Effects of GH/IGF-I Axis on Retinal Vascular Morphology: Retinal Vascular Characteristics in a Clinical Setting with Severe IGF-I Deficiency

Background: The purpose of this study was to assess retinal vascular characteristics of patients with Laron syndrome (LS) as a genetic model of IGF-I deficiency before and after rhIGF1/IGFBP3 treatment and to compare them with healthy controls.Methods: A total of 28 subjects (11 LS, and 17 controls) were enrolled. Patients with LS received combined rhIGF1/rhIGFBP3 1-2mg/kg/d in a single dose and digital fundus imaging was performed. The number of branching points and tortuosity of retinal vessels were studied. Pre- and post-treatment findings were compared with each other and with controls.Results: The number of branching points was significantly lower in patients with LS in comparison to controls (12.733.41, and 17.47 +/- 5.82 respectively, p=0.012). This difference persisted after treatment (12.09 +/- 2.66 post-treatment LS versus controls, p=0.017). Tortuosity indices of nasal arteries (NA) were significantly less in LS than that of controls (upper NA 1.07 +/- 0.04 and 1.12 +/- 0.06 respectively p=0.022; lower NA 1.07 +/- 0.03 and 1.13 +/- 0.07 respectively, p=0.004). This difference also persisted following treatment (p<0.05). Remaining vessels did not differ in tortuosity index. There was no significant difference of tortuosity index and number of branching points before and after treatment in patients with LS.Conclusion: Retinal vascular development may be adversely affected in the setting of severe IGF-I deficiency confirming a major role for GH/IGF-I axis during retinal vascular development in humans antenatally. Resolution of IGF-I deficiency following birth using rhIGF1, however, may not reverse these changes, suggesting that IGF-I may be necessary but insufficient by itself for postnatal angiogenesis.