# Ophthalmic Manifestation in Neurofibromatosisosis Type 2
## 4 Discussion  
Type 2 neurofibromatosisis is a complex, genetically determined pathology with a variable spectrum of manifestations. Genetical features have been characterized over time and brought together in a complex genetic severity score, which corresponds to clinical features. The tissue mosaic form (presumed and confirmed) includes patients with clinical signs of NF2 not confirmed by blood tests or patients with genetic alterations detectable only in specific tissues. The classic form includes mild and moderate NF2 clinical expression, with typical mutation identified in blood cells. The severe forms imply the presence of specific full truncating mutations involving exons 2-13, leading to aggressive phenotypes [8]. Age of diagnosis, age of onset, and the number of intracranial tumors, and mutation type remain the three major predictive factors of mortality in NF2 patients. Missense mutations have been linked to a lower risk of mortality. Moreover, clinical manifestations are more variable in patients with splice-site mutations [13]. In more than half of the cases, the most frequent symptoms at presentation are related to a vestibular schwannoma of the VIII cranial nerve. Spinal tumors are diagnosed in about 90% of patients, especially meningiomas in about 50% of patients [14]. The mild form of the disease (Gardner variant) occurs mainly with hearing loss (vestibular schwannoma) and presents a slower course and better prognosis than the severe early-onset form (Wishart variant). In the severe form, the ocular manifestations identified in childhood can lead to an early diagnosis of the disease as they often precede the other systemic manifestations. In the mild form, since the life expectancy of patients is 79 years (46 years in the severe form), the early identification of ocular manifestations is fundamental for preserving good visual function with targeted interventions [8]. In type 2 neurofibromatosisis, the ocular involvement is frequent. In 2006, [PERSON] first classified the ocular features of the disease into NF2-specific and NF2-associated. In the NF2-specific group, he included posterior and cortical subcapsular/capsular cataracts (67% of patients), epiretinal membranes (40% of patients), retinal hamardomas (3% of patients), gliomas of the optic disc (13% of patients), and optic nerve meningiomas (27% of patients). In the NF2-associated group disc edema, optic atrophy, motility disorder, pupil dysfunction, lid dysfunction, reduced corneal sensation, exophthalmos, and exposure or neurotrophic keratopathy are included. The manifestations inserted in the latter group are caused by direct or indirect damage to the nervous structures determined by tumors [9]. Most recruited patients (13 out of 14) had late onset of symptoms (\(>\)20 years), corresponding to the mild form of the disease (Gardner variant). Among our cohort, the severe early onset form was identified in a single 16-year-old patient, who presented ERMs and subcapsular cataract, typically associated with the severe form. In our study, in accordance with [PERSON] et al. the most frequently reported sign was cataract [9], which remains the only ophthalmological finding included among the NF2 diagnostic criteria [11]. \begin{table}
\begin{tabular}{l l l l l} \hline
**Patient** & **LCR Near** & **LCR Distance** & **CT Near** & **CT Distance** \\ \hline
2 & \(-8^{\circ}\) & \(-12^{\circ}\) & \(-18\) PD & \(-25\) PD \\ \hline
3 & \(-6^{\circ}\) & \(-10^{\circ}\) & \(-15\) PD & \(-20\) PD \\ \hline
4 & symm & symm & +6 PD & +6 PD \\ \hline
6 & \(-20^{\circ}\) & \(-15^{\circ}\) & \(-40\) DP & \(-35\) DP \\ \hline
9 & +20\({}^{\circ}\) & +20\({}^{\circ}\) & +40 PD & +40 PD \\  & & & (Krimsky test) & (Krimsky test) \\ \hline
12 & symm & symm & +7 PD & +5 PD \\ \hline
14 & symm & symm & +5 PD & +4 PD \\ \hline \end{tabular}
\end{table} 
Table 4: Quantification of prism diotters in patients presenting strabismus. LCR: light corneal reflexes, CT: cover test, symm: symmetrical, PD: prism diotters.