Principal Investigator: P. Ewen King-Smith

Co-investigators: Jason J. Nichols, Kelly K. Nichols, Barbara A. Fink

Lipid thickness measurements. This work has been performed by Erich Hinel, a graduate student in the College, with advice from Drs. Jason and Kelly Nichols and the Principal Investigator. The aim of the studies was to investigate the relationship between the thinning rate of the tear film between blinks and the thickness of the superficial lipid layer. This layer retards evaporation, which makes a major contribution to tear film thinning. We believe that the thinning of the tear film between blinks, as studied in our experiments, ultimately can cause "tear film breakup" which in turn can cause the ocular surface damage in dry eye conditions; thus we are interested in tear thinning rate because of its clinical implications. An improved method of measuring lipid layer thick was developed and applied, based on measuring the absolute value of the reflectance of the lipid layer as a function of wavelength. A preliminary report of this study "Measurement of the Thickness of the Lipid Layer of the Tear Film Using Reflection Spectra" was made at the 2008 Annual Meeting of ARVO – the Association for Research in Vision and Ophthalmology. Principal findings were:

1. The thinning rate of the tear film was significantly inversely correlated with the thickness of the lipid layer. This is to be expected if tear thinning is mainly due to evaporation, and evaporation rate is inversely related to the thickness of the lipid layer.
2. A histogram of the tear thinning rate showed a "bimodal" distribution with two peaks – one at a slow thinning rate and one at a rapid thinning rate. An interpretation is that the lipid layer is sometimes a good barrier to evaporation, so thinning rate is slow, but sometimes it is a poor barrier, so thinning rate is considerably more rapid. We call this the "Dichotomous Model" (good/poor) of the lipid layer.
3. The Dichotomous Model was a better fit to the thinning rate versus lipid thickness data than an alternative model derived by analogy with electrical theory (Ohm’s Law). For the Dichotomous Model, we assumed that thinning rate would have a (constant) slow value when the lipid layer was thicker than a critical thickness, but thinning rate would have a rapid value for thinner films. The critical thickness was about 30 nm, or about 12 lipid molecule layers.

A manuscript describing these results is currently in preparation.

Lipid interferometer development. The measurements described above are based on the assumption that the lipid layer has a uniform thickness within the measurement spot on the tear film (nominally 33 micrometers in diameter, but probably larger on account of aberrations, diffraction and any defocus). Recent evidence indicates that this is not true. It is therefore important to obtain high resolution images of the lipid layer, so that estimates of the spatial variability of the lipid layer within our measurement spot can be made. This new high resolution lipid imaging system, which is supported by the 2007 Ohio Lions Eye Research Foundation grant, is currently being developed. This is a complicated system with 4 optical channels – one of which is used for imaging the lipid layer, two being used for eye alignment, and one being used to monitor the light output from the stroboscopic source. It is intended that all these channels will be imaged on a single video camera (so that, for example, the eye alignment can be checked for any image of the lipid layer).

I have recently submitted a grant application to NIH for which the Lions funds have contributed importantly as a seed grant.

Satiani N, Green-Church K, Nichols JJ, King-Smith PE, Nichols KK (2007). Omega 3 fatty acids and dry eye: clinical, interferometric and proteomic considerations. American Academy of Optometry Annual Meeting.

Nichols JJ, Hinel E and King-Smith PE (2008) . Lipid Layer Thickness and Tear Film Thinning Before and After Application of a Lipid Emulsion Drop. ARVO annual meeting.

King-Smith PE, Hinel E and Nichols JJ (2008) . Measurement of the Thickness of the Lipid Layer of the Tear Film Using Reflection Spectra. ARVO annual meeting.

Heryudono, A; Braun, R J; Driscoll, T A; Maki, K L; Cook, L P; King-Smith, P E (2007) Single equation model for the tear film in a blink cycle: realistic lid motion. Mathematical medicine and biology : a journal of the IMA vol. 24, no. 4 347-77.

Nichols, JJ, Sinnott, LT, King-Smith, PE, Hidenobu, N, and Sadayasu, T (2008). Hydrogel contact lens binding induced by contact lens rewetting drops. Optom Vis Sci 85, 236-240.

Maki KL, Braun RJ, Driscoll TA and King-Smith PE. (2008) A Model of Reflex Tearing Using an Overset Grid Method. Math Med Biol, in press.

King-Smith PE, Fink BA, Nichols JJ, Nichols KK and Braun RJ. (2008) Contributions of Evaporation and Other Mechanisms to Tear Film Thinning and Break-Up. Optom Vis Sci, in press

Wu D, Boyer KL, Nichols JJ and King-Smith, PE. (2008) Texture based prelens tear film segmentation in interferometry images. Machine Vision and Applications Journal, in press

Blur, especially from uncorrected or under-corrected refractive error such as myopia

(nearsightedness), is an obvious cause for degraded quality of vision. However, interestingly, a

number of studies have shown that the response of the visual system to blur is not static.

Adaptation to blur can result in an improvement in visual performance following prolonged

periods without refractive correction or with induced refractive blur. These studies have

significant clinical implications as blur adaptation possibly may be a way to enhance visual

sensitivity in individuals with sub-optimal results following refractive surgery procedures such

as LASIK. Also, there have been speculations that if blur adaptation can produce an

improvement in vision, perhaps part-time spectacle wear or partial correction may be adequate

when correcting patients with myopia. However, differences between the methodologies used

and the visual outcome measures obtained across these studies make it difficult to draw firm

conclusions about the role of blur adaptation in the management of myopia.

In the protocol, for which I had received the 2007-08 fellowship, I had proposed to

explore the temporal aspects of blur adaptation. In this study we have tried to assess the influence

of two factors on the visual acuity measurements: initial adaptation time and acuity presentation

had developed, was employed to control for the practice effects and letter viewing time. In this

procedure individual letters were presented in a random order, thereby the possibility of

perceptual learning to occur is minimal. The study has been successfully completed and below is

the brief report.

The study was carried on 10 individuals with normal vision (emmetropes) between 18

and 35 years of age following a screening procedure to determine eligibility for participation. To

examined the induction of blur adaptation three initial blur exposure durations were employed –

15min, 5min and 1min, with a natural scene as the adapting target. Also the influence of two

durations of test target presentation (1.5min and 10min presentations) on blur adaptation was

assessed. There was also a condition for measuring visual acuity without any influence of blur

adaptation, which served as a comparison for the post-adaptation values. Hence each subject was

tested on eight different conditions, one condition per day. During all the eight conditions, a

myopic defocus of +1.00D was used. The data was analyzed using the with-in subject repeated

measures. The results show that there was no statistically significant influence (p=0.64) of any of

the four initial adaptation durations (0min, 1min, 5min and 15min) on the post adaptation visual

acuity measure. However, acuity was better (mean = 0.30 logMAR) with 10min acuity

presentation times compared to 1.5min presentation times (mean = 0.40 logMAR; p = 0.002).

Hence, this result indicates that the test presentation duration had a significant influence on the

visual acuity measure.

So these results possibly indicate that although blur adaptation might bring about an

improvement in visual sensitivity, its enhancement effects might be specific to the test visual

target and might not be transferable to normal "out of laboratory" viewing conditions. As the

visual acuity outcome is independent of the initial adaptation period, it indicates the possibility

of blur adaptation being feature-specific.

Subramanian, V. and Mutti, D.O. (2008). "Temporal Characteristics of Blur Adaptation."

Abstract to be presented at the 2008 meeting of the American Academy of Optometry.

I would like to take this opportunity to thank the Ohio Lions Eye Research Foundation for

selecting me to receive the fellowship for 2007-08.

Vidhya Subramanian, Donald O Mutti

College of Optometry, The Ohio State University

Purpose: Visual acuity in the presence of blur has been demonstrated to be dynamic;

there is an improvement in visual acuity following prolonged periods of uncorrected or

induced refractive blur (Mon-Williams et al., 1998). However the influences of the initial

blur exposure duration and the test stimuli presentation time on these adaptation effects is

less well known. In this study we assess the temporal aspects of blur adaptation by

measuring visual acuity following varying initial adaptation and test presentation

measured in 10 emmetropic subjects after adaptation to a natural scene whose amplitude

spectrum had a slope of -1.0. All measurements were made monocularly in the right eye.

Each subject was exposed to eight different conditions. The eight conditions included 4

initial blur exposure periods of 0min, 1min, 5min and 15min and two visual acuity

presentation times of 1.5min (1 sec per letter) and 10 min (21 sec per letter). Myopic

defocus of 1D was used during both the initial adaptation period and test stimuli

performed. The four initial adaptation durations did not show any statistically significant

effect on post adaptation visual acuity measure for either of the test presentation times (p

= 0.64). However, there was a statistically significant effect of test presentation duration.

Acuity was better (mean = 0.30 logMAR) with 10min acuity presentation times

Visual acuity was independent of the initial adaptation time, possibly indicating that blur

adaptation has a feature-specificity; viewing a blurred generic scene did not improve

optotype acuity. However exposures of at least 21 seconds to the letter to be identified

resulted in enhanced visual acuity. Such feature specificity might make blur adaptation of

limited value in dynamic viewing conditions.

Functional Significance of Lacritin, A Novel

Tear Film Glycoprotein, In Contact Lens-

Related Dry Eye and Meibum and Tear

Film Secretion

Principal Investigator:

Co-Investigator:

Lacritin is a recently identified glycoprotein associated with the tear film and ocular surface. Initial evidence

suggests that it is a prosecretory mitogen, with possible involvement in regulation of lacrimal gland secretion. It

has also recently been found in the meibomian gland secretion proteome, and although its functional

significance there is unknown, it may play a role in regulation of meibomian gland lipid secretion. The purpose

of this proposed work is to test the hypotheses that 1) lacritin expression is reduced in both the tear film and

meibum of individuals with contact lens dry eye, and 2) this reduction in lacritin expression in the tears and

meibum is associated with a reduced secretion of the tear film and lipid.