COMMENTS       

Stephen A. Dellostritto, OD

 

The funduscopic appearance and structural changes in patients with stellate non-hereditary idiopathic foveomacular retinoschisis (SNIFR) and congenital X-linked retinoschisis (XLRS) are grossly similar. The primary differences between the two conditions lie in the genetics and the functionality of the retina based on ERG interpretation. XLRS is associated with an inherited genetic mutation in the RS1 gene. This gene encodes retinoschisin, which is a protein expressed by the retinal photoreceptors and bipolar cells to help maintain the structural integrity of the retina. The full-field electroretinogram (ffERG) of patients will XLRS also show an electronegative response, although varying severities of the b-wave amplitude are reported in the literature. It has also been suggested that a lack of electronegative ERG response should not exclude the diagnosis of XLRS.1,2 Renner et al conducted a study of 24 patients with XLRS, confirmed with RS1 mutations, and found that almost half did not display an electronegative ERG, however all did have abnormal ERGs. 

It would not be farfetched to anticipate a reduced b-wave response in an individual with such drastic foveomacular retinoschisis as seen in this patient diagnosed with SNIFR, however this is not the case. The normal ERG associated with SNIFR compared to the electronegative response associated with XLRS is a great demonstration of the clear inner and outer retinal dysfunction in XLRS, despite similar structural changes seen in the two conditions. It’s been suggested the origins of the retinal dysfunction may be due to ON- and OFF- pathway abnormalities at the level of the bipolar cells, widespread cone dysfunction, and more.1 The pathophysiology of SNIFR is not clearly understood, as this is a relatively rare and newly recognized disease entity. Some have postulated that cause to be due to irregular vitreomacular adhesion in combination with increased susceptibility to retinoschisis, Valsalva incidences, and treatment with topical dorzolamide.3-6

Further differences between XLRS and SNIFR, of course, include the male predilection XLRS due to the x-linked inheritance pattern of the disease versus a potential female predilection in SNIFR. The visual acuity of XLRS patients is also typically significantly reduced, around 20/100, compared to those with SNIFR, which is typically 20/40 or better, however the progression and expression of XLRS is highly variable. 1, 2, 7 There are also subtle, but significant, structural differences shown between SNIFR and XLRS, such as vascular patterns on OCT-angiography (OCT-A) and the specific retinal layers affected.8

Previously, ERGs were frequently utilized in the diagnosis of XLRS, however OCT imaging advances have reduced the dependence on the need to electrodiagnostic testing for diagnosis.1 With the increased recognition of SNIFR considered in the differential diagnoses of foveomacular retinoschisis, there may be a more significant dependence on electrodiagnostic testing to differentiate between the XLRS and SNIFR. Also, the increase in utilization of genetic testing to rule out RS1 mutation may be indicated in differentiating these two disease entities in addition to imaging studies such as fundus autofluorescence (FAF), spectral domain OCT (SD-OCT) and OCT-A.