Current Eye Research, 2014; 39(4): 359–364 ! Informa Healthcare USA, Inc. ISSN: 0271-3683 print / 1460-2202 online DOI: 10.3109/02713683.2013.844262
ORIGINAL ARTICLE
Evaluation of Ocular Surface Temperature in Patients with Pterygium Johannes Gonnermann, Anna-Karina B. Maier, Julian Phillip Klein, Eckart Bertelmann, Uwe Pleyer, and Matthias K. J. Klamann
ABSTRACT Purpose: To investigate ocular surface temperature in eyes with pterygium and dry eye disease. Methods: Eighteen eyes of 18 patients with pterygium (group 1), 18 eyes of 18 patients diagnosed with dry eye disease (group 2), and 22 eyes of 22 healthy subjects with no signs of dry eye (group 3), were included in this prospective study. Schirmer’s test I and II, and tear film break up time (BUT) were evaluated. Infrared thermal imaging (Tomey TG 1000, Tomey Corp, Nagoya, Japan) was used to study the temperature of the ocular surface. All measurements were performed by one examiner only. Results: No significant difference in temperature course over ten seconds of eye opening was present between groups 1 and 2 (p = 0.551). However, a significant difference was present between groups 1 and 3 (p = 0.001) and between groups 2 and 3 (p = 0.003). Comparing group 1 and group 2, statistically significant differences in Schirmer’s test I (p50.001) and II (p50.001) and BUT (p = 0.04) were present. There were also significant differences in Schirmer‘s test I (p50.001) and II (p50.001) and BUT (p50.001) between group 2 and group 3. No significant difference in Schirmer’s test I (p = 0.785) and II (p = 0.871) was present between group 1 and group 3. However, a statistically significant difference in BUT was noted (p50.001). Conclusion: During sustained eye opening, a significant decrease in corneal surface temperature occurred in eyes with pterygium and dry eye disease. Thermography, in addition to other investigations, might be used to objectively identify dry eye symptoms in patients with pterygium. In addition to cosmetic appearance, increasing astigmatism, and expanding growth towards the center of the cornea, this new supplementary data may help to determine the proper time for intervention. Keywords: Dry eye, ocular surface temperature, pterygium, thermography, Tomey TG 1000
INTRODUCTION
leads to oxidative stress, which causes genetic damage and stimulates inflammatory pathways, leading to a hyperproliferative state.6 A focal alteration of limbal stem cells in pterygia is also a wellestablished feature and is the key to understanding pterygia pathogenesis.7 Furthermore, the limbal predilection may be explained by the phenomenon of peripheral light focusing, in which incidental light passes through the anterior chamber and is focused at the distal (nasal) limbus, where limbal stem cells reside.8 Symptoms of ocular dryness, irritation, and foreign body sensation may accompany the growth of pterygium onto the cornea, in addition to blurred
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Department of Ophthalmology, University Medicine Charite´ Berlin, Berlin, Germany
Pterygium is a common wing-shaped ocular surface disease traditionally described as an encroachment of bulbar conjunctiva onto the cornea, with a prevalence ranging from 1000 to 33,000 per 100,000, depending on geographic location, with a higher prevalence in regions closer to the equator.1,2 Theories of the pathogenesis of pterygium have implicated chronic ultraviolet light exposure as a major causative factor. Evidence for sunlight exposure as one of the prime etiological agents derives both from case-control studies and prevalence surveys.3–5 UV-exposure
Received 1 March 2013; revised 8 August 2013; accepted 9 September 2013; published online 11 November 2013 Correspondence: Johannes Gonnermann, MD, Department of Ophthalmology, University Medicine Charite´ Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail: [email protected]
359
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360 J. Gonnermann et al. vision, astigmatism, and an unfavorable cosmetic effect. The relationship between pterygium and tear film function has been difficult to define. Decreased tear breakup time (BUT), abnormal tear-ferning types, and/or insufficient tear secretion in pterygium patients have been noted by some, but not all, investigators.9,10 Additionally, there have been no reports on ocular surface temperature in this pathologic condition. In diagnosing dry eye symptoms, tear dynamics are currently evaluated clinically by the Schirmer’s test, break-up time, inspection of lids and conjunctiva (lidparallel conjunctival folds [LIPCOF]), measurement of the tear meniscus, osmolarity testing, and the Rose Bengal test.11–14 Previous studies demonstrated that measurement of the corneal surface temperature may complement these diagnostic tools. The surface temperature was shown to be significantly higher in dry eyes than in healthy subjects. Furthermore, the temperature at the center of the cornea of dry eyes was found to decrease more than the center of the cornea of healthy eyes after sustained eye opening.15–19 Ocular surface thermography is a well-known technique for temperature measurement of the anterior eye. Modern thermography, pioneered by Mapstone,18 is a non-invasive technique used to measure the surface temperature of an object by detecting the intensity of infrared light that is emitted from the object. Current studies have shown that noninvasive measurement with the Tomey TG-1000 (Tomey Corp, Nagoya, Japan) is a simple and quick tool for the screening of dry eye, enabling data to be collected quickly, objectively, and noninvasively, with high intraobserver reproducibility.15,19 The goal of this study was to investigate ocular surface temperature in eyes with pterygium and to describe an additional objective benchmark that might be used in order to potentially determine the right time for intervention.
PATIENTS AND METHODS Eighteen eyes of 18 patients with pterygium (group 1), 18 eyes of 18 patients diagnosed with dry eye disease (group 2), and 22 eyes of 22 healthy subjects with no signs of dry eyes (group 3) were included in this prospective study during the enrolment period from January 2011 to October 2011. This study followed the ethical standards of the Declaration of Helsinki. All subjects were over 18 years of age and provided informed consent before being recruited into the study and after receiving a full explanation of all procedures. After informed consent was provided, each study participant underwent a complete ophthalmological examination, including a medical history review, best-corrected
visual acuity (BCVA) measurement, Schirmer‘s test, tear break up time (BUT), slit-lamp biomicroscopy, and dilated fundus examination. Patients with primary unilateral pterygium were identified on the basis of clinical history and the evaluation of signs and symptoms. Pterygium morphologic features were graded according to the system described by Tan et al.20 According to this grading system, pterygia were graded as grade T1 (atrophic pterygium) if episcleral vessels were seen easily under the body of the pterygium, grade T3 (fleshy pterygium) if episcleral vessels were obscured completely, and grade T2 (between grades T1 and T3) if episcleral vessels were partially obscured. Only subjects with T2 were included in this study. None of the subjects included in the study had any evidence of ocular infection, contact lens wear, abnormal blinking, or prior ocular surgery. Subjects who fulfilled the following three criteria were diagnosed as having dry eye and were assigned to group 2: subjective symptoms related to dry eye like foreign body sensation, irritation, ocular pain, or dryness; abnormalities in tear dynamics, i.e. Schirmer‘s test I 5 mm; or BUT five seconds [16]. Schirmer‘s test I was analyzed after five minutes without any eye drops. Schirmer‘s test II was performed five minutes after administration of a drop of solution containing Oxybuprocain HCl (4.0 mg/ml) into the conjunctival sac [16]. The BUT was measured following a 15-minute rest interval using 2% sodium fluorescein solution that was instilled onto the inferior palpebral conjunctiva after gentle depression of the lower eyelid. The subject was then asked to blink gently, but completely, three times. The tear film was then examined with a broad beam and the cobalt blue filter of a slit lamp. The interval between the last blink and the appearance of the first precorneal hypofluorescent spot, streak or other irregularity interrupting the normal homogenous fluorescein pattern was recorded as the BUT (seconds). Individuals who had a history of atopy; allergic diseases; Stevens-Johnson syndrome; or chemical, thermal, or radiation injury were excluded. Subjects were also excluded if they had any other ocular or systemic disorders or had undergone any ocular surgery or contact lens use that would create an ocular surface problem or dry eye. As far as we were aware, all subjects in the healthy control group were free from ocular and systemic diseases. All measurements described above were performed by one examiner only (JG).
Procedures A non-contact thermography device (Tomey TG 1000) was used. Kamao et al. first described this ocular Current Eye Research
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Ocular Surface Temperature in Pterygium surface thermographer.15 In a previous study, we indicated a high reproducibility in ocular surface temperature measurements taken with this instrument.19 The instrument is equipped with an infrared camera module (HX083M1; NEC, Tokyo, Japan) and a color-charged coupled device onboard camera (PKD101; Pacific CO, Tokyo, Japan). Light can be directed into either an infrared or visible light camera. The direction of the light is changed with a sliding mirror, and both infrared and visible light images can be recorded coaxially. This instrument should detect temperatures in a target range between 30 C and 40 C, with a minimum temperature accuracy of 0.10 C. The manufacturer indicates a frame rate of four frames per second, which yields two frames per second each when measuring infrared and color images. Ten seconds are required to perform each measurement. Using the highest magnification, the infrared sensor can record images at a resolution of 320 240 pixels with a pixel size of 23.5 23.5 mm and spatial resolution of 70 mm. The infrared radiation detector module is sensitive to infrared radiation between 8 and 14 mm. Color images are obtained with a coupled device video camera that can record images at a resolution of 640 480 pixels, with a pixel size of 5.6 5.6 mm, and a detection range of 0.5 lux at 30 frames/second. To correct for background radiation entering the infrared camera, a black body plate is automatically inserted to cover the sensor immediately before beginning the measurements. A sensor is embedded in the camera and a program is installed in the instrument to correct for changes in the internal temperature of the interior of the instrument during measurements. An auto-alignment function is incorporated in the instrument to ensure that the instrument and object maintain a fixed location relative to each other. This auto-alignment function holds the position of the cameras constant with respect to the object to be measured, which allows measurements of the ocular surface temperature to be performed at the same position. This feature is identical to that of the RC-5000 Autorefractor/Keratometer (RC-5000; Tomey Corp), which recognizes the pupil and aligns the pupil in the center of the screen when the examiner touches the center of the touch panel. The head of the Ocular Surface Thermographer also moves along the z-axis automatically to maintain the instrument at a fixed distance from the eye. Each subject was examined in a room at 24.00 C 1.50, with standard indoor levels of illumination (300 lux) and humidity (þ43.5% 3.0), and no air drafts. Room settings were re-checked by the ocular surface thermographer and were displayed on the monitor in numeric data. The measurements were performed under the conditions described by Mori [17]: the subject blinked normally, then closed both eyes for five seconds, and then kept the eyes open for more than 10 seconds. The thermographic device !
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was set up 20 cm in front of the eye and the head was held steady with a frame. First, subjects were instructed to open their eyes naturally and look straight ahead to get a sharp image of the cornea on the monitor. Subsequently, subjects were asked to close their eyes. With closed eyes, the surrounding temperature of the ocular surface including the surrounding tissue and overall room temperature was measured over a period of five seconds. Afterwards, the subjects were requested to open both eyes naturally and look straight ahead again; after a blink, a measurement was made. The temperature was measured within 10 seconds of opening the eye. During that time the subject was asked not to blink. If the subject blinked anyway, a new measurement was performed. To avoid any unsteadiness, all thermographic measurements were performed in an examination room used for ocular thermography by one examiner (JG). Following these investigations, all images were converted to infrared and color pictures and were made visible on a monitor for analyzing. Minimum and maximum temperature readings as well as the temperature over the course of the ten seconds of eye opening were given in graphical order. The minimum, maximum, and mean temperature of the ocular surface of eyes with pterygium and the course over time of sustained eye opening were examined and compared to those of the group with dry eye disease and the control group.
Data Analysis Fifty-eight eyes were included in the analysis. All results are expressed in mean standard deviation (SD). Normality of data samples was evaluated using the Kolmogorov-Smirnov test. Normally-distributed variables were compared with the independent sample t-test. Numeric variables that were not normally distributed were compared with the Mann– Whitney U test. The Chi2-test was used to compare age and gender differences between the groups. Pearson’s correlation coefficient was used for examining correlation. The procedures of the analysis program PAWS (v 18.0, Version for Mac) were used. For all times, p values lower than 0.05 were determined to be significant.
RESULTS Demographic data are presented in Table 1. No statistically difference in age (group 1 versus group 2 [p = 0.873], group 1 versus group 3 [p = 0.562], and group 2 versus group 3 [p = 0.681], Chi2-test) and gender (group 1 versus group 2 [p = 0.811], group 1
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362 J. Gonnermann et al. versus group 3 [p = 0.413], and group 2 versus group 3 [p = 0.561], Chi2-test) was present. Table 2 shows the minimum, maximum, and mean ocular surface temperature, as well as the temperature course over 10 seconds of sustained eye opening, Schirmer‘s test I and II, and the BUT for the three groups examined. Comparing minimum, maximum, and mean ocular surface temperature, there were no statistically significant differences between any groups. No significant difference in the temperature course over 10 seconds of sustained eye opening was present between groups 1 and 2 (p = 0.551; Mann–Whitney U test). However, a significant difference was present between groups 1 and 3 (p = 0.001; Mann–Whitney U test) and between groups 2 and 3 (p = 0.003; Mann– Whitney U test) (Figure 1). Comparing group 1 and group 2, statistically significant differences in Schirmer’s test I (p50.001; Mann–Whitney U test) and II (p50.001; Mann– Whitney U test) and BUT (p = 0.04; Mann–Whitney U test) were present. There were also significant differences in Schirmer’s test I (p50.001; Mann– Whitney U test) and II (p50.001; Mann–Whitney U test) and BUT (p50.001; Mann–Whitney U test) between groups 2 and 3. No significant differences in Schirmer’s test I (p = 0.785; Mann–Whitney U test) and II (p = 0.871; Mann–Whitney U test) were present between group 1 and group 3. However, a statistically significant difference in BUT was noted (p50.001; Mann–Whitney U test). A negative correlation between the BUT and the temperature course over 10 seconds of sustained eye opening was present in either group (group 1: r = 0.454, p = 0.042; group 2: r = 0.431, p = 0.041; group 3: r = 0.707, p50.001; Pearson‘s correlation coefficient). However, no statistically significant
correlation between the minimum, maximum, and mean ocular surface temperature and the BUT or Schirmer‘s test I and II was present in any group. Ocular surface temperature examinations in two eyes in group 1 were repeated owing to blinks during the scanning process or to early patient movement. In these patients, the thermography device was not able to measure the ocular surface temperature over a time period of 10 seconds. After repetition, all 58 eyes could be included in this study.
DISCUSSION Due to the hyperproliferative growth of the conjuctiva onto the cornea, pterygia are often associated with symptoms of ocular dryness, irritation, and foreign body sensation.9,10,21 The relationship between pterygium and tear film function on the one hand, and subjective patient perceptions on the other hand, has been difficult to define. To date, assessments of dry eye symptoms in patients with pterygium have relied on indications of decreased BUT, abnormal tearferning types, and/or insufficient tear secretion.9,10,21 A non-invasive device providing objectively repeatable quantitative data could help to identify whether an early surgical treatment would be adequate to abate the symptoms or should be suspended due to minor disorders. To the best of our knowledge, this is the first study to attempt to capture the phenomenon of dry eye
TABLE 1 Demographic data.
Number of eyes Female:Male Age in years (mean STD)
Patients with pterygium (group 1)
Patients with dry eye disease (group 2)
Healthy subjects (group 3)
18 8:10 55.3 16.1
18 10:8 58.4 14.3
22 12:10 63.4 15.8
FIGURE 1 Temperature decrease over 10 seconds of sustained eye opening for the three groups conducted. Group 1 = pterygium; Group 2 = dry eye disease; Group 3 = control group.
TABLE 2 Overall corneal temperature ( C), Schirmer‘s test I and II (mm), break-up time (seconds) for the three groups conducted; group 1 = pterygium; group 2 = dry eye disease; group 3 = control group; Temperature course during 10 seconds of sustained eye opening; all data are mean standard deviation.
Group 1 (n = 18) Group 2 (n = 18) Group 3 (n = 22)
Temperature min ( C)
Temperature max ( C)
Temperature mean ( C)
Temperature course ( C)
Schirmer I (mm)
Schirmer II (mm)
Break-up time (sec)
34.6 0.7 34.3 0.5 34.5 0.7
34.7 0.8 34.9 0.5 34.8 0.7
34.6 0.9 34.6 0.6 34.7 0.7
0.4 0.1 0.5 0.3 0.2 0.2
21.58 8.54 7.08 5.16 23.18 9.64
13.71 7.43 4.67 4.21 15.82 9.93
6.54 4.56 2.94 1.30 12.64 3.49
Current Eye Research
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Ocular Surface Temperature in Pterygium symptoms in pterygium by ocular surface thermography. The intention was to describe an additional objective benchmark that may be used in order to potentially determine the right time for intervention. In the previous study, no significant differences in Schirmer‘s test I and II between patients with pterygium and healthy control subjects were found. However, Schirmer’s test I and II were significantly decreased in patients diagnosed with dry eye disease. Since patients with pterygium do not suffer from any lacrimal gland complications, Schirmer’s test is not expected to decrease. This implies that diagnosing dry eye symptoms with the Schirmer’s test alone may not be sufficient to detect irritation and foreign body sensation in patients with pterygium. Since a perygium is a wing-shaped ocular surface disease traditionally described as an encroachment of bulbar conjunctiva onto the cornea,1,2 the tear film layer remains unstable. To capture the disorder precisely, it may be more reasonable to use BUT. Ishioka et al. found a correlation between pterygium formation and shortened BUT.10 They concluded that an unstable tear film layer may contribute to the initiation of pterygium. However, although BUT was decreased in patients with pterygium in our study, BUT was even lower in patients diagnosed with dry eye disease. Nevertheless, since a Schirmer’s test I 5 mm, or BUT five seconds was an inclusion criteria for being diagnosed with dry eye disease in this study, interpretation of the differences in both tests between the groups should be interpreted carefully. In addition to the Schirmer’s tests and BUT, the ocular surface temperature was examined in our study. The latest generation of commercially available ocular thermography instrument was used. The measurement of the ocular surface leads to a highresolution color-coded infrared image. When read beside photographic documentation, data on the infrared image can be easily matched to real ocular conditions. A movable identification mark on the infrared image as well as on the corresponding color image at the same point of interest allows differences in temperature to be examined in context with changes on the ocular surface, i.e. the dimension of the pterygium. Additionally, it offers the opportunity to document changes in both temperature and anatomy in an easy way. Though high intraobserver reproducibility in ocular surface temperature measurements has been described,19 interindividual variability may influence the measurement and should be addressed as limitation of this study and as a potential influencing factor in daily clinical routine. In previous studies, a significant negative correlation between temperature gradient at the center of the cornea and BUT could be found in patients with dry eyes.15 This indicates that eyes with a shorter BUT are more likely to experience a decrease in ocular surface temperature over time. Regarding the results !
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of our study, a significant difference in temperature course over ten seconds of sustained eye opening (p = 0.001) was found between eyes with pterygium and those of healthy subjects. Nevertheless, no significant differences in temperature over 10 seconds of sustained eye opening were present between eyes with pterygium and eyes with dry eye disease (p = 0.551). Furthermore, a significant correlation between the temperature course over 10 seconds of sustained eye opening and the BUT was found in eyes with pterygium and eyes with dry eye disease. These findings may indicate the instability of the tear film layer in eyes with pterygium which worsens the tear fluid evaporation. The resulting heat of vaporization may result in a decrease in ocular surface temperature.15 However, it also clearly demonstrates that temperature plays a major role in ocular surface alterations. Thermography may be an useful additional tool to objectively identify ocular surface unsteadiness in patients with pterygium and dry eye disease.
CONCLUSION The present study shows that thermography, in addition to other investigations, might be useful to objectively identify dry eye symptoms in patients with pterygium. In addition to cosmetic appearance, increasing astigmatism, and expanding growth towards the center of the cornea, this new supplementary temperature data may help to determine the proper time for intervention.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES 1. Norn MS. Prevalence of pinguecula in Greenland and in Copenhagen, and its relation to pterygium and spheroid degeneration. Acta Ophthalmol 1979;57:96–105. 2. Panchapakesan J, Hourihan F, Mitchell P. Prevalence of pterygium and pinguecula: the Blue Mountains Eye Study. Aust N Z J Ophthalmol 1998;26:S2–S5. 3. Saw SM, Tan D. Pterygium: prevalence, demography and risk factors. Ophthalmic Epidemiol 1999;6:219–228. 4. Moran DJ, Hollows FC. Pterygium and ultraviolet radiation: a positive correlation. Br J Ophthalmol 1984;68: 343–346. 5. Coroneo MT, Muller-Stolzenburg NW, Ho A. Peripheral light focusing by the anterior eye and the ophthalmohelioses. Ophthalmic Surg 1991;22:705–711. 6. Di Girolamo N, Chui J, Coroneo MT, Wakefield D. Pathogenesis of pterygia: role of cytokines, growth factors,
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and matrix metalloproteinases. Prog Retin Eye Res 2004;23: 195–228. Reid TW, Dushku N. Pterygia and limbal epithelial cells: relationship and molecular mechanisms. Prog Retin Eye Res 1996;15:297–329. Coroneo MT. Pterygium as an early indicator of ultraviolet insolation: a hypothesis. Br J Ophthalmol 1993;77: 734–739. Kadayifc¸ilar SC, Orhan M, Irkec¸ M. Tear functions in patients with pterygium. Acta Ophthalmol 1998;76:176–179. Ishioka M, Shimmura S, Yagi Y, Tsubota K. Pterygium and dry eye. Ophthalmologica 2001;215:209–211. Craig JP, Singh I, Tomlinson A, Morgan PB, Efron N. The role of tear physiology in ocular surface temperature. Eye (Lond) 2000;14:635–641. Foulks GN. The correlation between the tear film lipid layer and dry eye disease. Surv Ophthalmol 2007;52: 369–374. Versura P, Profazio V, Campos EC. Performance of tear osmolarity compared to previous diagnostic tests for dry eye diseases. Curr Eye Res 2010;35:553–564. Hoh H, Schirra F, Kienecker C, Ruprecht KW. [Lid-parallel conjunctival folds are a sure diagnostic sign of dry eye]. Ophthalmologe 1995;92:802–808.
15. Kamao T, Yamaguchi M, Kawasaki S, Mizoue S, Shiraishi A, Ohashi Y. Screening for Dry Eye with Newly Developed Ocular Surface Thermographer. Am J Ophthalmol 2011; 151:782–791. 16. Fujishima H, Toda I, Yamada M, Sato N, Tsubota K. Corneal temperature in patients with dry eye evaluated by infrared radiation thermometry. Br J Ophthalmol 1996;80: 29–32. 17. Mori A, Oguchi Y, Okusawa Y, Ono M, Fujishima H, Tsubota K. Use of high-speed, high-resolution thermography to evaluate the tear film layer. Am J Ophthalmol 1992;124:729–735. 18. Mapstone R. Measurement of corneal temperature. Exp Eye Res 1968; 7:237–243. 19. Klamann MK, Maier AK, Gonnermann J, Klein JP, Pleyer U. Measurement of dynamic ocular surface temperature in healthy subjects using a new thermography device. Curr Eye Res 2012;37:678–683. 20. Tan DT, Chee SP, Dear KB, Lim AS. Effect of pterygium morphology on pterygium recurrence in a controlled trial comparing conjunctival autografting with bare sclera excision. Arch Ophthalmol 1997;115:1235–1240. 21. Rajiv, Mithal S, Sood AK. Pterygium and dry eye – a clinical correlation. Indian J Ophthalmol 1991;39:15–16.
Current Eye Research
ORIGINAL ARTICLE
Evaluation of Ocular Surface Temperature in Patients with Pterygium Johannes Gonnermann, Anna-Karina B. Maier, Julian Phillip Klein, Eckart Bertelmann, Uwe Pleyer, and Matthias K. J. Klamann
ABSTRACT Purpose: To investigate ocular surface temperature in eyes with pterygium and dry eye disease. Methods: Eighteen eyes of 18 patients with pterygium (group 1), 18 eyes of 18 patients diagnosed with dry eye disease (group 2), and 22 eyes of 22 healthy subjects with no signs of dry eye (group 3), were included in this prospective study. Schirmer’s test I and II, and tear film break up time (BUT) were evaluated. Infrared thermal imaging (Tomey TG 1000, Tomey Corp, Nagoya, Japan) was used to study the temperature of the ocular surface. All measurements were performed by one examiner only. Results: No significant difference in temperature course over ten seconds of eye opening was present between groups 1 and 2 (p = 0.551). However, a significant difference was present between groups 1 and 3 (p = 0.001) and between groups 2 and 3 (p = 0.003). Comparing group 1 and group 2, statistically significant differences in Schirmer’s test I (p50.001) and II (p50.001) and BUT (p = 0.04) were present. There were also significant differences in Schirmer‘s test I (p50.001) and II (p50.001) and BUT (p50.001) between group 2 and group 3. No significant difference in Schirmer’s test I (p = 0.785) and II (p = 0.871) was present between group 1 and group 3. However, a statistically significant difference in BUT was noted (p50.001). Conclusion: During sustained eye opening, a significant decrease in corneal surface temperature occurred in eyes with pterygium and dry eye disease. Thermography, in addition to other investigations, might be used to objectively identify dry eye symptoms in patients with pterygium. In addition to cosmetic appearance, increasing astigmatism, and expanding growth towards the center of the cornea, this new supplementary data may help to determine the proper time for intervention. Keywords: Dry eye, ocular surface temperature, pterygium, thermography, Tomey TG 1000
INTRODUCTION
leads to oxidative stress, which causes genetic damage and stimulates inflammatory pathways, leading to a hyperproliferative state.6 A focal alteration of limbal stem cells in pterygia is also a wellestablished feature and is the key to understanding pterygia pathogenesis.7 Furthermore, the limbal predilection may be explained by the phenomenon of peripheral light focusing, in which incidental light passes through the anterior chamber and is focused at the distal (nasal) limbus, where limbal stem cells reside.8 Symptoms of ocular dryness, irritation, and foreign body sensation may accompany the growth of pterygium onto the cornea, in addition to blurred
20 14
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Department of Ophthalmology, University Medicine Charite´ Berlin, Berlin, Germany
Pterygium is a common wing-shaped ocular surface disease traditionally described as an encroachment of bulbar conjunctiva onto the cornea, with a prevalence ranging from 1000 to 33,000 per 100,000, depending on geographic location, with a higher prevalence in regions closer to the equator.1,2 Theories of the pathogenesis of pterygium have implicated chronic ultraviolet light exposure as a major causative factor. Evidence for sunlight exposure as one of the prime etiological agents derives both from case-control studies and prevalence surveys.3–5 UV-exposure
Received 1 March 2013; revised 8 August 2013; accepted 9 September 2013; published online 11 November 2013 Correspondence: Johannes Gonnermann, MD, Department of Ophthalmology, University Medicine Charite´ Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail: [email protected]
359
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360 J. Gonnermann et al. vision, astigmatism, and an unfavorable cosmetic effect. The relationship between pterygium and tear film function has been difficult to define. Decreased tear breakup time (BUT), abnormal tear-ferning types, and/or insufficient tear secretion in pterygium patients have been noted by some, but not all, investigators.9,10 Additionally, there have been no reports on ocular surface temperature in this pathologic condition. In diagnosing dry eye symptoms, tear dynamics are currently evaluated clinically by the Schirmer’s test, break-up time, inspection of lids and conjunctiva (lidparallel conjunctival folds [LIPCOF]), measurement of the tear meniscus, osmolarity testing, and the Rose Bengal test.11–14 Previous studies demonstrated that measurement of the corneal surface temperature may complement these diagnostic tools. The surface temperature was shown to be significantly higher in dry eyes than in healthy subjects. Furthermore, the temperature at the center of the cornea of dry eyes was found to decrease more than the center of the cornea of healthy eyes after sustained eye opening.15–19 Ocular surface thermography is a well-known technique for temperature measurement of the anterior eye. Modern thermography, pioneered by Mapstone,18 is a non-invasive technique used to measure the surface temperature of an object by detecting the intensity of infrared light that is emitted from the object. Current studies have shown that noninvasive measurement with the Tomey TG-1000 (Tomey Corp, Nagoya, Japan) is a simple and quick tool for the screening of dry eye, enabling data to be collected quickly, objectively, and noninvasively, with high intraobserver reproducibility.15,19 The goal of this study was to investigate ocular surface temperature in eyes with pterygium and to describe an additional objective benchmark that might be used in order to potentially determine the right time for intervention.
PATIENTS AND METHODS Eighteen eyes of 18 patients with pterygium (group 1), 18 eyes of 18 patients diagnosed with dry eye disease (group 2), and 22 eyes of 22 healthy subjects with no signs of dry eyes (group 3) were included in this prospective study during the enrolment period from January 2011 to October 2011. This study followed the ethical standards of the Declaration of Helsinki. All subjects were over 18 years of age and provided informed consent before being recruited into the study and after receiving a full explanation of all procedures. After informed consent was provided, each study participant underwent a complete ophthalmological examination, including a medical history review, best-corrected
visual acuity (BCVA) measurement, Schirmer‘s test, tear break up time (BUT), slit-lamp biomicroscopy, and dilated fundus examination. Patients with primary unilateral pterygium were identified on the basis of clinical history and the evaluation of signs and symptoms. Pterygium morphologic features were graded according to the system described by Tan et al.20 According to this grading system, pterygia were graded as grade T1 (atrophic pterygium) if episcleral vessels were seen easily under the body of the pterygium, grade T3 (fleshy pterygium) if episcleral vessels were obscured completely, and grade T2 (between grades T1 and T3) if episcleral vessels were partially obscured. Only subjects with T2 were included in this study. None of the subjects included in the study had any evidence of ocular infection, contact lens wear, abnormal blinking, or prior ocular surgery. Subjects who fulfilled the following three criteria were diagnosed as having dry eye and were assigned to group 2: subjective symptoms related to dry eye like foreign body sensation, irritation, ocular pain, or dryness; abnormalities in tear dynamics, i.e. Schirmer‘s test I 5 mm; or BUT five seconds [16]. Schirmer‘s test I was analyzed after five minutes without any eye drops. Schirmer‘s test II was performed five minutes after administration of a drop of solution containing Oxybuprocain HCl (4.0 mg/ml) into the conjunctival sac [16]. The BUT was measured following a 15-minute rest interval using 2% sodium fluorescein solution that was instilled onto the inferior palpebral conjunctiva after gentle depression of the lower eyelid. The subject was then asked to blink gently, but completely, three times. The tear film was then examined with a broad beam and the cobalt blue filter of a slit lamp. The interval between the last blink and the appearance of the first precorneal hypofluorescent spot, streak or other irregularity interrupting the normal homogenous fluorescein pattern was recorded as the BUT (seconds). Individuals who had a history of atopy; allergic diseases; Stevens-Johnson syndrome; or chemical, thermal, or radiation injury were excluded. Subjects were also excluded if they had any other ocular or systemic disorders or had undergone any ocular surgery or contact lens use that would create an ocular surface problem or dry eye. As far as we were aware, all subjects in the healthy control group were free from ocular and systemic diseases. All measurements described above were performed by one examiner only (JG).
Procedures A non-contact thermography device (Tomey TG 1000) was used. Kamao et al. first described this ocular Current Eye Research
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Ocular Surface Temperature in Pterygium surface thermographer.15 In a previous study, we indicated a high reproducibility in ocular surface temperature measurements taken with this instrument.19 The instrument is equipped with an infrared camera module (HX083M1; NEC, Tokyo, Japan) and a color-charged coupled device onboard camera (PKD101; Pacific CO, Tokyo, Japan). Light can be directed into either an infrared or visible light camera. The direction of the light is changed with a sliding mirror, and both infrared and visible light images can be recorded coaxially. This instrument should detect temperatures in a target range between 30 C and 40 C, with a minimum temperature accuracy of 0.10 C. The manufacturer indicates a frame rate of four frames per second, which yields two frames per second each when measuring infrared and color images. Ten seconds are required to perform each measurement. Using the highest magnification, the infrared sensor can record images at a resolution of 320 240 pixels with a pixel size of 23.5 23.5 mm and spatial resolution of 70 mm. The infrared radiation detector module is sensitive to infrared radiation between 8 and 14 mm. Color images are obtained with a coupled device video camera that can record images at a resolution of 640 480 pixels, with a pixel size of 5.6 5.6 mm, and a detection range of 0.5 lux at 30 frames/second. To correct for background radiation entering the infrared camera, a black body plate is automatically inserted to cover the sensor immediately before beginning the measurements. A sensor is embedded in the camera and a program is installed in the instrument to correct for changes in the internal temperature of the interior of the instrument during measurements. An auto-alignment function is incorporated in the instrument to ensure that the instrument and object maintain a fixed location relative to each other. This auto-alignment function holds the position of the cameras constant with respect to the object to be measured, which allows measurements of the ocular surface temperature to be performed at the same position. This feature is identical to that of the RC-5000 Autorefractor/Keratometer (RC-5000; Tomey Corp), which recognizes the pupil and aligns the pupil in the center of the screen when the examiner touches the center of the touch panel. The head of the Ocular Surface Thermographer also moves along the z-axis automatically to maintain the instrument at a fixed distance from the eye. Each subject was examined in a room at 24.00 C 1.50, with standard indoor levels of illumination (300 lux) and humidity (þ43.5% 3.0), and no air drafts. Room settings were re-checked by the ocular surface thermographer and were displayed on the monitor in numeric data. The measurements were performed under the conditions described by Mori [17]: the subject blinked normally, then closed both eyes for five seconds, and then kept the eyes open for more than 10 seconds. The thermographic device !
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was set up 20 cm in front of the eye and the head was held steady with a frame. First, subjects were instructed to open their eyes naturally and look straight ahead to get a sharp image of the cornea on the monitor. Subsequently, subjects were asked to close their eyes. With closed eyes, the surrounding temperature of the ocular surface including the surrounding tissue and overall room temperature was measured over a period of five seconds. Afterwards, the subjects were requested to open both eyes naturally and look straight ahead again; after a blink, a measurement was made. The temperature was measured within 10 seconds of opening the eye. During that time the subject was asked not to blink. If the subject blinked anyway, a new measurement was performed. To avoid any unsteadiness, all thermographic measurements were performed in an examination room used for ocular thermography by one examiner (JG). Following these investigations, all images were converted to infrared and color pictures and were made visible on a monitor for analyzing. Minimum and maximum temperature readings as well as the temperature over the course of the ten seconds of eye opening were given in graphical order. The minimum, maximum, and mean temperature of the ocular surface of eyes with pterygium and the course over time of sustained eye opening were examined and compared to those of the group with dry eye disease and the control group.
Data Analysis Fifty-eight eyes were included in the analysis. All results are expressed in mean standard deviation (SD). Normality of data samples was evaluated using the Kolmogorov-Smirnov test. Normally-distributed variables were compared with the independent sample t-test. Numeric variables that were not normally distributed were compared with the Mann– Whitney U test. The Chi2-test was used to compare age and gender differences between the groups. Pearson’s correlation coefficient was used for examining correlation. The procedures of the analysis program PAWS (v 18.0, Version for Mac) were used. For all times, p values lower than 0.05 were determined to be significant.
RESULTS Demographic data are presented in Table 1. No statistically difference in age (group 1 versus group 2 [p = 0.873], group 1 versus group 3 [p = 0.562], and group 2 versus group 3 [p = 0.681], Chi2-test) and gender (group 1 versus group 2 [p = 0.811], group 1
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362 J. Gonnermann et al. versus group 3 [p = 0.413], and group 2 versus group 3 [p = 0.561], Chi2-test) was present. Table 2 shows the minimum, maximum, and mean ocular surface temperature, as well as the temperature course over 10 seconds of sustained eye opening, Schirmer‘s test I and II, and the BUT for the three groups examined. Comparing minimum, maximum, and mean ocular surface temperature, there were no statistically significant differences between any groups. No significant difference in the temperature course over 10 seconds of sustained eye opening was present between groups 1 and 2 (p = 0.551; Mann–Whitney U test). However, a significant difference was present between groups 1 and 3 (p = 0.001; Mann–Whitney U test) and between groups 2 and 3 (p = 0.003; Mann– Whitney U test) (Figure 1). Comparing group 1 and group 2, statistically significant differences in Schirmer’s test I (p50.001; Mann–Whitney U test) and II (p50.001; Mann– Whitney U test) and BUT (p = 0.04; Mann–Whitney U test) were present. There were also significant differences in Schirmer’s test I (p50.001; Mann– Whitney U test) and II (p50.001; Mann–Whitney U test) and BUT (p50.001; Mann–Whitney U test) between groups 2 and 3. No significant differences in Schirmer’s test I (p = 0.785; Mann–Whitney U test) and II (p = 0.871; Mann–Whitney U test) were present between group 1 and group 3. However, a statistically significant difference in BUT was noted (p50.001; Mann–Whitney U test). A negative correlation between the BUT and the temperature course over 10 seconds of sustained eye opening was present in either group (group 1: r = 0.454, p = 0.042; group 2: r = 0.431, p = 0.041; group 3: r = 0.707, p50.001; Pearson‘s correlation coefficient). However, no statistically significant
correlation between the minimum, maximum, and mean ocular surface temperature and the BUT or Schirmer‘s test I and II was present in any group. Ocular surface temperature examinations in two eyes in group 1 were repeated owing to blinks during the scanning process or to early patient movement. In these patients, the thermography device was not able to measure the ocular surface temperature over a time period of 10 seconds. After repetition, all 58 eyes could be included in this study.
DISCUSSION Due to the hyperproliferative growth of the conjuctiva onto the cornea, pterygia are often associated with symptoms of ocular dryness, irritation, and foreign body sensation.9,10,21 The relationship between pterygium and tear film function on the one hand, and subjective patient perceptions on the other hand, has been difficult to define. To date, assessments of dry eye symptoms in patients with pterygium have relied on indications of decreased BUT, abnormal tearferning types, and/or insufficient tear secretion.9,10,21 A non-invasive device providing objectively repeatable quantitative data could help to identify whether an early surgical treatment would be adequate to abate the symptoms or should be suspended due to minor disorders. To the best of our knowledge, this is the first study to attempt to capture the phenomenon of dry eye
TABLE 1 Demographic data.
Number of eyes Female:Male Age in years (mean STD)
Patients with pterygium (group 1)
Patients with dry eye disease (group 2)
Healthy subjects (group 3)
18 8:10 55.3 16.1
18 10:8 58.4 14.3
22 12:10 63.4 15.8
FIGURE 1 Temperature decrease over 10 seconds of sustained eye opening for the three groups conducted. Group 1 = pterygium; Group 2 = dry eye disease; Group 3 = control group.
TABLE 2 Overall corneal temperature ( C), Schirmer‘s test I and II (mm), break-up time (seconds) for the three groups conducted; group 1 = pterygium; group 2 = dry eye disease; group 3 = control group; Temperature course during 10 seconds of sustained eye opening; all data are mean standard deviation.
Group 1 (n = 18) Group 2 (n = 18) Group 3 (n = 22)
Temperature min ( C)
Temperature max ( C)
Temperature mean ( C)
Temperature course ( C)
Schirmer I (mm)
Schirmer II (mm)
Break-up time (sec)
34.6 0.7 34.3 0.5 34.5 0.7
34.7 0.8 34.9 0.5 34.8 0.7
34.6 0.9 34.6 0.6 34.7 0.7
0.4 0.1 0.5 0.3 0.2 0.2
21.58 8.54 7.08 5.16 23.18 9.64
13.71 7.43 4.67 4.21 15.82 9.93
6.54 4.56 2.94 1.30 12.64 3.49
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Ocular Surface Temperature in Pterygium symptoms in pterygium by ocular surface thermography. The intention was to describe an additional objective benchmark that may be used in order to potentially determine the right time for intervention. In the previous study, no significant differences in Schirmer‘s test I and II between patients with pterygium and healthy control subjects were found. However, Schirmer’s test I and II were significantly decreased in patients diagnosed with dry eye disease. Since patients with pterygium do not suffer from any lacrimal gland complications, Schirmer’s test is not expected to decrease. This implies that diagnosing dry eye symptoms with the Schirmer’s test alone may not be sufficient to detect irritation and foreign body sensation in patients with pterygium. Since a perygium is a wing-shaped ocular surface disease traditionally described as an encroachment of bulbar conjunctiva onto the cornea,1,2 the tear film layer remains unstable. To capture the disorder precisely, it may be more reasonable to use BUT. Ishioka et al. found a correlation between pterygium formation and shortened BUT.10 They concluded that an unstable tear film layer may contribute to the initiation of pterygium. However, although BUT was decreased in patients with pterygium in our study, BUT was even lower in patients diagnosed with dry eye disease. Nevertheless, since a Schirmer’s test I 5 mm, or BUT five seconds was an inclusion criteria for being diagnosed with dry eye disease in this study, interpretation of the differences in both tests between the groups should be interpreted carefully. In addition to the Schirmer’s tests and BUT, the ocular surface temperature was examined in our study. The latest generation of commercially available ocular thermography instrument was used. The measurement of the ocular surface leads to a highresolution color-coded infrared image. When read beside photographic documentation, data on the infrared image can be easily matched to real ocular conditions. A movable identification mark on the infrared image as well as on the corresponding color image at the same point of interest allows differences in temperature to be examined in context with changes on the ocular surface, i.e. the dimension of the pterygium. Additionally, it offers the opportunity to document changes in both temperature and anatomy in an easy way. Though high intraobserver reproducibility in ocular surface temperature measurements has been described,19 interindividual variability may influence the measurement and should be addressed as limitation of this study and as a potential influencing factor in daily clinical routine. In previous studies, a significant negative correlation between temperature gradient at the center of the cornea and BUT could be found in patients with dry eyes.15 This indicates that eyes with a shorter BUT are more likely to experience a decrease in ocular surface temperature over time. Regarding the results !
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of our study, a significant difference in temperature course over ten seconds of sustained eye opening (p = 0.001) was found between eyes with pterygium and those of healthy subjects. Nevertheless, no significant differences in temperature over 10 seconds of sustained eye opening were present between eyes with pterygium and eyes with dry eye disease (p = 0.551). Furthermore, a significant correlation between the temperature course over 10 seconds of sustained eye opening and the BUT was found in eyes with pterygium and eyes with dry eye disease. These findings may indicate the instability of the tear film layer in eyes with pterygium which worsens the tear fluid evaporation. The resulting heat of vaporization may result in a decrease in ocular surface temperature.15 However, it also clearly demonstrates that temperature plays a major role in ocular surface alterations. Thermography may be an useful additional tool to objectively identify ocular surface unsteadiness in patients with pterygium and dry eye disease.
CONCLUSION The present study shows that thermography, in addition to other investigations, might be useful to objectively identify dry eye symptoms in patients with pterygium. In addition to cosmetic appearance, increasing astigmatism, and expanding growth towards the center of the cornea, this new supplementary temperature data may help to determine the proper time for intervention.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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