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This study introduces a deep learning approach to predicting demographic features from meibography images. A total of 689 meibography images with corresponding subject demographic data were used to develop a deep learning model for predicting gland morphology and demographics from images. The model achieved on average 77%, 76%, and 86% accuracies for predicting Meibomian gland morphological features, subject age, and ethnicity, respectively. The model was further analyzed to identify the most highly weighted gland morphological features used by the algorithm to predict demographic characteristics. The two most important gland morphological features for predicting age were the percent area of gland atrophy and the percentage of ghost glands. The two most important morphological features for predicting ethnicity were gland density and the percentage of ghost glands. The approach offers an alternative to traditional associative modeling to identify relationships between Meibomian gland morphological features and subject demographic characteristics. This deep learning methodology can currently predict demographic features from de-identified meibography images with better than 75% accuracy, a number which is highly likely to improve in future models using larger training datasets, which has significant implications for patient privacy in biomedical imaging.

Significance Quantifying meibomian gland morphology from meibography images is used for the diagnosis, treatment, and management of meibomian gland dysfunction in clinics. A novel and automated method is described for quantifying meibomian gland morphology from meibography images. Purpose Meibomian gland morphological abnormality is a common clinical sign of meibomian gland dysfunction, yet there exist no automated methods that provide standard quantifications of morphological features for individual glands. This study introduces an automated artificial intelligence approach to segmenting individual meibomian gland regions in infrared meibography images and analyzing their morphological features. Methods A total of 1443 meibography images were collected and annotated. The dataset was then divided into development and evaluation sets. The development set was used to train and tune deep learning models for segmenting glands and identifying ghost glands from images, whereas the evaluation set was used to evaluate the performance of the model. The gland segmentations were further used to analyze individual gland features, including gland local contrast, length, width, and tortuosity. Results A total of 1039 meibography images (including 486 upper and 553 lower eyelids) were used for training and tuning the deep learning model, whereas the remaining 404 images (including 203 upper and 201 lower eyelids) were used for evaluations. The algorithm on average achieved 63% mean intersection over union in segmenting glands, and 84.4% sensitivity and 71.7% specificity in identifying ghost glands. Morphological features of each gland were also fed to a support vector machine for analyzing their associations with ghost glands. Analysis of model coefficients indicated that low gland local contrast was the primary indicator for ghost glands. Conclusions The proposed approach can automatically segment individual meibomian glands in infrared meibography images, identify ghost glands, and quantitatively analyze gland morphological features.

The surface of the human eye is covered with a protective tear film that refreshes with each blink. Natural blinking occurs involuntarily, but one can also voluntarily blink or refrain from blinking. The maximum time one can refrain from blinking until the onset of discomfort is the maximum inter-blink period (MIBP). In between blinks the tear film thins and evaporates from the ocular surface. Tear film evaporation can be measured with various instruments. Infrared thermography provides a non-invasive measure of the ocular surface temperature (OST). Due to evaporation, ocular surface cooling (OSC) generally occurs when the eyes are open and exposed to the environment. The purpose of our study was to investigate the effect of OSC on the MIBP, and to investigate the association of the MIBP with tear film characteristics in subjects who do and do not exhibit OSC. The MIBP was measured simultaneously with OST over time. Non-invasive tear breakup time, tear meniscus height, tear lipid layer thickness, and Schirmer I test strip wetted lengths were measured on a day prior to the thermography visit. Subjects were divided into cooling and non-cooling groups based on OSC rate, and demographic and tear film characteristics were tested for inter-group differences. A faster rate of OSC was associated with an exponentially shorter duration of the MIBP overall and within the cooling group alone. Faster non-invasive tear breakup time was significantly associated with a shorter MIBP in both groups. These results suggest that tear film evaporation initiates a pathway that results in the onset of ocular discomfort and the stimulus to blinking. The presence of a subset of subjects with no or minimal OSC who nevertheless have a short MIBP indicates that evaporative cooling is not the only mechanism responsible for the onset of ocular discomfort.

OBJECTIVES To compare subjective and clinical outcomes in three study groups: (1) asymptomatic contact lens (CL) wearers (ASYM); (2) symptomatic CL wearers who become asymptomatic on lens removal; and (3) symptomatic CL wearers who do not resolve on lens removal. METHODS Ninety-two subjects completed the Berkeley Dry Eye Flow Chart with and without lenses, ocular surface examinations, and a battery of questionnaires. RESULTS Thirty-seven subjects (40%) were ASYM, 30 (33%) had contact lens-induced dry eye (CLIDE), and 25 (27%) had underlying physiological DE. Visual Analog Scale ratings, OSDI score, and SPEED score were significantly better for the ASYM group (P

Purpose To examine the relationship between pre-corneal and pre-contact lens tear film stability (TFS), and to determine whether pre-corneal TFS is a reliable predictor of subsequent pre-lens TFS after a contact lens is placed on the eye. Methods 667 records met inclusion criteria and were extracted from a soft contact lens multi-study database. Multivariable linear mixed effects models were fit to examine the association between pre-corneal and pre-lens TFS, adjusting for potential confounders and accounting for repeated measures. Receiver Operating Characteristic (ROC) analysis was employed to assess the predictive performance of pre-corneal TFS for subsequent pre-lens TFS. TFS was quantified for this analysis as the non-invasive tear breakup time (NITBUT). Results Pre-corneal NITBUT was significantly related to the pre-lens NITBUT at both 10 min (p Conclusions Despite the association of pre-corneal and pre-lens TFS, the inherent lability and sensitivity to environmental exposures of the tear film introduce significant variability into NITBUT measurements. Using pre-corneal NITBUT to identify likely successful contact lens candidates prior to fitting is thus not sufficiently accurate to be relied upon in the clinical setting.

Author(s): Kim, Young Hyun; Graham, Andrew D; Li, Wing; Radke, Clayton J; Lin, Meng C | Abstract: PurposeTo assess and compare the wetting kinetics of sheathed and unsheathed Schirmer's tear test (STT) strips, and to determine the repeatability of 5-minute wetted length (WL) and basal tear production rate (BTPR).MethodsSeventeen subjects underwent two sheathed and unsheathed STTs each for both eyes on four visits on separate days. After administration of topical anesthetic, WLs were measured every 30 seconds for 5 minutes, and BTPRs were calculated for sheathed strips. Limits of agreement (LoA), difference-versus-mean plots (DVM), and the coefficient of repeatability (CR) assessed WL and BTPR repeatabilities. Variance estimates were used to calculate sample sizes for future study.ResultsFor the unsheathed STT, the mean (SD) difference in WLs between visits was 0.74 (5.05) mm, LoA were [-9.17, 10.64], and CR was 9.17 mm; for the sheathed STT, the mean (SD) intervisit difference was 0.16 (5.94) mm, LoA were [-11.49, 11.8], and CR was 10.53 mm. Eight of 48 sheathed STTs and 20 of 44 unsheathed STTs showed constant WL for the final 90 seconds of the test. The mean (SD) difference between repeated visits for BTPR was approximately 0.0 μL/min, LoA were [-1.82, 1.82], and CR was 1.91 μL/min.ConclusionsRepeatability of sheathed and unsheathed 5-minute WL and BTPR is inadequate for measuring within-subject changes, but is sufficient for group studies with moderate sample sizes. Constant WL for the final 90 seconds with the eight sheathed STT measurements suggests varying BTPR, whereas constant WL with the unsheathed STT can be explained by balancing evaporation and BTPR.Translational relevanceRepeatability of the modified STT is evaluated clinically to establish quantitative BTPRs rather than inference from a strip WL.

To quantify corneoscleral junction (CSJ) topography in soft contact lens (SCL) wearers, and assess the association between the CSJ and SCL performance and subjective comfort, forty-four adapted SCL wearers (16 Asians, 16 Caucasians, 12 Latinos) were recruited for the present study. Corneal topography was taken with a Medmont E300 (Medmont International, Pty Ltd.). CSJ images were taken with a commercial OCT (Bioptigen, Inc.). Our published CSJ image analysis technique was used to describe the geometric properties of the CSJ using the sum of squared orthogonalized residuals (SSRo). Multivariable mixed effects models were employed to examine associations between SSRo and subject demographics, ocular characteristics, SCL fit and performance, and comfort. The SSRo was significantly related to quadrant (p

There are a number of anatomical and physiological differences between Asian and Caucasian eyes. Anatomical characteristics specific to the Asian eye include an oblique angle of the palpebral fissure, a smaller vertical palpebral aperture, a smaller horizontal visible iris diameter, a flatter cornea and greater corneal toricity.1-4 Asian eyelids have greater herniation of the orbital fat in the upper and lower eyelids, combined with a narrower palpebral aperture, possibly resulting in higher lid tension.5-7 The physiology of the Asian eye differs from that of the Caucasian eye in having a shorter tear breakup time, smaller tear meniscus volume, and reduced pre-corneal tear film stability.8,9 (Yeh TN, Tran N, Graham AD, Green HM, Lin MC. Relationships among tear film stability, tear osmolarity, corneal staining history, and dryness symptoms. Invest Ophthalmol Vis Sci. 2013;54. ARVO E-Abstract 4332.) Adverse responses to contact lens wear have been documented more frequently in Asian eyes than in Caucasian eyes. In controlled experimental settings, Hamano, et al. reported a higher incidence of endothelial bleb formation under hypoxic conditions in Asians compared to Caucasians and African Americans.10 Other studies have shown that Asians are more susceptible to micro-trauma during rigid gas-permeable contact lens extended wear, as well as after eight hours of closed-eye soft contact lens wear.4,11 In a clinical setting, Asian eyes exhibit a higher incidence of observable biomicroscopic signs, including limbal and conjunctival injection, corneal and conjunctival staining, and neovascularization.12,13 (Sanders TL, French HM, Yeh TN, Tran N, Green HM, Graham AD, Lin MC. Effects of irrigation on adverse events during continuous contact lens wear. 2010. AAO E-Abstract 105123.) In recent years, researchers have focused on the relationship between solution toxicity and adverse ocular events during lens wear.14-19 Carnt, et al. found that eyes with solution-related staining are three times more likely to experience a corneal infiltrative event, suggesting that solution-related corneal staining could be a potential risk factor for developing low-level corneal inflammation. Although solution-related corneal staining has been well documented, the type of corneal staining reported has been mostly diffuse, superficial, and micropunctate in presentation, which is generally transient and asymptomatic. Lebow, et al. found that differences exist between different MPS with respect to the type, extent, and depth of solution-related corneal staining; however, the severity of staining, on average, was considered clinically insignificant. Although several authors have examined the ocular response of the Asian eye to contact lens wear, none to date has studied racial differences in the ocular response to the use of lens care solutions. Of particular interest in the present study is the moderate-to-severe level of corneal staining that would prompt practitioners to recommend discontinuation of lens wear and possibly to implement clinical treatment. The degree to which this level of corneal staining occurs in response to contact lens solution toxicity has not been fully documented, nor is it known whether such solution-related staining is more common in Asian eyes. In addition, there have been differing reports of the relationships between lens care solutions and biomicroscopic signs other than corneal staining, depending on the type of solution investigated.14,20-22 Finally, racial differences in symptoms of discomfort or dryness are known to exist,23-25 but have not been investigated with respect to the use of lens care solutions. In the present study, we address these questions by examining the Asian and Caucasian ocular surface response and subject symptomatology with two biguanide-preserved contact lens care solutions used with daily silicone hydrogel contact lens wear.

Purpose: To ascertain whether a difference in the permeability of the corneal epithelium to fluorescein (Pdc) exists between Asians and non-Asians. Methods: From a multi-study database we extracted 632 records of baseline, open-eye Pdcmeasurements taken on both eyes of 176 subjects. Subjects were awake for a minimum of 4h before measurement, and were free of ocular disease and central corneal staining. Pdcwas transformed by natural logarithm to better approximate normality for statistical tests. Results: The mean ln(Pdc) in the Asian group was significantly greater than in the non-Asian group [-2.34 ln(nm/s) vs. -2.58 ln(nm/s); p

PurposeTo determine whether there are significant differences in standard clinical measures of vision, progressive addition lens (PAL)-specific vision tests, or subjective ratings and preferences between customized free-form and standard non-free-form PALs in an experienced wearing population. In addition, we aim to determine whether subjective or objective clinical outcomes depend on demographic, PAL usage, spectacle prescription, or frame fitting characteristics.MethodsIn a randomized, double-masked cross-over trial, 95 experienced wearers wore Zeiss Individual customized free-form PAL spectacles (test) and standard non-free-form PAL spectacles (control) for 1 week each. At dispensing and after 1 week of wear, subjects were tested for distance and near visual acuity under both high and low contrast; in addition, 30° off-axis visual acuity was measured using a novel apparatus, as was the horizontal extent of clear, undistorted vision at reading distance. Subjects also completed a set of questionnaires detailing their satisfaction levels, adaptation times, and preferences for test or control spectacles for different visual tasks.ResultsThe test spectacles were preferred overall and for distance, midrange, transitional and active vision, and rated higher in overall satisfaction (p = 0.006). There were no clinically important differences between test and control spectacles in standard clinical vision assessments. In the PAL-specific assessments, however, the horizontal extent of clear vision at reading distance was significantly greater with the test spectacles (p = 0.004).ConclusionsThere were statistically significant preferences for the optically customized free-form lenses over the non-free-form lenses. Subjects also reported a wider field of undistorted vision when looking through the reading zone of the test spectacles. Although standard clinical vision assessments are not sufficiently refined to detect important objective differences between the spectacle types, customization taking into account back vertex distance, segment height, pantoscopic tilt, and wrap angle can result in a superior subjective wearing experience for many PAL patients.

© 2016 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Purpose: To utilize the Pain Sensitivity Questionnaire (PSQ) to assess the influence of pain sensitivity on perceptions of ocular discomfort and dryness. Methods: Subjects completed a battery of questionnaires, including history of ocular and general health, contact lens wear history, the Ocular Surface Disease Index (OSDI) questionnaire, visual analog scale (VAS) 100-point rating scales to assess severity and frequency of average and end of day (EOD) discomfort and dryness, and the PSQ to assess pain sensitivity level. Masked subjects were then instructed to wear one inverted and one normally oriented soft contact lens contralaterally for 30 minutes to induce an inter-eye difference in comfort and dryness sensations. Subjects rated comfort and dryness in each eye on VAS every 5 minutes during contact lens wear. A slit lamp examination was performed to evaluate ocular surface health and to assess contact lens fit. Results: One hundred and fifty-three subjects (111 females, 42 males) completed the study. In separate models, a higher PSQ score was significantly associated with higher OSDI score (p = 0.002), lower average and EOD comfort (p = 0.005 and 0.001, respectively), and greater EOD dryness (p = 0.04). The minimum (0.14) and maximum (7.14) PSQ scores observed in our subject cohort (i.e., from the subjects who were the least and most sensitive to pain, respectively) corresponded to an estimated difference of 11 points on the OSDI, 20 points on the VAS scale for average comfort, 31 points for EOD comfort and 17 points for EOD dryness. In a mixed effects model, a higher PSQ score was significantly associated with a greater inter-eye difference in comfort (p = 0.013) and dryness (p = 0.010) during CL wear. Conclusions: Pain sensitivity influences perceptions of ocular discomfort and dryness, and should be taken into account when evaluating subjective assessments of these symptoms.

© 2015 American Academy of Optometry. 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.

PURPOSE: To develop a semiautomatic method to analyze morphology of cells and guttae in corneal endothelium. METHODS: Specular endothelial pictures from 42 and 21 subjects with healthy and guttate corneas, respectively, were analyzed independently by two observers with cell contour-extracting routines. One observer also analyzed healthy endothelia with the Corner method (Bambi). Differences between observers and between methods in mean cell area (MCA), coefficient of variation (CV), and percentage of cells with five, six, or seven sides were tested for significance with paired t tests. The Contour analysis of pictures with guttae included their mean area. RESULTS: There were no significant differences in MCA, CV, or the percentage of cells with five, six, or seven sides between the measurements obtained on repeated analysis by the same observer or on a second analysis performed by a different observer with the Contour method. However, the differences between the Contour and Bambi methods were statistically significant for MCA (337.5 +/- 37.7 vs. 327.7 +/- 36.5), CV (0.32 +/- 0.05 vs. 0.30 +/- 0.05), and percentage of cells with six and seven sides, but not for the percentage of five-sided cells. In subjects with guttata, the MCA was 561 +/- 170 microm, and the mean area of guttae was 1,538 +/- 849 microm. CONCLUSIONS: This detection algorithm is repeatable and reproducible, and it generates a cell border overlay useful in analyzing the morphology of cells and guttae. The analysis of corneal guttae could become a useful follow-up procedure to discriminate between patients with corneal guttata and Fuchs dystrophy.

Author(s): Graham, Andrew D; Lundgrin, Erika L; Lin, Meng C | Abstract: PurposeIn this article, we introduce a novel flow chart-based screening tool for the categorization of contact lens-induced dryness (CLIDE) and its impact on daily visual activities: the Berkeley Dry Eye Flow Chart (DEFC).MethodsOne hundred thirty (130) experienced soft contact lens wearers discontinued lens wear for 24 hrs, passed a baseline screening and eye health examination, completed the Ocular Surface Disease Index (OSDI) then were dispensed fresh pairs of their habitual lenses. After 6 hrs of wear, subjects were administered a battery of symptom questionnaires, and underwent non-invasive tear breakup time (NITBUT) measurement, grading of distortion in reflected topographer mires, grading of lens surface wettability, and a fluorescein examination of the ocular surface. Subjects returned after at least 48 hrs and repeated all assessments after 6 hrs of wear of a second fresh pair of habitual lenses.ResultsThe repeatability of the DEFC between visits was within 1%, and Limits of Agreement and Coefficient of Repeatability were comparable to those of the other CLIDE assessments. Higher DEFC score was significantly related to shorter pre-lens NITBUT, higher OSDI score, and higher Visual Analog Scale (VAS) ratings of average and end-of-day severity and frequency of dryness (all p l 0.001). For CLIDE as diagnosed based on DEFC score, the highest sensitivities and specificities were achieved by the OSDI and VAS ratings; pre-lens NITBUT exhibited good sensitivity but poor specificity. The optimum pre-lens NITBUT diagnostic threshold was found to be ≤ 2.0 sec for debilitating CLIDE, and the OSDI threshold was ≥ 11.4.ConclusionsThe DEFC provides a means of quickly categorizing CLIDE patients based on severity and frequency of symptoms, and on the degree to which symptoms impact daily life. The DEFC has several potential advantages as a CLIDE screening and monitoring tool, has good repeatability, and is significantly related to commonly employed clinical assessments for CLIDE.

Tear hyperosmolarity and tear film instability are key factors in the development of dry eye (DE) disease.1 Low aqueous flow (aqueous-deficient DE) or high aqueous evaporation (evaporative DE) can both lead to tear hyperosmolarity, which is associated with many pathophysiological changes. Experimentally induced “dry eye,” with its attendant tear hyperosmolarity, has been shown to stimulate ocular surface inflammation through increased expression and production of proinflammatory cytokines and chemokines in the tears2–6 and to result in corneal epithelial cell death by apoptosis.7 Ocular surface disease and tear hyperosmolarity have also been associated with goblet cell loss,8,9 which can lead to altered mucin expression10 and tear film instability.8,11 Ocular surface cooling attributed to aqueous evaporation, which has also been associated with tear hyperosmolarity, may stimulate sensory nerve fibers innervating the ocular surface, including polymodal nociceptors, mechanonociceptors, or cold thermoreceptors, and generate sensations of ocular discomfort.12,13 Although tear osmolarity has gained widespread acceptance as a diagnostic for DE disease,14–23 recent findings suggest that tear osmolarity measurements do not possess the very high sensitivity and specificity claimed by some studies15,24 and that it may have limited value in the diagnosis of DE.25 Similarly, although tear film instability has been linked to symptoms of dryness and discomfort in several studies,16,26–30 other studies have found contradictory evidence.14,15,31–33 Even among tear film stability assessments, it is not clear how well correlated are noninvasive and invasive (i.e., using sodium fluorescein dye) tear breakup times (TBUTs), or whether the two methods are even assessing the same type or aspect of tear breakup.27,29,32,34,35 Additionally, information on the relationship between tear osmolarity and tear film stability is emerging, with some studies reaching opposing conclusions.11,15,19,24,36–40 Clearly, there is a lack of consensus on many facets of the relationships among tear osmolarity, tear film stability, and dryness symptoms.41,42 This study proposes to provide additional evidence by (1) examining the relationships among tear osmolarity, TBUT (noninvasive and with fluorescein), and dryness symptoms measured using both subjective symptom rating scale questionnaires and a previously published categorical classification tool43 and (2) determining whether these relationships differ with subject demographic characteristics or contact lens (CL) use. Our goal is to gain further understanding of the complex interrelationships among common clinical and subjective assessments used in the diagnosis and treatment of DE disease.

PURPOSE: To develop and test a novel quantitative method of describing the corneoscleral junction, including metrics that reflect both the angle and the topography in this region of the ocular surface. METHODS: Forty-eight neophyte subjects were recruited (16 Asian, 16 white, and 16 Latino). Optical coherence tomography images of the nasal, temporal, superior, and inferior quadrants in both eyes were taken. Custom image analysis software was written in Matlab to allow the observer to select a point defining the center of the junction, from which 20 concentric circles were automatically drawn. The surface of the junction in the image was automatically located by edge-detection routines, and the circles intersecting this edge defined a series of points in the Cartesian plane. A linear regression was fit to these points, and a set of metrics based on the regression residuals was calculated. RESULTS: The sum of the squared orthogonalized residuals (SSRo) was the most repeatable metric and had the advantage of being unaffected by the orientation of the image. The SSRo was significantly greater in the nasal quadrant (p < 0.001), reflecting a more pronounced angle and/or rougher surface. The flattest and smoothest topography was found in the temporal quadrant. Whites had significantly higher SSRo than Asians and Latinos (p < 0.001). CONCLUSIONS: This study presents a novel metric for characterizing the angle and topography of the corneoscleral junction using optical coherence tomography and establishes differences among quadrants and between ethnic groups. © 2014 American Academy of Optometry.

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. Copyright © 2014 American Academy of Optometry.

Objective The primary aim of the Berkeley Contact Lens Extended Wear Study (CLEWS) was to test the hypotheses that extended wear of rigid gas-permeable (RGP) contact lenses with greater oxygen permeability (Dk) reduces the incidence of contact lens–associated keratopathy (CLAK) and increases the survival rate in RGP extended wear (EW). In this article we describe the clinical trial design in detail, present the results of subject recruitment and retention, and provide the baseline demographic and ocular characteristics of the CLEWS subjects, whose data will be analyzed to address the study aims in a companion article. Design A randomized, concurrently controlled clinical trial. Intervention Subjects were fitted with day wear (DW) high-Dk RGP lenses and then adapted to EW. Subjects who adapted to EW were then randomly assigned to either high- or medium-Dk RGP lenses for 12 months of 6-nights/week EW. Main outcome measures Slit-lamp assessment and grading of 17 possible keratopathies, measurement of refractive error and corneal curvature, and symptoms. Follow-up data were collected every 3 months. Results From 545 subjects entering the DW adaptation phase, 201 adapted to EW and were randomly assigned to medium- or high-Dk lenses for 12 months of EW. The baseline characteristics of the two study groups were similar and did not differ from the 344 DW subjects who failed to adapt to EW. The distributions of oxygen transmissibility for the two study groups were disjoint, indicating that each group received distinctly different levels of hypoxia. Conclusions We show that CLEWS was appropriately designed to address the study hypotheses, was conducted with regard for the safety of the subjects, and adhered to rigorous protocols designed to control for bias and ensure the integrity of study data. We establish the internal validity of between-group statistical comparisons and characterize our study population to permit informed evaluation of the applicability of our results to the contact lens–wearing population in general.

Objective To describe the principal clinical outcomes associated with 12 months use of rigid gas-permeable (RGP) extended wear contact lenses and address two primary study questions: (1) does extended wear (EW) of high oxygen transmissibility (Dk/t) RGP lenses reduce the incidence of ocular complications, and (2) does the wearing of high-Dk/t lenses reduce the rate of failure to maintain 6-night RGPEW over 12 months? Design A randomized, concurrently controlled clinical trial. Intervention Subjects who adapted to EW with high Dk (oxygen permeability) RGP lenses were randomized to either high Dk or medium-Dk RGP lenses for 12 months of 6-night EW. Main outcome measures Contact lens-associated keratopathies (CLAK), changes in refractive error and corneal curvature, and survival in EW. Results Two hundred one subjects were randomized to medium or high-Dk lenses for 12 months of EW. Sixty-two percent of the subjects in each group completed 12 months of EW; however, the probability of failure was significantly greater for the medium-Dk group. Although the risk of complications was similar for the two groups, the number of CLAK events that led to termination were 16 versus 5 for the medium-Dk and high-Dk groups, respectively. This suggests that the type of adverse response or the inability to reverse an adverse event was different for the group being exposed to the lower oxygen dose. Conclusions The level of oxygen available to the cornea has a significant impact on maintaining successful RGP extended contact lens wear, but not on the initial onset of CLAK. The number of clinical events leading to termination was substantially higher for the medium Dk group, which suggests that corneal hypoxia is an important factor in the development of CLAK. Although overnight contact lens wear should be recommended with caution and carefully monitored for early detection of ocular complications, it appears that high-Dk RGP lenses can be a safe and effective treatment for correction of refractive error for most individuals who can adapt to EW.

Properties of presumed mechanisms controlling photoreceptor alignments are partially defined. A phototropic mechanism normally dominates alignment, but do modest changes in orientations occur with dark patching? Here, new photopic Stiles–Crawford (SCE-I) determinations were made before patching (pre-patch), just after 8-days of dark-patching (post-patch), and 3 days after patch removal (recovery test). We tested at 0, 11 and 22° in the temporal retina of both eyes. Ten eyes of adult subjects were tested. SCE-I peak positions and Stile's parameter ‘rho’ were assessed. Dark-patching effects were small. Observations revealed meaningful corrective alignment overshoots with recovery in the light. Results suggest (1) the presence of multiple weak mechanisms affecting receptor alignments in the dark; (2) the phototropic mechanism to be dominant in the light; (3) the need for multiple test loci to be sampled in such studies, and (4) small changes in the SCE-I in the pupil plane can reflect meaningful events occurring at the retina.

Author(s): Lin, Meng C; French, Heather M; Graham, Andrew D; Sanders, Timothy L | Abstract: PurposeTo 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.MethodsIn 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.ResultsEpithelial 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.ConclusionsThirty-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.

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 24. h 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. © 2013 British Contact Lens Association.

Purpose. Ethnic variations in accommodative amplitude (AA) are not uncommon. Accommodation can become reduced in response to short-term wear of first near spectacles. Whether ethnicity has an influence on the magnitude of this adaptation is not well understood. We investigated the impact of first near spectacles on changes in AA and on convergence cross-link interactions in incipient presbyopes of Chinese and Caucasian ethnicities. Methods. Forty-one subjects (22 Caucasians and 19 Chinese) aged 36 to 44 years completed the study. Accommodative stimulus response function, AA, and AC/A and CA/C ratios were measured before and after single vision reading spectacles were used for near tasks over a 2-month period and then again 2 months after discontinuing near spectacle wear. Results. After wearing reading spectacles for 2 months, the accommodative stimulus response slopes and AC/A and CA/C ratios remained invariant irrespective of ethnicity. The accommodative, but not vergence, bias decreased (p 0.05). The nearpoint of accommodation shifted distally producing an average decrease in AA of 0.52 D from baseline (p 0.05). Recovery to near baseline values occurred after discontinuing the reading glasses for 2 months. Differences based on ethnicity were not significant. The baseline AA vs. age plots showed steeper slopes for Chinese than the Caucasian subjects in the sample. Conclusions. The pattern of adaptation by accommodation and cross-link interactions to short-term first reading spectacles is not influenced by ethnicity. (Optom Vis Sci 2012;89:435–445)

PurposeTo determine whether corneal biomechanical properties and intraocular pressure (IOP) are affected by eye rubbing and breath holding.MethodsCorneal 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 (ER(0)) and before breath holding (BH(0)), immediately after 2 episodes of eye rubbing (ER(1) and ER(2)), and during 2 episodes of breath holding (BH(1) and BH(2)).ResultsCorneal hysteresis, corneal resistance factor, and IOPg were significantly lower after ER(1) compared with ER(0) and were significantly lower after ER(2) compared with ER(1). In contrast, IOPcc did not decrease significantly. There were no significant differences among BH(0), BH(1), and BH(2) in any of the 4 outcomes.ConclusionsEye 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.

Author(s): Graham, Andrew D; Truong, Tan N; Lin, Meng C | Abstract: PurposeComposed 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.MethodsTwo 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.ResultsOf 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.ConclusionsThere 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.

To measure the effect of hypoxia and eye closure on epithelial permeability to fluorescein (P(dc)) during rigid lens extended wear (EW).Central corneal thickness (CT) and P(dc) were measured in 42 subjects with an optical pachometer and automated scanning fluorophotometer, respectively. All subjects had been successfully wearing rigid gas-permeable (RGP) lenses on a 6-night EW regimen, and each individual was randomized to wear either medium- or high-oxygen-permeable (Dk) RGP lenses (two types of siloxane-fluorocarbon polymer lenses with Dk of 49 and 92). CT and P(dc) measurements were performed at an afternoon visit (baseline) and were repeated in the morning after 8 hours of overnight wear. Subjects slept with a patch over the right eye. The patch was not removed until immediately before the morning measurement.The mean overnight swelling response for subjects in the medium-Dk group was greater than that in the high-Dk group. Results of a paired t-test indicate that the eye wearing the medium-Dk lens with a patch overnight had a significant increase in epithelial permeability. Results of mixed-effect models suggest that eye closure and lens-induced hypoxia are significant factors in altering P(dc).The results indicate that corneal epithelial permeability increases with hypoxic dose and that epithelial barrier function is impaired by overnight rigid lens wear.

Purpose: Phacodonesis can occur in pseudoexfoliation syndrome because of impaired zonular support. This study investigates whether the increased mobility of the lens influences anterior chamber depth in patients with pseudoexfoliation while assuming a prone position. Methods: Central anterior chamber depth was measured in 39 patients with clinically apparent unilateral pseudoexfoliation and elevated intraocular pressure. Patients were placed in a face-up position for 5 minutes, at which time anterior chamber depth and axial length were measured by A scan, and intraocular pressure was measured by Tonopen (Oculab, La Jolla, CA) in both eyes. The measurements were repeated on both eyes after 5 minutes in a face-down position. Results: No significant differences in intraocular pressure or axial length between the prone and supine positions were found in either eye. Anterior chamber depth in eyes with pseudoexfoliation decreased from a mean of 3.08 mm in the supine position to a mean of 2.95 mm in the prone position, whereas mean anterior chamber depth in the fellow eyes decreased from 3.01 mm to 2.97 mm. The decrease in anterior chamber depth when facing down in the eyes with pseudoexfoliation was significantly greater than in the fellow eyes. Conclusions: In patients with clinically apparent unilateral pseudoexfoliation, the lens seems to be more mobile in the affected eye. This results in a shallower anterior chamber when the head is placed in a prone position. Whether this fact might potentially lead to transient pupillary block when engaging in activities such as facing down while reading warrants further study.

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° 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 Opthalmology 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].

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.

Auto-refractors are frequently used to provide a starting point for subjective examinations. Ancillary personnel use auto-refractors to obtain rapid estimates of patients' refractive errors which can then be refined by clinicians. Automated refraction has also found use in studies of refractive error (e.g., Zadnik et al., 1993), due to its superior repeatability to clinician refraction (Zadnik et al., 1992; Adams et al., 1995).

Author(s): Lin, Meng C; Yeh, Thao N; Graham, Andrew D; Truong, Tan; Hsiao, Carol; Wei, Guan; Louie, Audrey | Abstract: PurposeTo 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.MethodsNinety-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.ResultsEpithelial 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).ConclusionsSubclinical 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.