DEVELOPMENT AND VALIDATION OF AN EXPLAINABLE ARTIFICIAL INTELLIGENCE FRAMEWORK FOR MACULAR DISEASE DIAGNOSIS BASED ON OPTICAL COHERENCE TOMOGRAPHY IMAGES.

PURPOSE: To develop and validate an artificial intelligence framework for identifying multiple retinal lesions at image level and performing an explainable macular disease diagnosis at eye level in optical coherence tomography images. METHODS: A total of 26,815 optical coherence tomography images were collected from 865 eyes, and 9 retinal lesions and 3 macular diseases were labeled by ophthalmologists, including diabetic macular edema and dry/wet age-related macular degeneration. We applied deep learning to classify retinal lesions at image level and random forests to achieve an explainable disease diagnosis at eye level. The performance of the integrated two-stage framework was evaluated and compared with human experts. RESULTS: On testing data set of 2,480 optical coherence tomography images from 80 eyes, the deep learning model achieved an average area under curve of 0.978 (95% confidence interval, 0.971-0.983) for lesion classification. In addition, random forests performed accurate disease diagnosis with a 0% error rate, which achieved the same accuracy as one of the human experts and was better than the other three experts. It also revealed that the detection of specific lesions in the center of macular region had more contribution to macular disease diagnosis. CONCLUSION: The integrated method achieved high accuracy and interpretability in retinal lesion classification and macular disease diagnosis in optical coherence tomography images and could have the potential to facilitate the clinical diagnosis.

Optical coherence tomography-based short-term effect prediction of anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration using sensitive structure guided network.

PURPOSE: To predict short-term anti-vascular endothelial growth factor (anti-VEGF) treatment responder/non-responder for neovascular age-related macular degeneration (nAMD) patients based on optical coherence tomography (OCT) images. METHODS: A total of 4944 OCT scans from 206 patients with nAMD were involved to develop and evaluate a responder/non-responder prediction method for the short-term effect of anti-VEGF therapy. A deep learning architecture named sensitive structure guided network (SSG-Net) was proposed to make the prediction leveraging a sensitive structure guidance module trained from pre- and post-treatment images. To verify its clinical efficiency, other 2 deep learning methods and 4 experienced ophthalmologists were involved to evaluate the performance of the developed model. RESULTS: For the testing dataset, SSG-Net could predict the response by an accuracy of 84.6% and an area under the receiver curve (AUC) of 0.83, with a sensitivity of 0.692 and specificity of 1. In contrast, the 2 compared deep learning methods achieved an accuracy of 65.4% with a sensitivity of 0.461 and specificity of 0.846, and an accuracy of 73.1% with a sensitivity of 0.692 and specificity of 0.846, respectively. The predicted accuracy for 4 experienced ophthalmologists was 53.8 to 76.9%, with sensitivity of 0.538 to 0.923 and specificity of 0.385 to 0.846, respectively. CONCLUSION: Our proposed SSG-Net shows effective prediction on the short-term efficacy of anti-VEGF treatment for nAMD patients. This technique could potentially help clinicians explain the necessity of anti-VEGF treatment to the potential responder and avoid unnecessary treatment for the non-responder.

Optimized star sensors laboratory calibration method using a regularization neural network.

High-precision ground calibration is essential to ensure the performance of star sensors. However, the complex distortion and multi-error coupling have brought great difficulties to traditional calibration methods, especially for large field of view (FOV) star sensors. Although increasing the complexity of models is an effective way to improve the calibration accuracy, it significantly increases the demand for calibration data. In order to achieve high-precision calibration of star sensors with large FOV, a novel laboratory calibration method based on a regularization neural network is proposed. A multi-layer structure neural network is designed to represent the mapping of the star vector and the corresponding star point coordinate directly. To ensure the generalization performance of the network, regularization strategies are incorporated into the net structure and the training algorithm. Simulation and experiment results demonstrate that the proposed method can achieve high precision with less calibration data and without any other priori information. Compared with traditional methods, the calibration error of the star sensor decreased by about 30%. The proposed method can satisfy the precision requirement for large FOV star sensors.

On-orbit calibration for star sensors without priori information.

The star sensor is a prerequisite navigation device for a spacecraft. The on-orbit calibration is an essential guarantee for its operation performance. However, traditional calibration methods rely on ground information and are invalid without priori information. The uncertain on-orbit parameters will eventually influence the performance of guidance navigation and control system. In this paper, a novel calibration method without priori information for on-orbit star sensors is proposed. Firstly, the simplified back propagation neural network is designed for focal length and main point estimation along with system property evaluation, called coarse calibration. Then the unscented Kalman filter is adopted for the precise calibration of all parameters, including focal length, main point and distortion. The proposed method benefits from self-initialization and no attitude or preinstalled sensor parameter is required. Precise star sensor parameter estimation can be achieved without priori information, which is a significant improvement for on-orbit devices. Simulations and experiments results demonstrate that the calibration is easy for operation with high accuracy and robustness. The proposed method can satisfy the stringent requirement for most star sensors.

A novel splice site mutation in the COL4A5 gene in a Chinese female patient with rare ocular abnormalities.

PURPOSE: To describe an unusual ocular phenotype in a Chinese female patient with X-linked Alport syndrome (XLAS), and to characterize the type IV collagen alpha 5 (COL4A5) gene mutation in the patient and her son. METHODS: Detailed ophthalmologic examinations and optical coherence tomography were performed in the patient and her family members. For gene analysis of COL4A5, the entire coding region of COL4A5 mRNA from cultured skin fibroblast was analyzed by using reverse-transcription-polymerase chain reaction (RT-PCR) and direct sequencing, and genomic DNA was analyzed by using PCR and direct sequencing. RESULTS: The patient presented with progressive myopia at age 14 and bilateral giant macular holes (about 2 disc diameter) at age 28. At age 33 when presented to our hospital, slit lamp examination of the anterior segment showed bilateral anterior and posterior lenticonus; fundus photography and optical coherence tomography showed bilateral giant macular holes which were larger than photographed at age 28. Electron microscopy of renal biopsy showed irregular thinned and thickened areas of the glomerular basement membrane with splitting of the lamina densa. Her son was then found to have hematuria (at age 3), and indirect immunofluorescence of the epidermal basement membrane showed negative staining for the collagen α5(IV) chain. However, the ophthalmological examinations of her son were unremarkable. A novel COL4A5 mutation g. 4400_4400+1del, leading to an indel in exon 45 (r. 4198delins4198+2_ 4198+72), was detected in the patient and her son. This mutation produces a shift in the reading frame, resulting in a missense sequence of 13 codons followed by a premature stop codon. Her mother was not affected with the mutation. CONCLUSIONS: Our report extends the phenotypic and genotypic spectrum of X-linked Alport syndrome.

[Relationship between central visual acuity and retinal volume of macular fovea accessed by spectral domain optical coherence tomography in Stargardt disease].

OBJECTIVE: To assess the relationship between central visual acuity and retinal volume of macular fovea in patients with Stargardt disease by spectral-domain optical coherence tomography (SD OCT). METHODS: It was a retrospective case series study. Twenty eyes of 10 patients with Stargardt disease were investigated by three-dimensional spectral-domain optical coherence tomography. SD OCT images were obtained and retrospectively analyzed. The retinal volumes of macular fovea were measured by SD OCT, whose diameters were set as 3 mm and 1 mm separately (volume 3 and volume 1). The retinal thickness of macular fovea (macular thickness) and the width of IS/OS conjunction loss of macular fovea (IS/OS loss) were also measured by SD OCT. We correlated the logMAR BCVA with IS/OS loss, macular thickness, volume 3 and volume 1 by linear regression analysis. RESULTS: LogMAR BCVA was from 0.3 to 1.22. IS/OS loss was from 847 µm to 5306 µm. Macular thickness was from 20 µm to 126 µm. Volume 3 and volume 1 was from 1.06 to 1.76 mm(3) and 0.06 to 0.13 mm(3). LogMAR BCVA correlated with the IS/OS loss (r = 0.695, P < 0.05), macular thickness (r = -0.601, P < 0.05), and volume 3(r = -0.725, P < 0.05). LogMAR BCVA did not correlate with volume 1(r = -0.364, P > 0.05). CONCLUSIONS: SD OCT could demonstrate the retinal structure of Stargardt disease clearly. The retinal volume of macular fovea accessed by SD OCT correlated with the visual acuity of Stargardt disease.

[Clinical manifestation and follow-up of melanocytoma of the optic disc].

OBJECTIVE: To investigate the clinical manifestation and follow-up of melanocytoma of the optic disc. METHODS: Retrospective case series study was taken to study the clinical data of the cases with melanocytoma of the optic disc at Peking Union Medical College Hospital from 1978 to 2007. The examination included direct and indirect ophthalmoscopy, fundus photography, fundus fluorescein angiography (FFA), fundus indocyanine green angiography (ICGA), optical coherence tomography (OCT) and B-scan. The clinical manifestation and the outcome in follow-up period were analyzed. RESULTS: Ten cases aged 31-58 years (mean 43 years) were included in this study. Among them, 9 cases were male, 1 case was female. All cases were unilateral involved, 5 cases were right eye, 5 cases were left eye. The distribution of the visual acuity was follows: light perception in 2 eyes, 20/200 in one eye, 20/20 or above in 7 eyes. The tumor mass at the optic disc with extensive serous detachment of retina was detected on B-scan in one eye. The benign melanocytoma was diagnosed by vitreous fine needle biopsy for this eye. In other case, the tumor was found to be enlarged, visual field defect deteriorated, pigment granules appeared in the vitreous adjacent to the tumor during on year follow-up period. On the patient request, enucleation was performed to rule out the malignancy of the tumor. Pathologic study showed that the tumor cells were active, but benign state. The tumor size and visual acuity in other eight eyes remained stable in the follow-up period with one to 18 years (mean 3.5 years). On FFA and ICGA, bilateral choroidal nevi were found in one eye. CONCLUSIONS: Melanocytoma of the optic disc is a benign tumor that rarely causes visual impairment. However, visual acuity may be impaired due to enlargement of the tumor or necrosis in tumor. It is important to follow-up every case with melanocytoma of the optic disc as long as possible.

[Follow-up and management of Coats disease diagnosed in childhood].

OBJECTIVE: To investigate retrospectively the clinical manifestation and the final visual prognosis through a long-term fellow-up study. METHODS: It was retrospective case series study. Twenty four patients (26 eyes) were diagnosed with Coats disease from 1962 through 2006 at the Department of Ophthalmology, Peking Union Medical Hospital, Chinese Academy of Medical Sciences. Age, visual acuity, time of initial visit, method of treatment and the condition of eye fundus for each patient were documented. The time of follow-up ranged from 1-44 years, averaged 5 years. RESULTS: Age of the patients at initial visit ranged between 1 to 18 years old, 7 years on average. Eighteen patients (75%) were male and 6 were female (25%). Twenty two cases were unilateral and only 2 female patients were bilateral. In 26 eyes, 7 eyes exhibited capillary irregular dilatation, miliary aneurysms and nonperfusion area on fluorescein angiography located at peripheral fundus; 15 eyes were complicated with exudative retinal detachment. Four eyes reached end stage with no light perception or only finger count. Laser photocoagulation was performed in 21 eyes. In 10 eyes, retinal exudates and hemorrhages were absorbed with improvement of visual acuity. Ten eyes with extensive retinal detachment including macula underwent closed vitrectomy, the best visual acuity was 0.1 after surgery. CONCLUSIONS: The onset of Coats disease is in early young childhood. Abnormal vascular lesions and military aneurysms appeared at peripheral fundus with early retinal exudation involving the macula. Early treatment with laser coagulation could obtain good visual prognosis. The supplement treatment is required for new lesions occurring during the long- term follow-up period.

[Long-term follow-up and management of choroidal osteoma].

OBJECTIVE: To report the clinical characteristics, long-term follow-up and management of choroidal osteoma. METHODS: Eighteen eyes of 12 cases (5 male and 7 female) of choroidal osteoma were studied. Best corrected vision, intraocular pressure, perimetry, anterior segment and eye fundus were examined routinely. Special tests included phytochrome of eye fundus, fluorescein angiography and/or indocyanine green angiography; B-ultrasonogram, CT, perimetry and electrophysiology. (1) Eight eyes of 6 cases treated with vitamins and anti-inflammatory drug and followed-up periodically for 1-26 years (median 2.5 years). (2) Four eyes of 2 cases were treated with Krypton laser photocoagulation, 2 of them were superimposed with transpupillary thermotherapy (TTT). (3) TTT was given primarily for 6 eyes of 4 cases with infrared dione laser; the spot size was 3 mm, 1-5 spots were conducted conjunctly to cover the tumor surface. Power was 800-1200 mw at 60-90 seconds. The procedure was completed in 1-3 recessions with an interval of 4-6 weeks. RESULTS: (1) In the medical treatment group, gradual growth of the tumor with pseudopodium along the margin was disclosed. One eye showed spontaneously regression during the long-term follow-up. (2) Laser photocoagulation was effective for 2 eyes, but residual flat serous detachment around the optic disc persisted in another 2 eyes and subsided with TTT. (3) Choroidal osteoma complicated with CNV treated primarily with TTT, prominent improvement was demonstrated. CONCLUSIONS: Choroidal osteoma grows gradually in the natural course and shows pseudopodial margin. Laser photocoagulation was effective for certain cases. TTT is a method of choice either used primarily or supplementary after laser photocoagulation, it is recommended for cases complicated with CNV.

[Anticardiolipin antibodies and ocular diseases].

Anticardiolipin antibodies are a group of autoantibodies. It has been found that these antibodies were associated with thrombosis, recurrent spontaneous abortions and thrombocytopenia. This paper reviews the latest findings about the epidemiology, the mechanism for immunopathology, main systemic features, ocular features, diagnosis, differential diagnosis, prevention and treatment of anticardiolipin antibodies syndrome.

[Clinical trial of verteporfin photodynamic therapy in Chinese age-related macular degeneration with subfoveal predominant choroidal neovascularization patients].

OBJECTIVE: To determine the safety and efficacy of verteporfin (visudyne) photodynamic therapy in age-related macular degeneration patients with subfoveal predominant choroidal neovascularization in China. METHODS: Multicenter, open-label, non-controlled clinical study. The included patients are diagnosed AMD patients with predominant classic CNV. The included patients received verteporfin intravenously followed by 689 nm laser light administration 15 minutes after the infusion start. The patients were be followed up for 24 weeks (+/-12 days) after initial verteporfin PDT treatment. Clinical follow-up was done at the end of week 12 (+/-12 days) and week 24 (+/-12 days) after the initial treatment. Additional treatment was given after 12 weeks from initial treatment if leakage from CNV was observed on fundus fluorescein angiogram. The visual acuity with ETDRS visual chart and the retinal lesion changes were documented and compared with baseline. The adverse events both in the process of treatment and in the follow-up were recorded throughout the entire study period. RESULTS: Thirty-one patients (31 eyes) were included and completed the trial with verteporfin PDT treatment. During the 24 weeks of the trial, 38.7% of the treated eyes had a vision gain more than 5 letters, 83.9% of the treated eyes had less than 15 letters vision loss. At week 12 after the initial treatment, 12.9% of the treated eyes had no leakage; 61.3% of the treated eyes had leakages, but limited to the former lesion, 25.8% of the treated eyes had increased leakage. The results at week 24 after the initial treatment were similar to those at week 12. At week 24 after the initial treatment, there were only slight enlargements in the lesion size, area of retinal lesion, the lesion surrounding area, and greatest linear dimension (GLD) of the lesion, but no statistical significant difference was found between baseline and week 12 after initial treatment (P = 0.65, 0.31, 0.12, respectively). No obvious progress of the fibrosis was detected in most of the PDT treated eyes. Eleven cases of adverse events (AE) occurred in our trial and the incidence was 34.4%. Among the 11 patients with reported adverse event, 7 (21.9%) had mild adverse event; 3 (9.4%) had moderate adverse events; 1 (3.1%) had a serious adverse event. During the study period, no abnormal changes were found in most of the laboratory tests including serum and urine biochemistry, hematology and Electrocardiogram. CONCLUSIONS: The results of this trial showed positive efficacy of PDT with verteporfin in the treatment of predominantly subfoveal CNV secondary to AMD by reducing the risk of vision loss. The incidence of serious adverse events was only 3.1%. It is highly safe to use PDT with verteporfin in Chinese AMD patients with subfoveal predominant classical CNV.

[Transpupillary thermotherapy for circumscribed choroidal hemangioma].

OBJECTIVE: To evaluate the efficacy of transpupillary thermotherapy (TTT) on circumscribed choroidal hemangioma. METHODS: Ten eyes of 10 cases with circumscribed choroidal hemangioma (age 16-48, average 34.4) were included in the present study. Six cases had previous green laser (4 argon and 2 krypton) photocoagulation, TTT as a primary treatment was used for other 4 cases without previous laser application. Fluorescein angiography, visual acuity, anterior segment and fundus examination, perimetry test, FFA/ICGA and ultrasonography were performed in all patients before the treatment. One to five infra red diode laser spots (810 nm with power of 800-1200 mW, diameter of 3 mm) were delivered on the surface of tumor with 60 seconds exposure, additional 10-20 seconds exposure was used in some cases. Second treatment was given 1-3 month later if there was active leakage demonstrated by fluorescein angiography. The followed-up period was 6-36 months (averaged 14.5 month). RESULTS: After transpupillary thermotherapy, 9 eyes (90%) showed partial regression of the tumor. Average visual acuity was 0.25 and 0.6 before and after TTT, respectively. Six patients showed improvement of vision acuity, but vision acuity in 4 patients with cystic macular degeneration remained unchanged. No recurrences were observed within follow-up averaged 14.5 months. Transpupillary thermotherapy did not associate with any significant complications. CONCLUSION: Transpupillary thermotherapy is effective to treat circumscribed hemangioma of choroid either as a primary treatment or supplementary therapy to previous laser photocoagulation.

[Krypton laser photocoagulation at low power setting for age-related macular degeneration complicated with subfoveal choroidal neovascularization].

OBJECTIVE: To evaluate the efficacy of krypton laser photocoagulation for treatment of age-related macular degeneration (AMD) complicated with mainly subfoveal classic choroidal neovascularization (CNV). METHODS: Seventeen eyes of 17 cases, aged 50 - 74 years (averaged 60.8 years) with mainly subfoveal classic choroidal neovascularization were treated with krypton laser at lower power setting. The treatment was completed in one session. Another course of treatment was given 4 weeks later if there was active leakage demonstrated at the CNV area. Visual acuity, anterior segment and fundus examination, perimetry test, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed before and after treatment. The follow-up period was 3.5 years on average (1 - 8 years). RESULTS: There was no immediately decrease of visual acuity after treatment. All treated eyes showed absorption of hemorrhages and/or exudates and diminished leakages. Visual acuity was stable in 8 eyes; improved in 6 eyes (>/= 2 lines), and decreased in 3 eyes (

[Natural course and prognosis of visual acuity in patients of age-related macular degeneration with occult choroidal neovascularization].

OBJECTIVE: To investigate the natural course and the final visual acuity in patients of age-related macular degeneration with choroidal neovascularization. METHODS: Thirty five eyes of 29 patients diagnosed as AMD with occult choroidal neovascularization were studied. The eyes which had laser, radiation therapy or surgical treatment were excluded. Visual acuity, fundus examination, fluorescent angiography (FFA) and perimetry test were performed at the first time visit and 5 years following-up at an interval of 1 to 3 months. The average following-up period of time was 8 years (range from 5 to 16 years) which started in 1985 and ended in 2001. RESULTS: Initial visual acuity 0.1 or less was shown in 10 eyes (28.5%, only hands movement can be seen in 4 of 10 eyes), 23 eyes (65.7%) with visual acuity of 0.1 or less (14 eyes with vision acuity of hands movement) on the last visit. 7 of 35 eyes, the final visual acuity improved more than 2 lines, 12 eyes remained the same and 16 eyes had been lost vision more than two lines. At the baseline examination, 25 eyes had macular hemorrhages and 4 eyes had vitreous hemorrhages. The fundus hemorrhages occurred repeatedly 1 to 4 times in 23 eyes during following-up, the macular hemorrhages was detected in 7 eyes at the last visit. At the initial fundus examination, fibrotic membranes were found in 7 eyes; all 35 eyes had disc form scarring with various size in most recent following-up. CONCLUSION: The natural course of Age-related macular degeneration with choroidal neovascularization is prolonged and the final visual prognosis was poor especially in the cases with recurrent macular hemorrhages.

[Analysis of articles on ocular fundus diseases in Chinese medical journals].

OBJECTIVE: To find out evidence for the improvement of research resources of ocular fundus diseases in China. DATA SOURCES RESEARCH: articles about fundus oculi in 418 Chinese medical journals published in the mainland of China from January 1, 1999 to June 30, 2001. DATA SELECTION: A total of 2 352 articles about ocular fundus diseases included 1 651 original articles, 324 case reports, and 171 reviews. The original articles covered basic research (402 articles), clinical research (530), treatment with combined traditional Chinese and Western medicine (270), clinical application of testing technology (295), epidemiology (142), and others (12). RESULTS: Data showed that retinal detachment, trauma, retinal vein occlusion, and diabetic retinopathy were the major areas of clinical research. Ophthalmology periodicals published most of the achievements in the research of ocular fundus diseases, while less in general medical journals. Yet, reports on critical evaluation of these treatments were not available. The resources of research and utilization in ocular fundus diseases in China had not been documented. CONCLUSIONS: The research into ocular fundus diseases is an active area in China. Critical evaluation and application of the research resources of ocular fundus diseases should be improved.