WO2009058850A1

WO2009058850A1 - System and method for imaging tear film on an ocular surface

Info

Publication number: WO2009058850A1
Application number: PCT/US2008/081568
Authority: WO
Inventors: Jianhua Wang; Shuliang Jiao
Original assignee: University Of Miami
Priority date: 2007-10-30
Filing date: 2008-10-29
Publication date: 2009-05-07

Abstract

A method and system for imaging tear film on an ocular surface. The method and system includes depositing a contrasting agent onto the ocular surface. The method may further include positioning an ocular device about the ocular surface. An OCT scanner may then image the ocular surface to detect impairments in the boundary layer between the tear film and the ocular device or the boundary between the tear meniscus and the ocular device.

Description

SYSTEM AND METHOD FOR IMAGING TEAR FILM ON AN OCULAR SURFACE

FIELD OF THE INVENTION

The present invention relates to a system and method for ophthalmic imaging, and in particular, a method and system for imaging tear film on an ocular surface. BACKGROUND OF THE INVENTION

The cornea is the transparent light refracting part of the eye covering the iris, pupil, and anterior chamber. The cornea and the lens of the eye cooperate to help focus the eye and provide 80% of the eyes' optical power. While the cornea contributes to most of the eyes' focusing power, its shape and position at the front of the eye are fixed, resulting in the cornea being vulnerable to foreign bodies. Corneal abrasions, or surface injuries to the cornea, may be caused by foreign bodies, such as dust and sand, overuse of contact lenses, or exposure to ultraviolet radiation. Deep corneal injuries may occur with major trauma, often from high speed projectiles contacting the eye. The cornea is somewhat protected from these injuries, however, by a sensitive thin layer of fluid called the tear film, which coats the surface of the cornea.

The tear film of the eye is the fluid interface between the external environment and the ocular surface, and it has several different functions. Tears fulfill an essential role in maintaining ocular surface integrity, protecting against microbial challenge, and preserving visual acuity. These functions, in turn, are critically dependent upon the composition and stability of the tear film structure, which includes an underlying inner foundation, a middle aqueous component, and an overlying lipid layer. In particular, the inner layer is a mucous layer that coats the cornea and conjunctiva. The mucous layer consists of mucins, electrolytes, water, IgA, enzymes, glycocalyx, microvilli, immunoglobins, and glycoproteins. The middle layer is an aqueous layer containing electrolytes, water, IgA, and proteins, many of which are antibacterial enzymes. Finally, the outer layer is a lipid layer, which floats on the aqueous layer. The lipid layer contains a complex mixture of hydrocarbons, squalene, wax esters, cholesterol esters, triglycerides, diglycerides, monoglycerides, free fatty acids, free cholesterol, phospholipid, sterol esters, and polar lipids, which prevents the aqueous layer from evaporating and provides overall stability to the tear film. The tear film forms a smooth refractive surface over the otherwise irregular corneal surface and lubricates the eyelids. Moreover, it maintains an optimal extracellular environment for epithelial cells of the cornea and conjunctiva where the electrolyte composition, osmolarity, pH, oxygen and carbon dioxide concentrations, nutrient and growth factor concentrations are regulated within narrow limits.

Disruption, deficiency, or absence of the tear film can severely impact the eye. If unmanaged with artificial tear substitutes or tear film conservation therapy, these disorders can lead to intractable desiccation of the corneal epithelium, ulceration and perforation of the cornea, an increased incidence of infectious disease, and ultimately pronounced visual impairment and/or blindness.

For example, blinking causes the eye lids to compress the thin lipid layer of the tear film, leaving only the aqueous layer under the eye lid to lubricate the ocular surface. When the eye lids either provide too much or too little pressure on the tear film, the eye lids are not functioning properly and damage to the tear film may occur. Further, should the cornea become damaged, whether from injury or surgery, the integrity of the tear film may be compromised, leading to greater discomfort, dryness, and vision problems.

Additionally, inflammation of the eyelids from infection or irritation can result in number of symptoms such as dry eyes, redness, and swelling. The oil glands of the eyelid, which provide the cellular components of the lipid layer, may become clogged due to this inflammation. Because the oil cannot egress from the oil glands and coat the surface of the tear film, the aqueous layer may evaporate quickly leading to dry eyes and irritation. Moreover, bacteria or other microbes may colonize the plugged oil glands and secrete toxins, which then concentrate in the tear film and increase inflammation. In chronic or severe cases, blood vessels propagate into the cornea to fight the infection and affect the vision. Ulceration of the cornea can also occur in severe cases, leading to corneal scarring, pain and loss of vision. With severe cases, it may become difficult or impossible to wear contact lenses.

Moreover, with the increased use of Laser In-situ Keratomileusis (LASIK) procedures to correct refractive errors such as myopia, hyperopia, and astigmatism by selectively destroying parts of the cornea to change the curvature of the eye, the lipid layer of the tear film is often destroyed. The destruction of the lipid layer often results of patients experiencing dry to painful eyes due to the decrease instability of the tear film. "Dry eye" may occur because the mucin layer of the tear film becomes unstable, compromising the overall stability of the tear film. In extreme cases, the tear film can even break up, and become non-existent over time. In light of its importance to visual functions, the composition, behavior, and other characteristics of the tear film are often investigated and scrutinized during the development of ocular devices, such as contact lenses and the like, as well as during the development and testing of ophthalmic medications and other agents. Such investigation typically includes imaging of the tear film either on the cornea or on an intermediate ocular device.

A traditional method of imaging the structures of the eye, and in particular the cornea, is use of a slit-lamp microscope during an ocular exam. The slit-lamp is a low powered microscope combined with a high intensity light source that allows for visualization of the structures of the eye. A patient usually sits in a chair with his/her chin placed on a support to keep the head and eye steady during the exam. However, slit-lamp examinations alone do not provide a detailed view of the tear film in relation to the cornea or other structures.

One imaging method that does provide for visualization of the tear film employs tomography, which generally is a technique for creating a full three- dimensional image of a non-planar object through correlating or combining a series of two-dimensional image slices through the particular object. One of the more popular examples of this particular technique includes X-Ray Computed Axial Tomography (CAT) scanning. In addition, another technique, Optical Coherence Tomography (OCT), has become a versatile and useful tool that can perform micron-resolution, cross-sectional imaging of biological tissue, such as in the field of ophthalmology. In particular, OCT is a form of range-finding that makes use of the second-order coherence of a classical optical source to effectively section or "slice" a partially reflective sample with a resolution governed by the coherence length of the source. Sources of short coherence length (and consequently broad spectrum) are typically used in an OCT apparatus.

Despite the increasing use of OCT techniques for imaging, the success of imaging tear film may be highly dependent on both the resolution of the OCT system and contrast between the tear film and the background material. As tear film studies typically include a transparent interface beneath the tear film such as a clear contact lens or ocular device, obtaining useful images can be difficult. As such, it would be desirable to provide for the enhancement or improvement of imaging techniques used with tear film analysis.

SUMMARY OF THE INVENTION

The present invention advantageously provides a method and system for increasing the contrast between a tear film and an imaging background, which may include an ocular device, such as contact lens or the like. OCT imaging of tear film on contact lenses and other ocular devices plays an integral role in the study and analysis of the fitting and behavior of contact lenses when in use, and is also important in assessing the safety of wearing a particular lens or device. When OCT imaging is employed to analyze the tear film, usually a first boundary between the tear film and the surrounding atmosphere can be imaged clearly, but imaging a second boundary between the tear film and the cornea or contact lens is significantly impaired or barely recognizable.

The present invention provides the addition of a contrasting agent or enhancer that differentiates the optical properties of the tear film from its surrounding environment and/or structures. For example, the contrasting agent of the present invention may include, but is not limited to, a micro-bubble composition, and/or an opaque or other substantially non-transparent composition, such as diluted milk mixed into a tear film or artificial tear formula for application to the eye or to an ocular device. The contrasting agent may be composed of one or more substances of varying concentrations to provide the desired contrast for an imaging application. As a result of adding the contrasting agent, the tear film or tear meniscus has an increasingly optically scattering characteristic that improves imaging capabilities when surrounded by substantially optically transparent constructs or ambient air. The resulting optical scattering significantly enhances the ability to obtain OCT images of the pertinent features and/or boundaries of the tear film on an ocular device or the eye itself. BRIEF DESCRIPTION OF THE DRAWINGS

A more complete understanding of the present invention, and the attendant advantages and features thereof, will be more readily understood by reference to the following detailed description when considered in conjunction with the accompanying drawings wherein:

FIG. 1 is an in vitro optical coherence tomography image of an ocular device absent a contrasting agent; FIG. 2 is an in vitro optical coherence tomography image of the ocular device of FIG. 1 with a contrasting agent additive in accordance with the present invention; FIG. 3 is an optical coherence tomography image of a contact lens on an eye absent a contrasting agent; and

FIG. 4 is an optical coherence tomography image of the contact lens on an eye of FIG. 3 with a contrasting agent additive in accordance with the present invention. DETAILED DESCRIPTION OF THE INVENTION The present invention advantageously provides a method and system for increasing the contrast between a tear film 10 and an imaging background, which may include an ocular device or the like. During operation of an OCT apparatus, for example, a target object of interest may be placed in one arm of an interferometer and illuminated through a beamsplitter with short coherence length light. Light is reflected from all depths within the target object in proportion to the localized reflectivity, and subsequently returned towards the beamsplitter. At the same time, a mirror in the second arm of the interferometer also returns a portion of the original beam to the beamsplitter. Upon returning to the beamsplitter, the two beams are directed towards one or more detectors, where they are combined with each other. The combined beams coherently interfere only when the optical path lengths to the sample and to the mirror are equal. As a result, the presence and strength of interfering light in a detector is indicative of the reflectance of the target object at a depth into the object corresponding to the reference mirror position and at the spatial location corresponding to the location of the detector. If an array of detectors is placed in the sensing plane, an entire level-slice can be recorded simultaneously. The full three-dimensional image may be constructed by scanning the mirror and recording the obtained level slices. OCT imaging of tear film 10 on contact lenses and other ocular devices plays an integral role in the study and analysis of the fitting and behavior of contact lenses or other ocular devices, and is also important in assessing the safety of wearing a particular lens or device. In addition, OCT imaging of the tear film 10 can help detect tear film 10 degeneration, track pharmaceutical drug effects in the eye, and the damage caused by surgery. As discussed above, the tear film 10 of the eye is the fluid interface between the external environment and the ocular surface has several different functions, including maintaining ocular surface integrity, protecting against microbial challenge, and preserving visual acuity. In particular, a tear film 10 has two boundaries, the first of which is formed between the tear film 10 or tear meniscus and the air while the second is formed between the tear film 10 or tear meniscus and the epithelium of the cornea 12 (or between the tear and an ocular device, such as a contact lens). When OCT imaging is employed to analyze the tear film 10, usually the first boundary between the tear film 10 and the surrounding atmosphere can be imaged clearly, but imaging the second boundary between the tear film 10 and the cornea 12 or contact lens is significantly impaired or barely recognizable. The success of imaging tear film 10 depends highly on both the resolution of the OCT system being used, as well as the contrast between the tear film 10 and the background or material against which the tear film 10 is being analyzed. When studying or imaging a tear film 10 on a contact lens, the interface or boundaries are formed by substantially transparent media, i.e., the surrounding air, the tear film 10, and the contact lens itself. The transparent nature of the media of the combined ocular construct of the tear film 10, air, and the lens does not provide a significant amount of imaging contrast between the layers, and thus does not result in high optical scattering for OCT imaging.

The present invention provides the addition of a contrasting agent or enhancer that differentiates the optical properties of the tear film 10 from its surrounding environment and/or structures. For example, the contrasting agent of the present invention may include, but is not limited to, a micro-bubble composition, and/or an opaque or other substantially non-transparent composition, such as diluted milk into a tear film 10 or artificial tear formula for application to the eye or to an ocular device. The contrasting agent may be composed of one or more substances of varying concentrations, including an intralipid solution, to provide the desired contrast for an imaging application. For example, the contrasting agent may be a 10% intralipid solution, or may have an increased intralipid concentration for enhanced contrast. Solutions containing intralipids with varying concentrations, closely mimic the response of human or animal occular tissue to light at wavelengths in the red and infrared ranges where tissue has a rather low absorption coefficient. As a result of adding the contrasting agent, the tear film 10 or tear meniscus has an increasingly optically scattering characteristic that improves imaging capabilities when surrounded by substantially transparent constructs or ambient air. The resulting optical scattering significantly enhances the ability to obtain OCT images of the pertinent features and/or boundaries of the tear film 10 on an ocular device or the eye itself.

Now referring to FIG. 1 , which is an OCT image of an ocular device. The resulting image quality suffers due to the lack of contrast between the layers of the image, and the pertinent features are not readily visible in the recorded image.

Now turning to FIG. 2, which is an OCT image of an ocular device with a contrasting agent added. An ocular device, such as a contact lens, may be imaged using an OCT scanner sized to image the ocular surface. A contrasting agent additive may then be deposited onto the ocular surface and mixed into the tear film 10, and then an OCT image as may be captured. Increasing the concentration of diluted milk or micro-bubble solution deposited into the eye, may increase the contrast of the boundaries and improve the overall image contrast. The concentration of contrasting agent may be adjusted depending on the comfort of the patient or the need for more contrast detail.

The resulting profile of the contact lens about the tear film 10 is significantly enhanced for viewing and imaging purposes when scanned using the same OCT process as in FIG. 1. The aqueous layer 14 of the tear film 10 is also significantly enhanced such that volume measurements of the tear film 10 may be calculated. The calculated volume measurements, which were previously difficult to calculate, may then be correlated with volume measurements from normally function tear ducts to determine if the tear ducts are functioning properly. If the aqueous layer has been damaged due to surgery, the addition of the contrasting agent may identify leaks and damage to the overall integrity of the tear film 10. The first boundary between the tear film 10 and the surrounding atmosphere may also be more visible with the addition of the contrasting agent. Air has a refractive index of 1.00, while water has a refractive index of 1.33. Due to these refractive differences, visualizing the broad features of the first boundary may be accomplished, but fine details may not be visible. Addition of the contrasting agent, however, provides for a higher contrast of the first boundary, which may aid in detecting tear film 10 damage at the first boundary. Moreover, the second boundary between the tear film 10 layer and the contact lens, which is not readily visible in FIG.l, becomes even more pronounced with the addition of the contrasting agent. Typical glass has a refractive index of about 1.5. The addition of the contrasting agent enhances the second boundary significantly such that cracks in the lipid layer 16 may be detected and early disease formation or progression may be observed.

Now turning to FIG. 3, which is an OCT image of contact lens disposed about the cornea 12 of the eye without a contrasting agent. The eye about which the contact lens is disposed may be a human or animal eye. The OCT scanner may be sized to image tear film 10 and background structures of the particular eye chosen to be imaged, whether human or animal. As shown in FIG. 3, the tear meniscus and tear film 10 are not clearly visible or clearly delineated, making measurements and calculations difficult. Moreover, the curvature of the tear film 10 about the cornea 12 is difficult to visualize, particularly in the region proximate the tear meniscus. This tear film 10 curvature is important to analyze to help determine the integrity and volume of the tear film 10.

Now turning to FIG. 4, which is an OCT image of the same contact lens-eye portion of FIG. 3 having the contrasting agent added. As shown, the second boundary between the tear film 10 and the contact lens that was not readily visible in FIG. 3, is now more clearly visible in FIG. 4. Additionally, the contrast between the lens and tear menisci around the upper and lower eyelids has improved with the addition of the contrasting agent. The contrast between the cornea 12 and the mucin layer 18 is also improved. The cornea has a refractive index of 1.33, which makes the cornea appear dark in an OCT image. The addition of the contrasting agent to the tear film 10, however, further amplifies the boundary between the cornea and the mucin layer 18, as the mucin layer 18 will appear brighter in contrast to the cornea. Further, with the increased contrast of the surrounding eye tissue, biological measurements may be more readily taken to determine various properties of the eye tissue proximate the tear film 10 or tear meniscus. For example, cracks, gaps, fissures, or other impairments to both the mucin layer 18 and the lipid layer 16 are more readily visible.

Additionally, visual observation of the tear film 10 layer with the addition of the contrasting agent may help to track the course oil gland and eye infections that damage the tear film 10. Moreover, visualizing the tear film 10 during pre and post medical or therapeutic procedures, such as LASIK, may aid doctors in diagnosing problems with the tear film 10, and proactively treat future ailments or track ocular drug effectiveness. For example, application a tear film 10 solution mixed with a contrasting agent may be applied pre LASIK operation to determine the properties and integrity of the pre surgical tear film 10. After an optical procedure, the tear film 10 can again be imaged by the OCT scanner to determine the overall effect on the tear film 10 layer as a result of a surgical procedure.

It is further contemplated that OCT imaging of the tear film 10 be combined with existing slit-lamp examinations to precisely image a desired region of the eye. For example, if during a slit-lamp examination of the eye, an area of the eye appears red, irritated or otherwise damaged, an OCT image of the damaged portion of the eye can be captured to determine if the tear film 10 or other structures surrounding the cornea 12 are damaged. Once an area of interest in the eye is determined by a slit- lamp examination, the contrasting agent may be added to the eye and an OCT image obtained to aid in diagnosing the ocular condition.

Accordingly, the present invention provides enhancing an OCT image of a tear film 10 on an ocular surface. The contrast may be enhanced through the addition of a contrasting agent, and the contrast agent may be applied or otherwise deposited prior to recordation of an OCT image. The contrasting agent may be applied using automated fluid application systems as known in the art, and may contain varying amount of component concentrations in order to provide a desired imaging result.

It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described herein above. In addition, unless mention was made above to the contrary, it should be noted that all of the accompanying drawings are not to scale. A variety of modifications and variations are possible in light of the above teachings without departing from the scope and spirit of the invention, which is limited only by the following claims.

Claims

What is claimed is:

I. A method for imaging tear film on an ocular surface comprising: depositing a contrasting agent onto the ocular surface; and acquiring an OCT image of the ocular surface. 2. The method of claim 1, further comprising positioning an ocular device about the ocular surface.

3. The method of claim 2, wherein the ocular device is a contact lens.

4. The method of claim 1, wherein acquiring an OCT image of the ocular surface includes imaging the tear film layer. 5. The method of claim 1, wherein the contrasting agent is a micro-bubble solution.

6. The method of claim 1 , wherein the contrasting agent is a diluted milk solution.

7. The method of claim 1, wherein the contrasting agent is a 10% intralipid solution.

8. The method of claim 1, further comprising performing an optical procedure before acquiring the OCT image of the ocular surface.

9. The method of claim 1, further comprising performing an optical procedure after acquiring the OCT image of the ocular surface. 10. A system for imaging tear film on an ocular surface comprising: an OCT scanner positioned to acquire an image of the ocular surface, wherein the ocular surface is mixed with a contrasting agent affecting image properties of the tear film detectable by the OCT scanner.

I 1. The system of claim 10, further including an ocular device positioned about the ocular surface.

12. The system of claim 11 , wherein the ocular device is a contact lens.

13. The system of claim 10, wherein the contrasting agent is a micro-bubble solution.

14. The system of claim 10, wherein the contrasting agent is a diluted milk solution.

15. The system of claim 10, wherein the contrasting agent is a 10% intralipid solution.

16. The system of claim 10, wherein the detectable image properties of the tear film include a tear film reflectance.

17. A method for imaging tear film on an ocular surface comprising depositing a contrasting agent onto the ocular surface of a human eye, wherein the contrasting agent enhances reflectance properties of the tear film; engaging a contact lens with the ocular surface; coupling an OCT scanner to a slit-lamp; positioning the OCT scanner and the slit-lamp proximate the ocular surface; visualizing a target tear film region with the slit-lamp; and acquiring an OCT image of the target tear film region, such that a boundary between the tear film and the contact lens is visible in the OCT image.