Ophthalmological manifestations in VHL and NF 1: pathological and diagnostic implications

Abstract

Von Hippel-Lindau disease (VHL) and neurofibromatosis type 1 (NF 1) are hereditary multitumor syndromes that show associated ocular manifestations. Capillary retinal angioma, a benign vascular tumor, is the classical ocular lesion in VHL. It often appears as the first manifestation of the disease and may thus lead to the diagnosis of VHL. Since small angiomas can be treated easily by laser photocoagulation, a regular ocular screening of VHL patients is recommended. Ocular manifestations of NF 1 are more diverse as compared to VHL. Lisch nodules of the iris are an important diagnostic criteria of NF 1 since they can be found in almost every affected patient. Optic glioma can occur both intraorbitally and intracranially. The intraorbital form causes progressive protrusion of the globe and eventually blindness. Extension of the tumor beyond the chiasm worsens the prognosis quoad vitam. The hallmark of NF 1, namely cutaneous neurofibroma can cause visual impairment when affecting the skin of the eyelids. The rare intraorbital pexiform neurofibroma is associated with abnormal development of the orbital bones and infantile glaucoma. It may result in orbital mass effects and therefore may need surgical excision.

Clinical and genetic aspects of neurofibromatosis 1

“…Lisch nodules increase in frequency with age. 45 They are not present at birth 21 but can be found in Ͼ90% patients with NF1 aged 16 years or older. 45 …”

Renal cancer in von Hippel–Lindau disease and related syndromes

“…21,[31][32][33] The prototypic lesions of VHL disease include haemangioblastomas of the retina and the central nervous system (Figure 2a-d). 34,35 Retinal haemangio blastomas are often the initial lesion of VHL disease, occurring during early childhood. 35 At least 60-70% of VHLaffected patients develop retinal lesions.…”

“…34,35 Retinal haemangio blastomas are often the initial lesion of VHL disease, occurring during early childhood. 35 At least 60-70% of VHLaffected patients develop retinal lesions. The majority of central nervous system haem angioblastomas develop in the cerebellum and spinal cord.…”

Ciliary body cysts in neurofibromatosis: A new coexistence?

“…They are not present at birth, but can be found in more than 90% of patients with NF1 aged 16 years or older [5,6]. Other ocular manifestations of NF1 are subcutaneous neurofibromas of the eyelids and periocular area, optic pathway gliomas, ectropion uvea, multifocal choroid nevi and melanomas, and retinal astrocytomas [5,6]. Associated glaucoma and globe enlargement in NF1 has also been reported [7][8][9].…”