Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Documenta Ophthalmologica
Published in: Documenta Ophthalmologica 3/2015

01-06-2015 | Original Research Article

Electroretinography and optical coherence tomography reveal abnormal post-photoreceptoral activity and altered retinal lamination in patients with enhanced S-cone syndrome

Authors: M. Sustar, D. Perovšek, I. Cima, B. Stirn-Kranjc, M. Hawlina, J. Brecelj

Published in: Documenta Ophthalmologica | Issue 3/2015

Login to get access

Abstract

Purpose

To compare functional abnormalities of enhanced S-cone syndrome (ESCS), as examined using standard and extended electroretinography (ERG), with structural findings and retinal architecture obtained by spectral domain optical coherence tomography (SD-OCT).

Methods

Four patients with ESCS underwent standard full-field and multifocal ERGs, with extended S-cone and ON/OFF ERG protocols also performed. SD-OCT was also carried out, and longitudinal reflectivity profiles (LRPs) were calculated for the perifoveolar retina.

Results

All four patients exhibited pathognomonic full-field ERG findings for ESCS, with delayed responses of similar waveforms to the same intensity flash under both scotopic and photopic conditions. The amplitudes of the full-field ERGs showed considerable variation between patients, which were not related to the extent of the visual field defects. Multifocal ERGs reflected preserved central function in eyes with good visual acuity (Snellen visual acuity >0.7). The ERGs to S-cone-specific stimulation confirmed the expected predominant activity of the S-cone system in all four patients. The ON/OFF ERG recordings revealed abnormal presence of both ON-response and OFF-response activities in three patients; the remaining patient showed only OFF-response activity. SD-OCT showed a significantly thickened outer nuclear layer in all four patients, as obtained by LRP analysis. Furthermore, in the patient with selective preservation of the OFF-response activity, LRP showed reduced numbers of hyper-reflectivity sub-peaks in the inner plexiform layer.

Conclusion

Patients with ESCS show characteristic full-field ERG waveform abnormality, predominance of S-cone ERG activity, and thickening of the outer nuclear layer on SD-OCT. Moreover, they can also show abnormal post-photoreceptor connectivity through S-cone-related OFF-bipolar cell activity.
Literature
1.
Jacobson SG, Marmor MF, Kemp CM, Knighton RW (1990) SWS (blue) cone hypersensitivity in a newly identified retinal degeneration. Invest Ophthalmol Vis Sci 31:827–838PubMed
2.
Marmor MF, Jacobson SG, Foerster MH et al (1990) Diagnostic clinical findings of a new syndrome with night blindness, maculopathy, and enhanced S cone sensitivity. Am J Ophthalmol 110:124–134CrossRefPubMed
3.
4.
Haider NB, Jacobson SG, Cideciyan AV et al (2000) Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate. Nat Genet 24:127–131CrossRefPubMed
5.
Schorderet DF, Escher P (2009) NR2E3 mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP). Hum Mutat 30:1475–1485CrossRefPubMed
6.
Milam AH, Rose L, Cideciyan AV et al (2002) The nuclear receptor NR2E3 plays a role in human retinal photoreceptor differentiation and degeneration. Proc Natl Acad Sci USA 99:473–478CrossRefPubMedCentralPubMed
7.
Sharon D, Sandberg MA, Caruso RC et al (2003) Shared mutations in NR2E3 in enhanced S-cone syndrome, Goldmann-Favre syndrome, and many cases of clumped pigmentary retinal degeneration. Arch Ophthalmol 121:1316–1323CrossRefPubMed
8.
Audo I, Michaelides M, Robson AG et al (2008) Phenotypic variation in enhanced S-cone syndrome. Invest Ophthalmol Vis Sci 49:2082–2093CrossRefPubMed
9.
Marmor MF (1989) Large rod-like photopic signals in a possible new form of congenital night blindness. Doc Ophthalmol 71:265–269CrossRefPubMed
10.
Udar N, Small K, Chalukya M et al (2011) Developmental or degenerative–NR2E3 gene mutations in two patients with enhanced S cone syndrome. Mol Vis 17:519–525PubMedCentralPubMed
11.
Lam BL, Goldberg JL, Hartley KL et al (2007) Atypical mild enhanced S-cone syndrome with novel compound heterozygosity of the NR2E3 gene. Am J Ophthalmol 144:157–159CrossRefPubMed
12.
Kinori M, Pras E, Kolker A et al (2011) Enhanced S-cone function with preserved rod function: a new clinical phenotype. Mol Vis 17:2241–2247PubMedCentralPubMed
13.
Marmor MF, Tan F, Sutter EE, Bearse MA (1999) Topography of cone electrophysiology in the enhanced S cone syndrome. Invest Ophthalmol Vis Sci 40:1866–1873PubMed
14.
Román AJ, Jacobson SG (1991) S cone-driven but not S cone-type electroretinograms in the enhanced S cone syndrome. Exp Eye Res 53:685–690CrossRefPubMed
15.
Miyake Y (ed) (2006) Enhanced S-cone syndrome. In: Electrodiagnosis of retinal diseases. Springer, Tokyo, pp 68–71
16.
17.
Jacobson SG, Sumaroka A, Aleman TS et al (2004) Nuclear receptor NR2E3 gene mutations distort human retinal laminar architecture and cause an unusual degeneration. Hum Mol Genet 13:1893–1902CrossRefPubMed
18.
Hayashi T, Kitahara K (2005) Optical coherence tomography in enhanced S-cone syndrome: large macular retinoschisis with disorganized retinal lamination. Eur J Ophthalmol 15:643–646PubMed
19.
Park SP, Hong IH, Tsang SH et al (2013) Disruption of the human cone photoreceptor mosaic from a defect in NR2E3 transcription factor function in young adults. Graefes Arch Clin Exp Ophthalmol 251:2299–2309CrossRefPubMedCentralPubMed
20.
Cima I, Brecelj J, Sustar M et al (2012) Enhanced S-cone syndrome with preserved macular structure and severely depressed retinal function. Doc Ophthalmol 125:161–168CrossRefPubMed
21.
Sustar M, Hawlina M, Brecelj J (2011) Electroretinographic evaluation of the retinal S-cone system. Doc Ophthalmol 123:199–210CrossRefPubMed
22.
Beharic A, Stirn-Kranjc B, Brecelj J (2012) Electrophysiological assessment of the retina in children with congenital nystagmus. Zdr Vest 81:73–82
23.
Sustar M, Stirn-Kranjc B, Brecelj J (2012) Children with complete or incomplete congenital stationary night blindness: ophthalmological findings, standard ERGs and ON-OFF ERGs for differentiation between the types. Zdr Vest 81:16–28
24.
Hawlina M, Konec B (1992) New noncorneal HK-loop electrode for clinical electroretinography. Doc Ophthalmol 81:253–259CrossRefPubMed
25.
Hood DC, Bach M, Brigell M et al (2012) ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition). Doc Ophthalmol 124:1–13CrossRefPubMed
26.
Marmor MF, Fulton AB, Holder GE et al (2009) ISCEV Standard for full-field clinical electroretinography (2008 update). Doc Ophthalmol 118:69–77CrossRefPubMed
27.
Barthelmes D, Gillies MC, Sutter FKP (2008) Quantitative OCT analysis of idiopathic perifoveal telangiectasia. Invest Ophthalmol Vis Sci 49:2156–2162CrossRefPubMed
28.
Barthelmes D, Sutter FK, Kurz-Levin MM et al (2006) Quantitative analysis of OCT characteristics in patients with achromatopsia and blue-cone monochromatism. Invest Ophthalmol Vis Sci 47:1161–1166CrossRefPubMed
29.
Hood DC, Cideciyan AV, Roman AJ, Jacobson SG (1995) Enhanced S cone syndrome: evidence for an abnormally large number of S cones. Vision Res 35:1473–1481CrossRefPubMed
30.
Greenstein VC, Zaidi Q, Hood DC et al (1996) The enhanced S cone syndrome: an analysis of receptoral and post-receptoral changes. Vis Res 36:3711–3722CrossRefPubMed
31.
Bandah D, Merin S, Ashhab M et al (2009) The spectrum of retinal diseases caused by NR2E3 mutations in Israeli and Palestinian patients. Arch Ophthalmol 127:297–302CrossRefPubMed
32.
Iannaccone A, Fung KH, Eyestone ME, Stone EM (2009) Treatment of adult-onset acute macular retinoschisis in enhanced S-cone syndrome with oral acetazolamide. Am J Ophthalmol 147:307–312CrossRefPubMedCentralPubMed
33.
Pachydaki SI, Klaver CC, Barbazetto IA et al (2009) Phenotypic features of patients with NR2E3 mutations. Arch Ophthalmol 127:71–75CrossRefPubMed
34.
Bush RA, Sieving PA (1994) A proximal retinal component in the primate photopic ERG a-wave. Invest Ophthalmol Vis Sci 35:635–645PubMed
35.
Sieving PA (1993) Photopic ON- and OFF-pathway abnormalities in retinal dystrophies. Trans Am Ophthalmol Soc 91:701–773PubMedCentralPubMed
36.
Sieving PA, Murayama K, Naarendorp F (1994) Push-pull model of the primate photopic electroretinogram: a role for hyperpolarizing neurons in shaping the b-wave. Vis Neurosci 11:519–532CrossRefPubMed
37.
Ueno S, Kondo M, Ueno M et al (2006) Contribution of retinal neurons to d-wave of primate photopic electroretinograms. Vis Res 46:658–664CrossRefPubMed
38.
Evers HU, Gouras P (1986) Three cone mechanisms in the primate electroretinogram: two with, one without off-center bipolar responses. Vis Res 26:245–254CrossRefPubMed
39.
40.
Famiglietti EV, Kolb H (1976) Structural basis for ON-and OFF-center responses in retinal ganglion cells. Science 194:193–195CrossRefPubMed
41.
Nelson R, Famiglietti EV, Kolb H (1978) Intracellular staining reveals different levels of stratification for on- and off-center ganglion cells in cat retina. J Neurophysiol 41:472–483PubMed
Metadata
Title
Electroretinography and optical coherence tomography reveal abnormal post-photoreceptoral activity and altered retinal lamination in patients with enhanced S-cone syndrome
Authors
M. Sustar
D. Perovšek
I. Cima
B. Stirn-Kranjc
M. Hawlina
J. Brecelj
Publication date
01-06-2015
Publisher
Springer Berlin Heidelberg
Published in
Documenta Ophthalmologica / Issue 3/2015
Print ISSN: 0012-4486
Electronic ISSN: 1573-2622
DOI
https://doi.org/10.1007/s10633-015-9487-9

Other articles of this Issue 3/2015

Documenta Ophthalmologica 3/2015 Go to the issue

Original Research Article

Pattern visual evoked potentials for identifying malingering

Original Research Article

Structural and functional changes in glaucoma: comparing the two-flash multifocal electroretinogram to optical coherence tomography and visual fields

Original Research Article

Clinical and electrophysiology findings in Slovene patients with Leber hereditary optic neuropathy

Original Research Article

Influence of chloroquine intake on the multifocal electroretinogram in patients with and without maculopathy

Clinical Case Report

Multimodal imaging of a case of peripheral cone dystrophy

Original Research Article

Somatic instability of expanded CAG repeats of ATXN7 in Japanese patients with spinocerebellar ataxia type 7