Retinitis pigmentosa (RP) is an inherited rod–cone dystrophy in which the onset of symp- toms, rate of progression, severity, and mode of
inheritance are quite different for different patients. RP can be classified into two broad groups: typical and atypical.
2.1 Retinitis Pigmentosa
Typical RP is characterized by an abnormal course of dark adaptation, photophobia, night blindness, and loss of peripheral visual field.
These alterations can be found separately or in some combination. During the early stage, the patients may have minimal, if any, ophthalmo- scopic alterations. At more advanced stages, the characteristic fundus features of RP develop, including attenuated retinal vessels, intrare- tinal bone spicule pigmentation in the mid- peripheral fundus, and waxy pallor of the optic disks (Fig. 2.1). Several gene mutations have been detected in RP patients, but the genotype- phenotype correlation is not completely dis- tinct in most patients.
Electroretinograms are essentially unre- cordable in most patients, but patients at an early stage may have reduced ERGs to single flashes of light, and the cone ERGs are often better preserved than the rod ERGs (Fig. 2.2) [1–3]. The mixed rod–cone ERGs elicited by a
single bright flash are subnormal or unde- tectable. When the ERGs are reduced, the amplitudes of both a-waves and b-waves are reduced, indicating that the photoreceptors are extensively involved from the early stage. The rod ERGs are absent in most patients, but when present the implicit time of the b-wave is delayed. The cone ERGs and 30-Hz flicker ERGs are occasionally recordable at a relatively early stage of the disease but are significantly smaller than the comparable ERGs recorded from normal subjects. The implicit times of the cone and flicker ERGs are also prolonged.
Unlike the full-field ERGs, the focal macular ERGs in RP patients are often recordable and can even be within the normal range in some patients [4]. The fundus (Fig. 2.3), full-field ERGs, and focal macular ERGs (Fig. 2.4) as well as a topographic map of the amplitudes of the multifocal ERGs (Fig. 2.5) recorded from a rep- resentative patient with typical RP are shown.
2.1.1 Typical Retinitis Pigmentosa
Fig. 2.1. Fundus of a patient with typical retinitis pigmentosa (RP)
The visual acuity of this patient was 1.2, and the visual fields were normal only in the central 15°
in both eyes. The rod and cone components of the full-field ERGs were unrecordable, but the focal macular ERGs elicited by 5°, 10°, and 15°
stimuli were within normal limits. The ampli- tudes of the multifocal ERGs were within normal limits in the macular area, but the topo- graphic map of the multifocal ERGs showed an extremely reduced periphery, indicating marked reduction of the peripheral responses [5].
Among the RP patients with normal visual acuity, some have better preservation of the macular oscillatory potentials (OPs) than the a- waves and b-waves of the focal macular ERGs.
Such examples are shown in Fig. 2.6. The reason macular OPs are selectively preserved is still unknown, although Banin et al. [6] reported an increase in the amplitude OPs of the full-field ERGs in transgenic pigs with a rhodopsin mutation. Some enhancement of inner retinal function may occur at certain stages of RP.
Fig. 2.2. Full-field electroretinograms (ERGs) recorded from a normal control (top) and two RP patients at an early stage (case 1, middle) and a late stage (case 2, bottom)
Fig. 2.3. Fundus of an RP patient (44-year-old man) with good visual acuity
Fig. 2.4. Full-field ERGs (left) and focal macular ERGs recorded with three different spots and two differ- ent time constants (T.C., right) from an RP patient shown in Fig. 2.3. Despite the undetectable full-field ERGs, all components, including the oscillating potentials (OPs), of the focal macular ERGs are within normal limits
Fig. 2.6. Focal macular ERGs elicited by a 10° spot with two different time constants (TC) from a normal subject (top) and from four RP patients with normal visual acuity. The amplitudes of the a-waves and b-waves are reduced, but those of the OPs are well preserved
Fig. 2.5. Topographic map of a multifocal ERG in a normal control (top) and an RP patient (bottom) showing a normal peak in the macular area but an extremely reduced peripheral sector
Patients are diagnosed with unilateral RP [7]
when only one eye shows the characteristic changes of RP, and the other eye has normal psychophysical and electrophysiological findings. The ophthalmoscopic and fluorescein angiographic findings are also normal in the fellow eye. A follow-up period of at least 5 years is necessary to rule out delayed development in the second eye. In addition, inflammation, trauma, and other causes in the affected eye must be ruled out because these conditions can lead to ophthalmoscopic findings that resemble RP. To put it in concrete terms, diffuse unilat- eral subacute neuroretinitis (see Section 3.4.3), acute zonal occult outer retinopathy (AZOOR) (see Section 3.4.2), multifocal choroiditis, and panuveitis can present with unilateral fundus changes that may resemble typical RP [8].
The etiology of unilateral RP is unknown, and the patients with these characteristics rarely have other affected members in the family. Inflammation, trauma, and combined choroidal and retinal vascular occlusions are responsible for most cases.
Unilateral RP was seen in a 30-year-old woman who first visited our clinic when she was 14 years old. Visual acuity was 1.0 in both eyes, and her visual fields were significantly different in the two eyes: The visual field of the left eye was normal, but that of the right eye was extremely constricted with preservation of only the central 15°–20°. The fundus of the left eye was essentially normal, but the alterations in
the fundus of the right eye were similar to those seen in patients with typical RP with bone spicule pigmentation, attenuation of retinal vessels, and diffuse atrophic changes of the RPE (Fig. 2.7).
The full-field ERGs were normal in her left eye, and the rod and cone components in the right eye were nearly undetectable (Fig. 2.8).
The focal macular ERGs, elicited by 5°, 10°, and 15° stimuli from both eyes, are compared in Fig.
2.8. The amplitudes and implicit times of the focal macular ERGs of the affected right eye were comparable to that in the normal left eye. Only the response to the 15° stimulus was slightly smaller than that for the right eye.
These results indicate that our focal stimuli were indeed focal because normal ERGs (com- parable to that recorded from the normal left eye) can be elicited from the small functioning retina (5° and 10°) in the right eye. The topo- graphical map of the multifocal ERGs showed a central peak, but the peripheral zone was markedly reduced in the right eye (Fig. 2.8).
These ERG results indicate that although retinal function is normal in the left eye, only a small central retina is functioning normally in the right eye. The pathology of the right eye agrees well with the findings of typical RP. Because the ocular findings of the left eye did not show any significant change during the 16-year follow-up period, the diagnosis is most likely “unilateral RP.”
2.1.2 Atypical Retinitis Pigmentosa
2.1.2.1 Unilateral Retinitis Pigmentosa
OD OS Fig. 2.7. Fundus of a patient with unilateral RP. The right eye is affected
Fig. 2.8. Full-field ERGs (left), focal macular ERGs (mfERG) with three stimulus spots (right), and topography of multifocal ERGs from a patient with unilateral RP (bottom) shown in Fig. 2.7. Despite undetectable rod and cone responses in full-field ERGs of the right eye, the focal macular ERGs and central peak of multifocal ERG are nearly the same as those of the normal fellow eye
Paravenous retinochoroidal atrophy is a non- progressive, regional chorioretinal atrophy of unknown etiology. Although most cases are not familial, some do occur in siblings and in suc- cessive generations [9, 10]. Fundus photographs of a patient with paravenous retinochoroidal atrophy are shown in Fig. 2.9. This 36-year-old woman was referred about 25 years ago because of the abnormal appearance of her fundus, which was detected during clinical screening.
Her fundus showed clumps of pigment in the perivascular areas, predominantly paravenous.
The pigment clumps were associated with zones of peripapillary chorioretinal atrophy.
Between the affected zones, the appearance of the retina and choroid were normal. Fluores- cein angiography showed a defect of the retinal pigment epithelium (RPE) in the atrophic zones, suggesting degeneration of the RPE. The condition was bilateral, although the right eye was affected more extensively than the left eye.
The optic nerve head and the caliber of the retinal vessels were normal. Many of the patients with paravenous retinochoroidal atrophy are asymptomatic and have normal visual function. The visual acuity in this patient was 1.2 in both eyes.
The amplitudes of the full-field ERGs (Fig.
2.10) were smaller than normal, particularly in the right eye for both the rod and cone compo- nents. Although the amplitudes were smaller than normal, the implicit times were within normal limits, suggesting that the retina is not diffusely involved as it would be in RP [11].
Defects in the visual field were detected only in the areas corresponding to chorioretinal atrophy, and the amplitudes of the multifocal ERGs (mfERGs) were reduced only in the area corresponding to choroidal atrophy. This patient has been followed for 25 years, and the ocular findings have not shown any progression.
2.1.2.2 Paravenous Retinochoroidal Atrophy
Fig. 2.9. Fundi of both eyes of a patient with paravenous chorioretinal atrophy. The right fundus is more exten- sively affected than the left fundus
Fig. 2.10. Full-field ERGs (top) and topographic maps of multifocal ERGs (mfERG) from both eyes (bottom) in the patient whose fundi are shown in Fig. 2.9
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 repre- senting 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 pig- mented areas (Fig. 2.13).
2.1.2.3 Grouped Pigmentation of Retina
Fig. 2.11. Photograph of the fundus (left) and fluorescein angiogram (right) from a patient with grouped pigmentation of the retina
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Fig. 2.12. Full-field ERGs from a normal subject and from the patient with grouped pigmentation of the retina shown in Fig. 2.11
Fig. 2.13. Topographic map of multifocal ERGs in the patient with grouped pigmentation of the retina shown in Fig. 2.11
