Retinal angiomatosis in a patient with NF1 was reported in 1967 by Frenkel [
7]. Muci-Mendoza et al., in 2002, reported on 12 of 32 patients (37.5%) who presented retinal microvascular abnormalities [
5]. The present report is the second case series showing retinal microvascular alterations in six of 17 NF1 patients (35%).
In the present study, all abnormal retinal microvessels were overlying patchy choroidal alterations as shown on NIR imaging. However, they were localized to the retina and did not involve the choroid, as shown by spectralis EDI-OCT cross-sections. Although choroidal vasculature is altered by the space occupying choroidal nodules, it is difficult to establish whether there is any correlation between these nodules and the abnormal microvascular retinal vessels.
Choroidal nodules are ovoidal bodies consisting of proliferating Schwann cells arranged in concentric rings around an axon [
8]. They show similarities to cutaneous neurofibromata and Lisch nodules of the iris [
9]. This follows the principle of aberrant proliferation of tissues of neural crest origin in NF1 [
10] but does not directly justify the presence of vascular abnormalities, which can be an expression of changes in mesodermal germ layers
. The term “phakomatoses”, as described by Van der Hoeve, includes Recklinghausen’s neurofibromatosis, tuberous sclerosis, Hippel-Lindau disease, Sturge-Weber syndrome, Louis-Bar syndrome and Wyburn-Mason syndrome [
1]. Even before the modern era of DNA genomic studies, similarities in inheritance patterns and affected germ layers had been noted among the various phakomatoses. Today, there is still wide discussion regarding the interrelationships between these forms. Sporadic reports in the literature show that a relationship can exist between a chiefly ectodermal and a primarily mesodermal phakomatosis and NF1 has been reported in association with von Hippel’s disease [
11,
12]. Furthermore, in phakomatosis pigmentovascularis there is an association of vascular and pigmentary alterations [
13,
14]. There is evidence supporting developmental abnormalities of vasomotor nerve cells that originate in the embryonal neural crest and immunohistochemical studies have shown the presence of perivascular nerves in the port wine stains seen in Sturge-Weber Syndrome [
15]. Although this is an extremely complex field where both embryogenesis and genomic analysis must be taken into consideration, it can be speculated that functional disorders of vasomotor nerve cells which originate in the embryonal neural crest can lead to the retinal microvascular alterations observed in NF1 patients.