Ординатура / Офтальмология / Английские материалы / Electrophysiology of Vision_Lam_2005

(17) in 1980 because the fundus lesions have a pattern which resembles the scatter from a shotgun. Other less popular terms such as salmon patch choroidopathy and vitiligenous chorioretinitis have also been used to describe the same disorder. Other possible clinical features include epiretinal membrane, retinal neovascularization, subretinal neovascular membrane, cystoid macular edema, and optic nerve head edema or atrophy. Symptoms include decreased visual acuity, impaired peripheral visual field, floaters, photopsia, and nyctalopia. The pathogenesis of birdshot retinochoroidopathy is unclear but appears to be autoimmune in origin. The disease is strongly associated with HLA-A29, and persons with this human leukocyte antigen are at a much higher risk of developing the disorder (18). Middle-aged white persons of northern European descent are most commonly affected, and there is a higher prevalence in women.

The diagnosis of birdshot retinochoroidopathy is typically arrived on the basis of characteristic clinical features, a positive serum HLA-A29, and characteristic fluorescein angiographic findings of the fundus lesions and retinal vasculitis. The relatively unique but not completely specific ERG pattern may be useful in the diagnosis of birdshot retinochoroidopathy or as a measure of retinal function during follow-up.

The amount of ERG alteration in birdshot retinochoroidopathy is related not only to severity but also to variable expression of the disease, and this may in part explain the variability of results among studies. Although Hirose et al. (19) in their study of 15 patients reported supranormal ERG responses in some patients during the initial phase of the disorder, this is an extremely rare finding presumably due to acute retinal inflammation and have not been consistently confirmed by other investigators. More characteristically, patients with birdshot retinochoroidopathy have the following on standardized full-field ERG (Fig. 13.2): (1) scotopic rod flash response—reduced and prolonged b-wave, (2) scotopic combined rod–cone bright flash response—reduced a-wave and b-wave with variable prolongation with a possible greater selective decrease in the b-wave amplitude as compared to the a-wave, but usually not to such an extent as to produce a

Figure 13.2 Full-field ERG responses of a patient with birdshot retinochoroidopathy. The retinal appearance of the left eye of this patient is shown in Fig. 13.1. Note the progressive deterioration of ERG responses from 1997 to 2002 for both eyes. The relatively selective impairment of b-wave is most apparent on the 1997 scotopic combined rod–cone response for the left eye. In general, the scotopic responses are more affected than the photopic responses.

negative pattern (i.e., the reduced b-wave is still higher than the baseline), (3) oscillatory potentials—reduced, (4) photopic cone flash response—reduced a-wave and b-wave with variable prolongation with a more selective decrease in the b-wave amplitude, and (5) photopic cone flicker response— reduced and prolonged b-wave (19–22).

In general, the scotopic responses are more affected than the photopic responses, and the degree of selective impairment of b-wave is somewhat variable among studies. For example, Priem et al. (22) in their study of 16 patients found a very striking selective impairment of the b-wave with a well-preserved a-wave. In contrast, Gasch et al. (23) in their report of 22 patients found that the selective impairment of b-wave to be less prominent with some impairment of the a-wave in all study patients. This relative selective effect on the b-wave in birdshot retinochoroidopathy implies greater dysfunction in the inner retina in some cases despite the fact that the clinical lesions appear to be deep at the level of the choroid or the retinal pigment epithelium.

In general, ERG indices decrease over time in patients with birdshot retinochoroidopathy, indicating the progressive nature of the condition (Fig. 13.2) (24). In one study, abnormalities of the scotopic bright-flash rod–cone amplitude and photopic 30-Hz flicker implicit time were found to be associated with recurrence of inflammation as immunosuppressive therapy was tapered (25).

The EOG and VEP in birdshot retinochoroidopathy tend to parallel the ERG response, and reduced EOG light-peak to dark-trough ratio and delayed VEP response are common (19,21–23,26). Moreover, optic atrophy when present may also be a source of VEP impairment.

Diffuse Unilateral Subacute Neuroretinitis

Diffuse unilateral subacute neuroretinitis commonly called ‘‘DUSN’’ is caused by nematodes that wander in the subretinal space producing visual loss due to vitritis, retinal vasculitis, optic nerve inflammation, recurrent evanescent gray-white outer retinal lesions, and diffuse pigmentary degeneration (27).

Depending on the extent of retinal involvement, moderate to severe impaired ERG is typical in the DUSN eye as compared to responses of the normal, unaffected eye. Gass and Scelfo (28) reviewed findings in 37 DUSN patients, 36 of whom underwent full-field ERG. Moderate to marked impaired rod and cone responses were found in all but two patients who initially had responses in the normal range, which subsequently worsened. In general, the b-wave was more severely affected than the a- wave, and none of the patients had a non-detectable ERG. In the same series, EOG was performed on 29 patients, and 16 had impaired EOG. The VEP has not been extensively studied in DUSN but is likely to parallel the extent of the retinal as well as optic nerve involvement.

ZONAL INFLAMMATORY RETINAL DISORDERS

In 1993, ‘‘acute zonal occult outer retinopathy’’ was described by Gass (29) who proposed that this rare retinopathy is part of the spectrum of a single disorder which includes multiple

evanescent white-dot syndrome, acute idiopathic blind spot enlargement syndrome, acute macular neuroretinopathy, multifocal choroiditis, and punctate inner choroidopathy. The validity of this hypothesis is not clearly established. Regardless, these rare disorders share some common features such as zonal inflammatory retinopathy and occasional occurrence of enlarged blind spot on visual field testing.

Acute Zonal Occult Outer Retinopathy

Acute zonal occult outer retinopathy commonly referred to as ‘‘AZOOR’’ is characterized by: (1) acute loss of one or more large zones of outer retinal function with photophobia and photopsia, (2) minimal or no fundus changes initially with normal fluorescein angiography, (3) ERG abnormalities, and

(4) permanent visual field loss often associated with late development of atrophic or pigmentary retinal changes and narrowing of the retinal vessels in the affected zones. The diagnosis of AZOOR is given to patients with these clinical features; however, the term ‘‘AZOOR,’’ as mentioned, has also been used to encompass other disorders in this category including multiple evanescent white-dot syndrome, acute idiopathic blind spot enlargement syndrome, acute macular neuroretinopathy, and multifocal choroiditis (29). Visual acuity is usually mildly affected although the visual acuity may be as worse as 20=400. The disorder affects one or both eyes of predominantly young women. However, of the 13 patients initially reported by Gass, three were men. In addition, one of the 13 patients was as young as 13 years and another was as old as 63 years. In a subsequent long-term follow-up study of 51 patients with AZOOR (37 women and 14 men, median follow-up 96 months), Gass et al. (30) found that AZOOR was present in one eye of 12 (24%) patients and both eyes of 39 (76%) patients. Residual visual field defects were present in all patients, and ERG was essential for early diagnosis.

In AZOOR, the full-field ERG is usually abnormal but may occasionally be near normal in some cases (Fig. 13.3). Of the 13 patients initially reported by Gass (29), the full-field

Figure 13.3 Full-field ERG responses of a patient with acute zonal occult outer retinopathy (AZOOR) involving the left eye. Full-field ERG responses are highly variable in AZOOR, and the responses are often asymmetric between the two eyes.

ERG was abnormal in 17 out of 21 affected eyes. Most of the affected eyes showed only mild to moderate reduction in rod and cone amplitudes. In a few eyes, the responses were within the lower range of normal but were notably lower than in the unaffected eye. Jacobson et al. (31) examined a group of 24 patients with ‘‘AZOOR,’’ a term that they used to encompass patients with multiple evanescent white-dot syndrome, acute idiopathic blind spot enlargement syndrome, acute macular neuroretinopathy, and multifocal choroiditis. The investigators found that full-field ERG was significantly asymmetric between the two eyes in this group of patients, and that visual field area correlated well with ERG a-wave amplitude, suggesting that the visual dysfunction was photoreceptor in origin. Multifocal ERG may also be useful in determining retinal dysfunction and in documenting the location of retinal dysfunction in AZOOR (32). In the long-term follow-up study

of AZOOR by Gass et al. (30), the full-field or multifocal ERG amplitudes were diminished in all 51 patients. The EOG and VEP abnormalities are also reported but are thought to be related to retinal dysfunction. Taken together, the diagnosis of AZOOR is based on clinical findings and ERG is important for early diagnosis. The ERG abnormalities are often asymmetric, and the degree of impaired of ERG impairment is variable among patients.

Multiple Evanescent White-Dot Syndrome

Multiple evanescent white-dot syndrome, commonly referred to as ‘‘MEWDS,’’ is a rare, acute, usually unilateral ocular inflammatory disease characterized by the presence of small discrete white dots at the level of the outer retina or retinal pigment epithelium during the acute phase of the disorder. The syndrome was described by Jampol et al. (33) in 1984, and the cause is unknown. The disease often affects young to middle-age women, but men as well older persons may also be affected (34). Patients with MEWDS typically experience an acute onset of unilateral visual loss, which gradually improves over several weeks. Visual prognosis is generally favorable with the majority recovering to normal or near normal vision, and recurrences and bilateral involvement are rare (35). Aside from the characteristic retinal lesions during the acute phase, other findings include vitritis, retinal vascular sheathing, foveal granularity, and optic disc edema. In addition, an enlarged blind spot on visual field testing may occur and persists even after visual acuity recovery (36,37).

Of the 11 patients in the initial report of MEWDS by Jampol and associates, the full-field ERG was found to have profound diffuse impairment of both rod and cone responses, with greater rod impairment, during the acute phase of the disease (38). However, complete or almost complete ERG recovery occurred over weeks during clinical resolution of the disorder. In the same study, early receptor potential, an early ERG component due to bleaching of the photosensitive photoreceptor pigments, was assessed in two of the patients, and the R1 and R2 portions of the early receptor potential

were reduced but returned to normal with clinical recovery. Based on these findings, the investigators concluded that during the acute phase of MEWDS, diffuse retinal dysfunction occurs and that both rod and cone photoreceptor pigment densities are likely to be decreased with prolonged regeneration of the light-sensitive visual pigments. Subsequent case reports of MEWDS patients during the active phase indicate that focal and multifocal ERG amplitudes are markedly reduced in the retinal area corresponding to the visual field defect and are also moderately reduced in other retinal regions (39,40). The VEP impairment in patients with MEWDS is also found and is related in part to the reduced ERG response, although optic nerve involvement such as disc edema may also be a source of VEP impairment.

During the acute phase of MEWDS, diagnosis is arrived based on clinical features and characteristic funduscopic findings. The ERG reductions may lend support to the diagnosis. However, MEWDS is much more difficult to diagnose in patients in the recovered phase. An enlarged blind spot may be present on visual field testing, but an ERG may have improved and may not necessarily be helpful. Interestingly, patients with acute idiopathic blind spot enlargement syndrome are found to have impaired ERG responses relative to the other eye, and this has led to the proposal that MEWDS and acute idiopathic blind spot enlargement syndrome may be related disorders. Further, as mentioned, Gass has proposed that MEWDS and acute idiopathic blind spot enlargement syndrome may belong to a spectrum of a single disorder encompassed by AZOOR (29). Lastly, with specialized techniques, the ERG response of the short-wavelength-sensitive cone (S-cone) system is more impaired than those of the longand medium-wavelength-sensitive cone (L- and M-cone) systems (41).

Acute Macular Neuroretinopathy

Acute macular neuroretinopathy is a rare disorder characterized by gray to reddish brown petal-shaped macular lesions (Fig. 13.4). Visual acuity is typically reduced mildly to

Figure 13.4 Multifocal ERG responses and retinal appearance of a 20-year-old woman with acute macular neuroretinopathy. The impaired focal responses (circled) correlate with the gray-reddish petal-shaped macular abnormality in each eye (bottom left: right eye; bottom right: left eye). Visual acuity was 20=20 in each eye. (Refer to the color insert.)

20=40 or better. The onset may be preceded by a flu-like illness, and similar macular lesions are encountered in some patients with multiple evanescent white-dot syndrome and acute idiopathic blind spot enlargement syndrome. Multifocal ERG identifies focal areas of retinal dysfunction (Fig. 13.4). The full-field ERG responses may be asymmetric (31).

Multifocal Choroiditis

Multifocal choroiditis is a clinical syndrome described initially by Nozik and Dorsch (42) in 1973 and is characterized by vitreous and anterior chamber inflammation and multiple chorioretinal scars similar to those of patients with presumed ocular histoplasmosis syndrome (POHS). In contrast to POHS patients, patients with multifocal choroiditis have negative histoplasmin skin test and have no calcified granulomas on chest x-ray. In addition, patients with POHS do not typically have vitreous inflammation. Other names for multifocal

choroiditis include ‘‘pseudo-POHS,’’ and ‘‘multifocal choroiditis with panuveitis.’’

Dreyer and Gass (43) reviewed 28 cases of multifocal choroiditis and found that female outnumbered male patients 3:1 and nearly 80% of the cases were bilateral. Multiple etiologies were likely, and occasional unilateral cases may have similar retinal appearance to diffuse unilateral subacute neuroretinitis. In the same series, 29 affected eyes of 16 patients underwent full-field ERG with 16 (55%) eyes as having normal or borderline responses. Of the remaining 13 (45%) eyes which had moderately to severely reduced responses, all except two eyes from one patient, showed both impaired rod and cone responses. EOG light-peak to dark-trough ratios appear to parallel ERG responses (43,44). The VEP has not been extensively studied but is also likely to parallel ERG responses. Of interest, acute enlargement of the blind spot may occur in multifocal choroiditis (45,46), and as mentioned, in 1993 Gass (29) proposed multifocal choroiditis may belong to a spectrum of a single disorder encompassed by AZOOR.

Punctate Inner Choroidopathy

Punctate inner choroidopathy (PIC), described by Watzke et al. (47) in 1984, is a rare disorder characterized by numerous, scattered, often macular, small discrete yellow lesions that appear to be at the level of the retinal pigment epithelium and choroid. With time, the lesions become atrophic chorioretinal scars. Other manifestations include serous retinal detachment, choroidal neovascularization, optic nerve head edema or hyperemia, and enlarged blind spot on visual field testing (48). The condition is more commonly seen in young women and is often bilateral. The cause is unknown, and prognosis is variable but generally favorable (49).

Reddy et al. (48) noted full-field ERG in the normal range in seven PIC patients, three of whom had mild asymmetry in b-wave amplitudes between the two involved eyes, correlating with differences in the number of lesions. Focal retinal dysfunction from PIC is more likely to be detectable by Multifocal ERG. Reports of EOG and VEP in PIC are very scarce.

PARANEOPLASTIC AND IMMUNE-RELATED

RETINOPATHIES

Autoimmune retinopathy occurs when antibodies are produced against antigens expressed in retinal cells. Autoimmune retinopathy may occur with or without the presence of cancer. In paraneoplastic syndromes, autoimmune retinopathy is produced by the effect of immune responses initiated by antigens expressed in cancer cells. Antibodies against these antigens may recognize similar antigens expressed in normal neuronal tissue including the retina and the optic nerve. Only a small proportion of cancer patients will develop paraneoplastic syndromes associated mostly with small-cell lung carcinoma, melanoma, thymoma, breast carcinoma, colon carcinoma, breast carcinoma, prostate carcinoma, or gynecological tumors.

Cancer-Associated Retinopathy

Cancer-associated retinopathy (CAR) describes a paraneoplastic disorder that is often associated with small-cell carcinoma of the lung and characterized by antibodies against retinal cells, producing rod and cone dysfunction (50). This retinopathy may be produced by autoimmune reactions to retinal antigens including recoverin, 75-kDa heat shock cognate protein 70, and possibly enolase. The CAR associated with antirecoverin antibody is the most extensively studied. Recoverin is a 23-kDa retinal photoreceptor calcium-binding protein that regulates rhodopsin phosphorylation and is involved in light and dark adaptation (51,52). Aside from small-cell carcinoma, CAR is also rarely associated with endometrial, cervical, ovarian, and breast carcinomas.

Symptoms of CAR include bilateral diminished vision, impaired color vision, nyctalopia, and photopsias occurring over days to weeks. The symptoms may appear before or after the diagnosis of the carcinoma. Mild vitreous inflammation and retinal vascular attenuation may be evident on examination, but in the early stages, the retina may appear normal. Patients with CAR, in general, suffer progressive visual loss. Therapies such as systemic corticosteroids, intravenous immunoglobulin, and plasmophoresis have not consistently yielded favorable results.