Background: For the diagnosis of NF 2, ocular findings like juvenile cataract, retinal and combined hamartomas of the retinal pigment epithelium and the retina as well as tumours of the optic nerve play an important role. An early diagnosis is essential in order to inhibit deafness from bilateral vestibular schwannoma. But sometimes the Manchester diagnostic criteria for NF2 are not completely fulfilled. Frequently, suspicious macular anatomy is found in neurofibromatosis 2 (NF2) patients. We hypothesise that the underlying retinal pigment epithelium or the retina of the macular region alters in NF2 patients. Therefore, we have tested by fluorescence angiography whether NF2 is associated with chorioretinal changes.
Methods and patients: In a prospective study, 48 patients matching the criteria for NF2 with known genotype underwent a complete ophthalmic examination including funduscopy and fluorescence angiography. The influence of the genotype was statistically analysed by odds ratios and their 95% confidence intervals.
Results: Eleven eyes of nine patients showed choroidal hyperfluorescence in the macular region on fluorescence angiography. There was staining spreading from grainy hyperfluorescence to minor variants of a combined hamartoma of the retina and the retinal pigment epithelium. All of these manifestations presented without leakage in the late angiographic phases. These choroidal findings were present in one patient with frameshift mutation, in two patients with nonsense mutations and in six patients with splice site mutations of the NF2 gene. The statistical analysis showed a significant lower risk of choroidal alterations in patients with somatic mosaicism, deletions and unfound mutations.
Conclusion: Using fluorescence angiography pathological changes of the macular region can be detected in NF2 patients. The ophthalmic examination, which often is limited to the anterior eye segment, may play a role in finding the diagnosis in incomplete NIH criteria. The presented study shows chorioretinal hyperfluorecences without leakage of the macular region, which might be considered as a forme fruste of a hamartoma. Choroidal hyperfluorescences add to the spectrum of genotype-phenotype correlations in NF2.