We followed 91 patients with acromegaly and 123 patients with IFG for more than eight years to study and compare the incidence of retinopathy in patients with abnormal glucose homeostasis, who are thus at risk for developing retinopathy. To the best of our knowledge, this is the first study to compare the incidence of retinopathy in these patients. Both groups had similar HbA1c, cholesterol, and blood pressure levels. A significant intergroup difference was higher GH (8.05±16.18 vs. 0.78±1.25 ng/mL) and IGF-1 (547.0±342.1 vs. 146.7±51.4 ng/mL) levels in patients with acromegaly. During the follow-up period, eight patients with acromegaly (8.8%) and 12 with IFG (9.8%) developed some degree of retinopathy. Three patients with acromegaly (3.3%) and two with IFG (1.6%) progressed to proliferative retinopathy. Patients with acromegaly were noted to have the same incidence of non-proliferative retinopathy (OR: 0.830; 95% CI: 0.318–2.164) and a non-statistically significantly higher incidence of proliferative retinopathy (OR: 2.461, 95%; CI: 0.404–14.988).
Retinopathy is the most common complication in diabetes patients and can even develop during the prediabetes stage. Patients with acromegaly usually have elevated GH and IGF-1 levels, which can lead to insulin resistance and diabetes [16]. GH has been considered pathogenic for diabetes for nearly a century, and excessive GH secretion can cause microvascular complications, like retinopathy [17]. Füchtbauer et al. (2020) conducted a study to evaluate the morphology of retinal vessels in patients with acromegaly and the prevalence of diabetic retinopathy in patients with acromegaly and diabetes [18]. They reported a higher number of retinal blood vessel branches in patients with acromegaly. However, there was not a high prevalence of diabetic retinopathy in patients with acromegaly and diabetes [18].
Risk factors for diabetic retinopathy include the time since onset of diabetes, high blood glucose, high blood pressure, dyslipidemia, and insulin resistance [19, 20]. Yau et al. (2012) conducted a systematic study to examine the overall prevalence and risk factors for diabetic retinopathy in patients with diabetes [21]. The overall prevalence of any retinopathy was 34.6%, and the prevalence of proliferative retinopathy was 6.96%. The prevalence increase was associated with the time since onset of diabetes and HbA1c and blood pressure levels [21]. Song et al. (2018) conducted a systematic review and meta-analysis to investigate the prevalence and risk factors for retinopathy in China [22]. The observed prevalence for retinopathy was 1.14% in the general population and 0.07% for proliferative retinopathy. In patients with diabetes, the combined prevalence for any retinopathy was 18.45%, and the combined prevalence for proliferative retinopathy was 0.99% [22]. We retrospectively analyzed 43 patients with acromegaly and 129 age- and gender-matched type 2 diabetes patients [13]. We found that 9.3% of patients with acromegaly (4/43) and 9.3% of patients with type 2 diabetes (12/129) had proliferative retinopathy. However, non-proliferative retinopathy was not observed in patients with acromegaly, while it was observed in 25.9% of patients with type 2 diabetes (33/129) [13]. Even though non-proliferative retinopathy is not observed in patients with acromegaly, the frequency of proliferative retinopathy is the same as in patients with type 2 diabetes [13]. Füchtbauer et al. (2020) conducted a cross-sectional study to assess the prevalence of retinopathy in 39 patients with long-term acromegaly and diabetes in Sweden [18]. They diagnosed five cases (13%) of retinopathy (two cases of proliferative diabetic retinopathy and three cases of proliferative diabetic retinopathy) and concluded that the prevalence of retinopathy is not higher in patients with acromegaly compared to patients with diabetes [18]. In the current eight-year follow-up study, retinopathy was diagnosed in eight patients (8.8%) with acromegaly and 12 patients (9.8%) with IFG. According to our research and previous reports, we may assume that the prevalence of non-proliferative retinopathy in patients with acromegaly is higher than in the general population, lower than in patients with diabetes, and the same as in patients with IFG [13, 19–22]. Additionally, the prevalence of proliferative retinopathy in patients with acromegaly is higher compared to the general population and patients with prediabetes and may be similar to the prevalence in patients with diabetes [13, 19–22].
This study’s strengths include the recruitment of a relatively high number of patients with acromegaly and the regular follow-ups. This study is the first to compare the prevalence of retinopathy in patients with acromegaly and IFG. Both groups had identical major risk factors for retinopathy as reflected by their HbA1c, cholesterol, and blood pressure levels. The only significant intergroup difference was their GH and IGF-1 levels, enabling us to precisely investigate their effects on retinopathy development. Nevertheless, our study was limited by presenting only a small event rate for proliferative retinopathy, which prevents confirmation of our hypothesis. Therefore, including more participants and a longer follow-up period is required to confirm our hypothesis.
In conclusion, although not statistically significant, patients with acromegaly appear to have the same incidence of non-proliferative retinopathy and a non-statistically significantly higher incidence of proliferative retinopathy compared to patients with IFG. Our data revealed that GH or IGF-1 may play a crucial role in the development of proliferative retinopathy and may influence the progression of retinopathy. Although a future study with more patients and a longer follow-up period is warranted, the data suggest that patients with acromegaly, like patients with diabetes, should be screened for retinopathy.