Method and apparatus for corneal crosslinking under real-time monitoring

Abstract

A system and method for corneal crosslinking under real-time monitoring is provided. The method includes determining a plurality of measurement locations in a region of the cornea, and applying a corneal cross-linking treatment to the region of the cornea. During the application of the corneal crosslinking therapy, the method further includes acquiring a temporal OCT interferogram at each OCT measurement location, generating temporal complex OCT data based on the temporal OCT interferogram, determining biomechanical data based on the temporal complex OCT data, and adjusting the corneal crosslinking therapy based on the biomechanical data.

Description

[0001] Cross Reference to Related Applications

[0002] This application claims the benefit of U.S. Provisional Application Serial No. 63 / 579,403, filed August 29, 2023, the contents of which are incorporated by reference in their entirety. BACKGROUND

[0003] The present disclosure relates to methods and devices for performing corneal crosslinking under real-time monitoring. More specifically, the present disclosure relates to a corneal biomechanical measurement device for real-time monitoring of corneal crosslinking.

[0004] Corneal crosslinking (also referred to as corneal collagen crosslinking or CXL) is a medical procedure used to treat corneal ectasia caused by certain diseases (such as keratoconus, etc.), surgical complications (such as LASIK, etc.), and other conditions. The corneal stroma is a dense connective tissue that contains layers of tightly distributed collagen fibrils that are arranged in an orderly fashion, with strong chemical bonds or crosslinks between adjacent fibrils. The crosslinked collagen fibrils provide a strong mechanical structure that, among other things, maintains the proper curvature of the cornea. When the crosslinks between adjacent collagen fibrils begin to break due to disease, surgical complications, etc., the orderly layers weaken, the mechanical stability of the cornea decreases, and the curvature of the cornea begins to deform from a round shape to a conical shape (corneal ectasia).

[0005] CXL strengthens the cornea by forming new crosslinks between adjacent collagen fibrils, which can inhibit the progression of keratoconus, restore the strength of the cornea that was lost due to removal of corneal tissue during LASIK, etc. After the corneal epithelium has been removed and a photosensitizer (such as riboflavin) has been applied to the cornea for about 30 minutes, ultraviolet (UV) light is focused on the cornea for about 30 minutes. The photodynamic interaction between the UV light and the photosensitizer produces reactive oxygen species that induce the formation of new crosslinks between adjacent collagen fibrils to strengthen the cornea. The clinical outcome of CXL on a particular cornea is typically evaluated several weeks after treatment. SUMMARY

[0006] Embodiments of the present disclosure advantageously provide a system and method for performing corneal crosslinking under real-time monitoring. The method includes determining a plurality of measurement locations in a region of the cornea, and applying a corneal crosslinking treatment to the cornea. During the application of the corneal crosslinking treatment, the method further includes measuring a biomechanical property of the cornea at each measurement location, and adjusting the corneal crosslinking treatment based on the biomechanical data. BRIEF DESCRIPTION OF DRAWINGS

[0007] Figure 1A 、 Figure 1B and Figure 1CA block diagram depicting an example system according to embodiments of the present disclosure is depicted.

[0008] Figure 2 A block diagram depicting an example OCT engine according to embodiments of the present disclosure is depicted.

[0009] Figure 3A A block diagram depicting an example control computer according to embodiments of the present disclosure is depicted.

[0010] Figure 3B A block diagram depicting another example control computer according to embodiments of the present disclosure is depicted.

[0011] Figure 4 A flowchart depicting functionality associated with measuring corneal biomechanics according to embodiments of the present disclosure is depicted. DETAILED DESCRIPTION

[0012] Certain embodiments of the present disclosure advantageously provide a method of real-time application, monitoring, and adjustment of corneal cross-linking treatment and an integrated CXL and OCT system. The integrated CXL and OCT system advantageously provides OCT-based high-resolution imaging and biomechanical data determination, biomechanical data-based treatment adjustment, real-time feedback of treatment effectiveness, feedback-based personalized patient treatment, avoidance of under-treatment (e.g., insufficient UV light exposure or photosensitizer application), avoidance of over-treatment (e.g., excessive UV light exposure or photosensitizer application), and other advantages.

[0013] In the context of medical imaging, an OCT system directs a coherent light beam toward a biological tissue and then measures the interference between a portion of the original coherent light beam and the scattered light that reflects back to the OCT system from a particular location on (or within) the biological tissue. The interference is directly related to the reflectivity of the biological tissue at that location. For example, an ocular or ophthalmic OCT system can be used to acquire high-resolution images of the cornea and retina to determine ocular dimensions, diagnose various ocular pathologies, etc.

[0014] An OCT system generates a one-dimensional "A-scan" by measuring the reflectivity at different depths (axial dimension) of the same location using time-domain OCT (TD-OCT) or frequency-domain (Fourier-domain) OCT (FD-OCT). The OCT system generates a two-dimensional "B-scan" by combining A-scans acquired at different lateral locations (lateral dimension). The OCT system can also generate a "M-mode" (motion) scan by performing multiple A-scans at the same location, which generates time OCT data for that location. Additionally, the OCT system can generate a three-dimensional "C-scan" or volume scan by combining multiple B-scans at different elevations (elevation dimension), which can also include M-mode scans at each location (representing a fourth dimension, time).

[0015] Typically, a corneal cross-linking treatment lasts about one hour, including about 30 minutes of photosensitizer infiltration and 20 to 30 minutes of UV light exposure. Acquiring time-OCT data at all OCT measurement locations in the region of the cornea can take a few seconds. Because the OCT system is non-invasive and provides a non-contact measurement technique, the OCT measurements can be performed periodically and / or on-demand. For example, the OCT measurements can be performed every few minutes during the corneal cross-linking treatment, which allows for in-situ real-time monitoring of the corneal structure, determination of the corneal biomechanics, and control of the corneal cross-linking treatment.

[0016] Certain embodiments of the present disclosure provide a method and system for corneal cross-linking under real-time monitoring. Certain embodiments of the method include determining a plurality of measurement locations in a region of a cornea, and applying a corneal cross-linking treatment to the region of the cornea. During the application of the corneal cross-linking treatment, the method further includes acquiring time-OCT data at each OCT measurement location, generating time-complex OCT data based on the time-OCT data, determining biomechanics data based on the time-complex OCT data, and adjusting the corneal cross-linking treatment based on the biomechanics data.

[0017] Figure 1A A block diagram of a system 100 for corneal cross-linking under real-time monitoring according to embodiments of the present disclosure is depicted.

[0018] In certain embodiments, the system 100 includes, among other things, a beam delivery system (BDS) 110, a CXL radiation source 130, an OCT engine 200, and a control computer 300.

[0019] In certain embodiments, the OCT engine 200 and the control computer 300 are separate devices that are communicatively coupled using a wired or wireless connection, such as USB, Ethernet, Bluetooth, WiFi, etc. In certain other embodiments, the OCT engine 200 is a component of the control computer 300, such as one or more Peripheral Component Interconnect Express (PCIe) expansion boards, a PCIe expansion board coupled to one or more external modules, etc. In certain embodiments, the OCT engine 200 can be housed within an external PCIe expansion system enclosure that is coupled to the control computer 300 via a PCIe connection.

[0020] Typically, the BDS 110 is configured, among other things, to: (1) receive, propagate, and focus radiation (e.g., UV light) from the CXL radiation source 130 onto the cornea 12, (2) receive, propagate, and focus low-coherence (LC) light from the OCT engine 200 onto the cornea 12, and (3) receive, focus, and propagate reflected LC light from the cornea 12 to the OCT engine 200.

[0021] In certain embodiments, the BDS 110 is a free-space optical system that includes a dichroic mirror 112, a beam scanner 114, an alignment mirror 116, and a focusing lens 118 that define a common optical path 120. Radiation (e.g., UV light) emitted from the CXL radiation source 130 propagates along an optical path 122 to the BDS 110, light from the LC light source 212 of the OCT engine 200 propagates along an optical path 124 to the BDS 110, and reflected LC light from the BDS 110 propagates along the optical path 124 to the reflected LC light detector 214 of the OCT engine 200.

[0022] The dichroic mirror 112 is configured to reflect or deflect the radiation (e.g., UV light) propagating along the optical path 122 into the common optical path 120, pass the LC light propagating along the optical path 124 into the common optical path 120, and pass the reflected LC light propagating along the common optical path 120 into the optical path 124. In other words, the radiation propagating along the optical path 122 and the LC light propagating along the optical path 124 are combined by the dichroic mirror 112 and then passed to the beam scanner 114.

[0023] The beam scanner 114 is configured to adjust the OCT measurement position on the cornea 12 in two dimensions (e.g., a lateral dimension and a height dimension) in response to commands received from the OCT engine 200 or, alternatively, the control computer 300. Advantageously, the beam scanner 114 simultaneously scans the radiation (e.g., UV light) and the LC light, while the common optical path 120 ensures that the radiation and the LC light travel coaxially and are focused on the same position on the cornea 12 in order to properly align the application and monitoring components of the system 100. Typically, the beam scanner 114 reflects (or deflects) the radiation, the LC light, and the reflected LC light along the common optical path 120.

[0024] The beam scanner 114 can include a single mirror that rotates about two orthogonal axes to adjust the OCT measurement position on the cornea 12 in two dimensions. Alternatively, the beam scanner 114 can include two orthogonal mirrors, and each mirror independently rotates about an orthogonal axis to adjust the OCT measurement position on the cornea 12 in two dimensions. The single mirror can be driven by a pair of electric motors or galvanometers (or galvos), while each orthogonal mirror can be driven by a single electric motor or galvanometer. Other drive systems are also contemplated, such as piezoelectric actuators, piezoelectric galvanometers, magnetostrictive actuators, and the like.

[0025] The alignment mirror 116 is configured to mechanically align the cornea 12 with a common optical path 120 of the BDS 110. Typically, the alignment mirror 116 reflects or deflects the radiation (e.g., UV light), the LC light, and the reflected LC light along the common optical path 120 by 90°. In certain embodiments, the system 100 does not include the alignment mirror 116, and the common optical path 120 includes a straight optical path segment between the beam scanner 114 and the focusing lens 118.

[0026] The focusing lens 118 focuses the radiation (e.g., UV light) and the LC light traveling along the common optical path 120 onto the cornea 12, and focuses the reflected LC light from the cornea 12 into the common optical path 120.

[0027] In certain other embodiments, the BDS 110 can be a fiber-based system in which certain free-space optical elements are replaced by optical fibers, electro-optical elements, etc. For example, optical fibers can replace at least certain portions of the free-space optical paths, such as portions of the common optical path 120, the optical path 122, and the optical path 124, a fiber-based beam combiner can replace the dichroic mirror 112, electro-optical beam steering chips (e.g., acoustical scanners, etc.), optical phased arrays (OPAs) can replace the beam scanner 114, etc.

[0028] Figure 1B A block diagram of a system 100’ for corneal cross-linking under real-time monitoring according to embodiments of the present disclosure is depicted.

[0029] In certain embodiments, the system 100’ includes, among other things, a beam delivery system (BDS) 110, a CXL radiation source 130, an OCT engine 200, and a control computer 300. Typically, the system 100’ includes the same components as the system 100, with the exception of the alignment mirror 116 and the position swapping of the CXL radiation source 130 and the OCT engine 200 relative to the BDS 110. Additionally, the common optical path 120 includes a straight optical path segment between the beam scanner 114 and the focusing lens 118.

[0030] Figure 1C A block diagram of a system 100’’ for corneal cross-linking under real-time monitoring according to embodiments of the present disclosure is depicted.

[0031] In certain embodiments, the system 100’ includes, among other things, a beam delivery system (BDS) 110, a CXL radiation source 130, an OCT engine 200, and a control computer 300. Typically, the system 100’’ is a simplified version of the system 100’, including the same components as the system 100’, with the exception of the dichroic mirror 112 and the beam scanner 114.

[0032] Figure 2A block diagram of an OCT engine 200 according to an embodiment of this disclosure is depicted.

[0033] In some embodiments, the OCT engine 200 specifically includes an LC optical module 210, a signal processing circuitry system 220, one or more processors 230, a storage element or memory 240, and an I / O interface 250. The LC optical module 210 includes an LC light source 212 and a reflective LC photodetector 214. The signal processing circuitry system 220 may be coupled to the LC optical module 210 and the memory 240, and the processor 230 may be coupled to the LC optical module 210, the signal processing circuitry system 220, the memory 240, and the I / O interface 250. In some embodiments, the signal processing circuitry system 220 is not present, and the functionality provided by the signal processing circuitry system 220 is provided by the processor 230.

[0034] In some embodiments, the OCT engine 200 uses swept-frequency source OCT (SS-OCT) to provide FD-OCT measurement results. In some SS-OCT embodiments, the LC light source 212 may be a swept-frequency wavelength source, and the reflected LC photodetector 214 may be a high-speed photodetector. The swept-frequency wavelength source is configured to rapidly sweep a narrow-linewidth optical signal over a wide wavelength range during each A-scan, such as a Fourier domain mode-locked (FDML) laser with a center wavelength of 1050 nm and a scan rate of 5 MHz or higher. Typically, the sweep rate of the swept-frequency wavelength source may be 100 kHz or higher. The high-speed photodetector is configured to sequentially detect the wavelength components of the reflected LC light signal (or interference signal) during one wavelength sweep (A-scan). In other words, the reflected LC photodetector 214 is configured to generate a spectral interferogram with a fringe pattern during each wavelength sweep (A-scan). The spectral interferogram includes intensity data for each wavelength (or frequency) emitted by the swept-frequency wavelength source.

[0035] In other embodiments, the OCT engine 200 uses the spectral domain (SD-OCT) to provide FD-OCT measurement results. In some SD-OCT embodiments, the LC light source 212 may be a broadband light source, such as a superluminescent diode (SLD), and the reflective LC photodetector 214 may include a spectrometer and a high-speed linear array camera that generates a spectral interferogram with a fringe pattern during each A-scan.

[0036] A high-speed analog-to-digital (A / D) converter can be coupled to or included within the LC optical module 210 to convert analog interference signals into digital signals, which are commonly referred to as time-OCT interferograms.

[0037] In some embodiments, the signal processing circuitry 220 is coupled to the LC optical module 210 and includes one or more microprocessors, application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), etc., configured to generate complex OCT data based on a time-based OCT interferogram received from the reflective LC photodetector 214. In some embodiments, the signal processing circuitry 220 includes a high-speed A / D converter (instead of the LC optical module 210) that converts the analog spectral interferogram signal received from the reflective LC photodetector 214 into OCT data.

[0038] Advantageously, the OCT data also includes intensity information of all depth layers in the A-scan at the OCT measurement location.

[0039] In some embodiments, the signal processing circuitry 220 can extract intensity information for each depth layer in the A-scan by applying wavenumber remapping, dispersion compensation, Fourier transform, etc., to the time-based OCT interferogram to generate complex OCT data. For example, the signal processing circuitry 220 can apply a Fast Fourier Transform (FFT) to the time-based OCT interferogram to generate complex OCT data. The amplitude of the complex OCT data can be squared to produce the intensity at different depths, and the phase of the complex OCT data can be further processed to provide additional information, as described below.

[0040] During motion mode scanning (also known as M-mode scanning), OCT engine 200 performs multiple A-scans at the same location, generating a temporal OCT interferogram for that location. Furthermore, signal processing circuitry system 220 can apply FFT to the temporal OCT interferogram to generate temporal complex OCT data for that location.

[0041] Processor 230 may include one or more general-purpose or special-purpose microprocessors, microcontrollers, etc., that execute instructions to perform control, calculation, input / output, and other functions of OCT engine 200. For example, processor 230 may be configured to synchronize the triggering of CXL radiation source 130, the scanning of beam scanner 114, and the measurement operations of LC optical module 210 to acquire time-varying OCT interferograms and complex OCT data and send them to control computer 300. In some other embodiments, CXL radiation source 130 and / or beam scanner 114 may be controlled by control computer 300.

[0042] Processor 230 may include a single integrated circuit (such as a microprocessor device) or multiple integrated circuit devices and / or circuit boards that work together to perform appropriate functions. In some embodiments, signal processing circuitry system 220 is absent, and processor 230 may apply wavenumber remapping, dispersion compensation, Fourier transform (such as FFT), etc., to time-OCT interferograms to generate complex OCT data.

[0043] Typically, memory 240 may store instructions for execution by processor 230, as well as data such as time-based OCT interferograms, complex OCT data, etc. Memory 240 may include various non-transitory computer-readable media accessible by processor 230, and other components. In various embodiments, memory 240 may include volatile and non-volatile media, non-removable media, and / or removable media. For example, memory 240 may include random access memory (RAM), dynamic RAM (DRAM), static RAM (SRAM), read-only memory (ROM), flash memory, cache memory, and / or any other combination of non-transitory computer-readable media.

[0044] I / O interface 250 is configured to transmit and / or receive data (e.g., OCT measurement locations and complex OCT data) from control computer 300, send commands to CXL radiation source 130 to emit radiation (e.g., UV light), send commands to beam scanner 114 to focus common optical path 120 on different OCT measurement locations on cornea 12, etc. Typically, data can be transmitted via wired and / or wireless connections. For example, I / O interface 370 may include one or more wired communication interfaces (e.g., USB, Ethernet, etc.) and / or one or more wireless communication interfaces (e.g., Bluetooth, WiFi, etc.) coupled to one or more antennas.

[0045] Figure 3A A block diagram of a control computer 300 according to an embodiment of the present disclosure is depicted.

[0046] The control computer 300 includes a bus 320 coupled to one or more processors 330, storage elements or memories 340, one or more network interfaces 360, I / O interfaces 370, and a display interface 380. In some embodiments, the control computer 300 also includes one or more dedicated processors or processing circuitry systems 350, such as graphics processing units (GPUs), ASICs, FPGAs, etc. Typically, the network interfaces 360 use wired or wireless connections to couple to one or more networks 362, the I / O interfaces 370 use wired or wireless connections to couple to one or more I / O devices 372, and the display interface 380 typically uses a wired connection to couple to a display 382.

[0047] In some embodiments, the CXL radiation source 130 and the OCT engine 200 are coupled to the I / O interface 370 via wired or wireless connections (such as USB, Ethernet, Bluetooth, WiFi, etc.). In some embodiments, the CXL radiation source 130 can send status information to the control computer 300 via the connection, and the control computer 300 can send configuration information, power commands, etc. to the CXL radiation source 130 via the connection.

[0048] Bus 320 is a high-speed data transfer subsystem, such as a PCIe bus, that transfers data between processor 330, memory 340, network interfaces(s) 360, I / O interfaces 370, and display interfaces 380. In some embodiments, bus 320 also transfers data between these components and a dedicated processor or processing circuitry system 350.

[0049] Processor 330 includes one or more general-purpose or special-purpose microprocessors that execute instructions to perform control, calculation, input / output, and other functions of the computer 300. Each processor 330 may include a single integrated circuit (such as a microprocessor device) or multiple integrated circuit devices and / or circuit boards that work together to perform appropriate functions. Additionally, processor 330 may execute computer programs or modules stored in memory 340, such as operating system 342, software module 344, etc.

[0050] Typically, memory 340 stores instructions for execution by processor 330, as well as data. Memory 340 may include various non-transitory computer-readable media accessible by processor 330, as well as other components. In various embodiments, memory 340 may include volatile and non-volatile media, non-removable media, and / or removable media. For example, memory 340 may include any combination of random access memory (RAM), dynamic RAM (DRAM), static RAM (SRAM), read-only memory (ROM), flash memory, cache memory, and / or any other type of non-transitory computer-readable media.

[0051] Memory 340 stores various components used for retrieving, presenting, modifying, and storing data, such as operating system 342 and software module 344. Operating system 342 provides operating system functions for controlling computer 300, while software module 344 provides certain functions when executed by processor 330. Data 346 may include data associated with operating system 342, software module 344, etc.

[0052] Multiple network interfaces 360 are configured to transmit data to and from multiple networks 362 using wired and / or wireless connections. For example, multiple networks 362 may include a local area network (LAN) connected to a wide area network (WAN) via a router, and the WAN may be connected to the Internet via an Internet Service Provider (ISP), etc. Multiple networks 362 may execute various network protocols, such as wired and / or wireless Ethernet, Bluetooth, etc. Multiple networks 362 may also include various combinations of wired and / or wireless physical layers, such as copper wire or coaxial cable networks, fiber optic networks, WiFi networks, Bluetooth mesh networks, CDMA, FDMA, and TDMA cellular networks, etc.

[0053] I / O interface 370 is configured to transmit and / or receive data from I / O device 372. I / O interface 370 implements the connection between processor 330, memory 340, and I / O device 372 by encoding data to be transmitted from processor 330 or memory 340 to I / O device 372 and decoding data received from I / O device 372 for use by processor 330 or memory 340. Typically, data can be transmitted via wired and / or wireless connections. For example, I / O interface 370 may include one or more wired communication interfaces (such as USB, Ethernet, etc.) and / or one or more wireless communication interfaces (such as Bluetooth, WiFi, etc.) coupled to one or more antennas.

[0054] Typically, I / O device 372 provides input to and / or outputs from control computer 300. As discussed above, I / O device 372 is operatively connected to control computer 300 using wired and / or wireless connections. I / O device 372 may include a local processor coupled to a communication interface configured to communicate with control computer 300 using wired and / or wireless connections. For example, I / O device 372 may include a touchscreen, keyboard, mouse, touchpad, joystick, etc.

[0055] The display interface 380 is configured to transmit image data from the control computer 300 to the monitor or display 382.

[0056] Figure 3B A block diagram depicts a control computer 300' according to an embodiment of the present disclosure.

[0057] The control computer 300' includes a bus 320 coupled to one or more processors 330, storage elements or memories 340, one or more network interfaces 360, I / O interfaces 370, and display interfaces 380, as described above with respect to the control computer 300. Figure 3BIn this context, the OCT engine 200 is depicted as a component controlling the computer 300', such as one or more PCIe expansion boards, PCIe expansion boards coupled to one or more external modules, etc. In some embodiments, the OCT engine 200 may be housed within an external PCIe expansion system enclosure coupled to the bus 320 via a PCIe connection.

[0058] In order to use an integrated CXL and OCT system (such as system 100, 100', 100'') to apply, monitor and adjust corneal crosslinking treatment in real time, control computer 300 determines multiple OCT measurement locations in the treatment area of ​​cornea 12, and CXL radiation source 130 applies corneal crosslinking treatment to the treatment area, which may include irradiating a photosensitizer that has been applied to the treatment area of ​​cornea 12.

[0059] During corneal cross-linking treatment administered by the CXL radiation source 130, the OCT engine 200 acquires temporal OCT data at each OCT measurement location, generates temporal complex OCT data based on the temporal OCT data, and the control computer 300 determines biomechanical data based on the temporal complex OCT data received from the OCT engine 200. The corneal cross-linking treatment can be adjusted by the control computer 300 based on the biomechanical data, such as increasing or decreasing the intensity of radiation (e.g., UV light) emitted by the CXL radiation source 130, or increasing or decreasing the duration of radiation emitted by the CXL radiation source 130 relative to a treatment protocol threshold.

[0060] The control computer 300 first divides at least one treatment area of ​​the cornea 12 into multiple OCT measurement locations, which form a two-dimensional scanning pattern, such as a symmetrical or asymmetrical scanning pattern, a square or rectangular scanning pattern, a circular or elliptical scanning pattern, etc. In some embodiments, two or more treatment areas can be identified, and the method for corneal crosslinking under real-time monitoring can be repeated for each treatment area.

[0061] Typically, the diameter of the cornea 12 varies between approximately 11.5 mm and 12.5 mm, with an average diameter of approximately 11.7 mm. In some embodiments, the radiation is UV light with a spot diameter of 4 to 11 mm, and the LC light is near-infrared (IR) light with a spot diameter of 10 to 20 μm, and the treatment area can be approximately 65 mm. 2 The area, or more generally in the range of 15 mm 2 Up to 100 mm 2The size and number of treatment areas are typically determined by the UV spot diameter, the desired extent of corneal cross-linking treatment (as a percentage of the area of ​​the cornea 12), and the diameter of the cornea 12. Similarly, the number of OCT measurements for the treatment area can be determined based on the UV spot diameter, the LC spot diameter, and the degree of overlap of OCT measurement sites (e.g., 0%, 10%, 25%, etc.), the degree of dispersion or spacing of OCT measurement sites (e.g., 10%, 25%, etc.), and the measurement interval (e.g., 50 μm, 100 μm, etc.). For example, for a UV light with a spot diameter of 9 mm and an LC light with a spot diameter of 20 μm, a single treatment area with a diameter of 9 mm can be divided into 8,000 OCT measurement sites, with a 100 μm interval between the sites.

[0062] To acquire temporal OCT data in the treatment area, beam scanner 114 scans LC light at these OCT measurement locations without affecting the irradiation of the photosensitizer by the CXL radiation source.

[0063] Starting from the first OCT measurement position in the scan pattern, the OCT engine 200 performs an M-mode scan at that OCT measurement position, which generates temporal OCT data for that position. An M-mode scan may take 5 ms, 10 ms, 15 ms, etc., to complete, depending on the number of A-scans acquired. The signal processing circuitry system 220 can then apply an FFT to the temporal OCT interferogram to generate temporal complex OCT data for that position. The OCT engine 200 then commands the beam scanner 114 to move to the next OCT measurement position in the scan pattern until temporal OCT data and temporal complex OCT data for all OCT measurement positions in the scan pattern have been acquired. In some embodiments, the control computer 300 can command the beam scanner 114 to move to these OCT measurement positions in the scan pattern.

[0064] Typically, processor 330 (or dedicated processor 350) can be configured to determine one or more corneal biomechanical properties at each OCT measurement location based on complex OCT data. For example, tissue stiffness can be determined using the rate of change of the time-correlated signal at each OCT measurement location (e.g., decorrelation). The rate of change of the signal is directly and negatively correlated with the degree of collagen constraint, which represents the tightness and density of cross-linking of collagen fibrils. As new cross-links form between adjacent collagen fibrils during corneal cross-linking treatment, corneal stiffness increases and the decorrelation coefficient decreases. Collagen constraint and corneal stiffness are biomechanical data that can be used to adjust corneal cross-linking treatment.

[0065] In some embodiments, the intensity of the irradiation (e.g., UV light) emitted by the CXL radiation source 130 can be increased or decreased based on collagen constraint and corneal stiffness. For example, a rapid increase in collagen constraint and corneal stiffness may indicate that corneal crosslinking treatment is proceeding too quickly and may reduce the intensity of the irradiation (e.g., UV light) emitted by the CXL radiation source 130. Similarly, a slow increase in collagen constraint and corneal stiffness may indicate that corneal crosslinking treatment is proceeding too slowly and may increase the intensity of the irradiation (e.g., UV light) emitted by the CXL radiation source 130.

[0066] In some embodiments, the duration of corneal crosslinking treatment (compared to a treatment protocol threshold) can be increased or decreased based on collagen constraint and corneal stiffness. For example, when collagen constraint and corneal stiffness reach a stiffness threshold, radiation emitted by the CXL radiation source 130 can be stopped, which can result in an increase or decrease in the exposure time of radiation emitted by the CXL radiation source 130.

[0067] The use of other biomechanical data and control techniques was also envisioned.

[0068] Figure 4 A flowchart 400 depicting an embodiment of this disclosure illustrates a function associated with measuring corneal biomechanics.

[0069] At 410, multiple OCT measurement locations are determined within the corneal region. Box 410 can be executed, for example, by a control computer 300 or 300'. As discussed above, the control computer 300 or 300' can divide the treatment area into multiple OCT measurement locations that form a one-dimensional or two-dimensional scanning pattern of the area, such as a symmetrical or asymmetrical scanning pattern, a square or rectangular scanning pattern, a circular or elliptical scanning pattern, etc. The process continues to box 420.

[0070] At 420, corneal cross-linking treatment is applied to the region of the cornea. Box 420 can be performed, for example, by a CXL radiation source 130.

[0071] During the application of corneal crosslinking treatment to the corneal region (i.e., box 420), boxes 430, 440, and 450 are performed periodically (or as needed).

[0072] At 430, time-based OCT data is acquired at each OCT measurement location. Box 430 can be executed, for example, by OCT engine 200, as described above.

[0073] At position 440, time complex OCT data is generated. Position 440 can be executed, for example, by OCT engine 200, as described above.

[0074] At 450, biomechanical data for a region of the cornea 12 are determined based on time-complex OCT data. Box 450 can be executed, for example, by a control computer 300 or 300'. As discussed above, the biomechanical data generated at each OCT measurement location within the region may include, for example, collagen constraint, corneal stiffness, etc.

[0075] At 460, corneal cross-linking treatment can be adjusted based on biomechanical data. Box 450 can be executed, for example, by a control computer 300 or 300'. For example, the irradiation intensity emitted by the CXL radiation source 130 can be increased or decreased based on biomechanical data, and the exposure time of the radiation emitted by the CXL radiation source 130 can be increased or decreased, etc.

[0076] In some embodiments, at 470, the corneal structure can be displayed on a display 382 by a control computer 300 or 300' based on an OCT image.

[0077] Certain features and advantages of this disclosure are apparent from the detailed description, and therefore the appended claims are intended to cover all such features and advantages of this disclosure that fall within the scope of this disclosure. Furthermore, since many modifications and variations will readily occur to those skilled in the art, it is not intended to limit this disclosure to the exact construction and operation shown and described, and therefore all suitable modifications and equivalents falling within the scope of this disclosure may be invoked.

Claims

1. A method for performing corneal crosslinking under real-time monitoring, the method comprising: Determine multiple optical coherence tomography (OCT) measurement locations within a region of the cornea; Apply corneal cross-linking treatment to the area of ​​the cornea; as well as During the application of the corneal cross-linking treatment: Time-OCT interferograms were acquired at each OCT measurement location. Generating time complex OCT data based on the aforementioned time OCT interferogram. Biomechanical data were determined based on the aforementioned complex time OCT data, and The corneal cross-linking treatment is adjusted based on the biomechanical data.

2. The method as described in claim 1, wherein, The application of the corneal cross-linking treatment includes: The photosensitizer has been applied to the area of ​​the cornea by irradiating it with a corneal cross-linking radiation source.

3. The method as described in claim 2, wherein, The adjustment of the corneal crosslinking treatment includes: The intensity of radiation emitted by the corneal cross-linked radiation source may be increased or decreased based on the biomechanical data.

4. The method of claim 3, further comprising: During the application of the corneal cross-linking treatment: The corneal structure is displayed at each OCT measurement location.

5. The method of claim 1, wherein, The biomechanical data includes: Collagen constraint; and Corneal stiffness.

6. The method of claim 5, wherein: The acquisition of the time-of-flight OCT interferogram includes acquiring M-mode OCT data at each OCT measurement location; and The generation of time complex OCT data includes processing the time OCT interferogram based on wavenumber remapping, dispersion compensation, or fast Fourier transform (FFT).

7. The method of claim 6, wherein: The complex OCT data includes amplitude data and phase data; and The determination of the biomechanical data includes: The rate of signal change is determined based on the phase data of the aforementioned complex time OCT data. The collagen constraint is determined based on the rate of change of the signal, and The corneal stiffness is determined based on the collagen constraint.

8. The method of claim 6, wherein: The complex OCT data includes amplitude data and phase data; and The determination of the biomechanical data includes: The signal change rate is determined based on the amplitude data of the complex time OCT data. The collagen constraint is determined based on the rate of change of the signal, and The corneal stiffness is determined based on the collagen constraint.

9. The method of claim 6, wherein: The complex OCT data includes amplitude data and phase data; and The determination of the biomechanical data includes: The signal change rate is determined based on the amplitude and phase data of the aforementioned complex time OCT data. The collagen constraint is determined based on the rate of change of the signal, and The corneal stiffness is determined based on the collagen constraint.

10. The method of claim 2, wherein: The corneal crosslinked radiation source is configured to emit ultraviolet (UV) light, which propagates to the cornea along a common optical path; and The common optical route beam transmission system (BDS) is defined.

11. The method of claim 10, wherein, The acquired time-of-flight OCT interferogram includes: LC light is emitted from a low-coherence LC light source, and the LC light propagates along the common optical path to the OCT measurement position; The reflected LC light propagating along the common optical path from the OCT measurement position is detected by a reflected LC photodetector; and The time-OCT interferogram is generated by a processor or signal processing circuit system coupled to the reflected LC light.

12. The method of claim 11, wherein, The BDS includes a dichroic mirror, a beam scanner, and a focusing lens that define the common optical path.

13. The method of claim 12, wherein, The dichroic mirror is configured as follows: The UV light from the corneal crosslinking radiation source is transmitted into the common optical path; The LC light from the LC light source is reflected into the common optical path; as well as The reflected LC light from the common optical path is reflected to the reflected LC light detector.

14. The method of claim 13, wherein, The UV light and the LC light propagate coaxially along the common optical path to the OCT measurement position.

15. A system for performing corneal crosslinking under real-time monitoring, the system comprising: A beam transmission system (BDS) that defines a common optical path; A corneal crosslinking radiation source, the corneal crosslinking radiation source being configured to apply corneal crosslinking therapy to a region of the cornea; An optical coherence tomography (OCT) engine, the engine being configured to: Time-OCT interferograms are acquired at each of the multiple OCT measurement locations in the region via the common optical path, and Generate time complex OCT data based on the time OCT interferogram; as well as A control computer coupled to the OCT engine, the control computer including a processor configured to: Determine the plurality of OCT measurement locations within the region of the cornea. The OCT measurement location is sent to the OCT engine, and During the application of the corneal cross-linking treatment: Receive time-complex OCT data for each OCT measurement location from the OCT engine. Based on the aforementioned complex time OCT data, biomechanical data of the corneal region were determined, and The corneal crosslinking radiation source is adjusted based on the biomechanical data of the corneal region.

16. The system of claim 15, wherein: The time-based OCT interferogram includes M-mode OCT data; and The processor is configured to generate time complex OCT data, including the processor being configured to process the M-mode OCT data based on wavenumber remapping, dispersion compensation, or fast Fourier transform (FFT).

17. The system of claim 16, wherein: The complex OCT data includes amplitude data and phase data; The biomechanical data for the corneal region include collagen constraint and corneal stiffness; and The processor is configured to determine the biomechanical data, including the processor being configured to: The rate of signal change is determined based on the phase data of the aforementioned complex time OCT data; The collagen constraint is determined based on the rate of change of the signal; and The corneal stiffness is determined based on the collagen constraint.

18. The system of claim 17, wherein: The processor is configured to apply the corneal crosslinking treatment, including emitting ultraviolet (UV) light that propagates along the common optical path to the cornea; and The processor is configured to adjust the corneal crosslinked radiation source, including the processor being configured to increase or decrease the intensity of UV light emitted by the corneal crosslinked radiation source based on the biomechanical data.

19. The system of claim 18, wherein: The OCT engine includes a low-coherence LC light source, a reflective LC photodetector, and a processor or signal processing circuit system configured to generate the time-based OCT interferogram and the time-based complex OCT data; The LC light source is configured to emit LC light, which propagates along the common optical path to the OCT measurement position; and The reflected LC photodetector is configured to detect reflected LC light propagating from the OCT measurement location along the common optical path.

20. The system of claim 19, wherein, The BDS includes a dichroic mirror, a beam scanner, and a focusing lens that define the common optical path.

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