Lucy H.Y. Young,
Donald J. D'Amico
Acute macular neuroretinopathy was first described in 1975 by Bos and Deutman.[1] In their six patients, this entity was characterized by a sudden onset of paracentral scotomas and the presence of cloverleaf, wedge-shaped, darkish red lesions centered around the fovea. Only a small number of cases have been added subsequently.
Characteristically, visual acuity remains normal or is slightly reduced.[1-22] The chief complaint is usually related to the sudden appearance of paracentral scotomas. This rare macular disease can occur unilaterally or bilaterally, and the majority of patients are young adults, mostly women. Many of these patients are taking birth control pills.[1,3-5,11-15,17-20] The visual disturbance is often preceded by a bout of a flu-like syndrome, such as influenza, pharyngitis, or enteritis.[1,4,5,9,11,12,14,19-22]
When patients are tested with the Amsler grid, they can usually outline parafoveal negative scotomas, frequently in the shape of teardrops, corresponding exactly with the fundus lesions (Fig. 161.1).[9,11-13,16]In patients whose fundus lesions are less prominent, examination with red-free light may be useful in highlighting the lesions. As mentioned by Guzak and colleagues,[4] this enhancement is probably related to the color of the lesion rather than to the surface changes in the retina. Although Bos and Deutman[1] suggested that the fundus lesions seen in their six patients were located in the inner retina, thus the name acute macular neuroretinopathy, subsequent reports relying on biomicroscopic examination, stereophotographs, fluorescein angiography, and electrodiagnostic testing indicate that the acute macular neuroretinopathy lesions are located in the outer retinal layers.[9,11,13] Scanning laser ophthalmoscopy has been shown to be useful in enhancing the visibility of the macular lesions.[17,18] In addition to the deep, reddish brown lesions, a few small, superficial retinal hemorrhages may be present in the macula.[2,9] The retinal vasculature, nerve fiber layer, retinal pigment epithelium, and optic disk are normal, and there are no vitreous cells. In symptomatic patients with normal fundus examination, it is important to bear in mind that the onset of visual symptoms of acute macular neuroretinopathy may occur few days before retinal lesions can be visualized and thus close observation can be helpful.[19]
Fluorescein angiography studies are essentially normal. Questionably dilated perimacular capillaries without leakage and subtle hypofluorescence corresponding to the fundus lesions have been reported.[1,2,9] Similarly, no abnormalities are observed with indocyanine green angiography.[20] In two case reports, optical coherence tomography (OCT) demonstrated a band of hyperreflectivity at the outer retinal layer.[21,22]
Electrical testing, such as electroretinogram and electrooculogram studies, of patients afflicted with acute macular neuroretinopathy is normal.[1,7,9,12] This is not unexpected because both tests measure mass physiologic responses and are not sensitive to pathologic processes confined to the macula alone. To address this issue, Sieving and associates[13] recorded the early retinal potential responses from the posterior fundi in one patient with unilateral acute macular neuroretinopathy. The early retinal potential is generated in the photoreceptor outer segments, and by restricting the recording to the posterior fundus, the investigators made the recording more sensitive to localized lesions in the macula. They found a reduced amplitude in the affected eye when compared with the normal fellow eye. This recording was done 13 months after the initial onset of visual disturbances. A follow-up early retinal potential measurement 7 months later, or 20 months after the onset of symptoms, showed similar amplitude reduction. Their findings would suggest that the abnormality is located in the outer segments. Multifocal electroretinogram (ERG) has been shown to be more useful in the evaluation of acute macular neuroretinopathy and its findings support an outer retinal layer involvement.[20-22]
Although acute macular neuroretinopathy is associated with minimal, if any, decline in visual acuity, patients with this disorder rarely report improvement of symptoms. The paracentral scotomas may become less dense but usually persist despite resolution of the fundus lesions. Most of the follow-up examinations reported to date range from months to a few years only.[1,2,4-6,9,11-16,22] However, one patient[5] with bilateral involvement was followed up for 9 years. This patient had resolution of paracentral scotomas in the right eye but persistence of a large scotoma in the left eye 2 years later. During the following 7 years, the large paracentral scotoma remained but slowly became smaller.
Both the histopathologic features and the pathogenesis of these rare macular lesions are unknown. Although a large number of reported patients experienced a flu-like syndrome before the onset of their visual symptoms, a relationship to viral infection has not yet been established. It has also been suggested that there is an association with oral contraceptives because the condition affects predominantly healthy young women, many of whom are taking this medication. However, since the majority of women with this condition are of child-bearing age, it is highly likely that the use of birth control pills is merely coincidental; in addition, cases have been reported without birth control pill use. Furthermore, acute macular neuroretinopathy has been reported in male patients, although it is interesting to note that one of them was being treated with fosfestrol (an estrogen preparation) for a prostatic carcinoma at the time of the onset of visual symptoms.[6]
O'Brien and co-workers[8] reported three patients in whom acute macular neuroretinopathy developed after acute hypertension caused by intravenous sympathomimetics. Guzak and colleagues[4] reported two cases, and both of their patients experienced macular neuroretinopathy after intravenous injections of epinephrine for adverse reactions to contrast agents. However, blood pressure readings were not reported in these two cases. The temporal relationship between the development of acute macular neuroretinopathy and the use of intravenous epinephrine suggests an association with either the hypertensive episodes or the sympathomimetics themselves. However, this would not explain the other cases reported to date. Acute macular neuroretinopathy has also been reported in two patients treated with epinephrine for acute shock.[23] In another case report associated with epinephrine administration, multiple blood pressure recordings were taken and they were all normal.[16]
Gass and Hamed[3] reported acute macular neuroretinopathy and multiple evanescent white dot syndrome occurring in the same patients. They compared the clinical features of acute macular neuroretinopathy and multiple evanescent white dot syndrome and suggested that these two rare syndromes may be related pathogenetically and causally.
The milder forms of acute macular neuroretinopathy, i.e., when the characteristic macular lesions are not prominent, may be mistaken for acute retinal pigment epitheliitis[24-27] because both entities cause loss of central vision in young adults. Table 161.1 lists the differential diagnostic features of these two entities. The peculiar macular lesions may also be mistaken for subretinal hemorrhage; this is probably what happened in the case reported by Weinberg and Nerney.[15] No recurrence of this entity has been reported.
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FIGURE 161.1 This 42-year-old woman presented with a 3-week history of a flu-like syndrome before the onset of paracentral scotomas in the left eye. Her past medical history was significant, for she had undergone hysterectomy and oophorectomy 2 years previously and had since been using estradiol transdermal (Estroderm) patch. Her visual acuity was 20/20 in the left eye. (a) Note the darkish red lesions centered around the fovea. (b) These lesions are better appreciated with red-free light. (c and d) Angiography results were normal. (e) Amsler grid testing showed two paracentral scotomas. |
TABLE 161.1 -- Differential Diagnostic Features of Pigment Epitheliitis and Acute Macular Neuroretinopathy
Feature |
Pigment Epitheliitis[24-27] |
Acute Macular Neuroretinopathy |
Ophthalmoscopy |
Clusters of round, dark lesions surrounded by hypopigmented halos |
Red-brown wedges |
Lesion distribution |
Macular |
Macular |
Location |
Retinal pigment epithelium |
Sensory retina |
Laterality |
Usually unilateral |
Either |
Associated vitritis |
None |
None |
Diminished visual acuity |
Moderate |
Mild |
Sex predilection |
None |
Female |
Age of onset |
Young adults |
Young adults |
Associated |
None |
Often preceded by a flu-like systemic infection syndrome |
Visual recovery |
Complete in 7-10 weeks |
Minimal |
Cause |
Unknown |
Unknown |
Fluorescein angiography |
Normal or halos of hyperfluorescence |
Normal |
REFERENCES
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