X-linked Foveal Retinoschisis
Author: Ameen Marashi, MD
Documentation of age as patients are usually young at school age along with visual loss as in X-linked foveal retinoschisis (XLRS), which can range from normal vision to legal blindness , along with documentation of dyschromatopsia (red-green) and any visual field defect .
It is crucial to investigate family history to document the relatives that are suffering from visual loss.
A list of ocular examination should set
1) Best-corrected visual acuity (BCVA) for near and far is an essential step that can perform by a trained optometrist or certified ophthalmologist to document the visual impairment, which can range from 20/20 to less than 20/200, XLRS patients usually presented with hypermetropia.
2) Check eye orthoptics to rule out strabismus and nystagmus in rare and severe cases .
3) A slit-lamp examination done with a thorough exam of clarity and regularity of the cornea and to rule out any conjunctival abnormality such injection of conjunctival vessels should be documented. Any other inflammations of the conjunctiva or eyelids documented, along with iris exam and crystalline lens exam to rule out cataract or intraocular lens (IOL) to document the position and clarity of the posterior capsule.
4) Intra Ocular Pressure (IOP) documentation is essential as high IOP may be associated in severe cases of XLRS patients due to neovascular glaucoma. In cases of increased IOP, then gonioscopy is necessary, Note when high IOP spotted a corrected IOP documented after central corneal thickness measurement .
5) Bilateral dilated fundus exam is essential as XLRS is bilateral disease and fundus exam should include a detailed examination of the optic disc, macula, posterior pole, a mid-peripheral and peripheral retinal exam with specialized indirect wide-field lenses using slit-lamp biomicroscopy or indirect ophthalmoscopy to document the following:
The center of the macula has the form of spoke-wheel with folds irradiating from the center of the fovea.
Fifty percent of cases presented with peripheral retinoschisis (often inferior temporal), which has split the outer retinal from the inner and retinal vessels, can be located in inner or outer retinal layers .
Retinal breaks can be located, which can be small or large; however, in some cases, vitreous veils can be presented, which are a membranous remnant .
The presence of retinal detachment, which can be tractional or rhegmatogenous or/and vitreous hemorrhage, should be documented .
Some other retinal findings that can be associated with XLRS are retinal vessel attenuation or sheathing, subretinal fibrosis, and pigmentation.
It is an essential tool to document the presence of XLRS in young patients who are not cooperative for clinical examination, and foveal schisis can be highlighted in red-free images. However, wide-field images can help to document the presence of peripheral retinoschisis and monitor progression.
Optical Coherence Tomography (OCT)
OCT in XLRS features tubular cystic like changes mainly in inner retinal tissue which may include all retinal layers. Cystic changes can be small in the perifoveal area and quite large at the center of the fovea  with increased retinal thickness, with time, those cystic like spaces may coalesce. After adolescence, the OCT may appear free from cystic like spaces with irregular foveal contours , and OCT is essential to assess macular tissue changes post-treatment.
It is a useful technique to diagnose XLRS complicated with vitreous hemorrhage to rule out the presence of retinal detachment, especially if the other eye has the clinical findings of XLRS.
In the early stages of XLRS, presented with preserved a- wave and reduced b-wave amplitudes, which features a negative waveform ; though not all patients have reduced b-wave and ERG may appear normal .
Managing patients with X-linked foveal retinoschisis
Patients should understand the inheritance of XLRS as females are carries for this disease and have the 50% chance to transmit the XLRS mutation to her male children as for her female children will be carriers. However, a male patient affected with XLRS will only pass the mutation to his female children, and they will be carriers; although there is RS1 gene laboratory analysis for patients known to have or maybe carriers may be beneficial.
Medical treatment of XLRS patients
-Cystoid macular changes can be treated with topical Dorzolamide t.i.d. If this fails, then oral Acetazolamide 250 mg b.i.d. The effect of oral Acetazolamide can be noticeable within one week.
-Oral Acetazolamide may cause hand tingling and fatigue, but it is more effective than topical Dorzolamide and may have better visual outcomes.
-No role for laser treatment for peripheral retinoschisis and may get it worse .
Surgical options for XLRS patients
Pars plana vitrectomy can be indicated for cases complicated with retinal detachment or/and non-clearing vitreous hemorrhage  and thus can be done by doing core vitrectomy and inducing PVD with ILM peeling and gas tamponade .
Follow up and prognosis
- XLRS is a very slowly progressive disease, and patients may get legally blind in age 60 or 70 with BCVA less than 20/200; however, the average visual acuity is 20/70 .
- Third of patients may develop vitreous hemorrhage while retinal detachment can develop up to 20% of patients.  Other rare complications may cause visual loss such as neovascular glaucoma, optic disc atrophy, macular dragging, or retinal splitting involving the macula may occur as well .
- Patients should be followed up for amblyopia and should be encouraged to use low vision aids , and patients should avoid any head trauma.
1. Riveiro-Alvarez R, Trujillo-Tiebas MJ, Gimenez-Pardo A, et al. Correlation of genetic and clinical findings in Spanish patients with X-linked juvenile retinoschisis. Invest Ophthalmol Vis Sci 2009;50(9):4342–50.
2. McKibbin M, Booth AP, George ND. Foveal ectopia in X-linked retinoschisis. Retina 2001;21(4):361–6.
3. George ND, Yates JR, Moore AT. Clinical features in affected males with X-linked retinoschisis. Arch Ophthalmol 1996;114(3): 274–80.
4. Ando A, Takahashi K, Sho K, Matsushima M, Okamura A, Uyama M. Histopathological findings of X-linked retinoschisis with neovascular glaucoma. Graefes Arch Clin Exp Ophthalmol 2000; 238(1):1–7.
5. Peachey NS, Fishman GA, Derlacki DJ, Brigell MG. Psychophysi- cal and electroretinographic findings in X-linked juvenile reti- noschisis. Arch Ophthalmol 1987;105(4):513–16.
6. Kellner U, Brummer S, Foerster MH, Wessing A. X-linked con- genital retinoschisis. Graefes Arch Clin Exp Ophthalmol 1990; 228(5):432–7.
7. Campbell JP, Skalet AH, Lauer AK. Vitreous veils associated with congenital X-linked retinoschisis. JAMA Ophthalmol 2015; 133(8):e151155.
8. Sieving PA, MacDonald IM, Chan S. X-linked Juvenile Retinoschisis. 2003 Oct 24 [Updated 2014 Aug 28] In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
9. Chatziralli I, Theodossiadis G, Brouzas D, Emfietzoglou I, Theodossiadis P. Optical Coherence Tomography Evolution in a Case of X-Linked Juvenile Retinoschisis: 15 Years of Follow-Up. Case Rep Ophthalmol. 2017;8(3):459–464. Published 2017 Sep 14. doi:10.1159/000480069
10. Tanimoto N, Usui T, Takagi M, et al. Electroretinographic find- ings in three family members with X-linked juvenile retinoschisis associated with a novel Pro192Thr mutation of the XLRS1 gene. Jpn J Ophthalmol 2002;46(5):568–76.
11. Miyake Y, Shiroyama N, Ota I, Horiguchi M. Focal macular electroretinogram in X-linked congenital retinoschisis. Invest Ophthalmol Vis Sci 1993;34(3):512–15.
12. Zhang L, Reyes R, Lee W, et al. Rapid resolution of retinoschisis with acetazolamide. Doc Ophthalmol 2015;131(1):63–70.
13. Avitabile T, Ortisi E, Scott IU, Russo V, Gagliano C, Reibaldi A. Scleral buckle for progressive symptomatic retinal detachment complicating retinoschisis versus primary rhegmatogenous retinal detachment. Can J Ophthalmol 2010;45(2):161–5.
14. Tantri A, Vrabec TR, Cu-Unjieng A, Frost A, Annesley WH Jr, Donoso LA. X-linked retinoschisis: a clinical and molecular genetic review. Surv Ophthalmol 2004;49(2):214–30.
15. Ikeda F, Iida T, Kishi S. Resolution of retinoschisis after vitreous surgery in X-linked retinoschisis. Ophthalmology 2008;115(4): 718–22.e1.
16. Apushkin MA, Fishman GA, Rajagopalan AS. Fundus findings and longitudinal study of visual acuity loss in patients with X-linked retinoschisis. Retina 2005;25(5):612–18.
17. Tasman W, Greven C, Moreno R. Nasal retinal dragging in X-linked retinoschisis. Graefes Arch Clin Exp Ophthalmol 1991; 229(4):319–22.
18. George ND, Yates JR, Moore AT. Clinical features in affected males with X-linked retinoschisis. Arch Ophthalmol 1996;114(3): 274–80.
19. Sieving PA, MacDonald IM, Chan S. X-linked Juvenile Retinoschisis. 2003 Oct 24 [Updated 2014 Aug 28] In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
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These guidelines were reviewed and updated in September 2020