WO2015097183A2

WO2015097183A2 - A test method and assay for diagnosis and evaluation of clinical product performance

Info

Publication number: WO2015097183A2
Application number: PCT/EP2014/079070
Authority: WO
Inventors: David JAMESON
Original assignee: Oriflame Cosmetics S.A.
Priority date: 2013-12-23
Filing date: 2014-12-22
Publication date: 2015-07-02
Also published as: SE1650868A1; WO2015097183A3

Abstract

A clinical test method utilising one or more facial image comprising: image capture & display, aesthetic feature selection, application of method of measurement. Test method can be useful for diagnostic, reference generation, in addition to the evaluation and/or optimisation of products and demonstrating overall product performance.

Description

Title:

A test method and assay for diagnosis and evaluation of clinical product performance Field of the Invention

The present invention relates to a clinical diagnostic, predictive and product

performance method, tool and/or system. In particular, the invention relates to a clinical test method to determine the performance of products and optionally to benchmark these products against performance of similar known products on the marketplace.

Background to the Invention

As we age certain physiological changes take place due to extrinsic (e.g. UV light, pollution, radiation, stress and other environmental factors) and intrinsic (e.g. genetic predisposition, chronological aging etc.) factors that present themselves through undesirable symptoms that can be resolved through the use of beauty and cosmetic products.

The skin around the eye is thinner and more delicate than skin elsewhere on the body. As such, the eye can often show the first signs of fatigue, stress and aging. Fatigue, stress and aging may present as symptoms including but not limited to puffmess, dark circles, fine lines and wrinkles. Skincare compositions can provide both short and long term solutions to counter the effects and undesirable symptoms of aging, poor health and extrinsic factors.

Changes also occur to the eyelashes with age. Standard growth of an eyelash goes through four main phases: growth, resting, shedding and re-growth. As hair follicles age this four phase process slows and may stop altogether leading to a thinning of the eyelashes and reduced fullness and length. Greater definition and contrast of facial features is understood to provide a younger looking appearance (C.E.R.I.E.S & Gettysburg, 2013). Fatigue and stress can also impact on the general appearance of health and age of an individual. A more open looking eye is thought to improve and support a more refreshed, rested and overall younger appearance (Skinexigence & Helena Rubeinstein).

Lack lustre eyelashes as a result of thinning, reduced fullness, length and curl can therefore add to the increased appearance of aging of the eyes through reduced definition and perceived closing of the eye.

Changes in eyelash condition and health may also occur due to other influencing factors other than age such as excessive scrubbing and/or rubbing of the eye, hereditary, medical conditions, certain medications and/or treatments and other environmental factors.

Age perception influences not only how an individual feels about themselves, impacting on general health, well-being and confidence but is also said to impact social interactions, with perceived age influencing for example a persons rank, status, rights, responsibilities and professional development (C. E.R.I. E.S & Gettysburg, 2013). With women working longer hours and working later in life the need to look professional and younger looking has become increasingly important, with 36% of 55 to 64 year olds agreeing that wearing make-up makes them feel more professional and 69% agreeing that it makes them feel more confident.

Many options are available as a means to improve the appearance of fuller, longer lashes with more curl, lift and eye-opening capabilities. Make-up, including mascara, can offer women a temporary yet more immediate solution to a younger-looking appearance. Other cosmetic compositions applied to the eyelash, such as lash boosting serums provide nutrients, vitamins and active ingredients to improve the condition of the lashes for a more long term effect. False eyelashes and in more extreme cases eyelash transplants can provide longer lasting effects.

In addition targeted skincare compositions can provide both short term and long term solutions to a younger-looking appearance of the overall eye area.

The economic downturn has influenced consumer spending habits resulting in demands for a better performance profile for products purchased. Claim substantiation has therefore become increasingly important part of product development over the last ten years (Hickey & Barton). This has lead to an ever increasing trend for product performance in cosmetic, beauty and personal care goods and in-line with this trend there have been developments in the cosmetics regulation

(http://ec.europa.eu/consumers/sectors/cosmetics/files/pdf/guide_reg_claims_en.pdf) as a protective measure. This regulation sets out guidelines on making and substantiating claims.

Most mascaras and other lash applied cosmetic products on the market claim to be capable of lifting, lengthening, curling and thickening the eyelashes and to provide fuller lashes and an eye-opening effect. However, conventional performance testing of such products relies on subjective opinion-based consumer perception studies to demonstrate performance, which has its draw backs. Skincare effectiveness or performance is also often demonstrated through in vitro or subjective opinion-based consumer perception studies.

Consumer perception studies generally comprise of a panel of end-users for the marketed product. These end-users are provided with the test product and asked to use the product for a period of time. Over this period of use the panellist subjectively assesses the test product. Each member of the panel is then asked to complete a questionnaire, purposefully designed to capture the panels opinion as to whether the product does what it is intended for and how well the panel perceives the product to have performed this task. All tests are performed under standard clinical research procedures as a blind trial and following the standards set out in the cosmetics regulation 2013.

One such example of an at home skincare based consumer perception study invites consumers to purchase the product on offer and to use for a set period of time before assessing their progress. The consumer does this by comparing their skin condition against a series of photos/picture as examples/ representative scale of the skin condition progressively worsening, having also assessed their skin before using the product to decide where they sit on the scale. After using the product the aim is to see an improvement or lessening of the skin condition compared to where the consumer started.

Such testing, whether at home or under a more controlled clinical setting, is opinion- based, and thus subjective. In addition, most individuals tend to have a distorted view of their own appearance and the gravity of conditions presented, in extreme cases this might result in Body Dysmorphic Disorder (BDD). This means that application of the test varies considerably from individual to individual and outcomes vary depending on individual interpretation leading to less dependable results.

EP1298597 (L'Oreal) and EP1 134701 (INFINITEFACE) provide for an analytical method using a 3-D facial image designed to enable the consumer to virtually try out beauty products in store for their potentially desirable aesthetic attributes and promote consumer/retail interaction. Such a method is not designed to measure the performance of beauty products, but merely provides a virtual representation of certain features to the consumer for a more informed purchasing choice.

K 856169 (Shiseido) describes an in-store mascara selecting method and system. This system comprises a mascara selection step, which is based on information ascertained 100 from the consumer on their eyelashes and the desired effect they want to achieve. Such a method does not comprise of an analytical method for performance or objectively determine the clinical effect of mascara or other cosmetic compositions; it merely provides a means for a consumer to make an informed purchasing decision as to what mascara would best suit their needs.

105 Previous attempts have been made to demonstrate the effectiveness of mascara performance utilising more objective means (Skinexigence & Helena Rubeinstein). The Skinexigence/H. Rubenstein method sets forth a means to provide repeatable and consistent result generation.

The Rubinstein-Skinexigence method primarily utilises angle displacement between the 110 aesthetic and anatomical angles to generate an angle value measured in degrees to demonstrate the curl of the eyelashes. In addition the opening of the eye is measured independently by means of a vertical line through the iris and taking the mean change in distance (cm) between the aesthetic and anatomical angle. The results describe that the mean angle measurement of 12° corresponds to a 2mm increase in height. The means of 115 establishing the angle displacement and distance height are limited due to the manual selection of the mean curvature of the eyelash and thus the aesthetic angle and extrapolated line generated. Such selection of the mean curvature of the eye is inaccurate and unclear and thus unlikely to provide a true indication of the eyelash curl or eye-opening capability. Subjectivity in an assessment method is likely to lead to 120 false positive or false negative readouts. Such previous methods are limited in that the measurements and results do not provide an accurate, true and realistic representation of product performance.

An objective clinical test method to demonstrate effectiveness of targeted or localised skincare, mascaras and other beauty and cosmetic products would therefore be 125 advantageous.

As we age the eyes and surrounding area age and as such become prone to age-related disorders and/or conditions. Such conditions include but are not limited to, trichiasis, keratoconus, keratoglobus, glaucoma and localised inflammation of the eye. Such conditions may also result from other environmental and genetic stimuli and thus may 130 present themselves at any age.

Trichasis is a condition characterised by the inward projection of the eyelash(es). In more pronounced cases the eyelash can come into contact with the cornea, scratching and potentially damaging the eye as well as causing discomfort. There are several causes of misdirected eyelash growth. Entropion results from loss in normal elasticity of

135 the eyelid and presents itself as an inward flip/fold of the eyelid. Blepharitis results from eyelid infection and inflammation of the eyelids and lashes. Injury, surgical repair or cosmetic surgery of the eye area may cause the eyelid to become torn or injured; as a result the position of the eyelashes may change and grow inward. Distichiasis is when an extra row of eyelashes develops and grows inward, rubbing against the eye.

140 Occasionally, an eyelash will simply grow or bend in the wrong direction (Idiopathic Trichasis).

Keratoconus and Keratoglobus are degenerative disorders characterised by structural changes within the cornea that cause it to thin and change shape. In Keratoconus the eye becomes more conical in shape and in Keratoglobus the eye becomes more globular or

145 spherical in shape. Both conditions cause distortion to vision and light sensitivity.

Glaucoma is a multifactorial condition characterised by intraocular pressure-associated optic neuropathy and is the leading cause of blindness. Intraocular pressure fluctuations may result in fluctuations in the overall size and shape of the eye. Many diagnostics currently available involve practices which patients may find uncomfortable leading to

150 challenges in patient compliance, particularly with those who are squeamish about having things close to their eyes.

Inflammation of the eye area can arise due to many different factors, such as allergy irritation etc. The effects of which would be made apparent through a closing of the eye. The present invention may provide a quick, easy and convenient way to measure and 155 demonstrate clinical effectiveness/performance of localised inflammatory products.

Object of the Invention

Whilst various diagnostics exist for all of the above conditions there is a continual need for less invasive and remote means of diagnosis to enable early detection of changes in the eye. Equally an easy, reproducible and inexpensive means for testing performance

160 of therapeutic compositions in certain eye-related conditions would be advantageous.

The present invention sets out to provide a more objective means of evaluating product performance and resolve the long-standing issue of clear performance measurement of cosmetic, beauty and/or therapeutic products, and in particular of those products applied to the eyelashes and/or surrounding eye area.

165 Summary of the Invention According to the present invention there is provided a method of analysing two images of an eye of a subject to determine the change, between the two images, of the extent to which the eye appears to be open, wherein the images are profile- view images of the subject's eye taken from the same vantage point; wherein each image of the eye is 170 characterised by an eyeball area bounded by a lower eyelid, an upper eyelid, and an eyeball periphery; and wherein the lower and upper eyelids comprise lower and upper lashes respectively, the method characterised by the steps of:

for each image of the eye:

plotting a lower target point proximate to the eyeball periphery and the lower eyelid; 175 plotting an upper target point proximate to the eyeball periphery and the upper eyelid;

drawing a measurement line through the lower target point and the upper target point; and

calculating a value associated with the measurement line;

180 comparing the degree of change in the value associated with the measurement line of the first image and the value associated with the measurement line of the second image; and

inferring from the degree of change in the values associated with the measurement lines the change of the extent to which an eye appears to be open.

185 Preferably the lower target point comprises the point of intersection between the lower eyelid and the eyeball periphery;

the upper target point is plotted by:

drawing a vertical line through the lower target point such that it intersects with the upper lid at the base of the upper lashes, and plotting the point of vertical line

190 intersection;

plotting the point of upper/lower lid intersection where the upper lid intersects with the lower lid;

drawing an upper lid line through the point of vertical line intersection and the point of upper/lower lid intersection such that the upper lid line intersects with the eyeball 195 periphery;

designating the point of intersection between the upper lid line and the eyeball periphery as the upper target point; and the measurement line is drawn between the lower target point and the upper target point following the outline of the eyeball periphery.

200 In particular the upper target point may comprise the highest point on the upper lashes; the lower target point may comprise the lowest point on the lower lashes; and the measurement line is a straight line drawn between the lower target point and the upper target point.

The invention also provides a method of analysing two images of an eye of a subject to 205 determine the change, between the two images, of the extent to which the eye appears to be open, wherein the images are profile-view images of the subject's eye taken from the same vantage point; wherein each image of the eye is characterised by an eyeball area bounded by a lower eyelid, an upper eyelid, and an eyeball periphery; and wherein the lower and upper eyelids comprise lower and upper lashes respectively, the method 210 characterised by the steps of:

for each image of the eye:

plotting an upper/lower lid point of intersection at the point of intersection of the upper eyelid and the lower eyelid;

plotting a lower target point proximate to the eyeball periphery and the lower eyelid; 215 plotting an upper target point proximate to the eyeball periphery and the upper eyelid;

defining a triangle having apices respectively at each of said plotted points;

measuring a characteristic area within said triangle, wherein the characteristic area is optionally the white of the eye;

220 comparing the degree of change in the magnitude of the characteristic area of the first image and the magnitude of the characteristic area of the second image; and

inferring from the degree of magnitude change the extent to which an eye appears to be open.

Also provided is a method of determining the change over time in the extent to which an 225 eye of a subject appears to be open comprising the steps of:

taking a first pro file- view image of a subject at a first point in time;

taking a second profile-view image of a subject at a second point in time; and performing the method of any of claims 1 to 4 on said first and second images.

The invention also provides a non-transitory computer readable medium carrying 230 instructions thereon, which, when executed by a processor, cause the processor to carry out any of the methods described above; an image analysis apparatus configured to perform any of the methods in which the images are digital images.

Also provided is an image capture and analysis system configured to perform a method of determining the change over time in the extent to which an eye of a subject appears to 235 be open comprising an image capture device; and the image analysis apparatus defined above.

The present invention thus provides a clinical test method, apparatus and systems involving one or more facial images. The method, apparatus and systems can also provide for diagnostic and/or reference data generation purposes, and further optionally 240 comprises the evaluation and/or optimisation of products, whereby the clinical test

method comprises:

(1) Image capture

(2) Image analysis

Advantages of the present invention include but are not limited to demonstrating 245 product performance in an objective way with reduced error and variability over

standard consumer perception studies currently available. In addition the present invention advantageously provides a means to compare and benchmark products against competitor product offering to determine comparable activity. The present invention also enables a reduction in paper, staffing, contract research, travel and other study 250 costs, which also advantageously reduces production costs as well as reduces the carbon foot print of such products tested by said clinical method and thus affords greater sustainability of the products.

By comparison to the Rubinstein- Skinexigence method, the method(s) of the current invention provides for a more objective and easily repeatable method through the pixel 255 selection rule that is applied as part of the Variant Methods (VM 1,2 or 3) of the present invention and utilised in the image analysis step. The pixel selection rule of the present invention provides a means to remove subjectivity between investigators on defining where the measurement is taken from and to.

It has also been advantageously found that the method could be utilised in diagnosis of 260 certain disease states and/or conditions associated with the eye. Such age-related disorders and/or conditions include but are not limited to, trichiasis, keratoconus, keratoglobus, glaucoma and localised inflammation of the eye, as well as the result of environmental and genetic stimuli. Brief Description of the Drawings

265 The accompanying drawings, figures and diagrams incorporated in the specification, in conjunction with the description, serve to explain the features, advantages and other objects of the present invention, in which:

Figure 1 : Illustrates the general structure of the eye and eyelid showing the iris (the pigmented part); the cornea (a clear dome over the iris); the pupil (the black circular 270 opening in the iris that lets light in); the sclera (the white part).

Figure 2: Provides a flow diagram illustrating a method of determining and optimising and evaluating products in accordance with the invention.

Figure 3 : Demonstrates variant measurements (VM) applied in accordance with the invention. A is the Base Method, B is Method Variant 1 , C is Method Variant 2 and D 275 is Method Variant 3. The figure shows measurements taken before product application (untreated) and after product application using the claimed Base method in conjunction with the one or more method variant (VM) 1 , 2 or 3 singularly, sequentially or in paralell.

Figure 4: Shows significant and reproducible product performance compared to 280 untreated control. Statistically significant product performance on lash length, curl, lift and overall eye opening capabilities.* = P value <0.05

Figure 5 : Shows pixel selection as part of the clinical test method. Demonstrates the pixel selection process, as part of the variant methods applied. PI = lash point.

Figure 6: Validation of methodology : Figure shows comparison of benchmark product 285 (A), positive control (B), negative control (C) and untreated (D). * = p value of < 0.05 considered to be statistically significant.

Detailed Description of the Drawings

The current invention comprises of clinical test method whereby an image(s) is captured before and after product application and various points of assessment are selected and

290 measured to demonstrate effectiveness of the product applied.

It is understood that the figures and descriptions of the present invention have been simplified to illustrate elements that are relevant for a clear understanding of the present invention. The present invention comprises a plurality of elements and features (Fig 2), which are outlined in conjunction with figures, examples and data as described.

295 Facial images of panellists (n=4) were captured (1) and the resulting image generated is then displayed on a display device (~S2). Investigations performed under the present invention utilised the apparatus and analysis software Image Pro Plus that can be purchased from Media Cybernetics; however, there are many standard apparatus and software packages that exist, any of which could be utilised in conjunction with the

300 present invention. The aesthetic feature of interest is then selected (~S3a.), in particular where the aesthetic feature is the eye and surrounding areas. On selection of the aesthetic feature, method may further optionally comprise an additional step (~S3b.), whereby product is optionally applied to the aesthetic feature. For diagnostic purposes and/or untreated controls, (~S3b) is omitted. Image analysis (2) then takes place

305 starting with the intersection point (p) being established (~S4) and the alto line (LI) and base line (L2) are articulated outward from the point of intersection (~S5). A reference line (Rl) is drawn vertically through the mid reference point (r) which runs parallel to the intersection point (p), from LI downwards through the base line (L2) of the aesthetic feature (~S6). In accordance with the invention, one or more method variants, as

310 described in the examples, are then applied (~S7) singularly, sequentially or in parallel, which utilises a pixel selection method as further described in the examples (fig 5). Measurements are taken with the output determined (~S8) and represented as a numerical value (OP). Measurements taken from untreated (baseline value) are then compared to measurements obtained after product application (~S3b), or measurements

315 taken from one product is compared to one or more other products, as represented by the mathematical formula below:

(~S3a + VM(i,2,3)) = OPi (~S3b + VM(i,2,3)) = OP₂;

320 OP₂ - OPi =dRi OP₂ - OP₂ = dR₂₍n)

During comparison (~S9.) product application maybe compared against untreated data obtained or compared to other test products under analysis. The function 325 dR represents the difference in response obtained; dRi represents comparative response to control, dR₂(_n) represents intra-comparative responses between products. As part of the comparison step standard statistical analysis is applied to establish the significance of results obtained. From comparative data, products can be selected on the basis of defined parameters set by study led/objective. 330 Examples, below, are provided to explain additional detail as to some of the aspects of the present invention and is hereby understood to not limit the scope of the present invention.

Example 1

In accordance to the invention the variable aspect of the method may optionally

335 comprise of a length of curve of the eye visible under the lash line measurement (VMi).

Upper (LI) and base (L2) lines are articulated outward from the point (p) of intersection (~S5). A reference line (Rl) is drawn vertically through the mid reference point (r) which runs parallel to the intersection point (p), from LI downwards through the base line (L2) of the aesthetic feature (~S6). The curved line (Tl) is then drawn between the 340 lines (LI) and (L2), along a curved feature, for example the cornea. The output (OP) is defined by Tl .

Example 2

In accordance to the invention the variable aspect of the method may optionally comprise of a minimum to maximum measurement (VM₂). Upper (LI) and base (L2)

345 lines are articulated outward from the point (p) of intersection (~S5). A reference line (Rl) is drawn vertically through the mid reference point (r) which runs parallel to the intersection point (p), from LI downwards through the base line (L2) of the aesthetic feature (~S6). A connecting line (d) joins LI and L2 highlighting the minimum and maximum points. The output (OP) is defined by (d).

350 Example 3

In accordance to the invention the variable aspect of the method may optionally comprise of an area under the Line (AUL) measurement (VM₃). Upper (LI) and base (L2) lines are articulated outward from the point (p) of intersection (~S5). A reference line (Rl) is drawn vertically through the mid reference point (r) which runs parallel to

355 the intersection point (p), from LI downwards through the base line (L2) of the aesthetic feature (~S6). The area (A) within the confines of LI and L2 is then defined and measured resulting in an output (OP). The area between LI and L2 can be defined by a plurality of elements including but not limit to the white of the eye (as shown in fig 2), the pupil, iris, cornea, or any other visible outer portion of the eye structure or any

360 combination of these elements.

Example 4 To effectively perform the variant methods 1, 2 and 3, in addition to the standard methodology as described, the lash is differentiated from background 'noise' using a pixel selection process.

365 With the aid of image software, the image is refocused (Fig 5). By zooming in on the image but maintaining clear differentiation of where the end-point of the lash exists (Fig 5). Against the background, it is then possible from this view to select the pixels that define where the point and outer line of the lash exists. Such pixel selection enables a more accurate representation of the measurements taken in the test method used.

370 Measurements can then be expressed as an output value in the format of pixel count (fig 4), and statistically shown to be significantly different before and after product application (fig 4). Manual selection and characterisation of pixel colour for

inclusion/exclusion from measurement parameters is performed in accordance to standard protocols and technical information available from the apparatus/software

375 supplier, in this instance Media Cybernetics. This selection process is of particular

importance to VM₂ as defining the lash from the background noise is a key aspect to enable accurate measurements.

Example 5

The set-up of the imaging device ensures that the images are reproducible. Additional 380 images are taken to account for and minimise the less common errors during capture such as the panellist blinking, looking up, down or to the sides, as well as tilting the head. These checks are performed, as a rule, immediately after image capture and retakes are performed if necessary. These images are then rechecked by the responsible person trained in the analysis, and any images comprising of these types of errors are 385 discarded. Commonly, it is the case that all repeats are okay, and images are simply picked on the basis of one before and one after treatment.

Panellists sit on the same chair for both before and after images, placing their chin in a chin rest to assist in positioning. Specific points of reference are highlighted for the panellist to look at during the image capture.

390 The panellists are told that there will be a countdown "3, 2, 1" after which the image will be captured. They can blink during and up to the end of this countdown and then they have to keep their eyes open (fixated on the reference point) once the countdown is complete. The image is captured instantaneously at this point. The more powerful the image capture device, the sharper the image will be, leading to 395 increased clarity and better defined edges which enables more accurate pixel selection and measurement. For the purpose of analysis, selection of an appropriate image capture device provides for reduced variability upon selection of the desirable points on the image.

Example 6

400 The current invention has utility in assessing effectiveness of lash based products for certain desirable attributes. Depending on the desirable attributes under evaluation an appropriate variant method (1, 2 or 3) is selected.

The clinical test method as described and illustrated (Fig 2) is performed with the omission of (~S3b) to generate baseline data, which enables the assessment of

405 variability in measurements. Product is then applied to one eye of the panellist, as per standard protocols in clinical assessment and the clinical test method is performed again with the inclusion of (~S3b) utilising one or more of the method variants as described. Effectiveness of lash based products is usually achieved through a combination of both the composition and the device used to apply the composition, such as an applicator,

410 brush or comb etc. To be able to assess the impact of either the device or formulation, or any combination of both, on the overall performance of the product as a whole a positive and negative control must first be established. A number of applicator and composition combinations were trialled using the method of the current invention against a benchmark. The benchmark taken in this case was Helena Rubinstein, Lash

415 Queen Mascara, Fatal Blacks Waterproof a gold standard product for lash length, curl, lift and overall eye-opening capability.

The assessment is performed immediately after product application and, optionally, at various time points following application of the product under assessment. The outputs (OP) are then recorded as numerical values and statistical analysis performed. 420 Performance is shown as the mean percentage change in length of curve visible under the lash line, relative to the baseline measurement, where statistical significance is taken to be a p value of 0.05 or below.

The positive control was determined to comprise of a standard in- house mascara composition combined with GEKA 311164 bowling Brush. The negative control was 425 determined to be a standard in- house composition combined with a GEKA 311164 Helix brush. Untreated controls were performed in parallel to confirm that the method is reproducible and that the changes observed were due to product performance and not intrinsic alterations that naturally occur in the eyelashes over time (Fig 6).

Results demonstrate that a mean change in measurement (using VMi) relative to 430 baseline in the range of 23 - 28% provides optimal performance in lash, curling, lifting to provide a wider more open eye look.

Use of alternative measurement (VM 2 or 3) is anticipated to demonstrate a mean change relative to baseline that would provide a range of values where optimal performance can be demonstrated.

435 Example 7

The current invention has utility in assessing effectiveness of both topical compositions intended for localised application in and around the eye area, such as, but not limited to, cosmetic compositions intended to alleviate and/or prevent the signs of eye related aging.

440 The clinical test method as described and illustrated (Fig 2) is performed with the omission of (~S3b) to generate baseline data, which enables the assessment of variability in measurements. Facial images of panellists (n=x) were captured (1) and the resulting image generated is then displayed on a display device (~S2). The clinical test method is then performed again, and this time product is applied to one eye of the

445 panellist (~S3b), as per standard protocols in clinical assessment and analysis utilising variant method 3.

The assessment is performed immediately after product application and, optionally, at various time points following application of the product under assessment. The outputs (OP) are then recorded as numerical values and statistical analysis performed. 450 Performance is shown as the mean percentage change in area of the eye visible under the lash line, relative to the baseline measurement, where statistical significance is taken to be a p value of 0.05 or below.

Readouts derived from the described method provide an indication of skincare effectiveness in tightening, firming and wrinkle reduction.

455 Example 8

The current invention could feasibly be utilised to generate data that would be useful in diagnosis of select conditions associated with the eye.

The clinical test method as described and illustrated (Fig 2) is performed with the omission of (~S3b) in entirety. Facial images of the "control group" (n=x) were 460 captured (1) and the resulting image generated is then displayed on a display device (~S2). The clinical test method is then performed again, and this time facial images of the "patient" group (n=x) were captured (1) and the resulting image generated is then displayed on a display device (~S2).

The following assessment is performed utilising variant method 3 and the outputs (OP) 465 are recorded as numerical values and statistical analysis performed. Control conditions are demonstrated as the mean area of the eye visible under the lash line, where statistical significance is taken to be a p value of 0.05 or below. The "onset differential" is then taken to be the mean percentage change in area visible under the lash line in the disease state, relative to control conditions, where statistical significance is taken to be a p value 470 of 0.05 or below.

A database can be generated comprising of the range of acceptable fluctuations within measurements for control conditions as well as the percentage change measurement(s) that indicate the onset of a disease state as reference samples. Patients can then be subsequently tested and a value generated from the variant method, which can then be 475 compared to the reference samples within the database. Comparison will provide an indication of whether said patient is presenting symptoms of the disease state.

Example 9

The clinical method can feasibly be used to generate data useful in the assessment of product effectiveness in trials.

480 The clinical test method as described and illustrated (Fig 2) is performed with the omission of (~S3b) to generate baseline data, which enables the assessment of variability in measurements. Facial images of panellists (n=x) were captured (1) and the resulting image generated is then displayed on a display device (~S2). The clinical test method is then performed again, and this time product is applied to one eye of the

485 panellist (~S3b), as per standard protocols in clinical assessment and analysis utilising variant method 3.

The assessment is performed immediately after product application and, optionally, at various time points following application of the product under assessment. The outputs (OP) are then recorded as numerical values and statistical analysis performed. 490 Performance is shown as the mean percentage change in area of the eye visible under the lash line, relative to the baseline measurement, where statistical significance is taken to be a p value of 0.05 or below. Readouts derived from the described method provide an indication of product effectiveness in relation to reduction of localised inflammation, swelling and or water 495 retention.

Example 10

Below is provided a typical composition that could be evaluated using the present invention as described by way of example, which is intended for illustrative purposes and is hereby understood not to limit the scope of the present invention.

500

Table 1: Typical mascara composition

Material % wt

AQUA

CI 77499

STEARIC ACID

ORYZA SATIVA CERA

HYDROGENATED CETYL OLIVE ESTERS

GLUCAMINE

BUTYLENE GLYCOL

COPERNICIA CERIFERA CERA

HELIANTHUS ANNUUS SEED CERA

ACACIA SENEGAL GUM

PVP

CYCLOPENTASILOXANE

PVP/EICOSENE COPOLYMER

SILICA

CYCLOHEXASILOXANE

CERA ALBA

SYNTHETIC WAX

SHOREA ROBUSTA RESIN IMIDAZOLIDINYL UREA

DIMETHICONE

RHUS VERNICIFLUA PEEL CERA

HYDROXYETHYLCELLULOSE

METHYLPARABEN

DISODIUM EDTA

HYDROGENATED MYRISTYL OLIVE ESTERS

LECITHIN

CETEARETH-20

PANTHENOL

TOCOPHERYL ACETATE

PROPYLPARABEN

PHENOXYETHANOL

BHT

PEG-12 DIMETHICONE

ETHYLPARABEN

Utilising such methods as described in the examples, product performance can be 505 assessed, represented by objective statistically significant means (Fig 4; fig 6).

"Beauty Product" is taken to include natural and/or artificial hair filaments such as false eyelashes and extensions; as well as brushes, combs, applicators and delivery devices for the application of cosmetic and/or topical compositions.

The term "Cosmetic products" is taken to include but not limit to mascaras, 510 conditioning agents, primers, serums and any other cosmetic compositions applied to the eyelash, eyelash root, eyelid, eyeball, under eye, eyebrow and surrounding area, which are intended to impart advantageous properties such as lengthening, lifting, eye- opening, curling and/or thickening, as well as firming, tightening, brightening, reduce puffiness etc.

515 "Product performance" may include, but is not limited to testing the performance, efficacy and/or effectiveness of beauty products, particularly beauty products comprising natural and/or artificial hair filaments such as false eyelashes and extensions; cosmetic products including but not limited to mascaras, conditioning agents, primers, serums and any other cosmetic formulations applied to the eyelash, 520 eyelash root, eyelid, eyeball, under eye, eyebrow and surrounding area, which are intended to impart advantageous properties such as lengthening, eye-opening, curling and/or thickening as well as firming, tightening, toning, lifting, brightening, reduce puffiness etc. Also included is product performance of therapeutic (medicinal or veterinary) products intended for use on the eyelash, eyelash root, eyelid, eyeball,

525 eyebrow and the surrounding area of the eye. Product performance testing of such medical products may be useful to assess effectiveness of products in the treatment of various eye conditions including but not limited to trichiasis, keratoconus, keratoglobus, glaucoma and/or localised inflammation of the surrounding eye area (e.g. upper and/or lower eyelid, under eye and eyebrow).

530 "Diagnostic tool" may include use of the method, systems and apparatus to diagnose a pre-existing condition associated with the aesthetic feature or to predict the likelihood of developing a condition associated with the aesthetic feature, in particular a condition associated with the eye or surrounding area. Such conditions include but are not limited to trichiasis, keratoconus, keratoglobus, glaucoma and/or localised inflammation of the

535 eye area (e.g. upper and/or lower eyelid, under eye and eyebrow).

"Reference sample(s)" includes but does not limit to the use of the method to generate untreated control data as a means of reference to compare and evaluate product performance; generation of consumer/patient records, generation of database comprising readout information optionally with additional consumer/patient information that can be

540 used to tailor products to consumer/patient or predict incidence or occurrence of a condition or inclusion in population subgroup.

"Database" is taken to comprise of, but not limit to, the following elements: (i) collection of data/ information, such as consumer/patient records, reference samples, and/or readout information and (ii) a means of categorising, organising and retrieving

545 said collection in a systematic way.

"Disorder" is taken to include but not limit to conditions, particularly of the skin and/or eyelashes, brought about by an imbalance of the normal processes or a disease state thereof. Examples of conditions of interest within the scope of the present invention include but are not limited to trichiasis, keratoconus, keratoglobus, glaucoma and/or

550 localised inflammation of the eye area (e.g. upper and/or lower eyelid, under eye and eyebrow). "Panellist(s)" is taken to include but not limit to individuals taking part in, and under assessment with respect to effectiveness and product performance of a beauty or cosmetic nature.

555 "Patient(s)" is taken to include but not limit to individual(s) presenting with the condition of interest, which includes but not limited to the following: trichiasis, keratoconus, keratoglobus, glaucoma and/or localised inflammation of the eye area (e.g. upper and/or lower eyelid, under eye and eyebrow).

"Control Group" is taken to include but not limit to healthy individual(s) selected as per 560 standard clinical research protocols to meet the criteria set by the study. Such

individuals provide a "reference sample" to compare against the "patient(s)" group to establish onset of disease state or conditions.

"Onset differential" is taken to include but not limit to the potential for an individual or "patient" to be presenting the symptoms associated with the condition of interest, and 565 thus the likelihood that the patient requires treatment and/or further more invasive

diagnosis.

The words "comprises/comprising" and the words "having/including" when used herein with reference to the present invention are used to specify the presence of stated features, integers, steps or components but does not preclude the presence or addition of

570 one or more other features, integers, steps, components or groups thereof.

It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment, may also be provided separately or in

575 any suitable sub-combination.

Claims

1. A method of analysing two images of an eye of a subject to determine the change, 580 between the two images, of the extent to which the eye appears to be open, wherein the images are profile-view images of the subject's eye taken from the same vantage point; wherein each image of the eye is characterised by an eyeball area bounded by a lower eyelid, an upper eyelid, and an eyeball periphery; and wherein the lower and upper eyelids comprise lower and upper lashes respectively, the method characterised by the 585 steps of:

for each image of the eye:

plotting a lower target point proximate to the eyeball periphery and the lower eyelid;

plotting an upper target point proximate to the eyeball periphery and the upper

590 eyelid;

calculating a value associated with the measurement line;

comparing the degree of change in the value associated with the measurement 595 line of the first image and the value associated with the measurement line of the second image; and

600 2. The method of claim 1, wherein:

the lower target point comprises the point of intersection between the lower eyelid and the eyeball periphery;

the upper target point is plotted by:

drawing a vertical line through the lower target point such that it intersects with 605 the upper lid at the base of the upper lashes, and plotting the point of vertical line

intersection;

plotting the point of upper/lower lid intersection where the upper lid intersects with the lower lid; drawing an upper lid line through the point of vertical line intersection and the 610 point of upper/lower lid intersection such that the upper lid line intersects with the

eyeball periphery;

designating the point of intersection between the upper lid line and the eyeball periphery as the upper target point;

further wherein the measurement line is drawn between the lower target point 615 and the upper target point following the outline of the eyeball periphery.

3. The method of claim 1, wherein

the upper target point comprises the highest point on the upper lashes;

the lower target point comprises the lowest point on the lower lashes; and wherein the measurement line is a straight line drawn between the lower target point and the upper target point.

4. A method of analysing two images of an eye of a subject to determine the change, between the two images, of the extent to which the eye appears to be open, wherein the 625 images are profile-view images of the subject's eye taken from the same vantage point; wherein each image of the eye is characterised by an eyeball area bounded by a lower eyelid, an upper eyelid, and an eyeball periphery; and wherein the lower and upper eyelids comprise lower and upper lashes respectively, the method characterised by the steps of:

630 for each image of the eye:

635 plotting an upper target point proximate to the eyeball periphery and the upper eyelid;

defining a triangle having apices respectively at each of said plotted points; measuring a characteristic area within said triangle, wherein the characteristic area is optionally the white of the eye;

640 comparing the degree of change in the magnitude of the characteristic area of the first image and the magnitude of the characteristic area of the second image; and inferring from the degree of magnitude change the extent to which an eye appears to be open.

645 5. A method of determining the change over time in the extent to which an eye of a subject appears to be open comprising the steps of:

taking a first pro file- view image of a subject at a first point in time; taking a second profile-view image of a subject at a second point in time; and performing the method of any of claims 1 to 4 on said first and second images.

650

6. A method as claimed in any preceding claim for the diagnosis of disease states and/or conditions associated with the eye.

7. A method as claimed in claim 6 wherein the disease states or conditions are selected 655 from trichiasis, keratoconus, keratoglobus, glaucoma and localised inflammation of the eye, as well as the results of environmental and genetic stimuli.

8. A method as claimed in any of claims 1 to 5 for the assessment of cosmetic compositions which may be applied to the eyelash.

660

9. A non-transitory computer readable medium carrying instructions thereon, which, when executed by a processor, cause the processor to carry out the method of any of claims 1-8.

665 10. An image analysis apparatus configured to perform the method of any of claims 1-4 or 6 to 8 wherein the images are digital images.

11.An image capture and analysis system configured to perform the method of claim 5 comprising:

670 an image capture device; and

the image analysis apparatus of claimlO.