Abstract
This study aimed to analyze the expression and clinical significance of IGF-1 and PDGF in the aqueous humor and serum of diabetic patients with visually significant cataract. A retrospective study was conducted on 136 diabetic patients with visually significant cataract who underwent phacoemulsification. Patients were divided into non-complication (n = 82) and complication groups (n = 54) based on postoperative outcomes. Clinical baseline data, as well as IGF-1 and PDGF levels in aqueous humor and serum, were compared between groups. ROC curve analysis was utilized to evaluate the predictive value of IGF-1 and PDGF for postoperative complications. Logistic regression was employed to identify risk factors, and Kaplan–Meier analysis was adopted to assess the impact of IGF-1 and PDGF levels on postoperative complications. No significant differences were found between the two groups in terms of gender, age, BMI, intraocular pressure, surgical eye, phacoemulsification time, phacoemulsification energy, axial length, smoking, drinking history, hypertension, hyperlipidemia, FINS, HbA1C, CRP, or FPG. However, significant differences were observed in disease duration, presence of retinopathy, and IL-6 levels. Patients with complications had significantly higher IGF-1 and PDGF levels in both aqueous humor and serum compared to those without complications. Elevated IGF-1 and PDGF levels were independent risk factors for complications and increased the risk of postoperative complications. Elevated IGF-1 and PDGF levels in aqueous humor and serum are significant independent risk factors for postoperative complications in diabetic patients with visually significant cataract. Both markers can assist in predicting adverse outcomes and are associated with an increased risk of complications.
Keywords: Type 2 diabetes mellitus, Visually significant cataract, Serum, Aqueous humor, IGF-1, PDGF, Phacoemulsification, Complications
Introduction
Type 2 diabetes mellitus (T2DM) is a complicated and multifactorial metabolic disorder caused by insulin resistance/insensitivity or relative insufficiency (Rachdaoui 2020). Pancreatic β-cell failure resulting from a reduction in function and mass is considered a dominating contributor to the progression of T2DM (Cui et al. 2024). T2DM patients are associated with a high risk of microvascular (such as retinopathy and nephropathy) and macrovascular complications (like cardiovascular comorbidities) (DeFronzo et al. 2015). Diabetic patients also have an increased risk for visually significant cataract (Greenberg & Bamba 2021), a leading cause of global blindness and visual loss (Lee & Afshari 2017; Mishra et al. 2023). Cataracts develop earlier and faster in diabetic patients than non-diabetic patients, which often requires surgery (Xia 2022). It has been revealed that the risk of cataracts in diabetic population increases with the duration of diabetes and poor metabolic management (Mrugacz et al. 2023). Careful preoperative ocular examinations as well as the application of advanced phacoemulsification technologies and new intraocular lenses have been developed for improving the prognosis of cataract surgery in diabetic patients (Zarei-Ghanavati et al. 2024). However, diabetic patients with visually significant cataract still have some postoperative complications that affect vision, such as posterior capsular opacification (PCO), corneal edema, endophthalmitis, and diabetic retinopathy (DR) (Foster et al. 2019; Grzybowski et al. 2019; Liu et al. 2024; Peterson et al. 2018). Particularly, PCO constitutes one of the common long-term complications after cataract phacoemulsification (Foster et al. 2019). Typically, the incidence of PCO ranges from 11% to 43% for patients within one year post surgery depending on different interventions, like surgical technique, intraocular lens (IOL) design and material, and concomitant ocular disease (Findl et al. 2010). The proliferation, migration, differentiation, and transdifferentiation of lens epithelial cells (LECs) and cellular matrix deposition all contribute to deterioration of vision in PCO (Wormstone et al. 2009). The oxidative stress state in diabetic patients upregulates the levels of inflammatory factors (e.g. TGF-β), which accelerates persistent postoperative intraocular inflammation, expedites epithelial-mesenchymal transition in LECs, and further stimulates LEC proliferation and collagen synthesis (Kiziltoprak et al. 2019; Taiyab et al. 2023). Corneal edema is also one of the most common complications following cataract surgery (Sharma et al. 2017). Perfusion solution of cataract surgery and mechanical manipulation can cause transient corneal edema, which usually resolves on its own within a few days to a few weeks (Behndig and Lundberg 2002; Costagliola et al. 2013; Lundberg et al. 2005). However, a chronic or long-lasting swelling process may lead to bullous keratopathy or even blindness (Briceno-Lopez et al. 2023; Sharma et al. 2017). Diabetic patients have lower endothelial cell density compared to non-diabetic patients of the same age, and ultrasonic emulsification leads to increased corneal endothelial cell damage, and higher incidence and longer course of persistent postoperative corneal edema (Sharma et al. 2017). Endophthalmitis, characterized by bacterial or fungal infection inside the eye, involving the vitreous and/or aqueous humors, is a rare but serious post-cataract surgery complication (Durand 2013). Study has found that diabetic patients have an increased risk of postoperative endophthalmitis, which is associated with a poor visual prognosis (Chen et al. 2025). Diabetic patients undergoing phacoemulsification cataract surgery have twice the risk of DR at 12 months postoperatively (Chen et al. 2025). These complications pose a great challenge in successful phacoemulsification.
Insulin-like growth factor 1 (IGF-1), a peptide hormone of the insulin family, is essential for for the development, growth, and maintenance of organs and engaged in the pathogenesis of multiple diseases, such as neurodegenerative diseases and otopathy (Suzuki et al. 2019; Zhang et al. 2022). A dysregulation of growth hormone/IGF-1 axis has been proposed in patients with type 1 diabetes (Nambam and Schatz 2018). Moreover, peripheral IGF-1 concentrations has been linked to executive function, which may be dependent on diabetes status (Ryoo et al. 2024). Interestingly, this protein is highly involved in the regulation of pancreatic β cell growth, differentiation, and insulin release (F. Cui and He 2022), and also increase fatty acid β oxidation during fasting (Thankamony et al. 2014), exerting an important role in the progression of T2DM (Castilla-Cortazar et al. 2019). Also, involvement of IGF1 in endoplasmic reticulum stress is involved in the initiation of cataract by regulating the Nrf2/NF-κB signaling pathway (Peng et al. 2023). A recent study has shown that aqueous humor IGF-1 levels correlate with HOMA-IR and glycated hemoglobin (HbA1c) levels in individuals suffering from diabetic cataracts (DC) (Zhu et al. 2019). Study has suggested that measuring IGF-1 levels in serum and plasma can more effectively assess the prognosis of cataract surgery in diabetic patients (Hartnett et al. 2009).
The platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) is a key family participated in a vast array of physiological processes like cell migration (Kazlauskas 2017). PDGFs have shown a critical role in the pathology of diabetes and its harmful complications, such as diabetic neuropathies, nephropathy, and retinopathy (Shen et al. 2020). An upregulation of platelet-derived growth factor-C (PDGF-C) is reported in aqueous humor of patients who suffer from neovascular glaucoma, showing a great significance in ocular neovascular disorders (Li et al. 2020). Currently, there is no study mentioning the implication of IGF-1 and PDGF levels in aqueous humor and serum samples of diabetic patients with visually significant cataract. Thus, a retrospective research was conducted to analyze whether IGF-1 and PDGF levels may serve as predictive factors in the occurrence of postoperative in diabetic patients with visually significant cataract.
Materials and methods
Study subjects
A retrospective selection was made of 159 patients diagnosed with T2DM complicated with visually significant cataract who underwent phacoemulsification Bishan hospital of Chongqing medical university, Bishan Hospital of Chongqing between January 2023 and December 2023. Among these, 5 cases were excluded due to incomplete data, and 18 cases were excluded based on inclusion and exclusion criteria. Ultimately, 136 patients were included as study subjects. The patients were divided into a non-complication group (n = 82) and a complication group (n = 54) based on the presence of postoperative complications following phacoemulsification [14 cases of persistent corneal edema, 8 cases of endophthalmitis, 11 cases of retinopathy, and 30 cases of PCO]. In compliance with medical record management regulations and confidentiality principles, clinical characteristics and laboratory examination data of these patients were retrieved and collected from the hospital’s electronic medical record database. The study was ratified by the ethics committee of Bishan hospital of Chongqing medical university, Bishan Hospital of Chongqing.
Inclusion and exclusion criteria
Inclusion criteria included: (1) patients who were clinically diagnosed with T2DM complicated with visually significant cataract; (2) patients who had complete case data; (3) patients who were undergoing first-time treatment with phacoemulsification and had aqueous humor samples collected preoperatively; and (4) patients who completed timely follow-up within one year postoperatively.
Exclusion criteria included: (1) patients who had used cataract-related medications preoperatively; (2) patients who were diagnosed with other metabolic diseases; (3) patients who had severe damage to vital organs such as the heart, liver, or kidneys; (4) patients with incomplete case data; (5) patients complicated with DR or malignancies, such as gastric cancer, pancreatic cancer, or breast cancer; (6) patients with severe systemic diseases, including cardiovascular and cerebrovascular diseases, respiratory conditions, coagulation disorders, or hypertension; (7) patients with a history of previous ocular surgery or trauma; (8) patients with systemic infectious diseases; and (9) patients with postoperative anterior chamber inflammation, mild endophthalmitis, or transient corneal edema.
Diagnostic criteria
The diagnostic criteria for T2DM included meeting any of the following conditions: (1) fasting blood glucose (FBG) ≥ 7.0 mmol/L; (2) presence of the typical diabetes symptoms (“three polys and one less”—polyuria, polydipsia, polyphagia, and weight loss) along with random blood glucose ≥ 11.1 mmol/L; (3) postprandial 2-h blood glucose ≥ 11.1 mmol/L; (4) HbA1c ≥ 6.5%, or a prior clinical diagnosis of T2DM by a physician.
The diagnostic criteria for cataracts included patients presenting with reduced visual acuity and snowflake-like opacities in the lens region, and those classified as Grade III cortical cataracts based on the Lens Opacities Classification System III (LOCS III).
Specimen collection
Serum collection: Fasting venous blood (3–4 mL) was collected from all study subjects in the early morning prior to cataract surgery. Whole blood samples were processed using a 1.15 K low-temperature ultracentrifuge (4 °C, 3000 rpm, centrifuged for 10 min) to separate the serum.
Aqueous humor collection: Aqueous humor samples were obtained from the surgical eye of all subjects during phacoemulsification. After administering surface anesthesia and performing routine surgical disinfection and draping, an anterior chamber puncture was performed using a 25-gauge needle attached to a syringe, inserted 1 mm inside the corneal limbus. Approximately 0.15–0.2 mL of aqueous humor was aspirated and immediately transferred to a 0.5 mL Eppendorf tube. The samples were then stored at −70 °C in an ultra-low temperature freezer for future analysis.
Phacoemulsification
All study subjects underwent surface anesthesia with Oxybuprocaine Hydrochloride Eye Drops applied to the affected eye 30 min before surgery, followed by standard disinfection and draping. A clear corneal tunnel incision was made on the temporal side of the surgical eye. After injecting a viscoelastic agent, a continuous curvilinear capsulorrhexis with a diameter of approximately 5 mm was performed. Hydrodissection was then carried out, and the nucleus of the lens was emulsified using the divide-and-conquer phacoemulsification technique. Residual cortex was removed using irrigation/aspiration (I/A), and the posterior capsule was polished. A foldable intraocular lens was injected into the capsular bag, followed by aspiration of the viscoelastic agent. The incision was self-sealing without sutures, and the surgery was completed successfully.
Case data and sample collection
Case data for the study subjects were collected, including: (1) General baseline information such as gender, age, height, weight, body mass index (BMI), blood pressure (systolic and diastolic), disease duration, smoking history, alcohol consumption history, comorbid hypertension, and comorbid hyperlipidemia. (2) Blood markers, including FPG, fasting insulin (FINS), HbA1c, IGF-1, PDGF, interleukin-6 (IL-6), procalcitonin (PCT), white blood cell count (WBC), and C-reactive protein (CRP). (3) Postoperative complications observed within one year after surgery, including persistent corneal edema, endophthalmitis, retinopathy, and PCO. (4) Preoperative aqueous humor samples were collected, and the levels of IGF-1 and PDGF were measured.
Statistical analysis
Statistical analysis and graphing were performed using SPSS 27.0 statistical software (SPSS, Inc., Chicago, IL, USA) and GraphPad Prism 9.0 software (GraphPad Software Inc., San Diego, CA, USA). The Kolmogorov–Smirnov test was used to assess the normality of data distribution. Measurement data following a normal distribution were expressed as mean ± standard deviation, and comparisons between groups were made using an independent samples t-test. Non-normally distributed measurement data were expressed as median (minimum, maximum), and group comparisons were performed using the Mann–Whitney U test. Categorical data were expressed as case numbers and percentages, with group comparisons analyzed using the chi-square test. Logistic regression analysis was employed to calculate odds ratios (OR) and 95% confidence intervals (CI) to identify independent risk factors affecting the adverse outcomes in diabetic patients with visually significant cataract. Receiver operating characteristic (ROC) curve analysis was adopted to evaluate the auxiliary value of serum and aqueous humor IGF-1 and PDGF levels in predicting postoperative adverse outcomes in diabetic patients with visually significant cataract. Kaplan–Meier curves were implemented to analyze the impact of serum and aqueous humor IGF-1 and PDGF levels on the risk of postoperative complications in diabetic patients with visually significant cataract. P < 0.05 was considered statistically significant.
Results
Baseline data
An analysis of the clinical baseline data was made between the non-complication and complication groups of patients suffering from T2DM complicated with cataract. The results revealed no significant differences in gender, age, height, weight, BMI, intraocular pressure, surgical eye, phacoemulsification time, phacoemulsification energy, axial length, smoking history, drinking history, history of hypertension, history of hyperlipidemia, as well as levels of FINS, HbA1 C, or CRP (all P > 0.05). However, significant differences were observed in disease duration, presence of retinopathy, FPG, and IL-6 levels (all P < 0.05) (Table 1).
Table 1.
Comparison of baseline data between the two groups
| Item | Non-complication group (n = 82) | Complication group (n = 54) | P |
|---|---|---|---|
| Male (case, %) | 48 (58.54) | 30 (55.56) | 0.731 |
| Age (years) | 66.26 ± 3.27 | 67.30 ± 4.39 | 0.116 |
| Height (cm) | 162.80 ± 6.30 | 164.70 ± 5.09 | 0.062 |
| Weight (kg) | 69.98 ± 9.19 | 70.13 ± 10.32 | 0.932 |
| BMI (kg/m2) | 26.29 ± 3.50 | 27.13 ± 3.12 | 0.155 |
| Disease duration (year) | 7.17 ± 1.64 | 8.85 ± 2.70 | < 0.001 |
| Intraocular pressure (mmHg) | 15.96 ± 2.36 | 16.21 ± 2.18 | 0.535 |
| Left surgical eye (case, %) | 40 (48.78) | 30 (55.56) | 0.439 |
| Phacoemulsification time (min) | 19.73 ± 2.22 | 20.52 ± 2.93 | 0.079 |
| Phacoemulsification energy (ml) | 10.57 ± 2.17 | 11.20 ± 2.12 | 0.097 |
| Axial length (mean ± SD) | 23.09 ± 3.68 | 23.75 ± 4.13 | 0.332 |
| Presence of retinopathy (case, %) | 36 (43.90) | 13 (24.07) | 0.018 |
| Smoking history (case, %) | 30 (36.59) | 21 (38.89) | 0.785 |
| Drinking history (case, %) | 24 (29.27) | 13 (24.07) | 0.786 |
| History of hypertension (case, %) | 9 (10.98) | 8 (14.81) | 0.508 |
| History of hyperlipidemia (case, %) | 6 (7.32) | 3 (5.56) | 0.686 |
| FPG (mmol/l) | 6.27 ± 0.60 | 6.44 ± 0.51 | 0.083 |
| FINS (pmol/l) | 15.76 ± 7.70 | 16.42 ± 7.10 | 0.614 |
| HbA1 C (%) | 7.23 ± 0.81 | 7.51 ± 0.85 | 0.051 |
| IL-6 (pg/mL) | 42.95 ± 5.40 | 47.16 ± 4.57 | < 0.001 |
| CRP (mg/L) | 11.18 ± 2.07 | 11.68 ± 2.63 | 0.216 |
The Kolmogorov–Smirnov test was used to assess the normality of data distribution
Measurement data following a normal distribution were expressed as mean ± standard deviation, and comparisons between groups were made using an independent samples t-test
Non-normally distributed measurement data were expressed as median (minimum, maximum), and group comparisons were performed using the Mann–Whitney U test
Categorical data were expressed as case numbers and percentages, with group comparisons analyzed using the chi-square test
BMI body mass index, FPG fasting plasma glucose, FINS fasting serum insulin, HbA1 C hemoglobin A1c, IL-6 interleukin-6, CRP C-reactive protein, WBC white blood cell, PCT procalcitonin
Serum and aqueous humor IGF-1 and PDGF levels are significantly elevated in patients with postoperative complications
A comparison of serum and aqueous humor IGF-1 and PDGF levels between the two groups revealed significant differences, as shown in Table 2. In contrast to the non-complication group, IGF-1 and PDGF levels in both serum and aqueous humor were significantly elevated in the complication group (all P < 0.001).
Table 2.
Comparison of IGF-1 and PDGF in serum and aqueous humor between two groups of patients
| Group | Case | IGF-1 (ng/mL) | PDGF (μg/L) | ||
|---|---|---|---|---|---|
| Serum | Aqueous humor | Serum | Aqueous humor | ||
| Non-complication group | 82 | 15.54 ± 0.60 | 21.33 ± 0.73 | 48.15 ± 3.49 | 58.89 ± 3.99 |
| Complication group | 54 | 16.67 ± 0.91 | 22.45 ± 1.03 | 53.68 ± 3.95 | 64.93 ± 4.07 |
| t | 8.675 | 7.397 | 8.572 | 8.577 | |
| P | < 0.001 | < 0.001 | < 0.001 | < 0.001 | |
The Kolmogorov–Smirnov test was used to assess the normality of the data distribution
Measurement data following a normal distribution were expressed as mean ± standard deviation, and comparisons between groups were made using an independent samples t-test
IGF-1 insulin-like growth factor 1, PDGF platelet derived growth factor
Serum and aqueous humor IGF-1 and PDGF Levels can assist in predicting postoperative complications in diabetic patients with visually significant cataract
ROC curve analysis was employed to evaluate the predictive value of serum and aqueous humor IGF-1 and PDGF levels for postoperative complications in diabetic patients with visually significant cataract. The results unveiled that serum IGF-1 (AUC = 0.846, sensitivity = 70.40%, specificity = 86.60%, P < 0.001, 95% CI 0.779–0.913, cutoff value = 16.18) and serum PDGF (AUC = 0.852, sensitivity = 63.00%, specificity = 96.30%, P < 0.001, 95% CI 0.787–0.917, cutoff value = 53.12) (Fig. 1A–C), as well as aqueous humor IGF-1 (AUC = 0.815, sensitivity = 59.30%, specificity = 89.00%, P < 0.001, 95% CI 0.742–0.887, cutoff value = 22.15) and aqueous humor PDGF (AUC = 0.863, sensitivity = 64.80%, specificity = 95.10%, P < 0.001, 95% CI 0.800–0.926, cutoff value = 63.59) (Fig. 1B–D), could all effectively assist in predicting the occurrence of complications following phacoemulsification in diabetic patients with visually significant cataract.
Fig. 1.
Predictive value of serum and aqueous humor IGF-1 and PDGF Levels for postoperative complications in diabetic patients with visually significant cataract ROC curve analysis of serum IGF-1 (A), aqueous humor IGF-1 (B), serum PDGF (C), and aqueous humor PDGF (D) levels for predicting postoperative complications in diabetic patients with visually significant cataract
Elevated serum and aqueous humor IGF-1 and PDGF levels are independent risk factors for postoperative complications in diabetic patients with visually significant cataract
Postoperative complications in diabetic patients with visually significant cataract (0 = no complications, 1 = complications) were set as the dependent variable, and indicators with statistically significant differences (P < 0.05) were included as independent variables in a univariate logistic regression analysis. The results indicated that history of DR, disease duration, elevated IL-6 levels, serum IGF-1, serum PDGF, aqueous humor IGF-1, and aqueous humor PDGF levels were all risk factors for postoperative complications in diabetic patients with visually significant cataract. Further multivariate logistic regression analysis revealed that history of DR, elevated serum IGF-1, serum PDGF, aqueous humor IGF-1, and aqueous humor PDGF levels were independent risk factors for postoperative complications in these patients (all P < 0.05, Table 3).
Table 3.
Analysis of independent risk factors for postoperative complications in DC patients
| Logistics univariate regression analysis | Logistics multivariate regression analysis | |||||
|---|---|---|---|---|---|---|
| P value | OR value | 95% CI | P value | OR value | 95% CI | |
| Presence of DR | 0.020 | 2.468 | 1.153–5.284 | 0.040 | 3.373 | 1.061–13.147 |
| Disease duration | < 0.001 | 1.454 | 1.203–1.758 | 0.812 | 1.042 | 0.742–1.464 |
| IL-6 | < 0.001 | 1.180 | 1.090–1.277 | 0.886 | 1.012 | 0.856–1.197 |
| Serum IGF-1 | < 0.001 | 8.702 | 4.011–18.880 | 0.028 | 2.971 | 1.124–7.854 |
| Serum PDGF | < 0.001 | 1.545 | 1.330–1.795 | 0.048 | 1.223 | 1.002–1.494 |
| Aqueous humor IGF-1 | < 0.001 | 6.198 | 3.086–12.445 | 0.047 | 2.256 | 1.012–5.033 |
| Aqueous humor PDGF | < 0.001 | 1.597 | 1.357–1.880 | 0.046 | 1.272 | 1.004–1.610 |
DC diabetic cataract, FPG fasting plasma glucose, IL-6 interleukin-6, IGF-1 insulin-like growth factor 1, PDGF platelet derived growth factor
Elevated serum and aqueous humor IGF-1 and PDGF levels significantly increase the risk of postoperative complications in diabetic patients with visually significant cataract
Using the ROC cut-off values as thresholds (serum and aqueous humor IGF-1 = 16.18 and 22.15 ng/mL, PDGF = 53.12 and 63.59 μg/L, respectively), we further analyzed the impact of different levels of serum and aqueous humor IGF-1 and PDGF on the incidence of complications within one year after surgery in diabetic patients with visually significant cataract. The results reflected that the increase of serum and aqueous humor IGF-1 and PDGF levels notably increased the incidence of postoperative complications (all P < 0.001, Table 4).
Table 4.
Effects of different levels of IGF-1 and PDGF in serum and aqueous humor on postoperative complications in DC patients
| High levels | Low levels | P | ||
|---|---|---|---|---|
| Serum IGF-1 | With complications (n = 54) | 37 | 17 | < 0.001 |
| Without complications (n = 82) | 11 | 71 | ||
| Aqueous humor IGF-1 | With complications (n = 54) | 32 | 21 | < 0.001 |
| Without complications (n = 82) | 9 | 74 | ||
| Serum PDGF | With complications (n = 54) | 34 | 20 | < 0.001 |
| Without complications (n = 82) | 3 | 79 | ||
| Aqueous humor PDGF | With complications (n = 54) | 33 | 21 | < 0.001 |
| Without complications (n = 82) | 4 | 78 |
DC diabetic cataract, IGF-1 insulin-like growth factor 1, PDGF platelet derived growth factor
Kaplan–Meier analysis further revealed that patients with high serum and aqueous humor IGF-1 (HR = 5.503 and 4.858) and PDGF levels (HR = 7.634 and 6.016) showed upward shifts in Kaplan–Meier curves (all P < 0.05, Fig. 2). These findings indicate that elevated serum and aqueous humor IGF-1 and PDGF levels increase the likelihood of postoperative complications in diabetic patients with visually significant cataract, significantly raising the risk of complications (all P < 0.05).
Fig. 2.
The impact of different levels of serum and aqueous humor IGF-1 and PDGF on postoperative complications in diabetic patients with visually significant cataract Kaplan-Meier curve analysis illustrating the effect of serum IGF-1 (A), aqueous humor IGF-1 (B), serum PDGF (C), and aqueous humor PDGF (D) levels on the incidence of postoperative complications in diabetic patients with visually significant cataract
Discussion
Diabetes remains a crucial global public health issue in the elderly, particularly in China (Yan et al. 2022). Compared with the healthy population, diabetic patients have 3–5 times higher incidence of cataracts and faster development of this complication (Mrugacz et al. 2023). At present, cataract surgery represents one of the main approach for the treatment of DC (Haddad et al. 2014). However, some DC patients are prone to develop PCO following cataract surgery, mainly manifested with decreased vision, turbidity, blurred vision, and reduced contrast, which affect the medium and long-term surgical outcomes (Wu et al. 2018a, b). To achieve better therapeutic efficacy, this study paid major attention to the expression patterns and clinical significance of IGF-1 and PDGF in aqueous humor and serum of diabetic patients with visually significant cataract. The results of this study revealed that aqueous humor and serum IGF-1 and PDGF levels could aid in the prediction of adverse complications in diabetic patients with visually significant cataract and signally increase the risk of postoperative complications in patients.
Despite advances in ultrasound emulsification technology, poor postoperative vision in visually significant cataract in diabetic patients still exists. PCO, corneal edema, endophthalmitis, and retinopathy are common complications of diabetic patients with visually significant cataract (Grzybowski et al. 2019; Ivancic et al. 2005), among which PCO is one of the common long-term complications (Foster et al. 2019). Although improvements in surgical techniques and IOL technology have reduced the incidence of PCO, the abnormal proliferation of LECs and inflammatory response can induce the release of massive cytokines, which in turn triggers collagen production and fibrosis (Wormstone et al. 2009). Persistent corneal edema is a manifestation of corneal endothelial dysfunction, and endothelial decompensation may occur in severe cases (Sharma et al. 2017). The rate of postoperative keratocyte loss after phacoemulsification is generally 8.5%−15.4% in the diabetic patients with visually significant cataract compared to non-diabetic patients (Jing et al. 2023). In addition, diabetic patients with visually significant cataract have a worse prognosis of postoperative endophthalmitis and a higher risk of retinopathy progression as compared to non-diabetic patients (Hong et al. 2009; Park et al. 2022). We collected 136 patients with T2DM complicated with cataract who underwent phacoemulsification cataract surgery in this study, of which 54 patients had postoperative complications (persistent corneal edema in 14 cases, endophthalmitis in 8 cases, retinopathy in 11 cases, and PCO in 30 cases). We hence compared the levels of aqueous humor and serum IGF-1 and PDGF between the two groups of patients with and without postoperative complications and analyzed their predictive value for postoperative complications.
First of all, this article reported the upregulation of IGF-1 levels in both aqueous humor samples and serum samples of the enrolled patients with complications (corneal edema, persistent corneal edema, endophthalmitis, DR, or PCO). IGFs are peptides released in the liver and distributed throughout most tissues that stimulate mitogenic activity via communication with IGFRs. IGF-1 can affect the growth and development of the eye and participate in various biological functions, such as epithelial proliferation, retinal angiogenesis, and inflammatory response (Truong and Silkiss 2023). A review focusing on the recent findings of IGF and IGFBP expression in the eye in relation to various retinopathies proposes the involvement of IGF-1 axis in diabetes-associated retinopathy, such as proliferative DR (Nguyen et al. 2013). Another study has also shown the identification of growth hormones and their classical mediator IGF-1 as causal factors for the progression of DR (Harvey and Martinez-Moreno 2016). Elevated IGF-1 levels cause diabetes-like eye disease (Ruberte et al. 2004). High IGFBP-2 and IGF-1 in eyes of exudative age-associated macular degeneration indicate a significance of IGF-related molecules engaged in disease pathogenesis (Cha et al. 2013). Zhu et al. exhibited positive correlations of aqueous humor IGF-1 levels with HOMA-IR and HbA1c, important indicators for insulin resistance and glycemic control; their study also linked IGF-1 to the bFGF and IL-6 levels (inflammatory and angiogenic biomarkers for DR) in DC patients (Zhu et al. 2019). These findings contribute to demonstrating the predictive value of IGF-1 for disease conditions. To add new evidence, we evaluated the predictive value of IGF-1 for the occurrence of postoperative complications in diabetic patients with visually significant cataract. Interestingly, our data revealed that aqueous humor and serum IGF-1 levels were higher in diabetic patients with visually significant cataract with complications versus those without complications, and ROC curve analysis results showed that aqueous humor and serum IGF-1 levels (cut-off value of 22.15 and 16.18, respectively) could assist in the prediction of postoperative complications in diabetic patients with visually significant cataract following phacoemulsification. Furthermore, single/multi-factor logistic regression modeling was utilized to analyze that elevated aqueous humor and serum IGF-1 levels are independent dangerous factors for postoperative complications in diabetic patients with visually significant cataract. This may be attributed to the fact that IGF-1 can affect retinal endothelial cell survival by regulating the activation of multiple signals (Wilson et al. 2001). A prior study has revealed that IGF-1, heregulin beta, and activin A can induce the upregulation of the PI3 K/Akt and Smad2 pathways, which facilitates corneal endothelial cell proliferation and migration, consequently affecting corneal endothelial repair (Sabater et al. 2017).
Additionally, our data identified an upregulation of PDGF levels in the enrolled patients with postoperative complications. In diabetic patients with visually significant cataract, both aqueous humor and serum PDGF levels were notably elevated in patients who developed postoperative complications. The results of ROC curve analysis showed that the cutoff values of aqueous humor and serum PDGF (63.59 and 53.12) assisted in predicting the development of postoperative complications after cataract phacoemulsification surgery in diabetic patients with visually significant cataract. The single/multi-factor logistic regression analysis further revealed that elevated aqueous humor and serum PDGF levels were independent risk factors for postoperative complications in diabetic patients with visually significant cataract. PDGF-C is highly expressed together with VEGF in aqueous humor samples of patients with neovascular glaucoma (Li et al. 2020). PDGFs exert crucial effects on the processes of DM and its complications via various pathways (Shen et al. 2020). For instance, serum PDGFA levels are elevated during the progression of DR in T2DM rat models (Gong et al. 2016). Similarly, high PDGF levels of the aqueous humor are detected in eyes with macular edema secondary to DR or retinal vein occlusion (Hu et al. 2023). PDGF-AA is positively correlated with posterior capsular opacification (EPCO) score (Wu et al. 2018a, b). PDGF-BB binds to its receptor PDGFR, inducing the phosphorylation of Erk1/2, Akt, CREB, and ATF1 proteins, which in turn affects the proliferation and migration of LECs (Paensuwan et al. 2022). These findings possibly support the potential of PDGF as an important indicator of postoperative complications of diabetic cataract. Finally, we further assessed the impacts of different aqueous humor and serum IGF-1 and PDGF levels on the occurrence of complications in diabetic patients with visually significant cataract within one year after surgery using Kaplan–Meier curves based on their ROC cutoff values, respectively. Our research revealed that elevated levels of aqueous humor and serum IGF-1 and PDGF would increase the incidence of postoperative complications in diabetic patients with visually significant cataract.
Altogether, this study highlight the potential of aqueous humor and serum IGF-1 and PDGF to predict the occurrence of postoperative complications in diabetic patients with visually significant cataract, showing their promise as prognostic markers for the management of diabetic patients with visually significant cataract. However, this is a retrospective study with a relatively small sample size. Studies with an enlarged sample size are required to further investigate the application value of IGF-1 and PDGF expression in aqueous humor and serum in diabetic patients with visually significant cataract and strengthen the sensitivity and reliability of the results of this study.
Author Contributions
All authors contributed to the study conception and design, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed. JL guarantor of integrity of the entire study and responsible for literature research; JL, MC are responsible for research concepts, study design; MC, XD are responsible for data collection, manuscript preparation, JL and MC are responsible for manuscript editing;MC, JL are responsible for the definition of knowledge content, statistical analysis; JL, MC are responsible for manuscript review; JL, XD are responsible for data analysis; All authors read and approved the final manuscript.
Funding
The authors have not disclosed any funding.
Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Declarations
Conflict of interest
All authors declare that there is no conflict of interests in this study.
Ethical approval
The study was ratified by the ethics committee of Bishan hospital of Chongqing medical university, Bishan Hospital of Chongqing.
Consent for publication
Not applicable.
Footnotes
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References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.


