Alan C. Bird
INTRODUCTION
The condition was probably reported initially by neuroophthalmologists when patients were recognized as having a big blind spot without disk swelling or any other retinal abnormalities.[1,2] The field loss was reported to be persistent over many months. It was then identified that in some, it was progressive over a period extending temporally around the macula. Electro-physiological testing showed that the loss was due to retinal dysfunction.
Gass was the first to recognize and characterize the nature of the disorder which he named acute zonal occult outer retinopathy (AZOOR) which he described in 1993 in his Donder's lecture.[3] He reported 13 patients, mostly young women, who had rapid self limited loss of visual fields, photopsia, minimal ophthalmoscopic changes. Spontaneous recovery could occur during the first 5 years, but in its absence signs of retinal degeneration developed. The evidence that the loss was due to outer retinal dysfunction was based on the interpretation of electrophysiological (ERG) abnormalities. Gass, and subsequently others, described AZOOR as being associated with various inflammatory inner choroidal inflammatory disease and retinopathies of unknown etiology including the multiple evanescent white dot syndrome (MEWDS),[3-8] acute macular neuroretinopathy (AMN),[9-11] multifocal choroidopathy,[12-13] punctate inner choroidopathy (PIC)[14,15] or pseudopresumed ocular histoplasmosis syndrome (pseudo-POHS),[16-18]PIC being the most common. It is considered that AZOOR was a complication of disorders that cause inner choroidal inflammation rather than being intrinsic to the primary disorder.
CLINICAL PRESENTATION
The vast majority of patients are female, healthy, in their mid-thirties although the condition has been reported in the seventh decade of life. The sex predilection is determined by that of the precipitating disorders. The condition presents with progressive visual loss over a period of weeks or a few months. The visual field loss most frequently involves blind spot enlargement extending in an arcuate manner into the superior and inferior temporal quadrants. Photopsia extending over the whole of the affected field is a prominent symptom described as 'scintillating' or 'shimmering' lights. The visual acuity may or may not be affected. The severity is variable and visual acuity as bad as counting fingers has been recorded. The field defect increases in size within a few weeks or months before stabilizing. In most cases, the visual field loss and decrease in visual acuity are asymmetric and some have unilateral symptoms only.
CLINICAL FINDINGS
Characteristically, the fundus changes are those of the precipitating disorder, with inner choroidal infiltrates or scarring if it is PIC. In some cases, the fundi may be normal and it is assumed that MEWDS was the cause given and the retinal changes may be very limited in this disorder even a few weeks after its onset. Evidence of MEWDS may be evident on ICG angiography when the fundus appears to be normal on ophthalmoscopy. In the area of field loss, the retina appears normal including autofluorescence imaging. Visual fields show the characteristic loss.[19,20] Both rod and cone sensitivities may be reduced without there being an increase of time to recovery from bleach.
ERG FINDINGS
ERG tests show that retinal dysfunction accounts for the field loss.[21,19] The most sensitive test in flicker ERG in which the implicit time is invariably prolonged. The additional changes include photopic transient ERGs with abnormal b-wave amplitude and increased implicit time the reduced scotopic rod responses were abnormal in nine eyes, and abnormal pattern ERG. The light induced rise of ocular potential on electrooculography (EOG) is usually reduced to an extent not explained by reduced photoreceptor responses.
CLINICAL COURSE
The long term course has been well recorded.[21] Those who present with unilateral AZOOR may have affection of the other eye after weeks. Progression of the deficit has been recorded by both psychophysics and ERG testing over a period of a few weeks followed by stability.
In a proportion of cases, there is recovery of function over a period of months or years shown both on visual field and ERG testing although recovery is rarely complete. If after 5 years there is no recovery, widespread retinal changes occur that correspond with the field loss with retinal thinning and changes at the level of the retinal pigment epithelium (RPE).
PATHOGENESIS
The abolished EOG light rise and reduced photoreceptor cell, responses on ERG testing show that the abnormality is largely at the level of the RPE-photoreceptors complex. The greater reduction in EOG's light rise than is easily explained by photoreceptor functional loss implies the RPE affection is likely to be intrinsic to the disorder. Autofluorescence images obtained with a scanning laser ophthalmoscope are derived from lipofuscin in the retinal pigment epithelium.[22,23] The presence of lipofuscin is thought to reflect the metabolic activity of the RPE which is determined largely by the rate of turnover of photoreceptor outer segments. The finding of normal autofluorescence distribution early in disease implies that there is no significant loss of photoreceptors, and the presence of normal outer segment and retinoid turnover. That the loss is due to cell dysfunction and not cell loss might be expected from the normal appearance of the retina on clinical examination. The loss of b-wave amplitude in some cases that is greater than a-wave loss suggest that, in these, there is posttransduction abnormality as well.
The mechanism leading to malfunction of the retinal RPE-photoreceptor-epithelium complex in AZOOR and the causal relationship between the initiating event and the widespread function loss are still unknown. Why patients with multifocal choroiditis or punctate inner choroidopathy,[15] presumed ocular hystoplasmosis syndrome (POS), MEWDS are at high risk of developing AZOOR is not understood. An autoimmune etiology or toxic mechanism precipitated possibly by a virus has been proposed by some. It was suggested that persistence of virus may be the cause. Tiedeman[24] found evidence of persistent EBV infection in 10 patients with multifocal choroiditis and panuveitis. His findings were not confirmed by Spaide et al.[25] Candida famata was isolated from conjunctival exudates of a patient diagnosed with AZOOR.[26] Immunological tests revealed the presence of antigen-specific T lymphocytes by using C. famata as a challenge, and enzyme-linked immunosorbent assay (ELISA) analysis showed the presence of specific antibodies against this yeast in the patient's blood. Delayed hypersensitivity by use of a skin test was also positive.
Alternatively, it was considered that antibodies to retina may have been induced either by the infective agent or by release of antigens from the retina. However, Jacobson found no indication that patients with AZOOR as a group have autoantibodies that recognize a specific cell type in sections of human or rat retina. None of the AZOOR sera/IgGs produced specific labeling of rat retinal cells.[20] No similar antibodies reactive with a specific retinal antigen were found in AZOOR.
TREATMENT
As a result of finding hypersensitivity to C. famata antifungal treatment was tried and it was reported that there were improvements in several clinical symptoms, including fundoscopic analysis. This observation has not been repeated, and the general view is that treatment is unhelpful.[21]
REFERENCES
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22. von Rückmann A, Fitzke FW, Bird AC: Distribution of fundus autofluorescence with a scanning laser ophthalmoscope. Br J Ophthalmol 1995; 79:407-412.
23. von Rückmann A, Fitzke FW, Bird AC: In vivo fundus autofluorescence in macular dystrophies. Arch Ophthalmol 1997; 115:609-615.
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