Vascular Patterns & Pathophysiology in X-Linked Retinoschisis: Insights from OCTA

Advanced imaging, particularly swept-source optical coherence tomography angiography (SS-OCTA), continues to refine our understanding of retinal microanatomy and disease pathophysiology. Two recent publications shed light on the structural and vascular characteristics of X-linked retinoschisis (XLRS), offering insights critical for diagnosis, monitoring, and conceptualizing disease mechanisms.

Key Insights from the Literature

1. The Role of Bridging Vessels in XLRS Pattern Formation (Fragiotta et al., 2018):
   This seminal study compared XLRS with stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR). Using SS-OCTA, a critical difference was visualized:

   • In XLRS: The schisis within the inner nuclear layer (INL) contained numerous bridging structures that demonstrated clear vascular flow signals. These vessels connect the intermediate capillary plexus (ICP) and deep capillary plexus (DCP), forming part of the deep vascular complex (DVC). The authors propose that these regularly spaced vascular connections provide structural support, influencing the characteristic radial pattern of small cavities and limiting wider retinal layer separation.

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   • In SNIFR: The schisis occurs in the avascular Henle’s fiber layer. Corresponding OCTA shows no flow signal within the bridging tissue, resulting in a different structural pattern.

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   Clinical Implication: This work suggests the vascular anatomy within the INL is a key determinant of the “retinoschisis” pattern seen not only in XLRS but potentially in other conditions with INL cavitation (e.g., cystoid macular edema in RP, microcystic macular edema in optic neuropathies). It also provides strong evidence supporting a “serial” model of perifoveal capillary plexuses, with abundant connections between the ICP and DCP.

2. Ultra-Widefield SS-OCTA in Clinical Practice (Zhou et al., 2025):
   This case report demonstrates the application of ultra-widefield SS-OCTA in a 13-year-old with XLRS. It successfully correlates clinical findings (bullous retinoschisis, vitreous veil, spoke-wheel foveal schisis) with multimodal imaging:

   • Structural OCT B-scan: Confirmed schisis extending from the nerve fiber layer to the INL.

   • Ultra-widefield SS-OCTA: Highlighted multifocal flow defects that corresponded precisely to the schitic cavities seen clinically and on structural OCT.

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   Clinical Implication: Ultra-widefield SS-OCTA provides a comprehensive, non-invasive map of both structural schisis and associated perfusion abnormalities. This technology is poised to enhance our understanding of the natural history of XLRS, particularly the temporal relationship between structural changes and vascular flow, which may inform prognosis regarding risks like retinal detachment.

Synthesis for the Vitreoretinal Surgeon

• Diagnostic Precision: SS-OCTA can help differentiate XLRS from other forms of retinoschisis (like SNIFR) based on the presence or absence of vascular flow within the schitic bridges.

• Pathophysiological Understanding: The visualization of intact vasculature within INL schisis cavities in XLRS reinforces the concept of a structural weakness at the level of Müller cells and the ILM, rather than a primary vascular insult. However, these vessels may influence the disease morphology.

• Monitoring Tool: Ultra-widefield SS-OCTA offers a powerful method to monitor disease extent and progression over time, mapping both anatomical and functional vascular changes in a single scan.

• Surgical Planning: Understanding the full peripheral extent of schisis and associated vascular anomalies via ultra-widefield imaging could be valuable in pre-operative planning for complications like retinal detachment.

The integration of SS-OCTA into the assessment of XLRS moves us beyond static anatomy, offering a dynamic view of structure-function relationships that is deepening our grasp of this complex inherited vitreoretinopathy.