Retinoschisis

1. X-Linked (Juvenile) Retinoschisis

Genetics & Pathophysiology

• Rare, X-linked recessive condition caused by mutations in the RS1 gene (Xp22.13), which encodes retinoschisin — a protein secreted by photoreceptors involved in intercellular adhesion
• The basic defect involves splitting of the retinal nerve fibre layer (NFL) from the rest of the sensory retina (though recent evidence shows outer plexiform layer separation is also frequent)
• Males are affected; female carriers are asymptomatic with no retinal changes

Clinical Features

• Typically presents in boys aged 5–10 years with difficulty reading / reduced vision
• Less commonly: squint or nystagmus in infancy (associated with advanced peripheral retinoschisis + vitreous haemorrhage)

• Macular (foveal) schisis — the hallmark: spoke-like ("bicycle wheel" / petaloid) striae radiating from the foveola with underlying cystoid changes; the most common appearance
• Peripheral schisis (in ~50%): predominantly inferotemporal; inner layer (ILM + NFL only) can develop oval defects, and in extreme cases vessels float as "vitreous veils"
• Silvery peripheral dendritic figures, vascular sheathing, pigmentary changes, retinal flecks, nasal dragging of retinal vessels
• Drusen-like dots at the macula

• Vitreous / intra-schisis haemorrhage
• Neovascularization
• Subretinal exudation
• Rhegmatogenous or tractional retinal detachment (uncommon)
• Visual acuity deteriorates during the first two decades, may then stabilize until the 5th–6th decade

Fig. 15.38 — Juvenile retinoschisis. (A) 'Bicycle wheel' maculopathy; (B) large oval inner leaf defects; (C) vitreous veils; (D) peripheral dendritic lesions; (E) OCT: macular schisis with cystic spaces; (F) ERG: selective b-wave reduction (electronegative pattern). — Kanski's Clinical Ophthalmology, 10th ed.

Investigations

Treatment

• Topical or oral carbonic anhydrase inhibitors (e.g. dorzolamide TDS, acetazolamide) — reduce foveal schisis and may improve visual acuity in some patients
• Vitrectomy for non-clearing vitreous haemorrhage or retinal detachment (technically challenging)
• Patching for superimposed amblyopia in children < 11 years
• Gene therapy under investigation (aiming to restore retinoschisin function)
• Follow-up: every 6 months (more frequently if treating amblyopia)

2. Age-Related (Degenerative) Retinoschisis

Epidemiology & Pathology

• Present in ~5% of the population over age 20; particularly prevalent in hypermetropes
• Develops from coalescence of microcystoid degeneration → splitting of NSR into inner and outer layers with permanent loss of visual function in the affected area
• Typical form: split at the outer plexiform layer (most common)
• Reticular form: split at the nerve fibre layer — rarer, more prone to complications

Fig. 11.4.1 — Age-related degenerative retinoschisis showing the dome-shaped inferotemporal elevation. — Wills Eye Manual

Clinical Features

• Usually asymptomatic (photopsia and floaters absent — no vitreoretinal traction)
• Occasionally: decreased vision, vitreous haemorrhage, or progressive RD

• Bilateral in up to 80%
• Smooth, dome-shaped, convex, relatively immobile elevation — typically inferotemporally
• Inner leaf surface may show "snowflakes" (whitish Müller cell footplate remnants) and vascular sclerosis
• Bridging grey-white tissue strands across the schisis cavity
• Prominent cystoid degeneration near the ora serrata
• Inner leaf breaks: small and round
• Outer leaf breaks: larger, rolled edges, behind the equator — higher risk of RD
• Absolute scotoma corresponding to the schisis area (cf. relative scotoma in RRD)
• No pigment cells or haemorrhage in vitreous; no demarcation line (unless associated RD)

• RD is rare (~1% even with breaks in both layers); usually asymptomatic and rarely progressive
• Posterior extension to involve fovea — very rare

Investigations

Treatment

• Usually observation — discuss RD symptoms with all patients; return if floaters, flashing lights, or visual curtain appear
• Surgery only when a clinically significant RD develops
• A small RD walled off by a demarcation line is typically not treated
• Follow-up: every 6 months

Key Differentiating Features

Recent evidence note (PMID 41760155): A 2026 umbrella systematic review on inherited retinal diseases (including X-linked RS) highlights gene therapy as an emerging approach — consistent with the textbook note that RS1 gene replacement therapy is under active investigation.

B-Scan Ultrasonography (Ophthalmic)

Principle

Normal B-scan ultrasonography — Wills Eye Manual

Probe Placement

• Directly on the globe (topical anaesthetic applied) — preferred for locating specific pathology (e.g. retinal tear, tumour)
• Over the closed eyelid with sterile methylcellulose coupling gel — preferred in trauma or poorly cooperative patients (avoids pressure on the globe)

Technique

• The eye is examined with the patient looking straight ahead, up, down, left, right
• The probe moves in the opposite direction to gaze — e.g., patient looks left → probe moves nasally to scan the nasal fundus
• Dynamic scanning: patient moves the eye while the probe is held still — critical for assessing membrane mobility

• High gain → amplifies weak echoes (e.g., vitreous opacities, subtle haemorrhage)
• Low gain → shows only strong echoes (retina, sclera); improves resolution

Clinical Uses in Ophthalmology

B-Scan Findings in Specific Conditions

Retinal Detachment (RRD)

• High-reflectivity membrane with good mobility of retina and vitreous on dynamic scan
• Subretinal fluid (SRF) extending to the ora serrata
• Membrane tethered at optic disc

B-scan ultrasonogram showing retinal detachment — Kanski's Clinical Ophthalmology, 10th ed.

Retinoschisis vs. RD

Vitreous Haemorrhage

• Non-clotted: uniform, low-level echoes filling vitreous cavity
• Clotted/organising: particulate echoes; may show strand formation
• Critical use: to exclude underlying RD or choroidal melanoma behind a dense haemorrhage — always perform B-scan in dense VH

Posterior Scleritis

• Scleral thickening with fluid in the sub-Tenon space posterior to the globe → "T-sign" (the fluid creates a perpendicular dark line alongside the optic nerve shadow)

Choroidal Detachment

• Serous: smooth, dome-shaped elevations, low internal reflectivity
• Haemorrhagic: higher internal reflectivity, less mobile, may "kiss" (touch each other) anteriorly

Limitations / Pitfalls

• Dense intraocular calcifications (e.g. phthisis bulbi) → poor image quality
• Silicone oil or intraocular gas → distorts image; scan the patient upright to improve quality
• Known ruptured globe → relative contraindication to direct probe placement on globe; use over closed lid with copious gel and no pressure
• Anterior orbit / retrobulbar structures → B-scan has limited anterior orbital penetration; CT/MRI preferred for deeper orbital pathology