Chorioretinal biomarkers in hypothalamic amenorrhea

Abstract

Purpose: The aim of our study was to evaluate changes in the retinal and choriocapillaris circulations in patients with hypothalamic amenorrhea.

Methods: Prospective, cross-sectional observational study on 25 patients (50 eyes) diagnosed with hypothalamic amenorrhea and 25 age-matched healthy women. Optical coherence tomography angiography (OCTA) was used to evaluate the vessel density (VD) of superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris VD layers in whole 6.4 × 6.4-mm image and in fovea grid-based image. In patients' group, systemic parameters were collected: body mass index (BMI), endometrial rhyme thickness, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, insulin, and cortisol.

Results: SCP and DCP did not show any statistical difference when comparing patients and controls (all p > 0.05). Differently, choriocapillaris VD in the whole region showed a non-significant tendency toward higher values in the patients group in both eyes (p = 0.038 for right eye [RE], p = 0.044 for left eye [LE]). Foveal choriocapillaris VD was higher in hypothalamic amenorrhea women vs. healthy controls (66.0 ± 2.4 vs. 63.7 ± 6.6%, p = 0.136 for RE; 65.0 ± 2.4 vs. 61.6 ± 7.0%, p = 0.005 for LE). Focusing on correlation with systemic parameters, SCP and DCP foveal density had a medium/high effect size with endometrial rhyme, along with DCP in the fovea area vs. cortisol and SCP in the whole area vs. FSH.

Conclusion: When comparing hypothalamic amenorrhea patients to healthy subjects, OCTA detected changes in the choriocapillaris layer, showing increased VD in the early stage of the systemic pathology, suggesting that microvascular "compaction" could be a first phase of hypoestrogenism adaptation.

Keywords: Choriocapillaris vascular density; Hypothalamic amenorrhea; Optical coherence tomography angiography.

Fig. 1

Sample of a Solix full-range OCTA analysis of the CVD using the in-built software algorithm, showing en face OCTA image (A) and structural OCT image (B) of the choriocapillaris, after setting a customized layer from 9 to 30 μm below the Bruch’s membrane, identified by the red lines in fovea-centered B-scans (C and D). The CVD of the whole macular area (highlighted by the upper blue rectangle) and of the fovea only area (in the fovea grid-based image, highlighted by the lower blue rectangle), expressed in percentage, was collected. OCTA, optical coherence tomography angiography; OCT, optical coherence tomography; CVD, choriocapillaris vascular density

Fig. 2

Violin plots showing differences in CVD whole and fovea between controls and patients, divided into right and left eyes. CVD, choriocapillaris vascular density; ns = no significative difference; * indicates p < 0.05; ** indicates p < 0.01