Spotlight Case: Runs in the Family

James P. Berg, MD Christina Y. Weng, MD, MBA

Lead Image: Montage fundus photographs reveal inferior laser photocoagulation scars bilaterally, extending into the inferior macula of the left eye. In the inferotemporal periphery of the left eye, there is an area of elevation consistent with retinoschisis.

Case history

A 30-year-old male presented with a 6-week history of blurry vision OS. He was previously seen by an optometrist and another retinal specialist who both told the patient that he had a retinal detachment and referred him to our clinic. The patient states that he sees a “curtain” intermittently in the superior periphery of his left eye; his right eye is stable. His past ocular history is significant for bilateral scleral buckles (age 4) and multiple laser treatments in both eyes, and he reports having had chronically poor vision since early childhood. His family history is pertinent for a maternal grandfather and uncle with poor vision. He reports no history of trauma.

His best-corrected visual acuity was 20/100 OU with normal pupils and intraocular pressures.  Visual fields tested grossly by confrontation did confirm a superior deficit in both eyes. Anterior examination was notable only for trace nuclear sclerotic cataracts OU. Dilated funduscopic examination of his right eye revealed a normal disc and vessels, macular schisis without hemorrhage, and a peripheral encircling buckle with dense inferotemporal laser. Left fundus showed similar findings, but also had an area of elevation inferotemporally without tears or holes that was encroaching upon the anterior border of laser scars.

Spectral-domain optical coherence tomography (OCT) revealed bilateral macular retinoschisis without subretinal fluid (Figure 1). OCT scan was also performed through the inferotemporal elevation and confirmed the presence of retinoschisis without retinal detachment (Figure 2). B- and A-scan ultrasound (images not shown) of the left eye’s inferotemporal quadrant revealed a thin, taut area of elevation with a corresponding narrow spike on A-scan consistent with retinoschisis.  

Figure 1. Spectral-domain OCT of bilateral maculas demonstrating schisis cavities resulting from inner retinal splitting.

Figure 2. Spectral-domain OCT of the left eye’s inferotemporal quadrant revealing a large area of retinoschisis, but absence of subretinal fluid. 

Figure 3. Representative fundus photographs of macular retinoschisis6.  Red-free photographs (top row) illustrate the radial cartwheel pattern; correlating color fundus photographs are shown below. 

What’s your diagnosis?

X-linked retinoschisis

Discussion

The patient’s examination findings and family history are consistent with a diagnosis of X-linked retinoschisis (XLRS). This retinal dystrophy accounts for the vast majority of congenital retinoschisis cases and has an estimated prevalence of 1 in 15,000 to 1 in 30,000[1].  XLRS is caused by mutations in the RS1 gene located at Xp22.12[2] which lead to splitting within the inner retinal layers. The condition was first described in the 19th century, but it was not officially documented until 1997 when the RS1 gene was discovered; since then, multiple inactivating mutations have been identified[3],[4].  

The phenotypic presentation can vary greatly in patients with XLRS, even among those with the same causative RS1 mutation. The onset of symptoms often follows a bimodal distribution with one subset of patients presenting in infancy with strabismus or nystagmus and the other subset affected in early childhood with poor visual acuity[5]. Patients commonly have foveal schisis and can be identified by the classic cartwheel pattern radiating from the foveal center, best-visualized with red-free photography (Figure 3). In addition to macular involvement, patients can also have peripheral retinoschisis cavities.[6]  The inferotemporal quadrant is the most common peripheral location affected[7]. Similar to the cavities in senile degenerative retinoschisis, these areas may have inner and/or outer layer holes that can lead to accumulation of subretinal fluid and progress to retinal detachments. Presumably, our patient had prior scleral buckles at the age of 4 for retinal detachments with laser photocoagulation inferotemporally to prevent posterior extension.

Management of retinoschisis is primarily directed at its progressive complications such as retinal detachment which can be treated with cryotherapy, laser photocoagulation, scleral buckling, or pars plana vitrectomy. Vitreous hemorrhage, so long as it is not associated with retinal detachment, can be observed as it will usually self-resolve. Although there have been some studies to suggest that topical dorzolamide may lead to reduction of intraretinal cystoid cavities and subsequent visual improvement, results have been inconsistent[8], and the search for an effective treatment continues. Genetic testing in XLRS can be up to 90-95% effective in identifying a mutation[9].  It is important to offer genetic counseling to all XLRS patients and their family members. There are currently a handful of ongoing clinical trials studying the use of an adeno-associated virus vector to deliver gene therapy in XLRS patients. 

Our patient appeared to have stable, chronic macular schisis bilaterally with a subacute, large schisis cavity inferotemporally in his left eye. Because of the intermittent and non-progressive nature of his symptoms along with examination findings of retinoschisis without detachment or retinal holes, observation was the decided management plan after extensive discussion of options with the patient. Of course, strict retinal detachment symptoms were discussed, and the patient has remained stable thus far. 

Take-home points

  • XLRS is caused by a mutation in the RS1 gene, and represents one of the most common causes of progressive juvenile macular degeneration.
  • Symptoms can vary among affected patients; retinoschisis can generally be observed, but if a retinal detachment develops, it must be treated accordingly.
  • Genetic testing and counseling should be offered to patients and their families.
  • Gene therapy using an adeno-associated virus vector is being studied for this condition and may lead to more definitive treatment options in the near future.

 References:

  1. De La Chappelle A, Alitalo T, Forsius H. X‚Äźlinked juvenile retinoschisis. In: Wright AF, Jay B, eds. Molecular Genet Inherited Eye Disorders. Switzerland: Harwood Academic Publishers. 1994;339–357.
  2. Yassur Y, Nissenkorn I, Ben-Sira I, et al. Autosomal dominant inheritance of retinoschisis. Am J Ophthalmol. 1982;94(3):338–343.
  3. Haas J. Ueber das Zusammenvorkommen von Veranderungen der Retina und Choroidea. Arch Augenheilkd. 1898;37:343–348.
  4. Huang Y, Mei L, Gui B, et al. A novel deletion mutation in RS1 gene caused X-linked juvenile retinoschisis in a Chinese family. Eye (Lond.). 2014;28(11):1364–1369.           
  5. George ND, Yates JR, Bradshaw K, Moore AT. Infantile presentation of X linked retinoschisis. Br J Ophthalmol. 1995;79(7):653–657.
  6. Sikkink S, Biswas S, Parry NR, et al. X-linked retinoschisis: an update. J Med Genet. 2007r;44(4):225-232. doi:10.1136/jmg.2006.047340
  7. George ND, Yates JR, Moore AT. Clinical features in affected males with X-linked retinoschisis. Arch Ophthalmol. 1996;114(3):274–280.
  8.  Apushkin MA, Fishman GA. Use of dorzolamide for patients with X-linked retinoschisis. Retina. 2006;26(7):741–745.
  9. Wang T, Zhou A, Waters CT, et al. Molecular pathology of X linked retinoschisis: mutations interfere with retinoschisin secretion and oligomerisation. Br J Ophthalmol. 2006;90(1):81–86. doi:10.1136/bjo.2005.078048

Financial Disclosures:

Dr. Berg: None

Dr. Weng: Allergan (C)

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