With the rapid development of artificial intelligence, computational pathology has been seamlessly integrated into the entire clinical workflow, which encompasses diagnosis, treatment, prognosis, and biomarker discovery. This integration has significantly enhanced clinical accuracy and efficiency while reducing the workload for clinicians. Traditionally, research in this field has depended on the collection and labeling of large datasets for specific tasks, followed by the development of task-specific computational pathology models. However, this approach is labor intensive and does not scale efficiently for open-set identification or rare diseases. Given the diversity of clinical tasks, training individual models from scratch to address the whole spectrum of clinical tasks in the pathology workflow is impractical, which highlights the urgent need to transition from task-specific models to foundation models (FMs). In recent years, pathological FMs have proliferated. These FMs can be classified into three categories, namely, pathology image FMs, pathology image-text FMs, and pathology image-gene FMs, each of which results in distinct functionalities and application scenarios. This review provides an overview of the latest research advancements in pathological FMs, with a particular emphasis on their applications in oncology. The key challenges and opportunities presented by pathological FMs in precision oncology are also explored.
Humans ; Precision Medicine/methods* ; Medical Oncology/methods* ; Artificial Intelligence ; Neoplasms/pathology* ; Computational Biology/methods*

Objective:To assess the efficacy and safety of the treat-and-extend (TAE) regimen and pro re nata (PRN) regimen of intravitreal conbercept in polypoidal choroidal vasculopathy (PCV) patients.Methods:A non-randomized controlled study was performed.Ninety-one patients (91 eyes) diagnosed with treatment-na?ve PCV from October 2016 to January 2019 at Department of Ophthalmology, Peking University People's Hospital were enrolled.All the patients received the intravitreal injection of 0.5 mg conbercept.After the initial treatment, the patients were divided into 3+ PRN group and 3+ TAE group according to their willingness.The follow-up time was one year.All the eyes underwent visual acuity test with ETDRS chart, optical coherence tomography (OCT) examination, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA). Best corrected visual acuity (BCVA), central retinal thickness (CRT), maximum retinal thickness (MRT), pigment epithelium detachment (PED) height, the number and area of polypoidal lesions, the area of retinal hemorrhage and the area of branching vascular network (BVN) were recorded.Treatment interval and injection frequencies during the one-year follow-up were compared between the two groups.This study adhered to the Declaration of Helsinki.The study protocol was approved by Peking University People's Hospital (No.2020PHB250-01). Written informed consent was obtained from each patient.Results:One-year after treatment, the BCVA improvement in the 3+ PRN group and 3+ TAE group was 5.0(-2.0, 15.0) and 6.0(-1.0, 14.0) letters, respectively, showing no significant difference ( Z=-0.352, P=0.725). No significant differences were found in CRT, MRT and PED height between the two groups ( Z=-0.145, -0.529, -0.985, all at P>0.05). There was no significant difference in polypoidal lesions number, polypoidal lesions area, the number of eyes with different degrees of polyp regression, BVN area and retinal hemorrhage area between the two groups ( Z=-0.502, -0.300, -0.047, -0.265, -1.243, all at P>0.05). After the one-year follow-up, the mean injection frequency of 3+ PRN group was (7.6±0.9) times, which was lower than (8.4±2.0) times of 3+ TAE group, showing a significant difference ( t=2.432, P=0.019). The mean follow-up frequency was (11.3±1.5) times of 3+ PRN group, which was significantly higher than (10.1±1.7) times of 3+ TAE group ( t=3.403, P=0.001). For the 3+ TAE group, 17.1%(6/35) of patients achieved an extension interval of 12 weeks after the first 3 doses, and 48.5%(17/35) of patients achieved an extension interval of 8 weeks or more, with a mean maximum extension interval of (9.5±2.0) weeks.During the follow-up, 10 patients in 3+ PRN group and 8 patients in 3+ TAE group received photodynamic therapy as a rescue treatment. Conclusions:The 3+ PRN and 3+ TAE regimens of intravitreal injection of conbercept combined with photodynamic therapy as a rescue treatment have similar efficacy in visual and anatomical outcomes for PCV patients.3+ TAE regimen has a higher treatment frequency and fewer follow-up visits.

Neurodegenerative diseases are a type of disease characterized by specific types of neuronal loss and progressive progression,mainly represented by Alzheimer's disease and Parkinson's disease.This type of disease,due to its intractable and irreversible symptoms,brings great physical and psychological burden to patients,which is seriously disturbing their normal life.In terms of treatment,there is currently no specific treatment for Alzheimer's disease in clinical practice,and first-line treatment drugs for Parkinson's disease also have great limitations.In traditional Chinese medicine,kidney governs bone,generates marrow,and connects to the brain.In clinical evidence typing,premature aging,fatigue and forgetfulness,and tremor of limbs caused by kidney deficiency and medullary reduction are considered to be the main pathologies of these diseases.Di-Huang-Yin-Zi decoction which is derived from the"General Records of Holy Universal Relief",is recorded as a good formula for nourishing kidney yin and filling kidney yang.Clinical data shows that this formula has significant therapeutic effects in treating neurodegenerative diseases caused by kidney essence deficiency.Modern research results indicate that its mechanism of action involves inhibiting inflammatory reactions,regulating mitochondrial autophagy,reversing The hypothalamic-pituitary-adrenal axis abnormalities,and neuroprotection.The main effective ingredients in this formula include loganin,echinarin,and schisandrin A.This article aims to summarize and analyze the clinical efficacy,mechanism of action,and active ingredients of Di-Huang-Yin-Zi decoction in the treatment of Alzheimer's and Parkinson's disease in recent years,in order to clarify the research status of Di-Huang-Yin-Zi decoction in the neurodegenerative disease and provide reference for further research.

Objective:To observe the efficacy of optical coherence tomography angiography (OCTA) guided half-dose photodynamic therapy (PDT) in the treatment of acute central serous chorioretinopathy (CSC).Methods:A prospective randomized controlled trial. A total of 72 patients (72 eyes) with acute CSC in Peking University People's Hospital from April 2019 to April 2020 were included in the study. They were randomly divided into OCTA group (OCTA-guided PDT, 31 eyes of 31 patients) and indocyanine green angiography (ICGA) group (ICGA-guided PDT, 33 eyes of 33 patients). All patients underwent best corrected visual acuity (BCVA), fundus color photography, OCTA and ICGA examinations. International standard visual acuity chart was used for BCVA examination, which was converted into logarithm of the minimum angle of resolution (logMAR) visual acuity. In OCTA group, the hyper-reflective area on en face OCTA image at choriocapillaris level was identified as treating area. In ICGA group, the area of choroidal vascular hyperpermeability on ICGA which was related to the leakage on fundus fluorescein angiography (FFA) was identified as treating area. The area corresponding to the treating area on FFA or ICGA was outlined on the color fundus photograph to guide PDT laser spot. The complete subretinal fluid (SRF) resolution, BCVA, central retinal thickness (CRT) at 1, 3, 6 months and SRF recurrent rate at 3, 6 months were observed. Continuous variables between the two groups were compared by t-test or Wilcoxon rank sum test. The χ2 test was used to compare the categorical variables. Results:At 1, 3 and 6 months after treatment, the SRF absorption rate in OCTA group and ICGA group was 74.2% (23/31), 63.6% (21/33), 87.1% (27/31) and 84.8% (28/33), 96.8% (30/31), 91.9% (31/33), respectively. OCTA-guided PDT was demonstrated noninferior to ICGA-guided PDT for complete SRF resolution at 1, 3, 6 months [95% confidence interval ( CI) -11.9%-33.1%, P=0.402; 95% CI -14.7%-19.3%, P=0.107; 95% CI-6.3%-16.1%, P=0.226]. There was no significant difference in the recurrence rate of SRF between the two groups at 3 and 6 months after treatment ( χ2=0.009, 0.047; P=0.925, 0.828). The difference of CRT was statistically significant at 6 months ( t=2.017, P=0.047). There was no significant difference in logMAR BCVA at 1, 3 and 6 months after treatment ( t=0.529, 0.762, 1.017; P=0.581, 0.403, 0.243). Conclusions:During 6 months follow-up, OCTA-guided PDT was demonstrated noninferior to ICGA-guided PDT for the SRF absorption rate in patients with acute CSC.

Objective:To investigate and analyze the clinical manifestations and imaging features of the eyes with bullous retinal detachment.Methods:Retrospective case series study. Eleven eyes of 11 patients with bullous retinal detachment diagnosed in Department of Ophthalmology, Peking University People's Hospital from July 2015 to September 2021 were enrolled. There were 10 males and 1 female, with the mean age of (39.27±6.81) years. All patients had monocular bullous retinal detachment, with mean duration ranged from 3 months to 14 years. The basic information and medical history of all patients were collected. All patients underwent best corrected visual acuity (BCVA), indirect ophthalmoscopy, color fundus photography, optical coherence tomography (OCT), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and B-scan ultrasonography. BCVA was performed using a standard logarithmic visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity. The clinical data and imaging features of BCVA, OCT, FFA and ICGA were retrospectively analyzed and summarized.Results:The mean logMAR BCVA of the 11 eyes was 0.91±0.45. Nine patients had bilateral disease, but bullous retinal detachment occurred in only 1 eye, and CSC manifestations were present in the contralateral eye. Six patients had received systemic or topical hormone therapy prior to onset. Yellowish-white material was observed in 6 eyes and retinal folds were observed in 5 eyes. OCT examination showed serous retinal detachment in the macular area with granular or patchy hyperreflective signals in the subretinal area in all eyes, and a few granular hyperreflective substances in the neuroretina in 6 eyes. Neuroretina cystoid degeneration was observed in 6 eyes, adhesion between the detached neuroretina and retinal pigment epithelial (RPE) was observed in 6 eyes, RPE tear was observed in 6 eyes, and different forms of retinal pigment epithelial detachment (PED) were observed in 6 eyes. FFA showed multiple fluorescence leakage spots in 10 eyes, and the average number of fluorescence leakage spots in all eyes was 3.82±2.44. There were multiple diffuse RPE lesions in 9 eyes. The results of ICGA examination showed that choroidal vessels were dilated and multiple hyperfluorescent leaks were observed in all eyes. B-scan ultrasonography examination of all affected eyes showed retinal detachment. Retinal reattachment can be achieved at (2.0±1.0) months after photodynamic therapy (PDT), while SRF can be completely absorbed at (2.36±0.81) months. The mean logMAR BCVA can be improved to 0.50±0.33, and no recurrence was found in the follow-up period up to 6 months.Conclusions:Bullous retinal detachment is often associated with the use of hormones, while yellow-white material in the subretina and hyperreflective material in the OCT are common. It is characterized by neuroretina cystoid degeneration in the macular area, adhesion between the neuroretina and RPE, RPE tear and PED, with multiple fluorescence leakage spots and diffuse RPE lesions. PDT is an effective treatment for bullous retinal detachment.

Autoimmune retinopathy (AIR) is a rare immune retinopathy characterized by decreased visual acuity, scotoma, visual field defect, and photoreceptor dysfunction.AIR is divided into paraneoplastic AIR (pAIR) and non-neoplastic AIR (npAIR). pAIR is further divided into cancer-associated retinopathy (CAR), melanoma-associated retinopathy (MAR), and bilateral diffuse uveal melanocytic proliferation (BDUMP). Circulating anti-retinal antibodies often exist in peripheral blood of patients with various types of AIR, accompanied by electroretinogram abnormalities, but no significant abnormality in fundus examination (except BDUMP). A variety of anti-retinal antibodies such as anti-recoverin protein antibody and anti-α-enolase antibody have been identified in the serum of AIR patients.However, anti-retinal antibodies can also be negative in some AIR patients' serum.At present, the diagnostic criteria and laboratory examination criteria for AIR are not uniform, and there are large differences in clinical examination performance among patients, which may lead to misdiagnosis and missed diagnosis.Therefore, a thorough examination is required to rule out other possible causes before making a speculative diagnosis.So far, the treatments for different types of AIR are not unified.Most clinicians choose a combination of various immunomodulatory therapies, including systemic or topical application of corticosteroids, intravenous immunoglobulin, plasmapheresis, and the use of antimetabolites or anti-CD20 monoclonal antibody.The clinical characteristics of different AIR types, serum anti-retinal autoantibodies detection, differential diagnosis and treatment prognosis of AIR were reviewed in this article to improve the understanding of clinicians and researchers toward the disease, and to achieve early diagnosis and early treatment of AIR.

Objective:To investigate the clinical features and multimodal imaging features of eyes with perifoveal exudative vascular anomalous complex (PEVAC).Methods:A retrospective case study. From February 2014 to November 2020, 7 eyes of 7 patients with PEVAC diagnosed by ophthalmology examination in Department of Ophthalmologyof Peking University People's Hospital were included in this study. There were 6 males and 1 female. The age was 60.1±9.1 years. All were monocular. The chief complaints of visual deformation and vision loss were 3 and 1 cases, respectively. All patients underwent best corrected visual acuity (BCVA), fundus color photography, optical coherence tomography (OCT), fundus fluorescein angiography (FFA). BCVA examination was performed using the standard logarithmic visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity. OCT angiography (OCTA) and indocyanine green angiography (ICGA) were performed in 4 and 2 eyes, respectively. Three eyes were treated with intravitreal injection of anti-vascular endothelial growth factor (VEGF) combined with local laser photocoagulation. Two eyes were treated with laser photocoagulation alone. The follow-up time was 16.7±19.1 months. During follow-up, relevant examinations were performed with the same equipment and methods as at the initial diagnosis. The multimodal imaging characteristics and treatment response of the affected eyes were observed.Results:The baseline logMAR BCVA was 0.33±0.19 (0.20-0.80). All eyes showed isolated hemangiomatous lesions in the macular fovea with rigid retinal exudation, and 2 adjacent isolated hemangiomatous lesions were observed in 1 eye. FFA and ICGA examination showed that all eyes with macular hemangiomatous lesions showed clear boundary and strong fluorescence in the early stage. No other retinal or choroidal vascular abnormalities were observed. On OCT examination, circular lumen-like structures with strong reflective wall near the fovea were observed in the macular region of all eyes, accompanied by intraretinal cystic lumen. The macular central retinal thickness (CMT) was 326±125 (207-479) μm. In the four eyes examined by OCTA, blood flow signals were observed in the circular lumenoid structures with strong reflective walls adjacent to the fovea. Blood flow signals were observed in the superficial capillary layer (SCP) and deep capillary layer (DCP) of the retina in 3 eyes. SCP showed blood flow signal in 1 eye. In 4 eyes treated with intravitreal injection of anti-VEGF drugs, there was no significant improvement in the intraretinal capsule space after treatment. Subretinal fluid absorption, retinal cystoid edema persisted, and rigid exudation decreased in 1 eye. CMT decreased and BCVA increased in 5 eyes treated with laser photocoagulation or laser photocoagulation alone. At last follow-up, logMAR BCVA was 0.16±0.06 (0.10-0.20) and CMT was 212±34 (154-252) μm. Compared with baseline, the difference of BCVA was statistically significant ( t=2.661, P=0.037). Conclusions:The fundus of PEVAC patients is characterized by solitary or multiple solitary hemangiomatous lesions in the macular fovea. Round lumenoid structures with strong reflective walls, with or without intraretinal cystic lumen, rigid exudate, and subretinal fluid, in which blood flow signals can be seen in OCT.

Objective:To explore the outcome of extended internal limiting membrane (ILM) peeling combined with releasing the edge technique for primary failed idiopathic macular hole (IMH) surgery.Methods:A retrospective analysis was performed. The data of 18 eyes of 18 IMH patients who were failed in primary surgery from August 2013 to June 2019 in Peking University People’s Hospital were enrolled in the study. Among them, 5 patients were males and 13 patients were females. The average age was 66.2±6.4 years. The BCVA were measured by ETDRS charts. The minimum macular hole size was measured on OCT B-scan image. The average preoperative BCVA and minimum macular hole size of primary surgery was 32.6±13.1 letters and 621.1±161.8 μm. The average preoperative BCVA and minimum macular hole size of second surgery was 34.4±12.3 letters and 499.0±148.6 μm. Average interval period of first and second surgery was 3.4±1.3 weeks. The surgical technique used in the reoperation included the extended ILM peeling combined with releasing the MH edges. The extended ILM peeling area ranged from 4 DD diameter to vascular arcades. The technique of releasing the macular hole edges was performed by using a silicone soft-tip extrusion cannula, with which tapping the edges softly or aspirated vacuum the edges concentricly. The average follow-up was 9.3±5.2 months. The clear OCT image can be obtained for confirming MH closure which was considered as the closure time in the first time. The comparison of preoperative and postoperative was performed by paired t-test. Results:The closure rate of second surgery was 94.4% (17/18), and average closure time was 2.1±1.0 weeks. Only 1 eye experienced the second surgical failure and received the third surgery to achieved macular hole closure. Average final follow-up BCVA was 51.5±13.0 ETDRS letters, with average improvement of 18.9 ETDRS letters (>3 lines) compared with preoperative BCVA of primary surgery. There was significantly statistical difference between the final BCVA and preoperative BCVA ( t=5.412, P <0.001). Eleven patients (61.1%) had 3 lines BCVA improvement, 15 patients (83.3%) had more than 1 line improvement, and 3 patients (16.7%) had on improvement. The final BCVA of patients significantly improved compared with preoperative BCVA of the second surgery ( t=7.595, P<0.001), with average improvement of 17.1±9.5 letters. Conclusion:The extended ILM peeling combined with releasing macular hole edges technique is effective to improve the closure rate and BCVA of primary failed IMH eyes.

Objective: To observe the changes of retinal microstructure in lamellar macular hole (LMH) after vitrectomy. Methods: A retrospective clinical observational study. Forty patients (41 eyes) with LMH and received vitrectomy in Ophthalmology Department of Peking University People’s Hospital from January 2014 to September 2018 were included in this study. Among them, 14 patients (15 eyes) were males and 26 patients (26 eyes) were females, with an average age of 67.8±8.6 years. There were 37 eyes with a lens and 4 eyes with an IOL. There were 29 eyes with LMH of tractional type, 7 eyes of degenerative type, and 5 eyes of mixed type. All patients underwent BCVA and OCT examinations. The BCVA examination was performed using the international standard visual acuity chart, which was converted into logMAR visual acuity. The average logMAR BCVA was 0.57±0.27; the mean macular retinal thickness (CRT) was 192.3±108.9 μm, the mean macular thickness (MRT) was 427.5±110.2 μm. Among the 29 eyes of tractional type, there were 17 eyes with retinal cavity, 8 eyes with macular retinoschisis, and 3 eyes with incomplete ellipsoid zone. Among the 7 eyes of degenerative type, there were 5 eyes with lamellar hole-associated epiretinal proliferation (LHEP), 5 eyes with retinal cavity, and 5 eyes with incomplete ellipsoid zone. Among the 5 eyes of mixed type, 2 eyes with LHEP, 1 eye with macular epiretinal membrane, and 4 eyes with incomplete ellipsoid zone. The average follow-up time after surgery was 12.8±5.2 months. Among them, 10 eyes were followed up for equal or greater than 24 months. After the surgery, the same equipment and method before the surgery were used for relevant examination. The changes of BCVA, CRT, and MRT before and after surgery were observed. Continuous variables were compared by t test. Results: At the last follow-up, the mean logMAR BCVA was 0.37±0.26. Compared with before surgery, the difference was statistically significant (t=5.98, P<0.01). The mean CRT and MRT were (245.2±90.8) and (347.0±46.7) μm, respectively. Compared with before surgery, the differences were statistically significant (t=-2.49, -5.24; P<0.05, <0.01). CRT and MRT changed greatly within 6 months after surgery, and then tended to be gentle. Among the 3 eyes with incomplete ellipsoid zone of tractional type before surgery, ellipsoid zone recovered in 2 eyes and partially recovered in 1 eye. Among the 17 eyes with retinal cavity and 8 eyes with macular retinoschisis before surgery, there were still 4 eyes with retinal cavity, but all the retinoschisis were disappeared. Among the 5 eyes with retinal cavity of degenerative type before surgery, there were still 2 eyes with retinal cavity and all the eyes with incomplete ellipsoid zone. Among 10 eyes with a follow-up time of equal or greater than 24 months, the macular ganglion cell complex partially atrophied in 6 eyes, and the nerve fiber layer separated in 2 eyes. There was no full-thickness macular hole after surgery. Conclusion For most LMH patients, vitrectomy can effectively improve the visual acuity and promote the recovery of retinal microstructure.

Objective To observe the clinical and multimodel imaging characteristics ofparacentral acute middle maculopathy (PAMM).Methods Retrospective case series study.From January 2014 to August 2018,12 eyes of 12 patients with PAMM diagnosed in Department of Ophthalmology,Peking University People's Hospital,were included in this study.There were 9 males and 3 females,with the mean age of 57 years.All patients were referred for sudden impaired vision,with or without paracentral scotoma.The patients underwent BCVA,slit lamp examination,fundus photography,FFA and OCT.Simultaneously,OCT angiography (OCTA) was performed in 10 eyes,visual field was performed in 5 eyes,near infrared fundus photography was performed in 1 eye.Clinical and multimodal imaging findings were reviewed and analyzed.Results Among 12 eyes,there were 5 eyes with BCVA 0.05-≤0.1,4 eyes with BCVA 0.3-0.5,3 eyes with BCVA 0.6-1.0.There were 1 eye with central rentinal artery obstruction (CRAO),7 eyes with branch retinal artery obstruction (BRAO).Among them,BRAO with central retinal vein occlusion (CRVO) in 1 eye,with non-arteritic anterior ischemic optic neuropathy in 1 eye,with diabetic retinopathy in 1 eye;old BRAO in 3 eyes;pure BRAO in 1 eye.There were 4 eyes with pure CRVO,including 3 eyes with ischemic CRVO.All eyes demonstrated hyperreflective lesions at the level of the inner nuclear layer and/or outer plexus layer on OCT.En face OCT highlighted the areas with hyperreflectivity corresponding to these lesions.OCTA demonstrated significant deep capillary dropout,abnormal morphology and enlargement of foveal avascular zone.Conclusion Hyperreflective band-like lesions at the level of the inner nuclear layer on OCT and middle retinal perivascular hyperreflectivity on en face scan are characteristic in PAMM.