Article Text
Abstract
The precorneal tear film is maintained by blinking and exhibits different phases in the tear cycle. The tear film serves as the most anterior surface of the eye and plays an important role as a first refractive component of the eye. Alterations in tear film dynamics may cause both vision-related and ocular surface-related symptoms. Although the optical quality associated with the tear film dynamics previously received little attention, objective measurements of optical quality using wavefront sensors have enabled us to quantify optical aberrations induced by the tear film. This has provided an objective method for assessing reduced optical quality in dry eye; thus, visual disturbances were included in the definition of dry eye disease in the 2007 Dry Eye Workshop report. In addition, sequential measurements of wavefront aberrations have provided us with valuable insights into the dynamic optical changes associated with tear film dynamics. This review will focus on the current knowledge of the mechanisms of wavefront variations that are caused by different aspects of tear film dynamics: specifically, quality, quantity and properties of the tear film, demonstrating the respective effects of dry eye, epiphora and instillation of eye drops on the quality of vision.
- tears
- optics and refraction
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Introduction
The tear film is the eye’s first defence against the external environment. A deficiency in the tear film is often associated with symptoms of ocular discomfort. Concurrently, the tear film serves as the first refractive surface of the eye and is therefore an important optical element in preserving the quality of vision (QoV).1 Therefore, alteration of the tear film on the ocular surface may cause or contribute to both vision-related and ocular surface-related symptoms. A variety of factors influence tear film, including blinking, eyelids, the lacrimal system, external environments (eg, temperature, humidity and air flow) and internal emotions. The new Tear Film & Ocular Surface Dry Eye Workshop (TFOS DEWS) II definition (2017) recognises the multifactorial nature of dry eye as a disease where lost tear film homeostasis is the central pathophysiological concept.2 The quality, quantity and properties of the tear film can affect its homeostasis and these aspects ultimately influence QoV.
QoV can be assessed subjectively and objectively. The use of a questionnaire is a subjective evaluation method; the Ocular Surface Disease Index (OSDI),3 Impact of Dry Eye on Everyday Life (IDEEL),4 Dry Eye-Related Quality-of-Life Score (DEQS),5 Computer-Vision Symptom Scale (CVSS17)6 and the National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25) are frequently used in clinical practice.7 The conventional visual acuity test, contrast sensitivity measurement and functional visual acuity measurement8 9 are also subjective methods used to assess visual function.
It has been difficult to detect alterations of visual function that are associated with tear film behaviour, using conventional visual acuity measurements.10 Recent developments in optical quality assessment have enabled objective quantification of irregular astigmatism, which cannot be detected by conventional visual acuity tests. Corneal topography systems and wavefront sensors are now widely used in clinical practice to objectively assess optical quality. Moreover, sequential measurements of corneal topographic data or wavefront aberrations serve as a useful tool to assess which dynamic optical changes associated with precorneal tear film behaviour.11
Wavefront sensors are used to objectively evaluate aberrations of the whole eye; these sensors quantify irregular astigmatism as higher-order aberrations (HOAs).12 13 In this review, we discuss the effects of tear film on QoV, including current findings. In addition, we offer speculation on the mechanism of wavefront variation that may be caused by different tear film dynamics: specifically, quality, quantity and properties of the tear film.
Quality and quantity of the tear film
In our daily clinical practice, tear film is generally evaluated in terms of quality and quantity, which are essential factors when characterising tear film dynamics. A key factor is ‘tear film stability’, which is the ability of the tear film to retain a smooth refractive surface on the cornea. To maintain good tear film quality and optimal visual performance, an appropriate quantity of tears is needed.14 When tear quantity is either remarkably insufficient or excessive, the quality of the tear film may be reduced. A notable example of insufficient tear film is aqueous tear-deficient dry eye (ADDE), whereas an example of excessive tear film is found in eyes with epiphora. A commonly held view is that dry eye and epiphora represent different ends of the spectrum of tear film disorders. However, both dry eye and epiphora are similar in that they are multifactorial diseases which are characterised by unstable tear film and cause various vision-related symptoms.2 Cases with short tear film breakup time (BUT)-type dry eye, which are characterised by decreased wettability of the corneal surface (tear film stability) with an absence of tear deficiency,15 16 are notable examples where a decrease in the quality of the tear film is the primary factor impacting optical quality, in contrast to the typical aetiological factors (quantity or properties of the tear film).
Quality/quantity of the tear film and QoV: dry eye
Tear film instability plays an important aetiological role in the pathophysiology of dry eye, as tear stability is reduced in all forms of dry eye.16 17 According to the new TFOS DEWS II definition, visual disturbance is included as an ocular symptom of dry eye and remains a central feature of dry eye disease.2
Previous studies revealed that measurement of HOAs is sufficiently sensitive to monitor optical changes associated with tear film behaviour.18–22 Subsequently, sequential measurements of ocular or corneal wavefront aberrations have been used to investigate the effect of tear film stability on HOAs, with the assumption that tear film stability can reflect fluctuations or alterations in optical quality, as induced by tear film.23–35 This has led to a better understanding of the impaired QoV in cases of dry eye. Thus, visual disturbance was acknowledged for the first time in the original TFOS DEWS definition of dry eye (2007).36 Since tear film varies and exhibits different phases, synchronisation of data obtained from multiple devices does not reveal real-time tear film status. Moreover, simultaneous measurements of ocular aberrations and lower tear meniscus have been attempted37; these may provide an ideal method to evaluate the effects of tear film quality and quantity on optical quality.
HOAs in dry eye based on tear film breakup patterns
Local disruption of the tear film is known as tear film breakup, which is exacerbated by an unstable tear film. The phenomenon of tear breakup and its impact on dry eye symptoms have been investigated.38–42 A recent study has proposed five different fluorescein tear film breakup patterns based on the tear film dynamics after the eye is opened and kept open.42 This classification can aid in differential diagnosis of dry eye and subsequent selection of the optimal treatment for each individual case, regardless of the inherent variability of BUT measurements and breakup observations.43 44 According to this approach, each breakup pattern roughly corresponds to a severe or mild/moderate case of ADDE, dry eye with decreased wettability of the corneal surface (described as short BUT-type dry eye) and evaporative dry eye42 (figure 1). Area breakup pattern: severe ADDE, line breakup pattern: mild-to-moderate ADDE, spot breakup pattern: severe short BUT-type dry eye and dimple breakup pattern: mild-to-moderate short BUT-type dry eye. Random breakup pattern is assumed to be a kind of evaporative dry eye that is observed even in normal eyes. It should be noted that there are some cases with combined breakup patterns and cases that are difficult to classify. Based on the previous reports and this clinical-based breakup patterns, reported HOAs patterns can be summarised into these breakup patterns, for discussions of quality and quantity of tear film in cases of dry eye.
In the area breakup pattern (associated with severe ADDE), sequential HOAs exhibit consistently greater postblink values because of severe corneal epithelial damage, including within the central corneal region. Retinal image quality is impaired even immediately after the blink, and then remains poor for an extended duration after each blink. Very low tear volume may contribute to absence of sequential alterations in HOAs.30 Moreover, a relationship has been described between increased ocular HOAs and corneal epithelial damage overlying the optical zone in cases of dry eye.30 32
A line breakup pattern, with mild-to-moderate ADDE, is often accompanied by corneal epithelial damage in the inferior cornea. When no damage has occurred in the central corneal region, there is no observed increase in HOAs. Additionally, in cases of aqueous deficiency, there is no remarkable increase in observed HOAs; therefore, the sequential HOA pattern is similar to that of normal eyes with stable pattern.30
In the spot breakup pattern (associated with severe short BUT-type dry eye), breakup occurs during eye opening because of the severely decreased wettability of the corneal surface. Thus, there is difficulty in detecting tear film-induced alterations in HOAs, when using commercially available wavefront sensors. Recently, the formation of scatter-producing microaberrations associated with tear film breakup was reported; these are too fine to be resolved with a clinical Hartmann-Shack wavefront sensor.33 Measurement of wavefront aberrations on a microscopic scale would help in clarifying wavefront variations for detecting breakup patterns.
In eyes with the dimple breakup pattern (associated with mild-to-moderate short BUT-type dry eye), breakup is generally characterised by a streak-like breakup area around the central corneal region; this occurs during upward movement of fluorescein after the blink and results from decreased wettability of the corneal surface. Since tear deficiency is usually absent in these cases, HOAs increase after the blink (ie, there is deterioration in postblink retinal image quality).29 A positive correlation has been reported between the progression index for corneal HOAs and the subjective index of patient-reported visual outcomes,34 which may be linked to the severe symptoms associated with short BUT-type dry eye.15 16
A random breakup pattern (associated with evaporative dry eye) can be observed after the cessation of upward movement of fluorescein after the blink and is reported to be likely a result of evaporation of aqueous tears. As random breakup patterns can be seen even in normal eyes, it usually has longer BUT (>5 s), sometimes even longer than 10 s. It is reported that there are variations in sequential postblink HOA changes (for 10 s) even in normal healthy eyes: the stable pattern (defined as maintaining an almost constant HOA value with little variation), the small-fluctuation pattern (defined as having fluctuations in sequential values compared with the stable pattern without a tendency to increase or decrease) and the sawtooth pattern (defined as having total HOAs with an upward curve after blinking and decreasing at the blink).25 If the tear film is very stable and random breakup occurs after 10 s, a stable pattern would be observed sequential HOAs. Since the breakup region and shape sometimes differ with each blink in eyes with a random breakup pattern,42 such changes may lead to the manifestation of a small-fluctuation pattern in postblink sequential HOAs. Sequential HOAs in eyes with the sawtooth pattern are similar to those seen in eyes with the dimple breakup pattern. This pattern is reported to be an unstable variation of postblink changes in HOAs in normal eyes during the blink suppression condition.25 Such a pattern would possibly be observed in some normal eyes in which tear film breakup occurs in the central corneal region during the blink suppression condition. In addition, it is speculated that this pattern might be observed in patients with a combination of evaporative dry eye and short BUT-type dry eye.
In general, the influence of tear film breakup pattern on HOAs can be determined by whether the optical zone (the central corneal region) is involved. Thus, the area breakup pattern and dimple breakup pattern can affect HOAs. Indeed, a relationship has been reported between surface irregularities of the central cornea and visual function in dry eye, using corneal topographic analysis and contrast sensitivity measurements.45 46
Although it is well known that there are considerable differences in the tear film breakup pattern between dry eyes and normal eyes,42 some similarities are also noted.40 Recent papers have reported on the relationship of tear breakup to the lipid layer rather than to the wettability of the corneal surface, specifically in eyes with the spot breakup pattern.47 48 Further studies using mathematical analysis and modelling of the tear film and breakup should be performed to understand the clinical implications and to improve the diagnosis and treatment of dry eye.49 Moreover, use of shearing interferometry50 51 or high-speed videotopographic measurement52 would help clarify the effect of quality and quantity of tear film on QoV in each breakup pattern.
Treatment of dry eye and HOAs
Several studies have reported on the efficacy of dry eye treatment for HOAs.53–57 Use of artificial tears for 2 weeks resulted in fewer short-term effects, including a temporary increase in number of HOAs after instillation of artificial tears; this suggested improvement in tear film stability. However, baseline HOAs did not change with the treatment.53 Four-week treatment with diquafosol for ADDE significantly reduced HOAs, prolonged BUT and decreased corneal epithelial damage.54 In cases of short BUT-type dry eye, treatment with diquafosol significantly improved ocular HOAs.55 A previous investigation, using sequential wavefront measurements, revealed that diquafosol was effective for treating dry eye after cataract surgery, with prolonged BUT and improved optical quality. An upward pattern in HOAs after the blink observed before the cataract surgery shifted to a stable pattern after the 4-week treatment with diquafosol.56 Rebamipide was effective for improvement of optical quality and BUT in cases of short BUT-type dry eye.57
Insertion of punctal plugs is an effective treatment for dry eye that is refractory to maximum medical therapy.58 By conserving tear film and providing a smooth ocular surface, punctal plugs can dramatically improve corneal epithelial damage. Punctal plug placement significantly reduced HOAs by 47%–63%, in cases of postlaser in situ keratomileusis (LASIK) dry eye.59 However, a previous investigation, using sequential wavefront measurements, demonstrated that excessive retention of the tear film by punctal occlusion in cases of dry eye may paradoxically cause increased visual impairment, despite improvement in the extent of corneal epithelial damage.60 Taken together, these reports suggest that an appropriate tear quantity is highly important in dry eye treatment.
Quality/quantity of the tear film and QoV: epiphora
Epiphora (excessive tearing) is a commonly reported symptom, particularly in the elderly. Previous studies have assessed the impact of surgical treatments on quality of life (QoL) or vision-related QoL in patients with epiphora, using symptom-based questionnaires.61–68 However, the optical quality in eyes with epiphora has not yet been fully investigated. Recently,69 optical quality was quantified in patients with epiphora who were undergoing lacrimal passage intubation, using a wavefront sensor; in that study, postblink movement of epiphora-related excessive tear volume caused greater HOA values during the first few seconds after the blink, indicating that the unstable tear film caused by excessive tear volume decreased optical quality. This observation may explain the subjective blur reported by patients with epiphora. After lacrimal passage intubation, sequential HOAs exhibited a stable pattern that indicated improvement in optical quality, as the tear meniscus dimension decreased.69
Thus, quantitative wavefront measurements have led to a better understanding of impaired QoV in cases of dry eye10 70; we expect that these measurements will similarly aid in understanding of QoV in epiphora, thereby providing new QoV-based insights into lacrimal management or lacrimal surgery.
Properties of the tear film and on short-term QoV
The effect of properties of the tear film on optical quality can be demonstrated by assessments of eye drop instillation, using eye drops with unique properties, such as altered viscosity or suspensibility. In our clinical practice, some patients complain of resultant blurred vision after instillation of these agents. Currently, there are several commercially available eye drops with beneficial properties for treatment of glaucoma or dry eye including artificial tear eye drops. Since both glaucoma and dry eye are chronic and patients generally require lifelong use of eye drops, it is useful to measure the effect of eye drops on optical quality, in order to improve drug compliance in patients who are treated with these eye drops.
Antiglaucoma eye drops
Hiraoka et al quantitatively studied contrast sensitivity, HOAs and corneal backward light scattering instillation after the use of timolol gel-forming solution (GFS) and brinzolamide.71 Both eye drops tended to cause transient blurring of vision after instillation. A mean decrease in contrast sensitivity was noted, 2 min after instillation, in both groups. A temporary increase in HOAs was noted when instilling either timolol GFS or brinzolamide, but not when using standard timolol solution. Timolol GFS showed a greater magnitude and longer duration (5 min) of increase in HOAs, compared with brinzolamide (2 min’ duration). That study showed that corneal backward light scattering was noted at 5 min only when instilling brinzolamide. Corneal backward light scattering increased immediately after instillation, with a significant increase at 5 min, and a gradual decrease after 5 min. The authors suggested that the reduction in contrast sensitivity after timolol GFS instillation is mainly attributed to the increase in HOAs, whereas after the instillation of brinzolamide, the reduction is likely caused by a combination of increases in HOAs and corneal backward light scattering.
Notably, timolol GFS contains gellan gum, which converts to a gel after reacting with cations in the tear film, whereas brinzolamide is a suspension of insoluble white particles of carboxyvinyl polymer. The gellan gum in timolol GFS and the insoluble particles in brinzolamide may cause uneven spreading of the tear film, resulting in increased HOAs. The white particles contained in brinzolamide are suspected to increase corneal backward light scattering.
Artificial tears
Artificial tears are used clinically to treat dry eye syndrome by reducing irritation and lubricating the ocular surface.58 Instillation of eye drops can disrupt the smooth refractive surface; this surface is necessary to provide good QoV by reducing optical aberrations associated with an unstable tear film. In the literature, metrics such as contrast sensitivity, light scattering and corneal topographic indices have been useful in representing QoV.72–75 In particular, HOAs have been established as a useful way to objectively quantify optical quality in the human eye.12
Common ingredients found in artificial tears include polyethylene glycol (PEG), polyvinyl alcohol, carboxymethylcellulose (CMC) and glycerine. A randomised controlled trial76 used wavefront sensing and optical coherence tomography to objectively assess optical quality and tear volume. The investigators found that PEG-based eye drops cause a greater disturbance of optical quality at 5 min postinstillation, when compared with CMC. However, optical quality became similar to CMC at 20 min and 40 min. In particular, patients with severe dry eye syndrome seemed to benefit from improved optical quality after receiving CMC eye drops. A trend of decreasing optical quality with increasing tear meniscus was also noted.
Tear retention eye drops for dry eye
Koh et al reported the effect of viscosity and suspensibility of eye drops used for dry eye treatment on ocular HOAs and forward light scattering.77 They compared 0.3% sodium hyaluronate ophthalmic solution (with high viscosity), 3% diquafosol ophthalmic solution and 2% rebamipide ophthalmic suspension (with high suspensibility) and saline. A remarkable increase in HOAs was observed immediately after instillation of 0.3% sodium hyaluronate; thereafter, the HOAs recovered to baseline levels. Berger et al also showed that an increase in HOAs was observed after the instillation of viscous eye drops.78 Conversely, a significant increase in forward light scattering was observed immediately after the instillation of 1% rebamipide ophthalmic suspension, although this returned to preinstillation levels at 5 min after instillation. Ishioka et al reported decreased corneal regularity, immediately after the instillation of 0.3% sodium hyaluronate, as assessed using corneal topography.79 In addition to the previous findings, they concluded that temporal reduction in optical quality may be attributed mainly to increased HOAs after the instillation of highly viscous 0.3% sodium hyaluronate ophthalmic solution, as well as to increased forward light scattering after the instillation of 2% rebamipide ophthalmic suspension in healthy subjects.
A study by Koh et al 77 was crucial for outlining the differences between eye drops of high viscosity versus high suspensibility. Their findings were consistent with previous findings by Hiraoka et al regarding antiglaucoma eye drops.71 However, this study only tested healthy subjects.77 A study by Lekhanont et al 80 reviewed the impact of a single instillation of 0.18% sodium hyaluronate artificial tear on HOAs in dry eye patients, both at baseline and up to 120 min after instillation. They found that 0.18% sodium hyaluronate caused a significant decrease in spherical aberration at 1 min, which gradually returned to baseline, demonstrating a minimal impact of the 0.18% concentration on QoV. Future studies may explore the effect of these eye drops on optical quality and QoV in subjects with dry eyes and in settings of variable temperatures and humidities.
Conclusion
Given the high prevalence of tear film disorder diseases (eg, dry eye and epiphora) and the importance of understanding the role of the tear film in the pathophysiology of each disease, quantification of tear film-associated QoV is essential. Moreover, because many patients with ocular diseases or perioperative patients generally require the instillation of eye drops several times a day for a certain period or for their entire lifetimes, the effects of unique properties of ophthalmic drugs on QoV represent an important development. We anticipate increasing use of the wavefront sensor in clinical practice, because of the complementary information it can provide for diagnosis and management of tear film disorder diseases. Moreover, further studies are needed to clearly elucidate how wavefront sensor-based quantitative assessment of optical quality can advance our understanding of the relationship between tear film and QoV.
References
Footnotes
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent Not required.
Provenance and peer review Not commissioned; externally peer reviewed.