Jalaiah Varikooty

Tear breakup dynamics: a technique for quantifying tear film instability.

Purpose. The purpose of this study was to develop a novel, quantitative measurement of tear film breakup dynamics (TBUD) to study the phenomenon of tear breakup in dry eye and control subjects and its impact on dry eye symptoms. Methods. Ten control and 10 dry eye subjects completed the Dry Eye (DEQ) and other questionnaires. After the instillation of sodium fluorescein, subjects kept the tested eye open for as long as possible, similar to a staring contest, while tear film breakup was videotaped (S-TBUD). The maximum blink interval (MBI) and tear breakup time (TBUT) were measured from digital movies by a masked observer. Individual frames of movies were converted to gray-scale images, maps of relative tear film fluorescence were generated, and the total area of tear breakup (AB) of the exposed cornea was quantified. Results. On average, dry eye subjects demonstrated a higher AB and shorter TBUT and MBI, but only the AB was significantly different (p = 0.023). Subjects most often used the descriptors stinging and burning to describe their sensations during staring trials. The AB showed a high correlation between eyes and with some DEQ symptom measures. Conclusions. These methods allow objective quantification and tracking of the phenomenon of tear breakup. Our results suggest that tear breakup stresses the corneal surface, resulting in stimulation of underlying nociceptors. The tear film of dry eye subjects was less stable than controls. They had a larger AB measured from the last video frame before MBI (i.e., just before blinking) than did controls. This perhaps reflects adaptation to the repeated stress of tear instability in dry eye.

Protein deposition and clinical symptoms in daily wear of etafilcon lenses.

Purpose. To determine the relationship between clinical signs and symptoms and protein deposition over 8 h of wear of etafilcon A lenses in symptomatic and asymptomatic contact lens wearers. Methods. Thirty adapted soft contact lens wearers (16 symptomatic and 14 asymptomatic) were fitted with etafilcon A lenses. In vivo wettability, non-invasive tear break-up time, and subjective symptoms (vision, comfort, and dryness) were assessed at baseline and after 2, 4, 6, and 8 h. After 2, 4, 6, and 8 h time points, lenses were collected, and total protein, total lysozyme, and active lysozyme deposition were assessed. Results. There was a significant reduction (p = 0.032) in the non-invasive tear break-up time at 8 h in both groups. In the symptomatic group, there was a significant reduction in subjective comfort and dryness ratings at 6 and 8 h measurement with respect to baseline (p < 0.05). There was a significant increase in total lysozyme and total protein deposition (p = 0.027) across all time points in both groups; most of the lysozyme remained active (>94% at 8 h). Pearsons correlations between subjective symptoms and protein deposition showed poor correlations for total protein/lysozyme and any subjective factor (r < 0.3; p > 0.05), and only weak correlations between dryness and % active lysozyme (r = 0.3 to 0.5 for all time points). However, stronger correlations were found between active lysozyme and subjective comfort (r = 0.6 to 0.7; p < 0.001). Conclusions. In addition to investigating total protein deposited on contact lenses, it is of significant clinical relevance to determine the conformational state of the deposited protein.

Ex Vivo Protein Deposition on Bi-Weekly Silicone Hydrogel Contact Lenses

Purpose. This study investigated the protein deposition that occurs on daily wear silicone hydrogel (SH) lenses, after 2 weeks of wear. Methods. A total of 40 subjects were divided into equal groups, based on their habitual SH contact lens [CIBA Vision O2OPTIX (O2); Johnson & Johnson ACUVUE ADVANCE with HYDRACLEAR (ADV); Bausch & Lomb PureVision (PV); CIBA Vision Night & Day (ND)]. A randomized, double-masked, cross-over study was conducted in which subjects wore either their habitual SH material or Johnson & Johnson ACUVUE OASYS with HYDRACLEAR PLUS (OAS) for 2 weeks. At the end of the 2-week period, lenses were collected for analysis of total protein, total lysozyme, and percent denatured lysozyme. Results. Total protein was greatest for PV (33 ± 6 &mgr;g/lens), with other lenses depositing <10 &mgr;g/lens. The PV amount was greater than other materials (p < 0.001), with no significant differences between the other three materials (p > 0.05). Total lysozyme was also greatest for the PV lens (11 ± 3 &mgr;g/lens), with other lenses depositing <2 &mgr;g/lens. The PV amount was greater than all other materials (p < 0.001). ADV and OAS were greater than O2 (p < 0.01) but were not different from each other (p > 0.05). The percentage of lysozyme that was denatured was greatest for ND (90 ± 8%) and lowest for PV (23 ± 10%). The lysozyme extracted from ND and O2 lenses was significantly more denatured than that extracted from the other lens materials (p < 0.001). There were no significant differences for lysozyme activity between ND and O2 (p > 0.05) or between ADV, OAS, and PV (p > 0.05). The amount of denatured lysozyme/lens was <3 &mgr;g/lens for all materials. Lysozyme as a percentage of the total protein deposited ranged from 32 (PV) to 6% (O2). Conclusions. This study confirms that all SH lenses deposit low levels of protein, and that the amount and percentage of denatured lysozyme can vary, depending on the overall surface charge of the material and absence or type of surface treatment.

The Interblink Interval I: The Relationship between Sensation Intensity and Tear Film Disruption

PURPOSE To find the relationship between tear film drying and sensation during the interblink period. METHODS One eye was taped shut, and after a blink the subjects were required to keep the other eye open. Digital video images of the ocular surface (with fluorescein) were obtained using a slit lamp biomicroscope while 23 subjects rated the intensity of the ocular surface sensation by adjusting a one-turn potentiometer to represent the strength of the sensation. They were trained to use the potentiometer before the data were collected. In addition, the characteristics of the sensation as spoken by the subject were recorded. RESULTS The sensation was generally triphasic, with initial constant sensation and a subsequent biphasic period, with intensity increasing slowly followed by a rapid increase before the subjects blinked (correlations were all r > 0.95). Tear film drying dynamics were also biphasic, and drying and sensation were strongly associated, with a correlation of 0.94 between the break in the bilinear functions of sensation and drying. CONCLUSIONS The method provides novel information about the development of ocular sensation during ocular surface drying. As evidenced by the complex functions required to adequately describe the relationships, tear film drying and ocular surface sensations are associated in complex ways.

Distribution of overnight corneal swelling across subjects with 4 different silicone hydrogel lenses.

Purpose: To determine distribution of central corneal swelling (CCS) across subjects after 8 hr of sleep in eyes wearing silicone hydrogel lenses with various oxygen transmissibility (Dk/t) values and in eyes without lenses. Methods: Twenty-nine neophytes wore lotrafilcon A (Dk, 140), balafilcon A (Dk, 91), galyfilcon A (Dk, 60), and senofilcon A (Dk, 103) lenses in powers −3.00, −10.00, and +6.00 diopters on separate nights, in random order, and on 1 eye only. The contralateral eye (no lens) served as the control. Central corneal thickness was measured using a digital optical pachometer before lens insertion and immediately after lens removal on waking. Results: The average difference between the mean (7%) and the median (6.8%) CCS of all lenses was only 0.2%, suggesting a normal distribution. There was no correlation between the mean and the range of the CCS (r=0.058, P=0.766). Normal CCS distributions were also found with each lens-wearing eye and the control eye (P>0.20 for all). There was a significant correlation between lens-wearing eye and control eye (r=0.895, P<0.001) and between lotrafilcon A and each of the other 3 lenses for mean CCS across the study participants (P<0.001 for all). Conclusions: Distribution of corneal swelling in both lens-wearing eye and control eye followed a normal curve. An individuals corneal swelling response seems to be independent of lens type.

Clinical performance of three silicone hydrogel daily disposable lenses.

Purpose To determine the clinical performance of DAILIES TOTAL1 (DT1), Clariti 1Day (C1D), and 1-DAY ACUVUE TruEye (AVTE) silicone hydrogel daily disposable contact lenses (SiHy DDCLs). Methods Eligible participants, subdivided into asymptomatic and symptomatic groups, wore each SiHy DDCLs for three consecutive days. Each participant attended three visits (on day 1 at 0 hours; on days 1 and 3 after 8 hours of wear) per lens type. The order of lens wear was randomized, with at least 1 day washout between lenses. Lens-related performance was evaluated by assessing lens surface deposits, wettability, pre-lens noninvasive tear breakup time, lens movement, and centration; ocular response assessments included conjunctival redness, corneal staining, and conjunctival staining and indentation. Results Fifty-one asymptomatic and 53 symptomatic participants completed the study. For all visits, the mean noninvasive tear breakup time was about 1 second longer with DT1 than with C1D and AVTE (p < 0.01). Overall, the wettability of all three lenses was good; however, DT1 was graded marginally better than the other lenses (both p < 0.01). On day 3, eyes wearing AVTE had significantly more dehydration-induced corneal staining compared with DT1 (AVTE, 24%; DT1, 11%; p < 0.01). After 8 hours, conjunctival staining was different between lenses (greatest with C1D and least with DT1; all p < 0.01). Conjunctival indentation was more prevalent with the C1D lenses (n = 70) compared with DT1 (n = 1; p < 0.01) and AVTE (n = 11; p < 0.01). There were no differences between asymptomatic and symptomatic lens wearers for any of the clinical parameters (all p > 0.05). Conclusions Each of the three SiHy DDCLs performed well. Noninvasive tear breakup time was longest and wettability was greater with DT1. C1D had the most conjunctival staining conjunctival indentation. There was no difference between asymptomatic and symptomatic wearers with regard to ocular response and contact lens–related parameters. These results suggest that SiHy DDCLs may be an excellent contact lens modality for the symptomatic patient.

Comfort Response of Three Silicone Hydrogel Daily Disposable Contact Lenses

Purpose To evaluate subjective ocular comfort across the day with three silicone hydrogel daily disposables (SHDDs) in a group of adapted lens wearers. Methods Masked subjects (asymptomatic or symptomatic of end-of-day (EOD) dryness with habitual lenses) wore three SHDDs: DAILIES TOTAL1 (DT1), Clariti 1day (C1D), or 1-DAY ACUVUE TRUEYE (AVTE), each for 3 days. On day 2, wearing time (WT) and comfort ratings after insertion, at 4, 8, and 12 hours, and at EOD were recorded. Because not all subjects wore lenses for 12 hours, comfort was analyzed across the day (up to 8 hours, 8 to 12 hours), and a new variable (“cumulative comfort” [CC]) was calculated for EOD. Results One hundred four subjects completed the study (51 asymptomatic, 53 symptomatic). The two groups had different WTs (mean WT, 14.0 and 12.7 hours, respectively; p < 0.001). Ocular comfort was rated higher in the asymptomatic group throughout the day (p < 0.001). One hundred four subjects wore all three SHDDs for at least 8 hours, whereas 74 (45 asymptomatic, 29 symptomatic) subjects wore them for 12 hours or longer. Comfort ratings were higher with DT1 (least square means [LSM] = 91.0) than with C1D (LSM = 86.5; p < 0.001) and AVTE (LSM = 87.7; p = 0.011) for the first 8 hours and lower with C1D compared with DT1 (p = 0.012) from 8 to 12 hours. Mean EOD (± SD) comfort with the C1D lens was 72 ± 21, lower than both DT1 (mean, 79 ± 17; p = 0.001) and AVTE (mean, 78 ± 21; p = 0.010). Mean CC was higher in the asymptomatic group (mean, 1261 ± 59) compared with that in the symptomatic group (mean, 1009 ± 58; p < 0.001) and higher for DT1 (mean, 1184 ± 258) than C1D (mean, 1094 ± 318; p = 0.002) and AVTE (mean, 1122 ± 297; p = 0.046). Conclusions All three SHDDs had average WTs of 12 hours or longer for 1 day. Comfort during the first 12 hours was highest with DT1 (similar to AVTE between 8 and 12 hours) and lowest with C1D. End-of-day comfort was lowest with C1D, and CC was highest for DT1. Cumulative comfort may be a valuable new metric to assess ocular comfort during the day.

Estimating tear film spread and stability through tear hydrodynamics.

Purpose. The stability and ease of spread of the tear-film over the contact lens surface may be an indicator of contact lens surface dewetting. The present in vivo methods of determining lens dewetting are complex. This study introduces a novel and objective way of determining the upward spread and stability of the tear-film through measurement of tear-film particle dynamics. Methods. Ten adapted contact lens wearers wore the same type of contact lens. Using a video camera mounted to a slit-lamp, the tear-film spread over the lens surface was recorded after a blink, at 8× magnification and capture rate of 30 frames per second, at morning after lens insertion, and after 8 h of lens wear. Images from 20 videos, without blinks and without an observable change in fixation were analyzed without any further postprocessing of the images. Using a customized calibrated ImageJ macro for particle tracking, the velocity of naturally occurring reflective particles was determined. The results were analyzed using the R program and ProFit. Results. The results established that the upward particle velocity was highest immediately after a blink and declined with time. The spread of the tear film measured through upward particle velocity was different on lens insertion than after 8 h of lens wear (p = 0.001). The exponential time constants ± SE were 346.02 ± 29.0 for lens insertion at morning and 1413.13 ± 419.6 after 8 h of lens wear. Conclusions. A novel and non-invasive way to measure in vivo spread and stability of the prelens tear-film has been developed. Additional studies are needed to understand whether this simple measure is able to differentiate the performance of different soft contact lenses and how this method may help in the understanding other aspects of lens performance such as non-invasive tear breakup time, surface deposition, and lens comfort.

Overnight corneal swelling with high and low powered silicone hydrogel lenses.

PURPOSE To compare central corneal swelling after eight hours of sleep in eyes wearing four different silicone hydrogel lenses with three different powers. METHODS Twenty-nine neophyte subjects wore lotrafilcon A (Dk, 140), balafilcon A (Dk, 91), galyfilcon A (Dk, 60) and senofilcon A (Dk, 103) lenses in powers -3.00, -10.00 and +6.00 D on separate nights, in random order, and on one eye only. The contra-lateral eye (no lens) served as the control. Central corneal thickness was measured using a digital optical pachometer before lens insertion and immediately after lens removal on waking. RESULTS For the +6.00 D and -10.00 D, lotrafilcon A induced the least swelling and galyfilcon A the most. The +6.00 D power, averaged across lens materials, induced significantly greater central swelling than the -10.00 and -3.00 D (Re-ANOVA, p<0.001), (7.7±2.9% vs. 6.8±2.8% and 6.5±2.5% respectively) but there was no difference between -10.00 and -3.00 D. Averaged for power, lotrafilcon A induced the least (6.2±2.8%) and galyfilcon A the most (7.6±3.0%) swelling at the center (Re-ANOVA, p<0.001). Central corneal swelling with +6.00 D was significantly greater than -10.00 D lens power despite similar levels of average lens transmissibility of these two lens powers. CONCLUSIONS The differences in corneal swelling of the lens wearing eyes are consistent with the differences in oxygen transmission of the silicone hydrogel lenses. In silicone hydrogel lenses central corneal swelling is mainly driven by central lens oxygen transmissibility.

Variations in observable lid wiper epitheliopathy (LWE) staining patterns in wearers of silicone hydrogel lenses.

Lid wiper epitheliopathy (LWE) is believed to be an early sign of cular irritation, which is clinically observed through vital staining f the upper and lower lidmargin regions [1–3]. In the healthy eye, he lidmargin regionsare in closeproximity to theglobe [4], and the pper lid in particular executes a “wiping motion” during blinking 5]. The cause of the upper and lower lid margin staining is curently unknown, but in the healthy eye physiological factors such s the tear-film and the glycocalyx of the conjunctiva and cornea ct as a lubricant between the lid and the ocular surface, to reduce riction and prevent any damage to the ocular surface [6–8]. It is ostulated that LWEmay be due to an increase in friction between he palpebral lid and the apposing bulbar conjunctiva and cornea 2]. This is due to direct contact between these surfaces due to an ltered tear film [9,10], decreased mucins [11], and contact lens elated alterations in lens wearers [1]. These alterations are often xacerbated by adverse environmental conditions [12] and it has een shown that LWEcanbe induced after a 3-h exposure to a “conrolled adverse environment” [13]. In addition, meibomian gland ysfunction may also cause tear film alterations and result in LWE 14]. Upper LWE has been noted in both contact lens wearers 1,15,16] and non-lens wearers [2,16,17], with a higher prevalence n patients with symptoms of dry eye [1,10]. Staining similar to pper LWE has also been reported in the lower lid, at a higher