retinoschisis

Retinoschisis, Juvenile

Clinical Characteristics
Ocular Features: 

Retinoschisis is a retinal disorder characterized by a cystic degeneration of the retina, leading to a split of retinal layers mainly at the level of the nerve fiber layer. Almost all patients have macular involvement, most commonly with foveal spoke-like streaks consisting of microcystic cavities that may coalesce over time. Retinal pigment epithelium atrophy and pigment clumping may occur.  Peripheral schisis is evident in about 50% of patients with large bullous cavities that may resolve spontaneously leaving a pigmented demarcation line. Other retinal findings are white retinal flecks, exudative retinopathy with retinal detachment, perivascular sheathing and dendritiform vessels in the periphery. Vitreous veils are commonly seen that are caused by separation of the thin inner wall of a peripheral schisis cavity and inner wall holes. Bridging vessels may rupture into the cystic cavity or the vitreous. The onset of the disorder has been detected as early as three months, but the majority of cases are five years old or older. Many present with mildly decreased vision that cannot be corrected with glasses and the diagnosis is often delayed. Visual acuity is highly variable ranging from 20/20 to 20/200, but may decline with age and with complications such as vitreous hemorrhage and macular detachment.  The disorder is also associated with axial hyperopia, posterior subcapsular cataract and strabismus. Fluorescein angiography shows minimal or no leakage as opposed to cystoid macular edema. Focal areas of vascular leakage into schisis cavity may be present as well as peripheral capillary nonperfusion. Electroretinograms exhibit a reduced b-wave and a preserved a-wave.

Systemic Features: 

No general systemic manifestations are associated with juvenile retinoschisis.

Genetics

Juvenile retinoschisis is an X-linked recessive disorder that affects mainly males. The causative mutations involve the gene RS1 located on the X chromosome at Xp22. Female carriers may have peripheral schisis amd many allelic variants have been reported.  The encoded protein retinoschisin is a secreted protein produced by photoreceptors and bipolar cells and may be involved in cell-cell adhesion or ion channel regulation.

Treatment
Treatment Options: 

There is presently no effective treatment for the disorder, but decreased vision later in life can be aided with low vision aids. Cases with posterior subcapsular cataract can be treated with cataract extraction.  Improvement in the cystic macular lesions, central foveal zone thickness, and visual acuity have been reported to benefit from topical dorzolamide treatment.

References
Article Title: 

Peripheral fundus findings in X-linked retinoschisis

Fahim AT, Ali N, Blachley T, Michaelides M. Peripheral fundus findings in X-linked retinoschisis. Br J Ophthalmol. 2017 Mar 27. pii: bjophthalmol-2016-310110. doi: 10.1136/bjophthalmol-2016-310110. [Epub ahead of print].

PubMed ID: 
28348004

X-linked retinoschisis: an update

Sikkink SK, Biswas S, Parry NR, Stanga PE, Trump D. X-linked retinoschisis: an update. J Med Genet. 2007 Apr;44(4):225-32. 2006 Dec 15.

PubMed ID: 
17172462

Goldmann-Favre Syndrome/ESCS

Clinical Characteristics
Ocular Features: 

Enhanced S-cone syndrome, sometimes called Goldman-Favre syndrome, is a retinal disorder characterized by increased sensitivity to blue light, night blindness from an early age, and decreased vision.  Additional features include an optically empty liquefied vitreous, progressive foveal or peripheral retinoschisis, macular cysts, chorioretinal atrophy and pigmentary retinopathy as well as posterior subcapsular cataract formation.  Hyperopia is a feature, at least in childhood.   Enhanced S-cone syndrome is the only retinal disorder that has a gain of a subtype of photoreceptors, in this case the S-cones (short wave length) that detect blue light. Rod photoreceptors and red and green cone receptors are degenerated to a variable degree. Electroretinography shows an extinct rod photoreceptor response and hypersensitivity to shorter wavelengths.

There is considerable variation in the clinical features of NR2E3 mutations which has led to some confusion in the nosology.  Some cases are called juvenile retinoschisis, others are called retinitis pigmentosa, or clumped pigment retinopathy.  Central acuity ranges from near normal (20/40) in young people to 20/200 or worse especially in older adults.  Visual field constriction likewise varies from patient to patient.  Retinal pigmentary changes and the amount of cystic changes in the macula are somewhat age dependent.

Systemic Features: 

No general systemic manifestations are associated with enhanced S-cone syndrome and Goldman-Favre syndrome.

Genetics

This is an autosomal recessive retinal disorder caused by mutations in NR2E3, also known as PNR, located on chromosome 15q23.  It is a part of a transcription factor complex necessary for the development of photoreceptors.  Mutations in NR2E3 cause degeneration of rod photoreceptors and an increased number of S-cone photoreceptors resulting in an increased ratio of blue to red-green cone photoreceptors. Mutations in the NR2E3 gene can also cause a clinical picture resembling simple autosomal recessive retinitis pigmentosa.

Two brothers with an enhanced S-cone phenotype and normal rod function have been reported.  Scotopic b-wave ERG amplitudes were normal but OCT showed flattening of the macular area and thinning of the photoreceptor layer.  This may be the result of a different mutation in this family but no molecular defect was found.

Several Moroccan families have been reported with homozygous or compound heterozygous mutations in the NRL gene (162080).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

There is presently no effective treatment for the disorder, but visual function can be improved with low vision aids. Cataract surgery may be beneficial.

Improvement in vision has been reported with the use of topical carbonic anhydrase inhibitors.

References
Article Title: 

Expanded Clinical Spectrum of Enhanced S-Cone Syndrome

Yzer S, Barbazetto I, Allikmets R, van Schooneveld MJ, Bergen A, Tsang SH, Jacobson SG, Yannuzzi LA. Expanded Clinical Spectrum of Enhanced S-Cone Syndrome. JAMA Ophthalmol. 2013 Aug 29.  [Epub ahead of print] PubMed PMID: 23989059.

PubMed ID: 
23989059

Phenotypic variation in enhanced S-cone syndrome

Audo I, Michaelides M, Robson AG, Hawlina M, Vaclavik V, Sandbach JM, Neveu MM, Hogg CR, Hunt DM, Moore AT, Bird AC, Webster AR, Holder GE. Phenotypic variation in enhanced S-cone syndrome. Invest Ophthalmol Vis Sci. 2008 May;49(5):2082-93.

PubMed ID: 
18436841
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