Renal dysfunction negatively impacts effect of diabetic macular oedema therapy

Image credit: ©kikkerdirk – stock.adobe.com

Chinese investigators found that renal dysfunction is a risk factor associated with the efficacy of intravitreal conbercept (IVC) injections (Lumitin, Chengdu Kanghong Biotech Co., Ltd.) for treating diabetic macular oedema (DMO),¹ reported first author Wei Wu, MD. He is a member of the Department of Ophthalmology, GuangZhou Red Cross Hospital of Jinan University, Guangzhou, China.

The investigators explained that conbercept is an anti-vascular endothelial growth factor (VEGF) drug with a high affinity for all isoforms of VEGF-A, VEGF-B and placental growth factor² and was reported to be safe and effective for treating DMO, which could improve visual acuity (VA) and relieve macular oedema.^3-5 However, the authors said, “only some DMO patients responded well to conbercept treatment in real-life clinical practice, reinforcing the multifactorial nature of DMO.”

Diabetic oedema, nephropathy and retinopathy

Previous research into DMO has produced mixed results. Some reported that DMO develops because of systemic factors, i.e., aging, diabetes duration, hypertension and glycosylated hemoglobin (HbA1c) levels,^6-8 which called for study of the impact of systemic factors on the clinical outcomes of IVC.

“Diabetic nephropathy often coexists with diabetic retinopathy, indicating that they may have similar microvascular pathophysiology. A prospective study found that DMO patients had higher serum creatinine levels and lower estimated glomerular filtration rate (eGFR) levels than patients without DMO,”⁹ they said, and cited a retrospective study that found that severe proteinuria tended to gain better anatomic improvement after ranibizumab [Lucentis, Genentech] treatment. However, those with lower eGFR were more likely to have poorer visual improvement.¹⁰

In contrast, some studies showed that the baseline renal function impacted the functional and anatomic responses of conbercept in patients with DMO in a real-life clinical trial. “Preoperative evaluation of renal function was not only beneficial for preliminary prediction of the approximate number of conbercept injections and effectiveness, but also reduced DMO patients’ economic burden, established reasonable expectations, and promoted better doctor-patient communication,” the authors commented.

In light of this, they wanted to investigate the risk of renal dysfunction in real-life clinical responses to conbercept for DMO. The ability to predict the treatment effect has “great potential” for reducing the risk of blindness and economic burden, the authors said.

Analysis of renal dysfunction

Dr Wu and colleagues retrospectively analysed data from 100 eyes of 100 patients with DMO who had been treated with IVC.

After measurement of the eGFR, the patients were divided into three groups: those with normal renal function (n=37), impaired renal function (n=27) and renal insufficiency (n=36). The main outcome measures were the best-corrected VA (BCVA) and central subfield macular thickness (CST). The clinical parameters evaluated were the blood urea nitrogen, serum creatinine, serum uric acid, HbA1c and hemoglobin.

The patients were followed for a mean of 3.9 months. All patients received a mean of 2.07±1.22 IVCs. The mean BCVA among all patients improved significantly from the baseline 0.81±0.49 logarithm of the minimum angle of resolution (logMAR) VA to the final VA of 0.72±0.52 logMAR (P <0.001). Concomitantly, the mean CST decreased significantly from the baseline value of 427.85±148.99 µm to the final value of 275.31±108.31 µm (P <0.001).

When considering the three groups, the investigators reported that the patients with normal renal function had higher baseline hemoglobin levels and thinner baseline CST compared with the patients in the other two groups (P <0.001 for both comparisons).

The baseline HbA1c levels did not differ among the three groups (P>0.05). Good baseline BCVA (P =0.001) and thicker baseline CST (P =0.041) were associated with VA improvement. Higher eGFR (P <0.001), higher hemoglobin (P =0.032) and thicker baseline CST (P =0.017) were associated with macular oedema retrogression in the conbercept-treated diabetic patients, which showed a better anatomic response to IVC.

Dr Wu and colleagues concluded that DMO patients with good baseline BCVA and thicker baseline CST had a better functional response to IVC. In contrast, those with high eGFR, high hemoglobin, and thicker baseline CST had a better anatomic response to IVC. “The clinical response to IVC for DMO may rely to some extent on the regulation of renal function. The prognosis of macular oedema may also be an indicator for evaluating renal function,” the investigators said.

References

1. Wei Wu, Hui-Dong Liu, Xue Xiao,/et al. Renal dysfunction associated with clinical response to intravitreal conbercept therapy for diabetic macular edema. Int J Ophthalmol. 2025,(3):454-461. DOI:10.18240/ijo.2025.03.12

2. Chen XD, Li C, Ding GL, et al. Clinical efficacy and changes of serum VEGF-A, VEGF-B, and PLGF after conbercept treating neovascular age-related macular degeneration. Int J Ophthalmol. 2023;16:1489-1495.

3. Xu Y, Ye Q, Shen W. Intravitreal conbercept injection with panretinal photocoagulation for high-risk proliferative diabetic retinopathy with vitreous hemorrhage. Int J Ophthalmol. 2024;17:1066-1072.

4. Yao JJ, Huang WL, Gao LX, et al. Comparative efficacy of anti-vascular endothelial growth factor on diabetic macular edema diagnosed with different patterns of optical coherence tomography: a network metaanalysis. PLoS One. 2024;19:e0304283.

5. Wang HP, Guo JS, Tao SS, et al. One-year effectiveness study of intravitreously administered conbercept® monotherapy in diabetic macular degeneration: a systematic review and meta-analysis. Diabetes Ther. 2020;11(5):1103-1117.

6. Kiciński K, Gawęcki M. Wide-field optical coherence tomography in patients with diabetic macular edema. J Clin Med. 2024;13:4242.

7. Salvetat ML, Pellegrini F, Spadea L, et al. The treatment of diabetic retinal edema with intravitreal steroids: how and when. J Clin Med. 2024;13:1327.

8. Ku WN, Tien PT, Lin CJ, et al. Changes of estimated glomerular filtration rate and glycated hemoglobin A1c in diabetic macular edema patients treated by ranibizumab and aflibercept in the tertiary referral hospital. Medicina. 2022;58:1081.

9. Zhu YZ, Dou ZZ, Wang WY, et al. Intravitreal injection of conbercept for diabetic macular edema complicated with diabetic nephropathy. Int J Ophthalmol. 2024;17:304-310.

10. Lai IP, Huang WL, Yang CM, et al. Renal biomarkers for treatment effect of ranibizumab for diabetic macular edema. J Diabetes Res. 2020;2020:7239570.