Ординатура / Офтальмология / Английские материалы / Electrophysiology of Vision_Lam_2005

185.Rohrschneider K, Blankenagel A, Kruse FE, Fendrich T, Volcker HE. Macular function testing in a German pedigree with North Carolina macular dystrophy. Retina 1998; 18:453–459.

186.Small KW, Puech B, Mullen L, Yelchitis S. North Carolina macular dystrophy phenotype in France maps to the MCDR1 locus. Mol Vis 1997; 3:1–6.

187.Reichel MB, Kelsell RE, Fan J, Gregory CY, Evans K, Moore AT, Hunt DM, Fitzke FW, Bird AC. North Carolina macular dystrophy family linked to chromosome 6q. Br J Ophthalmol 1998; 82:1162–1168.

188.Small KW, Weber JL, Roses A, Lennon F, Vance JM, PericakVance MA. North Carolina macular dystrophy is assigned to chromosome 6. Genomics 1992; 13:681–685.

189.Small KW. North Carolina macular dystrophy: clinical features, genealogy, and genetic linkage analysis. Trans Am Ophthalmol Soc 1998; 96:925–961.

190.Small KW. North Carolina macular dystrophy. Revisited. Ophthalmology 1989; 96:1747–1754.

191.Voo I, Glasgow BJ, Flannery J, Udar N, Small KW. North Carolina macular dystrophy: clinicopathologic correlation. Am J Ophthalmol 2001; 132:933–935.

192.Small KW, Killian J, McLean WC. North Carolina’s dominant progressive foveal dystrophy: how progressive is it. Br J Ophthalmol 1991; 75:401–406.

193.Hermsen VM, Judisch GF. Central areolar pigment epithelial dystrophy. Ophthalmologica 1984; 189:69–72.

194.Douglas AA, Waheed I, Wyse CT. Progressive bifocal chorioretinal atrophy: a rare familial disease of the eyes. Br J Ophthalmol 1968; 52:742–751.

195.Kelsell RE, Godley BF, Evans K, Tiffin PA, Gregory CY, Plant C, Moore A, Bird AC, Hunt DM. Localization of the gene for progressive bifocal chorioretinal atrophy (PBVRA) to chromosome 6q. Hum Mol Genet 1995; 4:1653–1656.

196.Godley BF, Tiffin P, Evans K, Kelsell RE, Hunt DM, Bird AC. Clinical features of progressive bifocal chorioretinal atrophy:

a retinal dystrophy linked to chromosome 6q. Ophthalmology 1996; 103:893–898.

197.O’Donnell FE, Welch RB. Fenestrated sheen macular dystrophy. A new autosomal dominant maculopathy. Arch Ophthalmol 1979; 97:1292–1296.

198.Daily MJ, Mets MB. Fenestrated sheen macular dystrophy. Arch Ophthalmol 1984; 102:855–856.

199.Slagsvold JE. Fenestrated sheen macular dystrophy. A new autosomal dominant maculopathy. Acta Ophthalmol (Copenh) 1981; 59:683–688.

200.Sneed SR, Sieving PA. Fenestrated sheen macular dystrophy. Am J Ophthalmol 1991; 112:1–7.

201.Polk TD, Gass JD, Green WR, Novak MA, Johnson MW. Familial internal limiting membrane dystrophy. A new sheen retinal dystrophy. Arch Ophthalmol 1997; 115:878–885.

202.Lam BL. Hereditary retinal degenerations. In: Parrish R, ed. Bascom Palmer Eye Institute Atlas of Ophthalmology. Philadelphia: Current Medicine, 2000:343–349.

choroid. The disorder was first described in the 19th century and is now known to be produced by mutations of the gene encoding component A of Rab geranylgeranyl transferase called Rab escort protein-1 (REP-1) (1). The enzyme attaches geranylgeranyl lipid groups to selected intracellular proteins called Rab proteins. Rab proteins control cellular secretory and endocytic pathways. Choroideremia is a disease confined to the retina, because there are two Rab escort proteins, REP-1 and REP-2. In choroideremia patients, REP-1 is defective but REP-2 is functional. Retinal cells need both REP-1 and REP-2 to function properly but most cells elsewhere function adequately with only REP-2. Several different mutations of the REP-1 gene are found in association with choroideremia, and variable symptoms and features are frequently encountered. A recent histologic, immunocytochemistry study suggests rod photoreceptors as a primary site of pathology in choroideremia (2).

Affected males with choroideremia usually have poor night vision and decreased peripheral vision within the first two decades of life. Bilateral progressive degeneration of the retina and choroid occurs with initial sparing of the fovea. Areas of granularity and depigmentation are first visible in the peripheral regions of the retina, but bone-spicule-like pigmentary clumping and severe retinal vascular attenuation as seen in retinitis pigmentosa are not typical (Fig. 11.1). Visual acuity is minimally affected early but as the retinal degeneration progresses, central vision deteriorates gradually with generally favorable prognosis for visual acuity until the seventh decade of life (3). In contrast, female carriers of choroideremia are commonly asymptomatic with preserved visual function. However, patchy areas of peripheral retinal depigmentation, granularity, or pigmentary clumping are found in as high as 96% of female carriers (4).

The diagnosis of choroideremia is arrived on the basis of ocular history, characteristic clinical features, and genetic analysis if available. Examination of the mother of the suspected affected male and other possible female carriers within the family for patchy peripheral areas of retinal pigmentary disturbance is extremely helpful. A family history of X-linked retinal disease may or may not be present. Genetic analysis, if

Figure 11.1 Chorioretinal degeneration in a patient with choroideremia. (From Ref. 29.) (Refer to the color insert.)

available, will not only determine whether the patient has choroideremia but will also identify female carriers. Demonstrating the absence of REP-1 protein in peripheral blood samples with immunologic technique will identify affected individuals but not female carriers (5).

A useful measure of retinal function in affected males with choroideremia is the full-field ERG. But it has very low sensitivity in detecting female carriers (Fig. 11.2). The ERG is marked impaired early in the disease with reduced and prolonged rod and cone responses. During the early stage, the rod response is more impaired than the cone response, and ERG reductions are usually easily apparent even when symptoms are minimal. Only very rarely are normal ERG amplitudes observed in young patients with very early stage of disease

(6). With further disease progression, all components of the ERG responses deteriorate and become non-detectable. Sieving and associates (4) reviewed the full-field ERG records of 47 affected males and 26 carrier females with choroideremia. The rod response was markedly reduced or nondetectable in all affected males, and in those whom the cone response was still detectable, the cone implicit times were delayed even when cone amplitudes were in the normal range. Of the 26 females carriers, only four (15%) had

Figure 11.2 Full-field ERG responses of a 31-year-old choroideremia carrier and her 8-year-old affected son. Note the normal ERG responses in the carrier and the markedly impaired responses of the affected son with non-detectable rod response and severely impaired cone responses.

abnormal ERG. EOG impairment parallels ERG reductions, and EOG is normal in carriers (7). Likewise, VEP findings parallel ERG impairment.

GYRATE ATROPHY

Gyrate atrophy is an autosomal recessive dystrophy involving the retina and choroid, caused by mutations of the gene

identifiable genotypes are found in patients’ response to vitamin B6 supplementation (11,12). Low arginine diets also reduce serum ornithine level in some patients with gyrate atrophy (13). However, the effect of dietary therapies on the progression of retinal degeneration is conflicting, perhaps due in part to the genetic heterogeneity and variable expressivity of the disease. Berson and associates (14,15) found no visual improvement in patients treated with vitamin B6 or low arginine diets. Likewise, progressive visual loss in affected children treated with low arginine diet was reported by Vannas-Sulonen and colleagues (16). In contrast, KaiserKupfer and colleagues (17) noted only modest progressive visual loss in their group of affected children treated with low arginine diet.

The diagnosis of gyrate atrophy is based on characteristic clinical findings, elevated serum ornithine level, and genetic analysis if available. Full-field rod and cone ERG responses are typically markedly reduced or non-detectable at the time of diagnosis. Accordingly, ERG plays a supportive role in the diagnosis of the disorder. However, when the disease is not advanced and ERG responses are still detectable, ERG can serve as a measure of retinal function (14). In such cases, the amplitudes of the rod and cone responses are moderately to severely reduced, the implicit times are mildly to moderately prolonged, and the a-wave and b-wave components are equally affected (18). The degree of retinal involvement produces corresponding reductions in EOG and VEP. Interestingly, clinical and ERG findings similar to gyrate atrophy have been found in patients without elevated serum ornithine, some of whom have dominant disease (19). These patients with gyrate-atrophy-like findings have normal ornithine aminotransferase activity and by definition, do not have gyrate atrophy.

HEREDITARY CHOROIDAL ATROPHY

Aside from X-linked recessive choroideremia, other autosomal dominant and recessive forms of choroidal atrophy are found.

The choroidal atrophy may be more localized, located centrally or in the peripapillary region, or more diffuse. Krill and Archer (20) proposed a clinical classification of choroidal atrophy based on the extent of involvement, regional vs. diffuse, and whether choriocapillaris atrophy occurs with or without atrophy of the large choroidal vessels. However, regional choroidal atrophy may progress to diffuse involvement in some individuals and different clinical patterns of choroidal may occur within the same pedigree due to variable expressivity. The degree of involvement on clinical examination generally parallels ERG b-wave amplitudes, and the implicit times are less affected (Fig. 11.4) (20). Reduced EOG light-peak to dark-trough amplitudes ratios are common (20). Central areolar choroidal dystrophy discussed in chapter10.

HELICOID PERIPAPILLARY CHORIORETINAL

DEGENERATION

Helicoid peripapillary chorioretinal degeneration is a rare bilateral dominant dystrophy characterized by well-demar- cated, wing-shaped peripapillary atrophic areas of retinal pigmented epithelium and choroid radiating from the optic nerve head. The disorder was first reported by Sveinsson in 1939 as ‘‘chorioditis areata,’’ and received its current name from Francescetti in 1962 (21,22). The disease occurs mostly in European and Icelandic pedigrees and is linked to chromosome 11p15 (23). Dysfunction of the affected retinal areas produces variable decrease in vision, which becomes severe if the macula is involved. The diagnosis is made on clinical ophthalmoscopic appearance and positive family history.

Results of electrophysiology testing in helicoid peripapillary chorioretinal degeneration are rarely reported. However, Eysteinsson and associates (24) studied 17 affected members of a family and found the full-field ERG to be highly variable. Of the 17 patients, 5 had normal ERG, 6 had reduced photopic and scotopic responses with normal implicit times, and 6 had marked reduced scotopic and photopic a-wave and b-wave