Transient Expression of Lymphatic Markers in Retrobulbar Intraconal Orbital Vasculature During Fetal Development

PURPOSE: The aim of this study is to investigate the presence of orbital lymphatic vessels during fetal and neonatal development and in adults using a panel of lymphatic markers. METHODS: This was a retrospective observational case series. For analyzing lymphatic vessels, we used formalin-fixed paraffin-embedded enucleated eyes from 25 human fetuses between 13 and 24 weeks of gestation and postnatal eyes from 15 children and 5 adults. Immunohistochemical analysis of lymphatic vessels was performed for the markers: lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1), podoplanin (D2-40), Prospero-related homeobox gene-1 (Prox-1), pan-endothelial marker CD31, and blood vessel endothelium specific CD34. RESULTS: Vasculature showing endothelial expression of LYVE-1, D2-40, Prox-1, and CD31 in combination with absence or weak expression of CD34, as would be expected for lymphatic vessels, was seen in 11 of 25 fetuses in an age range from 14 weeks to 23 weeks of gestation (44%). This lymphatic vascular staining pattern was also observed in 4 of 15 liveborn children (27%), all within 1 month of age, of which two were born prematurely at 32 and 34 weeks of gestation. Interestingly, an incomplete lymphatic staining pattern was observed in another 4 fetuses and two liveborn children of 4 months and 7 years old. No expression of lymphatic markers was observed in adult orbital vasculature. CONCLUSIONS: No retrobulbar intraorbital lymphatic vessels were observed in adults, however, we did observe transient expression of lymphatic markers in retrobulbar intraconal orbital vasculature during fetal and early neonatal development. The orbit may, therefore, be proposed to possess a full range of lymphatic plasticity.