Original Article

Harnessing AI–human synergy for deep learning research analysis in ophthalmology with large language models assisting humans

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Background: Research innovations inoculardisease screening, diagnosis, and management have been boosted by deep learning (DL) in the last decade. To assess historical research trends and current advances, we conducted an artifcial intelligence (AI)–human hybrid analysis of publications on DL in ophthalmology.

Methods:
All DL-related articles in ophthalmology, which were published 
between 2012 and 2022 from Web of Science, were included. 500 high-impact articles annotated with key research information were used to fne-tune alarge language models (LLM) for reviewing medical literature and extracting information. After verifying the LLM's accuracy in extracting diseases and imaging modalities, we analyzed trend of DL in ophthalmology with 2 535 articles. 

Results:
Researchers using LLM for literature analysis were 70% (p = 0.000 1) faster than those who did not, while achieving comparable accuracy (97% versus 98%, p = 0.768 1). The field of 
DL in ophthalmology has grown 116% annually, paralleling trends of the broader DL domain. The publications focused mainly on diabetic retinopathy (p = 0.000 3), glaucoma (p = 0.001 1), and age-related macular diseases (p = 0.000 1) using retinal fundus photographs (FP, p = 0.001 5) and optical coherence tomography (OCT, p = 0.000 1). DL studies utilizing multimodal images have been growing, with FP and OCT combined being the most frequent. Among the 500 high-impact articles, laboratory studies constituted the majority at 65.3%. Notably, a discernible decline in model accuracy was observed when categorizing by study design, notwithstanding its statistical insignificance. Furthermore, 43 publicly available ocular image datasets were summarized. 

Conclusion:
This study 
has characterized the landscape of publications on DL in ophthalmology, by identifying the trends and breakthroughs among research topics and the fast-growing areas. This study provides an efcient framework for combined AI–human analysis to comprehensively assess the current status and future trends in the feld. 

The Kashgar Model for the Promotion and Application of Cataract Phacoemulsification Technology in Pakistan

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Phacoemulsification technology is an advanced method for treating cataracts, the leading cause of blindness worldwide. Kashgar, located in the westernmost part of China, has extensive economic, cultural, and medical exchanges with Central Asia. Promoting the application of cataract phacoemulsification technology in Pakistan aims to improve the treatment outcomes for local cataract patients and reduce the disease's blindness rate. The project leverages Pakistan's existing medical resources and technological equipment, relying on Kashgar's geographical and medical advantages, combined with the actual situation and needs of local medical staff. Through conducting doctor training, sending instructors to assist with surgeries in Pakistan, and refining surgical procedures, the project successfully implemented cataract phacoemulsification technology, effectively enhancing the treatment success rate and patient satisfaction. During the implementation process, the project encountered some difficulties and challenges but overcame them through team cooperation and scientific management, achieving good results. Ultimately, the project formed the distinctive Kashgar model, bringing a boon to cataract patients in the Pakistan region and potentially offering a reference for the promotion of other medical technologies.

The inhibitory effect of bilberry extract on RPE cells oxidative damage and angiogenesis

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To investigate the inhibitory effect of bilberry extract on retinal pigment epithelial (RPE) cells oxidative damage and angiogenesis. Methods: ①Human RPE cells (ARPE-19) were divided into three groups,control group, model group and bilberry extract group. The model group was treated with 0.5mmol/L SIN-1 for 24 hours, and the bilberry extract group was treated with 10ng/ml bilberry extract, followed by 0.5mmol/L SIN-1 for 24 hours. Cell viability was measured by CCK-8. Level of reactive oxygen species (ROS) was determined using flow cytometry.② Human umbilical vein endothelial cells (HUVEC) were divided into three groups,control group, model group and bilberry extract group. The model group was treated with 10ng/ml VEGF for 8 hours, and the bilberry extract group was treated with 10ng/ml bilberry extract for 12 hours, followed by 10ng/ml VEGF for 8 hours. Cell migration and invasion were measured by wound healing assay and Transwell assay. Cell angiogenesis was determined by tube formation assay. Results: ① Bilberry extract(≤10ng/ml)had no obvious toxicity to ARPE-19 cells. SIN-1 treatment significantly reduced the viability of ARPE-19 cells, while incubation with 10ng/ml bilberry extract could restore to the normal level(p<0.001). Therefore the following experiments were used by 10ng/ml bilberry extract. Meanwhile, bilberry extract could significantly reduce SIN-1-induced ROS levels in ARPE-19 cells(p<0.0001). ② VEGF treatment significantly enhanced the migration and invasion of HUVEC, while incubation with 10ng/ml bilberry extract could weaken(p<0.001). Meanwhile, bilberry extract could significantly inhibit VEGF-induced tube formation in HUVEC(p<0.0001). Conclusion: Bilberry extract is a potential treatment for AMD, which has significant antioxidant and anti-angiogenic activities.

The inhibitory effect of bilberry extract on RPE cells oxidative damage and angiogenesis

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To investigate the inhibitory effect of bilberry extract on retinal pigment epithelial (RPE) cells oxidative damage and angiogenesis. Methods: ①Human RPE cells (ARPE-19) were divided into three groups,control group, model group and bilberry extract group. The model group was treated with 0.5mmol/L SIN-1 for 24 hours, and the bilberry extract group was treated with 10ng/ml bilberry extract, followed by 0.5mmol/L SIN-1 for 24 hours. Cell viability was measured by CCK-8. Level of reactive oxygen species (ROS) was determined using flow cytometry.② Human umbilical vein endothelial cells (HUVEC) were divided into three groups,control group, model group and bilberry extract group. The model group was treated with 10ng/ml VEGF for 8 hours, and the bilberry extract group was treated with 10ng/ml bilberry extract for 12 hours, followed by 10ng/ml VEGF for 8 hours. Cell migration and invasion were measured by wound healing assay and Transwell assay. Cell angiogenesis was determined by tube formation assay. Results: ① Bilberry extract(≤10ng/ml)had no obvious toxicity to ARPE-19 cells. SIN-1 treatment significantly reduced the viability of ARPE-19 cells, while incubation with 10ng/ml bilberry extract could restore to the normal level(p<0.001). Therefore the following experiments were used by 10ng/ml bilberry extract. Meanwhile, bilberry extract could significantly reduce SIN-1-induced ROS levels in ARPE-19 cells(p<0.0001). ② VEGF treatment significantly enhanced the migration and invasion of HUVEC, while incubation with 10ng/ml bilberry extract could weaken(p<0.001). Meanwhile, bilberry extract could significantly inhibit VEGF-induced tube formation in HUVEC(p<0.0001). Conclusion: Bilberry extract is a potential treatment for AMD, which has significant antioxidant and anti-angiogenic activities.

Recent Advances in Research on Iron Homeostasis Imbalance in Keratoconus

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Iron ions are essential for normal metabolism, DNA synthesis, and cellular repair in corneal cells. Nevertheless, an excess of these ions can disrupt iron homeostasis, leading to cellular toxicity, damage, and death. Keratoconus, the most prevalent ectatic corneal disorder, is often marked by the Fleischer ring, which indicates an imbalance in iron homeostasis. A review of early studies on keratoconus and iron metabolism suggests that this imbalance may be a potential pathogenic mechanism contributing to the onset and progression of the disease. This article aims to provide a comprehensive overview of normal iron metabolism in the human body and cornea, highlighting the evidence of iron homeostasis imbalance in keratoconus. It also explores potential therapeutic strategies focused on maintaining iron homeostasis, thereby offering novel insights into the treatment of ectatic eye diseases.

Association between vascular endothelial function and circulating endothelial progenitor cells in patients with ocular hypertension and primary open-angle glaucoma

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Objective: To evaluate the vascular endothelial function in patients with ocular hypertension and primary open-angle glaucoma, and explore the role of circulating endothelial progenitor cells in this process. Methods: Ocular hypertension (OHT group), primary open-angle glaucoma patients (POAG group), and age- and gender-matched healthy subjects (control group) were included with 30 sample size in each group. All subjects were <65 years old and had no history of cardiovascular disease or cardiovascular risk factors. Routine physical examination, ophthalmic examination and biochemical detection were performed. Brachial artery flow mediated dilation (FMD) was measured using ultrasonic diagnostic system, and the number of circulating endothelial progenitor cells was measured by flow cytometry. Results: Compared with control group, FMD, endothelial progenitor cell count, plasma nitric oxide (NO) content decreased (P<0.05) in OHT group and POAG group, while there was no statistical significance in the comparison of indicators above between OHT group and POAG group (P>0.05). There were no statistical differences in cardiovascular risk factors among the three groups (P>0.05). Partial correlation analysis showed that the number of endothelial progenitor cells in the OHT group and POAG group was significantly positively correlated with FMD (r=0.436, P=0.013) and NO (r=0.385, P=0.036), and negatively correlated with baseline intraocular pressure (r=0.347, P=0.041). Conclusion: Patients with OHT or POAG have systemic endothelial dysfunction, and the mechanism may be related to reduced number of circulating endothelial progenitor cells. Promoting the mobilization of endothelial progenitor cells to improve endothelial function may be a new direction for clinical treatment of patients with OHT or POAG.

Advances in Artificial Intelligence for Cataract Diagnosis

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Cataract is one of the leading causes of blindness worldwide, accounting for 50 percent of blindness cases in low- and middle-income countries. With the increase in population aging, the number of cataract blindness cases in China is expected to reach 20 million by 2050. Low health expenditures, shortages of medical equipment and ophthalmologists, and high screening costs are still the main reasons why mass cataract screening is not possible in low- and middle-income countries. Artificial intelligence-assisted cataract diagnosis has the advantages of being convenient, low-cost, and able to be performed remotely, which is expected to reduce or even avoid cataract blindness. In this review, we will briefly summarize the research on automatic cataract diagnosis by artificial intelligence (AI) by combining optical images, fundus photographs, and swept source optical coherance tomography images.

Ozurdex? combined with ranibizumab for macular edema secondary to central retinal vein occlusion

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AIM:To evaluate the feasibility of intravitreal injection of dexamethasone intravitreal implant Ozurdex? combined with ranibizumab by comparing with ranibizumab alone for treatment of macular edema (ME) secondary to central retinal vein occlusion (CRVO). METHODS: Clinical data of fifty-one eyes of 51 CRVO-ME patients who were admitted to the eye center of the Second People's Hospital in Foshan from January 2022 to June 2023 were observed . They were divided into two groups: the combination (COM) group (11 patients with consecutive monthly intravitreal ranibizumab and Ozurdex? injections) and the anti-vascular endothelial growth factor (anti-VEGF) group (40 patients with “3+PRN”intravitreal ranibizumab injections). Best corrected visual acuity(BCVA),central retinal thickness(CRT), treatment costs. RESULTS: After 3.5mo and 6mo treatment, the differences in BCVA and CRT were statistically significantboth in the COM and anti-VEGF groups comparing with those pre-treatment(P<0.05).After 3.5mo treatment, there was no statistically significant difference in BCVA(P=0.917), or self-payment costs(P=0.097)in the COM versus anti-VEGF groups, but with statistically significant difference in CRT(P=0.026) and total treatment costs (P<0.01),. After 6mo treatment, no significant differences (P<0.05) were noted in BCVA and CRT between the COM and anti-VEGF groups. Within 6 months of follow-up, the number of injections was (2.27 ± 0.47) times in the COM group and (3.78 ± 1.00) times in the anti-VEGF group, and the difference between the two groups was statistically significant (P<0.01). CONCLUSION: The combination of Ozurdex? and ranibizumab has been shown to be comparable effective with anti-VEGF alone model in the treatment of CRVO-ME. Combination therapy reduces the amount of intravitreal injections and relieves the patients’ financial burden.

High-resolution imaging of limbus tissue with dual-mode full-field optical coherence tomography

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Objective: To develop a cellular-level, high-resolution, integrated dual-modal full-field optical coherence tomography (FFOCT) system capable of simultaneously imaging the structure and function of limbus tissue. Methods: Utilizing the Linnik interference imaging principle, a high-resolution dual-modal FFOCT system was designed and constructed using a high numerical aperture (NA=0.8) microscope objective and a high-speed flat CMOS camera. A functional imaging reconstruction algorithm based on four-phase modulation structure image extraction and dynamic frequency spectrum analysis of temporal interference signals was developed. The effectiveness of dual-mode FFOCT imaging at various depth layers of human corneal limbal tissue was validated. Results: The constructed dual-modal FFOCT imaging system achieved lateral resolution of 0.5 μm, axial resolution of 1.7 μm, imaging field of view of 320 μm × 320 μm, and camera acquisition speed of 100 Hz. The system enabled cellular-level resolution three-dimensional structural and intrinsic functional imaging of corneal limbal tissue without exogenous labeling. Static structural FFOCT images clearly displayed limbal epithelium, palisades of Vogt, crypts, stroma, blood vessels, and lymphatic vessels, while dynamic functional FFOCT images highlighted metabolically active cells (limbal epithelial cells, immune cells, etc.). Conclusion: The dual-modal FFOCT high-resolution imaging system provides visualization of corneal limbal microstructural and live cell intrinsic functional information without labeling, offering a novel imaging analysis technique for research and clinical diagnosis and treatment of limbal diseases.

Long-term effect of orthokeratology on choroidal thickness and choroidal contour in myopic children

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Purpose: To investigate the long-term effect of orthokeratology on the choroidal thickness and choroidal contour in myopic children. Methods: Subjects were from a conducted 2-year Randomized Clinical Trial. Children (n=80) aged 8-12 years with spherical equivalent refraction of -1.00 to -6.00D were randomly assigned to the control group (n=40) and ortho-k group (n=40). OCT images were collected at the baseline, 1-, 6-, 12-, 18-, and 24-month visits, then the choroidal thickness and choroid contour were calculated. Axial length (AL) and other ocular biometrics were also measured. Results: During two years, in the control group, the choroidal thickness became thinning and the choroidal contour became prolate with time at all visits (all P<0.001). Ortho-k can improve the choroidal thickness (all P<0.001) and maintain the choroidal contour at all visits (all P<0.05). In the ortho-k group, the choroidal contour was less changed in the temporal than nasal (P=0.008), and the choroidal thickness was more thickening in the temporal 3mm (P<0.001). Two-year change in choroidal thickness was significantly associated with the two-year AL change in the control group (r=-0.52, P<0.001), however, this trend was broken by ortho-k (r=-0.05, P=0.342). After being adjusted by other variables in the multivariable regression model, the effect of ortho-k on choroidal thickness was stable. Conclusion: In the current 2-year prospective study, ortho-k can improve the choroidal thickness and maintain the choroidal contour, but this effect diminished in a long term. Further study with larger sample size and longer follow-up is warranted to refine this issue.
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  • 眼科学报

    主管:中华人民共和国教育部
    主办:中山大学
    承办:中山大学中山眼科中心
    主编:林浩添
    主管:中华人民共和国教育部
    主办:中山大学
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  • Eye Science

    主管:中华人民共和国教育部
    主办:中山大学
    承办:中山大学中山眼科中心
    主编:林浩添
    主管:中华人民共和国教育部
    主办:中山大学
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