Ординатура / Офтальмология / Английские материалы / Electrodiagnosis of Retinal Disease_Miyake_2005

Grouped pigmentation of the retina, also called “bear-track” pigmentation, is a nonhereditary, nonprogressive congenital condition [12]. The fundus and fluorescein angiograms show round and irregularly shaped lesions representing RPE hypertrophy scattered throughout the retina (Fig. 2.11). The results of ERG (Fig.

2.12), electrooculography (EOG), and other visual functions tests are within normal limits. The multifocal ERGs are not reduced in the area of the spotty pigmentation, indicating that the retinal function is not impaired in the pigmented areas (Fig. 2.13).

References

1.Armington JC, Gouras P, Tepas DI, Gunkel RD (1961) Detection of the electroretinogram in retinitis pigmentosa. Exp Eye Res 1:74–80

2.Berson EL (1987) Electroretinographic findings in retinitis pigmentosa. Jpn J Ophthalmol 31:327–348

3.Heckenlively JR,Yoser SL, Friedman LH, Oversier JJ (1988) Clinical findings and common symptoms in retinitis pigmentosa. Am J Ophthalmol 105:504– 511

4.Miyake Y (1988) Studies of local macular ERG. Acta Soc Ophthalmol Jpn 92:1419–1449

5.Kondo M, Miyake Y, Horiguchi M, Suzuki S, Tanikawa A (1995) Clinical evaluation of multifocal electroretinogram. Invest Ophthalmol Vis Sci 36: 2146–2150

6.Banin E, Cideciyan AV, Aleman TS, Petters RM, Wong F, Milam AH, et al (1999) Retinal rod pho- toreceptor-specific gene mutation perturbs cone pathway development. Neuron 23:549–557

7.Carr RE Siegel IM (1973) Unilateral retinitis pigmentosa. Arch Ophthalmol 90:21–26

8.Gass JDM (1997) Unilateral retinitis pigmentosa. In: Stereoscopic atlas of macular diseases, diagnosis and treatment (4th edn). Mosby, St. Louis, pp 380–381

9.Noble KG (1989) Hereditary pigmented paravenous chorioretinal atrophy. Am J Ophthalmol 108:365– 369

10.Small KW, Anderson WB Jr (1991) Pigmented paravenous retinochoroidal atrophy; discordant expression in monozygotic twins.Arch Ophthalmol 109:1408–1410

11.Hirose T, Miyake Y (1979) Pigmentary paravenous chorioretinal degeneration: fundus appearance and retinal functions. Ann Ophthalmol 11:709–718

12.Buettner H (1975) Congenital hypertrophy of the retinal pigment epithelium in Maine. Am J Ophthalmol 79:177–189

Crystalline retinopathy is a condition first described by Bietti in 1937 [1]. Patients with crystalline retinopathy are initially seen when they are middle-aged because of reduced visual function. The alterations are often associated with night blindness and are slowly progressive. The fundus has numerous yellowish white glistening deposits resembling crystalline granules scattered throughout the posterior pole in all retinal layers bilaterally [1]. Typically, the optic disks and retinal vessels are normal.

There may be marginal crystalline deposits in the cornea, and when present the deposits are sparkling yellow or white, round, polygonal, or needle-like crystals located in the anterior stroma in the perilimbal region [1, 2]. It has been reported that the crystalline deposits in the cornea can be detected more clearly by specular microscopy than by conventional slitlamp examination [3]. Indeed, we have had cases in which the crystalline deposits were not detected by slit-lamp examination but were clearly seen by specular microscopy [4].

Photographs of the fundus and the cornea as seen by specular microscopy in two patients with crystalline retinopathy are shown in Fig. 2.14. Fluorescein angiography revealed diffuse atrophy of the RPE, and atrophy of the choriocapillaris is occasionally present in the areas corresponding to the depigmented areas.

The ophthalmoscopically observed crystalline deposits do not result in abnormal fluorescein findings. The progression of the disease process is similar in patients with and without crystalline deposits in the cornea.

Changes in the fluorescein angiograms and visual field in a patient with Bietti’s crystalline retinopathy during a 5- to 6-year follow-up are shown in Fig. 2.15. Extensive areas of nonperfusion of the choriocapillaries were present paracentrally that progressively enlarged and became confluent. The nonperfused areas extended to the periphery of the fundus during the 5- to 6-year follow-up. Visual field defects were detected in the areas corresponding to the nonperfused areas.

Full-field ERGs may be normal, reduced, or undetectable depending on the stage. The ERGs become progressively more depressed during the follow-up period as shown in Fig. 2.16. The amplitudes of the rod and cone components of the ERGs are reduced in parallel, indicating that both rods and cones are affected simultaneously and almost equally.

The mode of inheritance is autosomal recessive, and it was recently found that this disease is caused by mutations in the CYP4V2 gene [5]. All of the patients whose ERGs were shown in this section had a mutation in this gene [6].

References

1.Bietti GB (1937) Uber familiares Vorkommen von “Retinitis punctata albescens” (verbunden mit “Dystrophia marginalis cristallinea corneae”), Glitzern des Glaskorpers und anderen degenerativen Augenveranderungen. Klin Monatsbl Augenheilkd 99:737–756

2.Bagolini B, Ioli-Spada G (1968) Bietti’s tapetoretinal degeneration with marginal corneal dystrophy. Am J Ophthalmol 65:53–60

3.Wakita M, Hayakawa M, Kato K, Kanai J (1990) Cases with crystalline retinopathy. Research Committee on Chorioretinal Degeneration, The

Ministry of Health and Welfare of Japan, Tokyo, pp 231–233

4.Takikawa C, Miyake Y, Yagasaki K (1992) Reevaluation of crystalline retinopathy based on corneal findings. Folia Ophthalmol Jpn 43:969–978

5.Li A, Jiao X, Munier FL, Schorderet DF,Yao W, Iwata F, et al (2004) Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2. Am J Hum Genet 74:817–826

6.Lin J, Nishiguchi KM, Nakamura N, Dryja TP, Berson EL, Miyake Y (2005) Recessive mutations in the CYP4V2 gene in East Asian and Middle Eastern patients with Bietti crystalline corneoretinal dystrophy. J Med Genet 42:e38

The late infantile and juvenile forms of neuronal ceroid-lipofuscinosis are known as “Batten disease” [1]. The mode of inheritance of this disease is autosomal recessive. Although many cases of Batten disease have been reported worldwide, only a few patients have been reported to be Japanese [2], suggesting that the incidence of the disease is lower among the Japanese population.

Patients with Batten disease have a lysosomal storage disease that results in the accumulation of insoluble fluorescent lipoproteins, believed to be ceroid and lipofuscin pigments [3]. These pigments are normally associated with aging. Most of the patients with Batten disease who have been described in the literature were at an advanced stage, so the clinical findings in the early stages are still unknown.

We have monitored the visual functions and ocular findings in two siblings with Batten disease for more than 2 years. One of them visited our clinic initially at an early stage of the disease [4]. This 5-year-old boy was examined at the time his elder brother was examined. He had no complaints and no history of systemic or ocular disorders at that time. His visual acuity was 1.0 in both eyes. The fundus had a slightly abnormal reflex in the macula but was otherwise normal. The a-wave of the full-field ERGs was normal, but the b-wave was smaller than the a-wave, resulting in a negative-type ERG (Fig. 2.17).

During the 2- to 3-year follow-up, his visual acuity decreased to 0.1 in 10 months, and the full-field ERGs became nearly undetectable by 24 months, with progressive reduction of the b-wave/a-wave (b/a) ratio (Fig. 2.17). The

fundus developed bull’s-eye maculopathy at 18 months followed by diffuse degeneration of the RPE (Fig. 2.18, left) and attenuation of the retinal vessels associated with optic atrophy in 28 months. As for his older brother, electron microscopy of lymphocytes in the peripheral blood showed a fingerprint pattern (Fig. 2.18, right), and juvenile neuronal ceroid-lipofusci- nosis was diagnosed. Thus, we were able to follow the course of the disease process in this boy from an early stage to an advanced stage.

His older brother, a 7-year-old boy, was first examined by us because of visual disturbances. His visual acuity was 0.07 (OD) and 0.04 (OS), and his fundus showed bull’s-eye maculopathy and diffuse RPE degeneration with slight optic atrophy. The retinal vessels were attenuated. Electron microscopy of lymphocytes of peripheral blood showed a fingerprint pattern. The full-field mixed rod–cone ERGs elicited by bright stimuli were undetectable. His visual acuity decreased rapidly to hand motion vision 5–6 months later.In addition,the patient had epileptic seizures, and his disorder was diagnosed as juvenile neuronal ceroid-lipofuscinosis. This patient exhibited the ocular findings of a relatively advanced stage of Batten disease.

From a diagnostic point of view, the important finding was the negative ERGs even when the other ocular findings were essentially normal [2, 4]. During progression of the disease, the amplitudes of the a-wave and the b-wave decreased, and the b/a ratio became smaller, indicating enhancement of the negativity in the ERG. Although histological studies of the early stage of Batten disease have not been reported, histopathological examination

of the retina of an animal model of this disorder showed that the primary lesion is in the inner retinal layers [1, 5]. The ERG findings of the patient supports these animal results because such negative ERGs are usually observed in patients with inner retinal layer dysfunction, such as retinal circulatory disturbances, congenital retinoschisis, and congenital

References

1.Copenhaver RM, Goodman C (1960) The electroretinogram in infantile, late infantile and juvenile amaurotic family idiocy. Arch Ophthalmol 63:559–566

2.Shimada H, Tashiro T, Matsui M, Owada M, Kitagawa T (1983) Correlation of funduscopic and histological features in a case with Batten disease. Jpn J Clin Ophthalmol 37:385–393

stationary night blindness. The negative ERGs seen at the early stage of Batten disease may be useful when assigning an early diagnosis. Furthermore, rapid deterioration of the ERG and visual acuity are unusual in other hereditary retinal disorders and thus may be one of the characteristics of this disorder.

3.Beckerman BL, Rapin I (1975) Ceroid lipofuscinosis. Am J Ophthalmol 80:73–77

4.Horiguchi M, Miyake Y (1992) Batten disease: deteriorating course of ocular findings. Jpn J Ophthalmol 36:91–96

5.Goebel NH, Zeman W, Damaske E (1974) The fine structure of the retina in neuronal ceroidlipofuscinosis. Am J Ophthalmol 77:25–39

The association of pigmentary retinopathy with mitochondrial myopathy has been well recognized [1]. The Kearns-Sayre syndrome, strongly associated with deletions in mitochondrial DNA [2], is one of the distinct syndromes of mitochondrial myopathy [3]. It is characterized by a triad of signs—onset before 15 years of age, progressive external ophthalmoplegia, pigmentary retinopathy—as well as by one or more of the following problems: heart block, cerebellar ataxia, high cerebrospinal fluid protein [4].

The stage of the disease can be determined by analyzing the appearance of the fundus and the visual functions of patients with pigmen-

tary retinopathy [5] (Figs. 2.19, 2.20, 2.21): stage 0, fundus appearance, visual functions, and ERGs are within normal limits; stage 1, salt and pepper retinopathy is present over the entire retina, as in cases 1 and 2 (Fig. 2.19) but the visual functions and ERGs are still normal; stage 2, visual functions and ERGs are abnormal (case 3), with the fundus appearing similar to stage 1; stage 3, chorioretinal atrophy progresses around the optic disk and some areas of the retina (Fig. 2.21), and the ERGs are not detectable (case 3); and stage 4, more extensive chorioretinal atrophy, and the fundus appears similar to that seen with choroidal sclerosis.