Morphological changes of β-Zone Peripapillary Atrophy (β-PPA) in children with type 1 Diabetes: A longitudinal study

To investigate the morphological changes and long-term progression of optic disc peripapillary β-zone atrophy (β-PPA) in children with type 1 diabetes over a 3-year period, and to assess the independent predictive value of serum biochemical markers for β-PPA progression.

In this observational clinical cohort study, 24 children (24 eyes) with type 1 diabetes who met the inclusion criteria were followed for 3 years. At baseline and at follow-up, all subjects underwent comprehensive ophthalmic examinations (including uncorrected and best-corrected visual acuity, autorefraction, axial length measurement, and OCT imaging). Standardized methods were used on fundus images to identify and quantify the β-PPA area and the optic disc's ellipticity index. Baseline demographic data, duration of diabetes, BMI, and laboratory parameters (including HbA1c, liver and renal function tests, bilirubin, etc.) were recorded. Paired t-tests (or Wilcoxon signed-rank tests when appropriate) were used to compare continuous variables between baseline and follow-up, and the percentage change in β-PPA area was calculated. Potential influencing factors were first screened by univariable linear regression; variables with significance or clinical relevance were then entered into a multivariate stepwise linear regression model to identify independent predictors. Identified predictors were dichotomized at their median values, and inter-group comparisons and risk stratification analyses were performed.

After 3 years of follow-up, the mean axial length and β-PPA area significantly increased, and the spherical equivalent (SE) refraction shifted significantly toward myopia (P < 0.001). Univariable analysis showed that the percentage change in axial length (AL_change%, which is positively correlated) and a more hyperopic (higher) baseline SE were both associated with a greater relative increase in β-PPA area, whereas higher baseline direct bilirubin (DBil) was associated with a smaller increase in β-PPA (all P < 0.0001). Other factors negatively correlated with β-PPA increase included higher baseline BMI, total bilirubin (TBil), indirect bilirubin (UBil), and serum creatinine. In multivariate analysis, AL_change% was a positive independent predictor of β-PPA area growth, and baseline DBil was a negative independent predictor (adjusted R²=0.703; AL_change%: B = 13.55, p < 0.001; DBil: B=-20.31, p = 0.002). When subjects were divided into four groups based on median baseline DBil and AL_change%, the group with low DBil and high AL_change% had the largest relative β-PPA increase, whereas the high-DBil/low-AL_change% group had the smallest (one-way ANOVA, P < 0.001).

Serum direct bilirubin level, when considered together with axial elongation, may help identify children at higher risk for rapid β-PPA progression at an early stage, pending confirmation in larger and independent cohorts.