Ranjini Kottaiyan

Noninvasive, objective, multimodal tear dynamics evaluation of 5 over-the-counter tear drops in a randomized controlled trial.

Purpose: To assess the ability of a noninvasive, objective, multimodal system to compare the efficacy and optical quality of 4 different groups of 5 over-the-counter tear drops. Methods: Wavefront sensing and optical coherence tomography (OCT) were used to objectively assess visual quality and tear volume, respectively, after the over-the-counter tear drops [2 polyethylene glycol (PEG)-400, 1 carboxymethyl cellulose (CMC), 1 polyvinyl alcohol/PEG-400 (PVA), and 1 glycerine/polysorbate-80] were administered to 23 patients with aqueous-deficient dry eye in a randomized, controlled, double-masked trial. Measurements at each of the 5 visits were taken from both eyes at baseline and 5, 20, and 40 minutes after drop instillation. Results: At 5 minutes after drop instillation, the 2 PEG drops showed significant worsening of visual quality (−128.87%, P = 0.001) compared with CMC, PVA, and glycerine drops. Tear volume was elevated significantly with PEG and CMC drops at 5 minutes (+33.2%, P = 0.002; +29.9%, P < 0.001) compared with the other groups. Subjects with a Schirmer score of less than 5 mm at 5 minutes showed improvement in visual quality with PEG drops, whereas those with a fluorescein staining score of 1 to 2 showed improvement with both PEG and CMC drops. A trend toward decreasing visual quality with increasing tear meniscus was noted. Conclusions: Noninvasive multimodal imaging has the potential to evaluate tear dynamics and the efficacy of artificial tears objectively. Certain artificial tear components and the temporary increase in tear volume after instillation of artificial tears may contribute to transient reduction of visual quality.

Integrated Multimodal Metrology for Objective and Noninvasive Tear Evaluation

The clinical tests used to assess tear film and diagnose dry eye are invasive and produce results that are different from natural tear characteristics. There is a need to objectively and noninvasively assess tear parameters under controlled environmental circumstances to refine dry eye diagnosis and therapy. We have developed multimodal tear imaging systems integrated in a chamber in which individual environmental factors can be precisely varied to investigate their impacts on tear parameters. With the custom-built high-resolution wavefront sensor combined with placido disc, it is possible to objectively detect two-dimensional tear breakups in real time and evaluate its impact on visual quality. Micrometer ultra-high resolution optical coherence tomography (OCT) enables us to quantify thickness and volume of the tear over the cornea and tear menisci. The ocular surface imaging ellipsometer uses polarized illumination from which both the lipid refractive index and thickness can be measured at a very high resolution. Using an enhanced thermal camera, we measure the ocular surface temperature noninvasively, which makes it possible to study spatial and temporal changes in tear evaporation. The multimodal deployment of these four components in the controlled chamber will assist in better differentiating the various clinical dry eye entities and will lead to the development of specific dry eye treatments.

Epithelium and Bowman's layer thickness and light scatter in keratoconic cornea evaluated using ultrahigh resolution optical coherence tomography.

Abstract. A custom-developed ultrahigh resolution optical coherence tomography with an axial resolution of 1.1 μm in corneal tissue was used to characterize thickness and light scatter of the epithelium and Bowman’s layer in keratoconic (KC) cornea noninvasively. A 4-mm wide vertical corneal section around the apex in nine KC and eight normal eyes was imaged in vivo. The epithelium and Bowman’s layer were visualized and their thickness profiles were quantified. Scatter was quantified based on the sensitivity normalized mean signal intensity distribution. Average mean thickness of the epithelium and Bowman’s layer in KC eyes was significantly smaller (p<0.05) than the normal eyes. The epithelium thickness variation across a central 3-mm cornea was significantly larger in KC eyes than in normal eyes. The scatter in KC eyes was significantly increased only for Bowman’s layer. The changes observed in this study could improve our understanding of the underlying disease mechanism of KC and can provide new indications for early disease diagnosis.

Effect of Airflow Exposure on the Tear Meniscus

Purpose. To compare the effect of airflow exposure on the tear meniscus and blink frequency in normal and evaporative dry eye subjects. Methods. In 9 normal subjects and 9 short tear breakup time (SBUT) dry eye subjects, lower tear meniscus height (TMH) and area (TMA) and blink frequency were measured with anterior segment optical coherence tomography (OCT) before and after 5 minutes of airflow exposure (1.5 ± 0.5 m/s). Results. In SBUT dry eyes, both TMH and TMA decreased significantly (P = 0.027, P = 0.027) with a significant increase of blink frequency after airflow exposure, while significant increase in TMA was found in normal eyes. Conclusion. Measurement of the tear meniscus with anterior segment OCT seems to be useful as a noninvasive and objective method for evaluating the effect of airflow on tear film.

Temperatures of the Ocular Surface, Lid, and Periorbital Regions of Sjögren's, Evaporative, and Aqueous-Deficient Dry Eyes Relative to Normals

PURPOSE To compare the temperatures of the ocular surface, eyelid, and periorbital skin in normal eyes with Sjögrens syndrome (SS) eyes, evaporative dry eyes (EDE), and aqueous deficient dry eyes (ADDE). METHODS 10 eyes were analyzed in each age-matched group (normal, SS, EDE, and ADDE). A noninvasive infrared thermal camera captured two-dimensional images in three regions of interest (ROI) in each of three areas: the ocular surface, the upper eyelid, and the periorbital skin within a controlled environmental chamber. Mean temperatures in each ROI were calculated from the videos. Ocular surface time-segmented cooling rates were calculated over a 5-s blink interval. RESULTS Relative to normal eyes, dry eyes had lower initial central OSTs (SS -0.71°C, EDE -0.55°C, ADDE -0.95°C, KW P<.0001) and lower central upper lid temperatures (SS -0.24°C, ADDE -0.51°C, and EDE -0.54°C, KW P<.0001). ADDE eyes had the lowest initial central OST (P<.0001), while EDE eyes had the lowest central lid temperature and lower periorbital temperatures (P<.0001). Over the 5-s interblink interval, the greatest rate of temperature loss occurred following eyelid opening, but varied by group (normals -0.52, SS -0.73, EDE -0.63, and ADDE -0.75°C/s). The ADDE group also had the most substantial heat loss over the 5-s interblink interval (-0.97°C). CONCLUSIONS Differences in OST may be related to thermal differences in lids and periorbita along with an altered tear film. Thermography of the ocular surface, lids, and surrounding tissues may help to differentiate between different etiologies of dry eye.

Multimodal imaging of ocular surface of dry eye subjects

To study the relationship between the corneal lipid layer and the ocular surface temperature (OST), we conducted a clinical trial for 20 subjects. Subjects were clinically screened prior to the trial. Of the 20 subjects, 15 have Meibomian gland dysfunction (MGD), and 5 have aqueous-deficient dry eye (ADDE). A custom, circularly polarized illumination video tearscope measured the lipid layer thickness of the ocular tear film. A long-wave infrared video camera recorded the dynamic thermal properties of the ocular team film. The results of these two methods were analyzed and compared. Using principal component analysis (PCA) of the lipid layer distribution, we find that the 20 subjects could be categorized into five statistically significant groups, independent of their original clinical classification: thin (6 subjects), medium (5 subjects), medium and homogenous (3 subjects), thick (4 subjects), and very thick (2 subjects) lipids, respectively. We also conducted PCA of the OST data, and recategorized the subjects into two thermal groups by k-means clustering: one includes all ADDE subjects and some MGD subjects; the other includes the remaining MGD subjects. By comparing these two methods, we find that dry eye subjects with thin (≤ 40 nm) lipids have significantly lower OST, and a larger OST drop range, potentially due to more evaporation. However, as long as the lipid layer is not thin (> 40 nm), there is no strong correlation between the lipid layer thickness and heterogeneity and the OST patterns.