, the disorder is characterised by lisch nodules , optic gliomas , choroidal hamartomas and congenital hypertrophy of the retinal pigment epithelium ( chrpe ) .
it appears that reduction of neurofibromin expression can lead to abnormalities in the differentiation and migration of melanoblasts and melanocytes which gives rise to characteristic caf - au - lait spots of the skin .
caf - au - lait spots are characterised by increased levels of epidermal melanogenesis   and increased numbers of epidermal melanocytes   which contain abnormally large pigment granules , known as macromelanosomes . in the eye , lisch nodules consist of masses of melanocytes .
congenital hypertrophy of retinal pigment epithelium , a rare feature of patients with nf-1 , consists of focal areas of pigment epithelial cells that are more densely packed with pigmented granules . retinal pigment epithelium ( rpe ) also contains melanin .
it can be hypothesized that changes in neurofibromin expression are leading to some melanin changes also in rpe of patients with nf-1 .
it has been described in patients with albinism that the reduced level or absence of retinal pigment is associated with changes detectable by eog   - the most commonly used electrophysiological test of rpe function .
our initial eog   results suggested that dysfunction of the rpe may be a characteristic feature of individuals with nf-1 . in order to verify our preliminary findings we performed the eog examination in a two - fold larger group of patients diagnosed with nf-1 .
the eogs were performed on 36 patients ( 67 eyes ; 22 males , 14 females ; mean age : 26.6  10.9 years ; mean refractive error : -0.21  0.72 d ) who fulfilled the national institutes of health clinical diagnostic criteria for nf-1   and compared to 32 healthy subjects .
ocular findings in a group of patients with nf-1 are as follows : snellen visual acuity - 20/20 , lisch nodules - ( 65/67 ) 97% of analysed eyes , choroidal hamartoma - ( 5/67 ) 7.4% , chrpe ( congenital hypertrophy of the retinal pigment epithelium ) - ( 4/67 ) 5.9% , optic nerve glioma - ( 3/67 ) 4.4% , normal colour vision and visual field measured by kinetic perimetry .
the two groups were similar as far as age , sex and refractive error were concerned .
electro - oculography ( utas e-2000 ) was performed according to the standard for eogs of the international society for clinical electrophysiology of vision ( iscev ) standardisation committee . in the eog examination ,
patients ' pupils were dilated ( 10% neo - synephrine , 1% tropicamide ) and a stimulus intensity equal to ca .
1/2 ) was used , which has been recommended as a standard for the light adaptation phase in this case .
we analysed the values of the lowest potential reached during the dark phase ( dark - trough amplitude in v , dta ) , dark - trough latency ( dtl ) measured in minutes , the highest potential reached during light exposure ( light - peak amplitude in v , lpa ) , light - peak latency ( lpl ) in minutes and the ratio of the light - peak amplitude to dark - trough amplitude ( arden index , ai ) .
statistical analysis was performed using parametric ( shapiro - wilk test , student t - test ) and non - parametric ( mann - whitney test ) tests with a significance level of p  0.05 .
this study was approved by the committee of medical ethics of the medical university in szczecin .
descriptive statistics and statistical analysis of the eog parameters for two study groups ( nf-1 patients and normal controls ) are shown in table 1 .
the student t - test and the mann - whitney test revealed significant differences in the variables dta ( p < 0.001 ) , ai ( p < 0.001 ) , and lpl ( p < 0.001 ) .
figure 1 illustrates an example of an nf-1 patient with supernormal ai on eog examination .
eog in nf-1 patients - descriptive statistics and statistical analysis ( 36 patients ) n - number of eyes ; m - arithmetic mean ; min - minimum value ; med - median ; n - normal distribution ; sd - standard deviation ; max - maximum value * * * - p < 0.001 for the nf-1 group , the mean dta ( 305.0  81.2 v ) was significantly lower than that of the control group ( 408.1  112.9 v ) and the mean ai ( 3.42  0.62 ) was significantly higher ( 2.45  0.37 ) .
the mean lpl for the nf-1 group ( 7.6  1.1 min ) was significantly lower than that of the control group ( 8.4  1.3 min ) .
the mean lpa of the nf-1 group ( 971  229 v ) was lower than that of the normal subjects ( 982  242 v ) ; this difference was not statistically significant .
the mean dtl for the nf-1 group ( 11.6  2.2 min ) was almost the same as that of the control group ( 11.7  2.0 min ) .
supernormal eogs ( ai > mean+2sd - more than 3.19 ) were detected in 58.3% ( 21/36 ) of patients , 58.2% ( 34/67 ) of eyes .
the results of our studies suggest that dysfunction of rpe as measured by eog is present in patients with nf-1 .
enlargement of the analysed eyes of patients with nf-1 ( from 35 to 67 eyes ) did not change significantly the eog results obtained in a group of patients with nf-1 published previously .
we observed a supernormal eog ( increased ais ) in 58% of analyzed eyes in individuals with nf-1 .
detection of changes by eog and in parallel small changes in erg what was shown previously   indicating that the occurrence of abnormalities was mainly in the rpe .
the dark - trough potential is a result of polarisation differences between the apical and basal membranes of rpe cells .
the significantly lower amplitude of this potential suggests that the mechanisms underlying polarization differences are altered in nf-1 .
this variation in membrane potentials results from differences in the types and distribution of transport mechanisms between the two rpe membranes .
primarily kchannels generate the apical membrane potential with smaller contributions from the electrogenic na / kpump and nahco3cotransporter .
it is reasonable to expect that changes in any of above transport mechanisms can occur in nf-1 . as mentioned in the introduction
pigmented cells contain particularly high amounts of calcium , reflecting the enormous calcium binding capacity of melanin .
the data obtained in the current study suggest that supernormal eogs in nf-1 patients are a result of changes in calcium levels caused by melanin abnormalities , which is related to the reduction in expression of neurofibromin .
this disorder is characterised by congenital reduction or total absence of pigment in hair , skin and eyes .
this finding also supports the hypothesis that eog changes in nf-1 patients are associated to neurofibromin - mediated melanin alterations .
it is well known that in many ocular disorders electrophysiological changes can occur independently of alterations detectable by ophthalmoscopy .
also in our patients abnormal eogs were observed in individuals without characteristic nf-1 fundus changes detectable during routine examination .
nf-1 can be unequivocally diagnosed by the detection of nf-1 gene mutations by dna / rna analyses
. molecular analysis of large genes like nf-1 are still complex , time consuming and expensive .
due to cost implications genetic analysis of nf-1 has to be limited to the groups of pre - selected patients that have a high probability of carrying mutations . in order to identify such groups
it is important to find as many independent clinical features as possible that are closely correlated with nf-1 disease expression .
the high frequency of supernormal eogs in patients with nf-1 suggests that this type of analysis might be useful in the initial identification of patients with nf-1 who do not present with the typical spectrum of disease symptoms .
 purposeto asses the retinal pigment epithelium ( rpe ) function measured by eog testing in patients with neurofibromatosis type 1 ( nf-1 ) . 
 our preliminary eog results suggested dysfunction of the rpe in individuals with nf-1 . in order to confirm our initial results we performed eog examination on a larger group of nf-1 patients.patientsstudies 
 were performed on 36 patients with clinically diagnosed nf-1 and compared to normal healthy controls.methodsstandard eog recordings were performed in accordance with the international society for clinical electrophysiology of vision ( iscev ) standards.resultsin nf-1 patients the arden indexes of the eog test were significantly higher primarily due to the lower values of dark troughs . 
 supernormal eogs ( exceeding the value of the mean + 2 sd from the control group ) were present in 58% of nf-1 patients.conclusionsdysfunction of the rpe is a characteristic feature of individuals with nf-1 . 