Abstract
This paper outlines changes to the ocular surface caused by contact lenses and their degree of clinical significance. Substantial research and development to improve oxygen permeability of rigid and soft contact lenses has meant that in many countries the issues caused by hypoxia to the ocular surface have largely been negated. The ability of contact lenses to change the axial growth characteristics of the globe is being utilised to help reduce the myopia pandemic and several studies and meta-analyses have shown that wearing orthokeratology lenses or soft multifocal contact lenses can reduce axial length growth (and hence myopia).
However, effects on blinking, ptosis, the function of Meibomian glands, fluorescein and lissamine green staining of the conjunctiva and cornea, production of lid-parallel conjunctival folds and lid wiper epitheliopathy have received less research attention. Contact lens wear produces a subclinical inflammatory response manifested by increases in the number of dendritiform cells in the conjunctiva, cornea and limbus. Papillary conjunctivitis is also a complication of all types of contact lenses. Changes to wear schedule (daily disposable from overnight wear) or lens materials (hydrogel from SiHy) can reduce papillary conjunctivitis, but the effect of such changes on dendritic cell migration needs further study. These changes may be associated with decreased comfort but confirmatory studies are needed. Contact lenses can affect the sensitivity of the ocular surface to mechanical stimulation, but whether these changes affect comfort requires further investigation.
In conclusion, there have been changes to lens materials, design and wear schedules over the past 20+ years that have improved their safety and seen the development of lenses that can reduce the myopia development. However, several changes to the ocular surface still occur and warrant further research effort in order to optimise the lens wearing experience.
Keywords
Abbreviations
CEDCcorneal endothelial dendritic cells
CIconfidence interval
ECPeye care practitioner
LIPCOFlid parallel conjunctival folds
LWElid wiper epitheliopathy
Ortho-korthokeratology
PMMApoly methyl methacrylate
SICSsolution-induced corneal staining
SiHysilicone hydrogel
1. Introduction
Contact lenses are medical devices worn to offer refractive correction or a medical solution to a clinical problem at the ocular surface. In all circumstances, a key aim is for a contact lens to achieve its desired performance whilst either (a) leaving the anatomy and physiology of the eye unaffected or (b) altering ocular characteristics only as intended (e.g. the programmed, structural change of the eye during in myopia control with contact lenses). Given the complexity of the anatomical structures and physiological processes with which a contact lens interacts, this has proven to be a high threshold and one not yet fully met by modern lenses despite significant improvements in designs and materials, especially over the past 50 years.
This paper outlines the various changes caused by contact lens wear, how these alter with different contact lens types and their degree of clinical significance. The information is provided on a structure-by-structure basis and broadly follows the order in which an eye care practitioner might examine the integrity of the eye during a contact lens examination. This paper aims to review information which is different to the CLEAR Complications Report [
[1]
] which features as a sister paper in the CLEAR initiative. In general terms, the CLEAR Complications Report [[1]
] describes changes to the eye which require clinical intervention. The current paper covers physiological and anatomical alterations which do not require such intervention either because this is not considered to be helpful for patient care, or because the described ocular change has only recently been described and/or the appropriate clinical management is not yet established. Inevitably there is modest overlap in these papers but due to the deliberately different approaches taken (this paper takes an anatomy-based approach whereas the CLEAR Complications Report [[1]
] adopts an aetiology-based structure), where this occurs it is relevant, helpful and additive.2. The eyelids and adnexa
2.1 Blinking
Blinking is an important ocular surface physiological mechanism, maintaining physiology and providing good optics [
[2]
]. It involves both the upper and lower eyelids: the upper lid moves in the vertical and inward, whereas the lower lid moves in a temporal-to-nasal direction []. Blinking is either voluntary (a conscious and deliberate blink), reflex (elicited by external tactile, light, sound or electrical stimulation), or spontaneous (an unconscious blink in the absence of deliberate stimuli), with the latter the most common and most relevant to contact lens wear. The spontaneous blink-rate varies between 8 and 21 blinks per minute (in primary gaze) [[4]
], has a duration of about 300 ms and an upper blink excursion of 7−10 mm [[5]
,[6]
].These key blink variables can be influenced by various factors. For example, both dry eye disease (DED) and contact lens wear cause an increase in blink-rate [
7
, 8
, 9
]. Substantial variability in spontaneous blink rate has been reported in the literature, which may be attributed to a number of factors including methodology employed [[10]
], task performed during blink assessment [[7]
,11
, 12
, 13
, 14
], gaze direction [[12]
,[15]
,[16]
], cognitive and emotional factors [[17]
] and inter-participant variability [[18]
,[19]
]. The exact nature of the stimulus responsible for the increase in blink-rate during contact lens wear is not clear, but tear film instability, visual disturbance and symptoms of ocular irritation may provide stimulation for blinking [[7]
,[20]
]. One report has noted an association between greater subjective dryness and increased blink-rate [[21]
]. There appears to be little difference between the sexes [[22]
,[23]
] and although blink-rate increases with age, this may be due to age-related dry eye disease issues [[9]
].Increased blink-rate and unaltered blink completeness has been reported in the early stages of hard and rigid corneal lens wear [
[11]
,[24]
,[25]
], whereas no difference in overall blink-rate was found between long-term rigid corneal lens wearers and non-wearers [[26]
]. However, long-term rigid corneal lens wearers showed fewer complete blinks and more blink attempts than non-wearers. In addition, rigid corneal lens wearers with 3- and 9-o’clock staining showed more incomplete blinks and more blink attempts than wearers with minimal staining and non-wearers [[26]
]. A trend toward an increased blink-rate was also shown in neophytes fitted with soft lenses [[27]
,[28]
], as well as in adapted soft contact lens wearers [[7]
,[29]
,[30]
]. There was no clear effect of soft contact lens wear on blink completeness [27
, 28
, 29
], which appeared to be more influenced by the task performed during the assessment [[7]
].There is limited evidence of the effect of different soft lens materials and designs on blink characteristics. A shorter inter-blink interval (i.e. increased blink-rate) was reported after 10 min of soft contact lens wear, particularly for toric lenses (a periballast design and a double slab-off design), although none of the changes were statistically significant [
[25]
]. An increased blink-rate was found in subjects wearing a hydrogel contact lens (etafilcon A) after exposure to controlled adverse environmental conditions, whilst no change was observed in subjects wearing a SiHy lens (narafilcon A) [[31]
]. The authors suggested that the higher blink frequency was ‘a compensation mechanism to alleviate the relatively higher dryness over the lens surface.’ A higher blink-rate for SiHy lens wear (comfilcon A), compared with hydrogel lens wear (omafilcon A), was seen during exposure to controlled standard and adverse environmental conditions [[32]
]. According to the authors, the higher dehydration observed for the SiHy lens in the study could be the reason for the rise in blink-rate ‘in an attempt to refresh the tear film more frequently’, although other work has found dehydration to be greater with conventional hydrogels [[33]
,[34]
]. Contrary to these studies, other investigators found no significant difference in the increment of blink rate after two months of lens wear between hydrogel (hilafilcon B) and silicone hydrogel (lotrafilcon B) materials [[28]
]. The effects of contact lens wear on other aspects of blink dynamics, such as velocity and duration, have not yet been studied.The notion of incomplete blinking may be relevant to contact lens wear as incomplete blinking accounts for a two-fold increase in the risk of DED, meibomian gland atrophy and poor tear film stability []. Incomplete blinking might be more problematic for patients with low blink-rates, as this combination of effects will increase the exposure of the inferior ocular surface. This means that potential contact lens patients who are more predisposed to incomplete blinking, those who are using computers or ‘digital devices’ [
[9]
] or some ethnic groups (e.g. Asian patients [[35]
]), may require closer clinical attention prior to fitting and during the aftercare process.The measurement of blink characteristics has been challenging and complex using traditional methods [
[17]
,[36]
]. However, the increased availability and accessibility of technologies such as high-speed digital cameras [[10]
,[37]
,[38]
] and mobile phones [[39]
] have facilitated the investigation of human blinking. Additionally, commercially available instruments designed for tear film analysis, such as the LipiView II interferometer or the IDRA ocular surface analyser, have the capability to measure some aspects of blink dynamics, allowing eye care practitioners (ECPs) to assess blink characteristics in the clinical setting.2.2 Ptosis
Eyelid ptosis is the prolapse of the upper eyelid below its normal position [
[40]
]. Blepharoptosis is the more specific term for this ophthalmic condition and it can be either congenital or acquired [[41]
]. Ptosis related to contact lens use is described.Typically, the distance between the upper lid margin and the eyelid fold is minimal, but in contact lens induced ptosis this is enlarged, which may be of cosmetic concern []. Since the vast majority of patients wear contact lenses bilaterally, this condition may not be noticeable and so its prevalence may be higher than that reported in clinical practice. A systematic review has suggested that there is an increased risk of ptosis in rigid corneal (OR 17.4x) and soft contact (OR 8.1x) lens wearers compared to non-wearers [
[42]
]. Previous studies have highlighted the association of prolonged rigid corneal lens wear with acquired ptosis [43
, 44
, 45
, 46
, 47
, 48
, 49
, 50
]. Although the exact mechanism remains unknown, most authors agree that excessive physical manipulation of the eyelids during insertion and removal of rigid corneal lenses may be responsible for inducing damage to the levator aponeurosis [[43]
,[46]
,[48]
,[51]
]. Other proposed mechanisms include eyelid oedema or inflammation [[44]
] and contact lens-induced irritation [[46]
,[49]
]. There are fewer reports of contact lens induced ptosis in soft contact lens wearers [[49]
,[52]
]. Contact lens application and removal and contact lens induced-irritation may play a role in the pathogenesis of ptosis in soft contact lens wearers [[47]
,[49]
,[52]
].The vertical palpebral aperture size of rigid corneal lens wearers is significantly smaller than non-wearers, but this phenomenon does not occur with soft lens use [
[51]
]. This observation has been confirmed in long-term adapted rigid corneal and soft lens wearers, when compared to non-lens wearers. The palpebral aperture size of the rigid corneal lens, soft lens and non-lens wearer groups were: 9.76 ± 0.99 mm, 10.25 ± 0.94 mm and 10.10 ± 1.11 mm, respectively [[53]
]. Ptosis is a feature of the upper eyelid and rigid corneal lenses cause a reduction in palpebral aperture size of about 0.5 mm [[51]
,[53]
].Subjects fitted on an overnight wear basis with a rigid corneal lens in one eye and a soft lens in the other eye for 13 weeks had a maximal reduction in palpebral aperture size of 12 % with the rigid corneal lens at the 4–6 week time point versus 3 % for the soft lens eye [
[41]
]. At 13 weeks, the rigid corneal lens wearing eye had demonstrated a 3 % reduction in palpebral aperture size compared to a 7 % increase for the soft lens eye. These results suggest there may be an adaptation for many patients wearing contact lenses, with an initial reaction that may diminish over time, although the rigid corneal lens/soft lens contralateral nature of the study design may have influenced the findings. Most cases of ptosis can be managed by refitting into an alternative lens type or discontinuing lens wear, although surgery is an option in extreme cases where ptosis does not resolve after discontinuation of contact lens wear [].2.3 Meibomian gland changes
Meibomian glands are large sebaceous glands located in the upper and lower eyelids just posterior to the tarsal plate. They contribute most of the tear film lipid layer which protects the aqueous phase from evaporating too quickly and also stabilises the tear film by lowering surface tension. Any abnormalities in Meibomian gland function and/or anatomy lead to reduced meibum secretion and/or altered lipid composition which in turn disrupt the ocular surface integrity and influence contact lens success [
54
, 55
, 56
].There is no consensus on the impact of contact lenses on Meibomian glands (see Table 1). However, most recent data suggest that contact lens wear is not associated with Meibomian gland atrophy although it may affect Meibomian gland function [
57
, 58
, 59
, 60
, 61
]. Early findings on the relationship between contact lens wear and Meibomian glands showed that meibum in contact lens wearers has a 3 °C higher melting point than in non-wearers, with no difference between the three types of contact lenses (polymethyl methacrylate [PMMA] corneal, soft or rigid gas permeable corneal) [[62]
]. Another study examined the relationship between various ocular factors and self-reported contact lens-associated dry eye. The data did not show correlation between Meibomian gland dropout (i.e. apparent atrophy or loss of Meibomian glands when imaged) and dry eye in contact lens wearers suggesting that structural changes do not lead to altered or reduced meibum secretion. Furthermore, most patients (both contact lens wearers and non-wearers) had no signs of Meibomian gland dropout or had dropout of less than 25 %. However, the pre-lens lipid layer thickness was strongly associated with dry eye status [[57]
].Table 1Effect of contact lenses on Meibomian glands. The blank spaces indicate that either evaluation was not performed, or it was not possible to make a clear judgement whether results were relevant and appropriate. *Orthokeratology study. See also [
[86]
]. NIBUT = non-invasive breakup time; FBUT = fluorescein tear film breakup time; LLT = lipid layer thickness; MG = meibomian gland; CL = contact lens.| Study | Subjects | Symptoms | Plugging, obstruction | Meibum quality also expressibility | NIBUT, FBUT | LLT | Evaporation rate | MG appearance | |
|---|---|---|---|---|---|---|---|---|---|
| Ong and Larke (1990) [ [62] ] | CL wearers | 70 | yes | ||||||
| Non-wearers | 70 | ||||||||
| Nichols and Sinnott (2006) [ [57] ] | CL wearers | 360 | yes | yes | no | ||||
| Arita et al. (2009) [ [63] ] | CL wearers | 121 | yes | yes | |||||
| Non-wearers | 137 | ||||||||
| Villani et al. (2011) [ [66] ] | CL wearers | 20 | yes | yes | yes | ||||
| Non-wearers | 20 | ||||||||
| Arita et al. (2012) [ [58] ] | CL wearers | 64 + 77 | no | yes | no | ||||
| Non-wearers | 55 + 47 | ||||||||
| Michalinska et al. (2015) [ [59] ] | CL wearers | 41 | no | yes | yes (quality) / no (expressibility) | no | no | ||
| Non-wearers | 31 | ||||||||
| Pucker et al. (2015) [ [60] ] | CL wearers | 70 | no | no | no | no | |||
| Non-wearers | 70 | ||||||||
| Alghmandi et al. (2016) [ [71] ] | CL wearers | 60 | no | yes | yes | yes | no | no | yes |
| Non-wearers | 20 | ||||||||
| CL dropouts | 20 | ||||||||
| Na et al. (2016) [ [61] ]* | CL wearers | 58 | yes | no | no | ||||
| Ucakhan et al. (2018) [ [72] ] | CL wearers | 87 (173 eyes) | yes | yes | yes | yes | |||
| Non-wearers | 55 (103 eyes) | ||||||||
| Wang et al. (2019) [ [83] ]* | CL wearers | 59 | no | no | no | no | |||
| Pucker et al. (2019) [ [74] ] | CL wearers | 56 | no | no | |||||
| CL dropouts | 56 | ||||||||
| Gu et al. (2020) [ [65] ] | CL wearers | 85 | yes | yes | yes | ||||
| Non-wearers | 63 | ||||||||
| Yang et al. (2020) [ [84] ]* | CL wearers | 60 | no | yes | yes | ||||
| Non-wearers | 60 | ||||||||
| Llorens-Quintana et al. (2020) [ [73] ] | CL wearers | 33 | yes | ||||||
| CL dropouts | 8 |
A 2009 cross-sectional study found greater Meibomian gland dropout in 121 contact lens wearers than in 137 non-contact lens wearers, with the upper eyelid more affected than the lower. This work also noted that Meibomian gland dropout started not from the orifice side but from the distal side in contact lens wearers [
[63]
]. Another outcome of this study was the significant correlation between the duration of contact lens wear and Meibomian gland dropout [[63]
]. The study results were compared to the earlier findings of age-related changes of the Meibomian glands in a normal population where the authors found that aging increases the severity of Meibomian gland dropout. On average the Meibomian gland changes in contact lens wearers (mean age = 31.8 ± 8.0 years) from this study could be observed in a 60- to 69-year-old age group of non-contact lens wearers from the previous study [[64]
]. There was no significant difference in average Meibomian gland dropout between rigid corneal lens wearers and hydrogel lens wearers [[63]
]. Another, more recent study which also evaluated the effect of contact lens wear on Meibomian glands in an Asian population supports these findings in that contact lens wear negatively affects Meibomian glands and, furthermore, the structural changes worsen with years of wear [[65]
]. Other researchers have also reported apparent changes to Meibomian glands related to contact lens wear [[66]
,[67]
]. However, the methodology used (Meibomian gland acini reflectivity and acinar unit diameter measured by in vivo laser scanning confocal microscopy) is now considered to not image the Meibomian glands but rete ridges present at the dermal-epidermal junction [[68]
]. Furthermore, there is no association between rete ridges parameters measured by laser scanning confocal microscopy and actual Meibomian glands seen in meibography images [[69]
].The relationship between contact lens-related allergic conjunctivitis and morphological changes in the Meibomian glands has been investigated. It has been shown that allergic reaction, rather than contact lens wear, causes Meibomian gland distortion in patients with contact lens-related allergic conjunctivitis. However, contact lens wearers both with and without contact lens-related allergic conjunctivitis showed higher Meibomian gland dropout in contrast to non-wearers even though it was (marginally) not significant (p = 0.051). There was no significant difference between the mean Meibomian gland distortion between rigid corneal and hydrogel lens wearers [
[58]
].Other workers have found no association between changes in the Meibomian gland morphology (both in Meibomian gland distortion and dropout level) and contact lens use. Here, contact lens wearers had significantly worse meibum quality and orifice plugging and furthermore, abnormal meibum quality was strongly correlated to the duration of contact lens wear [
[59]
]. This group challenged previous findings [[58]
] suggesting that contact lens replacement schedule and wearing time should be considered when assessing the effect of contact lens wear on Meibomian gland morphology [[59]
]. Other studies have also failed to show that contact lens use affects Meibomian gland structure and function [[60]
,[70]
].The aforementioned findings suggesting that the duration of contact lens wear correlates with characteristics of the Meibomian glands stand in contrast to another study that did not find that correlation [
[71]
]. According to these authors, functional and structural Meibomian gland changes in soft contact lens wearers occur within the first two years of wear but do not worsen thereafter; however, the changes seem to be permanent as contact lens dropouts did not show signs of improvement [[71]
]. These results are consistent with other findings that found Meibomian gland characteristics in SiHy contact lens wearers worsen significantly after three years of contact lens wear but remain stable after seven years of wear [[72]
]. The earliest change that can be observed in Meibomian gland appearance caused by contact lens wear is thickening of the upper eyelid glands [[72]
].A detailed analysis of various characteristics of Meibomian glands, such as area of dropout, number of glands, Meibomian gland length, Meibomian gland width and Meibomian gland irregularity has been provided [
[73]
]. This showed that experienced contact lens wearers had larger areas of dropout and shorter glands when compared to non-contact lens wearers, but those changes were not correlated to years of wear. However, neophytes fitted with daily disposable soft contact lenses did not show any structural changes in Meibomian glands within the first 12 months of wear suggesting that changes happen later in time. Differences between contact lens materials were also examined. Here, hydrogel contact lens wearers showed some significant variations in the total number of glands and the area of gland atrophy in contrast to SiHy wearers. Non-invasive tear film breakup time also appeared to be dependent on the lens material. Furthermore, the changes in the percentage area of gland atrophy correlated with the fluorescein tear film breakup time in SiHy contact lens wearers. Moreover, the preferred habitual lens modality (monthly/fortnightly) seems to have an impact on the area of gland atrophy and gland width, although this relationship was not clearly explained by the authors [[73]
]. Meibomian gland width is a characteristic that does not seem to be affected by contact lens wear. Two studies found no correlation between this particular Meibomian gland characteristic and contact lens wear when successful contact lens wearers were compared to both contact lens dropouts and non-wearers [[73]
,[74]
].Larger areas of Meibomian gland dropout are associated with shorter fluorescein tear film breakup time [
[75]
]. A moderate negative correlation has been reported between daily lens wear duration and FBUT [[76]
]. No significant change in non-invasive tear film breakup time has been found after six months of SiHy contact lens wear, a similar finding to other studies in hydrogel contact lens wearers, but in contrast to one other study that reported reduced non-invasive tear film breakup time in neophytes after being fitted with hydrogel contact lenses [77
, 78
, 79
, 80
].The relation between subjective symptoms in contact lens wear and Meibomian glands is also ambiguous. One study found that disturbed Meibomian gland function characteristics (foam at Meibomian gland orifices, expressibility, meibum quality, lipid layer thickness, fluorescein tear film breakup time and evaporation rate) were associated with symptoms of discomfort among the symptomatic contact lens wearers [
[67]
] whereas another did not find a difference in lipid layer patterns between asymptomatic and symptomatic contact lens wearers [[81]
]. In addition, there was no difference in pre-lens tear break-up time between symptomatic or asymptomatic groups [[82]
]. Many other studies have shown that subjective symptoms are related to contact lens wear [[57]
,[61]
,[65]
,[66]
,[72]
] but on the other hand, there are also some that did not observe this relation [[59]
,[60]
,[71]
,[83]
,[84]
].The influence of overnight orthokeratology (ortho-k) on Meibomian glands has also received some attention in the literature. No significant differences in Meibomian gland appearance and fluorescein tear film breakup time after 3 years of ortho-k wear in children and adolescents have been reported [
[61]
]. These findings are supported by another study that did not find significant changes in non-invasive tear film breakup time, orifice plugging, meibum quality, difficulty of meibum excretion and Meibomian gland dropout level when comparing time points prior to and 2 years after the ortho-k wear in teenagers [[83]
]. These outcomes are contrary to that one study that found that Meibomian gland appearance in the upper eyelid got gradually worse and non-invasive tear film breakup time significantly decreased within 12 months of ortho-k wear [[84]
].Overall, then, the mechanism for Meibomian gland loss in contact lens wear is not fully understood. Possible explanations involve mechanical trauma, chronic irritation and aggregation of desquamated epithelial cells at the orifices of the glands [
[62]
,[63]
,[85]
].3. Conjunctiva
3.1 Bulbar and limbal conjunctiva
3.1.1 Hyperaemia
Hyperaemia is a visible response to the wearing of a contact lens (or to some other irritating or inflammatory factor) that is expressed as dilation of the conjunctival blood vessels [
[87]
]. This dilation changes the appearance of the exposed sclera and overlying bulbar and limbal conjunctiva within the palpebral aperture from a quiescent ‘white’ to a provoked ‘red’. The shift in hyperaemia is a sign that some underlying factor has altered the homeostatic conjunctival blood flow balance. No eye is ever perfectly ‘white’ as the conjunctiva contains visible blood vessels. There is a normal range in the hyperaemia appearance for the general population, reflecting physiological variation between individuals and non-irritative influences on the homeostatic balance [88
, 89
, 90
]. It is therefore important, when assessing change in hyperaemia with contact lens wear, to establish the non-lens wear baseline for each patient and to compare future change to that baseline.The hyperaemia is produced by increased dilation of the arterioles in the limbal corneal arcades and/or the bulbar conjunctival arteries []. The arteriolar walls are encircled by smooth muscle cells that control the diameter of the arteriole and thus blood flow through the arteriole. When stimulated, the smooth muscle relaxes leading to an increase in the arteriole diameter []. This changes the ratio between the hyperaemia of the blood vessels to the whiteness of the scleral background and the eye appears redder. The smooth muscle cells are innervated by sympathetic nerves [
[92]
], which provide central autonomic control over the arteriole diameter. The muscle cells are also affected by local factors. These locally-derived factors are moderated by chemical agents, such as prostaglandins or cytokines, that form part of the inflammatory response [[90]
,[93]
,[94]
].Increased dilation of the arterioles can be caused by mechanical irritation, hypoxia, hypercapnia, acidic shift (increase in lactic and carbonic acids), increased osmolarity, increased potassium, toxic reactions to a noxious agent, (e.g. preservatives, hydrogen peroxide), or as part of the inflammatory response to allergens or infection [
95
, 96
, 97
]. Many of these factors can be present in contact lens wear and can be acute or chronic in their expression.Hyperaemia is such a common response to contact lens wear [
[93]
,98
, 99
, 100
, 101
] that it is easy to forget that hyperaemia can be a sign the eye is experiencing stress [[90]
,[102]
,[103]
]. It is therefore important to include questions about any reported or observed ocular hyperaemia as part of the patient’s lens wear history during a clinical examination [[104]
]. The clinician should identify the potential causes for the hyperaemia and make suitable changes to the lens specifications, wear schedule, or lens care solution to prevent the condition becoming chronic. The clinician can use visual scales to grade hyperaemia severity and to monitor treatment effect [[105]
]. Significant efforts have been made to develop standardised grading scales that are easy to use by the clinician or that rely on computer analysis [106
, 107
, 108
, 109
, 110
, 111
, 112
].The main areas identified as possible causes for bulbar and limbal hyperaemia in contact lens wear are: lens surface/ocular surface mechanical interactions, pre-lens surface deposits, post-lens hypoxia, altered tear film, lens care solutions and ocular hygiene. All of these produce some form of inflammatory response from the ocular surface.
- ●Mechanical interactions can be produced by both tight-fitting and loose-fitting lenses, with a particular effect on the limbal arcades producing limbal hyperaemia [[113],[114]]. Lens edge design can have a particular effect on lens movement and on limbus/lens interaction [[115]]. Movement of the lens over the limbal area is the primary source of the mechanical interaction [[116]] and can be visibly observed as limbal hyperaemia and increased staining in the perilimbal area [[117]]. Treatment is by modification of lens specifications to improve the fit, with close attention to lens edge design [[118]].
- ●Pre-lens surface deposits are a feature of all contact lens wear modalities, including daily disposable, although with this modality the clinical consequences of deposits are negligible. Deposit formation occurs as a result of chemical interactions between the lens material and the tear film [[119]]. The deposits produce an allergic-type inflammatory reaction [[120],[121]]. Treatment is by initiating or increasing the frequency of the surface cleaning regime, or by changing lens wear modality.
- ●Post-lens hypoxia is produced by insufficient gas-exchange through the lens, principally due to low lens Dk [[122]]. Hypoxia was a particular feature of early low Dk soft lens materials [[93]]. Silicone hydrogel (SiHy) lens materials have effectively removed hypoxia (and thus hypercapnia) as a source for limbal and bulbar hyperaemia [[123],[124]]. Post-lens hypoxia is treated by choosing a lens material with a higher Dk [[125],[126]]. Hypoxia is still an issue for scleral/overnight medical wear due to the effect of the post-lens fluid reservoir [[127],[128]].
- ●A less stable tear film can be produced in contact lens wear, which induces increased tear evaporation [129,130,131], leading to partial dehydration of the lens material [[132],[133]]. This may produce mechanical effects from a tighter lens fit or increased friction from the lens surface [[131],[134]]. Treatment is by changing the lens material, lens wear modality, environmental conditions (if possible) and other lens wearer adaptations.
- ●Lens care solutions can produce limbal and bulbar hyperaemia [135,136,137,138]. This may be a direct effect from a biologically incompatible reaction between solution component and ocular surface, or indirectly through a failure of the product to work effectively, e.g. an ineffective protein cleaner. Treatment is by changing lens care solution modality or by lens wear modality.
- ●Lid-related infections, such as blepharitis or meibomian gland dysfunction, can be related to poor lid hygiene [[139]]. For these cases, improved lid hygiene can produce a significant improvement in ocular hyperaemia.
3.1.2 Sodium fluorescein, lissamine green and rose bengal staining
Two types of dye, sodium fluorescein and lissamine green, are currently used to examine the conjunctiva as part of contact lens pre-fitting and aftercare examinations [
[140]
]. Experimentally, fluorescein is actively taken up by healthy cells in cell culture [[141]
,[142]
]. Clinically, it is thought to permeate the cytoplasm of living but damaged cells, whereas lissamine green stains the cell membrane of dead or damaged cells. The presence of lissamine green staining is thus highly specific for dry eye disease [[143]
]. Both stains are enhanced by the use of filters: a yellow filter with blue light in the case of fluorescein and a red filter with white light for lissamine green. Lissamine green has largely replaced rose bengal, which is toxic, even in relatively low concentrations and uncomfortable, if not painful, for the patient [[144]
].Two main types of conjunctival staining are noted in soft contact lens wearers: i) dryness-related staining, primarily located on the nasal and temporal bulbar conjunctiva and ii) circumlimbal mechanical staining from contact lens edges.
Conjunctival fluorescein staining is commonly seen in non-contact lens wearers, but typically at lower levels than in contact lens wearers. Some conjunctival staining was seen in 98 % of a mixed group of contact lens wearers and non-wearers; however the proportion of subjects showing greater than Grade 1 staining (0–4 scale) was much higher in the contact lens group: 62 % versus 12 % [
[145]
]. Another study found conjunctival fluorescein staining in approximately half (53 %) of non-wearers versus 63 % of lens wearers [[146]
]. With both groups, the incidence of staining was significantly higher for those classified as symptomatic.Lissamine green conjunctival staining is less common than fluorescein staining in both contact lens wearers and non-wearers. However, lissamine green staining (outside of the limbal area normally covered by the lens edge) is more discriminating in identifying symptomatic patients, particularly contact lens wearers [
[146]
]. The authors hypothesised that reduced blinking in soft lens wearers results in greater evaporation and poorer conjunctival lubrication which, in turn, leads to increased friction during the blink and tissue damage.There has been little research on the effect of soft lens wear on conjunctival staining. However, two studies have thrown useful light on the significance of edge design [
[117]
,[147]
]. Soft lens edge profiles broadly fit into three categories: rounded, knife and chisel edge designs. Edge design was the primary factor in controlling circumlimbal fluorescein staining for SiHy lenses [[117]
]. A rounded edge produced the least circumlimbal staining, while a thin knife edge design produced the most, with an inverse association between staining and comfort. Comfort was poorest with the rounded design and highest with the knife edge (72 vs. 87 out of 100) [[117]
]. The study also noted lens rigidity as a secondary factor, finding that a lens of higher modulus generated more circumlimbal staining than a similar design of low modulus. Another study found broadly similar results with a wider range of lens types [[147]
]. With both chisel and knife edge designs, the higher modulus SiHy designs showed significantly more conjunctival staining than their hydrogel counterparts.Conjunctival staining induced by the lens edge is rarely symptomatic or accompanied by hyperaemia and, therefore, does not necessarily require a change of lens. An exception might be instances of significant conjunctival indentation which has been imaged by optical coherence tomography in soft lens wearers [
148
, 149
, 150
, 151
]. Clinically, this is revealed by pooling of fluorescein in circumlimbal indentations corresponding to the positioning of the lens edge. In one study of nine different soft lens types, conjunctival indentation was associated with poorer comfort [[152]
]. This can be alleviated by switching to a lens of thinner edge design and/or lower modulus.3.1.3 Lid-parallel conjunctival folds
Lid-parallel conjunctival folds (LIPCOF) are observed as small folds on the bulbar conjunctival surface, close to the lower lid margin and near to the limbus. They occur in both the lower temporal and nasal bulbar conjunctival areas (at around 4 and 8-o’clock of the corneal location), while the patient is looking in the primary gaze [
[118]
,[153]
]. The term lid-parallel conjunctival fold was first introduced in 1995 [[154]
] and the feature has been the subject of research by others subsequently [[82]
,[153]
,[155]
,[156]
].LIPCOF are thought to be caused by increased shearing forces during blinking, as a result of increased friction between the ocular surface and the lids, which, in turn, has been caused by reduced lubrication due to a deficient tear film [
[157]
]. These causal factors are particularly found in dry eye disease and studies have shown that LIPCOF is highly correlated with dry eye disease and associated symptoms [[153]
,156
, 157
, 158
, 159
]. The movement of the eyelids on the conjunctiva causes it to wrinkle into the folds. The model proposes that the greater the friction, the greater the size or extent of the LIPCOF. The folds are not permanent, but are maintained by the position of the eyelid. If the lower lid is retracted, the LIPCOF will disappear, but will reappear after normal blinking [[157]
]. LIPCOF can also occur in subjects showing no other signs or symptoms of dry eye disease [[160]
].LIPCOF are classified in two ways: by assessing the height of the folds [
[154]
] or by counting the number of folds [161
, 162
, 163
]. The number of folds approach has been adopted for both slit-lamp biomicroscopy and optical coherence tomography assessment [[153]
,[155]
,[164]
].LIPCOF interfere with tear meniscus assessment, either of the tear meniscus radius [
[165]
], height [[165]
,[166]
] volume [[167]
,[168]
], curvature, depth or cross-sectional area [[162]
]. LIPCOF may affect tear film mixing, spreading and thus ocular surface lubrication, although the precise mechanism for this is unclear [[169]
].‘Contact lens discomfort’ is an adverse clinical response to contact lens wear, characterised by the wearer reporting symptoms of discomfort and possible reduced lens wear time. Symptoms are not always associated with clinical signs. LIPCOF has been proposed as a feature of contact lens discomfort [
[82]
,[161]
,170
, 171
, 172
].The aetiology of LIPCOF in contact lens wear is thought to be similar to that in dry eye disease - increased friction between the moving eyelid and the ocular surface. The presence of the contact lens in the eye alters the normal spreading and stability of the tear film over the ocular surface and the normal apposition of the eyelid against the bulbar conjunctival surface. These changes lead to an increase in friction at the ocular surface between the eyelid and conjunctiva during blinking, particularly in the 4 and 8 o’clock area where the shear forces are thought to be greatest [
[170]
,[173]
]. Within this model, improving the wettability of the lens surface and thus the distribution of the tear film over the lens and exposed conjunctiva, should also reduce friction and the incidence of LIPCOF. However, it should be noted that a clear relationship between the coefficient of friction and LIPCOF is yet to be proven [[118]
].There is a limited literature on the effects of different contact lens types, materials and designs on LIPCOF. Most studies report a positive correlation between the presence of LIPCOF and discomfort symptoms or with the extent of lens wear experience. In a series of studies on subjects experiencing discomfort when using low to medium water content (24–62 %) monthly disposable hydrogel contact lenses, LIPCOF was strongly positively correlated to discomfort symptoms, older age, lid wiper epitheliopathy (LWE) and to a lower mucin production [
[82]
,[171]
,[174]
].The effect is also seen with neophyte lens wearers. One study reported that the main discriminators for contact lens-induced dry eye in neophyte contact lens wearers wearing vifilcon A hydrogel contact lens and senofilcon A SiHy contact lenses was LIPCOF [
[160]
]. Similarly, neophytes who wore SiHy lenses full time for six months showed an increase in LIPCOF [[80]
]. The extent of lens wear experience is also a factor in the development of LIPCOF. Using the term ‘conjunctivochalasis’, but using the Hoh LIPCOF scale to describe conjunctival changes (suggesting LIPCOF might have actually been reported), an increase in LIPCOF with lens wear experience and with lens wearer age has been reported [[175]
]. Also, a positive correlation between LIPCOF and duration of contact lens wear (with LIPCOF findings higher after at least a year of SiHy usage) has been found [[176]
].There is one contrasting report that found no relationship between LIPCOF and contact lens materials (hydrogel contact lens and SiHy contact lenses) or lens wear modality (yearly disposable contact lens and monthly disposable contact lens) [
[155]
], although this could be due to the small number of study subjects in this work.It has been proposed that LIPCOF should be incorporated into the clinical assessment of lens wearers to identify those wearers at greater risk of developing contact lens discomfort symptoms. This is based on the finding that ocular dryness symptoms are strongly linked to a combination of LIPCOF and non-invasive tear film breakup time [
[156]
- Pult H.