Occult Macular Dystrophy

Occult macular dystrophy is an unusual, inherited macular dystrophy characterized by progressively decreased visual acuity due to macular dysfunction, but the fundus and fluorescein angiograms are essentially normal. In 1989 we reported three patients in one family with hereditary macular dystrophy without a visible fundus abnormality [1]. Since then we have diagnosed 43 patients (26 men and 17 women) with this disease from 14 families and termed the disorder "occult macular dystrophy"^] ("occult" meaning "hidden from sight").

The pedigrees of eight families with two or more affected members in each family are shown in Fig. 2.129 [3]. Many of the pedigrees

suggest autosomal dominant heredity. The fundus photographs and fluorescein angio-grams from three affected members of Family C [1] are shown in Fig. 2.130; the fundus and angiograms were normal. Full-field ERGs were normal in all these patients, but the focal macular ERGs were absent, indicating that the pathological basis for the depressed visual acuity lies in the macula. Recently, this localized dysfunction in the macula was confirmed by multifocal ERGs, which showed depressed responses in the central areas (Fig. 2.131). Our recent studies [4] of many patients indicated that the amplitudes of the multifocal ERGs are markedly reduced in the central 7° of the retina.

Fig. 2.129. Occult macular dystrophy. Family pedigrees with two or more affected members in a single family are shown. Filled symbols, affected male or female; open symbols, normal male or female; arrow, propositus; cross mark, examined; oblique line, deceased. (From Miyake [3])
Fig. 2.130. Fundus photographs (left) and fluorescein angiograms (right) of three patients with occult macular dystrophy in Family C of Fig. 2.128. Cases 1,2, and 3 are a 29-year-old woman, a 19-year-old man, and a 55-year-old man, respectively. (From Miyake et al. [1])
Fig.2.131. Full-field ERGs and focal macular ERG recorded from a normal subject and a patient with occult macular dystrophy (OMD). Full-field ERGs are normal but the focal macular ERG recorded with a 5° spot is absent in the OMD patient

The differences in the amplitudes of the ERGs recorded from patients with occult macular dystrophy and from normal subjects become smaller toward the peripheral field. Most patients have a slight but significant delay in the implicit times across the whole testing field, and the differences in the implicit times between occult macular dystrophy and normal subjects do not change with retinal eccentricity. This suggests that the retinal dysfunction has a broader boundary than expected from the ERG amplitudes and psychophysical perimetric results (Fig. 2.132). Based on these findings, the pathology of this disorder was thought to be limited to the macula, although the macula appears normal ophthalmoscopically.

Normal Controls

Long-term follow-up examinations have been undertaken with some of our patients. A comparison of the fundus of a 29-year-old woman with occult macular dystrophy abserved in 1988 and then again in 2002 is shown in Fig. 2.133. The fundus remained normal during the 14 years of follow-up. The full-field ERGs also did not change significantly, whereas the focal macular ERGs deteriorated significantly during this period.

The age of the affected members ranged from 9 to 71 years (mean 42 years). The distribution of visual acuity and age in this disease is shown in Fig. 2.134. It is interesting that some of the patients had normal visual acuity despite the fact that focal macular ERGs were definitely

Normal Controls (n=20)

Fig. 2.132. Three-dimensional topography (left) and averaged waveforms (right) of multifocal ERGs for five eccentric rings in a normal subject and an OMD patient. Responses for 20 normal subjects and 8 patients with OMD are superimposed in the averaged waveforms.The vertical dotted line indicates an implicit time of 29.4 ms. (From Piao et al. [4], with permission)

Fig. 2.132. Three-dimensional topography (left) and averaged waveforms (right) of multifocal ERGs for five eccentric rings in a normal subject and an OMD patient. Responses for 20 normal subjects and 8 patients with OMD are superimposed in the averaged waveforms.The vertical dotted line indicates an implicit time of 29.4 ms. (From Piao et al. [4], with permission)

Fig. 2.133. Fundus photograph (top) and fluorescein angiography (bottom) of case 1 in Fig. 130 after 14 years of follow-up.The fundus and fluorescein angiography are still normal

Fig. 2.134. Distribution of visual acuity (horizontal axis) versus age (vertical axis) in patients with occult macular dystrophy. Note that some patients show normal visual acuity

reduced. These findings indicate that the focal macular ERG is key to diagnosing occult macular dystrophy. The cone and rod sensitivity profile showed that all patients had depressed cone sensitivity only in the macula, although many relatively young patients had normal rod sensitivity in the macula. All patients with good visual acuity also had decreased cone sensitivity in the macula, although the function of one point in the foveola may still be relatively well preserved (Fig. 2.135). It may be that the small center of the fovea in such patients functions well and thus accounts for the good visual acuity, but that the parafovea is dysfunctional, resulting in the poor response of focal macular ERGs.

In many patients, the waveform of the focal macular ERG has a depolarizing pattern (the on type; Fig. 2.136), and the good preservation of rod function in the macula may be related to this property.A red-green defect in color vision is found in many patients, although some show a blue-yellow defect.

Although the ophthalmoscopic appearance of the macula is normal, OCT shows thinning of the macular area in many patients [5] (Fig. 2.137). Detailed analyses of the images indicate that the thinning is mainly of the outer nuclear layer.

Because only the central cone system is impaired and the peripheral cone, peripheral rod, and central rod systems remain intact during the early stage of this disorder, the most suitable pathophysiological name for occult macular dystrophy may be "central cone dystrophy," in contrast to "peripheral cone dystrophy," [6] which was described in Section 2.13.3. During the advanced stage, however, the macular rods may also become involved because patients with only macular cone involvement are significantly younger than those with both macular cone and rod involvement. Even at this stage, the macular appearance is still normal. Furthermore, it should be noted that even at an advanced stage the full-field cone and rod ERGs are still within the normal range, indicating that this disorder does not produce widespread dysfunction even at the advanced stage.

An essentially normal fundus has been reported with diffuse cone dystrophy [7] even though such eyes have shown significant deterioration of full-field cone ERGs (see Section 2.13.2). The impression is that occult macular dystrophy may not be a rare disease and that many patients with this disorder may be mis-diagnosed as having several other diseases, such as a psychological eye problem, optic nerve problem, central nerve problem, or amblyopia.

Case 1

RETINAL ECCENTRICITY (degree)

Case 2

Fig.2.135. Rod-cone (two color) perimetry (left) and cone perimetry (right) in two patients with occult macular dystrophy.The visual acuities of cases 1 and 2 are 0.2 and 1.0,respectively.In case 1,the macular cone sensitivity is depressed, but macular rod sensitivity is within the normal range. In case 2, the macular cone sensitivity is depressed, but only a small area of the fovea has good sensitivity.The dotted lines (left) and solid lines (right) indicate the normal range

Fig. 2.136. Focal macular ERGs elicited by 10° or 15° stimuli recorded from patients with occult macular dystrophy. The waveform of the focal macular ERGs is a depolarizing pattern (the on type), showing a small a-wave, if any, and a relatively large b-wave

Fig. 2.137. Optical convergence tomography (OCT) images from an age-matched normal control and a patient with occult macular dystrophy (OMD). (From Kondo et al. [5], with permission)

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