Andrew D. Graham

Tear mixing under a soft contact lens: effects of lens diameter.

PURPOSE Tear exchange under a soft contact lens is modest, and higher exchange rates may be necessary to reduce extended-wear complications; what is not known is the optimal soft lens design to increase tear mixing. We explored the effect of lens diameter on tear mixing. METHODS Twenty-three subjects wore four different soft contact lenses with diameters of 12.0, 12.5, 13.0, and 13.5 mm. Tear mixing was quantified by placing fluorescein isothiocyanate-dextran on the posterior lens surface, inserting the lens, and monitoring the changes in fluorescence intensity in the postlens tear film. Tear mixing, expressed as the percentage decrease in fluorescence intensity per blink, was estimated using an exponential model. Lens movement was videotaped and lens comfort was graded on a 50-point scale (50 = excellent comfort). Subjects reporting a comfort level of less than 35 were excluded. RESULTS The mean +/- SE tear mixing rates were 1.82% +/- 0.17%, 1.61% +/- 0.16%, 1.34% +/- 0.17%, and 1.24% +/- 0.17% per blink for the 12.0-, 12.5-, 13.0-, and 13.5-mm diameter lenses, respectively. By regression analysis we found that, on average, mixing under the 12.0-mm lens was 0.59% per blink greater than with the 13.5-mm lens (P = .0024). Lens diameter was a significant predictor of lens comfort, and adjusting for the effects of comfort weakened the relationship between diameter and tear replenishment rate, although the mean rate under the 12.0-mm lens was still 0.43% per blink greater than with the 13.5-mm lens (P = .0468). CONCLUSIONS These data suggest that smaller-diameter soft lenses provide substantially better tear mixing than larger lenses; however, even small lenses provide modest tear mixing compared with rigid contact lenses.

Saccades reduce latency and increase velocity of ocular accommodation

Horizontal vergence can be stimulated binocularly with disparity (disparity vergence) or monocularly with accommodation (accommodative vergence). The latter results from a neural cross-coupling that causes both horizontal vergence and accommodation to respond when either one is stimulated [Alpern, M., & Ellen, P. (1956). American Journal of Ophthalmology, 42, 289-303]. The velocity of disparity and accommodative vergence is enhanced when accompanied by saccades [Enright, J. T. (1984). Journal of Physiology (London) 350, 9-31; Enright, J. T. (1986). Journal of Physiology (London) 371, 69-89]. Based upon the coupling between accommodation and vergence, we predicted that accommodation should also be facilitated by saccades. An SRI Dual Purkinje Eyetracker was used to measure left and right eye position, and the accommodation of the left eye, in response to stimulation. Horizontal saccades were stimulated by targets separated by 2-6 degrees and accommodation was stimulated monocularly over a range of +/- 2 diopters (D). When saccades occurred within 0-400 ms following a monocular step stimulus to accommodation, latency of accommodation decreased and the associated accommodative-vergence response was synchronized with the saccade. Saccades also enhanced the velocity of accommodation and accommodative-vergence, and this facilitation increased with saccade amplitude. Transient vergence responses that are normally associated with saccades [Erkelens, C. J., Steinman, R. M., & Collewijn, H. (1989). Proceedings of the Royal Society of London B. Biological Sciences, 236, 441-465; Maxwell, J. S., & King, W. M. (1992). Journal of Neurophysiology, 68 (4), 1248-1260] did not affect accommodation when it was not stimulated by defocus. Because saccades and accommodation utilize separate plants and final common pathways, the synchronization of saccades and accommodation and the enhanced velocity of accommodation and accommodative-vergence must occur at more central sites. Possibilities include the superior colliculus, which represents both accommodation and saccades [Nagasaka, Y., & Ohtsuka, K., (1998). Investigative Ophthalmology AVRO supplement], vestibular nuclei which project to regions near the oculomotor nuclei [Lang, W., Buttner-Ennever, J. A., & Buttner, U. (1979). Brain Research, 177, 3-17], and interactions between omni pause neurons and near response cells of the mesencephalic reticular formation (MRF) [Mays, L. E., & Gamlin, P. D. R. (1995a). Current Opinions in Neurobiology, 5, 763-768; Mays, L. E., & Gamlin, P. D. R. (1995b). Eye movement research: Mechanisms, processes and applications. New York: Elsevier] which represent both accommodation and vergence [Judge, S. J., & Cumming, B. G. (1986). Journal of Neurophysiology, 55, 915-930; Zhang, Y., Mays, L. E., & Gamli, P. D. R. (1992). Journal of Neurophysiology, 67, 944-960].

Relationships among Tear Film Stability, Osmolarity, and Dryness Symptoms

Purpose To examine the relationships among tear osmolarity, tear film stability, and several measures of dry eye (DE) symptoms in a multivariable analysis. Methods A cross-sectional study was conducted with 137 subjects (68 non–contact lens [CL] wearers and 69 soft CL wearers) recruited from a university campus. Tear breakup time (TBUT) was measured noninvasively (NITBUT) and with fluorescein (FTBUT). Tear osmolarity was measured by an osmometer. Dry eye symptoms were assessed using the Dry Eye Flow Chart and several different questionnaires. Results Subjects ranged in age from 18 to 67 years, with a mean of 28 years. Subjects had a mean (SD) osmolarity of 293 (10) mOsm/L, NITBUT of 14.1 (10.9) seconds, and FTBUT of 14.8 (12.6) seconds. Shorter NITBUT and FTBUT were significantly associated with female sex (p = 0.001 and p = 0.027, respectively) and Asian ethnicity (p = 0.030 and p = 0.004, respectively). There were no clinically significant relationships between tear osmolarity and FTBUT, NITBUT, or DE symptoms. Higher Dry Eye Flow Chart score (i.e., worse symptoms) was associated with older age (p < 0.001), female sex (p = 0.014), CL wear (p < 0.001), shorter NITBUT (p < 0.001), and shorter FTBUT (p = 0.028). The sensitivities and specificities for using clinical measurements to diagnose moderate to severe DE were as follows: osmolarity, 0.67 and 0.46, respectively; NITBUT, 0.72 and 0.52, respectively; and FTBUT, 0.68 and 0.57, respectively. Conclusions In a population of asymptomatic, mild and moderate DE patients, increased tear osmolarity was not significantly associated with reported symptom severity and frequency. Tear osmolarity, NITBUT, and FTBUT exhibited similar sensitivities and specificities when used to diagnose moderate to severe DE.

Factors in Contact Lens Symptoms: Evidence from a Multistudy Database

Purpose This study aimed to examine the effects of demographic, lens performance, and ocular surface response measures on contact lens–related discomfort and dryness, using a large contact lens study database. Methods A total of 4164 records were extracted from a database of 220 subjects participating in 46 silicone hydrogel contact lens studies. Subjects discontinued lens wear for 24 hours and were then fit with either comfilcon A or enfilcon A lenses. The fit and performance of the lenses, along with subjective comfort and dryness, were assessed on insertion and after 3 and 6 hours of wear. After 6 hours of wear, ocular surface health was also assessed by fluorescein slitlamp examination. Results Decreased comfort at 3 hours after insertion was associated with excessive lens movement (p < 0.001), front surface deposits (p = 0.004), poor wettability (p = 0.014), and Asian ethnicity (p < 0.001). After 6 hours of wear, decreased comfort remained associated with greater lens movement (p = 0.032) and Asian ethnicity (p < 0.001), along with inferior corneal staining (p < 0.001). Dryness after 3 hours of wear was associated with greater lens movement (p < 0.001), Asian ethnicity (p < 0.001), increased deposits (p < 0.001), and poor wettability (p < 0.001). Dryness after 6 hours of wear remained associated with greater lens movement (p < 0.001) and Asian ethnicity (p < 0.001), along with inferior corneal staining (p < 0.001) and inferior lens decentration (p = 0.001). Conclusions Excessive lens movement, inferior lens decentration, poor surface wettability and deposits, inferior corneal staining, and Asian ethnicity are associated with discomfort and dryness. Clinicians should consider all these factors to achieve the most comfortable and successful contact lens fit.

Ethnic differences in dry eye symptoms: Effects of corneal staining and length of contact lens wear☆

PURPOSE To explore the relationships among length of contact lens (CL) wear, degree of corneal staining and severity of dryness symptoms, and to determine whether these relationships differ between Asians and non-Asians. METHODS Adapted soft CL wearers (n=395; 180 Asian, 215 non-Asian) were required to discontinue CL wear for at least 24h and report to the University of California, Berkeley Clinical Research Center (UCB-CRC). Fluorescein corneal staining was graded according to Brien Holden Vision Institute scales. Length of CL wear was reported by subjects and subjective dryness ratings were collected using the UCB-CRC Dry Eye Flow Chart (DEFC). RESULTS More Asian CL wearers exhibited corneal staining compared to non-Asians, and Asian CL wearers had a higher mean grade of corneal staining (p<0.001), as well as a higher mean DEFC classification (p<0.001). The difference between Asians and non-Asians in grades of corneal staining extent and depth were significant (p<0.001). Among non-Asian CL wearers, dryness symptoms decreased with more years of CL wear and increased in the presence of corneal staining, which was not the case for Asian CL wearers. CONCLUSIONS Asian soft CL wearers reported more severe dryness symptoms and demonstrated more severe corneal staining overall compared to non-Asians. Among non-Asians, dryness symptoms were less severe on average with increased years of CL wear and more severe in the presence of corneal staining. Dryness severity does not appear to be related to years of CL wear or corneal staining among Asians.

Conjunctival epithelial flap in continuous contact lens wear.

Purpose. Composed of sheets of cells detached from the underlying conjunctiva, conjunctival epithelial flap (CEF) is a recently reported phenomenon associated with contact lens wear with potential consequences for ocular health. Although CEF is generally asymptomatic, it is not known to what extent it might increase the longer-term risk of discomfort, inflammatory response, or infection. In this study, we use survival analysis methods to obtain unbiased estimates of the probability of developing CEF, the mean survival time free of CEF, and the effects of age, gender, ethnicity, and contact lens type. Methods. Two hundred four subjects were recruited for a continuous wear (CW) study of silicone hydrogel (SiH) and gas permeable (GP) contact lenses. Subjects were examined by optometrists throughout contact lens adaptation and CW periods. Statistical methods included the Kaplan-Meier nonparametric estimator of the survival function and the Cox proportional hazards model for estimating the relative effects of covariates. Results. Of the 204 subjects, 72 (35%) developed CEF. In 64% of cases, CEFs were observed bilaterally. The majority of cases (90.3%) presented with CEF in the superior conjunctiva. Mean survival time free of CEF was longer for GP lenses (94.3 days) than for SiH lenses (76.5 days), and the probability of developing CEF was significantly greater for SiH lenses (p = 0.002). Although there was some evidence that women and non-Asians remain free of CEF longer, the effects of age, gender, and ethnicity were not statistically significant. Conclusions. There was a significantly increased risk of CEF in subjects wearing SiH lenses, compared with GP lenses. Subjects wearing SiH lenses remained free of CEF for a shorter time on average. Further study is needed to determine whether the increased incidence of CEF in CW with SiH lenses poses an increased risk of adverse ocular response or infection.

Effects of Eye Rubbing and Breath Holding on Corneal Biomechanical Properties and Intraocular Pressure

Purpose: To determine whether corneal biomechanical properties and intraocular pressure (IOP) are affected by eye rubbing and breath holding. Methods: Corneal hysteresis, corneal resistance factor, corneal compensated IOP (IOPcc), and Goldmann equivalent IOP (IOPg) were measured on both eyes of 40 subjects. Measurements were taken at baseline before eye rubbing (ER0) and before breath holding (BH0), immediately after 2 episodes of eye rubbing (ER1 and ER2), and during 2 episodes of breath holding (BH1 and BH2). Results: Corneal hysteresis, corneal resistance factor, and IOPg were significantly lower after ER1 compared with ER0 and were significantly lower after ER2 compared with ER1. In contrast, IOPcc did not decrease significantly. There were no significant differences among BH0, BH1, and BH2 in any of the 4 outcomes. Conclusions: Eye rubbing should be avoided before measurements of corneal biomechanical properties and IOPg. In contrast, breath holding during measurements is not likely to cause a significant change in IOPg and IOPcc or corneal biomechanical properties.

Ocular surface health during 30-day continuous wear: rigid gas-permeable versus silicone hydrogel hyper-O2 transmitted contact lenses.

PURPOSE To determine the effects on corneal epithelial permeability and ocular response of 30 nights of continuous wear (CW) of gas permeable (GP) and silicone hydrogel (SiH) contact lenses. METHODS Ninety-one subjects successfully completed 30 days of CW of either GP (n = 42) or SiH (n = 49) contact lenses. Epithelial permeability (P(dc)) was measured by scanning fluorometer at an afternoon (PM) baseline session and again the next morning (AM). One randomly selected eye of each subject was patched overnight and the patch removed immediately before the AM visit. P(dc) measurements and ocular examinations were conducted at baseline and after 30 days of CW. RESULTS Epithelial permeability increased significantly after 30 days of CW in the patched eyes of the GP group (P = 0.022) and in the unpatched eyes of the SiH group (P = 0.004). The increase was driven primarily by the Asian subjects in each group (GP, P = 0.015; SiH, P = 0.001). There was no significant increase in either lens group in the non-Asian subjects. Multivariate models suggest that the change in AM P(dc) from baseline to 30 days of CW was also related to lens type (P = 0.035), time awake before measurement (P = 0.001), palpebral aperture size (P = 0.003), lens deposits (P = 0.020), and horizontal lens bearing (P = 0.003). CONCLUSIONS Subclinical increases in epithelial permeability can be caused by contact lens CW, despite the elimination of hypoxia. GP lenses permit recovery of the epithelium more quickly than do SiH lenses. Asians appear to be more susceptible to contact lens-induced epithelial changes than do non-Asians.

Ocular Surface Cooling Corresponds to Tear Film Thinning and Breakup.

Purpose To investigate the relationship between ocular surface temperature (OST) and tear film thinning and breakup. Methods Simultaneous imaging of OST and fluorescein tear thinning and breakup (FTBU) was performed on 20 subjects. Subjects were asked to open their eyes and refrain from blinking for as long as they could during testing. Ocular surface temperature was measured using an infrared thermographic camera (FLIR A655sc) and rates of ocular surface cooling (OSC) were analyzed using commercially available software. A method was developed to quantify the rate of FTBU formation using image-processing software. Results Areas of FTBU and regions of OSC were observed to be colocalized, with localized cooling preceding the formation of FTBU. The rates of OSC and FTBU formation were positively correlated (r = 0.74). A second-order polynomial model accurately describes the physiological relationship between the area of FTBU and OST (p < 0.001). A linear approximation provides a more clinically interpretable rate of FTBU formation with decreasing OST (p < 0.001), while still retaining high R2. Conclusions The results suggest a direct relationship between FTBU formation and OSC. That cooling of the ocular surface precedes FTBU formation implies a process of evaporation contributing to tear film thinning and breakup. Our study suggests that measuring the OSC rate could be an indirect assessment of tear evaporation and could contribute to the management of evaporative dry eye.

Effects of Daily Irrigation on Corneal Epithelial Permeability and Adverse Events With Silicone Hydrogel Contact Lens Continuous Wear

PURPOSE To determine whether daily irrigation with sterile saline solution during silicone hydrogel (SiH) contact lens continuous wear (CW) can mitigate increases in corneal epithelial permeability (Pdc) and reduce the risk of adverse events. METHODS In this study, 161 non-contact lens wearers were fit with SiH contact lenses and randomized to either a treatment (n = 81) or control (n = 80) group for 30-day CW. Subjects in the treatment group irrigated every morning and whenever dryness symptoms occurred; subjects in the control group did not. Mixed effects models were employed to assess the changes in Pdc, and survival analysis methods were employed to estimate the risk for adverse events. RESULTS Epithelial permeability increased over 30-day CW with SiH lenses (P = 0.001). Risk of inflammatory (odds ratio [OR] = 1.94) and lens-induced (OR = 1.90) adverse events increased with irrigation; these events also occurred sooner, on average, in the irrigation group. Although the overall risk for Asians was higher than for non-Asians, irrigation had no significant impact on risk among Asians, but significantly increased risk among non-Asians. CONCLUSIONS Thirty-day CW results in a measurable increase in epithelial permeability. Risk of inflammatory and lens-induced adverse events also increase over time during CW. Daily irrigation with sterile saline solution did not mitigate increases in epithelial permeability or decrease risk of adverse events.