From the University of Glasgow (SH, GND), Glasgow, United Kingdom; the Department of Ophthalmology (SH, GND), Royal Hospital for Sick Children, Yorkhill, Glasgow, United Kingdom; and Glasgow Caledonian University (DLM, GND), Glasgow, United Kingdom.
The authors have no financial or proprietary interest in the materials presented herein.
The authors thank Ailsa MacInnes for providing the fundus photographs and Dr. David Keating for the multifocal electroretinograms.
Address correspondence to Sijie Heng, BSc(Hons), Department of Ophthalmology, Royal Hospital for Sick Children, Dalnair Street, Yorkhill, Glasgow, G3 8SJ, United Kingdom. E-mail: firstname.lastname@example.org
Visual field constriction with relatively preserved central visual acuity caused by Leber’s congenital amaurosis, retinitis pigmentosa, and related diseases is an uncommon condition rarely described in the literature. We report a case of a 17-year-old girl with a unique clinical history of such a condition.
A 17-year-old girl presented with visual field constriction and relative preservation of central visual acuity. The patient had first presented to a regional hospital with esotropia associated with myopic astigmatism at 8 months of age. At 2 years of age, it became apparent that she had difficulties with mobility and visual search tasks. In particular, she tripped, bumped into obstacles, and took time to locate a person in the room with her. She was unable to function independently in dim illumination. Between 6 and 7 years of age, her parents and teachers became concerned that her visual skills were limiting her activities although she had no documented change in visual function over time. At 7 years of age, she was referred by her optician, who had measured profoundly constricted visual fields. There was no significant family ocular history. She was otherwise healthy with no systemic pathology.
Her best-corrected visual acuities were 6/24 (right eye) and 6/26 (left eye), with her refraction being −7.75/+4.00 at 100 (right eye) and −7.50/+4.00 at 85 (left eye), indicating preserved central retinal function. Her best-corrected visual acuities 10 years previously had been 6/12 (right eye) and 6/15 (left eye) with refraction −3.50/−2.50 axis 10 (right eye) and −3.00/−3.00 axis 150 (left eye). Contrast sensitivity was reduced compared with 10 years previously (Pelli–Robson score of 1.50 to 0.60). She had markedly constricted visual field of 20° (Goldmann perimetry), although this was a slight improvement from 10° (same instrument) 10 years previously. Ocular fundus examination revealed subtle bilateral widespread retinal and choroidal atrophy with slight attenuation of retinal vessels, optic disc pallor, a granular appearance of the maculae, and fine pigmentary retinal stippling (Fig. 1). City University color vision tests were normal, as they had been 10 years previously, but a significant degree of red-green impairment was detected with the Ishihara plates.
Figure 1. Fundus photographs of the patient’s (A) right and (B) left eyes showing subtle bilateral widespread retinal and choroidal atrophy with slight attenuation of retinal vessels, optic disc pallor, and granular appearance of the maculae. Fine pigmentary retinal stippling was observed by biomicroscopy.
Both scotopic and photopic electroretinograms (ERGs) performed according to International Society for Clinical Electrophysiology of Vision standards were undetectable from the age of 7 years, indicating widespread dysfunction of both the rod and cone systems. A multifocal ERG at that time showed no detectable response from the macula or any other part of the central retina (Fig. 2). However, visual evoked potentials to International Society for Clinical Electrophysiology of Vision standard checkerboards were remarkably normal.
Figure 2. Wide-field multifocal electroretinogram of the patient at 7 years of age over a 90° field showing no significant response in the (A) left eye and (B) right eye. (C) A normal tracing is shown for comparison.
The patient underwent genetic testing using the LCA microarray chip (Asper Biotech, Tartu, Estonia) but none of the 641 disease-associated sequence variants were identified in RPE65, GU-CY2D, CRB1, AIPL1, CRX, RPGRIP1, MERTK, CEP290, RDH12, TULP1, LCA5, LRAT, and SPATA7.
In a child with an incidental finding of visual field constriction, a variety of organic and non-organic pathologies needs to be considered. Organic causes include chiasmal compression causing bitemporal hemianopia, retinal artery occlusion with a cilioretinal macular blood supply, bilateral occipital blindness with macular sparing, visual field loss in some forms of pigmentary and non-pigmentary retinal dystrophy,1 and the toxic effects of vigabatrin.2 Alternatively, classic “tubular vision” may be found with “hysterical” or “functional” visual impairment.3
An inconsistency between relatively preserved visual function but alleged gross constriction of visual fields raises the suspicion of functional visual impairment, although no specific clinical history is pathognomonic for this condition.3 The most common visual defect reported in functional visual impairment is the classic tubular visual field, which tends to spiral on perimetry.4 There is concentric loss of peripheral vision leaving 5° to 10° of central vision, yet on tangent screen testing the circular constriction does not expand accordingly with increasing distance between the patient and the tangent screen. Despite this, an affected patient often has no difficulty maneuvering around peripheral obstacles. Estimated to account for 1% to 5% of outpatient workload, hysterical visual impairment is known to be more common in females and younger age groups.3
However, the retinal pigmentary abnormalities and ERG findings in this patient point to a form of widespread retinal dystrophy. Although these findings are likely to exclude any visual impairment of a solely non-organic nature, it should be noted that organic and non-organic pathologies do not infrequently coexist.5 Moreover, ERG findings have been known to be abnormal in some cases of non-organic pathology.3
The reported constancy of symptoms suggests that this patient’s condition was likely to be congenital or of very early onset. This presumed early age of onset,6 when taken together with absent ERGs,6 mild visual field improvement, and the relatively non-progressive nature of her condition,7,8 suggests a diagnosis of Leber’s congenital amaurosis, but the visual field constriction and preservation of central visual acuity,9 subsequent high myopia, and the absence of nystagmus and night blindness6 suggest a differential diagnosis of juvenile retinitis pigmentosa.
A distinct possibility in this case is Leber’s congenital amaurosis with relatively preserved visual acuity, which has been sporadically described before. In the pre-genomic era, a study by Vaizey et al.7 of 27 children described three children with visual acuity between 6/36 and 6/60 and two with 6/12 or better, but they were only followed up for the first decade of life. Stanley et al. described two patients with visual acuities of 6/30 or better, albeit with some degree of nystagmus.10 Moore and Taylor11 described three cases of Leber’s congenital amaurosis with relatively good visual acuities in the region of 6/18 with correction in the best eye, but these were present with saccadic palsies and other systemic anomalies. Since the advent of genomics, visual acuities of 6/15 have been described in patients with CRB1, LRAT, and RPE65 mutations, but these acuities did not remain stable.8
Fundus findings alone are not diagnostic of either retinitis pigmentosa or Leber’s congenital amaurosis. Schroder et al.12 reviewed 43 cases of Leber’s congenital amaurosis and found that 20 of them resembled retinitis pigmentosa, whereas the rest of them had variable abnormalities or normal appearances. Vessel attenuation, pigmentary changes, and optic disc pallor seen in our patient are frequently reported in both conditions.6,12 Indeed, the diagnosis of Leber’s congenital amaurosis has not been uncommonly revised retrospectively to juvenile retinitis pigmentosa,13 indicating considerable clinical overlap. The two conditions even share common candidate genes8 and genetic modifiers may be responsible for the differential phenotypic expression in the same putative mutations,8 giving rise to a spectrum of diseases encompassing Leber’s congenital amaurosis, juvenile retinitis pigmentosa, and some intermediate conditions between the two.8,14
Acknowledging the overlap between Leber’s congenital amaurosis and juvenile retinitis pigmentosa, Yzer et al.14 classified 14 patients as having “early onset severe retinal dystrophy” characterized by a Tyr368His RPE65 “founder” mutation. Similar to our patient, the age of onset in these patients is indicative of Leber’s congenital amaurosis, but visual acuity, visual fields, and night blindness are in keeping with juvenile retinitis pigmentosa. Notably, one patient retained a visual acuity of 6/18 in one eye at 19 years of age, but with a recordable photopic response on electrophysiology.
Our patient’s condition may represent a rare variant lying on the spectrum between Leber’s congenital amaurosis and juvenile retinitis pigmentosa. Although the genetic microarray analysis excluded almost all known mutations in 13 genes associated with Leber’s congenital amaurosis, a diagnosis of Leber’s congenital amaurosis has not been excluded because unknown mutations in the tested genes or mutations in novel genes such as the RD3 and IM-PDH1 are still possible. Moreover, in approximately 30% of clinically diagnosed cases of Leber’s congenital amaurosis, a pathogenic mutation has yet to be identified.8
- Weller M, Wiedemann P. Hysterical symptoms in ophthalmology. Doc Ophthalmol. 1989;73:1–33. doi:10.1007/BF00174124 [CrossRef]
- Iannetti P, Spalice A, Perla FM, Conicella E, Raucci U, Bizzarri B. Visual field constriction in children with epilepsy on vigabatrin treatment. Pediatrics. 2000;106:838–842. doi:10.1542/peds.106.4.838 [CrossRef]
- Beatty S. Non-organic visual loss. Postgrad Med J. 1999;75:201–207.
- Newman NJ. Neuro-ophthalmology and psychiatry. Gen Hosp Psychiatry. 1993;15:102–114. doi:10.1016/0163-8343(93)90106-X [CrossRef]
- Kathol RG, Cox TA, Corbett JJ, Thompson HS. Functional visual loss: follow-up of 42 cases. Arch Ophthalmol. 1983;101:729–735.
- Foxman SG, Heckenlively JR, Bateman JB, Wirtschafter JD. Classification of congenital and early onset retinitis pigmentosa. Arch Ophthalmol. 1985;103:1502–1506.
- Vaizey MJ, Sanders MD, Wybar KC, Wilson J. Neurological abnormalities in congenital amaurosis of Leber: review of 30 cases. Arch Dis Child. 1977;52:399–402. doi:10.1136/adc.52.5.399 [CrossRef]
- den Hollander AI, Roepman R, Koenekoop RK, Cremers FP. Leber congenital amaurosis: genes, proteins and disease mechanisms. Prog Retin Eye Res. 2008;27:391–419. doi:10.1016/j.preteyeres.2008.05.003 [CrossRef]
- Grover S, Fishman GA, Alexander KR, Anderson RJ, Derlacki DJ. Visual acuity impairment in patients with retinitis pigmentosa. Ophthalmology. 1996;103:1593–1600.
- Stanley JH, MacDonald J, Flynn JT. Leber’s congenital amaurosis: a clinical study. In: Lawton Smith J, ed. Neuro-ophthalmology Update. New York: Maison; 1977:91–97.
- Moore AT, Taylor DS. A syndrome of congenital retinal dystrophy and saccade palsy: a subset of Leber’s amaurosis. Br J Ophthalmol. 1984;68:421–431. doi:10.1136/bjo.68.6.421 [CrossRef]
- Schroeder R, Mets MB, Maumenee IH. Leber’s congenital amaurosis: retrospective review of 43 cases and a new fundus finding in two cases. Arch Ophthalmol. 1987;105:356–359.
- Ashaye AO. Presumed hereditary retinal degenerations: Ibadan experience. West Afr J Med. 2005;24:49–53.
- Yzer S, van den Born LI, Schuil J, et al. A Tyr368His RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population. J Med Genet. 2003;40:709–713. doi:10.1136/jmg.40.9.709 [CrossRef]