This study investigated predictors of DR-worsening after PRP. After adjusting for various confounders, younger age, lower baseline BCVA, and diabetic nephropathy or hyperlipidemia at the start of PRP were found to be independent predictors of a higher probability of DR-worsening after PRP. We then incorporated these four risk factors and developed a new model to predict the risk of DR-worsening following PRP treatment within 5 years.
Age at the onset of diabetes has been proved to be one of the key factors in the development and progression of PDR . Studies have shown that younger patients with PDR had a higher risk of visual loss than older patients, and the onset age of type 2 diabetes under 45 years old was an independent risk factor for the development and progression of PDR [24, 25]. Previous studies have shown that more severe retinal proliferation, greater surgical difficulty, and poorer anatomical success rate due to rapid progression of retinal neovascularization could be found in younger PDR patients undergoing vitrectomy [26, 27]. This study also reached a similar conclusion that younger age was an independent risk factor for DR-worsening after PRP. In addition, younger patients have higher prognostic requirements and higher social burdens associated with visual loss. Therefore, age may be an important but often underappreciated prognostic factor of DR in clinical practice.
This study showed that DR progressed significantly after PRP treatment when the baseline BCVA was low. Because increased visual loss is associated with increased DR severity , once DR becomes advanced, active treatment such as PRP or intravitreal anti-vascular endothelial growth factor (VEGF) injection becomes the best way to reduce DR-related blindness . However, in cases where the retinal ischemic is severe, diffusion of oxygen needed by macular may remain insufficient and even lead to macular edema in spite of PRP, which could cause lower vision [15, 29]. This finding is also in line with the study that lower vision is associated with the larger avascular zone area of foveal in DR patients . Therefore, prevention of DR-worsening may be an important strategy to reduce DR-related blindness.
In our study, the association of diabetic nephropathy with DR-worsening after PRP was observed to be statistically significant (P < 0.05 in both univariate and multivariate logistic regression analysis), in addition, the laboratory parameters related to renal function including creatinine, urea, and serum cystatin C had a statistically significant association with DR-worsening in the univariate logistic analysis, suggesting that with increasing severity of renal function there will be more likelihood of the DR-worsening. Furthermore, compared with the non-DR-worsening group, the patients in the DR-worsening group had worse kidney function and a greater frequency of diabetic nephropathy. Current studies have confirmed that diabetic nephropathy is closely related to DR, especially PDR or severe NPDR in diabetic patients [31–33]. Similarly, diabetic nephropathy was found to be an independent risk factor of DR-worsening after PRP. The pathophysiology of both DR and diabetic nephropathy is similar. The development of DR and diabetic nephropathy influences and promotes each other, which supports the view that the two diseases share a common etiological basis, and emphasizes that the treatment and care of DR should be combined with a multidisciplinary integrated treatment management model .
Our study found that hyperlipidemia is the risk factor for the presence of DR-worsening after PRP treatment. In recent years, hyperlipidemia has been considered one of the strongest risk factors for the occurrence and development of DR [35, 36]. As reported in some studies, lipid-lowing therapy reduces the progression of DR and the need for laser treatment [37, 38], and total cholesterol and low-density lipoprotein are risk factors for the occurrence of any DR , in addition, poor control of serum triglycerides is associated with progression of PDR , which indicates that intensive lipid control may be associated with better clinical prognosis of DR after PRP treatment.
At present, some studies have suggested that poor blood glucose control, long diabetes duration, hypertension, anemia, and other variables are also independent risk factors for DR-worsening [18, 40, 41]. However, this study did not produce similar results, possibly because of the following limitations: in this study, patients with stable DR tend to lack regular review and even lose follow-up, which results in fewer patients in the non-DR-worsening group than in the DR-worsening group, which may have introduced bias. In addition, this study was a retrospective analysis without diagnostic tests on patients, so there may be differences in the collection of patient’s history. While this model is useful for internal validation, external validation is also necessary. Therefore, prospective and multicenter studies are necessary to confirm these findings.
Our Model has 4 risk factors that are easy to obtain in medical records and further explores the interaction between these risk factors and DR-worsening, which have rarely been reported in previous studies and will provide a reference for future studies. Furthermore, the Model can provide patients with an immediate and reliable assessment of DR-worsening within 5 years after PRP treatment. This estimate could guide clinicians to identify ones at high risk of DR-worsening at an early stage and prescribe additional treatment, such as more frequent follow-up, supplemental laser photocoagulation therapy, or intravitreal anti–VEGF injection.