Use of growth differentiation factor 15 in the preparation of products for the diagnosis, prognosis and treatment of retinal arterial obstruction

Abstract

The application discloses application of growth differentiation factor 15 in preparation of products for diagnosis, prognosis and treatment of retinal arterial obstruction, and finds that serum GDF15 level of a patient with RAO is greater than or equal to 442.64 pg / mL, and is significantly positively correlated with the risk of RAO (OR=12.6), and the diagnostic accuracy can be improved by combining glucose, triglyceride and other indexes (AUC=0.922). The recombinant human GDF15 protein can inhibit ischemia and hypoxia RGC apoptosis and protect visual function. The application has important application value in early diagnosis of RAO, visual prognosis evaluation and targeted treatment.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to the application of growth differentiation factor 15 (GDF15) in the preparation of products for the diagnosis, prognosis and treatment of retinal artery occlusion. Background Technology

[0002] Retinal artery occlusion (RAO) is an acute disorder of retinal blood supply caused by microemboli and other factors, falling under the category of small vessel stroke. It has a sudden onset, often presenting as unilateral, painless, and severe vision loss. RAO rapidly leads to ischemic necrosis of retinal ganglion cells, followed by pathological changes such as retinal edema and tissue atrophy, making it a highly blinding ophthalmic emergency. Due to its complex pathogenesis and rapid progression, there is currently a lack of early, sensitive biomarkers and standard treatment protocols in clinical practice, severely impacting patients' visual prognosis.

[0003] Therefore, there is an urgent need to develop a product for the diagnosis, prognosis, and treatment of retinal artery occlusion. Summary of the Invention

[0004] The purpose of this invention is to provide the application of growth differentiation factor 15 in the preparation of products for the diagnosis, prognosis and treatment of retinal artery occlusion. This application found that the serum GDF15 level of RAO patients was significantly elevated (≥442.64 pg / mL) and positively correlated with the degree of visual impairment. Therefore, products for the diagnosis, risk assessment and visual prognosis assessment of retinal artery occlusion were developed.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] In a first aspect of the invention, the use of a reagent for detecting GDF15 is provided in the preparation of products for the diagnosis of retinal artery occlusion, risk assessment of disease, and visual prognosis assessment.

[0007] Furthermore, the reagents for detecting GDF15 include reagents, kits, chips, systems, or instruments for detecting GDF15 levels in serum.

[0008] In a second aspect of the invention, the use of a reagent for detecting a combination of biomarkers in the preparation of products for the diagnosis of retinal artery occlusion, risk assessment of disease, and visual prognosis assessment is provided, said biomarkers including GDF15, glucose, triglycerides, high-density lipoprotein cholesterol, neutrophils, and TYG index.

[0009] In one implementation scheme, the product used for retinal artery occlusion diagnosis, disease risk assessment, and complication risk assessment is one or more of reagents, kits, chips, systems, and instruments; the reagents, kits, and chips use GDF15 as the detection target, or use a combination of GDF15, glucose, triglycerides, high-density lipoprotein cholesterol, neutrophils, and TYG index as the detection target.

[0010] In one embodiment, the product for diagnosing or assessing the prognosis of retinal artery occlusion (RAO) is used to detect serum GDF15 levels and compare the statistical results of GDF15 levels in the subject's serum with those in healthy individuals. When there is a significant difference between the statistical results of GDF15 levels in the subject's serum and those in healthy individuals, the subject is considered to have a high risk of retinal artery occlusion. For patients who have already developed RAO, the higher the serum GDF15 level, the worse their visual prognosis.

[0011] In one embodiment, the serum is preferably circulating blood serum.

[0012] In a third aspect of the invention, the use of GDF15 in the preparation of products for treating retinal artery occlusion is provided.

[0013] Furthermore, the product comprises recombinant human GDF15 protein. In one embodiment, the product for the treatment of retinal artery occlusion includes a drug for treating retinal artery occlusion.

[0014] In a fourth aspect of the invention, a risk assessment system is provided, comprising:

[0015] An acquisition module is used to acquire the levels of biomarkers in the serum of subjects; the biomarkers include GDF15;

[0016] An assessment module is used to assess the visual prognostic risk of subjects (i) those with retinal artery occlusion and (ii) those who have developed RAO, based on the levels of the biomarkers.

[0017] The acquisition module and the evaluation module are connected wirelessly and / or via wired means.

[0018] In a specific embodiment of the risk assessment system of the present invention, when the absolute concentration of GDF15 is ≥442.64 pg / mL, the risk assessment result output by the assessment module is: the subject is prone to retinal artery occlusion.

[0019] In a specific embodiment of the risk assessment system described above in this invention, the level of GDF15 in the subject's serum refers to the absolute concentration of GDF15 in the subject's serum, or the relative concentration of GDF15 in the subject's serum. The relative concentration refers to the ratio of the absolute concentration of GDF15 in the subject's serum to the statistical result of the absolute concentration of GDF15 in the serum of a healthy person.

[0020] In a specific embodiment of the risk assessment system of the present invention, the assessment module is used to perform a risk assessment on the GDF15 level obtained by the acquisition module and output the risk assessment result. The assessment module includes a risk assessment model, and the formula of the risk assessment model is: Logit(P) = -1.744 + 0.004 × GDF15 level, where P represents the probability of RAO incidence.

[0021] In a specific embodiment of the risk assessment system of the present invention, the biomarker is a combination of GDF15, glucose, triglycerides, high-density lipoprotein cholesterol, neutrophils, and the TYG index. The assessment module is used to perform risk assessment on the levels of GDF15, glucose, triglycerides, high-density lipoprotein cholesterol, neutrophils, and the TYG index obtained by the acquisition module, and outputs the risk assessment result. The assessment module includes a risk assessment model, and the formula of the risk assessment model is:

[0022] Logit (P) = 18.728 + 0.003 × GDF15 level + 2.268 × glucose level + 5.38 × triglyceride level - 3.951 × high-density lipoprotein cholesterol level + 2.457 × neutrophil count - 4.165 × TYG index, where P represents the probability of RAO.

[0023] The risk assessment system is a tangible medium that stores risk assessment methods. In one embodiment, tests are performed using a software program executed by a suitable processor. In some embodiments, the program is embodied in software stored on the tangible medium. In some other embodiments, the tangible medium is selected from flash drives, CD-ROMs, floppy disks, hard disks, DVDs, and processor-associated memory.

[0024] In one embodiment, the acquisition module detects the level of GDF15 in serum by one or more of the following methods: chromatography, spectroscopy, mass spectrometry, and chemical analysis.

[0025] In a fifth aspect of the invention, an auxiliary diagnostic instrument is provided, including the aforementioned risk assessment system.

[0026] One or more technical solutions in the embodiments of the present invention have at least the following technical effects or advantages:

[0027] This invention discloses the use of GDF15 in the preparation of products for the diagnosis, prognosis, and treatment of recurrent acute exacerbation (RAO). Serum GDF15 levels ≥442.64 pg / mL were significantly positively correlated with the risk of RAO (OR=12.6), and combining it with glucose and triglyceride levels improved diagnostic accuracy (AUC=0.922). Furthermore, recombinant human GDF15 protein can inhibit RGC apoptosis in ischemic hypoxia and protect visual function. This invention has significant application value in the early diagnosis, visual prognostic assessment, and targeted therapy of RAO. Attached Figure Description

[0028] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below.

[0029] Figure 1 ROC curve of serum GDF15 levels in RAO patients.

[0030] Figure 2 ROC curve of serum GDF15 level combined with other blood indicators in RAO patients.

[0031] Figure 3 Restricted cubic spline analysis showed a positive correlation between the prevalence of RAO and serum GDF15 levels.

[0032] Figure 4 ROC curves of serum GDF15 and other blood markers in the independent validation set of RAO patients.

[0033] Figure 5 GDF15 plays a protective role in the RAO cell model. (A) CCK8 assay detects the activity of ischemic and hypoxic R28 cells treated with GDF15. (B) TUNEL assay detects apoptosis in ischemic and hypoxic R28 cells treated with GDF15.

[0034] Figure 6 GDF15 plays a protective role in the RAO mouse model. (A) Immunofluorescence detection of retinal ganglion cell survival in the RAO mouse model. (B) OCT detection of nerve fiber layer thickness in the RAO mouse model. Detailed Implementation

[0035] The following detailed description of the embodiments and examples will illustrate the present invention in more detail, thereby making the advantages and various effects of the embodiments more clearly apparent. Those skilled in the art should understand that these detailed embodiments and examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

[0036] Throughout this specification, unless otherwise specified, the terminology used herein should be understood as having the meaning commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the embodiments of this invention pertain. In the event of any conflict, this specification shall prevail.

[0037] The term "treatment" refers to therapeutic and preventative or preventive measures aimed at preventing or slowing (alleviating) a target pathological condition or symptom. People who need treatment include those who already have the condition, those who are susceptible to the condition, or those who want to prevent the condition.

[0038] The term "level" refers to absolute concentration.

[0039] The term "high risk" refers to a high prevalence rate in morbidity statistics. The terms "morbidity rate," "probability of disease," and "risk of disease" all have the same meaning.

[0040] In the risk assessment model formula, Logit(P) = log(P / 1-P), where P is the probability of RAO onset.

[0041] This invention uses statistical methods to study the relationship between serum GDF15 levels and the prevalence of recurrent acute exanthematous lesions (RAO) and the degree of visual improvement in RAO patients. The study found a significant correlation between serum GDF15 levels and an increased risk of RAO; higher GDF15 levels correlated with a higher risk of RAO. Logistic regression analysis showed that the ratio (95% confidence interval) between the quartile 4 (highest) and the quartile 1 (lowest) of GDF15 levels was 12.6 (4.59, 32.016). Furthermore, when serum GDF15 levels were ≥442.64 pg / mL, RAO patients exhibited significantly worse visual acuity upon admission and upon discharge.

[0042] The risk assessment system provided by this invention primarily assesses the risk of retinal artery occlusion (RAO) and the visual prognosis of RAO patients by using the level of GDF15 in the subject's serum. Furthermore, it can be combined with indicators such as glucose, triglycerides, high-density lipoprotein cholesterol, neutrophils, and the TYG index for disease risk assessment or prognostic risk assessment. In the optimized model of this invention, GDF15, glucose, triglycerides, high-density lipoprotein cholesterol, neutrophils, and the TYG index are used as biomarkers for combined assessment. See [link to relevant documentation]. Figure 2 Joint assessments are more accurate.

[0043] Unless otherwise specified, all raw materials, reagents, instruments and equipment used in the embodiments of the present invention can be purchased from the market or prepared by existing methods.

[0044] The following will provide a detailed description of a Parkinson's disease comorbid depression risk prediction system and its application, in conjunction with embodiments, comparative examples and experimental data.

[0045] Example 1: Serum GDF15 levels were significantly elevated in RAO patients (≥442.64 pg / mL), and were positively correlated with the degree of visual impairment.

[0046] 1. GDF15 testing

[0047] Blood samples were collected from patients diagnosed with RAO and healthy individuals undergoing routine intravenous venipuncture. GDF15 levels in serum samples were measured using a sandwich ELISA kit (R&D Systems, USA, catalog number: DGD150). The chromogenic system of the sandwich ELISA kit contains streptavidin-HRP, hydrogen peroxide, and tetramethylbenzidine. Intra-batch and inter-batch coefficients of variation were 2.9%–3.9% and 5.2%–10.9%, respectively.

[0048] 2. Visual acuity prognosis measurement for RAO patients

[0049] All RAO ​​patients were assessed by clinically experienced ophthalmologists before admission and discharge. Visual acuity (VA) was assessed using a standard logarithmic visual acuity chart, and the results were converted to the logarithm of the minimum resolution angle (logMAR) according to the formula logMAR = lg(1 / decimal VA). Furthermore, for low visual acuity categories such as "finger counting," "hand movements," "light perception," and "no light perception," the corresponding logMAR values ​​were determined to be 2.0, 2.3, 2.6, and 2.9, respectively. Significant visual improvement was defined as a discharge standard of a ≥0.3 decrease in logMAR relative to admission visual acuity.

[0050] 3. Statistical Analysis

[0051] Continuous variables were described as median and interquartile ranges. The Mann-Whitney test was used for intergroup comparisons of continuous data. Categorical variables were presented as numbers and percentages. A chi-square test was performed to compare categorical data. Logistic regression analysis in IBM SPSS (version 26) was used to assess the association between serum GDF15 levels and the occurrence and visual prognosis of recurrent acute excitation (RAO). Restricted cubic regression splines in R (version 4.2.3) were used to assess the potential nonlinear relationship between GDF15 levels and the prevalence of RAO. A p-value <0.05 was considered statistically significant.

[0052] 4. Analyze the correlation between serum GDF15 levels and the prevalence of RAO.

[0053] As shown in Table 1, this invention divides GDF15 levels into quartiles. The GDF15 levels in serum samples are divided into quartiles, with the first quartile (level 1) representing the lowest level, ≤297.46 pg / mL. This quartile is used as the baseline for assessing the RAO odds ratio (Table 1). It was found that in different models, increased GDF15 levels significantly increased the RAO hazard ratio.

[0054] In the coarse model and Model 1 (adjusted for clinical data such as sex, age, diabetes, and hypertension), serum GDF15 levels were positively correlated with the prevalence of recurrent acute exacerbation (RAO). In Model 2, after additional adjustments for confounding factors including neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, monocytes, glutamate-oxaloacetate transaminase, triglycerides, high-density lipoprotein cholesterol, glomerular filtration rate, and glucose, the correlation between serum GDF15 levels and RAO prevalence remained statistically significant. In the fully adjusted Model 2, the odds ratio (95% confidence interval) of serum GDF15 levels at level 4 (highest) compared to level 1 (lowest) was 12.6 (4.59, 32.016) (see Table 1).

[0055] Table 1. Logistic regression analysis of serum GDF15 levels on RAO

[0056]

[0057] Rough model: No adjustments.

[0058] Model 1: Adjusted for gender, age, hypertension, and diabetes.

[0059] Model 2: Adjusted based on the same variables as Model 1, as well as variables such as neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, monocytes, glutamate-oxaloacetate transaminase, triglycerides, high-density lipoprotein cholesterol, glomerular filtration rate, and glucose.

[0060] Limitation cubic spline analysis of fully adjusted data also showed a positive correlation between the prevalence of RAO and serum GDF15. Figure 3 As shown in the curve, the risk of RAO increases significantly when the GDF15 level exceeds the threshold of 442.64 pg / mL.

[0061] like Figure 1As shown, the univariate logistic regression model for predicting the risk of RAO (Recurrent Occurrence) using serum GDF15 level is: Logit(P) = -1.744 + 0.004 × GDF15 level. The area under the curve (AUC) for GDF15 is 0.748 ([95% CI] = [0.681, 0.814]), with a sensitivity of 54.29%, a specificity of 86.67%, and a Youden index of 0.4096. This indicates that GDF15 level has a certain degree of accuracy in predicting the probability of RAO.

[0062] Example 2: Model for RAO diagnosis and disease risk assessment

[0063] 1. Construct a model for RAO diagnosis and disease risk assessment using GDF15 as a biomarker.

[0064] Logit(P) = -1.744 + 0.004 × GDF15 level, where P represents the probability of RAO onset.

[0065] like Figure 1 As shown, the univariate logistic regression model for predicting the risk of RAO (Recurrent Occurrence) using serum GDF15 level is: Logit(P) = -1.744 + 0.004 × GDF15 level. The area under the curve (AUC) for GDF15 is 0.748 ([95% CI] = [0.681, 0.814]), with a sensitivity of 54.29%, a specificity of 86.67%, and a Youden index of 0.4096. This indicates that GDF15 level has a certain degree of accuracy in predicting the probability of RAO.

[0066] 2. A model for the diagnosis and risk assessment of retinal artery occlusion was constructed using a combination of GDF15, glucose, triglycerides, high-density lipoprotein cholesterol, neutrophils, and the TYG index.

[0067] The formula for the risk assessment model is:

[0068] Logit (P) = 18.728 + 0.003 × GDF15 level + 2.268 × glucose level + 5.38 × triglyceride level - 3.951 × high-density lipoprotein cholesterol level + 2.457 × neutrophil count - 4.165 × TYG index, where P represents the probability of RAO.

[0069] The formula for calculating the TYG index is: TYG Index = ln[(TG (mg / dL) × Glu (mg / dL) / 2).

[0070] like Figure 2As shown, the levels of GDF15 (pg / mL), glucose (mmol / L), triglycerides (mmol / L), high-density lipoprotein cholesterol (mmol / L), and neutrophils in serum [Neu (×10] were used to measure the levels of these parameters. 9 When GDF15 and TYG index were used in a combined assessment, the area under the curve in the Logistic risk prediction model was 0.922 (95% CI = 0.886, 0.959), with a sensitivity of 71.88%, a specificity of 98.08%, and a Youden index of 0.6996. This indicates that GDF15 combined with glucose, triglycerides, high-density lipoprotein cholesterol, neutrophils, and TYG index has higher accuracy in predicting the prevalence of RAO.

[0071] In addition, to further validate the accuracy of the GDF15 index and the combined assessment of the risk of RAO prevalence using the GDF15 index in conjunction with glucose, triglycerides, high-density lipoprotein cholesterol, neutrophil levels, and TYG index, we selected 82 healthy individuals and 82 RAO patients as an independent validation set.

[0072] Table 2 - GDF15 ROC curve analysis combined with laboratory indicators for the diagnosis of RAO

[0073]

[0074] Depend on Figure 4 It can be seen that the area under the curve (AUC) of GDF15 in the independent validation set is 0.811 ([95% CI]=[0.744, 0.878]), the sensitivity is 59.31%, the specificity is 88.53%, and the Youden index is 0.4615.

[0075] When combined with serum GDF15, glucose, triglycerides, high-density lipoprotein cholesterol, neutrophil levels and TYG index, the area under the curve was 0.934 ([95% CI] = [0.900, 0.971]), with a sensitivity of 72.15%, a specificity of 97.12%, and a Youden index of 0.71.

[0076] In summary, GDF15 and GDF15 combined with glucose, triglycerides, high-density lipoprotein cholesterol, neutrophils, and TYG index have excellent accuracy and stability in predicting RAO risk.

[0077] Example 3: Used for visual prognostic assessment of RAO

[0078] Regarding the percentage improvement in visual acuity, we divided GDF15 levels into high and low groups based on the risk of RAO, using a threshold of 442.64 pg / mL. The results are shown in Table 3.

[0079] Table 3. Relationship between serum GDF15 levels and visual prognosis in RAO patients.

[0080]

[0081] As shown in Table 3, the group with higher GDF15 levels had worse visual acuity upon admission and upon discharge, suggesting that GDF15 levels in RAO patients are significantly negatively correlated with visual prognosis.

[0082] Example 4: Use of GDF15 in the preparation of products for treating RAO

[0083] We used an ischemic-hypoxic R28 cell model to simulate the pathological process of retinal ganglion cell death after central retinal artery occlusion in RAO patients. The results showed that treatment of ischemic-hypoxic R28 cells with GDF15 recombinant human protein significantly inhibited apoptosis and exerted a protective effect. Figure 5 ).

[0084] Simultaneously, using a RAO mouse model, we found that GDF15 significantly inhibited retinal ganglion cell death, and OCT results showed that the thickness of the retinal nerve fiber layer was significantly higher after GDF15 treatment than in the control group. These results indicate that GDF15 can exert a protective effect on vision in the RAO mouse model. Figure 6 ).

[0085] Example 5: Risk Assessment System

[0086] This invention provides a risk assessment system, the system comprising:

[0087] An acquisition module is used to acquire the levels of biomarkers in the serum of subjects; the biomarkers include GDF15;

[0088] An assessment module is used to assess the visual prognostic risk of subjects (i) those with retinal artery occlusion and (ii) those who have developed RAO, based on the levels of the biomarkers.

[0089] The acquisition module and the evaluation module are connected wirelessly and / or via wired means.

[0090] In a specific embodiment of the risk assessment system of the present invention, when the absolute concentration of GDF15 is ≥442.64 pg / mL, the risk assessment result output by the assessment module is: the subject is susceptible to RAO.

[0091] In a specific embodiment of the risk assessment system described above in this invention, the level of GDF15 in the subject's serum refers to the absolute concentration of GDF15 in the subject's serum, or the relative concentration of GDF15 in the subject's serum. The relative concentration refers to the ratio of the absolute concentration of GDF15 in the subject's serum to the statistical result of the absolute concentration of GDF15 in the serum of a healthy person.

[0092] In a specific embodiment of the risk assessment system of the present invention, the assessment module is used to perform a risk assessment on the GDF15 level obtained by the acquisition module and output the risk assessment result. The assessment module includes a risk assessment model, and the formula of the risk assessment model is: Logit(P) = -1.744 + 0.004 × GDF15 level, where P represents the probability of RAO incidence.

[0093] In a specific embodiment of the risk assessment system of the present invention, the biomarker is a combination of GDF15, glucose, triglycerides, high-density lipoprotein cholesterol, neutrophils, and the TYG index. The assessment module is used to perform risk assessment on the levels of GDF15, glucose, triglycerides, high-density lipoprotein cholesterol, neutrophils, and the TYG index obtained by the acquisition module, and outputs the risk assessment result. The assessment module includes a risk assessment model, and the formula of the risk assessment model is:

[0094] Logit (P) = 18.728 + 0.003 × GDF15 level + 2.268 × glucose level + 5.38 × triglyceride level - 3.951 × high-density lipoprotein cholesterol level + 2.457 × neutrophil count - 4.165 × TYG index, where P represents the probability of RAO.

[0095] Example 6: Computer-readable storage medium

[0096] This invention provides a computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, implements the steps of the method of embodiment 5.

[0097] Of course, the computer-executable instructions provided in the embodiments of the present invention are not limited to the method operations described above, but can also perform related operations in the methods provided in any embodiment of the present invention.

[0098] Based on the above description of the implementation methods, those skilled in the art can clearly understand that the present invention can be implemented using software and necessary general-purpose hardware, and of course, it can also be implemented using hardware, but in many cases the former is a better implementation method. Based on this understanding, the technical solution of the present invention, or the part that contributes to the prior art, can be embodied in the form of a software product. This computer software product can be stored in a computer-readable storage medium, such as a computer floppy disk, read-only memory (ROM), random access memory (RAM), flash memory, hard disk, or optical disk, etc., including several instructions to cause an electronic device (which may be a personal computer, server, or network device, etc.) to execute the methods described in the various embodiments of the present invention.

[0099] It is worth noting that the various units and modules included in the above embodiments are only divided according to functional logic, but are not limited to the above division, as long as the corresponding functions can be achieved; in addition, the specific names of each functional unit are only for easy differentiation and are not used to limit the scope of protection of the present invention.

[0100] Finally, it should be noted that the terms “comprising,” “including,” or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0101] Although preferred embodiments of the present invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments as well as all changes and modifications falling within the scope of the embodiments of the present invention.

[0102] Obviously, those skilled in the art can make various modifications and variations to the embodiments of the present invention without departing from the spirit and scope of the embodiments of the present invention. Therefore, if these modifications and variations to the embodiments of the present invention fall within the scope of the claims of the embodiments of the present invention and their equivalents, the embodiments of the present invention are also intended to include these modifications and variations.

Claims

1. Use of reagents for detecting growth differentiation factor 15 in the preparation of kits for the diagnosis, risk assessment or visual prognosis of retinal artery occlusion.

2. The use of reagents for detecting biomarkers in the preparation of kits for the diagnosis, risk assessment, or visual prognosis assessment of retinal artery occlusion, characterized in that, The biomarkers include GDF15, glucose, triglycerides, high-density lipoprotein cholesterol, neutrophils, and the TYG index.

3. A risk assessment system, characterized in that, include: An acquisition module is used to acquire the levels of biomarkers in the serum of subjects; the biomarkers include GDF15; An assessment module is used to assess the visual prognostic risk of subjects (i) those with retinal artery occlusion and (ii) those who have developed RAO, based on the levels of the biomarkers. The acquisition module and the evaluation module are connected wirelessly and / or via wired means.

4. The risk assessment system according to claim 3, characterized in that, When the absolute concentration of GDF15 is ≥442.64 pg / mL, the risk assessment result output by the assessment module is: the subject is susceptible to retinal artery occlusion.

5. The risk assessment system according to claim 3, characterized in that, The assessment module includes a risk assessment model, the formula of which is: Logit(P) = -1.744 + 0.004 × GDF15 level, where P represents the probability of RAO, and the unit of GDF15 level is pg / mL.

6. The risk assessment system according to claim 3, characterized in that, The biomarkers are a combination of GDF15, glucose, triglycerides, high-density lipoprotein cholesterol, neutrophils, and the TYG index. The assessment module includes a risk assessment model, the formula of which is: Logit (P) = 18.728 + 0.003 × GDF15 level + 2.268 × glucose level + 5.38 × triglyceride level - 3.951 × high-density lipoprotein cholesterol level + 2.457 × neutrophil count - 4.165 × TYG index, where P represents the probability of RAO. The units for GDF15 levels are pg / mL, glucose levels are mmol / L, triglyceride levels are mmol / L, high-density lipoprotein cholesterol levels are mmol / L, and neutrophil counts are [Neu (×10] mmol / L]. 9 The formula for calculating the TYG index is: TYG Index = ln[(TG (mg / dL) × Glu (mg / dL) / 2).

7. An auxiliary diagnostic instrument, characterized in that, Includes the risk assessment system described in any one of claims 3-6.

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