Ординатура / Офтальмология / Английские материалы / Electrodiagnosis of Retinal Disease_Miyake_2005

The characteristic features of the fundus of patients with XLRS (Fig. 2.31) are schisis in the foveal area (foveoschisis) with either a wheellike configuration with radiating spoke-like striations (Fig. 2.31A) or clearly visible microcysts (Fig. 2.31B); an absence of vascular leakage in the macula as seen by fluorescein angiography (Fig. 2.31C); cystic spaces in the macula revealed by OCT (Fig. 2.31D); and peripheral retinoschisis in about 50% of the

eyes, often with inner retinal breaks (Fig. 2.31E). Breaks in the outer retina may be associated with retinoschisis (Fig. 2.31F) and can be sealed by photocoagulation (Fig. 2.31G). A golden tapetal reflex is frequently observed in the peripheral retina (Fig. 2.31H), and some patients have flecks in the posterior pole (Fig. 2.31I).

During the course of the disease process, the appearance of the fundus in patients with XLRS

varies considerably, as shown in Fig. 2.32. The cystic appearance of the macula may change to nonspecific macular degeneration (Fig. 2.32A), and fluorescein angiography may show hyperfluorescence due to window defects in the RPE (Fig. 2.32B). Extensive pigmentary changes of the retina (Fig. 2.32C) may be present, sometimes associated with sheathing of the vessels and abnormal appearance of the optic disks (Fig. 2.32D). Fluorescein angiography shows extensive RPE degeneration (Fig. 2.32E), and

closure of retinal vessels may be seen resulting in avascular zones (Fig. 2.32F,G) with new vessel formation (Fig. 2.32H,I). Some patients have a retinal detachment associated with outer retinal breaks and vitreous hemorrhage. All of these changes make the correct diagnosis difficult.

The schisis occurs in the plane of the nerve fiber and ganglion cell layers of the retina. It has long been suggested that degenerating Mueller cells or inner retinal cells may be the primary cause of the pathological changes [5].

The visual acuity of patients with XLRS at various ages is shown in Fig. 2.33. Most patients, including young ones, show moderately poor visual acuity that gradually decreases with increasing age. Hypermetropia has been shown to be a frequent accompaniment of this disorder. In fact, many patients with XLRS are first diagnosed with hyperme-

tropic amblyopia or with heterotropia during infancy, and only during follow-up examinations are they found to have XLRS. A plot of the axial length as a function of the refractive error is shown in Fig. 2.34 for patients with XLRS, demonstrating that the hypermetropia is axial hypermetropia, not refractive hypermetropia [6].

Full-field ERGs are of significant diagnostic value [1–4]. The ERGs elicited by relatively bright flash stimuli under dark-adapted conditions have a negative configuration in most patients with XLRS (Fig. 2.35).Abnormalities in the full-field ERGs are present even when the retinoschisis is confined to the fovea ophthalmoscopically. This indicates a diffuse functional abnormality in the entire retina.

During the early stage the amplitude of the a-wave is normal, but that of the b-wave is smaller than the a-wave. The OPs are smaller than normal or may be absent. At an intermediate stage the a-wave may also be reduced, but the b-wave is even more reduced, keeping the negative configuration. ERGs may become undetectable at the most advanced stage. This is a rare observation, and we have observed

only two such eyes among our 57 patients with XLRS [7]. However, once the ERGs become undetectable, the diagnosis may be difficult. The alterations of the fundus may be similar to those in patients with RP (Fig. 2.32C), and a differential diagnosis from RP is crucial. The correct diagnosis can be made by a family survey, the ocular findings of the other eye, and molecular genetic analysis. The full-field rod and cone ERGs recorded from a representative patient with XLRS are shown in Fig. 2.36. The rod and cone ERGs are both reduced with delayed b-wave implicit times. The EOG is normal [2, 3].

These ERG and EOG findings suggest that the abnormal ERGs in patients with XLRS result from dysfunction of the on and off bipolar cells in the rod and cone pathways.

Because the negative ERGs and subnormal rod, cone ERGs resemble the ERGs of patients with the incomplete type of congenital stationary night blindness (incomplete CSNB) [8], differential diagnostic tests to distinguish XLRS and incomplete CSNB are important, particularly when the macular changes in patients with

XLRS are subtle (see Section 2.10.5). One of the differential diagnostic tests is the S (blue)-cone ERG. The S-cone ERG is essentially absent in patients with XLRS (Fig. 2.37), as in complete CSNB, whereas it is clearly present in incomplete CSNB [9] (see Section 2.10.5.5).

To characterize focal macular ERGs from patients with XLRS, we have divided the patients into two groups [10]. Group 1 includes those who have foveoschisis with little or no change in their foveal fluorescein angiograms, and group 2 includes those with advanced macular changes with nonspecific macular degeneration.

The focal macular ERGs elicited by 5°, 10°, and 15° spots from representative patients from both groups are compared with those from a normal subject in Fig. 2.38. In group 1 (case 1), the a-wave amplitudes are within the normal limits, but the amplitudes of the b-waves and OPs are significantly smaller than those for normal control subjects. The mean b-wave/

a-wave (b/a) ratios are significantly smaller than in normal eyes, and the ratio decreases with decreasing spot size. The implicit times of the a-waves, b-waves, and OPs are significantly delayed. In group 2 (case 2), the focal macular ERG is nearly absent.

These results of focal macular ERGs suggest that the pathology in the macula during the early stage of XLRS may be mainly in the bipolar cell layer. The on bipolar cells may be more severely affected than the off bipolar cells because the a-wave is relatively better preserved than the b-wave. During the late stage, when fluorescein angiography shows window defects of the RPE, the macular cones may also be affected, resulting in undetectable ERGs.

The amplitudes of the first-order kernel of the multifocal ERGs in group 1 patients with XLRS are markedly reduced in the central retina, corresponding to the area of the foveal schisis (Fig. 2.39) [11]. The amplitude of the focal responses outside the foveal area varies widely, but most patients show some degree of reduced amplitude, although the implicit times are significantly delayed. These findings suggest that the pathology of XLRS affects the implicit times more than the amplitude.

As mentioned, a schisis is present in the periphery in about 50% of patients with XLRS. It is interesting to study how the peripheral retinoschisis affects the ERG responses in these areas. Two patients with peripheral retinoschisis were examined [11]. Drawings of their fundus and their visual field maps are shown in Fig. 2.40. The gray areas of the multifocal ERGs in Fig. 2.41 indicate the retinal areas corresponding to peripheral retinoschisis. The multifocal ERG amplitudes in the areas of peripheral retinoschisis are within the normal range and are not different from those from the

adjacent retinal areas without retinoschisis. These results suggest that the outer and middle retinal layers are still functioning relatively well despite the balloon-like retinoschisis. This is reasonable because the splitting of the retina is in the nerve fiber layer, and the nerve fiber layer does not contribute to the multifocal ERGs.

In the patients in group 2, the amplitudes of the local cone responses are smaller than the 95% confidence limits at nearly all loci in the 30° field. The amplitude of the second-order kernel is substantially smaller and essentially absent at nearly all locations. This is true even in retinal areas where the amplitudes of the first-order kernels are normal.

The summated first-order kernel and the second-order kernel waveforms in normal subjects and XLRS patients are compared in Fig. 2.42. The amplitude of the summated secondorder kernel is more reduced than that of normal controls, and the second-order kernel is more reduced than the first-order kernels, presumably owing to widespread dysfunction of the proximal retina.

The ophthalmoscopic appearance of the fundi of patients with XLRS is either a homogeneous or streaked tapetal-like reflex in the midperipheral retina. The appearance has been described as flaking gold, gold-dusted, goldenyellow, grayish white, or yellowish white (Fig. 2.31H). The mechanism underlying this reflex remains to be determined. This reflex in the eyes of patients with XLRS closely resembles the color of the fundus of eyes with Oguchi’s disease. The abnormal reflex in Oguchi’s disease disappears after extensive dark adaptation (Mizuo phenomenon, see Section 2.12) [12]. De Jong et al. reported that this change in the appearance of the fundus with dark adaptation can also be seen in eyes with XLRS [13]. They hypothesized that excess extracellular K+ in the retina causes the golden reflex.

We have had two patients with XLRS who had the tapetal-like reflex and developed vitreous hemorrhage. Vitrectomy was performed by peeling the posterior hyaloid membrane. The tapetal-like reflex, which had been present before the massive vitreous hemorrhage, disappeared after the posterior hyaloid was peeled from the retinal surface [14] (Fig. 2.43). If the hypothesis of de Jong et al. is correct, our findings suggest that the flow of K+ toward the vitreous cavity may be accelerated by peeling the posterior hyaloid, leading to a decrease in K+ concentration in the inner retina and disappearance of the golden reflex. However, despite the disappearance of the golden reflex following peeling of the posterior hyaloid, the postoperative ERG did not change significantly (Fig. 2.44).

Fig. 2.43. tapetal-like golden reflex in the inferior retina of a 42-year-old man wth XLRS before peeling the posterior hyaloid (A) and the disappearance of the tapetallike reflex afterward (B). (From Miyake and Terasaki [14], with permission)

Fig. 2.44. ERGs recorded with bright white light before (A) and after (B) surgery in the patient with XLRS shown in Fig. 2.43. A normal control is shown at the bottom (C). Arrowheads indicate the stimulus onset. (From Miyake and Terasaki [14], with permission)