]). A significant difference was found between 8 of the 12 questions items (all p ≤ 0.01). However, the mean difference for each was <0.6 and was not considered to be clinically significant. Conclusion There was no clinically significant difference in OSDI score between SG and EG administration, however having instructions provided with EG administration affected variability of scores in the older group more than the younger group.