The Effect of Tear Film Degradation on Contrast Sensitivity Function

Student: Farraj ALghamdi
Supervisor: Dr Anita Simmers

Contents
1. Introduction
2. Structure of the tear film
2.1 Lipid layer
2.2 Aqueous Layer
2.3 Mucus Layer
3. Precorneal tear film functions
3.1 Optical function
3.2 Mechanical
3.3 Defence
3.4 Nutrition
4. Dry eye
4.1 Classification of dry eye
4.2 Symptoms
5. Tear stability assessment
5.1 Tear break-up time (BUT)
5.2 Non-invasive tear break-up time (NITBUT)
6. Contrast sensitivity

6.1 Contrast sensitivity vs visual acuity

6.2 Tear film and vision function

7. References
1. Introduction
Tear film is a thin layer consisting of a mix of elements, such as water, proteins and lipids. The main components of the tear film are lipid layers, aqueous layers and mucus layers (Rolando & Zierhut 2001). Dry eye is a disorder which occurs as a result of a deficiency in producing tear film or by the increased evaporation of tear film. This can cause damage to the ocular surface of the eye, which can cause different symptoms in turn, such as foreign body sensation, eye irritation, visual disturbances, and possibly other symptoms that have not been discovered yet (Schaumberg et al. 2001).
The methods used in the treatment of dry eye depend on the determined degree of dryness, which can be mild, moderate or severe. In the case of mild dryness no signs occur on the ocular surface and the only treatment prescribed is artificial tears to be used four times per day. The effect on the ocular surface starts to be slightly observed in moderate dryness, especially on the surface of the cornea, such as superficial punctate keratopathy (SPK). In this case the patient should use both artificial tear film and lubricant. In severe dryness SPK becomes clearer than in moderate cases and the patient requires more treatment and a new type of drops that enhance the production of tear film in the eye. (Calonge, et al., 2001)
Dry eye diseases can also cause some visual function problems, such as blurred vision and glare (Carolyn, et al., 2003 cited in Ridder, et al., 2011) and these symptoms can have a severe impact on an individual’s quality of life (Schiffman, et al., 2003). According to the study conducted by Goto, et al. (2002), dry eye can cause a reduction in visual acuity. A study carried out by (Huang et al. 2002) showed that Contrast Sensitivity (CS), which is the ability of the eye to distinguish the object from its background at varying levels of contrast, was also negatively affected in the case of dry eye, as well as daily activities performed in bright or dark environments.
Patients with a reduction in visual function (contrast sensitivity) due to dry eye may still maintain good levels of visual acuity (Huang et al. 2002). Contrast sensitivity changes with spatial frequencies, thus sine-wave grating targets are used for doing full contrast sensitivity function (CSF). The area under the curve provides mathematical information (Campbell & Robson 1968) and small variations on this area are a good indicative for changes in neurologic and ophthalmologic vision (Owsley et al. 1983; Cravo et al. 2013).The CS test therefore provides a sensitive measure to changes in overall visual function and not just the smallest high contrast resolvable detail measured by traditional Snellen acuity measures (Jindra & Zemon 1989).
The pre-corneal tear film is the first optical surface of the eye and any degradation of this medium introduces additional aberration into the optical system as a whole. Several clinical studies have found that these aberrations reduce retinal image quality and contrast sensitivity in patients with dry eye. The same results have been found in normal subjects just after they have blinked.
The aim of this study is to measure contrast sensitivity function in a group of adult subjects before and after exposure to an environmental chamber that will temporarily degrade the quality of the tear film.
An assessment of tear film will be carried out to ensure that each subject does not have dry eye. An ocular and systemic history will be taken to rule out any exclusion criteria. Contrast sensitivity will be measured psychophysically on a high resolution monitor before and after the subject spends time in the environmental chamber.

2. Structure of the tear film
The precorneal tear film thin film covers the ocular surface. This complex structure is composed by three different layers and each layer has a particular structure as well as many important functions (Pflugfelder et al. 2004; Patel & Blades 2003). The three layers are:
Outer lipid or oil layer, aqueous layer and inner mucus layer (Holly & Lemp 1977; Wolff 1946)(Figure. 1).
The normal thickness of the tear film is 7 µm (King-Smith et al. 2004)and it depends on factors such as low blink ratio or large palpebral fissure (Lemp 1995); however, it was found different range of tear thickness according to different studies and different techniques used for measuring it. Values form 3-11 µm has been found in some studies (King-Smith et al. 2004; Benedetto et al. 1984; Danjo et al. 1994; Wang et al. 2003)meanwhile values of 41 µm to 45 µm have also been reported using an laser interferometer (Prydal et al. 1992). This variability in values may be a result of using different techniques some of which may be considered invasive thereby altering tear film production (Lemp et al. 2007).
2.1 Lipid layer
This is the most superficial layer. It is a very thin layer with a thickness around 0.1μm. It is composed of polar and non-polar lipids which are produced by the meibomian glands, Glands of Zeiss and Glands of Möll all of which are located in the lids. The lipids extend over the aqueous layer which contains lipocalin, an enzyme that helps the spread of lipids (McCulley & Shine 2001). The composition of this layer plays an essential role in tear film stability providing a smooth optical surface as well as reducing the aqueous layer evaporation and preventing tear overflow (Bron et al. 2004).
2.2 Aqueous Layer
It is located between the lipid and the mucus layers. It is almost the total thickness of the tear film layer with a thickness of 6.5 -10μm(Garg et al. 2006). It is produced by the lacrimal gland but also to a lesser extent the Glands of Krause and Glands of Wolfring. It is mostly comprised of water and its composition consists of a series of electrolytes (Na+, K+ & Ca2+) and hydrogen ions apart from carbon hydrates, glucose, cholesterol among others, that contribute to maintain ph. tear at 7.4 as well as tonicity and help to keeps epithelial integrity(Carney & Hill 1976).
The proteins and enzymes have bacteriostatic function(Mackie & Seal 1984; Garg et al. 2006). The most relevant are lysozyme, lactoferrin, lipocalin and a series of immunoglobulins (IgA, IgG, IgM, IgE). They are produced by the lacrimal gland, and the glands of Krause and Wolfring. The aqueous layer is responsible for eye lubrication, wash particles , and due to enzymes present, prevent infections (Holly & Lemp 1977).
Tear production is regulated by afferent and efferent trigeminal nerves that stimulate parasympathetic and sympathetic nerves of the lacrimal gland. This allows a fast response against unexpected environment circumstances. Cornea or annexes structures stimulation produce and increment the tear production knows as reflexive lacrimation (Dartt 2009).
2.3 Mucus Layer
It is the deepest and densest layer of the tear film. Its thickness is 0.02-0.04 μm (Garg et al. 2006). It is composed of mucins, high molecular weight glycoproteins, produced by Goblet Cells: (Glands of Manz and Crypts of Henle), non-goblet epithelial cells and lacrimal gland (soluble mucins) (Watanabe 2002). Its composition allows the aqueous layer spread evenly over the corneal epithelium and it is important for maintaining s tear stability.

Figure.1. Tear film structure From Allegan Laboratories

3. Precorneal tear film functions
As describe above the three layers film has different functions, the most relevant functions are:
3.1. Optical: Keep a regular and smooth ocular surface to maintain a high quality retinal image (Lemp & Blackman 1981)Tear film is the first refractive surface for light entering the eyes; tear film irregularities or lack of stability may influence retinal image (Rolando & Zierhut 2001).
3.2. Mechanical : The cornea, conjunctiva and eyelid protect the ocular surface from mechanical damage that may result from the blinking process (Ohashi et al. 2006) as well as wash away foreign particles, debris and water from the cornea.
3.3. Defence: Help to protect the ocular surface against environmental factors such as temperature and humidity and external organisms that may affect the ocular surface through antibacterial agents (Rolando & Zierhut 2001).
Reflex tears clean the conjunctiva and the cornea from any irritating or foreign bodies (Holly & Lemp 1977).
3.4. Nutrition: Provide a nutrition and oxygen supply to the cornea. Also, the corneal epithelium receives oxygen, electrolyte and growth factors from the tear film (Pflugfelder et al. 2004)
The special distribution and composition of tear layers give to film particular physical features such as basic pH 7.45±0.2, similar to blood plasma, Osmolarity 303.7 ± 22.9 m Osm kg-1; due to the high presence of electrolytes or others like refractive index and viscosity (Table.1(Garg et al. 2006).
Refractive index 1.33698 ± 0.00110
pH 7.45+/-0.2
Osmolarity 303.7 ± 22.9 m Osm kg-1
Viscosity Non-Newtonian 9 mPa sec (low shear) 2 mPa sec (high shear)
Surface tension 43.6 ± 2.7 mNm-1
Table 1. Physical features of tear film composition

4. Dry eye
The tear film is a thin layer consisting of a mix of components, such as water, proteins and lipids. The integrity of the precorneal film is essential for maintaining a healthy ocular surface and a clear retinal image (Lemp & Blackman 1981; Rolando & Zierhut 2001). A deficiency in the tear film or in the increasing tear film evaporation leads to dry eye disorder (Javadi & Feizi 2011).
Dry eye was defined by the National Eye Workshop in 1995 as “a disorder of tear film due to tear deficiency or excessive evaporation, which causes damage to interpalpebral ocular surface and is associated with symptoms of ocular discomfort” (Lemp 1995). In 2007 subcommittee of DEWS ( Dry Eye Workshop, and industry/ academic organisation set up by the Tear film and Ocular Surface Society (TFOSS) ) considered that definition should include the factors that contribute to dry eye such as ocular surface inflammation, tear osmolarity or impairments (Lemp et al. 2007); it set up a new definition for dry eye as “a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear film instability, with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface” (Lemp et al. 2007).

4.1 Classification of dry eye
Taking into account the description above, dry eye is classified according to two main different types: aqueous deficient dry eye (ADDE) and evaporative dry eye (EDE) (Figure 2) (Schein, Tielsch, et al. 1997). Aqueous deficient dry eye is in turn divided in Sjögren Syndrome dry eye and Non-Sjögren dry eye. Whereas evaporative dry eye is divided according to environment causing factor as intrinsic and extrinsic.
Figure.2 DEWS dry eye classification. DEWS classifies dry eye according to two major causes: aqueous deficient and evaporative dry eye. Aqueous-deficient dry eye is divided itself in Sjögren syndrome dry eye and non-Sjögren syndrome dry eye. Meanwhile evaporative dry eye has to subgroups classified according to its caused factors, intrinsic or extrinsic factors.(Lemp et al. 2007)
4.2 Symptoms
Alterations in the precorneal film can cause damage to the ocular surface of the eye, which can cause different symptoms in turn, such as foreign body sensation, eye irritation, burning, or stinging and possibly other symptoms that have not been documented (Schaumberg et al. 2001)(Lemp 1995). Blurred vision and visual disturbance are frequently reported by patients with dry eye (Vitali et al. 1994; Rieger 1992). It has been documented that symptoms of blurred and intermittent vision are frequently reported by patients with low tear break up time values (de Paiva CS et al. 2003; Kallarackal et al. 2002; Begley et al. 2003).
Some studies had remarked that there seems not to be a clear correlation between signs and symptoms reported in individuals with moderate or mild dry eye (Schein, Tielsch, et al. 1997; Schein, Muñoz, et al. 1997); whereas, reported symptoms by patient are highly significant and contribute to diagnosis of dry eye (Nichols et al. 2004; Nichols 2006).
This led to the development of the twelve question Ocular Surface Disease Index (OSDI) to help classify and assess the three major dry eye categories with relation to ocular symptoms, visual function and environment related symptoms (Schiffman et al. 2000).
5. Tear stability assessment
Under normal circumstances tear film stability is maintained through blinking (Ohashi et al. 2006). When the eyes reduces blink frequency or is not blinking for a long time, the tear film starts breaking its structure forcing the blink or producing discomfort.
5.1 Tear break-up time (BUT)
This measures the interval between last complete blink and the break-up of the tear film. In this technique it is necessary to instil fluorescein; through the slip lamp and using a cobalt blue filter it is possible to measure the time from the last blink until the first patch or spot appears in the green-dyed tear film on the cornea. It was suggested that values under 10 sec can be considered as diagnostic of dry eye (Kallarackal et al. 2002).
5.2 Non-invasive tear break-up time (NITBUT)
They are called “non-invasive” because the eye is not touched and is not necessary to install any substances. It measures the interval between last complete blink and the break-up of the tear film observing the reflected white and black concentric circles image known as Placido’s disc projected on the corneal tear film. Measurement can be achieved during this period by observing when distortion is produced pre-rupture or tear thinning time (TTT) (Hirji et al. 1989) or/ and break up (NIBUT). NIBUT values of less than 15 seconds are consistent with dry eyes. For this technique instruments such as a Keratometer (Hirji et al. 1989), hand-held Keratoscope or Tearscope are required (Guillon 1998). They project a cold light in order to avoid tear reflex production and can be used directly in front of the eye or using the slip-lamp.
5.3 Controlled environment chamber
The tear film as the first optical barrier of the eye is continuously exposed to environmental factors. According to DEWS dry eye classification evaporative dry eye can be produced due to extrinsic factors such as low relative humidity, high wind velocity and occupational environment (Lemp et al. 2007).
For investigating how these factors can affect the tear stability a “controlled environment chamber” (CEC) was tested with animals (Barabino et al., 2005). Using CEC was able to demonstrate that under very low humidity percentage environments animals showed alteration in tears secretion, goblet cells density and corneal signs related to dry eye. Therefore, it was concluded that the chamber can be used to produce specific environmental condition of temperature and relative humidity.

6. Contrast sensitivity
Contrast is defined as the ability to distinguish between different levels of luminance in a static image. The contrast threshold can be defined as the minimum contrast that can be resolved by the patient. Sensitivity is the reciprocal of threshold Therefore, the contrast sensitivity function is the reciprocal of the contrast-threshold (Pelli & Bex 2013). Threshold contrast was established by Fechner’s 1860 in 1% in a large number of targets and under different conditions, independent of size and luminance. (Fechner 1966).
Human visual system can be considered an optical system and every image in visual field can be represented in a mathematical way in terms of spatial frequencies. (Fourier) When the pattern is repeated once and again, this will be represented like a sum of sinusoids with a particular frequency and amplitude, known as Fourier Transformed. When an image passes through an optical system is possible to predict the quality of final image if you know the quality of initial image. For pure gratings image with same contrast the optical system will be defined by the image contrast. The graphical representation of relative image contrast against frequency is called modulation Transfer function (MTF)(Levine 2000).
The contrast sensitivity function (CSF) represents contrast sensitivity (the reciprocal of contrast threshold) against stimuli spatial frequency. These values are represented in a scale where the horizontal axis shows spatial frequency in cycles per degree from 1-16 cycles/degree and the vertical axis plots contrast threshold values in a logarithm scale. CSF is considered the result of optical and neural factors (Green & Campbell 1965). According to Artal the Modulation Transfer Function (MTF) determines the quality of the retinal image (Artal & Navarro 1994)
Campbell determined what channels are stimulated for each different spatial frequency (Campbell & Robson 1968). Low spatial frequencies (0.5- 1 cycles/degree) are seen by magnocellular system providing general feature information to image recognition; meanwhile high spatial frequencies (8-16 cycles/degree) are seen by parvocellular system and together with information from magnocellular system are related to fine detail of image during visual process (Campbell & Maffei 1974). It had been demonstrated that intermediate spatial frequencies (5-7 cycles per degree) are easily detected by most individuals in comparison with low or high spatial frequencies. Values under the curve indicate a reduction in normal contrast sensitivity function. Changes in contrast perception leads to a loss of normal performance even in daily life (Bansback et al. 2007).
Contrast sensitivity varies with age maximum sensitivity has been reported at around 20 years of age at spatial frequencies of 2-5 cycles/degree (Figure 3). Other pathologies like retinal diseases, amblyopia, lens abnormalities or neural dysfunctions can reduce the contrast sensitivity function (Cravo et al. 2013). The ability to perceive contrast also decreases naturally with age and becomes worst with the lack of transparency of the media or sensory alterations (Owsley et al. 1983).
Figure 3. Contrast sensitivity variation with age. (Owsley et al. 1983)
Contrast sensitivity tests have been shown to be an excellent and reliable measure which provides information on a patients functional vision and not simply the ability to resolve a small high contrast object i.e. visual acuity (Snellen chart) (Arden, 1978; Jindra & Zemon, 1989 Jin, Wu, & Wu, 1992)
For this reason this CSF measures have been recently incorporated into clinical procedures, not only by its ability for early prediction of visual disorders but also by detect abnormality visual acuities (Monés et al. 2005).

6.1 Contrast sensitivity vs visual acuity
Contrary to contrast sensitivity, visual acuity is related to spatial resolution and it is the minimum separation of detail that can be distinguished. Targets are made in high contrast black letter over white background according to specific dimensions. Visual acuity test in unable to provide information about how is viewed an object of low contrast (Owsley & Sloane 1987). So that, visual acuity test is considered not a good indicative for visual function since real life offers large variety of contrast and spatial frequencies (Pelli & Bex 2013). It has even been demonstrated that under particular circumstances such as laser in situ keratomileusis surgery visual acuity remained constant while contrast sensitivity low band frequencies are reduced (Yamane et al. 2004). Diseases like glaucoma produce a reduction in low frequencies for parvocellular and magnocellular pathways (McKendrick, Sampson, Walland, & Badcock, 2007), diabetic retinopathy decrease values for both low and medium contrast sensitivity frequencies (Stavrou & Wood 2003) or the geography atrophy due to dry age macular degeneration that produce change in sensitivity for large targets (Sunness et al. 1997).
6.2 Tear film and vision function
The tear film is considered the first optical surface of the eye. Alterations on the tear film structure produce highly irregular optical aberrations that in turn can decrease the modulation transfer function producing an decrement in visual acuity and contrast sensitivity and a correspondent increment of optical aberrations (Himebaugh et al. 2003). Ocular aberrations increase in a natural way with age which can be explained by a decompensation between the cornea and crystalline lens aberrations (Artal, Berrio, Guirao, & Piers, 2002). Not only the impact of the eye’s higher order aberration on visual acuity was widely proved (Artal et al. 2006)(Applegate et al. 2006), but also the effect of higher aberrations and spherical aberrations on contrast sensitivity (Yamane et al. 2004) and (van Gaalen et al. 2009). The correlation between dry eye, in pathologies like keratoconjunctivitis sicca, and alterations in contrast sensitivity was demonstrate by (Rolando et al. 1998). Ridder in 2009 demonstrated in his study that the use of artificial tears in dry eye individuals produced a reduction in contrast sensitivity and an increment in optical aberrations when tested immediately after administration, but CSF improved after a couple of weeks of treatment. He proposed that optical aberration were responsible for loss of contrast sensitivity and that these aberrations consequently improved after tear normalization (Ridder et al. 2009).
7. References
Applegate, R.A., Marsack, J.D. & Thibos, N.L., 2006. Metrics of Retinal Image Quality Predict Visual Performance in Eyes With 20/17 or Better Visual Acuity. Optometry and Vision Science, 83(9), pp.635–640.
Arden, G.B., 1978. The importance of measuring contrast sensitivity in cases of visual disturbance. The British journal of ophthalmology, 62(4), pp.198–209.
Artal, P., Benito, A. & Tabernero, J., 2006. The human eye is an example of robust optical design. Journal of vision, 6(1), pp.1–7.
Artal, P. & Navarro, R., 1994. Monochromatic modulation transfer function of the human eye for different pupil diameters: an analytical expression. Journal of the Optical Society of America, 11(1), pp.246–249.
Bansback, N. et al., 2007. Determinants of health related quality of life and health state utility in patients with age related macular degeneration: the association of contrast sensitivity and visual acuity. Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation, 16(3), pp.533–543.
Begley, C.G. et al., 2003. The Relationship between Habitual Patient-Reported Symptoms and Clinical Signs among Patients with Dry Eye of Varying Severity. Investigative Ophthalmology and Visual Science, 44(11), pp.4753–4761.
Benedetto, D., Clinch, T. & Laibson, P., 1984. Invivo observation of tear dynamics using fluorophotometry. Archives of Ophthalmology, 102, pp.410–2.
Bron, A.J. et al., 2004. Functional aspects of the tear film lipid layer. Experimental Eye Research, 78(3), pp.347–360.
Campbell, F.W. & Maffei, L., 1974. Contrast and spatial frequency. Scientific American, 231(5), pp.106–114.
Campbell, F.W. & Robson, J.G., 1968. Application of fourier analysis to the visibility of gratings. Journal of Physiology, 197, pp.551–566.
Carney, L.G. & Hill, R.M., 1976. Human tear pH. Diurnal variations. Archives of Ophthalmology, 94(5), pp.821–824.
Cravo, A.M. et al., 2013. Temporal expectation enhances contrast sensitivity by phase entrainment of low-frequency oscillations in visual cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience, 33(9), pp.4002–10. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3638366&tool=pmcentrez&rendertype=abstract.
Danjo, Y., Nakamura, M. & Hamano, T., 1994. Measurement of the precorneal tear film thickness with a noncontact optical interferometry film thickness measurement system. Jpn J opthalmol, 38, pp.260–6.
Dartt, D. a., 2009. Neural regulation of lacrimal gland secretory processes: Relevance in dry eye diseases. Progress in Retinal and Eye Research, 28(3), pp.155–177.
Fechner, G., 1966. Elements of Psychophysics Helmut E. . Holt, Rinehart, & Winston, eds., New York.
Van Gaalen, K.W. et al., 2009. Relationship between contrast sensitivity and spherical aberration. Journal of Cataract & Refractive Surgery, 35(1), pp.47–56.
Garg, A. et al., 2006. Clinical Diagnosis and Management of Dry Eye and Ocular Surface Disorders. In Clinical Diagnosis and Management of Dry Eye and Ocular Surface Disorders. Jaypee Brothers Medical Publishers (P) Ltd., p. 536.
Green, D.G. & Campbell, F.W., 1965. Effect of Focus on the Visual Response to a Sinusoidally Modulated Spatial Stimulus. Journal of the Optical Society of America, 55(9), p.1154.
Guillon, J.P., 1998. Non-invasive Tearscope Plus routine for contact lens fitting. Contact Lens & Anterior Eye : The Journal of the British Contact Lens Association, 21 Suppl 1, pp.S31–S40.
Himebaugh, N.L. et al., 2003. Use of retroillumination to visualize optical aberrations caused by tear film break-up. Optometry and vision science : official publication of the American Academy of Optometry, 80(1), pp.69–78.
Hirji, N., Patel, S. & Callender, M., 1989. Human tear film pre-rupture phase time (TP-RPT)): a non-invasive technique for evaluating the pre-corneal tear film using a novel keratometer wire. Ophthalmic & Physiological Optics, 9(4), pp.139–142.
Holly, F.J. & Lemp, M. a, 1977. Tear physiology and dry eyes. Survey of ophthalmology, 22(2), pp.69–87.
Huang, F.C. et al., 2002. Effect of artificial tears on corneal surface regularity, contrast sensitivity, and glare disability in dry eyes. Ophthalmology, 109(10), pp.1934–1940.
Javadi, M. a & Feizi, S., 2011. Dry eye syndrome. J Ophthalmic Vis Res, 6(3), pp.192–198. Available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22454735.
Jin, C.J., Wu, D.Z. & Wu, L., 1992. The contrast sensitivity function in low vision. Yan ke xue bao = Eye science / “Yan ke xue bao” bian ji bu, 8(1), pp.45–48.
Jindra, L.F. & Zemon, V., 1989. Contrast sensitivity testing: a more complete assessment of vision. Journal of cataract and refractive surgery, 15(2), pp.141–148.
Kallarackal, G. et al., 2002. A comparative study to assess the clinical use of Fluorescein Meniscus Time (FMT) with Tear Break up Time (TBUT) and Schirmer’s tests (ST) in the diagnosis of dry eyes. Eye, 16, pp.594–600.
King-Smith, P.E. et al., 2004. The thickness of the tear film. Current eye research, 29, pp.357–368.
Lemp, A. et al., 2007. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). The ocular surface, 5(2), pp.75–92.
Lemp, M. a, 1995. Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. The CLAO journal : official publication of the Contact Lens Association of Ophthalmologists, Inc, 21(4), pp.221–232.
Lemp, M. & Blackman, H., 1981. Ocular Surface mechanism. Annal Ophthalmology, (13), pp.61–3.
Levine, M.W., 2000. Chapter 9. Spatial frequency representation. In Levine and Shefner’s Fundamentals of Sensation and Perception. New York: Oxford University Press, p. 582.
Mackie, I.A. & Seal, D.V., 1984. Diagnostic implications of tear protein profiles. British Journal of Ophthalmology, 68, pp.321–324.
McCulley, J.P. & Shine, W.E., 2001. The lipid layer: The outer surface of the ocular surface tear film. Bioscience Reports, 21(4), pp.407–418.
Monés, J. et al., 2005. Contrast sensitivity as an outcome measure in patients with subfoveal choroidal neovascularisation due to age-related macular degeneration. Eye (London, England), 19(11), pp.1142–50. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15467700.
Nichols, K.K., 2006. Patient-reported symptoms in dry dye disease. The ocular surface, 4(3), pp.137–145.
Nichols, K.K., Nichols, J.J. & Mitchell, G.L., 2004. The reliability and validity of McMonnies Dry Eye Index. Cornea, 23(4), pp.365–371.
Ohashi, Y., Dogru, M. & Tsubota, K., 2006. Laboratory findings in tear fluid analysis. Clin Chim Acta, 369(1), pp.17–28. Available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16516878.
Owsley, C., Sekuler, R. & Siemsen, D., 1983. Contrast sensitivity throughout adulthood. Vision research, 23(7), pp.689–699.
Owsley, C. & Sloane, M.E., 1987. Contrast sensitivity, acuity, and the perception of “real-world” targets. The British Journal of Ophthalmology, 71(10), pp.791–6.
De Paiva CS, Lindsey, J. & SCPflugfelder, 2003. Assessing the severity of keratitis sicca with videokeratoscopic indices. Ophthalmic epidemiology, 110, pp.1102–9.
Patel, S. & Blades, K.J., 2003. The dry eye : a practical approach, Butterworth-Heinemann.
Pelli, D.G. & Bex, P., 2013. Measuring contrast sensitivity. Vision Research, 90, pp.10–14. Available at: http://dx.doi.org/10.1016/j.visres.2013.04.015.
Pflugfelder, S.C., Beuerman, R.W. & Stern, M.E., 2004. Dry Eye and Ocular Surface Disorders. Informa Healthcare. Available at: http://books.google.com.my/books?id=uWy1QvsuDCsC.
Prydal, J.I. et al., 1992. Study of human precorneal tear film thickness and structure using laser interferometry. Investigative Ophthalmology & Visual Science, 33(6), pp.2006–2011.
Ridder, W.H. et al., 2009. Contrast sensitivity and tear layer aberrometry in dry eye patients. Optometry and vision science : official publication of the American Academy of Optometry, 86(9), pp.E1059–E1068.
Rieger, G., 1992. The importance of the precorneal tear film for the quality of optical imaging. The British journal of ophthalmology, 76(3), pp.157–158.
Rolando, M. et al., 1998. Low spatial-contrast sensitivity in dry eyes. Cornea, 17(4), pp.376–379.
Rolando, M. & Zierhut, M., 2001. The ocular surface and tear film and their dysfunction in dry eye disease. Survey of Ophthalmology, 45(SUPPL. 2), pp.203–10.
Schaumberg, D. a et al., 2001. Hormone Replacement Therapy and Dry Eye Syndrome FREE. JAMA : the journal of the American Medical Association, 286(17), pp.2114–2119.
Schein, O.D., Muñoz, B., et al., 1997. Prevalence of dry eye among the elderly. American journal of ophthalmology, 124(6), pp.723–728.
Schein, O.D., Tielsch, J.M., et al., 1997. Relation between signs and symptoms of dry eye in the elderly. A population-based perspective. Ophthalmology, 104(9), pp.1395–1401.
Schiffman, R.M. et al., 2000. Reliability and validity of the Ocular Surface Disease Index. Archives of ophthalmology, 118(5), pp.615–621.
Stavrou, E. & Wood, J., 2003. Letter contrast sensitivity changes in early diabetic retinopathy. Clinical and Experimental Optometry, 86(3), pp.152–156.
Sunness, J.S. et al., 1997. Visual function abnormalities and prognosis in eyes with age-related geographic atrophy of the macula and good visual acuity. Ophthalmology, 104(10), pp.1677–1691.
Vitali, C., Moutsopoulos, H. & Bombardieri, S., 1994. The European Community Study Group on diagnostic criteria for Sjogren’s syndrome. Sensitivity and specificity of tests for ocular and oral involvement in Sjogren’s syndrome. Ann Rheum Dis, 53, pp.637–47.
Wang, J. et al., 2003. Precorneal and pre- and postlens tear film thickness measured indirectly with optical coherence tomography. Investigative Ophthalmology and Visual Science, 44(6), pp.2524–2528.
Watanabe, H., 2002. Significance of mucin on the ocular surface. Cornea, 21(2 Suppl 1), pp.S17–S22.
Wolff, E., 1946. Mucocutenous Junction of the Lid Margin and Distribution of Tear Fluid. Trans Ophthalmol Soc UK, 66, pp.291–308.
Yamane, N. et al., 2004. Ocular higher-order aberrations and contrast sensitivity after conventional laser in situ keratomileusis. Investigative Ophthalmology and Visual Science, 45(11), pp.3986–3990.
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