At present, no treatment to halt the natural progression of schisis formation is available. Because of the slowly progressive nature of the disease, a conservative approach is advocated for majority of XLRS cases. Supportive measures include refractive correction, educational support and low vision aids such as large-print textbooks, preferential seating in the front of the classroom, use of handouts with high contrast.

Amblyopia prevention therapy is indicated in cases of hypermetropia or severe retinoschisis. General avoidance of head trauma and high-contact sports is recommended to reduce the risk of retinal detachment and vitreous hemorrhage.

Retinal holes or tears can be treated with laser therapy or cryotherapy to prevent their progression to a full-scale detachment. Vitreous hemorrhage when not associated with retinal detachment may resolve spontaneously. Surgery (scleral buckling, pneumatic retinopexy, vitrectomy) may be required for the management of the vision-threatening complications, such as severe vitreous hemorrhage and retinal detachment.

Some success of treatment on schisis cavities and visual acuity with topical carbonic anhydrase inhibitor dorzolamide has recently been reported but need further studies to confirm the effect and its duration. Gene therapy research on a mouse model of human retinoschisis has shown a restoration of the expression of retinoschisin protein in photoreceptors and normal ERG configuration, making gene therapy a viable therapeutic option in the future.