ARTICLE
Prominent Decrease of Tear Meniscus Height With Contact Lens Wear and Efficacy of Eye Drop Instillation Yukiko Nagahara, M.D., Shizuka Koh, M.D., Naoyuki Maeda, M.D., Kohji Nishida, M.D., and Hitoshi Watanabe, M.D.
Objective: To investigate the change in tear meniscus height (TMH) before and after wearing soft contact lenses (CLs) of different water contents (WCs) and the influence of eye drop instillation on TMH during CL wear. Methods: Tear meniscus heights were measured using anterior segment optical coherence tomography in 20 normal subjects wearing a high-WC CL (WC, 69%) in 1 eye and a low-WC CL (WC, 24%) in the other. Tear meniscus height change after eye drop instillation with 3% diquafosol ophthalmic solution or saline with CL wear was evaluated at 5, 15, 30, and 60 min after instillation. Results: A significant decrease in TMH was observed after lens insertions of both CLs. Tear meniscus height was significantly decreased with highWC CL wear compared with that with low-WC CL wear. With high-WC CL wear, TMH increased significantly (P,0.001) at 5 min after the instillation of 3% diquafosol ophthalmic solution compared with the baseline values and then returned to the pre-instillation level. No significant TMH changes were found with the instillation of either eye drop (diquafosol or saline) with low-WC CL wear. Conclusions: Tear meniscus height decreased with CL wear, especially with high-WC CL wear. Significant increases in TMH were observed at 5 min after the instillation of diquafosol ophthalmic solution with high-WC CL wear. The increases in TMH after diquafosol instillation tended to be greater than those after saline instillation at least for 30 min with both highWC and low-WC CLs. Key Words: Tear meniscus—Dry eye—Contact lens—Water content— Diquafosol ophthalmic solution. (Eye & Contact Lens 2015;41: 318–322)
A
s stated in the Dry Eye WorkShop report in 2007, the major classes of dry eye are still aqueous tear-deficient dry eye and evaporative dry eye.1 Contact lens (CL) wear is one of the major extrinsic causes of evaporative dry eye.1 In healthy eyes, the corneal and conjunctival epithelium have a mechanism that maintains the tear film by presenting transmembrane mucins, such as MUC1, 4, and 16, at the epithelial-tear interface.2,3 The thin outermost lipid layer of the tear film can spread over the mucoaqueous layer of the tear film. The lipid layer stabilizes the tear film itself and prevents aqueous tear evaporation from the ocular surface. However, once From the Department of Ophthalmology (Y.N., S.K., N.M., K.N., H.W.), Osaka University Graduate School of Medicine, Suita, Osaka, Japan; and Department of Ophthalmology (H.W.), Kansai Rosai Hospital, Amagasaki, Hyogo, Japan. The authors have no funding or conflicts of interest to disclose. Address correspondence to Hitoshi Watanabe, M.D., Department of Ophthalmology, Osaka University Graduate School of Medicine, Room E7, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; e-mail: [email protected] Accepted December 23, 2014. DOI: 10.1097/ICL.0000000000000134
318
the CL is on the cornea, the prelens tear film cannot steadily maintain the tear film structure over the lens because transmembrane mucins are not present in the prelens tear film. Furthermore, the lipid layer fails to spread across the mucoaqueous layer. Because of the irregular and nonuniform lipid layer in the eyes with CLs, the evaporation of the tear film increases from the postlens tear film and the prelens tear film. Several studies have demonstrated that the tear film evaporation rate in eyes with CLs is higher than that in eyes without CLs.4–7 According to the recently published report on “Contact Lens Discomfort” by the Tear Film & Ocular Surface Society, several biophysical tear film changes have been associated with CL wear.8 Along with increased evaporation, other factors, such as tear film stability, prelens lipid layer thickness, tear volume, and changes in the tear composition have been associated with CL discomfort.8 A previous report proposed that among these factors, decreased tear volume may be a major factor inducing CL-related dry eye symptoms and intolerance.9 Because 75% to 90% of the tear volume exists in the upper and lower tear menisci,10 the tear meniscus dimensions can be a good indicator for estimating total tear volume. The measurement of tear meniscus height (TMH) using anterior segment optical coherence tomography (AS-OCT) is a common method used to quantify tear volume. Several studies have performed TMH measurements using AS-OCT in eyes with CLs.11–14 Moreover, the material and design of CLs may affect the interactions between the tear film and CLs.15 The water content (WC) of CLs can potentially influence the lens dehydration throughout the course of the wearing period, which can affect the prelens and postlens tear film. Several studies have evaluated TMH in eyes with CLs11–14; however, the effect of WC of the lens on TMH during CL wear is unknown. Artificial tears and tear retention agents have been used to lubricate the ocular surface and improve symptoms of irritation in CL wearers. The use of these eye drops has been expected to provide an aqueous component to the tear film and increase the tear volume. Diquafosol ophthalmic solution is a new, topical pharmacologic agent that has recently become commercially available for treating dry eye. Diquafosol is a P2Y2 purinergic receptor agonist that activates P2Y2 receptors on the ocular surface. Diquafosol stimulates both fluid secretion from the conjunctival epithelial cells and mucin secretion from the conjunctival goblet cells directly on the ocular surface, thereby rehydrating the ocular surface independent of tear film secretion from the lacrimal glands.16–18 The clinical efficacy of diquafosol for treating dry eye has been reported in recent articles19–27; however, its effect in eyes with CLs is not clear. Yokoi et al.28 have reported an increase in tear fluid volume induced by diquafosol in normal eyes. Because the decrease in Eye & Contact Lens Volume 41, Number 5, September 2015
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Eye & Contact Lens Volume 41, Number 5, September 2015 the tear meniscus is believed to be partly responsible for CL discomfort,12 it will be of interest to investigate the fluid secretion effect of diquafosol in eyes with CLs. In this study, we examined TMH change in eyes with CLs of different WCs. Furthermore, we evaluated the time course of TMH after eye drop instillation during CL wear using AS-OCT for the TMH measurement.
METHODS The Institutional Review Board of Osaka University Hospital approved this study, which adhered to the tenets of the Declaration of Helsinki. All patients provided informed consent after receiving an explanation of the nature and possible consequences of the study. Two studies were conducted. In the first study, the TMHs before and after the insertion of CLs with different WCs were examined. In the second study, the instillation effects of different eye drops on TMH during CL wear were evaluated.
Subjects The studies included 20 eyes of 10 normal volunteers (7 men, 3 women; average age, 36.767.3 years) who experienced no ocular diseases except refractive errors. No subject wore CLs. All participants met the following criteria: no ocular pathologic condition or systemic disorders and no drug administration with any known effects on visual acuity.
Types of Soft Contact Lens Two commercially available CLs of different WCs, nelfilcon A lenses (Dailies AquaComfort Plus; Alcon, Tokyo, Japan) (WC of 69%, high-WC CL) and lotrafilcon A lenses (Air Optix EX Aqua; Alcon) (WC of 24%, low-WC CL), were compared. The details of both products are shown in Table 1. We confirmed that both types of CLs fit each subject properly and that the lenses were similar in movement, central placement, and comfort. Subjects were randomly provided with a high-WC CL for one eye and a low-WC CL for the other eye.
Tear Meniscus Measurement Cross-sectional images of the lower TMH were taken vertically across the central cornea using Fourier-domain swept-source ASOCT (SS-1000; Tomey Corp., Nagoya, Japan). This system attains high-resolution imaging at 10 mm (axial) and 30 mm (transverse) TABLE 1.
Parameters of Lenses Used in the Study High-WC CL
Brand name (Japan) Brand name (USA) Manufacturer Lens material FDA classification Water content (%) Base curve (mm) Diameter (mm) Center thickness (mm) (at 23.00 D)
Dailies AquaComfort Plus Dailies AquaComfort Plus Alcon Nelfilcon A Group II 69.4 8.7 14.0 0.10
Low-WC CL Air Optix EX Aqua Air Optix Night and Day Aqua Alcon Lotrafilcon A Group I 24.0 8.4/8.6 13.8 0.08
CL, contact lens; D, diopters; WC, water content.
© 2015 Contact Lens Association of Ophthalmologists
Prominent Decrease of TMH With CL Wear and high-speed scanning of 30,000 A-scans per second. The principles, technique, and reproducibility of this device have been described previously.29,30 Briefly, subjects were asked to rest their head on the chin rest of the AS-OCT and instructed to blink spontaneously during the measurement. All subjects underwent ASOCT examination 1 sec after blinking. In accordance with previous studies,29,30 all AS-OCT images were processed by a single trained observer. Briefly, the procedures for the measurement of the TMH values were performed on 300% magnified images. Tear meniscus height was defined as the line distance starting at the fluid surface from the inferior cornea–meniscus junction to the lower eyelid– meniscus junction. The line distance between the two points was decided manually using the calipers on the magnified image and calculated automatically by the software.
Experimental Protocol
In the first study, the effect of different WCs of CLs on TMH was investigated. Anterior segment optical coherence tomography imaging was performed twice for each subject: before CL insertion (without the lens) and at 20 min after lens insertion. The change in TMH (DTMH) was calculated as the difference between the baseline TMH without the lens and TMH with the lens. In the second study, the time course of TMH after the eye drop instillation during CL wear was investigated in the six subjects who consented to the following procedure. Each subject randomly received a single drop of 3% diquafosol ophthalmic solution (3% Diquas; Santen Pharmaceutical Co., Osaka, Japan) in one eye and an isotonic borate-buffered saline (Soft Santear; Santen Pharmaceutical Co.) in the other eye while wearing both high-WC CL and low-WC CL. Tear meniscus height measurements were performed at 5, 15, 30, and 60 min after the eye drop instillation for both eyes in each subject. The DTMH was calculated as the difference between the baseline TMH and TMH after the instillation.
Statistical Analysis Data were analyzed using JMP ver. 9 (SAS Institute, Cary, NC). The Friedman repeated-measures analysis of variance on ranks test was used to assess the time course of DTMH. The appropriate post hoc Dunnett correction for multiple comparisons was used. The Kruskal–Wallis test was performed to compare the DTMH between high-WC CL and low-WC CL at each time point. The appropriate post hoc Tukey correction for multiple comparisons was used in this comparison. A P,0.05 was considered significant for all analyses.
RESULTS Tear Meniscus Height Change With Contact Lens Wear Figure 1 shows the representative lower tear meniscus images without and 20 min after high-WC CL insertion. Tear meniscus height values without and with a high-WC CL were 226 and 110 mm, respectively. In comparison to baseline TMH without CL, remarkable decrease in TMH was observed with the high-WC CL (Fig. 1). Tear meniscus height values without and with high-WC CLs were 244653 and 161638 mm, respectively. Tear meniscus height values without and with low-WC CLs were 257644 and 319
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Y. Nagahara et al.
Eye & Contact Lens Volume 41, Number 5, September 2015
FIG. 1. Representative lower tear meniscus images without (A) and with a high-WC CL (B). Tear meniscus height values without and with the high-WC CL were 226 and 110 mm, respectively. WC, water content; CL, contact lens.
198626 mm, respectively. After lens insertion, significant decreases in TMH were found with both high-WC CL and lowWC CL wear (P,0.001, P,0.001, respectively). Although there was no significant difference in the baseline TMHs (before the lens insertion) between high-WC CL and low-WC CL, TMH for highWC CL was significantly decreased compared with that for lowWC CL (P¼0.005). The calculated DTMH values for high-WC CL and low-WC CL were 298649 and 246638 mm, respectively. The DTMH value for high-WC CL was significantly greater than that with low-WC CL (Fig. 2).
DISCUSSION This showed a significant decrease in TMH after CL wear and the effects of different eye drop instillations on TMH during CL wear. Tear meniscus height was imaged and easily quantified using AS-OCT in eyes with both high-WC CLs and low-WC CLs. According to the previous study measuring TMH with 2 different silicone hydrogel CLs using AS-OCT, TMH values at 20 min after CL wear returned to the baseline values and remained that way for at least 4 hr.12 However, in this study, TMHs measured at 20 min after both high-WC CL and low-WC CL wear were
Tear Meniscus Height Change With Eye Drop Instillation
The DTMH data obtained before and after the instillation of 3% diquafosol ophthalmic solution or saline in the eyes with both high-WC CLs and low-WC CLs are shown in Figure 3. In eyes with high-WC CLs, the mean DTMHs after diquafosol instillation were 57.6, 49.2, 19.4, and 25.4 at 5, 15, 30, and 60 min after instillation, respectively. Tear meniscus height increased significantly (P,0.001) at 5 min after the instillation of diquafosol ophthalmic solution compared with the baseline values and then returned to pre-instillation levels. In contrast, the mean DTMHs after saline instillation were 20, 14.8, 0.8, and 5.3 at 5, 15, 30, and 60 min after instillation, respectively. No significant DTMH was found with the instillation of saline. In the eyes with low-WC CLs, the mean DTMHs were 46, 35.4, 6, and 218.4 at 5, 15, 30, and 60 min after diquafosol instillation and 7.8, 2.8, 224.6, and 224.2 at 5, 15, 30, and 60 min after saline instillation, respectively. There were no significant DTMHs after the instillation of both eye drops. At 60 min after the instillation of both eye drops, TMH tended to be lower than the baseline levels. 320
FIG. 2. The lower TMH change before and after the wearing highWC and low-WC CLs. The change in TMH (DTMH) with the high-WC CLs was significantly greater than that with low-WC CLs. TMH, tear meniscus height; DTMH, change in tear meniscus height; WC, water content; and CL, contact lens. *P,0.001 (high-WC CLs vs. low-WC CLs), †P,0.001 (baseline and 20 min after high-WC CL insertion), and ‡P,0.001 (baseline and 20 min after low-WC CL insertion).
Eye & Contact Lens Volume 41, Number 5, September 2015
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Eye & Contact Lens Volume 41, Number 5, September 2015
FIG. 3. The time course of the lower TMH after eye drop instillation with high-WC and low-WC CLs wear. With high-WC CL wear, TMH increased significantly (P,0.001) at 5 min after diquafosol instillation compared with the baseline values and then returned to pre-instillation levels. No significant TMH changes were found with both diquafosol and saline instillation with low-WC CL wear. TMH, tear meniscus height; DTMH, change in tear meniscus height; WC, water content; and CL, contact lens. *P,0.001 (in comparison with baseline).
significantly decreased compared with the baseline TMHs. Moreover, at 20 min after CL wear, TMH with high-WC CL wear was significantly lower than that with low-WC CL, which has not been reported previously. Dehydration has been reported to be more pronounced with high-WC hydrogel CLs leading to decreased end-of-day comfort.31–33 Furthermore, improved comfort for lowWC CLs compared with high-WC CLs has been reported.34,35 In the normal tear system, the tear drainage system maintains a dynamic balance so that the tear volume sustains a relatively steady state and keeps the ocular surface wet.8 Palakuru et al.36,37 have reported that the lower tear meniscus may regulate the tear drainage system. If such a system can function, it may be possible that an increase in tear secretion by the lacrimal gland, contributing to the increase of TMH, could compensate for dehydration or increased evaporation with CL wear. However, the decrease in corneal sensitivity with CL wear38,39 may lead to a reduction in tear secretion through the reflex sensory loop.40 Therefore, even when greater evaporation occurs with high-WC CL wear in the setting of a dehydrated surface, a decrease in corneal sensitivity can result in a decrease of TMH. Although the actual mechanism of CL wear and ocular surface sensitivity is still unclear, the relation© 2015 Contact Lens Association of Ophthalmologists
Prominent Decrease of TMH With CL Wear ship among CL materials, tear parameters, and corneal sensitivity during CL wear is of interest and should be clarified in future studies. Because end-of-day dryness is one hallmark symptom of CLrelated dry eye, future studies with longer observation periods will be needed. Previous studies have shown decreased tear volume during CL wear for 10 hr11 and a significant relationship between ocular comfort and tear volume after 10 hr of CL wear.12 Based on these findings, it could be expected that both high-WC CLs and low-WC CLs could cause a decrease in TMH with longer periods of CL wear. It is important to investigate how the difference in WCs of CLs influences TMH after longer periods of CL wear. Moreover, the difference in the subjective dry eye–related symptoms between high-WC and low-WC CLs is also of interest. Although we did not evaluate subjective dry eye–related symptoms, such TMH decrease may easily lead to discomfort and irritation with CL wear. In this study, a significant increase in TMH was observed at 5 min after the instillation of diquafosol in eyes with high-WC CLs, whereas no significant change was observed with saline. Previous studies that investigated TMH or tear volume change after artificial eye drop instillation in eyes with CLs reported that TMH or tear volume increased after rewetting, but this increase only lasted for 10 to 20 min.12,13 In this study, the results obtained with diquafosol instillation with high-WC and low-WC CL wear were similar to the previous findings. Conversely, the time course of DTMH with saline instillation in this study showed no change at up to 60 min with high-WC CLs. At 60 min after the instillation of both eye drops, TMH with low-WC CL wear tended to be lower than the baseline levels. According to Yokoi et al.,28 diquafosol increased the radius value of the tear meniscus curvature from 5 to 30 min after instillation in normal eyes without CLs, and the effect was significant compared with that of artificial tears. Although we did not investigate TMH change with eye drop instillation in eyes without CLs, we assume that eyes with high-WC CL that have a remarkable decrease in TMH might benefit from a transient increase in wetness by diquafosol. Although the observation for longer period after instillation is needed, it is possible that evaporation or dehydration associated with high-WC CL might be improved owing to the increase in wetness with diquafosol. Further studies are needed to demonstrate the effect of diquafosol in symptomatic CL wearers. We report for the first time that TMH was remarkably decreased with high-WC CL wear compared with low-WC CL wear and that a significant increase of TMH was observed at 5 min after the instillation of diquafosol ophthalmic solution during high-WC CL wear. The limitations of this study were the small sample size and the limited time duration after eye drop instillation. Although we were specifically interested in exploring TMH change in eyes wearing CLs of different WCs and the time course of TMH after eye drop instillation, the relationship between the subjective symptoms of CL discomfort and TMH should be clarified in future studies. Based on the preliminary examination of a few subjects from this study, we anticipate further studies demonstrating the efficacy of diquafosol ophthalmic solution for CL-related dry eye. REFERENCES 1. 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;5:75–92.
321
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Y. Nagahara et al. 2. Spurr-Michaud S, Argüeso P, Gipson I. Assay of mucins in human tear fluid. Exp Eye Res 2007;84:939–950. 3. Watanabe H. Significance of mucin on the ocular surface. Cornea 2002;21: S17–S22. 4. Guillon M, Maissa C. Contact lens wear affects tear film evaporation. Eye Contact Lens 2008;34:326–330. 5. Tomlinson A, Cedarstaff T. Tear evaporation from the human eye: The effects of contact lens wear. J Br Contact Lens Assoc 1982;5:141–150. 6. Thai LC, Tomlinson A, Doane MG. Effect of contact lens materials on tear physiology. Optom Vis Sci 2004;81:194–204. 7. Cedarstaff TH, Tomlinson A. A comparative study of tear evaporation rates and water content of soft contact lenses. Am J Optom Physiol Opt 1983;60: 167–174. 8. Craig JP, Willcox MD, Argüeso P, et al. The TFOS International workshop on contact lens discomfort: Report of the contact lens interactions with the tear film subcommittee. Invest Ophthalmol Vis Sci 2013;54:123–156. 9. Glasson MJ, Stapleton F, Keay L, et al. The effect of short term contact lens wear on the tear film and ocular surface characteristics of tolerant and intolerant wearers. Contact Lens Anterior Eye 2006;29:41–47. 10. Holly FJ. Physical chemistry of the normal and disordered tear film. Trans Ophthalmol Soc U K 1985;104:374–380. 11. Chen Q, Wang J, Sen M, et al. Lower volumes of tear menisci in contact lens wearers with dry eye symptoms. Invest Ophthalmol Vis Sci 2009;50: 3159–3163. 12. Chen Q, Wang J, Shen M, et al. Tear menisci and ocular discomfort during daily contact lens wear in symptomatic wearers. Invest Ophthalmol Vis Sci 2011;52:2175–2180. 13. Wang J, Cox I, Reindel WT. Upper and lower tear menisci on contact lenses. Invest Ophthalmol Vis Sci 2009;50:1106–1111. 14. Le Q, Jiang C, Jiang AC, et al. The analysis of tear meniscus in soft contact lens wearers by spectral optical coherence tomography. Cornea 2009;28: 851–855. 15. Jones L, Brennan NA, González-Méijome J, et al. The TFOS International workshop on contact lens discomfort: Report of the contact lens materials, design, and care subcommittee. Invest Ophthalmol Vis Sci 2013;54:37–70. 16. Li Y, Kuang K, Yerxa B, et al. Rabbit conjunctival epithelium transports fluid, and P2Y2(2) receptor agonists stimulate Cl(-) and fluid secretion. Am J Physiol Cell Physiol 2001;281:C595–C602. 17. Jumblatt JE, Jumblatt MM. Regulation of ocular mucin secretion by P2Y2 nucleotide receptors in rabbit and human conjunctiva. Exp Eye Res 1998;67: 341–346. 18. Murakami T, Fujihara T, Horibe Y, et al. Diquafosol elicits increases in net Cl- transport through P2Y2 receptor stimulation in rabbit conjunctiva. Ophthalmic Res 2004;36:89–93. 19. Matsumoto Y, Ohashi Y, Watanabe H, et al. Diquafosol Ophthalmic Solution Phase 2 Study Group. Efficacy and safety of diquafosol ophthalmic solution in patients with dry eye syndrome: A Japanese phase 2 clinical trial. Ophthalmology 2012;119:1954–1960. 20. Kamiya K, Nakanishi M, Ishii R, et al. Clinical evaluation of the additive effect of diquafosol tetrasodium on sodium hyaluronate monotherapy in patients with dry eye syndrome: A prospective, randomized, multicenter study. Eye (Lond) 2012;26:1363–1368. 21. Takamura E, Tsubota K, Watanabe H, et al. Diquafosol Ophthalmic Solution Phase 3 Study Group. A randomised, double-masked comparison study
322
Eye & Contact Lens Volume 41, Number 5, September 2015
22.
23.
24.
25.
26.
27.
28.
29.
30.
31. 32. 33.
34. 35. 36. 37.
38.
39. 40.
of diquafosol versus sodium hyaluronate ophthalmic solutions in dry eye patients. Br J Ophthalmol 2012;96:1310–1315. Kaido M, Uchino M, Kojima T, et al. Effects of diquafosol tetrasodium administration on visual function in short break-up time dry eye. J Ocul Pharmacol Ther 2013;29:595–603. Shimazaki-Den S, Iseda H, Dogru M, et al. Effects of diquafosol sodium eye drops on tear film stability in short BUT type of dry eye. Cornea 2013;32: 1120–1125. Koh S, Ikeda C, Takai Y, et al. Long-term results of treatment with diquafosol ophthalmic solution for aqueous-deficient dry eye. Jpn J Ophthalmol 2013;57:440–446. Koh S, Maeda N, Ikeda C, et al. Effect of diquafosol ophthalmic solution on the optical quality of the eyes in patients with aqueous-deficient dry eye. Acta Ophthalmol 2014;92:e671–e675. Mori Y, Nejima R, Masuda A, et al. Effect of diquafosol tetrasodium eye drop for persistent dry eye after laser in situ keratomileusis. Cornea 2014; 33:659–662. Toda I, Ide T, Fukumoto T, et al. Combination therapy with diquafosol tetrasodium and sodium hyaluronate in patients with dry eye after laser in situ keratomileusis. Am J Ophthalmol 2014;157:616–622. Yokoi N, Kato H, Kinoshita S. Facilitation of tear fluid secretion by 3% diquafosol ophthalmic solution in normal human eyes. Am J Ophthalmol 2014;157:85–92. Fukuda R, Usui T, Miyai T, et al. Tear meniscus evaluation by anterior segment swept-source optical coherence tomography. Am J Ophthalmol 2013;155:620–624. Ohtomo K, Ueta T, Fukuda R, et al. Tear meniscus volume changes in dacryocystorhinostomy evaluated with quantitative measurement using anterior segment optical coherence tomography. Invest Ophthalmol Vis Sci 2014;55:2057–2061. Martin DK. Water transport in dehydrating hydrogel contact lenses: Implications for corneal desiccation. J Biomed Mater Res 1995;29:857–865. McConville P, Pope JM. Diffusion limited evaporation rates in hydrogel contact lenses. CLAO J 2001;27:186–191. Nichols JJ, Sinnott LT. Tear film, contact lens, and patient-related factors associated with contact lens-related dry eye. Invest Ophthalmol Vis Sci 2006;47:1319–1328. Efron N, Brennan NA, Currie JM, et al. Determinants of the initial comfort of hydrogel contact lenses. Am J Optom Physiol Opt 1986;63:819–823. Young G. Evaluation of soft contact lens fitting characteristics. Optom Vis Sci 1996;73:247–254. Palakuru JR, Wang J, Aquavella JV. Effect of blinking on tear dynamics. Invest Ophthalmol Vis Sci 2007;48:3032–3037. Palakuru JR, Wang J, Aquavella JV. Effect of blinking on tear volume after instillation of midviscosity artificial tears. Am J Ophthalmol 2008;146: 920–924. Lowther GE, Hill RM. Sensitivity threshold of the lower lid margin in the course of adaptation to contact lenses. Am J Optom Arch Am Acad Optom 1968;45:587–594. Polse KA. Etiology of corneal sensitivity changes accompanying contact lens wear. Invest Ophthalmol Vis Sci 1978;17:1202–1206. Stern ME, Beuerman RW, Fox RI, et al. The pathology of dry eye: The interaction between the ocular surface and lacrimal glands. Cornea 1998;17: 584–589.
Eye & Contact Lens Volume 41, Number 5, September 2015
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Prominent Decrease of Tear Meniscus Height With Contact Lens Wear and Efficacy of Eye Drop Instillation Yukiko Nagahara, M.D., Shizuka Koh, M.D., Naoyuki Maeda, M.D., Kohji Nishida, M.D., and Hitoshi Watanabe, M.D.
Objective: To investigate the change in tear meniscus height (TMH) before and after wearing soft contact lenses (CLs) of different water contents (WCs) and the influence of eye drop instillation on TMH during CL wear. Methods: Tear meniscus heights were measured using anterior segment optical coherence tomography in 20 normal subjects wearing a high-WC CL (WC, 69%) in 1 eye and a low-WC CL (WC, 24%) in the other. Tear meniscus height change after eye drop instillation with 3% diquafosol ophthalmic solution or saline with CL wear was evaluated at 5, 15, 30, and 60 min after instillation. Results: A significant decrease in TMH was observed after lens insertions of both CLs. Tear meniscus height was significantly decreased with highWC CL wear compared with that with low-WC CL wear. With high-WC CL wear, TMH increased significantly (P,0.001) at 5 min after the instillation of 3% diquafosol ophthalmic solution compared with the baseline values and then returned to the pre-instillation level. No significant TMH changes were found with the instillation of either eye drop (diquafosol or saline) with low-WC CL wear. Conclusions: Tear meniscus height decreased with CL wear, especially with high-WC CL wear. Significant increases in TMH were observed at 5 min after the instillation of diquafosol ophthalmic solution with high-WC CL wear. The increases in TMH after diquafosol instillation tended to be greater than those after saline instillation at least for 30 min with both highWC and low-WC CLs. Key Words: Tear meniscus—Dry eye—Contact lens—Water content— Diquafosol ophthalmic solution. (Eye & Contact Lens 2015;41: 318–322)
A
s stated in the Dry Eye WorkShop report in 2007, the major classes of dry eye are still aqueous tear-deficient dry eye and evaporative dry eye.1 Contact lens (CL) wear is one of the major extrinsic causes of evaporative dry eye.1 In healthy eyes, the corneal and conjunctival epithelium have a mechanism that maintains the tear film by presenting transmembrane mucins, such as MUC1, 4, and 16, at the epithelial-tear interface.2,3 The thin outermost lipid layer of the tear film can spread over the mucoaqueous layer of the tear film. The lipid layer stabilizes the tear film itself and prevents aqueous tear evaporation from the ocular surface. However, once From the Department of Ophthalmology (Y.N., S.K., N.M., K.N., H.W.), Osaka University Graduate School of Medicine, Suita, Osaka, Japan; and Department of Ophthalmology (H.W.), Kansai Rosai Hospital, Amagasaki, Hyogo, Japan. The authors have no funding or conflicts of interest to disclose. Address correspondence to Hitoshi Watanabe, M.D., Department of Ophthalmology, Osaka University Graduate School of Medicine, Room E7, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; e-mail: [email protected] Accepted December 23, 2014. DOI: 10.1097/ICL.0000000000000134
318
the CL is on the cornea, the prelens tear film cannot steadily maintain the tear film structure over the lens because transmembrane mucins are not present in the prelens tear film. Furthermore, the lipid layer fails to spread across the mucoaqueous layer. Because of the irregular and nonuniform lipid layer in the eyes with CLs, the evaporation of the tear film increases from the postlens tear film and the prelens tear film. Several studies have demonstrated that the tear film evaporation rate in eyes with CLs is higher than that in eyes without CLs.4–7 According to the recently published report on “Contact Lens Discomfort” by the Tear Film & Ocular Surface Society, several biophysical tear film changes have been associated with CL wear.8 Along with increased evaporation, other factors, such as tear film stability, prelens lipid layer thickness, tear volume, and changes in the tear composition have been associated with CL discomfort.8 A previous report proposed that among these factors, decreased tear volume may be a major factor inducing CL-related dry eye symptoms and intolerance.9 Because 75% to 90% of the tear volume exists in the upper and lower tear menisci,10 the tear meniscus dimensions can be a good indicator for estimating total tear volume. The measurement of tear meniscus height (TMH) using anterior segment optical coherence tomography (AS-OCT) is a common method used to quantify tear volume. Several studies have performed TMH measurements using AS-OCT in eyes with CLs.11–14 Moreover, the material and design of CLs may affect the interactions between the tear film and CLs.15 The water content (WC) of CLs can potentially influence the lens dehydration throughout the course of the wearing period, which can affect the prelens and postlens tear film. Several studies have evaluated TMH in eyes with CLs11–14; however, the effect of WC of the lens on TMH during CL wear is unknown. Artificial tears and tear retention agents have been used to lubricate the ocular surface and improve symptoms of irritation in CL wearers. The use of these eye drops has been expected to provide an aqueous component to the tear film and increase the tear volume. Diquafosol ophthalmic solution is a new, topical pharmacologic agent that has recently become commercially available for treating dry eye. Diquafosol is a P2Y2 purinergic receptor agonist that activates P2Y2 receptors on the ocular surface. Diquafosol stimulates both fluid secretion from the conjunctival epithelial cells and mucin secretion from the conjunctival goblet cells directly on the ocular surface, thereby rehydrating the ocular surface independent of tear film secretion from the lacrimal glands.16–18 The clinical efficacy of diquafosol for treating dry eye has been reported in recent articles19–27; however, its effect in eyes with CLs is not clear. Yokoi et al.28 have reported an increase in tear fluid volume induced by diquafosol in normal eyes. Because the decrease in Eye & Contact Lens Volume 41, Number 5, September 2015
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Eye & Contact Lens Volume 41, Number 5, September 2015 the tear meniscus is believed to be partly responsible for CL discomfort,12 it will be of interest to investigate the fluid secretion effect of diquafosol in eyes with CLs. In this study, we examined TMH change in eyes with CLs of different WCs. Furthermore, we evaluated the time course of TMH after eye drop instillation during CL wear using AS-OCT for the TMH measurement.
METHODS The Institutional Review Board of Osaka University Hospital approved this study, which adhered to the tenets of the Declaration of Helsinki. All patients provided informed consent after receiving an explanation of the nature and possible consequences of the study. Two studies were conducted. In the first study, the TMHs before and after the insertion of CLs with different WCs were examined. In the second study, the instillation effects of different eye drops on TMH during CL wear were evaluated.
Subjects The studies included 20 eyes of 10 normal volunteers (7 men, 3 women; average age, 36.767.3 years) who experienced no ocular diseases except refractive errors. No subject wore CLs. All participants met the following criteria: no ocular pathologic condition or systemic disorders and no drug administration with any known effects on visual acuity.
Types of Soft Contact Lens Two commercially available CLs of different WCs, nelfilcon A lenses (Dailies AquaComfort Plus; Alcon, Tokyo, Japan) (WC of 69%, high-WC CL) and lotrafilcon A lenses (Air Optix EX Aqua; Alcon) (WC of 24%, low-WC CL), were compared. The details of both products are shown in Table 1. We confirmed that both types of CLs fit each subject properly and that the lenses were similar in movement, central placement, and comfort. Subjects were randomly provided with a high-WC CL for one eye and a low-WC CL for the other eye.
Tear Meniscus Measurement Cross-sectional images of the lower TMH were taken vertically across the central cornea using Fourier-domain swept-source ASOCT (SS-1000; Tomey Corp., Nagoya, Japan). This system attains high-resolution imaging at 10 mm (axial) and 30 mm (transverse) TABLE 1.
Parameters of Lenses Used in the Study High-WC CL
Brand name (Japan) Brand name (USA) Manufacturer Lens material FDA classification Water content (%) Base curve (mm) Diameter (mm) Center thickness (mm) (at 23.00 D)
Dailies AquaComfort Plus Dailies AquaComfort Plus Alcon Nelfilcon A Group II 69.4 8.7 14.0 0.10
Low-WC CL Air Optix EX Aqua Air Optix Night and Day Aqua Alcon Lotrafilcon A Group I 24.0 8.4/8.6 13.8 0.08
CL, contact lens; D, diopters; WC, water content.
© 2015 Contact Lens Association of Ophthalmologists
Prominent Decrease of TMH With CL Wear and high-speed scanning of 30,000 A-scans per second. The principles, technique, and reproducibility of this device have been described previously.29,30 Briefly, subjects were asked to rest their head on the chin rest of the AS-OCT and instructed to blink spontaneously during the measurement. All subjects underwent ASOCT examination 1 sec after blinking. In accordance with previous studies,29,30 all AS-OCT images were processed by a single trained observer. Briefly, the procedures for the measurement of the TMH values were performed on 300% magnified images. Tear meniscus height was defined as the line distance starting at the fluid surface from the inferior cornea–meniscus junction to the lower eyelid– meniscus junction. The line distance between the two points was decided manually using the calipers on the magnified image and calculated automatically by the software.
Experimental Protocol
In the first study, the effect of different WCs of CLs on TMH was investigated. Anterior segment optical coherence tomography imaging was performed twice for each subject: before CL insertion (without the lens) and at 20 min after lens insertion. The change in TMH (DTMH) was calculated as the difference between the baseline TMH without the lens and TMH with the lens. In the second study, the time course of TMH after the eye drop instillation during CL wear was investigated in the six subjects who consented to the following procedure. Each subject randomly received a single drop of 3% diquafosol ophthalmic solution (3% Diquas; Santen Pharmaceutical Co., Osaka, Japan) in one eye and an isotonic borate-buffered saline (Soft Santear; Santen Pharmaceutical Co.) in the other eye while wearing both high-WC CL and low-WC CL. Tear meniscus height measurements were performed at 5, 15, 30, and 60 min after the eye drop instillation for both eyes in each subject. The DTMH was calculated as the difference between the baseline TMH and TMH after the instillation.
Statistical Analysis Data were analyzed using JMP ver. 9 (SAS Institute, Cary, NC). The Friedman repeated-measures analysis of variance on ranks test was used to assess the time course of DTMH. The appropriate post hoc Dunnett correction for multiple comparisons was used. The Kruskal–Wallis test was performed to compare the DTMH between high-WC CL and low-WC CL at each time point. The appropriate post hoc Tukey correction for multiple comparisons was used in this comparison. A P,0.05 was considered significant for all analyses.
RESULTS Tear Meniscus Height Change With Contact Lens Wear Figure 1 shows the representative lower tear meniscus images without and 20 min after high-WC CL insertion. Tear meniscus height values without and with a high-WC CL were 226 and 110 mm, respectively. In comparison to baseline TMH without CL, remarkable decrease in TMH was observed with the high-WC CL (Fig. 1). Tear meniscus height values without and with high-WC CLs were 244653 and 161638 mm, respectively. Tear meniscus height values without and with low-WC CLs were 257644 and 319
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Y. Nagahara et al.
Eye & Contact Lens Volume 41, Number 5, September 2015
FIG. 1. Representative lower tear meniscus images without (A) and with a high-WC CL (B). Tear meniscus height values without and with the high-WC CL were 226 and 110 mm, respectively. WC, water content; CL, contact lens.
198626 mm, respectively. After lens insertion, significant decreases in TMH were found with both high-WC CL and lowWC CL wear (P,0.001, P,0.001, respectively). Although there was no significant difference in the baseline TMHs (before the lens insertion) between high-WC CL and low-WC CL, TMH for highWC CL was significantly decreased compared with that for lowWC CL (P¼0.005). The calculated DTMH values for high-WC CL and low-WC CL were 298649 and 246638 mm, respectively. The DTMH value for high-WC CL was significantly greater than that with low-WC CL (Fig. 2).
DISCUSSION This showed a significant decrease in TMH after CL wear and the effects of different eye drop instillations on TMH during CL wear. Tear meniscus height was imaged and easily quantified using AS-OCT in eyes with both high-WC CLs and low-WC CLs. According to the previous study measuring TMH with 2 different silicone hydrogel CLs using AS-OCT, TMH values at 20 min after CL wear returned to the baseline values and remained that way for at least 4 hr.12 However, in this study, TMHs measured at 20 min after both high-WC CL and low-WC CL wear were
Tear Meniscus Height Change With Eye Drop Instillation
The DTMH data obtained before and after the instillation of 3% diquafosol ophthalmic solution or saline in the eyes with both high-WC CLs and low-WC CLs are shown in Figure 3. In eyes with high-WC CLs, the mean DTMHs after diquafosol instillation were 57.6, 49.2, 19.4, and 25.4 at 5, 15, 30, and 60 min after instillation, respectively. Tear meniscus height increased significantly (P,0.001) at 5 min after the instillation of diquafosol ophthalmic solution compared with the baseline values and then returned to pre-instillation levels. In contrast, the mean DTMHs after saline instillation were 20, 14.8, 0.8, and 5.3 at 5, 15, 30, and 60 min after instillation, respectively. No significant DTMH was found with the instillation of saline. In the eyes with low-WC CLs, the mean DTMHs were 46, 35.4, 6, and 218.4 at 5, 15, 30, and 60 min after diquafosol instillation and 7.8, 2.8, 224.6, and 224.2 at 5, 15, 30, and 60 min after saline instillation, respectively. There were no significant DTMHs after the instillation of both eye drops. At 60 min after the instillation of both eye drops, TMH tended to be lower than the baseline levels. 320
FIG. 2. The lower TMH change before and after the wearing highWC and low-WC CLs. The change in TMH (DTMH) with the high-WC CLs was significantly greater than that with low-WC CLs. TMH, tear meniscus height; DTMH, change in tear meniscus height; WC, water content; and CL, contact lens. *P,0.001 (high-WC CLs vs. low-WC CLs), †P,0.001 (baseline and 20 min after high-WC CL insertion), and ‡P,0.001 (baseline and 20 min after low-WC CL insertion).
Eye & Contact Lens Volume 41, Number 5, September 2015
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Eye & Contact Lens Volume 41, Number 5, September 2015
FIG. 3. The time course of the lower TMH after eye drop instillation with high-WC and low-WC CLs wear. With high-WC CL wear, TMH increased significantly (P,0.001) at 5 min after diquafosol instillation compared with the baseline values and then returned to pre-instillation levels. No significant TMH changes were found with both diquafosol and saline instillation with low-WC CL wear. TMH, tear meniscus height; DTMH, change in tear meniscus height; WC, water content; and CL, contact lens. *P,0.001 (in comparison with baseline).
significantly decreased compared with the baseline TMHs. Moreover, at 20 min after CL wear, TMH with high-WC CL wear was significantly lower than that with low-WC CL, which has not been reported previously. Dehydration has been reported to be more pronounced with high-WC hydrogel CLs leading to decreased end-of-day comfort.31–33 Furthermore, improved comfort for lowWC CLs compared with high-WC CLs has been reported.34,35 In the normal tear system, the tear drainage system maintains a dynamic balance so that the tear volume sustains a relatively steady state and keeps the ocular surface wet.8 Palakuru et al.36,37 have reported that the lower tear meniscus may regulate the tear drainage system. If such a system can function, it may be possible that an increase in tear secretion by the lacrimal gland, contributing to the increase of TMH, could compensate for dehydration or increased evaporation with CL wear. However, the decrease in corneal sensitivity with CL wear38,39 may lead to a reduction in tear secretion through the reflex sensory loop.40 Therefore, even when greater evaporation occurs with high-WC CL wear in the setting of a dehydrated surface, a decrease in corneal sensitivity can result in a decrease of TMH. Although the actual mechanism of CL wear and ocular surface sensitivity is still unclear, the relation© 2015 Contact Lens Association of Ophthalmologists
Prominent Decrease of TMH With CL Wear ship among CL materials, tear parameters, and corneal sensitivity during CL wear is of interest and should be clarified in future studies. Because end-of-day dryness is one hallmark symptom of CLrelated dry eye, future studies with longer observation periods will be needed. Previous studies have shown decreased tear volume during CL wear for 10 hr11 and a significant relationship between ocular comfort and tear volume after 10 hr of CL wear.12 Based on these findings, it could be expected that both high-WC CLs and low-WC CLs could cause a decrease in TMH with longer periods of CL wear. It is important to investigate how the difference in WCs of CLs influences TMH after longer periods of CL wear. Moreover, the difference in the subjective dry eye–related symptoms between high-WC and low-WC CLs is also of interest. Although we did not evaluate subjective dry eye–related symptoms, such TMH decrease may easily lead to discomfort and irritation with CL wear. In this study, a significant increase in TMH was observed at 5 min after the instillation of diquafosol in eyes with high-WC CLs, whereas no significant change was observed with saline. Previous studies that investigated TMH or tear volume change after artificial eye drop instillation in eyes with CLs reported that TMH or tear volume increased after rewetting, but this increase only lasted for 10 to 20 min.12,13 In this study, the results obtained with diquafosol instillation with high-WC and low-WC CL wear were similar to the previous findings. Conversely, the time course of DTMH with saline instillation in this study showed no change at up to 60 min with high-WC CLs. At 60 min after the instillation of both eye drops, TMH with low-WC CL wear tended to be lower than the baseline levels. According to Yokoi et al.,28 diquafosol increased the radius value of the tear meniscus curvature from 5 to 30 min after instillation in normal eyes without CLs, and the effect was significant compared with that of artificial tears. Although we did not investigate TMH change with eye drop instillation in eyes without CLs, we assume that eyes with high-WC CL that have a remarkable decrease in TMH might benefit from a transient increase in wetness by diquafosol. Although the observation for longer period after instillation is needed, it is possible that evaporation or dehydration associated with high-WC CL might be improved owing to the increase in wetness with diquafosol. Further studies are needed to demonstrate the effect of diquafosol in symptomatic CL wearers. We report for the first time that TMH was remarkably decreased with high-WC CL wear compared with low-WC CL wear and that a significant increase of TMH was observed at 5 min after the instillation of diquafosol ophthalmic solution during high-WC CL wear. The limitations of this study were the small sample size and the limited time duration after eye drop instillation. Although we were specifically interested in exploring TMH change in eyes wearing CLs of different WCs and the time course of TMH after eye drop instillation, the relationship between the subjective symptoms of CL discomfort and TMH should be clarified in future studies. Based on the preliminary examination of a few subjects from this study, we anticipate further studies demonstrating the efficacy of diquafosol ophthalmic solution for CL-related dry eye. REFERENCES 1. 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;5:75–92.
321
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Y. Nagahara et al. 2. Spurr-Michaud S, Argüeso P, Gipson I. Assay of mucins in human tear fluid. Exp Eye Res 2007;84:939–950. 3. Watanabe H. Significance of mucin on the ocular surface. Cornea 2002;21: S17–S22. 4. Guillon M, Maissa C. Contact lens wear affects tear film evaporation. Eye Contact Lens 2008;34:326–330. 5. Tomlinson A, Cedarstaff T. Tear evaporation from the human eye: The effects of contact lens wear. J Br Contact Lens Assoc 1982;5:141–150. 6. Thai LC, Tomlinson A, Doane MG. Effect of contact lens materials on tear physiology. Optom Vis Sci 2004;81:194–204. 7. Cedarstaff TH, Tomlinson A. A comparative study of tear evaporation rates and water content of soft contact lenses. Am J Optom Physiol Opt 1983;60: 167–174. 8. Craig JP, Willcox MD, Argüeso P, et al. The TFOS International workshop on contact lens discomfort: Report of the contact lens interactions with the tear film subcommittee. Invest Ophthalmol Vis Sci 2013;54:123–156. 9. Glasson MJ, Stapleton F, Keay L, et al. The effect of short term contact lens wear on the tear film and ocular surface characteristics of tolerant and intolerant wearers. Contact Lens Anterior Eye 2006;29:41–47. 10. Holly FJ. Physical chemistry of the normal and disordered tear film. Trans Ophthalmol Soc U K 1985;104:374–380. 11. Chen Q, Wang J, Sen M, et al. Lower volumes of tear menisci in contact lens wearers with dry eye symptoms. Invest Ophthalmol Vis Sci 2009;50: 3159–3163. 12. Chen Q, Wang J, Shen M, et al. Tear menisci and ocular discomfort during daily contact lens wear in symptomatic wearers. Invest Ophthalmol Vis Sci 2011;52:2175–2180. 13. Wang J, Cox I, Reindel WT. Upper and lower tear menisci on contact lenses. Invest Ophthalmol Vis Sci 2009;50:1106–1111. 14. Le Q, Jiang C, Jiang AC, et al. The analysis of tear meniscus in soft contact lens wearers by spectral optical coherence tomography. Cornea 2009;28: 851–855. 15. Jones L, Brennan NA, González-Méijome J, et al. The TFOS International workshop on contact lens discomfort: Report of the contact lens materials, design, and care subcommittee. Invest Ophthalmol Vis Sci 2013;54:37–70. 16. Li Y, Kuang K, Yerxa B, et al. Rabbit conjunctival epithelium transports fluid, and P2Y2(2) receptor agonists stimulate Cl(-) and fluid secretion. Am J Physiol Cell Physiol 2001;281:C595–C602. 17. Jumblatt JE, Jumblatt MM. Regulation of ocular mucin secretion by P2Y2 nucleotide receptors in rabbit and human conjunctiva. Exp Eye Res 1998;67: 341–346. 18. Murakami T, Fujihara T, Horibe Y, et al. Diquafosol elicits increases in net Cl- transport through P2Y2 receptor stimulation in rabbit conjunctiva. Ophthalmic Res 2004;36:89–93. 19. Matsumoto Y, Ohashi Y, Watanabe H, et al. Diquafosol Ophthalmic Solution Phase 2 Study Group. Efficacy and safety of diquafosol ophthalmic solution in patients with dry eye syndrome: A Japanese phase 2 clinical trial. Ophthalmology 2012;119:1954–1960. 20. Kamiya K, Nakanishi M, Ishii R, et al. Clinical evaluation of the additive effect of diquafosol tetrasodium on sodium hyaluronate monotherapy in patients with dry eye syndrome: A prospective, randomized, multicenter study. Eye (Lond) 2012;26:1363–1368. 21. Takamura E, Tsubota K, Watanabe H, et al. Diquafosol Ophthalmic Solution Phase 3 Study Group. A randomised, double-masked comparison study
322
Eye & Contact Lens Volume 41, Number 5, September 2015
22.
23.
24.
25.
26.
27.
28.
29.
30.
31. 32. 33.
34. 35. 36. 37.
38.
39. 40.
of diquafosol versus sodium hyaluronate ophthalmic solutions in dry eye patients. Br J Ophthalmol 2012;96:1310–1315. Kaido M, Uchino M, Kojima T, et al. Effects of diquafosol tetrasodium administration on visual function in short break-up time dry eye. J Ocul Pharmacol Ther 2013;29:595–603. Shimazaki-Den S, Iseda H, Dogru M, et al. Effects of diquafosol sodium eye drops on tear film stability in short BUT type of dry eye. Cornea 2013;32: 1120–1125. Koh S, Ikeda C, Takai Y, et al. Long-term results of treatment with diquafosol ophthalmic solution for aqueous-deficient dry eye. Jpn J Ophthalmol 2013;57:440–446. Koh S, Maeda N, Ikeda C, et al. Effect of diquafosol ophthalmic solution on the optical quality of the eyes in patients with aqueous-deficient dry eye. Acta Ophthalmol 2014;92:e671–e675. Mori Y, Nejima R, Masuda A, et al. Effect of diquafosol tetrasodium eye drop for persistent dry eye after laser in situ keratomileusis. Cornea 2014; 33:659–662. Toda I, Ide T, Fukumoto T, et al. Combination therapy with diquafosol tetrasodium and sodium hyaluronate in patients with dry eye after laser in situ keratomileusis. Am J Ophthalmol 2014;157:616–622. Yokoi N, Kato H, Kinoshita S. Facilitation of tear fluid secretion by 3% diquafosol ophthalmic solution in normal human eyes. Am J Ophthalmol 2014;157:85–92. Fukuda R, Usui T, Miyai T, et al. Tear meniscus evaluation by anterior segment swept-source optical coherence tomography. Am J Ophthalmol 2013;155:620–624. Ohtomo K, Ueta T, Fukuda R, et al. Tear meniscus volume changes in dacryocystorhinostomy evaluated with quantitative measurement using anterior segment optical coherence tomography. Invest Ophthalmol Vis Sci 2014;55:2057–2061. Martin DK. Water transport in dehydrating hydrogel contact lenses: Implications for corneal desiccation. J Biomed Mater Res 1995;29:857–865. McConville P, Pope JM. Diffusion limited evaporation rates in hydrogel contact lenses. CLAO J 2001;27:186–191. Nichols JJ, Sinnott LT. Tear film, contact lens, and patient-related factors associated with contact lens-related dry eye. Invest Ophthalmol Vis Sci 2006;47:1319–1328. Efron N, Brennan NA, Currie JM, et al. Determinants of the initial comfort of hydrogel contact lenses. Am J Optom Physiol Opt 1986;63:819–823. Young G. Evaluation of soft contact lens fitting characteristics. Optom Vis Sci 1996;73:247–254. Palakuru JR, Wang J, Aquavella JV. Effect of blinking on tear dynamics. Invest Ophthalmol Vis Sci 2007;48:3032–3037. Palakuru JR, Wang J, Aquavella JV. Effect of blinking on tear volume after instillation of midviscosity artificial tears. Am J Ophthalmol 2008;146: 920–924. Lowther GE, Hill RM. Sensitivity threshold of the lower lid margin in the course of adaptation to contact lenses. Am J Optom Arch Am Acad Optom 1968;45:587–594. Polse KA. Etiology of corneal sensitivity changes accompanying contact lens wear. Invest Ophthalmol Vis Sci 1978;17:1202–1206. Stern ME, Beuerman RW, Fox RI, et al. The pathology of dry eye: The interaction between the ocular surface and lacrimal glands. Cornea 1998;17: 584–589.
Eye & Contact Lens Volume 41, Number 5, September 2015
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
