Optical Coherence Tomography Image Quality Research Articles

PSCAT: a lightweight transformer for simultaneous denoising and super-resolution of OCT images

Optical coherence tomography (OCT), owing to its non-invasive nature, has demonstrated tremendous potential in clinical practice and has become a prevalent diagnostic method. Nevertheless, the inherent speckle noise and low sampling rate in OCT imaging often limit the quality of OCT images. In this paper, we propose a lightweight Transformer to efficiently reconstruct high-quality images from noisy and low-resolution OCT images acquired by short scans. Our method, PSCAT, parallelly employs spatial window self-attention and channel attention in the Transformer block to aggregate features from both spatial and channel dimensions. It explores the potential of the Transformer in denoising and super-resolution for OCT, reducing computational costs and enhancing the speed of image processing. To effectively assist in restoring high-frequency details, we introduce a hybrid loss function in both spatial and frequency domains. Extensive experiments demonstrate that our PSCAT has fewer network parameters and lower computational costs compared to state-of-the-art methods while delivering a competitive performance both qualitatively and quantitatively.

Denoising OCT videos based on temporal redundancy

The identification of eye diseases and their progression often relies on a clear visualization of the anatomy and on different metrics extracted from Optical Coherence Tomography (OCT) B-scans. However, speckle noise hinders the quality of rapid OCT imaging, hampering the extraction and reliability of biomarkers that require time series. By synchronizing the acquisition of OCT images with the timing of the cardiac pulse, we transform a low-quality OCT video into a clear version by phase-wrapping each frame to the heart pulsation and averaging frames that correspond to the same instant in the cardiac cycle. Here, we compare the performance of our one-cycle denoising strategy with a deep-learning architecture, Noise2Noise, as well as classical denoising methods such as BM3D and Non-Local Means (NLM). We systematically analyze different image quality descriptors as well as region-specific metrics to assess the denoising performance based on the anatomy of the eye. The one-cycle method achieves the highest denoising performance, increases image quality and preserves the high-resolution structures within the eye tissues. The proposed workflow can be readily implemented in a clinical setting.

Super-resolution of Retinal Optical Coherence Tomography Images Using Statistical Modeling.

Optical coherence tomography (OCT) imaging has emerged as a promising diagnostic tool, especially in ophthalmology. However, speckle noise and downsampling significantly degrade the quality of OCT images and hinder the development of OCT-assisted diagnostics. In this article, we address the super-resolution (SR) problem of retinal OCT images using a statistical modeling point of view. In the first step, we utilized Weibull mixture model (WMM) as a comprehensive model to establish the specific features of the intensity distribution of retinal OCT data, such as asymmetry and heavy tailed. To fit the WMM to the low-resolution OCT images, expectation-maximization algorithm is used to estimate the parameters of the model. Then, to reduce the existing noise in the data, a combination of Gaussian transform and spatially constraint Gaussian mixture model is applied. Now, to super-resolve OCT images, the expected patch log-likelihood is used which is a patch-based algorithm with multivariate GMM prior assumption. It restores the high-resolution (HR) images with maximum a posteriori (MAP) estimator. The proposed method is compared with some well-known super-resolution algorithms visually and numerically. In terms of the mean-to-standard deviation ratio (MSR) and the equivalent number of looks, our method makes a great superiority compared to the other competitors. The proposed method is simple and does not require any special preprocessing or measurements. The results illustrate that our method not only significantly suppresses the noise but also successfully reconstructs the image, leading to improved visual quality.

Are intravitreal hyperreflective particles alike in eyes with acute toxoplasma chorioretinitis and non-infectious uveitis?

BackgroundTo compare distinctive features of hyperreflective particles observed on spectral-domain optical coherence tomography (OCT) sections in eyes with acute toxoplasma chorioretinitis (TC) and non-infectious uveitis (NIU). MethodsMedical records and the spectral-domain OCT images of the patients with TC and NIU were retrospectively reviewed. The TC and NIU groups were compared in terms of age, sex, mean OCT image quality, mean central macular thickness (CMT), presence of intraretinal fluid (IRF), presence of subretinal fluid (SRF), number of hyperreflective particles in the posterior vitreous area and mean particle measurement in the posterior vitreous area. ResultsNon-infectious uveitis group included nine patients (60 %) with Behcet's uveitis, five patients (33.3 %) with idiopathic posterior uveitis or panuveitis, and the remaining patient (6.7 %) with HLA-B27 associated uveitis. Comparison of the mean age, sex distribution, mean OCT image quality, mean CMT, presence of IRF, presence of SRF and the mean number of hyperreflective particles in the posterior vitreous area between the two groups showed no statistically significant differences (p = 0.085, p = 0.051, p = 0.748, p = 0.431, p = 0.109, p = 0.080 and p = 0.152, respectively). However, the mean length of the hyperreflective particles in the posterior vitreous area was 27.22 ± 8.60 μm in the TC group, and 21.91 ± 3.58 μm in the NIU group, with a significant difference between the two groups (p = 0.036). ConclusionThis pilot study aimed to assess the hyperreflective particles in the posterior vitreous area using spectral-domain OCT images and image processing software. Despite its limitations, such as the small sample size, limited understanding of the nature of hyperreflective particles, and the absence of differentiation between acute and chronic uveitis, our study points out the potential role of the measurement of the hyperreflective particle length located in the posterior vitreous in differentiating the acute infectious versus non-infectious uveitis as the hyperreflective particles tend to be larger in infectious cases.

FMMAS-OCT: Aberration correction for high-resolution cellular imaging

In optical coherence tomography (OCT), spatial resolution and signal strength often suffer due to aberrations from both the imaging system and the sample. In this work, we introduce a novel method, FMMAS (Forward-Model Multiple Aperture Synthesis), which effectively compensates for these aberrations. It combines forward-model (FM) based method for transverse resolution restoration and multiple aperture synthesis (MAS) to mitigate depth domain aberrations. Our proof-of-concept experiment demonstrates a significant improvement in the mean transverse full width at half maximum (FWHM) of microparticles by 46.1 %. Compared to original OCT and FM method, FMMAS produces sharper, 'pencil beam'-like imaging, resolving cell nuclei in swine esophagus ex vivo and human blood cells in vivo, suggesting a potential for significant enhancements in OCT image quality.

Detecting Structural Changes in the Choroidal Layer of the Eye in Neurodegenerative Disease Patients through Optical Coherence Tomography Image Processing.

To evaluate alterations of the choroid in patients with a neurodegenerative disease versus healthy controls, a custom algorithm based on superpixel segmentation was used. A cross-sectional study was conducted on data obtained in a previous cohort study. Swept-source optical coherence tomography (OCT) B-scan images obtained using a Triton (Topcon, Japan) device were compiled according to current OSCAR IB and APOSTEL OCT image quality criteria. Images were included from three cohorts: multiple sclerosis (MS) patients, Parkinson disease (PD) patients, and healthy subjects. Only patients with early-stage MS and PD were included. In total, 104 OCT B-scan images were processed using a custom superpixel segmentation (SpS) algorithm to detect boundary limits in the choroidal layer and the optical properties of the image. The algorithm groups pixels with similar structural properties to generate clusters with similar meaningful properties. SpS selects and groups the superpixels in a segmented choroidal area, computing the choroidal optical image density (COID), measured as the standard mean gray level, and the total choroidal area (CA), measured as px2. The CA and choroidal density (CD) were significantly reduced in the two neurodegenerative disease groups (higher in PD than in MS) versus the healthy subjects (p < 0.001); choroidal area was also significantly reduced in the MS group versus the healthy subjects. The COID increased significantly in the PD patients versus the MS patients and in the MS patients versus the healthy controls (p < 0.001). The SpS algorithm detected choroidal tissue boundary limits and differences optical density in MS and PD patients versus healthy controls. The application of the SpS algorithm to OCT images potentially acts as a non-invasive biomarker for the early diagnosis of MS and PD.

Super-resolution algorithm for the characterization of sweat glands in fingerprint OCT images.

Optical coherence tomography (OCT) is a noninvasive optical imaging technique that can be used to produce three-dimensional images of fingerprints. However, the low quality and poor resolution of the regions of interest (ROIs) in OCT images make it challenging to segment small tissues accurately. To address this issue, a super-resolution (SR) network called ESRNet has been developed to enhance the quality of OCT images, facilitating their applications in research. Firstly, the performance of the SR images produced by ESRNet is evaluated by comparing it to those generated by five other SR methods. Specifically, the SR performance is evaluated using three upscale factors (2×, 3×, and 4×) to assess the quality of the enhanced images. Based on the results obtained from the three datasets, it is evident that ESRNet outperforms current advanced networks in terms of SR performance. Furthermore, the segmentation accuracy of sweat glands has been significantly improved by the SR images. The number of sweat glands in the top view increased from 102 to 117, further substantiating the performance of the ESRNet network. The spiral structure of sweat glands is clear to human eyes and has been verified by showing similar left-right-handed spiral numbers. Finally, a sweat gland recognition method for the SR 3D images is proposed.

DME-DeepLabV3+: a lightweight model for diabetic macular edema extraction based on DeepLabV3+ architecture.

Diabetic macular edema (DME) is a major cause of vision impairment in the patients with diabetes. Optical Coherence Tomography (OCT) is an important ophthalmic imaging method, which can enable early detection of DME. However, it is difficult to achieve high-efficiency and high-precision extraction of DME in OCT images because the sources of OCT images are diverse and the quality of OCT images is not stable. Thus, it is still required to design a model to improve the accuracy of DME extraction in OCT images. A lightweight model (DME-DeepLabV3+) was proposed for DME extraction using a DeepLabV3+ architecture. In this model, MobileNetV2 model was used as the backbone for extracting low-level features of DME. The improved ASPP with sawtooth wave-like dilation rate was used for extracting high-level features of DME. Then, the decoder was used to fuse and refine low-level and high-level features of DME. Finally, 1711 OCT images were collected from the Kermany dataset and the Affiliated Eye Hospital. 1369, 171, and 171 OCT images were randomly selected for training, validation, and testing, respectively. In ablation experiment, the proposed DME-DeepLabV3+ model was compared against DeepLabV3+ model with different setting to evaluate the effects of MobileNetV2 and improved ASPP on DME extraction. DME-DeepLabV3+ had better extraction performance, especially in small-scale macular edema regions. The extraction results of DME-DeepLabV3+ were close to ground truth. In comparative experiment, the proposed DME-DeepLabV3+ model was compared against other models, including FCN, UNet, PSPNet, ICNet, and DANet, to evaluate DME extraction performance. DME-DeepLabV3+ model had better DME extraction performance than other models as shown by greater pixel accuracy (PA), mean pixel accuracy (MPA), precision (Pre), recall (Re), F1-score (F1), and mean Intersection over Union (MIoU), which were 98.71%, 95.23%, 91.19%, 91.12%, 91.15%, and 91.18%, respectively. DME-DeepLabV3+ model is suitable for DME extraction in OCT images and can assist the ophthalmologists in the management of ocular diseases.

Optical coherence tomography image despeckling based on tensor singular value decomposition and fractional edge detection

Optical coherence tomography (OCT) imaging is a technique that is frequently used to diagnose medical conditions. However, coherent noise, sometimes referred to as speckle noise, can dramatically reduce the quality of OCT images, which has an adverse effect on how OCT images are used. In order to enhance the quality of OCT images, a speckle noise reduction technique is developed, and this method is modelled as a low-rank tensor approximation issue. The grouped 3D tensors are first transformed into the transform domain using tensor singular value decomposition (t-SVD). Then, to cut down on speckle noise, transform coefficients are thresholded. Finally, the inverse transform can be used to produce images with speckle suppression. To further enhance the despeckling results, a feature-guided thresholding approach based on fractional edge detection and an adaptive backward projection technique are also presented. Experimental results indicate that the presented algorithm outperforms several comparison methods in relation to speckle suppression, objective metrics, and edge preservation.

SmartOCT: smartphone-integrated optical coherence tomography.

Smartphone devices have seen unprecedented technical innovation in computational power and optical imaging capabilities, making them potentially invaluable tools in scientific imaging applications. The smartphone's compact form-factor and broad accessibility has motivated researchers to develop smartphone-integrated imaging systems for a wide array of applications. Optical coherence tomography (OCT) is one such technique that could benefit from smartphone-integration. Here, we demonstrate smartOCT, a smartphone-integrated OCT system that leverages built-in components of a smartphone for detection, processing and display of OCT data. SmartOCT uses a broadband visible-light source and line-field OCT design that enables snapshot 2D cross-sectional imaging. Furthermore, we describe methods for processing smartphone data acquired in a RAW data format for scientific applications that improves the quality of OCT images. The results presented here demonstrate the potential of smartphone-integrated OCT systems for low-resource environments.

A Lightweight Swin Transformer-Based Pipeline for Optical Coherence Tomography Image Denoising in Skin Application

Optical coherence tomography (OCT) has attracted attention in dermatology applications for skin disease characterization and diagnosis because it provides high-resolution (&lt;10 μm) of tissue non-invasively with high imaging speed (2–8 s). However, the quality of OCT images can be significantly degraded by speckle noise, which results from light waves scattering in multiple directions. This noise can hinder the accuracy of disease diagnosis, and the conventional frame averaging method requires multiple repeated (e.g., four to six) scans, which is time consuming and introduces motion artifacts. To overcome these limitations, we proposed a lightweight U-shape Swin (LUSwin) transformer-based denoising pipeline to recover high-quality OCT images from the noisy OCT images by utilizing a fast one-repeated OCT scan. In terms of the peak signal-to-noise-ratio (PSNR) performance, the results reveal that the denoised images from the LUSwin transformer (26.92) are of a higher quality than the four-repeated frame-averaging method (26.19). Compared to the state-of-the-art networks in image denoising, the proposed LUSwin transformer has the smallest floating points operation (3.9299 G) and has the second highest PSNR results, only 0.02 lower than the Swin-UNet, which has the highest PSNR results (26.94). This study demonstrates that the transformer model has the capacity to denoise the noisy OCT image from a fast one-repeated OCT scan.

Speckle attenuation for optical coherence tomography images using the generalized low rank approximations of matrices.

A frequently used technology in medical diagnosis is optical coherence tomography (OCT). However, coherent noise, also known as speckle noise, has the potential to severely reduce the quality of OCT images, which would be detrimental to the use of OCT images for disease diagnosis. In this paper, a despeckling method is proposed to effectively reduce the speckle noise in OCT images using the generalized low rank approximations of matrices (GLRAM). Specifically, the Manhattan distance (MD)-based block matching method is first used to find nonlocal similar blocks for the reference one. The left and right projection matrices shared by these image blocks are then found using the GLRAM approach, and an adaptive method based on asymptotic matrix reconstruction is proposed to determine how many eigenvectors are present in the left and right projection matrices. Finally, all the reconstructed image blocks are aggregated to create the despeckled OCT image. In addition, an edge-guided adaptive back-projection strategy is used to improve the despeckling performance of the proposed method. Experiments with synthetic and real OCT images show that the presented method performs well in both objective measurements and visual evaluation.

Predicting OCT images of short-term response to anti-VEGF treatment for retinal vein occlusion using generative adversarial network.

To generate and evaluate post-therapeutic optical coherence tomography (OCT) images based on pre-therapeutic images with generative adversarial network (GAN) to predict the short-term response of patients with retinal vein occlusion (RVO) to anti-vascular endothelial growth factor (anti-VEGF) therapy. Real-world imaging data were retrospectively collected from 1 May 2017, to 1 June 2021. A total of 515 pairs of pre-and post-therapeutic OCT images of patients with RVO were included in the training set, while 68 pre-and post-therapeutic OCT images were included in the validation set. A pix2pixHD method was adopted to predict post-therapeutic OCT images in RVO patients after anti-VEGF therapy. The quality and similarity of synthetic OCT images were evaluated by screening and evaluation experiments. We quantitatively and qualitatively assessed the prognostic accuracy of the synthetic post-therapeutic OCT images. The post-therapeutic OCT images generated by the pix2pixHD algorithm were comparable to the actual images in edema resorption response. Retinal specialists found most synthetic images (62/68) difficult to differentiate from the real ones. The mean absolute error (MAE) of the central macular thickness (CMT) between the synthetic and real OCT images was 26.33 ± 15.81 μm. There was no statistical difference in CMT between the synthetic and the real images. In this retrospective study, the application of the pix2pixHD algorithm objectively predicted the short-term response of each patient to anti-VEGF therapy based on OCT images with high accuracy, suggestive of its clinical value, especially for screening patients with relatively poor prognosis and potentially guiding clinical treatment. Importantly, our artificial intelligence-based prediction approach’s non-invasiveness, repeatability, and cost-effectiveness can improve compliance and follow-up management of this patient population.

Optical coherence tomography image despeckling based on edge feature-guided higher-order singular value decomposition

As an emerging tomographic technique, optical coherence tomography (OCT) has been widely used in clinical practice in a short period of time. Unfortunately, the quality of OCT images is inevitably deteriorated by the coherent noise known as speckle noise. To effectively reduce the speckle noise in OCT images while preserving local structures, we present a speckle noise reduction method based on feature-guided higher-order singular value decomposition (HOSVD). Specifically, the grouped 3D tensors are first decomposed by HOSVD. And then, the corresponding core tensors are thresholded according to the Eckart-Young-Mirsky theorem and are shrunk by the dectected edge features, which are defined as the local mean absolute deviation (LMAD). Finally, the filtered OCT images can be obtained by the inverse transform and an aggregation strategy. Compared with several state-of-the-art methods, the proposed method has better performance on despeckling OCT images in terms of both speckle noise reduction and edge preservation.

One-Step Enhancer: Deblurring and Denoising of OCT Images

Optical coherence tomography (OCT) is a rapidly evolving imaging technology that combines a broadband and low-coherence light source with interferometry and signal processing to produce high-resolution images of living tissues. However, the speckle noise introduced by the low-coherence interferometry and the blur from device motions significantly degrade the quality of OCT images. Convolutional neural networks (CNNs) are a potential solution to deal with these issues and enhance OCT image quality. However, training such networks based on traditional supervised learning methods is impractical due to the lack of clean ground truth images. Consequently, this research proposes an unsupervised learning method for OCT image enhancement, termed one-step enhancer (OSE). Specifically, OSE performs denoising and deblurring based on a single step process. A generative adversarial network (GAN) is used for this. Encoders disentangle the raw images into a content domain, blur domain and noise domain to extract features. Then, the generator can generate clean images from the extracted features. To regularize the distribution range of retrieved blur characteristics, KL divergence loss is employed. Meanwhile, noise patches are enforced to promote more accurate disentanglement. These strategies considerably increase the effectiveness of GAN training for OCT image enhancement when used jointly. Both quantitative and qualitative visual findings demonstrate that the proposed method is effective for OCT image denoising and deblurring. These results are significant not only to provide an enhanced visual experience for clinicians but also to supply good quality data for OCT-guide operations. The enhanced images are needed, e.g., for the development of robust, reliable and accurate autonomous OCT-guided surgical robotic systems.

The Use of Optical Coherence Tomography for Gross Examination and Sampling of Fixed Breast Specimens: A Pilot Study.

Thorough gross examination of breast cancer specimens is critical in order to sample relevant portions for subsequent microscopic examination. This task would benefit from an imaging tool which permits targeted and accurate block selection. Optical coherence tomography (OCT) is a non-destructive imaging technique that visualizes tissue architecture and has the potential to be an adjunct at the gross bench. Our objectives were: (1) to familiarize pathologists with the appearance of breast tissue entities on OCT; and (2) to evaluate the yield and quality of OCT images of unprocessed, formalin-fixed breast specimens for the purpose of learning and establishment of an OCT–histopathology library. Methods: Firstly, 175 samples from 40 formalin-fixed, unprocessed breast specimens with residual tissue after final diagnosis were imaged with OCT and then processed into histology slides. Histology findings were correlated with features on OCT. Results: Residual malignancy was seen in 30% of tissue samples. Corresponding OCT images demonstrated that tumor can be differentiated from fibrous stroma, based on features such as irregular boundary, heterogeneous texture and reduced penetration depth. Ductal carcinoma in situ can be subtle, and it is made more recognizable by the presence of comedo necrosis and calcifications. OCT features of benign and malignant breast entities were compiled in a granular but user-friendly reference tool. Conclusion: OCT images of fixed breast tissue were of sufficient quality to reproduce features of breast entities previously described in fresh tissue specimens. Our findings support the use of readily available unprocessed, fixed breast specimens for the establishment of an OCT–histopathology library.

DHNet: High-resolution and hierarchical network for cross-domain OCT speckle noise reduction.

Optical coherence tomography (OCT) imaging uses the principle of Michelson interferometry to obtain high-resolution images by coherent superposing of multiple forward and backward scattered light waves with random phases. This process inevitably produces speckle noise that severely compromises visual quality of OCT images and degrades performances of subsequent image analysis tasks. In addition, datasets obtained by different OCT scanners have distribution shifts, making a speckle noise suppression model difficult to be generalized across multiple datasets. In order to solve the above issues, we propose a novel end-to-end denoising framework for OCT images collected by differentscanners. The proposed model utilizes the high-resolution network (HRNet) as backbone for image restoration, which reconstructs high-fidelity images by maintaining high-resolution representations throughout the entire learning process. To compensate distribution shifts among datasets collected by different scanners, we develop a hierarchical adversarial learning strategy for domain adaption. The proposed model is trained using datasets with clean ground truth produced by two commercial OCT scanners, and then applied to suppress speckle noise in OCT images collected by our recently developed OCT scanner, BV-1000 (China Bigvision Corporation). We name the proposed model as DHNet (Double-H-Net, High-resolution and Hierarchical Network). We compare DHNet with state-of-the-art methods and experiment results show that DHNet improves signal-to-noise ratio by a large margin of 18.137 dB as compared to the best of our previous method. In addition, DHNet achieves a testing time of 25 ms, which satisfies the real-time processing requirement for the BV-1000 scanner. We also conduct retinal layer segmentation experiment on OCT images before and after denoising and show that DHNet can also improvesegmentation. The proposed DHNet can compensate domain shifts between different data sets while significantly improve speckle noise suppression. The HRNet backbone is utilized to carry low- and high-resolution information to recover fidelity images. Domain adaptation is achieved by a hierarchical module through adversarial learning. In addition, DHNet achieved a testing time of 25 ms, which satisfied the real-time processingrequirement.

Despeckling of OCT images using DT-CWT based fusion technique

Optical Coherence Tomography (OCT) is a non-invasive diagnostic method used to identify and manage a variety of retinal illnesses. However, the OCT image formation method gives rise to speckle noise that can drastically degrade the quality of OCT images. These low-quality images have a detrimental effect on subsequent illness diagnoses. There are numerous software-based speckle reduction techniques, each with its own advantages. Hence, combining even some of them maximizes the benefits. We propose a fusion approach based on spatial domain filtering and a sparsity-based denoising method for speckle noise removal in OCT images. Our hybrid methodology employs the Dual-Tree Complex Wavelet Transform (DT-CWT) to integrate both spatial domain filtering and the sparsity-based denoising method and uses a multi-scale fusion technique to merge the two transformed output images. Experimental findings indicate that the proposed algorithm could successfully combine two images, resulting in an output OCT image with significant speckle reduction and image structure preservation.

Prediction of the Short-Term Therapeutic Effect of Anti-VEGF Therapy for Diabetic Macular Edema Using a Generative Adversarial Network with OCT Images.

Purpose: To generate and evaluate individualized post-therapeutic optical coherence tomography (OCT) images that could predict the short-term response of anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) based on pre-therapeutic images using generative adversarial network (GAN). Methods: Real-world imaging data were collected at the Department of Ophthalmology, Qilu Hospital. A total of 561 pairs of pre-therapeutic and post-therapeutic OCT images of patients with DME were retrospectively included in the training set, 71 pre-therapeutic OCT images were included in the validation set, and their corresponding post-therapeutic OCT images were used to evaluate the synthetic images. A pix2pixHD method was adopted to predict post-therapeutic OCT images in DME patients that received anti-VEGF therapy. The quality and similarity of synthetic OCT images were evaluated independently by a screening experiment and an evaluation experiment. Results: The post-therapeutic OCT images generated by the GAN model based on big data were comparable to the actual images, and the response of edema resorption was also close to the ground truth. Most synthetic images (65/71) were difficult to differentiate from the actual OCT images by retinal specialists. The mean absolute error (MAE) of the central macular thickness (CMT) between the synthetic OCT images and the actual images was 24.51 ± 18.56 μm. Conclusions: The application of GAN can objectively demonstrate the individual short-term response of anti-VEGF therapy one month in advance based on OCT images with high accuracy, which could potentially help to improve treatment compliance of DME patients, identify patients who are not responding well to treatment and optimize the treatment program.

Unsupervised despeckling of optical coherence tomography images by combining cross-scale CNN with an intra-patch and inter-patch based transformer.

Optical coherence tomography (OCT) has found wide application to the diagnosis of ophthalmic diseases, but the quality of OCT images is degraded by speckle noise. The convolutional neural network (CNN) based methods have attracted much attention in OCT image despeckling. However, these methods generally need noisy-clean image pairs for training and they are difficult to capture the global context information effectively. To address these issues, we have proposed a novel unsupervised despeckling method. This method uses the cross-scale CNN to extract the local features and uses the intra-patch and inter-patch based transformer to extract and merge the local and global feature information. Based on these extracted features, a reconstruction network is used to produce the final denoised result. The proposed network is trained using a hybrid unsupervised loss function, which is defined by the loss produced from Nerighbor2Neighbor, the structural similarity between the despeckled results of the probabilistic non-local means method and our method as well as the mean squared error between their features extracted by the VGG network. Experiments on two clinical OCT image datasets show that our method performs better than several popular despeckling algorithms in terms of visual evaluation and quantitative indexes.