Stellate Nonhereditary Idiopathic Foveomacular Retinoschisis (SNIFR) is a relatively new disease concept first reported by Ober et al. in 2014. 7)
As the name suggests, it is a diagnosis of exclusion with the following characteristics:
Epidemiologically, it is more common in women in their 60s to 70s 1, 2). It is often bilateral and may show asynchronous onset (different timing of onset between eyes) 2).
It is not a disease defined by specific diagnostic criteria, but rather a diagnosis of exclusion made after ruling out myopic traction, optic pit, CXLRS, traumatic retinoschisis, and other conditions. The key diagnostic features are stellate cystoid changes in the fovea on OCT and negative RS1 gene testing. For details, see the section on Diagnosis and Testing Methods.
Many cases are asymptomatic and are often discovered incidentally during examination for other diseases or health checkups1, 2, 3).
When symptoms are present, the main complaints are as follows.
OCT is the most important test for diagnosing this disease1, 2, 3, 4).
OCT angiography (OCTA) is useful for excluding vascular lesions 3, 5).
OCT
Foveal cystoid spaces: Stellate or multilocular hyporeflective cavities form in the HFL, ONL, and INL.
Tissue pillars: Vertical bridges within the cystoid spaces. Cause of the stellate pattern.
Partial PVD (VMA): Present in 86%. Residual vitreomacular adhesion 2).
FA
No fluorescein leakage: A distinguishing point from cystoid macular edema (CME). Fluorescein angiography typically shows no leakage.
OCTA
Electroretinography (ERG) shows reduced amplitude in the foveal area on multifocal ERG (mfERG) 5). Full-field ERG also shows a decrease in the b-wave 5, 6). However, ERG abnormalities are often mild and may differ in degree from the marked b-wave reduction seen in CXLRS.
The cystoid spaces in SNIFR are not due to increased vascular permeability (cystoid macular edema) but rather result from separation and cavity formation within the retinal tissue itself. Therefore, no fluorescein leakage is observed on FA, which is an important distinguishing feature from cystoid macular edema.
The established cause of SNIFR is unknown, and specific risk factors are not clear. The currently proposed etiological hypotheses are as follows.
The fact that it is more common in elderly women in their 60s to 70s suggests a possible association with the progression of age-related posterior vitreous detachment (PVD) 1, 2).
OCT, which can visualize the stellate cystoid changes in the fovea with high resolution, is the core of diagnosis 1, 2, 3, 4). Various OCT modes are used to evaluate the extent, depth, and structure of the separation cavity.
This is essential for differentiation from CXLRS (X-linked congenital retinoschisis). In SNIFR, RS1 gene mutations are negative 2, 3, 6). It should always be performed in male patients to rule out CXLRS.
In the diagnosis of SNIFR, differentiation from the following is important.
| Disease | Main differentiating points |
|---|---|
| CXLRS | RS1 mutation positive, male, young onset |
| Myopic traction | High myopia, posterior staphyloma |
| Optic pit maculopathy | Congenital anomaly of the optic disc |
A detailed comparison with CXLRS (X-linked congenital retinoschisis) is shown below.
| Item | SNIFR | CXLRS |
|---|---|---|
| Sex/Age | Often elderly women | Male, young |
| RS1 gene | Negative | Positive2, 3, 6) |
| ERG b-wave | Mildly reduced | Markedly reduced5) |
There is no established standard treatment for SNIFR, and in many cases, observation is chosen1, 2, 3).
For asymptomatic cases or those with good visual acuity, regular OCT follow-up is the basic approach. The fact that spontaneous regression has been reported also supports avoiding unnecessary treatment intervention2, 4).
Carbonic anhydrase inhibitors (CAI), sometimes used for cystic macular diseases, have low efficacy in SNIFR.
Spontaneous resolution (disappearance or reduction of the lesion during natural course) has been observed in a certain proportion of cases2, 4).
Machado Nogueira et al. (2021) reported a case in which SNIFR lesions resolved after vitreomacular adhesion (VMA) released4). This observation supports the possibility that VMA is involved in the onset and maintenance of SNIFR.
Cataract surgery can be safely performed in SNIFR cases with cataract, and the use of multifocal intraocular lenses (multifocal IOLs) has also been reported2, 6). There is no evidence that cataract surgery itself worsens SNIFR, and surgery may be considered in cases with cataract where visual improvement is expected.
The efficacy of CAI (carbonic anhydrase inhibitors) for SNIFR is currently considered low1, 3). This is thought to be because the pathology differs from cystoid macular edema, which involves fluid accumulation due to increased vascular permeability. Since spontaneous resolution also occurs, observation is prioritized first.
The pathophysiology of SNIFR is not yet fully understood, but the following mechanisms are considered likely.
When posterior vitreous detachment (PVD) is incomplete, vitreomacular adhesion (VMA) persists in the macula. This mechanical traction is thought to trigger the following cascade4).
The HFL is a tissue unique to the fovea, where axons of photoreceptors run obliquely from the outer nuclear layer. This oblique structure is thought to be vulnerable to mechanical stress and serves as a starting point for the formation of separation cavities1, 4).
Machado Nogueira et al. (2021) reported a case in which cystoid changes in SNIFR resolved after VMA release, suggesting that Müller cell dysfunction mediated by VMA may be the main pathology of SNIFR4). According to this hypothesis, release of VMA and elimination of mechanical traction allow Müller cell function to recover, leading to fluid reabsorption and tissue repair.
Bayram-Suverza (2025) reported that SNIFR occurs asynchronously in both eyes and argued that regular OCT follow-up of the contralateral eye is necessary after definitive diagnosis in one eye2). This finding deepens the understanding of the natural history of SNIFR and contributes to the establishment of examination protocols.
The existence of cases in which SNIFR resolves spontaneously without treatment provides important clues for understanding the pathophysiology4). An association with VMA release has been suggested, and research is expected to verify the efficacy of methods to confirm and control VMA involvement (e.g., pharmacologic vitreous liquefaction, release of vitreous traction).
Hassanpoor (2025) reported that multimodal imaging including OCTA is useful for differentiating vascular lesions and CXLRS 3). In the future, multimodal imaging analysis including OCTA is expected to contribute to elucidation of the pathology of SNIFR and improvement of diagnostic accuracy.
Currently, indications for active treatment are limited due to the existence of spontaneous regression cases, but if the association with VMA becomes clear, minimally invasive vitreous traction release therapies such as pharmacologic vitreolysis (e.g., ocriplasmin) may become a viable option. Furthermore, as the disease concept becomes established, prospective studies with case accumulation are expected 2, 4).
