Ординатура / Офтальмология / Английские материалы / Electrophysiology of Vision_Lam_2005
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Figure 11.4 Top (left and right): Diffuse choroidal atrophy in a 68-year-old woman who reported progressive worsening of vision for 1 year. In contrast to pigmentary retinal degeneration, the retinal arterioles are not significantly attenuated. Bottom: Note the reduced, mildly prolonged full-field ERG responses. (Refer to the color insert.)
amplitudes with prolonged b-wave. Interestingly, a-wave implicit times were normal in all patients. Of the 17 patients, 3 had normal light-peak to dark-trough EOG ratios and 14 had reduced EOG ratios. These results suggest that dysfunction of the retinal pigment epithelium is greater than that of the sensory retina. The findings of VEP have not been
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extensively studied and are likely to parallel the degree of retinal involvement.
PIGMENTED PARAVENOUS
RETINOCHOROIDAL ATROPHY
Pigmented paravenous retinochoroidal atrophy (PPRCA) is a rare bilateral progressive condition diagnosed solely by the prominent perivascular retinal pigment epithelium disturbance. The disorder was first described in 1937 by Brown as ‘‘retino-choroiditis radiata’’ (25). The cause of PPRCA is likely numerous. Most reported cases are sporadic, but a few familial occurrences including dominant pedigrees are also observed (26). Interestingly, in a report of monozygotic twins, only one twin had the disease, implicating that the cause may not always be genetic or that the expressivity of the disease is highly variable (27).
Reports of ERG responses in PPRCA are scarce. Fullfield ERG is variable depending on the extent of the disease. Mild to severe reduction of photopic and scotopic responses is found and selective reduction of b-wave amplitude may occur (26). Focal areas of retinal dysfunction produced by the perivascular atrophy are apparent on multifocal ERG. In general, EOG and VEP responses parallel ERG responses (26,28).
REFERENCES
1.Seabra MC, Brown MS, Goldstein JL. Retinal degeneration in choroideremic: deficiency of RAb geranylgeranyl transferase. Science 1993; 259:377–381.
2.Syed N, Smith JE, John SK, Seabra MC, Aquirre GD, Milam AH. Evaluation of retinal photoreceptors and pigment epithelium in a female carrier of choroideremia. Ophthalmology 2001; 108:711–720.
3.Roberts MF, Fishman GA, Roberts DK, Heckenlively JR, Weleber RG, Anderson RJ, Grover S. Retrospective, longitudinal, and cross sectional study of visual acuity impairment in choroideraemia. Br J Ophthalmol 2002; 86:658–662.
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4.Sieving PA, Niffenegger JH, Berson EL. Electroretinographic findings in selected pedigrees with choroideremia. Am J Ophthalmol 1986; 101:361–367.
5.MacDonald IM, Mah DY, Ho YK, Lewis RA, Seabra MC. A practical diagnostic test for choroideremia. Ophthalmology 1998; 1998:1637–1640.
6.Fishman GA, Birch DG, Holder GE, Brigell MG. Choroideremia. Electro-physiologic Testing in Disorders of the Retina, Optic Nerve, and Visual Pathway. San Francisco: The Foundation of the American Academy of Ophthalmology, 2001:66–68.
7.Pinckers A, van Aarem A, Brink H. The electrooculogram in heterozygote carriers of Usher syndrome, retinitis pigmentosa, neuronal ceroid lipofuscinosis, senior syndrome and choroideremia. Ophthalmic Genet 1994; 15:25–30.
8.Mashima Y, Murakami A, Weleber RG, Kennaway NG, Clarke L, Shiono T, Inana G. Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy. Am J Hum Genet 1992; 51:81–91.
9.Peltola KE, Nanto-Salonen K, Heinonen OJ, Ja¨a¨skela¨inen S, Heina¨nen K, Simell O, Nikoskelainen E. Ophthalmologic heterogeneity in subjects with gyrate atrophy of choroid and retina harboring the L402P mutation of ornithine aminotransferase. Ophthalmology 2001; 108:721–729.
10.Weleber RG, Kennaway NG. Clinical trial of vitamin B6 for gyrate atrophy of the choroid and retina. Ophthalmology 1981; 88:316–324.
11.Dougherty KM, Swanson DA, Brody LC, Valle D. Molecular basis of ornithine aminotransferase deficiency in B-6-respon- sive and -nonresponsive forms of gyrate atrophy. Proc Natl Acad Sci USA 1988; 85:3777–3780.
12.Mashima Y, Weleber RG, Kennaway NG, Inana G. Genotype– phenotype correlation of a pyridoxine-responsive form of gyrate atrophy. Ophthalmic Genet 1999; 20:219–224.
13.Valle D, Walser M, Brusilow SW, Kaiser-Kupfer MI, Takki K. Gyrate atrophy of the choroid and retina: amino acid metabolism and correction of hyperornithinemia with an argininedeficient diet. J Clin Invest 1980; 65:371–378.
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14.Berson EL, Shih VE, Sullivan PL. Ocular findings in patients with gyrate atrophy on pyridoxine and low-protein, low arginine diets. Ophthalmology 1981; 88:311–315.
15.Berson E, Hanson AHI, Rosner B, Shih VE. A two year trial of low protein, low arginine diets or vitamin B6 for patients with gyrate atrophy. Birth Defects 1982; 18:209–218.
16.Vannas-Sulonen K, Simell O, Sipila I. Gyrate atrophy of the choroid and retina: the ocular disease progresses in juvenile patients despite normal or near normal plasma ornithine concentration. Ophthalmology 1987; 1987:1428–1433.
17.Kaiser-Kupfer MI, Caruso RC, Valle D. Gyrate atrophy of the choroid and retina: long-term reduction of ornithine slows retinal degeneration. Arch Ophthalmol 1991; 109:1539–1548.
18.Raitta C, Carlson S, Vannas-Sulonen K. Gyrate atrophy of the choroid and retina: ERG of the neural retina and the pigment epithelium. Br J Ophthalmol 1990; 74:363–367.
19.Kellner U, Weleber RG, Kennaway NG, Fishman GA, Foerster MH. Gyrate atrophy-like phenotype with normal plasma ornithine. Retina 1997; 17:403–413.
20.Krill AE, Archer D. Classification of the choroidal atrophies. Am J Ophthalmol 1971; 72:562–585.
21.Francescetti A. A curious affection of the fundus oculi: helicoidal peripapillar chorioretinal degeneration: its relation to pigmentary paravenous chorioretinal degeneration. Doc Ophthalmol 1962; 16:81–110.
22.Sveinsson K. Choroiditis areata. Acta Ophthalmol 1939; 17:73–80.
23.Fossdal R, Magnussion L, Weber JL, Jensson O. Mapping the focus of atrophia areata, a hellicoid peripapillary chorioretinal degeneration with autosomal dominant inheritance, to chromosome 11p15. Hum Mol Genet 1995; 4:479–483.
24.Eysteinsson T, Jo´nasson F, Jo´nsson V, Bird AC. Helicoidal peripapillary chorioretinal degeneration: electrophysiology and psychophysics in 17 patients. Br J Ophthalmol 1998; 82:280–285.
25.Brown TH. Retino-choroiditis radiata. Br J Ophthalmol 1936; 21:645–648.
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26.Skalka HW. Hereditary pigmented paravenous retinochoroidal atrophy. Am J Ophthalmol 1979; 87:286–291.
27.Small KW, Anderson WB. Pigmented paravenous retinochoroidal atrophy. Discordant expression in monozygotic twins. Arch Ophthalmol 1991; 109:1408–1410.
28.Parafita M, Diaz A, Torrijos IG, Gomez-Ulla F. Pigmented paravenous retinochoroidal atrophy. Optom Vis Sci 1993; 70:75–78.
29.Lam BL. Hereditary retinal degenerations. In: Parrish R, ed. Bascom Palmer Eye Institute Atlas of Ophthalmology. Philadelphia: Current Medicine, 2000:343–349.
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Vitreoretinal Disorders
Diseases exhibiting prominent clinical retinal and vitreous abnormalities are categorized as ‘‘vitreoretinal’’ disorders. Electrophysiologic responses typically reflect the degree of retinal involvement in this group of rare conditions. X-linked retinoschisis previously considered as a vitreoretinal disorder is due to genetic mutations involving a protein expressed mostly in photoreceptors and is discussed in Chapter 10. Goldmann–Favre syndrome, a disorder that also demonstrates retinal and vitreous abnormalities, has similar ERG and genotypes as enhanced S-cone syndrome and is covered in Chapter 8. The outline of this chapter is as follows:
Stickler syndrome
Wagner vitreoretinopathy
Familial exudative vitreoretinopathy
Autosomal dominant vitreoretinochoroidopathy
Autosomal dominant neovascular inflammatory vitreoretinopathy
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STICKLER SYNDROME
Stickler syndrome is an autosomal dominant disorder caused by mutations of the gene encoding type II collagen, COL2A1, which is located on chromosome 12 (1). The syndrome was described by Stickler et al. (2) in 1965 and termed ‘‘hereditary progressive arthro-ophthalmopathy.’’ Common ocular features include high myopia, vitreous syneresis, and rhegmatogenous retinal detachment with a high risk of multiple and giant retinal tears. Other ocular findings include cataract and retinal perivascular pigmentary clumping (Fig. 12.1). Common systemic features include arthropathy, cleft palate, sensorineural hearing loss, and midfacial hypoplasia. Genetic mutations producing Stickler syndrome show a high degree of heterogeneity, and clinical expression is highly variable both between and within families. Variations of the vitreous syneresis are associated with different genotypes (3). Stickler syndrome is categorized into two subtypes, the more common ocular Stickler syndrome (type 1) and ‘‘non-ocular’’ Stickler syndrome (type 2). Type 2 is associated with mutations on another collagen gene, COL11A1.
Full-field ERG is generally normal in Sticker syndrome but the associated high myopia may produce mild to moderate reduction of scotopic and photopic b-wave amplitudes
Figure 12.1 Stickler syndrome. Photographs of a 14-year-old boy showing significant cataract in the right eye (left). The view of the retina of the left eye (right) is obscured by cataract and vitreous syneresis, and shows myopic and perivascular pigmentary changes.
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corresponding to the degree of the myopic retinal degeneration. The ERG responses are also impaired if retinal detachment occurs with the amount of impairment relating to the size and chronicity of the retinal detachment. In addition, if associated cataract is present, mild ERG a-wave and b-wave reduction with prolonged implicit time may occur. In general, EOG and VEP findings parallel ERG responses.
WAGNER VITREORETINOPATHY
Wagner vitreoretinopathy is a rare autosomal dominant disorder characterized by high myopia, vitreous strands, and occasional rhegmatogenous retinal detachment. Funduscopic findings are variable and include vitreous avascular strands or condensed bands, retinal pigmentary epithelium and choroidal atrophy, retinal perivascular pigmentary clumping, optic nerve atrophy, and situs inversus of the optic nerve head vessels. The disease was described by Wagner (4) in 1938 in a Swiss family and has no associated systemic features. In the past, Wagner vitreoretinopathy and Stickler syndrome have been confused with one another, and affected persons have been reported as having the same disorder. Wagner vitreoretinopathy is genetically heterogeneous. A frame shift mutation of the gene encoding type II collagen, COL2A1, was found to be associated with Wagner vitreoretinopathy in one kindred (5). Mutations of COL2A1 are also associated with Stickler syndrome. However, in other kindreds, Wagner vitreoretinopathy is genetically linked to chromosome 5q14, a region which contains genes encoding two extracellular macromolecules, link protein (CRTL1) and versican (CSPG2), which are important in binding hyaluronan, a component of the vitreous (6,7).
In Wagner disease, ERG may be normal but both the a-wave and the b-wave may be impaired if retinal and choroidal atrophy is present (8). In addition, the associated high myopia may produce mild to moderate reduction of scotopic and photopic b-wave amplitudes corresponding to the degree
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of the myopic retinal degeneration. If retinal detachment occurs, the ERG responses are impaired with the amount of impairment depending on the size and chronicity of the retinal detachment. The EOG and VEP findings parallel ERG responses, but the VEP may be impaired further if associated optic atrophy is present.
FAMILIAL EXUDATIVE VITREORETINOPATHY
Familial exudative vitreoretinopathy commonly called ‘‘FEVR’’ is a rare dominant or X-linked hereditary disorder with variable expressivity (9–11). Clinical manifestation of FEVR ranges from subtle termination of retinal vessels in the peripheral temporal equatorial region to vitreal fibrovascular mass with marked traction of the retina and optic nerve head (Fig. 12.2). Clinical findings of FEVR may mimic residual changes of retinopathy of prematurity and may lead to misdiagnosis in some patients.
In FEVR, ERG and EOG findings are related to the degree of retinal involvement and correlates with visual function. The ERG is generally normal in mildly affected persons and becomes impaired or even non-detectable with severe disease (12–14). The VEP findings parallel ERG responses.
Figure 12.2 Familial exudative vitreoretinopathy. Left: Right eye of a 5-year-old boy with mild temporal retinal atrophic changes. Right: Right eye of an unrelated 4-year-old boy with severe fibrovascular proliferation and retinal detachment.
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AUTOSOMAL DOMINANT
VITREORETINOCHOROIDOPATHY
Autosomal dominant vitreoretinochoroidopathy (ADVIRC) is a very rare hereditary disorder found in a few families in the United States and Germany. Characteristic feature is the circumferential chorioretinal hypopigmentary or hyperpigmentary disturbance between the vortex veins and the ora serrata (15–18). In this zone, there are a discrete posterior boundary, preretinal punctate white opacities, retinal arteriolar narrowing and occlusion, and occasional choroidal atrophy. Other findings include retinal neovascularization, vitreous abnormalities, macular edema, vitreous hemorrhage, and early cataract. Histopathology reveals a retinal pigment epithelial response with marked intraretinal migration and extracellular matrix deposition (19,20).
Han and Lewandowski (21) performed EOG and full-field ERG on four affected patients with ADVIRC and found reduced EOG Arden light-peak to dark-trough ratios of 1.1– 1.5 (normal 1.8) despite full-field ERG consisting of mildly affected rod function and normal cone function. However, Kellner et al. (22) noted reduced full-field ERG with a normal EOG in an affected patient, but the patient’s affected mother had normal full-field ERG and EOG. Therefore, the expression of the disease may be variable within the same family, and a reduced EOG is not a typical sign for all affected persons (22). The VEP response in ADVIRC has not been extensively studied but is likely related to ERG impairment.
AUTOSOMAL DOMINANT NEOVASCULAR
INFLAMMATORY VITREORETINOPATHY
Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is a very rare hereditary disorder reported in a large kindred in the United States. The disorder is characterized by peripheral retinal scarring and pigmentation, peripheral arteriolar closure, and neovascularization of the peripheral retina at the ora serrata (23). Neovascularization