Index for quanitification of bowman's layer roughness for diagnosis of disease and prognosis of treatments in human cornea

Abstract

A Bowman's Refractive Index (BRI) for quantification of microdistortions in Bowman's Layer (BL) after Small Incision Lenticule Extraction (SMILE) is defined for a patient. BRI is summation of one or more areas of the OCT image of anterior edge of Bowman's layer, quantifies the smoothness of the Bowman's layer. The anterior edge of Bowman's layer is segmented into pixels. After segmentation, a 3.sup.rd order polynomial is curve fit to the segmented pixels of the edge of Bowman's layer. BRI is calculated by segmentation of the 3-Dimensional (3-D) OCT image. BRI acts as a marker for mechanical stability and is useful for diagnosis of disease and prognosis of treatments in human.

Claims

1. A method of evaluating microdistortions in a Bowman's layer of a cornea, the method comprising: imaging the cornea using spectral domain optical coherence tomography to obtain an image that includes the anterior edge of the Bowman's layer; overlaying a smooth representation of the anterior edge of the Bowman's layer on the image of an anterior edge of the Bowman's layer; segmenting the anterior edge of a Bowman's layer of the cornea in the image into a selected number of pixels or voxels to obtain segmented areas of pixels or segmented volumes of voxels representing microdistortions of the Bowman's layer, each segmented area or volume being the area or volume above or below the anterior edge of the Bowman's layer to the smooth representation of the anterior edge of the Bowman's layer such that 3rd order polynomial is curve fit to the segmented areas of pixels or the segmented volumes of voxels of the anterior edge of the Bowman's layer; calculating Bowman's Roughness Index (BRI) based on the segmented areas of pixels or the segmented volumes of voxels; and comparing the calculated index to a previous index obtained from a previously taken image to evaluate relative changes in microdistortions of the Bowman's layer.

2. The method as claimed in claim 1, wherein BRI is calculated by analyzing the regional corneal imaging without the need for peripheral corneal imaging.

3. The method as claimed in claim 1, wherein the roughness of the Bowman's layer is analyzed by subjecting the Bowman's layer to 3-D mapping using the calculated BRI.

4. The method as claimed in claim 1, wherein BRI is useful as for diagnosis of diseases and prognosis for treatment of diseases in human.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1 illustrates the segmentation of optical coherence tomography images before and after surgery.

(2) FIG. 2 illustrates the schematic overlay of the segmented edge of Bowman's layer.

(3) FIG. 3 illustrates the mean BRI before and after surgery.

DETAILED DESCRIPTION OF THE INVENTION

(4) In order to make the matter of the invention clear and concise, the following definitions are provided for specific terms used in the following description.

(5) The term “Bowman's Layer” means smooth, acellular, non-regenerating layer, located between the superficial epithelium and the stroma in the cornea of the eye.

(6) The term “Prognosis” refers to prediction of key outcome of one's current standing.

(7) The present invention defines a Bowman's Roughness Index for quantification of microdistortions in Bowman's layer in patients undergoing SMILE for refractive surgery especially myopia. Bowman's Roughness Index is a parameter for quantification of the microdistortions in Bowman's layer and acts as a biomarker to diagnosis of the diseases in human.

(8) Usually, SMILE results in the formation of microdistortions in Bowman's layer, which results in altered biomechanical changes. The Bowman's Roughness Index is defined by considering the anterior edge of the Bowman's layer.

(9) The cornea samples are isolated from patients undergoing SMILE. The preliminary biomechanics of the cornea is assessed with the air-puff method. Images of the Bowman's layer in the central 3 mm layer of the cornea are acquired using high resolution spectral domain optical coherence tomography, which has a resolution of 2.4 μm in tissue to allow image of the Bowman's layer with sufficient number of pixels. The optical coherence tomography is performed along the nasal-temporal direction. The location of the 2-D scan is set at each follow-up such that it subdivided the projection image of the cornea into nearly two equal halves upon careful visual examination. Further, at least three 2-D scans are acquired in quick succession at each follow-up time point.

(10) One month after the surgery, the parameters such as Uncorrected Distance Visual Acuity (UDVA), Corrected Distance Visual Acuity (CDVA), sphere, cylinder and corneal deformation are measured.

(11) FIG. 1 illustrates the segmentation of optical coherence tomography images before and after surgery. After SMILE, the posterior edge of the Bowman's layer is less evident and hence only the anterior edge of the Bowman's layer is considered for further examination. The anterior edge of the Bowman's layer is segmented into number of pixels from the optical coherence tomography images before and after surgery using gradient based thresholding. After segmentation, a 3.sup.rd order polynomial is curve fit to the segmented pixels of the Bowman's layer edge.

(12) FIG. 2 illustrates the schematic overlay of the segmented edge of Bowman's layer. The segmented edge of Bowman's layer and the 3.sup.rd order polynomial curve fit to the segmented pixels of the Bowman's layer edge is used to identify the microdistortions. The areas represent the areas enclosed between the microdistortions (104) and 3.sup.rd order polynomial curve fit (105). These areas in the segmented edge are represented as A.sub.1 (101), A.sub.2 (102), A.sub.3 . . . A.sub.n (103), where n is the number of areas enclosed.

(13) The microdistortions in Bowman's layer are quantified using the analysis of these areas. In order to quantify the microdistortions in the Bowman's layer, a Bowman's Roughness Index is defined in the present invention. Bowman's Roughness Index is calculated based on the areas represented in the segmented edge.

(14) Bowman's Roughness Index is defined as follows:
BRI=Σ.sub.k=1.sup.nA.sub.k=A.sub.1+A.sub.2+ . . . A.sub.k  (1)

(15) The magnitude of Bowman's Roughness Index is directly proportional to the number of the microdistortions in the Bowman's layer i.e. if BRI value is zero, the microdistortions are absent. The mean BRI from the three images of each eye is calculated and used for further analyses.

(16) The present invention also discloses the calculation of BRI in 3-D image. A smoothened Bowman's surface is created by segmenting the surface from volume imaging or 2-D interpolated scanning using cubic spline interpolation, multi-dimensional polynomials. The 3-D image is created by segmenting the surface from volume imaging or 2-D interpolated scanning BRI and by replacing the shaded areas by shaded volumes. BRI is calculated by segmentation of the 3-Dimensional (3-D) OCT image. BRI calculation in 3-D is as follows:
BRI=∫∫(z−f(x,y))dxdy

(17) Where, (x,y,z) represent the co-ordinates of the pixels or voxels on the surface, z′=f(x,y) represents 2-D interpolation method where f is the smoothing function and z′ are the smoothened z co-ordinates.

(18) BRI is also useful for 3-D mapping of the roughness of the Bowman's layer. The present invention is useful to calculate the curvature and wave front aberrations of the different layers of the cornea using the detected edges and surface reconstruction [f(x,y)]. Wave front aberrations are calculated using techniques such as ray tracing.

(19) FIG. 3 illustrates the mean BRI before and after surgery. The results showed that mean BRI is 1.86×10.sup.−3±6.9×10.sup.−5 mm.sup.2, 2.56×10.sup.−3±3.7×10.sup.−5 mm.sup.2, 3.14×10.sup.−3±8.5×10.sup.−5 mm.sup.2 and 2.43×10.sup.−3±8.5×10.sup.−5 mm.sup.2 before, 1 day after, 1 week after and 1 month after surgery, respectively. The mean ratio of post to preoperative BRI at 1 day, 1 week and 1 month after surgery is 1.40±0.04, 1.64±0.07 and 1.34±0.05, respectively. The results further showed that mean BRI before surgery is significantly different from mean BRI at day 1 (p<0.0001), week 1 (p<0.0001) and month 1 (p<0.0001). Mean BRI at week 1 is significantly different from mean BRI at day 1 (p<0.0001) and month 1 (p<0.0001) after surgery. The Co-efficient of Variation (CV) of BRI is 0.1%. The mean coefficient of regression of the 3.sup.rd order polynomial curve fit on segmented Bowman's layer edge is 0.99±1×10.sup.−3. The mean ratio of post to preoperative BRI correlated significantly with postoperative decrease in spherical equivalent refractive error (r=+0.51, p=0.02) and with postoperative improvement in UDVA (r=+0.38, p=0.03) at 1 month.

EXAMPLE 1

(20) The study includes the analysis of eyes of patients between 18 to 50 years of age undergoing SMILE with a stable moderate to high myopia for a minimum period of one year, a corrected distance visual acuity of 20/25 or better, a spherical equivalent refraction less than −10D and a refractive astigmatism less than −3D. The Bowman's layer in the central 3 mm cornea is imaged with high resolution optical coherence tomography (Envisu, Bioptigen Inc., Morrisville, USA). The optical coherence tomography exhibited a resolution of 2.4 μm in tissue, which allowed Bowman's layer image with sufficient number of pixels. The optical coherence tomography imaging is performed not only at 1 month but also at day 1 and week 1 after surgery to evaluate the longitudinal variation of the microdistortions.

(21) The location of the 2-Dimensional (D) scan is set at each follow-up such that it subdivided the projection image of the cornea into nearly two equal halves. Further, at least three 2-D scans are acquired in quick succession at each follow-up time point.

(22) The anterior edge of the Bowman's layer is segmented into number of pixels from the optical coherence tomography images before and after surgery using gradient based thresholding. After segmentation, a 3.sup.rd order polynomial is curve fit to the segmented pixels of the Bowman's layer edge.

(23) The areas represent the areas enclosed between the microdistortions and curve fit. These areas in the segmented edge are represented as A.sub.1, A.sub.2, A.sub.3 . . . A.sub.n, where n is the number of areas enclosed.

(24) BRI is defined as the summation:

(25) $\mathrm{BRI}=\underset{k=1}{\overset{n}{.Math.}}{A}_k=A_1+A_2+\mathrm{.Math.}+A_k$

(26) The mean BRI from the three images of each eye is calculated and used for further analyses.

(27) The present invention employs fully automated image segmentation method to define BRI as an index of quantification of microdistortions using high resolution optical coherence tomography, which has a resolution of 2.4 μm in tissue and is advantageous over the existing methods. Further, the visual examination of microdistortions showed that they remain stable after 1 week and reduces marginally. The results also showed that the ratio of post to preoperative BRI correlated positively with the magnitude of refractive correction and change in visual acuity, which implies that the magnitude of microdistortions increased as more tissue is removed after SMILE. BRI quantifies the smoothness of the layer and is useful for regional analyses without the need for peripheral corneal imaging. BRI is useful for diagnosis of disease and prognosis of treatments in human.

(28) In addition to Bowman's layer, the present invention is also useful to quantify the roughness of other layers of the cornea such as epithelium, stroma, Descemet's membrane, Dua's layer and endothelium in response to surgery or disease.