Enhanced S-cone syndrome (ESCS) is a rare autosomal recessive retinal dystrophy caused by mutations of the NR2E3 gene.1 Patients with ESCS often have macular retinoschisis, in addition to pigmentary degenerations ranging from the vascular arcade to the midperipheral retina.2,3 Although macular retinoschisis may be one of the causes of decreased visual acuity in ESCS, there have yet to be any effective treatments established for macular retinoschisis.
We previously reported the details for a 23-year-old ESCS patient with a homozygous NR2E3 mutation (p.Q350X),4 who had large bilateral macular retinoschisis.5 After a subsequent longitudinal optical coherence tomography (OCT) follow-up of this patient, we report here further details on the dramatic improvement in the large bilateral macular retinoschisis that occurred in the absence of any further treatments.
A 17-year-old Japanese male ESCS patient with a homozygous NR2E3 mutation (p.Q350X) was previously examined and followed up at our department.4 At 23 years of age, his best-corrected visual acuity (BCVA) decreased to 0.1, and time-domain OCT revealed large macular retinoschisis in both eyes.5 Subsequent follow-up of the patient at the age of 28 years revealed that his BCVA remained at 0.1 (with +1.75 diopter [D], cylinder [cyl] −2.00 D, axis 120°) and 0.1 (with +0.50 D, cyl −2.25 D, axis 30°) in his right and left eyes. Spectral-domain OCT (Cirrus HD OCT; Carl Zeiss Meditec, Dublin, CA) continued to show the presence of large macular retinoschisis in both eyes (Figure 1A). At the age of 29, the large macular retinoschisis dramatically improved in his right eye, with slight improvement in his left eye (Figure 1B). Splitting of the right retina only appeared to occur in the outer plexiform layer (Figure 1B). At the age of 32, OCT revealed only small cystoid changes in both of the patient's eyes (Figure 1C). The patient is now 34 years old and his BCVA has slightly increased to 0.15, with the central scotomas noted in Goldmann perimetry found to be smaller than those observed during the large macular retinoschisis stage in both eyes (Figure 2). Current OCT findings indicated there was resolution of the large macular retinoschisis, along with a partially visible external limiting membrane (ELM), and an ellipsoid zone (EZ; also called the inner/outer segment junction) in both eyes (Figure 1D). The posterior vitreous was attached to the macula at all times at ages 28, 29, 32, and 34, indicating no abnormal vitreomacular adhesion. We further evaluated his fundus and autofluorescence (AF) images using the Optos 200Tx imaging system (Optos, Dunfermline, United Kingdom). The pigmentary changes observed from the arcade to the midperiphery area (Figure 3A) corresponded to the hypoautofluorescence areas of the AF images (Figure 3B). Interestingly, in the areas where there was resolution of the large macular retinoschisis, we observed marked AF signals within the vascular arcades in both eyes (Figure 3B). There was no evidence of retinal vascular attenuation noted in the periphery (Figures 3A and 3B).
Horizontal scan images (6 mm) of spectral-domain optical coherence tomography. Large macular retinoschisis is seen in both eyes of a 28-year-old patient (A). Dramatic improvement of the large macular retinoschisis is seen in the right eye, and slight improvement is seen in the left eye at the age of 29 (B). Splitting of the right retina (arrow) only seemed to occur in the outer plexiform layer (B). At the age of 32, only small cystoid changes are seen in both eyes (C), with the large macular retinoschisis completely resolved by the age of 34 (D). In addition to the visible external limiting membrane, the ellipsoid zone is partially observed in both eyes (D).
Visual fields using Goldmann perimetry. The central scotomas (B) at the age of 34 are smaller than those (A) observed at the age of 28 during the large macular retinoschisis stage in both eyes.
Fundus and autofluorescence (AF) images using the Optos 200Tx imaging system. The pigmentary changes from the arcade to midperiphery area (A) correspond to the hypoautofluorescence areas of the AF images (B). Interestingly, marked AF signals were observed within the vascular arcades in both eyes (B), specifically in the areas in which there was resolution of the large macular retinoschisis.
We report the follow-up of one ESCS patient who exhibited spontaneous resolution of large bilateral macular retinoschisis. At the present time, the mechanism responsible for the development of macular retinoschisis in ESCS patients has yet to be definitively clarified. There have been two prior interventional case reports of ESCS patients with retinoschisis or cystoid changes.6,7 Iannaccone et al. examined an ESCS patient with adult-onset acute macular retinoschisis who was being treated with the oral carbonic anhydrase inhibitor (CAI), acetazolamide. After 12 weeks of treatment, they reported finding a complete resolution of the macular retinoschisis.6 Hajali et al. reported finding that 8 weeks of topical CAI dorzolamide treatment in one ESCS patient resulted in an improvement of the macular cysts.7 When taken together, the outcomes observed in these previous reports suggest that oral or topical CAI might be effective for treating macular retinoschisis or cystoid changes complicated by ESCS.
In contrast, Sohn et al. used microperimetry, AF, and OCT to examine nine patients with ESCS with a wide variance in the age range and found a natural clinical course that did not require medical intervention.8 In their study, the authors found that although at least three older adults had documented evidence of foveal retinoschisis, it resolved in one or both eyes without any further treatment.8 Similarly, our current patient had large bilateral macular retinoschisis that lasted for more than 5 years (from ages 23 to 28 years old), after which it spontaneously resolved (Figure 1). These findings indicate that in some patients, the retinoschisis complicated by ESCS can resolve spontaneously.
The previous study by Sohn et al. also found that there was a strong AF signal that persisted in the macula in one ESCS patient (patient 7 in the original article), even after resolution of the retinoschisis.8 We also found similar strong AF findings in our patient (Figure 3B) after the resolution of the macular retinoschisis. Even though the reason why there is a strong AF signal that persists after resolution of retinoschisis remains unclear, pertinent clues might be able to be determined from the resolved OCT images (Figure 1D), in which the EZ can be partially observed in addition to the visible ELM. Thus, it is possible that the partly preserved outer retinal morphology could, in fact, help to relieve the damage to the retinal pigment epithelium (RPE). Furthermore, the areas that corresponded to the pigmentary changes also showed hypoautofluorescence (Figure 3B), which is suggestive of severe RPE damage.
In conclusion, although there have yet to be any established treatments for macular retinoschisis complicated by ESCS, current findings suggest that some patients with ESCS may not require any intervention, as the disease resolves on its own.
- Haider NB, Jacobson SG, Cideciyan AV, et al. Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate. Nat Genet. 2000;24(2):127–131. doi:10.1038/72777 [CrossRef]
- Marmor MF, Jacobson SG, Foerster MH, et al. Diagnostic clinical findings of a new syndrome with night blindness, maculopathy, and enhanced S cone sensitivity. Am J Ophthalmol. 1990;110(2):124–134. doi:10.1016/S0002-9394(14)76980-6 [CrossRef]
- Jacobson SG, Marmor MF, Kemp CM, et al. SWS (blue) cone hypersensitivity in a newly identified retinal degeneration. Invest Ophthalmol Vis Sci. 1990;31(5):827–838.
- Nakamura Y, Hayashi T, Kozaki K, et al. Enhanced S-cone syndrome in a Japanese family with a nonsense NR2E3 mutation (Q350X). Acta Ophthalmol Scand. 2004;82(5):616–622. doi:10.1111/j.1600-0420.2004.00328.x [CrossRef]
- Hayashi T, Kitahara K. Optical coherence tomography in enhanced S-cone syndrome: large macular retinoschisis with disorganized retinal lamination. Eur J Ophthalmol. 2005;15(5):643–646.
- Iannaccone A, Fung KH, Eyestone ME, et al. Treatment of adult-onset acute macular retinoschisis in enhanced s-cone syndrome with oral acetazolamide. Am J Ophthalmol. 2009;147(2):307–312 e302. doi:10.1016/j.ajo.2008.08.003 [CrossRef]
- Hajali M, Fishman GA. Dorzolamide use in the management of macular cysts in a patient with enhanced s-cone syndrome. Retin Cases Brief Rep. 2009;3(2):121–124. doi:10.1097/ICB.0b013e31818faa21 [CrossRef]
- Sohn EH, Chen FK, Rubin GS, Moore AT, Webster AR, MacLaren RE. Macular function assessed by microperimetry in patients with enhanced S-cone syndrome. Ophthalmology. 2010;117(6):1199–1206 e1191. doi:10.1016/j.ophtha.2009.10.046 [CrossRef]