LASER IN SITU KERATOMILEUSIS (LASIK) HAS BECOME

Transcription

1 The Effect of Punctal Occlusion on Wavefront Aberrations in Dry Eye Patients After Laser in Situ Keratomileusis BO HUANG, MD, PHD, M. AZIM MIRZA, MD, MUJTABA A. QAZI, MD, AND JAY S. PEPOSE, MD, PHD PURPOSE: To compare the wavefront aberrations in post-laser in situ keratomileusis (LASIK) dry eye patients before and after punctal occlusion. DESIGN: Prospective, comparative, nonrandomized study. METHODS: Wavefront aberrometry was performed on 16 eyes of eight patients with dry eyes after LASIK surgery. Wavefront measurements were taken before and 1 month after punctal plug placement and compared with 10 eyes of post-lasik patients without clinically dry eyes measured twice 1 month apart. Student t tests were used to assess the statistical significance of differences between pre- and post-punctal plug measurements. RESULTS: Punctal occlusion in the post-lasik dry eye patients significantly reduced total, lower, and higher order wavefront aberrations by 47% to 63% (P <.01). Among higher-order aberrations, there were significant reductions in coma and spherical aberration but not in trefoil, after punctal occlusion. The reduction of wavefront aberrations by punctal occlusion in post-lasik dry eye patients resulted in a significant improvement in quantitative visual acuity assessed using an Early Treatment of Diabetic Retinopathy Study chart and in subjective qualitative vision, confirmed by convolutional analysis using image simulation. No statistically significant differences in any of these metrics were found in the post-lasik control group without clinically dry eyes measured twice at a similar time interval. CONCLUSIONS: Wavefront aberrometry provides a useful, objective assessment of post-lasik dry eye Additional material for this article can be found on ajo.com. Accepted for publication July 29, From the Pepose Vision Institute, St. Louis, Missouri (B.H., M.A.M., M.A.Q., J.S.P.), and the Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri (M.A.Q., J.S.P.). This study was supported in part by the Midwest Cornea Research Foundation, Inc, St. Louis, Missouri. Inquiries to Jay S. Pepose, MD, PhD, Pepose Vision Institute, Baxter Rd, Suite 205, Chesterfield, MO 63017; fax: (636) ; jpepose@peposevision.com patients before and after punctal plug placement. Aggressive treatment of dry eyes may be important before obtaining wavefront measurements that serve as the basis for planning refractive corneal laser treatments and retreatments. (Am J Ophthalmol 2004;137: by Elsevier Inc. All rights reserved.) LASER IN SITU KERATOMILEUSIS (LASIK) HAS BECOME the most frequently performed lamellar keratorefractive surgery. That is, in part, because of more rapid visual recovery, less discomfort, lower regression, and minimal stromal haze when compared with laser surface ablation. Despite these positive attributes, however, dry eyes appear to be a common finding during the postoperative healing phase after LASIK surgery. 1 4 Typical dry eye symptoms, including ocular irritation, grittiness, burning, foreign body sensation, photophobia, and fluctuation of vision with blink, 5 7 are frequently reported after LASIK surgery, and an associated neurotrophic corneal epitheliopathy has been observed by various authors. 8 These signs and symptoms of LASIK-induced dry eye are common, usually temporary side effects lasting up to 18 months after surgery. 2,4 Previous studies suggest that ocular irritation linked to LASIK-induced dry eye syndrome is the result of a multifactorial process, which includes decreased corneal sensation and alteration of ocular surface and lacrimal gland function after surgery The LASIK procedure severs the nerves that course from the limbus in a centripetal fashion to innervate the stroma and epithelium of the central cornea. 9,11 Denervation of the corneal flap then results in a loss of trophic influence to the epithelium, 8 as well as a decrease in adequate tear production and clearance. 2,11 Recent studies have also indicated a significant decrease in blink rate up to 1 year after LASIK. 3 Many of the subjective, qualitative complaints of patients with post-lasik dry eyes cannot be fully assessed by conventional measures of visual acuity testing that assess the minimal angle of resolution using high contrast optotypes. The quality of vision is perhaps more sensitively measured by other metrics, such as spatial-contrast sensi BY ELSEVIER INC. ALL RIGHTS RESERVED /04/$30.00 doi: /s (03)

2 tivity and glare disability testing 12 after LASIK surgery. The dry eye induced by LASIK could result in decreased image quality on the retina by causing scattering of light or optical aberration, which can be measured by a wavefront sensor. 13 A recent study has provided evidence for significantly increased higher-order aberrations after tear film breakup measured with a Hartmann-Shack wavefront sensor. 14 In this study we sought to analyze and compare changes in whole eye wavefront and subjective refraction before and after insertion of punctal plugs in patients with post-lasik dry eye syndrome. Convolutional analysis was also performed to simulate these patients vision before and after punctal plug placement. METHODS SIXTEEN EYES OF EIGHT PATIENTS WHO UNDERWENT LASER in situ keratomileusis from February 2000 to August 2002 were enrolled in the study. The patients ranged in age from 35 to 61 years (mean, 48.9, standard deviation (SD) 7.7 years). The attempted correction ranged from 1to 9.75 diopters (mean diopters). The LASIK surgery was performed using both VISX Star 3 Excimer Laser system (Santa Clara, California, USA) and a Technolas 217A laser (Bausch & Lomb, San Dimas, California, USA). In all cases, a Hansatome microkeratome (Bausch & Lomb, Rochester, New York, USA) with a 160 m head and either 8.5 or 9.5 mm diameter ring was used to create cornea flaps. Full informed consent was obtained from each patient enrolled in this study. Inclusion criteria for the diagnosis of dry eye was made on the basis of (1) symptoms typical of dry eye (that is, complaints of dryness, foreign body sensation, pain, burning, grittiness, sensitivity to light, fluctuation of vision with blink); (2) Schirmer test results of less than 10 mm without or less than 5 mm with topical 0.5% proparacaine hydrochloride anesthesia; (3) tear film breakup time of less than 5 seconds; and (4) fluorescein staining characteristic of punctate epithelial keratopathy. Using topical anesthesia, punctal plugs were inserted in the lower punctae after symptoms and clinical findings associated with dry eyes were diagnosed. Slit-lamp examination, visual acuity testing, Schirmer, and fluorescein breakup time measurements were repeated at the 1-month visit. Visual acuity measurements were recorded with standard Early Treatment of Diabetic Retinopathy Study charts. In assessing the visual outcome of the procedure, both spherical and defocus equivalents were calculated. Both parameters were calculated as previously described. 15 Briefly, the spherical equivalent was calculated by adding the sphere and half the cylinder, respecting the sign. The defocus equivalent was calculated by taking the spherical equivalent and adding one half of the absolute value of the cylinder, ignoring the sign. The study was divided into two stages. First, post-lasik dry eye patients were identified using the prescribed criteria. The median time from LASIK to punctal plug placement was 280 days. A Shack-Hartmann wavefront sensor (Zywave; Bausch & Lomb, Rochester, New York, USA) was used to measure the monochromatic wave aberration of the eyes under scotopic conditions. Punctal plugs were then inserted into the lower punctum of the patients. In the second stage, the wavefront measurements were performed on the same patients approximately 1 month (mean, 39 days; SD, 7.5) after punctal occlusion. The wave aberration was expressed as a Zernike polynomial up to and including fifth-order aberrations (18 Zernike terms) over the patients natural (undilated) mesopic pupil sizes at the time of measurement. The mean measured pre-punctal plug pupil was 5.93 mm (SD, 0.30) and the post-punctal plug pupil was 5.91 mm (SD, 0.32) at the wavefront measurement (P.05). The correlation of the before and after plug pupil measurements was 0.81 (P.0001). As a control group, repeat wavefront measurements were taken approximately 1 month apart in 10 eyes of post-lasik patients without clinical signs of dry eyes. No punctal plugs were placed in this post-lasik control group. Mean pupil size at the initial wavefront measurement was 5.05 mm (SD, 0.37) and at the second measurement 4.99 mm (SD, 0.36); correlation was 0.76 (P.05). The Zernike polynomials and double indexing scheme used to label the Zernike coefficients correspond with the standard normalized polynomials and representation established by the Optical Society of America s Vision Science and Its Application (VSIA). The wavefront analysis and measurement were performed with CTVIEW software (Sarver and Associates, Celebration, Florida, USA). A two-tailed Student t test was used to assess statistical significance when comparing the differences in wavefront aberrations before and after punctal occlusion. A value of P less than.05 was considered to be statistically significant in the tests. Statistical analysis was performed using Shazam version 8.1 (K. J. White). RESULTS WAVEFRONT MEASUREMENTS WERE OBTAINED OF DRY EYE patients before and after punctal occlusion. The total root mean square (RMS) wavefront errors for the patients before and after insertion of punctal plugs are shown in Figure 1. Significant changes were observed in the total RMS wavefront error values before and 1 month after punctal occlusion. The average pre-punctal plug total RMS wavefront error (mean SEM) was m, whereas that for the post-plug eyes was m, with a reduction of approximately 20% (P.01). Significant differences were also observed in lower-order VOL. 137, NO. 1 EFFECT OF PUNCTAL OCCLUSION ON WAVEFRONT ABERRATIONS 53

3 FIGURE 1. Average root mean square (RMS) wavefront errors for total, lower, and higher-order aberrations before and approximately 1 month after punctal occlusion. wavefront errors, defocus, and astigmatism, measured in patients diagnosed with dry eyes before and after punctal occlusion, as shown in Figure 1. The wavefront RMS for these lower-order terms were m (mean SEM) vs m before and after plugs, respectively, with an average reduction of 47% (P.01). In accordance with the change in lower-order aberration RMS before and after the punctal occlusion, there were also changes in both subjective and objective clinical measurements of spherical equivalent and defocus equivalent. Patients who received punctal plugs showed improvements in manifest refraction, as shown in Figure 2, with a statistically significant reduction of spherical equivalent from 0.92D 0.16 before plug to 0.69D 0.13 after plug (P.05). There were also significant reductions in defocus equivalent before and after plug placement, with an average decrease from to (P.05). Objective measurements of spherical equivalent and defocus equivalent were also performed with a Zywave wavefront aberrometer. The predicted phoropter refraction (PPR) measurements by Zywave were recorded at both 3.5 mm and 5.7 mm pupil sizes as shown in Figures 2 and 3. The spherical equivalents of the PPR at a 3.5 mm pupil before and after punctal occlusion were 0.78D 0.17 and (P.05). The spherical equivalents of the PPR at a 5.7 mm pupil size were 1.37D 0.19 and 1.21D 0.18 (P.05). The defocus equivalents of the PPR at a 3.5 mm pupil before and after punctal occlusion were and (P.05). The defocus equivalents for the 5.7 mm PPRs were and (P.05). The average changes in higher-order RMS wavefront error in patients before and after punctal plug insertion is shown in Figure 1. The values of higher-order RMS were m and m before and 1 month after the punctal occlusion, respectively. The average reduction of higher-order aberration RMS was 63% (P.01). As shown in Figure 4, significant reduction in RMS wavefront measurements were found in third; fourth; and fifth-order aberrations after punctal occlusion (P.01). The RMS wavefront errors for the third-order aberration were m before and m after punctal occlusion, with an average reduction of 61% (P.01). The fourth-order wavefronts were m before and m after plug insertion, with an average reduction of 67% (P.01). Smaller reductions were seen in the fifth-order RMS measurements, which were m before and m after punctal occlusion. Among higher-order aberrations, there were significant reductions in coma and spherical aberration, but not in trefoil, after punctal occlusion. As shown in Figure 5, for coma, the RMS wavefront errors were m and m, with a reduction of 66% (P.01); for spherical aberration, the RMS errors were m and m, with a reduction of 42% (P.01); and for trefoil, the measurements were m and m, with a reduction of only 34% (P.01). 54 AMERICAN JOURNAL OF OPHTHALMOLOGY JANUARY 2004

4 FIGURE 2. Average spherical equivalent values measured by manifest refraction (MR), predicted phoropter refractions (PPR) at 3.5 mm and 5.7 mm pupil sizes before and approximately 1 month after punctal occlusion. FIGURE 3. Average defocus equivalent values measured by manifest refraction (MR), predicted phoropter refractions (PPR) at 3.5 mm and 5.7 mm pupil sizes before and approximately 1 month after punctal occlusion. As a control, a cohort of 10 eyes of post-lasik patients without clinical symptoms of dry eye were measured twice with wavefront aberrometry at similar intervals to the punctal plug patients. This control group did not have punctal plugs placed. As shown in Figure 6, no statistically significant differences were found in higher-order aberrations, coma, trefoil, or spherical aberration. No significant differences were seen in total or lower-order aberrations, predicted phoropter, VOL. 137, NO. 1 EFFECT OF PUNCTAL OCCLUSION ON WAVEFRONT ABERRATIONS 55

5 FIGURE 4. Average root mean square (RMS) wavefront errors for higher-order, third-order, fourth-order, and fifth-order aberrations before and approximately 1 month after punctal occlusion. FIGURE 5. Average root mean square (RMS) wavefront errors for coma, trefoil, and spherical aberrations before and approximately 1 month after punctal occlusion. or manifest refraction. This finding indicates that the statistically significant differences found in the post-lasik patients before and after punctal plugs were not just a reflection of poor repeatability of measurement. Punctal occlusion in dry eye patients also resulted in substantial improvement in visual acuity. As shown in Figure 7, 62.5% of eyes had visual acuity better than 20/20 1 month after the punctal occlusion compared with 43.75% of the eyes 56 AMERICAN JOURNAL OF OPHTHALMOLOGY JANUARY 2004

6 FIGURE 6. Repeat wavefront measurements taken 1 month apart show no statistically significant differences in total higherorder root mean square (RMS), coma, trefoil, and spherical aberration in 10 eyes of post-lasik control patients without clinical signs of dry eye and without placement of punctal plugs. before the plugs. No eyes had visual acuity worse than 20/40 1 month after the plugs. Along with the aforementioned quantitative improvement in visual acuity, many patients described noticeable subjective improvement in their quality of vision (that is, less ghosting, glare, and fluctuation, along with increased image sharpness, contrast, and crispness). We utilized the retinal point spread function derived from wavefront data to perform a convolutional analysis of the quality of simulated images in post-lasik patients before and after punctal plug placement. A typical image convolution in a LASIK dry eye patient is shown in Figure 8 (top left) demonstrated with the EDTRS acuity chart. Much of the poor quality of vision in this case was related to the higher-order aberrations alone (compare Figure 8, top left and bottom left). One month after punctal occlusion, significant improvement could be seen in the chart image convolution, as seen in Figure 8 (top right). Corresponding changes could also be appreciated in the 2-dimensional wavefront, 3-dimensional wavefront aberrations, and retinal point spread function (Figure 9). In selected patients after punctal occlusion, a crisper, less ghosted ETDRS image was convolved based upon the entire wavefront (Figure 8, top right) in comparison with the ETDRS image convolution derived from the residual higher-order aberrations alone (that is, zeroing the lower order Zernike terms; Figure 8, bottom right). This finding demonstrates that selected higher-order aberrations may, in effect, offset some lower-order wave deformities, producing, in aggregate, a crisper, less aberrated image. DISCUSSION THIS STUDY HAS DEMONSTRATED A SIGNIFICANT REDUCtion in total, lower-, and higher-order aberrations in post-lasik dry eye patients after punctal occlusion. Given the importance of a smooth and regular anterior optical surface in the formation of a high-quality retinal image, it is reasonable to hypothesize that instability of the precorneal film in patients with dry eyes will have detrimental effects on their quality of vision. This study provides direct evidence that post-lasik dry eye results in a decrease in quality of vision, in part by increasing both lower and higher-order aberrations, and also that punctal occlusion can lessen some of this visual distortion by reducing both lower- and higher-order aberrations. Previous studies have shown that there were changes in the cornea surface regularity index and surface asymmetry index in dry eye patients Liu and associates 17 reported that the topographic changes in the cornea surface regularity index and asymmetry index could be used as objective diagnostic indices for dry eye and for evaluating the effect of artificial tears on corneal surface regularity. They have observed that surface regularity index, surface asymmetry index, and mean astigmatism all decreased significantly and potential visual acuity improved in dry eyes after instillation of artificial tears. An improvement in visual acuity of at least 1 line on the Snellen chart has been demonstrated in the first 3 to 10 seconds after a blink, based on the amount of change in surface regularity index and surface asymmetry index. 20,21 High-speed videotopographic measurement of surface regularity index and surface asymmetry index in both the normal and dry eyes has also provided useful information regarding the pattern of rapid changes in tear film surface regularity during the first 15 seconds after a blink. 16 A recent report by Koh and associates 14 has indicated an increase in higher-order aberrations after tear film breakup, as measured by a Hartmann-Shack type aberrometer. In our study, we have shown that there are significant reductions of both lower- and higher-order aberrations that correspond to significant improvements in visual acuity and manifest refraction. Among higher-order aberrations, there were significant reduction of coma and spherical aberration after punctal plug insertion, both of which can have a markedly detrimental effect on image quality. 22 There was also some reduction in trefoil after plug placement, but the changes were not statistically significant. We have used image simulation software to simulate the improvement of quality of vision after punctal occlusion in dry eyes. An analysis of the quality of convolved simulated images in post-lasik patients after punctal occlusion showed significant improvement of both the ETDRS chart and image quality. Significant improvements were also evident in 2-dimensional wavefront, 3-dimensional wavefront, and retinal point spread function. In analyzing the impact of reduction in both lower- and higher-order RMS produced after punctal occlusion, it is of interest that the convolutional analysis demonstrated a crisper, sharper image derived utilizing the whole eye wavefront (Figure 8, top right) than the same wavefront with lower-order VOL. 137, NO. 1 EFFECT OF PUNCTAL OCCLUSION ON WAVEFRONT ABERRATIONS 57

7 FIGURE 7. Cumulative Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuities before and approximately 1 month after punctal occlusion. SCVA uncorrected visual acuity. aberrations removed (Figure 8, bottom right). This demonstration shows the importance of determining the retinal point spread function and the benefit of convolving this with images in analyzing visual function, rather than solely focusing on reductions in overall higher-order RMS out of context of the total wave aberration of the eye. Different mechanisms have been proposed to explain the symptoms of dry eyes after LASIK. These possible mechanisms include a mechanical change in tear dynamics, a decrease in blink rate (accelerating tear evaporation and affecting tear stability), and a decrease in tear secretion resulting from severance of the sensory innervation of the corneal flap in LASIK surgery. The latter mechanism has been supported by studies indicating that corneal sensitivity is decreased immediately after LASIK but is generally recovered by 6 to 9 months postoperatively, influenced by factors including keratectomy and ablation depth. 4,9,23,24 The changes in corneal sensitivity are consistent with the morphologic changes of corneal nerves after LASIK. The sensory innervation of the cornea is provided by the ophthalmic and maxillary branches of the trigeminal nerve, which penetrate the limbus to form thick nerve bundles in the anterior third of corneal stroma before penetrating the Bowman layer to form the basal subepithelial nerve plexus. Major loss of superficial stromal and subepithelial nerves has been observed at the center of cornea after flap creation. 4,9,24 The dry eye symptoms after LASIK could also contribute to the decrease in blink rate as a result of loss of sensory nerve innervation to the cornea. Unlike decreased corneal sensitivity, however, which has been shown to recover to preoperative baseline level within 1 year, the decreased blink rate may never recover to preoperative levels. 2,3 In dry eyes after LASIK, this decrease in blink rate could significantly affect the stability of tear film layer 7,23 and increase tear evaporation. The resulting impaired visual acuity can be exacerbated further when the dry eye patient is gazing at an object (for example, driving, reading), during which there is involuntary blink suppression. 5 Our study was focused on wavefront measurements in post-lasik dry eye patients before and after punctal plug placement. Future studies should to assess the effect of punctal occlusion on the regularity of the corneal surface in post-lasik dry eyes. 18,19 The reduction of RMS measurement after punctal occlusion is associated with decreases in spherical and defocus equivalents and improvement of ETDRS visual acuity in our study. We would predict that these changes likely correlate with significant improvement in corneal surface regularity and spatial contrast sensitivity after punctal occlusion in patients with post-lasik dry eye syndrome, but this needs to be substantiated. Recent studies by Goto and associates 25 have demonstrated improved functional visual acuity and surface regularity index after 10 seconds of sustained eye 58 AMERICAN JOURNAL OF OPHTHALMOLOGY JANUARY 2004

8 FIGURE 8. Image convolution of a LASIK dry eye patient with a cumulative Early Treatment of Diabetic Retinopathy Study acuity chart before (left panels) and approximately 1 month after (right panels) punctal occlusion. Bottom panels show chart convolutions derived from higher-order aberrations alone (zeroing the lower order zernike terms). opening after punctal occlusion in a cohort of patients with aqueous tear deficiency and with Sjögren syndrome. We propose three possible explanations for the improvement of higher-order RMS and visual acuity after punctal occlusion. First, punctal occlusion may create a change in the curvature, surface tension, tonicity, composition, volume, and dynamics of the tear film covering the corneal epithelium after LASIK. Clinically, many post-lasik patients noticed immediate (albeit temporary) improvement in visual acuity after blinking and instillation of artificial tears, 18 and in some cases, within minutes after punctal plug placement. Although no change of the surface regularity index was observed in normal eyes after instillation of artificial tears, 17,27 significant reductions of the surface regularity index and surface asymmetry index and improvement of visual acuity as well as spatial contrast sensitivity have been reported in dry eyes after instillation of artificial tears. 17,18,28 It has also been shown that shortened tear film breakup time increases higher-order aberrations and degrades the quality of vision. 6,7,14 The results of our study support the notion that the punctal plugs may improve the optical regularity of the corneal surface by stabilizing the tear film, 25 as reflected by a decrease in the level of wavefront aberrations. Given the importance of accurate and stable wavefront aberrometry in planning laser corneal ablation, our results emphasize the importance of aggressively treating dry eyes before both laser refractive treatment and retreatment. In cases of retreatment, higher-order aberrations may be at more elevated levels than in eyes that have not been operated on, and potentially a greater error of measurement could be introduced. Also, the change in the eye wave aberration after punctal occlusion might potentially obviate the need for retreatment in some cases. Second, we hypothesize that the heightened tear film after punctal occlusion may decrease punctate keratopathy and improve the smoothness and regularity of corneal surface by affecting local homeostatic mechanisms that control epithelial thickness, including epithelial hyperplasia. 29,30 Finally, it is possible that post-lasik dry eye patients have induced biomechanical shifts in corneal curvature and thickness 31 as a result of permeability changes associated with punctate keratopathy. Further studies are needed to test the hypothesis that punctal occlusion may change these dynamics. Currently, no objective wavefront or topographic method is in routine clinical use to diagnose dry eyes and the effects of various treatment modalities on corneal surface regularity and optical quality. Topographic indices such as the surface regularity index and the surface asymmetry index have been proposed to serve such a role VOL. 137, NO. 1 EFFECT OF PUNCTAL OCCLUSION ON WAVEFRONT ABERRATIONS 59

9 FIGURE 9. Changes in retinal point spread function before (left) and approximately 1 month after (right) punctal occlusion. in the clinical evaluation of surface regularity in dry eyes, 12,17,18 but variable results have been reported in applying these indices to reliably evaluate the outcomes of dry eye treatment. In data processing for wavefront reconstruction, dry eyes tend to degrade the focus of the individual Hartmann-Shack spot centroids comprising the grid pattern. 6,13 The compromised tear film and diseased cornea are likely to scatter light that is reflected back out of the eye, adding additional blur to the raw data spot images captured by the aberrometer. These findings may not be pathognomonic to dry eye, however, and can be also seen in patients with cataract and with forms of corneal ectasia. 13 Whereas a specific and sensitive wavefront signature to diagnose dry eye patients is currently lacking, our results indicate that it is possible to evaluate and compare the quality of vision in post-lasik dry eye patients before and after punctal plug placement using convolutional analysis of wavefront aberrometry data. REFERENCES 1. Aras C, Ozdamar A, Bahcecioglu H, Karacorlu M, Sener B, Ozkan S. Decreased tear secretion after laser in situ keratomileusis for high myopia. J Refract Surg 2000;16: Battat L, Macri A, Dursun D, Pflugfelder SC. Effects of laser in situ keratomileusis on tear production, clearance, and the ocular surface. Ophthalmology 2001;108: Toda I, Asano-Kato N, Komai-Hori Y, Tsubota K. Dry eye after laser in situ keratomileusis. Am J Ophthalmol 2001; 132: Nassaralla BA, McLeod SD, Nassarala JJ Jr. Effect of myopic LASIK on human corneal sensitivity. Ophthalmology 2003; 110: Goto E, Yagi Y, Matsumoto Y, Tsubota K. Impaired functional visual acuity of dry eye patients. Am J Ophthalmol 2002;133: Hofer H, Artal P, Singer B, Aragón JL, Williams DR. Dynamics of the eye s wave aberration. J Opt Soc Am A Opt Image Sci Vis 2001;18: Tutt R, Bradley A, Bengley C, Thibos LN. Optical and visual impact of tear break-up time in human eyes. Invest Ophthalmol Vis Sci 2000;41: Wilson SE, Ambrosio R. Laser in situ keratomileusis-induced neurotrophic epitheliopathy. Am J Ophthalmol 2001;132: Linna TU, Vesaluoma MH, Perez-Santonja JJ, Petroll WM, Alio JL, Tervo TM. Effect of myopic LASIK on corneal sensitivity and morphology of subbasal nerves. Invest Ophthalmol Vis Sci 2000;41: Stern ME, Beuerman RW, Fox RI, Gao J, Mircheff AK, Pflugfelder SC. The pathology of dry eye: the interaction between the ocular surface and lacrimal glands. Cornea 1998;17: Heigle TJ, Pflugfelder SC. Aqueous tear production in patients with neurotrophic keratitis. Cornea 1996;15: 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: Munson K, Hong X, Thibos LN. Use of a Shack-Hartmann aberrometer to assess the optical outcome of corneal transplantation in a keratoconic eye. Optom Vis Sci 2001;78: 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: Waring GO. Standard graphs for reporting refractive surgery. J Refract Surg 2000;16: Németh J, Erdélyi B, Csákány B, et al. High-speed videotopographic measurement of tear film build-up time. Invest Ophthalmol Vis Sci 2002;43: Liu Z, Pflugfelder SC. Corneal surface regularity and the effect of artificial tears in aqueous tear deficiency. Ophthalmology 1999;106: Iskeleli G, Kizilkaya M, Arslan OS, Ozkan S. The effect of 60 AMERICAN JOURNAL OF OPHTHALMOLOGY JANUARY 2004

10 artificial tears on corneal surface regularity in patients with Sjögren syndrome. Ophthalmologica 2002;216: Özkan Y, Bozkurt B, Gedik Ş, Irkeç M, Orhan M. Corneal topographical study of the effect of lacrimal punctum occlusion on corneal surface regularity in dry eye patients. Eur J Ophthalmol 2001;11: Wilson SE, Klyce SD. Quantitative descriptors of corneal topography. A clinical study. Arch Ophthalmol 1991;109: Shiotani Y, Maeda N, Inoue T, et al. Comparison of topographic indices that correlate with visual acuity in videokeratography. Ophthalmology 2000;107: Porter J, Yoon G, Roberts C, Cox I, Williams DR, MacRae SM. Separate effects of the microkeratome incision and laser ablation on the eye s wave aberration. Am J Ophthalmol 2003;136: Kim W, Kim J. Change in corneal sensitivity following laser in situ keratomileusis. J Cataract Refract Surg 1999;25: Wilson SE. Corneal sensitivity after photorefractive keratectomy and laser in situ keratomileusis for low myopia. J Refract Surg 1999;15: Goto E, Yagi Y, Kaido M, Matsumoto Y, Konomi K, Tsubota K. Improved functional visual acuity after punctal occlusion in dry eye patients. Am J Ophthalmol 2003;135: Nemeth J, Erdélyi B, Csákány B. Corneal topography changes after a 15 second pause in blinking. J Cataract Refract Surg 2001;27: Pavlopoulos PG, Horn J, Feldman ST. The effect of artificial tears on computer-assisted corneal topography in normal eyes and after penetrating keratoplasty. Am J Ophthalmol 1995; 119: Rolando M, Lester M, Macri A, Calabria G. Low spatial contrast sensitivity in dry eyes. Cornea 1998;17: Erie JC, Pael SV, McLaren JW, et al. Effect of myopic laser in situ keratomileusis on epithelial and stromal thickness: a confocal microscopic study. Ophthalmology 2002;109: Reinstein DZ, Silverman RH, Raevsky T, et al. Arc-scanning very high-frequency ultrasound for 3D pachymetric mapping of the corneal epithelium and stroma in laser in situ keratomileusis. J Refract Surg 2000;16: Roberts C. Biomechanics of the cornea and wavefrontguided laser refractive surgery. J Refract Surg 2002;18:S VOL. 137, NO. 1 EFFECT OF PUNCTAL OCCLUSION ON WAVEFRONT ABERRATIONS 61