Mucin balls Ð Part 1

Various forms of organic and inorganic matter can accumulate in the post-lens tear film. These include intrinsic matter such as desquamated epithelial cells, inflammatory cells and micro-organisms, and extrinsic matter such as dust particles that may have entered the eye from the atmosphere.
Most of this matter is flushed away during daily lens wear as a result of the blink-activated tear pump. The accumulation of such debris during extended lens wear is potentially more problematic because it can be retained at the corneal surface for longer periods Ð such as overnight during sleep.
An important requirement of extended wear lenses is that such matter is flushed out from beneath the lens as soon as the patient begins to blink upon awakening in the morning.
A characteristic form of debris known as 'mucin balls' has been observed in patients who wear high oxygen performance silicone hydrogel contact lenses. Although the appearance of mucin balls was first formally reported in the literature in 20001,2 Ð corresponding with the market release of silicone hydrogel lenses Ð earlier anecdotal reports suggested that this phenomenon had been observed previously.
Other descriptive terms used include lipid plugs,3 tear microspheres,4 microdeposits5 and spherical post-lens debris.2 Some authors6,7 suggest that a small number of mucin balls can be observed in some patients who use conventional hydrogel lenses on an extended wear basis.

Signs
Mucin balls are observed within minutes of lens insertion between the posterior lens surface and the corneal epithelium.
Under direct white light at low illumination they appear as a mass of discrete grey dots that seem to be fixed in position; that is, they do not move in synchrony with the contact lens after a blink.
At higher magnification under direct white light illumination, mucin balls appear as cream/grey, round or ovoid inclusions that may be near spherical or somewhat flattened (Figure 1). When viewed using indirect retro-illumination, mucin balls display reversed illumination, which indicates that the material from which the mucin ball is composed (presumably mucin, see later) is of a higher refractive index than the surrounding medium (tear aqueous).
Under these illumination conditions, some mucin balls take on a distinct doughnut-like appearance with a thick annular rim and membrane across the centre (Figure 2).
Tan et al4 and Craig et al8 suggest that mucin balls are observed more commonly in the superior cornea, although this characteristic has not been reported by other authors.1,2,9
Mucin balls can also become embedded in the conjunctival epithelium close to the limbus. Estimates of the size (diameter) of individual mucin balls vary: Fonn et al1 and Dumbleton et al2 reported 20mmÐ200mm and Craig et al8 made a similar estimate of 10mm-200 mm, whereas Bourassa and Benjamin5 and Tan et al4 reported 40mm-120mm.
Sweeney et al7 suggested that mucin balls fall into two size categories: small (10mm-20mm) and large (20mm-50mm). Ladage et al10 measured the size of mucin balls in three patients using corneal confocal microscopy, and reported a size range from 33.9mm to 78.8mm (mean 57.9 ± 14 mm). These estimates are quite large in comparison with the thickness of the tear film beneath silicone hydrogel lenses (1mm-2mm)11 and the corneal epithelium (about 50Ð70 mm).12
Various factors govern the number of mucin balls present at any given time. In their respective case reports, Bourassa and Benjamin5 observed 20-30 mucin balls and Fonn et al1 observed up to 50 mucin balls over a number of visits. In clinical trials of patients who wore silicone hydrogel lenses, Fonn et al1 reported that 95 per cent of the patients displayed less than 50 mucin balls over a three-month period, and Sweeney et al7 and Tan et al6 reported that the mean number of mucin balls over a 12-month period did not exceed an average of 20.
All seven patients who wore silicone hydrogel lenses in the clinical trial of Craig et al8 demonstrated between 60 and 100 mucin balls within 22 days of commencing lens wear. Sometimes in excess of 100 mucin balls may be observed.1,6 Craig et al8 reported 230 mucin balls in one subject.
After lens removal, the majority of mucin balls are blinked away to leave depressions (also termed 'imprints' or 'pits') in the epithelial surface. These depressions fill with tear aqueous and appear as transparent spherical inclusions that display unreversed illumination when viewed at high magnification with a slit-lamp biomicroscope using retro-illumination (Figure 3).
Some mucin balls appear to remain lodged in the surface of the epithelium; these continue to display reversed illumination, which thus allows these two entities to be differentiated.
Upon instillation of fluorescein into the eye, both the remaining mucin balls and the aqueous in the epithelial depressions stain with fluorescein, which results in a pattern of punctate spots over the cornea. It is virtually impossible to distinguish between mucin balls and the aqueous-filled epithelial depressions; both appear as discrete, solid, fluorescent-green spots of similar size when viewed under fluorescent light (Figure 4).
Mucin balls do not stain with rose bengal, which suggests that there is no co-existing disturbance of corneal surface integrity.7

Time course
Sweeney et al7 and Tan et al6 reported that mucin balls increase in number and size over the initial few months of silicone hydrogel lens extended wear.
Morgan and Efron9 conducted a randomised, cross-over clinical trial in which 30 subjects each wore a pair of PureVision (Bausch & Lomb) and Focus Night & Day (Ciba Vision) silicone hydrogel contact lenses for eight weeks on an extended-wear basis.
The percentage of patients who presented with mucin balls increased to 37 per cent and 54 per cent of patients for PureVision and Focus Night & Day, respectively, after four weeks, and began to decline thereafter (Figure 5). Dumbleton et al2 did not detect a change in the mean grade of mucin ball appearance over a six-month period among 92 patients who wore Focus Night & Day lenses.

Prevalence
As stated above, Morgan and Efron9 reported that between 37 per cent and 54 per cent of patients who wear silicone hydrogel lenses display mucin balls after about four weeks.
Tan et al6 observed that the percentage of all subjects who wear silicone hydrogel lenses and have mucin balls varied from 37 per cent to 82 per cent during the year. Dumbleton et al2 reported that mucin balls were observed in 70 per cent of patients at one or more visits of their clinical trial, and in 29 per cent of subjects at all three visits, while wearing Focus Night & Day lenses.

Associated observations
Morgan and Efron9 analysed the results of their clinical trial to see if the presence of mucin balls was related to any other clinical results.
Paradoxically, high-contrast visual acuity was demonstrated to be about one letter better in the presence of mucin balls;9 this is consistent with the report of Dumbleton et al,2 who showed that the subjective appreciation of vision was superior in the presence of mucin balls after six months of wear. There was no difference for low-contrast visual acuity.9 It is not clear why vision should be better in the presence of mucin balls.
Some biomicroscopic signs appear to be related to mucin balls.9 An unexpected finding in the study of Morgan and Efron9 was that conjunctival and limbal redness were both reduced and the number of microcysts appeared to increase in subjects who exhibited mucin balls. The apparent association between the appearance of mucin balls and epithelial microcysts, also observed by Tan et al,6 may be an artefact that relates to the difficulty in differentiating mucin balls from microcysts.
An association was revealed between the presence of mucin balls and increased corneal fluorescein staining;9 this is probably because the remaining mucin balls and fluid-filled epithelial pits stain with fluorescein. The above associations concerning mucin balls contrast with those of other authors,2,4,7 who found no relationship between biomicroscopic signs and mucin balls.
Naduvilath13 demonstrated an association between the appearance of mucin balls and the development of contact lens-induced peripheral ulcer (CLPU). Specifically, patients who display mucin balls have a x1.6 probability of developing CLPU compared with patients who do not display mucin balls.
Symptoms
Dumbleton et al2 found no association between the appearance of mucin balls and overall comfort, waking comfort, waking dryness or day-end dryness, although the process of lens removal was reported as being slightly less comfortable in the presence of mucin balls.
Other authors4,7,9 reported that subjective comfort is unaffected by the presence of mucin balls.

aEtiology
The reasons for the formation of mucin balls are unclear and likely to be complex.
The prevailing hypothesis is that the low deposition rate of silicone hydrogel materials prevents any significant uptake of deposits (protein, lipid and mucins) onto or into the lens matrix during lens wear. The depletion of aqueous during overnight wear of silicone hydrogel lenses Ð as evidenced by the very thin post-lens tear film Ð results in a viscous, mucin-lipid layer between the lens and epithelial surface. This layer is likely to contain much more mucin than lipid, which reflects the respective proportions of these two entities in the tear film.
Silicone hydrogel lenses are thought to induce high interfacial forces, which, when coupled with the high modulus of elasticity (greater stiffness) of such lenses, creates a sheering of this viscous, mucin-rich post-lens layer in the course of lens movement induced by normal blinking (daytime wear) and rapid eye movements (during sleep). These sheering forces have the effect of rolling the mucin-rich post-lens layers into spheres, which are observed as mucin balls.
The difference in mucin-ball response between the PureVision (Bausch & Lomb) and Focus Night & Day (Ciba Vision) silicone hydrogel contact lenses reported by Morgan and Efron9 may be related to differences in interfacial shear forces as a result of the different types of surface treatments applied to each lens.
A classic plasma surface modification is used to render the surface of the PureVision lens hydrophilic, whereas a plasma coating is applied to the Focus Night & Day lens to enhance surface wettability.
Certainly, the chemical composition and nature of the lens mould used in the manufacture of silicone hydrogel lenses can affect mucin ball formation; for example, Lai and Friends14 found that the use of polar plastic moulds minimised mucin ball formation. Dumbleton et al2 further postulated that a greater mismatch in shape between the back surface of the lens and the epithelial surface may increase the degree of lens movement over the ocular surface and thus create more sheering and, consequently, more mucin balls.
In support of this theory, they demonstrated that subjects who exhibited mucin balls had significantly steeper keratometry readings along the flatter meridian than those who did not (bearing in mind that all lenses in their experiment had the same back optic zone radius, BOZR);2 that is, those with relatively flatter, looser lens fits exhibited a greater number of mucin balls. No such association between corneal curvature and mucin formation was found by other authors who fitted single-BOZR lenses.4,9

References
1 Fonn D, Pritchard N and Dumbleton K. Factors affecting the success of silicone hydrogels. In: Silicone Hydrogels. The Rebirth of Continuous Wear Contact Lenses, Ed. Sweeney DF, 2000; p 214Ð234. (Oxford: ButterworthÐHeinemann).
2 Dumbleton K, Jones L, Chalmers R, et al. Clinical characterization of spherical post-lens debris associated with Lotrafilcon high-Dk silicone lenses. CLAO J, 2000; 26, 186Ð92.
3 Fleming C, Austen R and Davies S. Pre-corneal deposits during soft contact lens wear. Optom Vis Sci, 1994; 71, 152SÐ153S.
4 Tan J, Keay L and Jalbert I. Tear microspheres (TMSS) with high Dk lenses. Optom Vis Sci, 1999; 76S, 226.
5 Bourassa S and Benjamin WJ. Transient corneal surface 'microdeposits' and associated epithelial surface pits occurring with gel contact lens extended wear. Int Contact Lens Clin, 1988; 15, 338Ð340.
6 Tan J, Keay L, Jalbert I, et al. Mucin balls with wear of conventional and silicone hydrogel contact lenses. Optom Vis Sci, 2003; 80, 291Ð297.
7 Sweeney DF, Keay L, Jalbert I, et al. Clinical performance of silicone hydrogel lenses. In: Silicone Hydrogels. The Rebirth of Continuous Wear Contact Lenses, Ed. Sweeney DF, 2000; p 90Ð149. (Oxford: ButterworthÐHeinemann).
8 Craig JP, Sherwin T, Grupcheva CN and McGhee CN. An evaluation of mucin balls associated with high-Dk silicone hydrogel contact lens wear. Adv Exp Med Biol, 2002; 506, 917Ð923.
9 Morgan PB and Efron N. Comparative clinical performance of two silicone hydrogel contact lenses for continuous wear. Clin Exp Optom, 2002; 85, 183Ð192.
10 Ladage PM, Petroll WM, Jester JV, et al. Spherical indentations of human and rabbit corneal epithelium following extended contact lens wear. CLAO J, 2002; 28, 177Ð180.
11 Nichols J and King-Smith E. In-vivo thickness of the pre- and post-lens tear film and silicone hydrogel contact lenses measured by interferometry. Optom Vis Sci, 2001; 78, 51S.
12 Bron AJ, Tripathi RC and Tripathi BJ. Wolff's Anatomy of the Eye and Orbit, 1997; Eighth Edition. (London: Chapman & Hall Medical).
13 Naduvilath TJ. Statistical Modelling of Risk Factors Associated with Soft Contact Lens-Related Corneal Infiltrative Events. PhD Thesis (Newcastle: University of Newcastle), 2003.
14 Lai YC and Friends GD. Surface wettability enhancement of silicone hydrogel lenses by processing with polar plastic molds. J Biomed Mater Res, 1997; 35, 349Ð356.

Professor Nathan Efron is director of Eurolens Research, UMISTVarious forms of organic and inorganic matter can accumulate in the post-lens tear film. These include intrinsic matter such as desquamated epithelial cells, inflammatory cells and micro-organisms, and extrinsic matter such as dust particles that may have entered the eye from the atmosphere.
Most of this matter is flushed away during daily lens wear as a result of the blink-activated tear pump. The accumulation of such debris during extended lens wear is potentially more problematic because it can be retained at the corneal surface for longer periods Ð such as overnight during sleep.
An important requirement of extended wear lenses is that such matter is flushed out from beneath the lens as soon as the patient begins to blink upon awakening in the morning.
A characteristic form of debris known as 'mucin balls' has been observed in patients who wear high oxygen performance silicone hydrogel contact lenses. Although the appearance of mucin balls was first formally reported in the literature in 20001,2 Ð corresponding with the market release of silicone hydrogel lenses Ð earlier anecdotal reports suggested that this phenomenon had been observed previously.
Other descriptive terms used include lipid plugs,3 tear microspheres,4 microdeposits5 and spherical post-lens debris.2 Some authors6,7 suggest that a small number of mucin balls can be observed in some patients who use conventional hydrogel lenses on an extended wear basis.

Signs
Mucin balls are observed within minutes of lens insertion between the posterior lens surface and the corneal epithelium.
Under direct white light at low illumination they appear as a mass of discrete grey dots that seem to be fixed in position; that is, they do not move in synchrony with the contact lens after a blink.
At higher magnification under direct white light illumination, mucin balls appear as cream/grey, round or ovoid inclusions that may be near spherical or somewhat flattened (Figure 1). When viewed using indirect retro-illumination, mucin balls display reversed illumination, which indicates that the material from which the mucin ball is composed (presumably mucin, see later) is of a higher refractive index than the surrounding medium (tear aqueous).
Under these illumination conditions, some mucin balls take on a distinct doughnut-like appearance with a thick annular rim and membrane across the centre (Figure 2).
Tan et al4 and Craig et al8 suggest that mucin balls are observed more commonly in the superior cornea, although this characteristic has not been reported by other authors.1,2,9
Mucin balls can also become embedded in the conjunctival epithelium close to the limbus. Estimates of the size (diameter) of individual mucin balls vary: Fonn et al1 and Dumbleton et al2 reported 20mmÐ200mm and Craig et al8 made a similar estimate of 10mm-200 mm, whereas Bourassa and Benjamin5 and Tan et al4 reported 40mm-120mm.
Sweeney et al7 suggested that mucin balls fall into two size categories: small (10mm-20mm) and large (20mm-50mm). Ladage et al10 measured the size of mucin balls in three patients using corneal confocal microscopy, and reported a size range from 33.9mm to 78.8mm (mean 57.9 ± 14 mm). These estimates are quite large in comparison with the thickness of the tear film beneath silicone hydrogel lenses (1mm-2mm)11 and the corneal epithelium (about 50Ð70 mm).12
Various factors govern the number of mucin balls present at any given time. In their respective case reports, Bourassa and Benjamin5 observed 20-30 mucin balls and Fonn et al1 observed up to 50 mucin balls over a number of visits. In clinical trials of patients who wore silicone hydrogel lenses, Fonn et al1 reported that 95 per cent of the patients displayed less than 50 mucin balls over a three-month period, and Sweeney et al7 and Tan et al6 reported that the mean number of mucin balls over a 12-month period did not exceed an average of 20.
All seven patients who wore silicone hydrogel lenses in the clinical trial of Craig et al8 demonstrated between 60 and 100 mucin balls within 22 days of commencing lens wear. Sometimes in excess of 100 mucin balls may be observed.1,6 Craig et al8 reported 230 mucin balls in one subject.
After lens removal, the majority of mucin balls are blinked away to leave depressions (also termed 'imprints' or 'pits') in the epithelial surface. These depressions fill with tear aqueous and appear as transparent spherical inclusions that display unreversed illumination when viewed at high magnification with a slit-lamp biomicroscope using retro-illumination (Figure 3).
Some mucin balls appear to remain lodged in the surface of the epithelium; these continue to display reversed illumination, which thus allows these two entities to be differentiated.
Upon instillation of fluorescein into the eye, both the remaining mucin balls and the aqueous in the epithelial depressions stain with fluorescein, which results in a pattern of punctate spots over the cornea. It is virtually impossible to distinguish between mucin balls and the aqueous-filled epithelial depressions; both appear as discrete, solid, fluorescent-green spots of similar size when viewed under fluorescent light (Figure 4).
Mucin balls do not stain with rose bengal, which suggests that there is no co-existing disturbance of corneal surface integrity.7

Time course
Sweeney et al7 and Tan et al6 reported that mucin balls increase in number and size over the initial few months of silicone hydrogel lens extended wear.
Morgan and Efron9 conducted a randomised, cross-over clinical trial in which 30 subjects each wore a pair of PureVision (Bausch & Lomb) and Focus Night & Day (Ciba Vision) silicone hydrogel contact lenses for eight weeks on an extended-wear basis.
The percentage of patients who presented with mucin balls increased to 37 per cent and 54 per cent of patients for PureVision and Focus Night & Day, respectively, after four weeks, and began to decline thereafter (Figure 5). Dumbleton et al2 did not detect a change in the mean grade of mucin ball appearance over a six-month period among 92 patients who wore Focus Night & Day lenses.

Prevalence
As stated above, Morgan and Efron9 reported that between 37 per cent and 54 per cent of patients who wear silicone hydrogel lenses display mucin balls after about four weeks.
Tan et al6 observed that the percentage of all subjects who wear silicone hydrogel lenses and have mucin balls varied from 37 per cent to 82 per cent during the year. Dumbleton et al2 reported that mucin balls were observed in 70 per cent of patients at one or more visits of their clinical trial, and in 29 per cent of subjects at all three visits, while wearing Focus Night & Day lenses.

Associated observations
Morgan and Efron9 analysed the results of their clinical trial to see if the presence of mucin balls was related to any other clinical results.
Paradoxically, high-contrast visual acuity was demonstrated to be about one letter better in the presence of mucin balls;9 this is consistent with the report of Dumbleton et al,2 who showed that the subjective appreciation of vision was superior in the presence of mucin balls after six months of wear. There was no difference for low-contrast visual acuity.9 It is not clear why vision should be better in the presence of mucin balls.
Some biomicroscopic signs appear to be related to mucin balls.9 An unexpected finding in the study of Morgan and Efron9 was that conjunctival and limbal redness were both reduced and the number of microcysts appeared to increase in subjects who exhibited mucin balls. The apparent association between the appearance of mucin balls and epithelial microcysts, also observed by Tan et al,6 may be an artefact that relates to the difficulty in differentiating mucin balls from microcysts.
An association was revealed between the presence of mucin balls and increased corneal fluorescein staining;9 this is probably because the remaining mucin balls and fluid-filled epithelial pits stain with fluorescein. The above associations concerning mucin balls contrast with those of other authors,2,4,7 who found no relationship between biomicroscopic signs and mucin balls.
Naduvilath13 demonstrated an association between the appearance of mucin balls and the development of contact lens-induced peripheral ulcer (CLPU). Specifically, patients who display mucin balls have a x1.6 probability of developing CLPU compared with patients who do not display mucin balls.
Symptoms
Dumbleton et al2 found no association between the appearance of mucin balls and overall comfort, waking comfort, waking dryness or day-end dryness, although the process of lens removal was reported as being slightly less comfortable in the presence of mucin balls.
Other authors4,7,9 reported that subjective comfort is unaffected by the presence of mucin balls.

aEtiology
The reasons for the formation of mucin balls are unclear and likely to be complex.
The prevailing hypothesis is that the low deposition rate of silicone hydrogel materials prevents any significant uptake of deposits (protein, lipid and mucins) onto or into the lens matrix during lens wear. The depletion of aqueous during overnight wear of silicone hydrogel lenses Ð as evidenced by the very thin post-lens tear film Ð results in a viscous, mucin-lipid layer between the lens and epithelial surface. This layer is likely to contain much more mucin than lipid, which reflects the respective proportions of these two entities in the tear film.
Silicone hydrogel lenses are thought to induce high interfacial forces, which, when coupled with the high modulus of elasticity (greater stiffness) of such lenses, creates a sheering of this viscous, mucin-rich post-lens layer in the course of lens movement induced by normal blinking (daytime wear) and rapid eye movements (during sleep). These sheering forces have the effect of rolling the mucin-rich post-lens layers into spheres, which are observed as mucin balls.
The difference in mucin-ball response between the PureVision (Bausch & Lomb) and Focus Night & Day (Ciba Vision) silicone hydrogel contact lenses reported by Morgan and Efron9 may be related to differences in interfacial shear forces as a result of the different types of surface treatments applied to each lens.
A classic plasma surface modification is used to render the surface of the PureVision lens hydrophilic, whereas a plasma coating is applied to the Focus Night & Day lens to enhance surface wettability.
Certainly, the chemical composition and nature of the lens mould used in the manufacture of silicone hydrogel lenses can affect mucin ball formation; for example, Lai and Friends14 found that the use of polar plastic moulds minimised mucin ball formation. Dumbleton et al2 further postulated that a greater mismatch in shape between the back surface of the lens and the epithelial surface may increase the degree of lens movement over the ocular surface and thus create more sheering and, consequently, more mucin balls.
In support of this theory, they demonstrated that subjects who exhibited mucin balls had significantly steeper keratometry readings along the flatter meridian than those who did not (bearing in mind that all lenses in their experiment had the same back optic zone radius, BOZR);2 that is, those with relatively flatter, looser lens fits exhibited a greater number of mucin balls. No such association between corneal curvature and mucin formation was found by other authors who fitted single-BOZR lenses.4,9

References
1 Fonn D, Pritchard N and Dumbleton K. Factors affecting the success of silicone hydrogels. In: Silicone Hydrogels. The Rebirth of Continuous Wear Contact Lenses, Ed. Sweeney DF, 2000; p 214Ð234. (Oxford: ButterworthÐHeinemann).
2 Dumbleton K, Jones L, Chalmers R, et al. Clinical characterization of spherical post-lens debris associated with Lotrafilcon high-Dk silicone lenses. CLAO J, 2000; 26, 186Ð92.
3 Fleming C, Austen R and Davies S. Pre-corneal deposits during soft contact lens wear. Optom Vis Sci, 1994; 71, 152SÐ153S.
4 Tan J, Keay L and Jalbert I. Tear microspheres (TMSS) with high Dk lenses. Optom Vis Sci, 1999; 76S, 226.
5 Bourassa S and Benjamin WJ. Transient corneal surface 'microdeposits' and associated epithelial surface pits occurring with gel contact lens extended wear. Int Contact Lens Clin, 1988; 15, 338Ð340.
6 Tan J, Keay L, Jalbert I, et al. Mucin balls with wear of conventional and silicone hydrogel contact lenses. Optom Vis Sci, 2003; 80, 291Ð297.
7 Sweeney DF, Keay L, Jalbert I, et al. Clinical performance of silicone hydrogel lenses. In: Silicone Hydrogels. The Rebirth of Continuous Wear Contact Lenses, Ed. Sweeney DF, 2000; p 90Ð149. (Oxford: ButterworthÐHeinemann).
8 Craig JP, Sherwin T, Grupcheva CN and McGhee CN. An evaluation of mucin balls associated with high-Dk silicone hydrogel contact lens wear. Adv Exp Med Biol, 2002; 506, 917Ð923.
9 Morgan PB and Efron N. Comparative clinical performance of two silicone hydrogel contact lenses for continuous wear. Clin Exp Optom, 2002; 85, 183Ð192.
10 Ladage PM, Petroll WM, Jester JV, et al. Spherical indentations of human and rabbit corneal epithelium following extended contact lens wear. CLAO J, 2002; 28, 177Ð180.
11 Nichols J and King-Smith E. In-vivo thickness of the pre- and post-lens tear film and silicone hydrogel contact lenses measured by interferometry. Optom Vis Sci, 2001; 78, 51S.
12 Bron AJ, Tripathi RC and Tripathi BJ. Wolff's Anatomy of the Eye and Orbit, 1997; Eighth Edition. (London: Chapman & Hall Medical).
13 Naduvilath TJ. Statistical Modelling of Risk Factors Associated with Soft Contact Lens-Related Corneal Infiltrative Events. PhD Thesis (Newcastle: University of Newcastle), 2003.
14 Lai YC and Friends GD. Surface wettability enhancement of silicone hydrogel lenses by processing with polar plastic molds. J Biomed Mater Res, 1997; 35, 349Ð356.

Professor Nathan Efron is director of Eurolens Research, UMISTVarious forms of organic and inorganic matter can accumulate in the post-lens tear film. These include intrinsic matter such as desquamated epithelial cells, inflammatory cells and micro-organisms, and extrinsic matter such as dust particles that may have entered the eye from the atmosphere.
Most of this matter is flushed away during daily lens wear as a result of the blink-activated tear pump. The accumulation of such debris during extended lens wear is potentially more problematic because it can be retained at the corneal surface for longer periods Ð such as overnight during sleep.
An important requirement of extended wear lenses is that such matter is flushed out from beneath the lens as soon as the patient begins to blink upon awakening in the morning.
A characteristic form of debris known as 'mucin balls' has been observed in patients who wear high oxygen performance silicone hydrogel contact lenses. Although the appearance of mucin balls was first formally reported in the literature in 20001,2 Ð corresponding with the market release of silicone hydrogel lenses Ð earlier anecdotal reports suggested that this phenomenon had been observed previously.
Other descriptive terms used include lipid plugs,3 tear microspheres,4 microdeposits5 and spherical post-lens debris.2 Some authors6,7 suggest that a small number of mucin balls can be observed in some patients who use conventional hydrogel lenses on an extended wear basis.

Signs
Mucin balls are observed within minutes of lens insertion between the posterior lens surface and the corneal epithelium.
Under direct white light at low illumination they appear as a mass of discrete grey dots that seem to be fixed in position; that is, they do not move in synchrony with the contact lens after a blink.
At higher magnification under direct white light illumination, mucin balls appear as cream/grey, round or ovoid inclusions that may be near spherical or somewhat flattened (Figure 1). When viewed using indirect retro-illumination, mucin balls display reversed illumination, which indicates that the material from which the mucin ball is composed (presumably mucin, see later) is of a higher refractive index than the surrounding medium (tear aqueous).
Under these illumination conditions, some mucin balls take on a distinct doughnut-like appearance with a thick annular rim and membrane across the centre (Figure 2).
Tan et al4 and Craig et al8 suggest that mucin balls are observed more commonly in the superior cornea, although this characteristic has not been reported by other authors.1,2,9
Mucin balls can also become embedded in the conjunctival epithelium close to the limbus. Estimates of the size (diameter) of individual mucin balls vary: Fonn et al1 and Dumbleton et al2 reported 20mmÐ200mm and Craig et al8 made a similar estimate of 10mm-200 mm, whereas Bourassa and Benjamin5 and Tan et al4 reported 40mm-120mm.
Sweeney et al7 suggested that mucin balls fall into two size categories: small (10mm-20mm) and large (20mm-50mm). Ladage et al10 measured the size of mucin balls in three patients using corneal confocal microscopy, and reported a size range from 33.9mm to 78.8mm (mean 57.9 ± 14 mm). These estimates are quite large in comparison with the thickness of the tear film beneath silicone hydrogel lenses (1mm-2mm)11 and the corneal epithelium (about 50Ð70 mm).12
Various factors govern the number of mucin balls present at any given time. In their respective case reports, Bourassa and Benjamin5 observed 20-30 mucin balls and Fonn et al1 observed up to 50 mucin balls over a number of visits. In clinical trials of patients who wore silicone hydrogel lenses, Fonn et al1 reported that 95 per cent of the patients displayed less than 50 mucin balls over a three-month period, and Sweeney et al7 and Tan et al6 reported that the mean number of mucin balls over a 12-month period did not exceed an average of 20.
All seven patients who wore silicone hydrogel lenses in the clinical trial of Craig et al8 demonstrated between 60 and 100 mucin balls within 22 days of commencing lens wear. Sometimes in excess of 100 mucin balls may be observed.1,6 Craig et al8 reported 230 mucin balls in one subject.
After lens removal, the majority of mucin balls are blinked away to leave depressions (also termed 'imprints' or 'pits') in the epithelial surface. These depressions fill with tear aqueous and appear as transparent spherical inclusions that display unreversed illumination when viewed at high magnification with a slit-lamp biomicroscope using retro-illumination (Figure 3).
Some mucin balls appear to remain lodged in the surface of the epithelium; these continue to display reversed illumination, which thus allows these two entities to be differentiated.
Upon instillation of fluorescein into the eye, both the remaining mucin balls and the aqueous in the epithelial depressions stain with fluorescein, which results in a pattern of punctate spots over the cornea. It is virtually impossible to distinguish between mucin balls and the aqueous-filled epithelial depressions; both appear as discrete, solid, fluorescent-green spots of similar size when viewed under fluorescent light (Figure 4).
Mucin balls do not stain with rose bengal, which suggests that there is no co-existing disturbance of corneal surface integrity.7

Time course
Sweeney et al7 and Tan et al6 reported that mucin balls increase in number and size over the initial few months of silicone hydrogel lens extended wear.
Morgan and Efron9 conducted a randomised, cross-over clinical trial in which 30 subjects each wore a pair of PureVision (Bausch & Lomb) and Focus Night & Day (Ciba Vision) silicone hydrogel contact lenses for eight weeks on an extended-wear basis.
The percentage of patients who presented with mucin balls increased to 37 per cent and 54 per cent of patients for PureVision and Focus Night & Day, respectively, after four weeks, and began to decline thereafter (Figure 5). Dumbleton et al2 did not detect a change in the mean grade of mucin ball appearance over a six-month period among 92 patients who wore Focus Night & Day lenses.

Prevalence
As stated above, Morgan and Efron9 reported that between 37 per cent and 54 per cent of patients who wear silicone hydrogel lenses display mucin balls after about four weeks.
Tan et al6 observed that the percentage of all subjects who wear silicone hydrogel lenses and have mucin balls varied from 37 per cent to 82 per cent during the year. Dumbleton et al2 reported that mucin balls were observed in 70 per cent of patients at one or more visits of their clinical trial, and in 29 per cent of subjects at all three visits, while wearing Focus Night & Day lenses.

Associated observations
Morgan and Efron9 analysed the results of their clinical trial to see if the presence of mucin balls was related to any other clinical results.
Paradoxically, high-contrast visual acuity was demonstrated to be about one letter better in the presence of mucin balls;9 this is consistent with the report of Dumbleton et al,2 who showed that the subjective appreciation of vision was superior in the presence of mucin balls after six months of wear. There was no difference for low-contrast visual acuity.9 It is not clear why vision should be better in the presence of mucin balls.
Some biomicroscopic signs appear to be related to mucin balls.9 An unexpected finding in the study of Morgan and Efron9 was that conjunctival and limbal redness were both reduced and the number of microcysts appeared to increase in subjects who exhibited mucin balls. The apparent association between the appearance of mucin balls and epithelial microcysts, also observed by Tan et al,6 may be an artefact that relates to the difficulty in differentiating mucin balls from microcysts.
An association was revealed between the presence of mucin balls and increased corneal fluorescein staining;9 this is probably because the remaining mucin balls and fluid-filled epithelial pits stain with fluorescein. The above associations concerning mucin balls contrast with those of other authors,2,4,7 who found no relationship between biomicroscopic signs and mucin balls.
Naduvilath13 demonstrated an association between the appearance of mucin balls and the development of contact lens-induced peripheral ulcer (CLPU). Specifically, patients who display mucin balls have a x1.6 probability of developing CLPU compared with patients who do not display mucin balls.
Symptoms
Dumbleton et al2 found no association between the appearance of mucin balls and overall comfort, waking comfort, waking dryness or day-end dryness, although the process of lens removal was reported as being slightly less comfortable in the presence of mucin balls.
Other authors4,7,9 reported that subjective comfort is unaffected by the presence of mucin balls.

aEtiology
The reasons for the formation of mucin balls are unclear and likely to be complex.
The prevailing hypothesis is that the low deposition rate of silicone hydrogel materials prevents any significant uptake of deposits (protein, lipid and mucins) onto or into the lens matrix during lens wear. The depletion of aqueous during overnight wear of silicone hydrogel lenses Ð as evidenced by the very thin post-lens tear film Ð results in a viscous, mucin-lipid layer between the lens and epithelial surface. This layer is likely to contain much more mucin than lipid, which reflects the respective proportions of these two entities in the tear film.
Silicone hydrogel lenses are thought to induce high interfacial forces, which, when coupled with the high modulus of elasticity (greater stiffness) of such lenses, creates a sheering of this viscous, mucin-rich post-lens layer in the course of lens movement induced by normal blinking (daytime wear) and rapid eye movements (during sleep). These sheering forces have the effect of rolling the mucin-rich post-lens layers into spheres, which are observed as mucin balls.
The difference in mucin-ball response between the PureVision (Bausch & Lomb) and Focus Night & Day (Ciba Vision) silicone hydrogel contact lenses reported by Morgan and Efron9 may be related to differences in interfacial shear forces as a result of the different types of surface treatments applied to each lens.
A classic plasma surface modification is used to render the surface of the PureVision lens hydrophilic, whereas a plasma coating is applied to the Focus Night & Day lens to enhance surface wettability.
Certainly, the chemical composition and nature of the lens mould used in the manufacture of silicone hydrogel lenses can affect mucin ball formation; for example, Lai and Friends14 found that the use of polar plastic moulds minimised mucin ball formation. Dumbleton et al2 further postulated that a greater mismatch in shape between the back surface of the lens and the epithelial surface may increase the degree of lens movement over the ocular surface and thus create more sheering and, consequently, more mucin balls.
In support of this theory, they demonstrated that subjects who exhibited mucin balls had significantly steeper keratometry readings along the flatter meridian than those who did not (bearing in mind that all lenses in their experiment had the same back optic zone radius, BOZR);2 that is, those with relatively flatter, looser lens fits exhibited a greater number of mucin balls. No such association between corneal curvature and mucin formation was found by other authors who fitted single-BOZR lenses.4,9

References
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2 Dumbleton K, Jones L, Chalmers R, et al. Clinical characterization of spherical post-lens debris associated with Lotrafilcon high-Dk silicone lenses. CLAO J, 2000; 26, 186Ð92.
3 Fleming C, Austen R and Davies S. Pre-corneal deposits during soft contact lens wear. Optom Vis Sci, 1994; 71, 152SÐ153S.
4 Tan J, Keay L and Jalbert I. Tear microspheres (TMSS) with high Dk lenses. Optom Vis Sci, 1999; 76S, 226.
5 Bourassa S and Benjamin WJ. Transient corneal surface 'microdeposits' and associated epithelial surface pits occurring with gel contact lens extended wear. Int Contact Lens Clin, 1988; 15, 338Ð340.
6 Tan J, Keay L, Jalbert I, et al. Mucin balls with wear of conventional and silicone hydrogel contact lenses. Optom Vis Sci, 2003; 80, 291Ð297.
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8 Craig JP, Sherwin T, Grupcheva CN and McGhee CN. An evaluation of mucin balls associated with high-Dk silicone hydrogel contact lens wear. Adv Exp Med Biol, 2002; 506, 917Ð923.
9 Morgan PB and Efron N. Comparative clinical performance of two silicone hydrogel contact lenses for continuous wear. Clin Exp Optom, 2002; 85, 183Ð192.
10 Ladage PM, Petroll WM, Jester JV, et al. Spherical indentations of human and rabbit corneal epithelium following extended contact lens wear. CLAO J, 2002; 28, 177Ð180.
11 Nichols J and King-Smith E. In-vivo thickness of the pre- and post-lens tear film and silicone hydrogel contact lenses measured by interferometry. Optom Vis Sci, 2001; 78, 51S.
12 Bron AJ, Tripathi RC and Tripathi BJ. Wolff's Anatomy of the Eye and Orbit, 1997; Eighth Edition. (London: Chapman & Hall Medical).
13 Naduvilath TJ. Statistical Modelling of Risk Factors Associated with Soft Contact Lens-Related Corneal Infiltrative Events. PhD Thesis (Newcastle: University of Newcastle), 2003.
14 Lai YC and Friends GD. Surface wettability enhancement of silicone hydrogel lenses by processing with polar plastic molds. J Biomed Mater Res, 1997; 35, 349Ð356.

Professor Nathan Efron is director of Eurolens Research, UMIST