C L I N I C A L A N D E X P E R I M E N T A L OPTOMETRY

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1 C L I N I C A L A N D E X P E R I M E N T A L OPTOMETRY The characteristics of corneal staining in successful daily and extended disposable contact lens wearers Isabelle Jalbert OD Deborah F Sweeney BOptom PhD Brien A Holden PhD Cornea and Contact Lens Research Unit, School of Optometry, and Cooperative Research Centre for Eye Research and Technology, The University of New South Wales Accepted for publication: 1 September 1998 Purpose: The aim of this investigation was to measure levels of corneal staining in successful daily and extended wearers of disposable hydrogel contact lenses. Methods: Twenty-four subjects on a daily wear (DW) schedule and 20 subjects on an extended wear (EW) schedule were examined at six-monthly intervals over a two-year period. Subjects wore two types of disposable hydrogel lenses. Measurements were taken from the eye wearing an etafilcon A contact lens only. The cornea was divided into five equally sized zones and the extent and depth of corneal staining were assessed on a zero to four scale. Results: The overall levels of corneal staining were low with median values below or equal to grade 0.5 in all groups. There was no difference in the extent, depth or geographical distribution of corneal staining between the DW and EW groups. Staining was more frequently recorded in the superior and inferior areas of the cornea than in the central, nasal or temporal regions (Pearson s Chi-Square, p < 0.10). Conclusions: The mode of wear with disposable contact lenses is not a contributing factor to the amount of corneal staining seen in successful wearers. Low levels of corneal staining should be expected in successful DW and EW wearers. (Clin Exp Optom 1999; 82: 1: 4 10) Key words: corneal epithelium, corneal staining, daily wear, extended wear, sodium fluorescein Corneal staining is an accepted clinical measure of epithelial integrity that is widely used in clinical and research settings. Sodium fluorescein is thought to penetrate and stain damaged cells and intracellular spaces 1,2 although recent evidence suggests that healthy corneal cells may stain with fluorescein. 3 While staining has been demonstrated in asymptomatic non-contact lens wearers, 4,5 the assumption has been that physiological or mechanical damage to the cornea induced by contact lens wear can be assessed with the use of fluorescein stain. Staining studies in contact lens wearers have shown characteristic patterns associated with certain types of contact lenses such as three to nine o clock staining with rigid gas permeable lenses and dehydration staining with high water content hydrogel lenses. 6 Extended wear (EW) of soft contact lenses reduces the oxygen supply to the cornea compared with daily wear (DW) of soft contact lenses. Long term EW induces physiological changes to the corneal epithelium in the form of microcysts, 7 reduced mitotic rate, 8 epithelial thinning, 9 reduced epithelial adhesion 10 and enlarged epithelial cells. 11 From this evidence, one can propose that the physiological stress induced by EW on the corneal epithelium could lead to an impairment of tight junction integrity between cells and, therefore, an increase in the uptake of sodium fluorescein dye by the superficial layers of the cornea. To our knowledge, no previous investigation on the effect of wear schedule on the levels of corneal staining has been conducted. The primary aim of our study was to compare the extent and depth of corneal staining observed in successful wearers of DW and EW hydrogel lenses. Second, we wanted to characterise the geographical 4

2 distribution of positive staining with the two wear modalities. MATERIALS AND METHODS An analysis of subjects enrolled in two clinical trials at the Cornea and Contact Lens Research Unit (CCLRU), School of Optometry, at The University of New South Wales in Sydney, Australia, was conducted. Because these clinical trials were initiated in May 1992, prior to the design of this staining evaluation, the data for this study was collected at scheduled study visits 42, 48, 54 and 60 months after commencement of lens wear. Of the 27 subjects initially enrolled in the first group wearing lenses on a DW basis, 24 remained in the study at the 42 months visit as three subjects had been lost to follow-up. Twenty of the 36 subjects initially enrolled in the second group wearing lenses on a six nights per week EW basis remained in the study at the 42 months visit. Patients had discontinued EW for non lens-related reasons such as moving or travelling overseas (five patients), time constraints (four), dislike of EW (one), significant staining without contact lenses (one) and for lensrelated reasons such as significant corneal infiltrates (three), hypoxia or corneal striae (one) and contact lens papillary conjunctivitis (one). Therefore, our study sample consisted of two groups of 24 and 20 successful subjects who were examined at six-monthly intervals over a two-year period. All subjects were free of ocular disease and signed a record of informed consent prior to enrolment. This study was conducted in accordance with the National Health and Medical Research Council Statement on Human Experimentation. Subjects wore a 58 per cent water content ionic disposable hydrogel (etafilcon A) contact lens in one eye and a 38 per cent water content non-ionic disposable hydrogel (polymacon) contact lens in the other eye. Twelve optometrists from the CCLRU clinic participated in the data collection for this study. To ensure consistency of data, all clinicians were trained in the use of the CCLRU corneal staining scale 12 (Table 1) prior to the commencement of the study. In most cases Grade Extent Depth 0 Absent Absent % surface involvement Superficial epithelial involvement % surface involvement Stromal glow present within 30 s % surface involvement Immediate localised stromal glow 4 46% or greater surface Immediate diffuse stromal glow involvement Table 1. CCLRU scale for evaluation of corneal staining Right eye Figure 1. The extent and depth of corneal staining are assessed in areas one to five (75 per cent), a single observer (IJ) collected staining data. Measurements were taken from the eye wearing an etafilcon A contact lens only. In a previous series, Koetting, Von Gunten and Peebles 13 demonstrated that although tearing and subsequent tear hypotonicity induced sympathetic corneal oedema in 50 per cent of cases of monocular corneal abrasion, no case demonstrated fluorescein staining in the non lens-wearing eye. Based on these results, we expected no sympathetic or contralateral response in our subjects to the wear of a different hydrogel lens in the other eye. Corneal staining was assessed immediately following lens removal at each follow-up visit by applying a sodium fluorescein strip wetted with unpreserved saline Left eye against the upper bulbar conjunctiva and observing the cornea using a Wratten No 12 yellow fluorescein enhancement filter and the slit lamp biomicroscope with cobalt blue light. The cornea was divided into five equally-sized zones (Figure 1) and corneal staining was assessed for extent (Figure 2) and depth (Figure 3) in each zone using a previously described zero to four scale. 12 Observers were allowed to use only whole grades in their assessment (no decimalisation). Statistical analysis was performed using the student group t-test, Mann-Whitney Exact Test, and Pearson s Chi-Square Exact Test. Correlation was analysed using Spearman s rho test. We combined data for repeated measures by taking the average value across the four visits for each 5

3 subject as the response variable. Several authors recommend such response feature analysis using summary measures. 14,15 The additive property of the Chi-Square distribution was invoked to obtain an overall test across all visits. RESULTS Figure 2. The CCLRU grading scale for extent of corneal staining A. Grade 1: one to 15 per cent surface involvement B. Grade 2: 16 to 30 per cent surface involvement C. Grade 3: 31 to 45 per cent surface involvement D. Grade 4: 46 per cent or greater surface involvement Figure 3. The CCLRU grading scale for depth of corneal staining A. Grade 1: superficial epithelial involvement B. Grade 2: stromal glow present within 30 seconds C. Grade 3: immediate localised stromal glow D. Grade 4: immediate diffuse stromal glow Demographic details of the study population are presented in Table 2. There was no difference in the male to female distribution between groups. However, subjects in the EW group were younger than subjects in the DW group (student group t-test, p = 0.003). Over the two-year period, data were missing on 18 occasions for the DW group and on 31 occasions for the EW group, as subjects did not present for their scheduled visits. Median and interquartile range values for the extent (Table 3) and depth (Table 4) of staining in each area were compared between wear schedules. No differences were noted in the extent and depth of corneal staining between the DW and EW groups. However, there was a tendency for higher depth of staining in the inferior region for the EW group (p = 0.09). Levels of corneal staining observed were generally very low with median staining levels below or equal to grade 0.5 on the zero to four scale. There were no differences in the distribution of extent (Figure 4) or depth (Figure 5) of corneal staining between subjects on a DW or EW schedule. Although in rare cases (one per cent of visits) the extent of corneal staining involved up to 45 per cent of the area measured, in no case was the depth of corneal staining recorded as greater than grade 1 (superficial epithelial involvement). There were significant differences in the frequency of staining between different areas of the cornea (Figure 6). When comparing the distribution of corneal staining between wear schedules, we could demonstrate no significant differences in the geographical distribution of corneal staining between DW and EW lens wearers. However, staining was recorded more often in the superior area than the central and nasal areas for both wear sched- 6

4 ules. There was a tendency for more staining to be recorded in the superior area than in the temporal area for the DW group. Staining was also recorded more frequently in the inferior area than in the central, nasal and temporal areas for both wear schedules (Table 5). A highly significant positive correlation between the extent and depth of staining in each region (Spearman s rho test r = 0.49, p = 0.001) was also found. DISCUSSION Corneal staining is an integral part of a routine optometric examination, particularly for contact lens wearers. It is used to detect damage to the epithelial surface, whether caused by injury, physiological stress or infection. The sodium fluorescein dye penetrates the corneal epithelium where there are empty spaces (shed cells, trauma) or loose adhesion between cells (oedema) and staining can be viewed through a slit lamp biomicroscope using the cobalt blue light and a Wratten No 12 filter. The characteristics of corneal staining were examined in a group of DW and EW disposable hydrogel lens wearers using two grading scales for measuring the extent and depth of staining (Table 1). Other investigators have used the standard scale recommended by the Food and Drug Administration (FDA) in the United States to grade corneal staining (Table 6). Our grading system was designed to allow more sensitive evaluation of corneal staining. For example, we found that a single scale would not allow differentiation between a single small superficial abrasion and multiple deep abrasions covering the majority of the cornea. As a result of these scaling differences, it is not possible to make a direct comparison of our results and previously published results. In our study, very low levels of corneal staining were measured in all disposable hydrogel contact lens wearers, regardless of wear schedule. Our results are similar to those which have been reported previously by other investigators. 5,16 The median extent of staining ranged from 0.0 to 0.3 in the DW group and from 0.1 to 0.5 in the EW group. This corresponds to Daily wear Extended wear p-value Sex (M:F) 12:12 10: Age (mean ± SD) 37 ± 8 30 ± Table 2. Demographic details of study population at the start of the study Daily wear Extended wear (n = 24) (n = 20) Area Median IQR Median IQR p-value Central Nasal Temporal Superior Inferior Table 3. The extent of corneal staining in daily and extended wear disposable hydrogel lens wearers (values combined for all visits) measured with the CCLRU grading scale IQR = interquartile range Daily wear Extended wear (n = 24) (n = 20) Area Median IQR Median IQR p-value Central Nasal Temporal Superior Inferior Table 4. The depth of corneal staining in daily and extended wear disposable hydrogel lens wearers (values combined for all visits) measured with the CCLRU grading scale IQR = interquartile range 7

5 Percentage observed Figure 4. The frequency distribution of extent of corneal staining in daily wear (DW) and extended wear (EW) disposable hydrogel lens wearers (values combined for all visits) Percentage observed Grade (0 4) Grade (0 4) Figure 5. The frequency distribution of depth of corneal staining in daily wear (DW) and extended wear (EW) disposable hydrogel lens wearers (values combined for all visits) less than 15 per cent involvement of the epithelial surface. Over the two-year study period, 55 per cent of eyes had positive staining. In the literature, the reported percentage of eyes with positive staining varies from 19 per cent to 78 per cent of observations. 5,16,17 Since it was proposed by Josephson and Caffery 18 in 1988, the use of a grid dividing the cornea into five zones has been widespread. In our study, corneal staining was observed more frequently in the superior and inferior areas than the central, nasal and temporal areas. Various studies in contact lens wearers and non-lens wearers have demonstrated a reduced level of staining in the central region 5,19 and higher amounts of staining in the inferior region. 1,4,19,20 A recent study in daily soft contact lens wearers 16 and studies using sequential staining techniques 4,21 found that staining occurred more frequently in the superior and inferior zones than in all other zones. Other studies in non-lens wearers report that staining is more common in the inferior and nasal areas. 5,18,22 Several theories have been proposed to explain the differences in geographical distribution of corneal staining. It has been suggested that this may be explained by the longer exposure of those regions to sodium fluorescein because of the dye remaining in the tear meniscus at the upper and lower eyelid margins. 17 Alternatively, there may be a difference in mitotic activity between the peripheral and central cornea and as the peripheral cornea sheds more cells, more holes are left behind where fluorescein can penetrate, giving the higher incidence of staining in the peripheral regions. 18 Inferior and superior staining may be due to desiccation or hypoxia. Our study population consisted of successful contact lens wearers with varying prior experience and exposure to contact lens wear. It is possible that subjects who discontinue EW or contact lens wear altogether are more prone to damage of the epithelial surface due to contact lens wear. In fact, in a study using sequential instillation of fluorescein dye, subjects who had experienced previous contact lens wear failure demonstrated more frequent stain- 8

6 ing (34 per cent) than non-lens wearers (six per cent) or successful lens wearers (four per cent). 17 Our measurements of corneal staining may be artificially low and not an accurate reflection of the overall population. Controlled studies are thought to result in fewer complications than would occur in general practice. However, careful observation by trained observers is likely to reveal greater amounts of low grade staining. Future study plans include a comparison of staining levels between continuing and discontinuing patients in prospective clinical trials conducted at the CCLRU. We have suggested previously that the gold standard for success in contact lens wear should be no persistent staining of the cornea of more than grade 1 in depth or extent. 12 Our results support the use of this criteria as our successful lens wearers demonstrated low levels of corneal staining regardless of their wear schedule. ACKNOWLEDGEMENTS This work was supported in part by the Australian Federal Government through the Cooperative Research Centre (CRC) and Vistakon, a division of Johnson & Johnson Vision Products Inc. The authors thank Mr Eric Papas and Mr Reginald Wong for their help. REFERENCES 1. Norn MS. Micropunctate fluorescein vital staining of the cornea. Acta Ophthalmol 1970; 48: Tabery HM. Micropunctate fluorescein staining of the human corneal surface: microerosions or cystic spaces? Acta Ophthalmol 1997; 75: Wilson G, Ren H, Laurent J. Corneal epithelial fluorescein staining. J Amer Optom Assoc 1995; 66: Korb DR, Korb JME. Corneal staining prior to contact lens wearing. J Amer Optom Assoc 1970; 41: Schwallie JD, McKenney CD, Long WD, McNeil A. Corneal staining patterns in normal non-contact lens wearers. Optom Vis Sci 1997; 74: Kline LN, Deluca TJ. Corneal staining. In: White PF, Miller D, eds. Complications of Contact Lenses. Int Ophthalmol Clin 1981; 21: Zantos SG, Holden BA. Ocular changes associated with continuous wear of contact lenses. Aust J Optom 1978; 61: DW Figure 6. The geographical distribution of positive corneal staining in daily wear (DW) and extended wear (EW) disposable hydrogel lens wearers (values combined for all visits). The cornea is divided in central (C), nasal (N), temporal (T), superior (S), and inferior (I) regions. The percentage of cases showing any positive staining is shown for each region. EW Daily wear Extended wear χ 2 DF p-value χ 2 DF p-value Central vs Nasal Central vs Temporal Central vs Superior Central vs Inferior Nasal vs Temporal Nasal vs Superior Nasal vs Inferior Temporal vs Superior Temporal vs Inferior Superior vs Inferior Table 5. The geographical distribution of corneal staining. Pearson s Chi-Square (χ 2 ), degree of freedom (DF) and p-values for tests between corneal regions. Grade Category Description 0 None No staining 1 Trace Minimal superficial staining or stippling 2 Mild Regional or diffuse punctate staining 3 Moderate Significant dense coalesced staining or abrasion or foreign body tracks 4 Severe Severe abrasions, ulcerations, epithelial loss or full thickness abrasion Table 6. FDA recommended slit lamp grading scale for corneal staining 9

7 8. Hamano J, Hori M. Effect of contact lens wear on the mitoses of corneal epithelial cells: Preliminary report. CLAO J 1983; 9: Holden BA. The ocular response to contact lens wear. Optom Vis Sci 1989; 66: Madigan MC, Holden BA. Reduced epithelial adhesion after extended contact lens wear correlates with reduced hemidesmosome density in cat cornea. Invest Ophthalmol Vis Sci 1992; 33: Tsubota K, Toda I, Fujishima H, Yamada M, Sugawara T, Shimazaki J. Extended wear soft contact lenses induce corneal epithelial changes. Brit J Ophthalmol 1994; 78: Terry RL, Schnider CM, Holden BA, Cornish R, Grant T, Sweeney D, La Hood D, Back A. CCLRU standards for success of daily and extended wear contact lenses. Optom Vis Sci 1993; 70: Koetting RA, Von Gunten TL, Peebles J. Some unexplained effects of contact lens abrasion on the contralateral eye. J Amer Optom Assoc 1972; 43: Matthews JNS, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. Brit Med J 1990; 300: Everitt BS. The analysis of repeated measures: a practical review with examples. The Statistician 1995; 44: Begley CG, Barr JT, Edrington TB, Long WD, McKenney CD, Chalmers RL. Characteristics of corneal staining in hydrogel contact lens wearers. Optom Vis Sci 1996; 73: Korb DR, Herman JP. Corneal staining subsequent to sequential fluorescein instillations. J Amer Optom Assoc 1979; 50: Josephson JE, Caffery BE. Corneal staining after instillation of topical anesthetic (SSII). Invest Ophthalmol Vis Sci 1988; 29: Caffery BE, Josephson JE. Corneal staining after sequential instillations of fluorescein over 30 days. Optom Vis Sci 1991; 68: Guillon JP, Guillon M, Malgouyres S. Corneal desiccation staining with hydrogel lenses: tear film and contact lens factors. Ophthal Physiol Opt 1990; 10: Thomas ML, Szeto VR, Gan CM, Polse KA. Sequential staining: the effects of sodium fluorescein, osmolarity, and ph on human corneal epithelium. Optom Vis Sci 1997; 74: Josephson JE, Caffery BE. Corneal staining characteristics after sequential instillations of fluorescein. Optom Vis Sci 1992; 69: Author s address: Isabelle Jalbert Cornea and Contact Lens Research Unit The University of New South Wales Sydney NSW 2052 AUSTRALIA 10