Of the major vascular systems in the human eye, the choriocapillaris and foetal vasculature of the vitreous, including the hyaloid vasculature, vasa hyaloidea propria and tunica vasculosa lentis, develop first by hemo-vasculogenesis around 4–6 gestational weeks [1]. This is followed by angiogenesis of intermediate choroidal blood vessels, budding from the choriocapillaris [1]. Vasculogenesis of the human retinal vasculature is the last to evolve [1].
The HA, a branch of the ophthalmic artery, is located in the optic canal and extends from the optic disc to the crystalline lens through the vitreous humour [3]. HA branches throughout the vitreous, forming the vasa hyaloidea propria [8]. This vascular network forms anastomoses with the tunica vasculosa lentis, the vasculature surrounding the lens [8]. The anterior foetal vasculature supplies the developing lens and inner retina with oxygen and nutrients until the retinal vasculature forms [1].
HA is formed by 7 weeks of gestation [1]. The vasculature expands and matures throughout 12 weeks of gestation, and, at this stage, proliferation ensues in both endothelial cells and pericytes [1]. This angiogenic growth is led by the vascular endothelial growth factor (VEGF) mainly secreted by astrocytes [9]. At 13 weeks of gestation, regression and apoptosis of hyaloid vasculature is triggered [1, 10], terminating around the middle of the eighth month of gestation with retinal vasculature almost fully developed [11]. The programmed endothelial cell apoptosis and regression of hyaloid network is facilitated by physical separation of the VEGF-producing cells, due to differentiation of the lens epithelial cells into lens fibre cells and formation of the lenticular capsule [12], macrophages that secrete factors such as Wnt7b [13] and neurons [14, 15]. By titrating VEGF in retina, neurons limit angiogenesis through up-regulation of VEGF receptor 2 (VEGFR2), sequestering excessive VEGF [14, 15]. The absence of neuronal VEGFR2 results in misdirected angiogenesis, impeding transition from the foetal to postnatal circulatory network [14, 15].
In a healthy foetus, regression of the HA itself starts at 18 weeks, and by 29 gestational weeks it disappears leaving clear central zone in the vitreous humour, called Cloquet’s canal [3, 5, 16]. The main trunk of the HA finally closes centrally by the end of gestation [11].
Therefore, based upon gestational age, the hyaloid system is expected to be persistent in many very low birth weight infants [17], as in case of our patient. However, at the time of birth, some remnants of HA may persist and exceptionally the entire HA remains, constituting PHA [7].
There is a single case reporting combined CRVO and CRAO in a patient with PHA caused by cataract surgery [7]. The authors hypothesized that during hydrodissection, sudden disruption of the joining tissue caused arterial wall dissection and CRA collapse [7]. Consequently, the formation of this compartment could have generated a spatial compromise, giving rise to secondary CRVO [7]. Combined CRAO and CRVO in patients with FVL mutation, even though very rare, is described in the literature [18]. However, genetic analysis excluded this cause in our patient.
Contrary to the secondary cause [7], this case presented spontaneous combined CRAO and CRVO event related to patent PHA. We speculated that in our patient, PHA twisting led to torsion of the residual primordial common bulb, branching off to HA and CRA. In this case, we considered that CRAO would have occurred first, opposed to the inflammatory and thrombotic aetiology of combined CRVO and CRAO [18, 19]. The consequential CRVO advanced by venous stasis due to decrease in arterial inflow. As torsion itself caused irreversible ischemic injury, vision loss and neovascular glaucoma resulted.
By the third year of age, the vitreous is primarily a collagen gel. Thereafter, liquefaction occurs typically in its central part, suggesting that there is a gradual change in the vitreous collagen [7]. More liquid vitreous enables PHA to whirl more freely. The limitations of this case report include limited and insufficient quality of the clinical data prior to our examination. We cannot entirely exclude external factors such as physical activity or minor physical force applied to the eye as part of the gaming or other physical activity by the child, that may have led to the complication of PHA, which may have been unnoticed by the parents.
Thus, in case of PHA, we advocate FA to be performed and if connection with retinal artery is proven, parents should be informed on the possible devastating complications and vision loss. Accordingly, prompt surgical treatment should be considered.
