Vascular Endothelial Growth Factor Concentration in Vitreous Humor of Patients with Severe Proliferative Diabetic Retinopathy after Intravitreal Injection of Conbercept as an Adjunctive Therapy for Vitrectomy

Vascular Endothelial Growth Factor Concentration in Vitreous Humor of Patients with Severe Proliferative Diabetic Retinopathy after Intravitreal Injection of Conbercept as an Adjunctive Therapy for Vitrectomy

Introduction

Diabetic retinopathy (DR) is a severe, vision-threatening complication of diabetes and remains one of the leading causes of legal blindness in the working-age population worldwide. Proliferative diabetic retinopathy (PDR) is an advanced stage of DR characterized by retinal ischemia, neovascularization (NV), vitreous hemorrhage (VH), and tractional retinal detachment (TRD). These complications are the primary causes of vision loss in diabetic patients. Pars plana vitrectomy (PPV) is a widely accepted surgical intervention for managing PDR. However, the presence of neovascularization often complicates the procedure by causing intraoperative bleeding, obscuring the surgical field, and increasing the risk of iatrogenic retinal tears. These challenges prolong surgical time and elevate the risk of postoperative inflammation and recurrent TRD.

Vascular endothelial growth factor (VEGF) is a pivotal factor in the development of neovascularization. Anti-VEGF agents have been introduced as adjunctive therapies before PPV to reduce intraoperative bleeding, shorten surgical time, and improve surgical outcomes. Conbercept, a recombinant fusion protein, has shown efficacy in ophthalmic treatments due to its high binding affinity to VEGF receptors. This study aimed to investigate the changes in intravitreal VEGF concentrations in patients with severe PDR after intravitreal injection of conbercept (IVC) and evaluate its potential benefits in facilitating subsequent vitrectomy.

Methods

This prospective, interventional, randomized controlled study enrolled 80 eyes from 80 patients, including 60 eyes with severe PDR and 20 eyes with rhegmatogenous retinal detachment complicated by proliferative vitreoretinopathy (PVR) as the control group. The PDR patients were randomly assigned to three groups based on the interval between preoperative IVC and vitrectomy: Group A (7 days), Group B (14 days), and Group C (no IVC). Group D consisted of 20 non-diabetic control patients who underwent PPV directly.

All patients underwent comprehensive ophthalmic and systemic evaluations, including best-corrected visual acuity (BCVA), intraocular pressure measurement, ophthalmoscopy, fundus color photography, and ultrasound B-scan. Vitreous samples were collected at the beginning of PPV and cryopreserved for VEGF concentration measurement using enzyme-linked immunosorbent assay (ELISA). Intraoperative bleeding and total surgical time were recorded to assess the surgical outcomes.

Results

The mean intravitreal VEGF concentrations in Groups A–D were 66.6 ± 43.3, 93.1 ± 52.3, 161.4 ± 106.1, and 1.8 ± 1.2 pg/mL, respectively. VEGF levels were significantly higher in PDR patients (Groups A, B, and C) compared to the non-diabetic control group (Group D). PDR patients with preoperative IVC (Groups A and B) exhibited significantly lower VEGF concentrations, intraoperative bleeding rates, and total surgical times compared to Group C. No significant differences were observed between Groups A and B in these parameters.

Intraoperative bleeding occurred in 6, 6, and 15 cases in Groups A, B, and C, respectively. In Groups A and B, bleeding was minimal and resolved spontaneously without hemostatic interventions. In contrast, 15 cases in Group C required hemostatic techniques such as elevating infusion pressure, endodiathermy, or fluid-air exchange. The mean total surgical times for Groups A–C were 54.0 ± 12.6, 59.0 ± 17.8, and 78.9 ± 24.1 minutes, respectively, with significantly shorter times in Groups A and B compared to Group C.

Discussion

The study demonstrated that intravitreal VEGF concentrations were significantly elevated in patients with severe PDR compared to non-diabetic controls. Preoperative IVC effectively reduced VEGF levels, intraoperative bleeding, and total surgical time, facilitating the vitrectomy procedure. The findings suggest that both 7-day and 14-day intervals between IVC and PPV are equally effective and safe for managing severe PDR.

VEGF plays a critical role in the pathogenesis of PDR by promoting neovascularization and contributing to complications such as VH and TRD. The reduction of VEGF levels through IVC helps mitigate these complications, making the surgical procedure safer and more efficient. The study’s results align with previous research indicating the benefits of anti-VEGF therapy in PDR management.

Conbercept’s high binding affinity to VEGF receptors likely contributes to its prolonged efficacy, as evidenced by the sustained reduction in VEGF levels up to 14 days post-injection. This extended duration of action provides flexibility in scheduling preoperative IVC, allowing for optimal surgical planning.

The study also highlighted the practical benefits of preoperative IVC in reducing intraoperative bleeding and shortening surgical time. These improvements enhance surgical precision and reduce the risk of postoperative complications, ultimately benefiting both surgeons and patients.

Conclusion

The study concluded that preoperative IVC significantly reduces intravitreal VEGF concentrations, intraoperative bleeding, and total surgical time in patients with severe PDR. Both 7-day and 14-day intervals between IVC and PPV are equally effective and safe, offering valuable adjunctive therapy for vitrectomy in PDR management. These findings support the integration of preoperative IVC into the surgical treatment protocol for severe PDR, improving surgical outcomes and patient care.

doi.org/10.1097/CM9.0000000000000687

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