Ординатура / Офтальмология / Английские материалы / Electrodiagnosis of Retinal Disease_Miyake_2005

References

1.Kearns TP (1965) External ophthalmoplegia, pigmentary degeneration of the retina, and cardiomyopathy: a newly recognized syndrome. Trans Am Ophthalmol Soc 63:559–625

2.Moraes CT, DiMauro S, Zeviani M (1989) Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N Engl J Med 320:1293–1299

3.Mullie MA,Harding AE,Petty RK (1985) The retinal manifestations of mitochondrial myopathy: a study of 22 cases. Arch Ophthalmol 103:1825–1830

4.Zeviani M, Bonilla E, De Vivo DC, DiMaruro S (1989) Mitochondrial diseases. Neurol Clin 7:123– 156

5.Ota I, Miyake Y, Awaya S (1989) Studies of ocular fundus and visual functions in Kearns-Sayre syndrome: with special reference to the new stage classification. Acta Soc Ophthalmol Jpn 93:329–338

Choroideremia is an X-linked recessive chorioretinal dystrophy [1]. The course of visual function deterioration is similar to that of RP. Affected men usually report the onset of night blindness at 10–30 years of age and later become aware of the loss of peripheral visual fields. The central vision is affected only during middle age or later. It has been reported that aberrant splicing of the choroideremia gene (CHM) is the most likely cause of choroideremia [2].

Despite such functional similarities to RP, the appearance of the fundus is different. Unlike RP, the fundus of choroideremia patients exhibits atrophy of the choroid,normal retinal vessels, and an absence of optic atrophy (Fig. 2.22) [1]. In late-stage, fluorescein angiography demonstrates marked loss of the RPE and the choroidal vessels, including the choriocapillaris in the central macular area. However, many choroidal vessels are revealed that had been difficult to see ophthalmoscopically. The carrier state is important for diagnosing this disease [1, 3]. The fundi of female carriers almost always have characteristic mottling and depigmentation of the RPE, which is most marked in the mid-periphery (Fig. 2.23).

The ERG is often unrecordable from the early stage of the disease (Fig. 2.24) [1, 3]. Despite such marked changes in the fundus of female carriers, the visual functions, including the ERGs, are essentially normal in most carriers (Fig. 2.24). These findings in carriers are important for making a correct diagnosis of hemizygotes [1, 3].

References

1.Heckenlively JR, Bird AC (1988) Choroideremia. In: Heckenlively JR (ed) retinitis pigmentosa. Lippincott, Philadelphia, pp 25–36

2.Van der Hurk JAJM, Schwartz M, van Bokhaven H, van de Pol TJR (1997) Molecular basis of choroi-

deremia (CHM): mutations involving the Rab escort protein-1 (REP-1) gene. Hum Mutat 9:110– 117

3.Rubin ML, Fishman RS, McKay RA (1966) Choroideremia; study of a family and literature review. Arch Ophthalmol 76:563–574

Gyrate atrophy of the choroid is a rare, recessively inherited chorioretinal atrophy that results from an inborn error of metabolism. Gyrate atrophy is caused by generalized deficiency of the mitochondrial matrix enzyme, ornithine aminotransferase [1] and is manifested early in life as sharply demarcated garland-shaped zones of chorioretinal atrophy in the mid-periphery of the fundus (Fig. 2.25) [2]. The macula is usually involved later in life. Pallor of the optic disk, vitreous opacities, and narrowing of the retinal vessels may develop at a relatively advanced stage of the disease. Most patients have a high degree of myopia and night

blindness, and loss of the peripheral visual field accompanies the fundus changes. The ERG is usually markedly reduced or absent during early childhood even when the fundus changes are minimal (Fig. 2.26).

An expression defect of the ornithine aminotransferase gene was identified in gyrate atrophy [3]. There are two clinical subtypes of gyrate atrophy based on the in vivo response to vitamin B6: patients who are B6-responsive and those who are not responsive. The patients who are vitamin B6-responsive generally have a milder disease than those who are vitamin B6–unresponsive [4].

References

1.Takki KK (1974) Gyrate atrophy of the choroid and retina associated with hyperornithinaemia. Br J Ophthalmol 58:3–23

2.Ota I, Miyake Y, Ichikawa H (1985) A family with gyrate atrophy. Jpn Rev Clin Ophthalmol 79:1221– 1223

3.Inana G, Hotta Y, Zintz C, Takki K, Weleber RG, Kennaway NG, et al (1988) Expression defect of ornithine aminotransferase gene in gyrate atrophy. Invest Ophthalmol Vis Sci 29:1001–1005

4.Wilson DJ, Weleber RG, Green WR (1991) Ocular clinicopathologic study of gyrate atrophy. Am J Ophthalmol 111:24–33

Enhanced S-cone syndrome (ESCS) is a newly identified hereditary retinal disorder with several unique functional properties [1, 2]. Initially, this disorder was classified as a type of congenital stationary night blindness,but it was later found that most of the cones in these eyes were the short-wavelength-sensitive cones (S-cones) [3, 4].

The syndrome is caused by mutations in the PNR (photoreceptor-specific nuclear receptor) gene [5]. The PNR gene is a retinal orphan nuclear receptor that determines the phenotype of the cones during embryogenesis; it is required for the differentiating middleand

long-wavelength-sensitive cones (ML-cones) from S-cones. Mutation of the PNR gene arrests cone differentiation at a stage where most cones are still S-cones.

The clinical findings associated with ECSC include congenital night blindness,progressively decreasing visual acuity, supernormal S-cone ERGs, and characteristic fundus alterations. The inheritance is autosomal recessive [1–5].

At present, we have studied three patients with ESCS who had PNR gene mutations [6, 7]. The fundus shows cystic changes in the macula with or without annular pigmentary retinopathy just outside the vascular arcades (Fig. 2.27).

One of our younger patients (a 10-year-old boy) had neovascular maculopathy in one eye [7]. Fluorescein angiography is essentially normal in the macular area of these patients without leakage of fluorescein dye. These findings indicate that the cystoid changes in the macula are not similar to that in eyes with macular edema, and the pathology is more comparable to that of retinoschisis.

Optical coherence tomography (OCT) images of an eye with ESCS show the cystic changes in the macula that are present in most patients. The macular changes are subtle in some patients, but OCT can detect the small cysts.

Full-field ERGs reveal the diagnostic findings in this disorder (Fig. 2.28). The rod

ERGs are undetectable. The amplitudes of the a-wave and b-wave of the bright flash, mixed rod–cone ERGs may be normal or supernormal, with a significant delay in the implicit times; the OPs are essentially absent. The cone ERGs are larger than that of normal controls with delayed implicit times. It is interesting that the amplitude and shape of the cone ERGs recorded under light-adapted conditions are almost identical to the ERGs recorded under dark-adapted conditions (bright flash ERGs). This finding is one of the keys to the diagnosis of ESCS. It indicates that the main component of the ERG is cone-driven. Despite such large cone ERGs, the 30Hz flicker ERG is extremely small with delayed implicit times, suggesting

that the large cone ERGs reflect the function of the S-cone.

The unusual enhancement of the S-cone ERGs in these patients can be clearly demonstrated by comparing the cone ERGs recorded with stimuli that selectively stimulate S-cones and selectively stimulate the ML-cones. When the intensities of the red (ML-cones) and blue (S-cones) wavelength stimuli are balanced to produce equal-amplitude cone ERG b-waves from normal eyes, the blue stimuli elicit much larger b-waves than the red stimuli in ESCS patients (Fig. 2.29). These ERG results indicate

that the supernormal ERGs elicited by bright white stimuli are S-cone driven in ESCS patients.

As was shown in Section 1-1-3-5, the S-cone ERG has a depolarizing waveform with a large b-wave (on response), and the a-wave and d- wave (off response) are essentially absent. This is because S-cones connect only to on bipolar cells in primates. However, it is interesting that the S-cone ERGs in patients with ESCS have large a-waves and d-waves (Fig. 2.30), indicating that the S-cones in eyes with ESCS may have connections not only to on bipolar cells but also to off bipolar cells [8].

References

1.Marmor MF, Jacobson SG, Foerster MH, Kellner U, Weleber RG (1990) Diagnostic clinical findings of a new syndrome with night blindness, maculopathy and enhanced S cone sensitivity. Am J Ophthalmol 110:124–134

2.Hood DC, Cideciyan AV, Roman AJ, Jacobson SG (1995) Enhanced S-cone syndrome: evidence for an abnormally large number of S cones. Vis Res 35: 1473–1481

3.Fishman GA, Peachey NS (1989) Rod-cone dystrophy associated with a rod system electroretinogram obtained under photopic conditions. Ophthalmology 96:913–918

4.Marmor MF (1989) Large rod-like photopic signals in a possible new form of congenital stationary night blindness. Doc Ophthalmol 71:265–269

5.Haider NB, Jacobson SG, Cideciyan AV, Swiderski R, Streb LM, Searby C, et al. (2000) Mutation of a

nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate. Nat Genet 24:127–131

6.Miyake Y (2003) Hereditary retinal diseases with selective abnormalities in blue cone function. Folia Ophthalmol Jpn 54:673–682

7.Nakamura M, Hotta Y, Piao CH, Kondo M, Terasaki H, Miyake Y (2002) Enhanced S-cone syndrome with subfoveal neovascularization. Am J Ophthalmol 133:575–577

8.Kolb H, Lipets LE (1991) The anatomical basis for color vision in the vertebrate retina. In: Gouras P (ed) The perception of colour. Macmillan, London, pp 128–145

X-Linked retinoschisis (XLRS) is a slowly progressive disease. It is not rare, and it is occasionally misdiagnosed as several other disorders, including amblyopia, nonspecific macular

degeneration, retinal pigmentary dystrophy, and rhegmatogenous retinal detachment [1]. ERGs provide decisive information for the diagnosis [2–4].