Punctal occlusion is now the most common nonmedication

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1 Cornea Upper Punctal Occlusion versus Lower Punctal Occlusion in Dry Eye Feng Chen, 1 Jianhua Wang, 2 Wei Chen, 1 Meixiao Shen, 1 Suzhong Xu, 1 and Fan Lu 1 PURPOSE. To compare the effectiveness of upper punctal occlusion versus that of lower punctal occlusion in dry eye patients. METHODS. One eye s upper punctum and the contralateral eye s lower punctum were occluded with collagen plugs in 20 dry eye patients. The same procedure was performed in 20 normal subjects. The upper and lower tear menisci were imaged simultaneously by real-time OCT before punctal occlusion and repeated on days 1, 4, 7, and afterward. The subjective symptom score, corneal fluorescein staining intensity, Schirmer I test result, and tear breakup time (TUT) were also determined. RESULTS. In dry eye patients, occlusion of either punctum improved symptom scores, fluorescein staining scores, TUT, and lower tear meniscus height (LTMH, P 0.05); however, Schirmer test scores and upper tear meniscus height (UTMH) did not change after occlusion (P 0.05). There was no significant difference for any of these variables between upper punctum and lower punctum occluded eyes, before or after occlusion (P 0.05). In normal subjects, Schirmer test scores, TUT, UTMH, and LTMH did not change over time (P 0.05). CONCLUSIONS. Punctal occlusion with collagen plugs in dry eye patients leads to the relief of subjective symptoms and the improvement of objective signs. The effectiveness of occluding the upper or lower punctum is similar. The LTMH is a valid indicator of the success of punctal occlusion. (Invest Ophthalmol Vis Sci. 20;51: ) DOI:.1167/iovs Punctal occlusion is now the most common nonmedication therapy for dry eye. 1 It decreases the drainage of tears, thus prolonging the retention time of natural or artificial tears on the ocular surface and relieving symptoms. 2 s occlusion of upper and lower puncta at the same time may increase the risk of epiphora, ophthalmologists usually perform the procedures one at a time. 3 However, which canaliculus plays the more important role in tear drainage has been a subject of debate for many years. Some believe that the lower one is more responsible for tear drainage. 4,5 Other studies conclude that both have a similar ability to eliminate tears. 6,7 Some limitations of From the 1 School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang, China; and the 2 ascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida. Supported by Research Grant 7I1809 from the Chinese National Science and Technology Development Supporting Program of the Eleventh-Five-Year, eijing, China (FL), and a grant from the Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents (FL). Submitted for publication December 20, 9; revised pril 6, 20; accepted pril 27, 20. Disclosure: F. Chen, None; J. Wang, None; W. Chen, None; M. Shen, None; S. Xu, None; F. Lu, None Corresponding author: Fan Lu, School of Ophthalmology and Optometry, Wenzhou Medical College, 270 Xueyuan Road, Wenzhou, Zhejiang, China, 327; dscl@wz.zj.cn. those studies, such as the absence of a control group and small sample size, impair the strength of the results. This study is designed to detect whether there is a difference between the effectiveness of upper punctal occlusion and that of lower punctal occlusion in dry eye patients. esides the conventional measurements such as dry eye symptom scoring, corneal fluorescein staining, Schirmer I test, and tear breakup time (TUT), we added measurement of the tear meniscus height (TMH) to the array of tests. Recently, reduced TMH in dry eye patients has been well documented, and it is regarded as a valuable diagnostic tool for dry eye. 8 However, the value of it in evaluating the effectiveness of punctal occlusion has not been fully explored until now. In this study, we determined the effectiveness of upper punctal occlusion versus lower punctal occlusion in dry eye patients by studying the changes in symptoms and signs after collagen plug insertion. METHODS Subjects This prospective, randomized study was conducted in accordance with the tenets of the Declaration of Helsinki and was approved by the Wenzhou Medical College Review oard, Wenzhou, Zhejiang, China. Informed consent was obtained from each subject after a full explanation of the procedure. Included were 20 patients with clinically diagnosed dry eye (group I, 16 women and 4 men) and 20 healthy control subjects (group II, 12 women and 8 men). The inclusion criteria for the dry eye patients was similar to those of the Japanese Dry Eye Society 11 and comprised the presence of subjective symptoms of dry eye, a Schirmer I test result 5 mm or tear breakup time 5 seconds, and evidence of corneal surface damage on fluorescein staining. The healthy subjects had no dry eye related symptoms, no cornea fluorescein staining, and a Schirmer I test result 5 mm. Patients and control subjects who had a history of atopy; allergic diseases; Stevens-Johnson syndrome; chemical, thermal, or radiation injury; or any other ocular or systemic disorder or had undergone any ocular surgery or contact lens use that would create an ocular surface problem or dry eye were excluded from the study. Subjects were also excluded if they had lacrimal dysfunction, as determined by slit lamp examination and irrigation. The mean age SD of the two groups was and years, respectively. The 20 dry eye patients included with aqueous-deficient dry eye and with evaporative dry eye. Half of them had primary dry eye syndrome ( patients; 50%), with other associations, including blepharitis (2 patients; %) and Meibomian gland dysfunction (8 patients; 40%). Symptom Scoring The dry eye symptom questionnaire developed by Schein et al. 12 was adopted for use in the study. It comprises six symptoms: dryness, gritty or sandy sensation, burning sensation, redness, crusting or discharge on the lashes, and having eyelids stuck shut in the morning. Each symptom was graded as follows: 0, no symptom; 1, mild; 2, moderate; and 3, severe. The sum of the scores of the six symptoms was treated as the total symptoms score. Investigative Ophthalmology & Visual Science, November 20, Vol. 51, No. 11 Copyright ssociation for Research in Vision and Ophthalmology 5571

2 5572 Chen et al. IOVS, November 20, Vol. 51, No. 11 Upper and Lower Tear Menisci The method of obtaining the upper and lower tear meniscus heights (UTMH and LTMH respectively) has been published in our other studies.,13,14 In brief, a custom-built, real-time optical coherence tomography (OCT) instrument was used to scan the subjects eyes. The scan width was set to 12.8 mm in air, and the scan depth was 2 mm in air. The subjects were instructed to fix on an external target and blink normally during scanning. The images were recorded as the OCT device scanned vertically across the apex of the cornea. The first good image showing both upper and lower tear menisci, obtained immediately after a blink, was used in the analysis. Operator inputs identified the middle point of the tear meniscus front edge and touch points between the eyelids, cornea, and tear menisci. These points were used to obtain the UTMH and LTMH by custom software analysis. Tear reakup Time Tear film stability was estimated based on tear breakup time (TUT). fluorescein-impregnated strip (Jingming, Tianjing, China) wetted with nonpreservative saline solution was placed in the lower conjunctival sac. The time between the last blink and the first appearance of a black spot on the stained tear film, revealed by the cobalt blue light of the slit lamp, was recorded. Corneal Fluorescein Staining The ocular surface was examined by fluorescein staining of the cornea. fluorescein-impregnated strip (Jingming) wetted with nonpreservative saline solution was placed in the lower conjunctival sac. Corneal fluorescein staining was recorded in the upper, middle, and lower areas of the cornea, each graded on a scale of 0 to 3 points, with 0 being no stain and 3 the most intense stain. The total score was from 0 to 9 points. 15 Schirmer I Test Tear production was measured by the Schirmer I test with anesthesia. Five minutes after a drop of proparacaine (lcon, Puurs, elgium), the Schirmer I test was performed by placing a dry Schirmer test strip (Jingming) over the lower lid margin into the tear lake at the junction of the middle and lateral one third of the eye lid for 5 minutes. The strip was then removed, and the amount of wetting in millimeters was recorded as the Schirmer I test score. Procedure ll subjects were tested between M and 4 PM in a dimly lit consulting room where the temperature (15 25 C) and humidity (30% 50%) were controlled by air conditioning and a dehumidifier. During the first visit, dry eye symptom scoring, simultaneous upper and lower tear meniscus images, TUT, corneal fluorescein staining, and Schirmer I test were sequentially obtained from each eye of every subject. fter that, two absorbable collagen plugs (Lacrimedics, Eastsound, W) were implanted into two puncta of every subject. The plugs were 0.4 mm in diameter and 1.75 mm in length, and the dissolution time reported by the manufacturer was 4 to 7 days. The 20 dry eye patients were randomly divided into two groups. I underwent upper punctal occlusion in the right eye and lower punctal occlusion in the left eye. II underwent upper punctal occlusion in the left eye and lower punctal occlusion in the right eye. The control subjects underwent the same procedure. Thus, the 40 eyes of group I subjects were randomly assigned to group I, which had upper punctal occlusion (n 20 eyes), or group I, which had lower punctal occlusion (n 20 eyes). The 40 eyes of the normal subjects (group II) were similarly assigned to group II (upper punctal occlusion group, n 20 eyes) or group II (lower punctal occlusion group, n 20 eyes). ll tests were repeated during visits at 1, 4, 7, and days after punctal occlusion with the same procedure. Data nalysis ll data are presented as the mean SD. Post hoc test analyses were used to assess the changes in all variables after punctal occlusion. n independent-samples t-test was used to compare differences between groups. The 2 test was used to compare the percentage of eyes with improved symptom scores, fluorescein scores, TUT, and LTMH at 1 day after occlusion in groups I and I. P 0.05 was accepted as statistically significant (SPSS, ver for Windows XP; SPSS, Chicago, IL). RESULTS t baseline (before punctal occlusion), there were no statistically significant differences in any variable between the eyes of each dry eye patient (independent-samples t-test: fluorescein scores, P 0.196; TUT, P 0.14; Schirmer I test scores, P 0.79; UTMH, P 0.30; and LTMH, P 0.48). Similarly, there were also no significant differences in any variable between the eyes of the normal subjects (TUT, P 0.80; Schirmer I test scores, P 0.69; UTMH, P 0.30; and LTMH, P 0.44). The Schirmer I test scores in dry eye patients (group I, mm; group I, mm) were significantly lower than those in the control subjects (group II, mm; group II, mm; independent-samples t-test, P 0.05; Table 1). The TUT in dry eye patients (group I, seconds; group I, seconds) was significantly lower than that in the control subjects (group II, seconds; group II, seconds; P 0.05; Table 1). The UTMH and LTMH in dry eye patients (groups I and I) were also lower than those in the control subjects (group II and II; P 0.05; Table 1). There were no statistically significant differences in symptom scores, fluorescein scores, Schirmer I test scores, TUT, UTMH, or LTMH between groups I and I (P 0.05, Table 1). In the normal subjects, no statistically significant differences in Schirmer I test scores, TUT, UTMH, or LTMH were detected between groups II and II (P 0.05; Table 1). No complication was observed in dry eye patients or control subjects during the period of this study. Upper and lower tear menisci in dry eye patients and control subjects were clearly visualized at baseline before punctal occlusion and after punctal occlusion (Fig. 1). Symptom scores in dry eye patients improved up to days after occlusion of either the upper (group I) or the lower (group I) punctum, compared with baseline values (post hoc test, P 0.05; Table 1, Fig. 2). In both groups, fluorescein scores, TUT, and LTMH also improved after occlusion (P 0.05; Table 1, Figs. 2, 3, 4). However, Schirmer I test scores and UTMH did not change significantly after punctal occlusion in group I or I (P 0.05; Table 1, Figs. 3, 4). There was no significant difference in any of these variables between groups I and I (independentsamples t-test, P 0.05) after occlusion. The percentage of eyes showing improvement on the first day after occlusion was similar for every variable in both groups ( 2 test, P 0.05; Table 2). In normal subjects (group II), Schirmer I test scores, TUT, UTMH, and LTMH did not change over time compared with baseline values, regardless of which punctum was occluded (groups II, II; post hoc test, P 0.05; Table 1, Figs. 3, 4). There were no significant differences in these variables between eyes with occluded upper punctum (group II) and eyes with occluded lower punctum (group II) after occlusion (independent-samples t-test, P 0.05). DISCUSSION fter mono-occlusion of the punctum in the normal group, there was no change in Schirmer I test scores, TUT, or TMHs.

3 IOVS, November 20, Vol. 51, No. 11 Punctal Occlusion in Dry Eye 5573 TLE 1. Symptom Scores, Fluorescein Scores, Schirmer I Test Scores, TUT, and TMH after Punctal Occlusion in Dry Eye Patients and Normal Subjects (n 20 eyes) aseline Symptom Scores I I Fluorescein Scores I I Schirmer Test, mm I I II II TUT, s I I II II UTMH, m I I II II LTMH, m I I II II I, 20 eyes with upper punctal occlusion in dry eye patients; group I, 20 eyes with lower punctal occlusion in dry eye patients. group II, 20 eyes with upper punctal occlusion in normal subjects; group II, 20 eyes with upper punctal occlusion in normal subjects. P 0.05 compared with baseline (post hoc test). This finding supports the idea of an autoregulatory mechanism that compensates for dynamic changes in the tear system. 16,17 Since tear secretion was not reduced, the compensation for the reduced tear drainage due to the occlusion may take place by adjustments within the tear drainage system. The most plausible explanation is that the tear drainage through the nonoccluded canaliculus increased, thus maintaining tear volume and avoiding excess fluid buildup on the ocular surface. Gravity, siphonage, capillary action, and pumping action combine to conduct tears down the nasolacrimal duct. The tear drainage of each canaliculus may adjust to the altered tear dynamics. Clearly, a balanced tear system, regulated to maintain the appropriate amount of high-quality tears, is important for optimal vision and protection of the ocular surface. The present study confirmed the clinical observation that unrepaired monocanalicular lesions do not induce tearing. 18 Lemp and Weiler 19 also reported that reduced drainage by the occlusion of the inferior punctum can be compensated for by drainage through the superior punctum. However, Yen et al. 20 found that punctal occlusion affects the interaction between the ocular surface and the lacrimal gland and decreases tear production in normal subjects. It is possible that, if the effect of mono-occlusion of the canaliculus exceeds the compensation of the ipsilateral, nonoccluded canaliculus, the tear system would respond by decreasing tear secretion to maintain the appropriate tear quantity. In contrast to the reaction in the normal subjects, this study showed that punctal mono-occlusion improved both the tear quantity and tear film stability in dry eye patients and brought about the relief of symptoms and signs. The dry eye symptoms were relieved on the first day after occlusion and remained so throughout the study period. Correspondingly, fluorescein scores, TUT, and LTMH were improved, but the times at which they reached statistical significance compared with baseline values varied. This result is in general agreement with those in other studies. 8,16,21 We postulate that the demand for tears in dry eye patients suppresses the compensation mechanism of the tear drainage duct so that the tear retention quantity and time increase after punctal occlusion, because of the improved health of the ocular surface. That the Schirmer I test scores did not change after occlusion in the present study indicates that punctal mono-occlusion may have no effect on tear secretion. The Schirmer I test measures the tear flow, which may not reflect the tear retention on the ocular surface, especially in punctum-occluded eyes. Some studies have documented increased Schirmer test scores after punctal occlusion in dry eye patients. 8,21,22 The exact mechanism by which punctal occlusion increases tear secretion is not very clear. Perhaps the underlying cause of aqueous tear deficiency in some dry eye patients is excessive negative feedback from the ocular surface or the tear drainage apparatus on secretion of tears by the lacrimal gland. Placing plugs in the puncta may in some way reverse this process. 20 lthough the benefit of punctal occlusion for treatment of dry eye is evident, it should be kept in mind that the tear dynamics in patients with punctum-occluded dry eye are dif-

4 5574 Chen et al. IOVS, November 20, Vol. 51, No. 11 UL C D UTM CO FIGURE 1. OCT images of one dry eye patient before and 1 day after punctal occlusion. The upper eyelid (UL), lower eyelid (LL), cornea (CO), and tear menisci (TM) around both eyelids were visualized. This patient underwent upper punctal occlusion in the right eye and lower punctal occlusion in the left eye. The lower tear menisci (LTM) of the right eye at 1 day after occlusion () was larger than that before occlusion (), whereas the size of the upper tear menisci (UTM) did not change. For the left eye, the LTM swelled at 1 day after occlusion (D) compared with baseline (C), whereas the UTM did not. ar, 500 m. LTM LL ferent from those in normal subjects.23 Yuan et al. (IOVS 9;50:RVO E-bstract 1233) found that the blinking output of the lower tear meniscus in patients with aqueous-deficient dry eye was reduced, which suggested reduced tear drainage, even without punctal occlusion. fter occlusion, the tear drainage was further decreased, although the tear production showed no increase. Therefore, the tear dynamics in patients with punctum-occluded dry eye showed lower tear secretion with lower tear drainage, different from those in normal subjects (without occlusion) with higher tear drainage and higher tear secretion. Obviously, the latter is superior for the purpose of refreshing tear film and protecting the ocular surface. In addition, restoring tear quality may be as important as retaining tear volume. This point is supported by the improved results of a combination of punctal occlusion and anti-inflammation medication over those obtained with either treatment alone.22 Several studies have been conducted to determine the separate contributions of the upper and lower canaliculi to tear drainage.4 7 Using the drop test, Murgatroyd et al.4 reported that more outflow occurs through the inferior canaliculus. However, Ogut et al.,6 using the fluorescein dye disappearance test, found that the rate of tear drainage was similar through both canaliculi. ecause of the invasive methods of those studies, it is likely that the results provide little information that is useful in making decisions for treatment of dry eye. In contrast, we indirectly determined the relative drainage capacity of the upper and lower canaliculi by comparing the effectiveness of upper punctal occlusion with that of lower punctal occlusion. ased on our data, we believe that upper or lower punctum mono-occlusion has similar effects, which include increasing the retention tear volume and tear film stability and relieving symptoms in most dry eye patients. Most ophthalmologists prefer to occlude the inferior punctum of dry eye patients first, because they have the impression that the inferior punctum contributes more to tear drainage than does the superior one.24,25 In addition, the lower punctum is more accessible for the procedure. lthough the lower punctum is reported to be larger than the upper one,26 it appears that such a difference

5 IOVS, November 20, Vol. 51, No. 11 Punctal Occlusion in Dry Eye 5575 Symptom scores Fluorescein scores FIGURE 2. Symptom and fluorescein scores after upper or lower punctal occlusion in dry eye patients. Left: symptom scores were decreased from 1 day after occlusion through the end of the study (P 0.05). Right: fluorescein scores decreased at 7 days after occlusion in the 20 eyes with upper punctal occlusion (group I, P 0.05). In the 20 eyes with lower punctal occlusion (group I), the scores decreased at 1, 4, and 7 days after occlusion. P 0.05, significant difference compared with baseline, post hoc test. Vertical bars, SD. is not associated with any difference in tear drainage between the upper and lower canaliculi. When occlusion of the lower punctum is not sufficient, the upper punctum can be occluded, usually achieving improved results. 3 n important finding in the present study is that the LTMH in dry eye patients significantly increased after punctal monoocclusion, whereas the UTMH did not. This result indicates that, no matter which punctum is blocked, the LTMH becomes elevated more prominently. Tears are produced by the lacrimal gland and held in the upper and lower tear menisci, from which they spread onto the ocular surface. The menisci hold approximately 75% to 90% of the total tear volume of the exposed ocular surface. 27 In a previous study, we found that the lower tear meniscus variables were more sensitive and specific than the upper ones in the diagnosis of dry eye. The results of the present study show that LTMH can also serve as a good guide for evaluating the effect of punctal occlusion. The increase in LTMH is in agreement with results in other studies. 16,25 Farrell et al. 16 occluded the lower puncta with dissolvable collagen plugs in aqueous-deficient dry eye patients and found that the LTMH increased to normal levels. In another study, eyes with the inferior punctum occluded by the SmartPlug (Medennium, Irvine, C) showed significant improvement in LTMH. 25 To the best of our knowledge, no study has demonstrated any change in the UTMH after punctal occlusion. The unaltered UTMH after punctal mono-occlusion in dry eye patients may be due to the limited occlusion of one punctum and the unchanged rate of tear secretion. Perhaps with simultaneous occlusion of upper and lower puncta, the UTMH would increase. Schirmer test values (mm) Schirmer test values (mm) TUT (s) TUT (s) FIGURE 3. Schirmer I test scores and TUT after upper or lower punctal occlusion in dry eye patients and normal subjects. Schirmer I test scores did not change in either dry eye patients (groups I and I) or normal subjects (groups II and II) after punctal occlusion (top left, top right, P 0.05). TUT was increased at 1, 4, and 7 days after occlusion in dry eye patients (groups I and I, bottom left, P 0.05), but not in normal subjects (groups II and II, bottom right, P 0.05). Significant difference compared with baseline, post hoc test. Vertical bars, SD.

6 5576 Chen et al. IOVS, November 20, Vol. 51, No. 11 UTMH (µm) UTMH (µm) LTMH (µm) LTMH (µm) FIGURE 4. TMHs after upper or lower punctal occlusion in dry eye patients and normal subjects. UTMH did not change in dry eye patients (groups I and I) or normal subjects (groups II and II) after punctal occlusion (top left, top right; P 0.05). LTMH increased up to days after occlusion in dry eye patients (groups I and I, bottom left; P 0.05), but not in normal subjects (groups II and II; bottom right, P 0.05). Significant difference compared with baseline; post hoc test. Vertical bars, SD. Our study may have some limitation in. First, the collagen plugs used were of a uniform size, but the size of each punctum may vary. The difference in the degree of occlusion obtained may have caused our results to be somewhat in error. However, occlusion of the upper punctum in one eye and the lower punctum in the contralateral eye in every subject may have decreased the error to a minimum. nother limitation is that the manual outlining of the tear menisci introduced some error in obtaining the UTMH and LTMH. Image-processing software should be improved to detect the tear meniscus variables automatically in future studies. The third limitation is that, although we found no differences in meniscus and clinical variables between right and left eyes at baseline and the eyes were randomly assigned to the subgroups, differences among individual subjects may still have been present. The use of a crossover design, which should enhance the power of the results, should be considered in future studies. In summary, mono-occlusion of the upper or lower punctum with collagen plugs led to the relief of symptoms and improved signs in our dry eye patients. Similar results were obtained regardless of which punctum was occluded. The LTMH was a valid indicator of the success of the punctal occlusion. TLE 2. Comparison of the Percentage of Eyes with Improved Parameters Measured at 1 after Punctal Occlusion in Dry Eye Patients I n (%) I n (%) P Symptom scores 17 (85) 17 (85) Fluorescein scores 9 (45) 11 (55) TUT, s 18 (90) 17 (85) LTMH, m 14 (70) 13 (65) I, 20 eyes with upper punctal occlusion in dry eye patients; group I, 20 eyes with lower punctal occlusion in dry eye patients; n, number of improved eyes; %, percent of improved eyes. 2 test, P 0.05 for each comparison between groups. cknowledgments The authors thank Ruide Medical (Hangzhou, China) for supplying some of the punctal plugs used in the study and ritt romberg of Xenofile Editing (New Orleans, L) for providing editing services. References 1. Murube J, Murube E. Treatment of dry eye by blocking the lacrimal canaliculi. Surv Ophthalmol. 1996;40: Calonge M. The treatment of dry eye. Surv Ophthalmol. 1; 45(suppl 2):S227 S Tai MC, Cosar C, Cohen EJ, Rapuano CJ, Laibson PR. The clinical efficacy of silicone punctal plug therapy. Cornea. 2;21: Murgatroyd H, Craig JP, Sloan. Determination of relative contribution of the superior and inferior canaliculi to the lacrimal drainage system in health using the drop test. Clin Exp Ophthalmol. 4;32: Jones LT, Marquis MM, Vincent NJ. Lacrimal function. m J Ophthalmol. 1972;73: Ogut MS, avbek T, Kazokoglu H. ssessment of tear drainage by fluorescein disappearance test after experimental canalicular obstruction. cta Ophthalmol. 1993;71: White WL, Glover T, uckner, Hartshorne MF. Relative canalicular tear flow as assessed by dacryoscintigraphy. Ophthalmology. 1989;96: Dogru M, Ishida K, Matsumoto Y, et al. Strip meniscometry: a new and simple method of tear meniscus evaluation. Invest Ophthalmol Vis Sci. 6;47: Savini G, arboni P, Zanini M. Tear meniscus evaluation by optical coherence tomography. Ophthalmic Surg Lasers Imaging. 6; 37: Shen M, Li J, Wang J, et al. Upper and lower tear menisci in the diagnosis of dry eye. Invest Ophthalmol Vis Sci. 9;50: Methodologies to diagnose and monitor dry eye disease: report of the Diagnostic Methodology Subcommittee of the International Dry Eye Work Shop (7). Ocul Surf. 7;5:8 152.

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