Tear Film Aberration Dynamics and Vision- Related Quality of Life in Patients with Dry Eye Disease

Transcription

1 Tear Film Aberration Dynamics and Vision- Related Quality of Life in Patients with Dry Eye Disease Alexandre Denoyer, MD, PhD, 1,2 Ghislaine Rabut, OD, 1 Christophe Baudouin, MD, PhD 1,2,3 Objective: Corneal and ocular wavefront aberrations were recorded together with clinical examination results and patient-reported vision-related quality-of-life evaluation results to define the relevance of dynamic optical analysis of the eye in dry eye disease (DED). Design: Prospective and comparative clinical study. Participants: Forty DED patients and 40 age- and gender-matched control subjects. Methods: Serial measurements of ocular and corneal higher-order aberrations (HOAs) after blink were performed for 10 seconds using the KR-1 aberrometer (Topcon, Clichy, France). Vision-related health-targeted quality of life was evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. The clinical examination included tear film assessment (tear film break-up time and Schirmer I test), ocular surface damage assessment with the Oxford and van Bijsterveld indexes, and Meibomian dysfunction grading. Tear osmolarity also was measured. Main Outcome Measures: The time course of HOAs and modulation transfer function (MTF) was compared between groups and was analyzed in comparison with the OSDI and clinical data in DED patients. Results: The root mean square of ocular and corneal total HOAs, particularly third-order aberrations, significantly increased over the 10-second period in DED patients, whereas no change occurred in controls. Analysis of MTF revealed progressive degradation of ocular optical quality resulting from loss of contrast at intermediate and high spatial frequencies in DED patients compared with controls. The progression index for corneal HOAs was correlated with the subjective index of patient-reported visual outcomes and with objective clinical findings of tear film and ocular surface damage. Conclusions: Objective measurement of the time course of HOAs may constitute a new single instrument to evaluate and manage patients with DED because it reliably reflects the completeness of the disease. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119: by the American Academy of Ophthalmology. Dry eye disease (DED) is a common disorder of the tear film and ocular surface whose definition has evolved with recent epidemiologic studies as well as a better understanding of the pathophysiologic features of the disease. It is estimated to affect from 5% to more than 30% of the population, depending on the diagnostic criteria. 1 Dry eye ranges from mild to severe disease, but most patients experience chronic ocular discomfort associated with impaired daily visual function and subsequent vision-related qualityof-life disturbances that can impact health status. 2 In clinical practice, the main difficulty in managing DED stems from the variability of the symptoms, the lack of a single reliable diagnostic test, and weak correlations between clinical tests, optical and biological examinations, and patient-reported deterioration in quality of life. Specific questionnaires such as the Ocular Surface Disease Index (OSDI) have been developed to assess the vision-related health-targeted quality of life with DED. 3 However, poor correlations between signs and symptoms have been found in DED, 4,5 so a reliable instrument to measure the impact of DED on daily life is still a critical aspect of characterizing the disease and managing treatment. The precorneal tear film plays an important role in ocular optical quality because it is the most anterior refractive surface of the eye. Homogenous thinning of the tear film can have little effect on the surface s optical quality, whereas pathologic tear film irregularities can significantly affect the light pathway. 6,7 According to a recent overview arising from the 2007 International Dry Eye Workshop, DED in many patients results in mixed aqueous tear deficiency which comprises Sjögren syndrome and non-sjögren syndrome dry eye and tear hyperevaporation. 8 In every case, DED-related instability of the tear film introduces wavefront higher-order aberration (HOA) changes that contribute to a decrease in the quality of vision. Interest has increased in new methods to quantify involvement of the tear film in ocular optical properties. 9 Wavefront aberrometry with simultaneous acquisition has been reported to detect fluctuations accurately with time of ocular aberrations. 10 In addition, previous studies investigated ocular optical fluctuations using the double-pass method to assess the modulation transfer function (MTF) changes after blink 11 or retroillumination to correlate the distribution of tear thickness with changes in ocular optical properties. 12,13 Others performed 2012 by the American Academy of Ophthalmology ISSN /12/$ see front matter Published by Elsevier Inc

2 Ophthalmology Volume 119, Number 9, September 2012 serial corneal topography measurement 14,15 or videokeratoscopy 16,17 to determine aberrations from corneal elevation data to specify the cornea tear film system contribution to overall wavefront aberration changes with time. To date, accurate surrogate markers are still needed for dry eye to facilitate multicenter and international collaborative clinical trials and to reach the standards of regulatory authorities. Questionnaires of vision-related health-targeted quality of life are used to assess patient-centered daily visual function. In addition, optical methods are being developed to study the impact of DED-related tear film changes on visual function. Little is known, however, about the true correlation between objective measurements of optical quality of the eye and subjective consequences in vision-related quality of life. This prospective and casecontrolled clinical study was conducted to evaluate DEDrelated changes in the time course of tear film HOAs in comparison with patient-reported degradation in quality of life and with clinical damage. The aim was to determine whether a targeted quantitative analysis of optical properties of the eye could reflect reliably the entire disease and thus constitute a new single method to standardize the diagnosis of DED as well as to assess eligibility and changes over time in clinical trials. Methods The study was conducted in the Clinical Investigation Centre for Ocular Surface Pathology (Centre Hospitalier National d Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503, Paris, France) in accordance with the Declaration of Helsinki, Scotland amendment, Ethics committee approval was obtained from the Comité de Protection des Personnes (Ile de France V, agreement number 10793), and all patients gave informed consent. Subjects Forty patients with DED and 40 controls were included prospectively. Dry eye was diagnosed by the association of ocular symptoms, tear film abnormalities (Schirmer I test results 5 mm/5 minutes, tear film breakup time [TBUT] 10 seconds) and ocular surface damage (corneal and conjunctival staining) according to the 2007 International Dry Eye Workshop criteria. 8 Only the subjects with a best-corrected visual acuity of at least 0 logarithm of the minimum angle of resolution and without any superficial punctuate keratitis in the central 4 mm of the cornea were included because this study focused on visual impairments related to pathologic tear film dynamics but not to extensive corneal damage. Exclusion criteria were any ocular pathologic features but DED, eyelid malpositions or dynamic disorders, previous ocular or eyelid surgery, contact lens wear, local or general treatment changes within the last 3 months, and pregnancy. Healthy age- and gendermatched subjects with no ocular pathologic features were included as controls. Clinical Examination Slit-lamp evaluations included TBUT measurement (seconds), Schirmer I test (mm/5 minutes), ocular surface fluorescein staining (grade 0 5, according to the Oxford score), lissamine green staining (0 9, according to the van Bijsterveld score), and Meibomian dysfunction grading based on the quality of expressed secretions (range, 0 3; 0 clear; 1 cloudy; 2 granular; 3 toothpaste) averaged in 8 glands of the lower lid. 18 All the patients had been tested previously for Sjögren syndrome. Vision-Related Quality of Life Before the clinical examination, a trained interviewer (G.R.) administered the French version of the OSDI questionnaire, which was developed to quantify the specific impact of DED on visiontargeted health-related quality of life. 3 This specific disease questionnaire includes 3 subscales: ocular symptoms, vision-related activities of daily living, and environmental triggers. The 3 subscale scores (0 100) were computed for OSDI ocular symptoms, OSDI vision-related activities of daily living, and OSDI environmental triggers, as well as an overall averaged score (0 100). Tear Osmolarity Tear osmolarity was measured before the clinical examination using the Tearlab osmolarity system (Tearlab, San Diego, CA). Table 1. Comparative Analysis of Group Profiles, Tear Osmolarity, and Ocular Surface Disease Index Scores between Dry Eye Patients and Age- and Gender-Matched Controls with Characteristics of Sjögren Syndrome and non-sjögren Dry Eye Patients Detailed Dry Eye Group (n 40) [Sjögren Syndrome/Non-Sjögren Syndrome] Control Group (n 40) P Value (t test) Age (yrs) [51.9/56.1] Gender ratio (M/F) 0.25 [0.14/0.31] 0.25 TBUT (s) [4.2/5] Schirmer I test results (mm/5 min) [4.8/11.8] Oxford grade (0 5) [1.3/1.1] Van Bijsterveld score (0 9) [3.3/2.3] Meibomian dysfunction (0 3) [1.3/0.9] Tear osmolarity (mosm) [309.9/300.1] OSDI overall score (0 100) [45.7/40] OSDI symptoms [45.7/40] OSDI function [46.4/38.5] OSDI triggers [54.8/60.3] F female; M male; OSDI Ocular Surface Disease Index; TBUT tear film break-up time. 1812

3 Denoyer et al Tear Film Aberrations and QoL in DED Dynamic Aberrometry Serial measurements of corneal and ocular wavefront aberrations were performed simultaneously every second for 10 seconds after blinking using the recently developed KR-1W aberrometer (Topcon, Clichy, France). All the patients were examined between 2:00 and 4:00 PM to minimize the bias related to nyctohemeral variations of the tear film and corneal topography. One drop of preservative-free topical anesthesia was applied at least 5 minutes before the measurement to prevent blinking and to minimize patient discomfort. Corneal and ocular HOAs were recorded in mesopic conditions without any pharmacologic mydriasis, were analyzed by expanding the set of Zernike polynomials up to the sixth order, and were expressed for the central 4-mm diameter according to the recommendations of Thibos et al. 19 The root mean square as well as the point spread function and area under the curve of modulation transfer function (aucmtf; from 3 to 30 cycles per degree) were calculated. The progression index of third- to sixth-order HOAs was defined as the slope of the linear regression line of HOAs throughout the recording period. Figure 1. Comparative analysis of wavefront aberration dynamics between dry eye patients and age- and gender-matched controls. A, B, Significant progression with time of corneal higher-order aberrations in dry eye patients only (**P 0.01, repeated-measures 1-way analysis of variance). C, Significant difference in the progression index for ocular and corneal higher-order aberrations between dry eye patients and controls (*P 0.05, **P 0.01, t test). HOA higher-order aberration. Figure 2. Comparison of the modulation transfer function progression with time between dry eye patients and age- and gender-matched controls. A, Area under the curve of modulation transfer function (aucmtf) decreased significantly in dry eye patients at 7 to 10 seconds (s) after blinking compared with controls (**P 0.01, t test). B, Light transmission decreased progressively at intermediate (12 cycles per degree [cpd]) and high (30 cpd) spatial frequencies in dry eye patients. DED dry eye disease. 1813

4 Ophthalmology Volume 119, Number 9, September 2012 Statistical Analysis All data are given as mean standard deviation. For ocular examinations clinical evaluation, tear osmolarity measurement, and wavefront aberrometry 1 eye per patient was selected using a random number table so as not to bias the statistical relevance of the results. Data were controlled for normality, homogeneity of variances, and sphericity to perform the adequate tests. A repeatedmeasures 1-way analysis of variance was used to analyze sequential changes in aberrations. The 2 groups were compared using parametric t tests. In the DED group, scatter plots and Spearman correlation coefficients were used to assess the association between pairs of variables. A stepwise regression procedure was performed for multiple correlations. The probability level of significance was adjusted according to the post hoc Bonferroni procedure to maintain an overall type I error equal to Results Patient Features and Vision-Related Quality of Life The profile, clinical features, tear osmolarity, and OSDI scores of each group are detailed and compared in Table 1. A significant difference in the OSDI overall score as well as in OSDI subscores was found between DED patients and controls. Comparative Analysis of Aberration Dynamics Between Groups The time course of corneal HOAs is detailed for each group in Figure 1A, B. In dry eye patients, there was a significant variation in total corneal HOAs (P 0.01, repeated-measures analysis of variance), third-order coma (P 0.01), and third-order trefoil (P 0.01), whereas no significant change was found in the control group throughout the recording period. The progression index of ocular total HOAs, corneal total HOAs, and corneal third-order aberrations was higher in dry eye patients than in controls (Fig 1C). The aucmtf was significantly lower in DED patients than in controls at 7, 8, 9, and 10 seconds after blinking (P 0.01 at each time, t test), as detailed in Figure 2A. Degradation of ocular optical quality in dry eye was related to a progressive decrease in MTF at intermediate and high spatial frequencies (Fig 2B). Differences in the time course of the point spread function and MTF between groups are illustrated in Figure 3. Relationships Between Clinical Examination, Vision-Related Quality of Life, and Corneal Aberration Dynamics in Dry Eye Correlations between clinical data, OSDI scores, and the HOA progression index are detailed in Table 2. Considering clinical data, the OSDI overall score was correlated negatively with TBUT and Schirmer I test results; in parallel, the progression index for third- to sixth-order aberrations was correlated negatively with TBUT and correlated positively with the van Bijsterveld score. Analysis of the relation between patient-centered vision-related quality of life and objective measurement of corneal aberration dynamics revealed that the HOA progression index was correlated with the OSDI overall score as well as with the OSDI ocular symptoms and OSDI vision-related activities of daily living subscores. No significant relation was found between any specific Zernike expanded HOA neither third-order, fourth-order, fifth-order, or sixthorder HOAs, nor third-coma, third-trefoil, or fourth-spherical and any other data. After a stepwise regression procedure, the OSDI overall score was found to depend significantly on the HOA progression index only (R 2 increment 0.37; P 0.01). In parallel, the HOA progression index depended on the TBUT (R 2 increment 0.42; P 0.01) and OSDI overall score (R 2 increment 0.07; P 0.05). The linear relations between these data are shown in Figure 4. Discussion Approximately 5 million Americans 50 years and older are estimated to have dry eye. 1 Dry eye disease refers to a multifactorial disease that can present in various ways; it recently was defined as the association of symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. 8 All DED patients have in common pathologic tear film instability that impacts visual performance, adversely affecting activities of daily living. A consensus needs to be reached OSDI Symptoms OSDI Function OSDI Triggers Table 2. Correlations among the Ocular Optical Analysis, Third Sixth HOA PI with Time Third-Order Coma PI with Time OSDI 0.79* 0.67* 0.32* 0.29* 0.01 OSDI symptoms 0.48* OSDI function OSDI triggers Third-/sixth-order 0.23 HOA PI Third-order coma PI Third-order trefoil PI Tear osmolarity TBUT Schirmer Oxford Van Bijsterveld HOA higher-order aberration; OSDI Ocular Surface Disease Index; PI progression index with time; TBUT tear film break-up time. Optical data are presented as the progression index with time of higher-order aberrations (Pearson coefficient correlation r 2,*P 0.01, P 0.05). 1814

5 Denoyer et al Tear Film Aberrations and QoL in DED Figure 3. Time-course of the point spread function (PSF) and modulation transfer function (MTF) in healthy subjects and in dry eye patients. Optical quality of the eye was degraded over time in dry eye patients (solid line) compared with controls (dashed line). DED dry eye disease; s seconds. based on the diagnostic criteria, and accurate surrogate markers must be identified reflecting both clinical signs and patient-reported symptoms and subsequent consequences on daily living, which have been considered inadequately in the past. Through a prospective analysis of the clinical examination, tear film HOA dynamics and vision-related quality of life in a cohort of dry eye patients and their age- and gender-matched controls, this study demonstrates for the first time that the time course of tear film HOAs accurately correlates with both the clinical examination and patient-centered visual outcomes, recommending this examination as a potential new single method to manage DED. Most patients with DED report discomfort or irritancy symptoms, and problems performing daily visual tasks that require specific lacrimal and blinking conditions such as reading or driving. Patient-reported measurements of eye disease based on symptoms, functioning, and perception are referred to as vision-related, health-targeted quality-of-life instruments. Interest has increased in the development of valid and reliable indexes of vision-related quality of life for both the diagnosis and assessment of treatment effectiveness for DED. 20 Generic questionnaires, such as the National Eye Institute Visual Function Questionnaire, and disease-specific questionnaires, such as the OSDI, 4 have been used to assess better the general impact of DED. Nevertheless, nonexistent or weak correlations have been found previously between ocular symptoms and signs. 4,21 24 Actually, patient-reported symptoms are likely correlated with a global clinical score, as reported by Begley et al, 5 meaning that symptoms are more influential than clinical signs for grading disease severity. In this study, the OSDI overall score was correlated with the TBUT and Schirmer test results but not with conjunctival or corneal damage. Indeed, symptoms and tolerance of DED as well as patient-centered daily discomfort with ocular symptoms are found to vary widely between patients. Accuracy of quality-of-life instruments also depends on the interviewer as well as on the time it is administrated. Moreover, the repeatability and responsiveness of these instruments are questionable, as pointed out by the 2007 International Dry Eye Workshop, because ocular symptoms and their perception over time are known to be integrated by patients in this type of chronic disease. Hence, vision-related quality-of-life questionnaires seem to be essential and complementary instruments in DED evaluation but are not sufficient alone. Reduction in visual function, commonly manifested as blurred vision and glare, can impact quality of life widely, even though the best-corrected visual acuity is considered normal with standard charts. It may result from tear film Ocular Surface Disease Index Scores, and Clinical Examination Third-Order Trefoil PI Tear Osmolarity TBUT Schirmer Score Oxford Van Bijsterveld Blepharitis * * * *

6 Ophthalmology Volume 119, Number 9, September 2012 Figure 4. Linear relations between the progression index for higher-order aberrations (HOAs), tear film break-up time (TBUT), and ocular surface disease index (OSDI) overall score. After a stepwise regression procedure, the progression index for HOAs was found to be correlated significantly with TBUT (P 0.01) and with OSDI overall score (P 0.05). instability causing a decrease in TBUT and irregular tear film layer. 12,25 Indeed, any local change in the tear film thickness introduces HOAs into the optical system of the eye, as initially studied by Rieger. 6 Recording of ocular wavefront aberrations has been used previously to determine fluctuations of optical properties accurately in healthy and DED patients as well as to assess the efficacy of topical treatments on optical quality In addition, the involvement of the tear film behavior in the ocular optical quality has been studied objectively by the double-pass method 11,29 and retroillumination, 12,13 or by assessing anterior eye aberrations with interferometry, with corneal topography, and with videokeratoscopy extended to wavefront aberration analysis ,33 In this study, serial measurements of corneal aberrations together with Hartmann-Shack wavefront aberrometry were performed prospectively in 40 DED patients and their age- and gender-matched controls. This study found a significant increase over time, defined as the progression index, in both corneal and total HOAs of DED patients compared with healthy controls. Previous studies revealed either higher HOAs, significant increase in time of HOAs, or instability of HOA dynamics in DED compared with healthy subjects In 2006, Koh et al 10 originally defined the stability index as the slope of progression with time of total ocular HOAs. They reported 3 different profiles of aberration changes in healthy subjects, namely a stable pattern, a small-fluctuation pattern, and a sawtooth pattern, suggesting putative tear film instability for those presenting a sawtooth pattern. The same authors reported a significant upward curve for ocular HOAs in patients with short TBUTs compared with controls. 37 More precisely, they found an increase in ocular coma-like and spherical-like aberrations for a 4-mm central diameter from 5 and 6 seconds after blinking, respectively. In accordance with these findings relative to entire eye aberrations, the progression index of HOAs was related to a progressive increase in corneal third-order coma and trefoil. However, significant changes in fourth-spherical aberration were not found. Montés-Mico et al 35 reported a progressive increase in coma-like aberrations in 13 DED patients. The authors also suggested that an increase in coma-like aberration, especially in its vertical components, could result from gravity and lid movements together with relative tear film thinning in the superior cornea. Contrary to these findings reported for a 7-mm diameter pupil, the present study did not find any specific enhancement in vertical coma. Higher-order aberrations could have been measured for a large diameter pupil, but the results were computed for a 4-mm pupil because the study aimed to measure the optical qualities of the eye in daily living conditions, which may explain these differences. Qualitative analysis of the point spread function and the MTF also revealed progressive degradation of the optical quality of the front cornea resulting from DED. In healthy subjects, aucmtf reached a maximum value at approximately 5 seconds after a blink, as previously reported for total or corneal HOAs, 11,15 without, however, significant variation over the recording period. On the contrary, maximum aucmtf of DED patients was achieved earlier (approximately 1 second after a blink) and then decreased as a linear function of time until being significantly lower in DED patients than in controls. Accordingly, Montés-Mico et al 35 reported that wavefront aberrations achieved the lowest value at less than 3 seconds after a blink as opposed to 6 seconds in healthy subjects. Interestingly, the decrease in aucmtf observed in this study was mainly the result of a drop in light transmission at intermediate and high spatial frequencies. Using a subjective contrast sensitivity tester, Puell et al 38 reported that DED patients presented low-contrast sensitivities for intermediate and high frequencies compared with normal subjects. However, contrast sensitivity testing in DED has given conflicting reports (Teson M, Castellanos E, Gonzales-Garcia MJ, et al. Analysis of visual function in subjects with evaporative-type dry eye disease. Invest Ophthalmol Vis Sci 50:527, 2009) 39,40 because of several drawbacks, such as the type of test used, the patient-related learning curve for these subjective tests, and the variability in disease severity of the patients included. Very little is known about the correlations between the analysis of ocular optical properties and the other data collected in DED. Herein, the progression index of corneal HOAs was found to be correlated with TBUT and with the van Bijsterveld index, contrary to the OSDI score, which was not significantly associated with any clinical score of 1816

7 Denoyer et al Tear Film Aberrations and QoL in DED ocular surface damage, as previously reported. 23,24 Continuous recording of topography data has been used previously to determine tear film build-up and TBUT. 33,41 Koh et al 27 reported higher ocular HOAs in DED patients with central punctuate keratitis than in patients with clear central cornea, but did not find any difference in the time course of HOAs between DED and healthy subjects. This difference may find an explanation in the difference in aberration measurement, that is, ocular versus corneal aberrations, in the patients epidemiologic characteristics, in the difference in diagnosis criteria that combine clinical signs with symptoms in this study, and in the absence of use of a mydriatic agent. However, the use of topical anesthesia, which was necessary to keep the eyes from blinking for 10 seconds, may have influenced the measurements, even if used in both DED and control groups. Because the study aimed at precisely determining the influence of tear film degradation, patients with 4-mm central superficial punctual keratitis were not included, without affecting the severity range of the panel. Hence, no difference in ocular and corneal aberrations measured immediately after a blink was found, but a correlation between the degradation of optical qualities over time and the clinical grading of the disease was found. Interestingly, the progression index of HOAs also was correlated with the OSDI overall score together with OSDI ocular symptoms and OSDI vision-related activities of daily living subscores. Ridder et al 42 reported a correlation between objective measurement of anterior HOAs and subjective assessment of contrast sensitivity. Despite the limitations explained previously, it would have been interesting to measure subjective contrast sensitivity to reinforce the findings. Nevertheless, this is the first study, to the authors knowledge, reporting a significant correlation in DED between an objective index of degradation of optical quality of the eye and both the clinical grading and patient-reported, vision-related quality of life. Assessment of disease severity is still a crucial point for the management of DED. Many procedures exist to measure all aspects of the disease: symptoms, clinical signs, visual function, and vision-related health-targeted quality of life. The ideal test for detecting and following up dry eye must be objective, quantitative, sensitive, 43 and easy to administer, and it should consider the disease from every angle. This study demonstrated that a specific analysis of the time course of tear film related HOAs provides objective and quantitative data that are correlated with both clinical signs and patient-reported outcomes, supporting this procedure as a powerful tool for the management of DED from diagnosis in daily practice to treatment efficacy assessment in clinical trials. References 1. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye Workshop (2007). Ocul Surf 2007;5: Goto E, Yagi Y, Matsumoto Y, Tsubota K. Impaired functional visual acuity of dry eye patients. Am J Ophthalmol 2002;133: Schiffman RM, Christianson MD, Jacobsen G, et al. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol 2000;118: Schein OD, Tielsch JM, Munoz B, et al. Relation between signs and symptoms of dry eye in the elderly: a populationbased perspective. Ophthalmology 1997;104: Begley CG, Chalmers RL, Abetz L, et al. The relationship between habitual patient-reported symptoms and clinical signs among patients with dry eye of varying severity. Invest Ophthalmol Vis Sci 2003:44: Rieger G. The importance of the precorneal tear film for the quality of optical imaging. Br J Ophthalmol 1992;76: Koh S, Maeda N, Kuroda T, et al. Effect of tear film break-up on higher-order aberrations measured with wavefront sensor. Am J Ophthalmol 2002:134: The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye Workshop (2007). Ocul Surf 2007;5: Montés-Mico R, Cervino A, Ferrer-Blasco T, et al. The tear film and the optical quality if the eye. Ocul Surf 2010;8: Koh S, Maeda N, Hirohara Y, et al. Serial measurements of higher-order aberrations after blinking in normal subjects. Invest Opthalmol Vis Sci 2006;47: Montés-Mico R, Alio JL, Charman WN. Postblink changes in the ocular modulation transfer function measured by a doublepass method. Invest Ophthalmol Vis Sci 2005;46: Tutt R, Bradley A, Begley C, Thibos LN. Optical and visual impact of tear break-up in human eyes. Invest Ophthalmol Vis Sci 2000;41: Himebaugh NL, Wright AR, Bradley A, et al. Use of retroillumination to visualize optical aberrations caused by tear film break-up. Optom Vis Sci 2003;80: Montés-Mico R, Alio JL, Muñoz G, et al. Postblink changes in total and corneal ocular aberrations. Ophthalmology 2004; 111: Ferrer-Blasco T, Garcia-Lazaro S, Montés-Mico R, et al. Dynamics changes in the air-tear film interface modulation transfer function. Graefes Arch Clin Exp Ophthalmol 2010; 248: Guiaro A, Artal P. Corneal wave aberration from videokeratography: accuracy and limitations of the procedure. J Opt Soc Am A Opt Image Sci Vis 2000;17: Goto T, Zheng X, Klyce SD, et al. A new method for tear film stability analysis using videokeratography. Am J Ophthalmol 2003;135: Bron AJ, Benjamin L, Snibson GR. Meibomian gland disease: classification and grading of lid changes. Eye (Lond) 1991;5: Thibos LN, Applegated RA, Schwiegerling JT, Webb R. Report from the VSIA taskforce on standards for reporting optical aberrations of the eye. J Refract Surg 2000;16: S Bandeen-Roche K, Munoz B, Thielsch JM, et al. Self-reported assessment of dry eye in a population-based setting. Invest Ophthalmol Vis Sci 1997;38: Bjerrum KB. Test and symptoms in keratoconjunctivitis sicca and their correlation. Acta Ophthalmol Scand 1996; 74: Nichols KK, Nichols JJ, Mitchell GL. The lack of association between signs and symptoms in patients with dry eye disease. Cornea 2004;23:

8 Ophthalmology Volume 119, Number 9, September Vitale S, Goodman LA, Reed GF, Smith JA. Comparison of the NEI-VFQ and OSDI questionnaires in patients with Sjögren s syndrome-related dry eye. Health Qual Life Outcomes [serial online] 2004;2:44. Available at: Accessed February 28, Mizuno Y, Yamada M, Miyake Y, Dry Eye Survey Group of the National Hospital Organization of Japan. Association between clinical diagnostic tests and health-related quality of life surveys in patients with dry eye syndrome. Jpn J Ophthalmol 2010;54: Liu H, Thibos L, Begley CG, Bradley A. Measurement of the time course of optical quality and visual deterioration during tear break-up. Invest Ophthalmol Vis Sci 2010;51: Airiani S, Rozell J, Lee SM, Braunstein RE. The effect of lubricant eye drops on ocular wavefront aberrations. J Refract Surg 2005;21: Koh S, Maeda N, Hirohara Y, et al. Serial measurements of higher-order aberrations after blinking in patients with dry eye. Invest Ophthalmol Vis Sci 2008;49: Hirohara Y, Mihashi T, Koh S, et al. Optical quality of the eye degraded by time-varying wavefront aberrations with tear film dynamics. Jpn J Ophthalmol 2007;51: Albarran C, Pons AM, Lorente A, et al. Influence of the tear film on optical quality of the eye. Cont Lens Anterior Eye 1997;20: Doane MG. An instrument for in vivo tear film interferometry. Optom Vis Sci 1989;66: Nichols JJ, Nichols KK, Puent B, et al. Evaluation of tear film interference patterns and measures of tear break-up time. Optom Vis Sci 2002;79: Goto E, Tseng SC. Differentiation of lipid tear deficiency dry eye by kinetic analysis of tear interference images. Arch Ophthalmol 2003;121: Iskander DR, Collins MJ, Davis B. Evaluating tear film stability in the human eye with high-speed videokeratoscopy. IEEE Trans Biomed Eng 2005;52: Montés-Micó R, Cáliz A, Alió JL. Wavefront analysis of higher order aberrations in dry eye patients. J Refract Surg 2004;20: Montés-Mico R, Alio JL, Charman WN. Dynamic changes in the tear film in dry eyes. Invest Ophthalmol Vis Sci 2005;46: Wang Y, Xu J, Sun X, et al. Dynamic wavefront aberrations and visual acuity in normal and dry eyes. Clin Exp Optom 2009;92: Koh S, Maeda N, Hori Y, et al. Effects of suppression of blinking on quality of vision in borderline cases of evaporative dry eye. Cornea 2008;27: Puell MC, Benitez-del-Castillo JM, Martinez-de-la-Casa J, et al. Contrast sensitivity and disability glare in patients with dry eye. Acta Ophthalmol Scand 2006;84: Huang FC, Tseng SH, Shih MH, Chen FK. Effect of artificial tears on corneal surface regularity, contrast sensitivity, and glare disability in dry eyes. Ophthalmology 2002; 109: Rolando M, Lester M, Macri A, Calabria G. Low spatialcontrast sensitivity in dry eyes. Cornea 1998;17: Iskander DR, Collins MJ. Applications of high-speed videokeratoscopy. Clin Exp Optom 2005;88: Ridder WH III, LaMotte J, Hall JQ Jr, et al. Contrast sensitivity and tear layer aberrometry in dry eye patients. Optom Vis Sci 2009;86:E Szczesna DH, Alonso-Caneiro D, Iskander DR, et al. Predicting dry eye using noninvasive techniques of tear film surface assessment. Invest Ophthalmol Vis Sci 2011;52: Footnotes and Financial Disclosures Originally received: September 27, Final revision: March 2, Accepted: March 2, Available online: May 15, Manuscript no Quinze-Vingts National Ophthalmology Hospital, Paris, France. 2 INSERM, UPMC University Paris, Institut de la Vision, Paris, France. 3 Ambroise Paré Hospital, APHP, University of Versailles St. Quentin en Yvelines, Versailles, France. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Correspondence: Alexandre Denoyer, MD, PhD, Centre Hospitalier National d Ophtalmologie des Quinze-Vingts, 28 rue de Charenton, Paris, France. alexandre.denoyer@gmail.com. 1818