50-Year Retrospective Study Highlights Pediatric Ocular Complication Differences in T1D, T2D

To prevent serious ocular complications, children with type 2 diabetes (T2D) may require ophthalmoscopic evaluations at least as frequently as, or more frequently than, children with type 1 diabetes (T1D), according to results of a retrospective, population-based review. Findings were published in JAMA Ophthalmology.

Specifically, the analysis of 525 individuals younger than age 22 found “diabetic retinopathy, proliferative diabetic retinopathy (PDR), and the need for pars plana vitrectomy (PPV) occurred within a shorter diabetes duration for children with T2D compared with T1D,” the authors explained, while “children with T2D had almost twice the risk of developing retinopathy compared with those with T1D.”

Diabetic retinopathy, the leading cause of blindness among young adults, is caused by retinal neurodegeneration and a breakdown of the blood-retinal barrier. Although the ocular sequalae of T1D and T2D are well researched, less is known regarding the progression of diabetic retinopathy among children with T2D, despite rising prevalence of the disease, the researchers said.

In addition, there are limited data on the management of diabetic retinopathy for patients with childhood-onset T2D. To address this knowledge gap, the investigators assessed the risk of developing diabetes-associated ocular complications (DAOC) over 50 years.

All individuals with T1D or T2D diagnosed between January 1, 1970, and December 31, 2019, residing in Olmsted County, Minnesota (95.7% White in 1990), were included in the retrospective chart review. Using data from the Rochester Epidemiology Project, the researchers used diagnostic codes to determine diagnoses and subsequent ocular diabetes complications.

Of the 606 children who received their diagnosis in this window, 86.6% underwent at least 1 eye examination following their diabetes diagnosis (n = 461 with T1D; n = 64 with T2D), while “follow-up eye examinations were recorded for any change in retinopathy status through 40 years of age,” the authors wrote.

Patients with T1D were followed for a mean (SD) of 13.6 (9.4) years, and those with T2D, 8.6 (6.9) years. The mean age at diagnosis was 12.1 (5.4) years, and a slight majority of patients (50.3%) were male. Overall, DAOC occurred in 31.2% of children with T1D and in 26.6% of those with T2D.

However, analyses revealed the following HR for specific ocular complication risk between T2D and T1D rates, respectively:

• 1.88 (95% CI, 1.13-3.12; P = .02) for developing any diabetic retinopathy (nonproliferative or greater)
• 2.33 (95% CI, 0.99-5.50; P = .048) for PDR
• 1.49 (95% CI, 0.46-4.89; P = .50) for diabetic macular edema
• 2.43 (95% CI, 0.54-11.07; P = .24) for a visually significant cataract
• 4.06 (95% CI, 1.34-12.33; P = .007) for requiring PPV by 15 years after the diagnosis of diabetes

Approximately 83% of the T1D cohort was White compared with 55% of the T2D cohort. The T2D cohort also included a higher percentage of Asian and Black youth compared with the T1D cohort; these differences are consistent with previous research showing youth-onset T2D is more common among American Indian, Asian, Black, and Hispanic youth than White youth. T1D has been found to occur at a higher rate in White youth.

According to the researchers, their findings suggest “the natural history of retinopathy development among youth diagnosed with T2D may differ from that in youth diagnosed with T1D, where patients with T2D may be more susceptible to developing retinopathy than those with T1D despite controlling for diabetes disease duration.”

Due to the retrospective nature of the study, incomplete data and irregular follow-up mark limitations, while changes in diagnostics and management of diabetes over the past 50 years could have affected comparisons across decades.

The predominantly White population of Olmsted County also limits generalizability of the findings to more racially diverse populations. “Because racial and ethnic minority populations have experienced higher rates of diabetes and retinopathy in other studies, in a more racially diverse population, rates of diabetes and DAOC may be higher than what was observed in this population-based cohort,” the authors explained.

In an accompanying editorial, Jennifer K. Sun, MD, MPH, an associate professor of ophthalmology at Harvard Medical School, stressed the need to better understand diabetic retinopathy outcomes in youth, as the number of young people with T1D is expected to nearly triple and those with T2D to nearly quadruple by 2050.

Despite improvements in medical care and patient education seen in the United States in recent years, “the increased global incidence of diabetes implies that there will be a growing number of individuals at risk for vision loss due to diabetic retinopathy during the following decades,” Sun wrote.

Noting the limitations of the study conducted among Minnesota residents, Sun also highlighted its valuable contribution to the field. “Accurate risk estimates for onset of vision-threatening complications such as PDR and diabetic macular edema are crucial in setting appropriate screening guidelines for baseline and follow-up retinal examinations,” she said.

The report confirms the very low risk for developing advanced retinopathy before puberty and underscores the need to elucidate any differences in ocular outcomes between youth with T1D vs those with T2D.

Further epidemiological studies across diverse cohorts are warranted to help optimize guidelines for baseline screenings in the modern era, Sun concluded. “Such efforts may potentially lead to increased understanding of the mechanistic differences between pathology in T1D vs T2D and ideally provide insight into therapeutic targets to preserve vision in youth with diabetes across subsequent decades of hyperglycemia.”