Acute zonal occult outer retinopathy: A case report

Transcription

1 Optometry (2010) 81, Acute zonal occult outer retinopathy: A case report Josephine O. Ibironke, O.D., a and Andrew S. Gurwood, O.D. b a The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; and b The Eye Institute, Pennsylvania College of Optometry, Philadelphia, Pennsylvania. KEYWORDS Acute zonal occult outer retinopathy; Retinal pigment epithelium; Retina; Electroretinogram Abstract BACKGROUND: Acute zonal occult outer retinopathy (AZOOR) is a disorder of unknown etiology with a predilection for young women. AZOOR is characterized by an acute loss of one or more zones of outer retinal function with a corresponding loss of visual field in one or both eyes. Patients present with photopsia, variable funduscopic changes, and abnormal electroretinogram (ERG) findings. There are no proven treatments. Diagnosed cases have a reasonable prognosis because central vision is often spared. CASE REPORT: A 24-year-old white woman presented with acute photopsia with clouded temporal vision in the right eye (O.D.). Initial evaluation found a slightly swollen nerve fiber layer with no other outstanding lesions O.D. Over a 7-week follow-up period, there was significant progression into the deep chorioretinal tissues O.D. with an anterior chamber response. At 3 months, an afferent pupillary defect (APD) developed with significant retinal pigment epithelium (RPE) changes. After extensive testing, the consulting retinal specialist identified AZOOR as the etiology. At 21 and 31 months, the process remained in remission. Although primary symptoms subsided, the dense inferior-temporal field defect remained O.D. CONCLUSION: AZOOR is a rare condition with subtle and often vague signs and symptoms making diagnosis difficult. The course of AZOOR, its clinical presentations, hypothesis of etiology, differential diagnosis, workup, management, and prognosis are reviewed. Optometry 2010;81:22-27 In 1993, J. Donald M. Gass described the syndrome of acute zonal occult outer retinopathy (AZOOR) in 13 patients with sudden onset of photopsia and visual field defects. 1 Today, this relatively new disorder with a predilection for young, healthy, myopic women remains poorly understood with an unknown etiology. 1-6 AZOOR is characterized by an acute loss of 1 or more zones of outer retinal layer function with corresponding losses of visual field in one or both eyes. It is usually asymmetric when both eyes are involved. 1,7 Patients present with photopsia, normal visual acuities, and minimal to no funduscopic or angiographic changes, initially, but with an abnormal Corresponding author: Josephine O. Ibironke, O.D., The Wilmer Institute, 233, 600 North Wolfe Street, Baltimore, Maryland jibiron1@jhmi.edu electroretinogram (ERG) when tested. 1,2,5,6 Fundoscopic changes often develop over time in the retinal zones corresponding to thevisual field loss. 4 In most cases, the visual field loss is permanent. The abnormal ERG is an important discovery with regard to diagnosis, demonstrating outer retinal dysfunction at the level of the photoreceptors. 8 There is still no known treatment for the disorder. Prognosis is generally good because the disorder is self-limiting; however, although symptoms eventually subside and visual function stabilizes, visual function that is lost often is not recovered. Case report A 24-year-old white woman presented to the office with a chief complaint of acute, constant, flashing, and spinning white lines temporally in the right eye of 3 days duration /10/$ -see front matter Ó 2010 American Optometric Association. All rights reserved. doi: /j.optm

2 Ibironke and Gurwood Clinical Care 23 She also complained that her vision seemed cloudy in the temporal field of the right eye along with a sensation of feeling pressure over the right eye with an occasional accompanying frontal headache. She reported no numbness or tingling of the limbs or extremities, no muscle weakness, and no loss of balance or changes in mentation. Her previous ocular history was unremarkable. Her medical history was significant for chronic back pain, successfully treated endometriosis, migraine headache, depression, and bipolar disorder. Her family medical and ocular histories were noncontributory. She denied taking medication of any kind. She reported no allergies. Her best-corrected visual acuities measured 20/20 in the right eye (O.D.) and in the left eye (O.S.). External findings were normal. Pupils and color vision were normal with no evidence of afferent defect. Refraction found myopia in both eyes (OU) with negligible changes to her current spectacle prescription. Biomicroscopy found normal anterior segment structures. Goldmann applanation intraocular pressures measured 16 mmhg OU. Dilated fundus evaluation found retinal edema in the superior nasal quadrant of the right eye. The optic nerve in the right eye was slightly elevated with some deep chorioretinal thickening emanating nasally into the equatorial region. Visual field testing found a slightly enlarged blind spot O.D. There was no vitritis or pars planitis, OU. Dilated fundoscopy of the left eye found normal structures free from pathology. The patient was referred to a retinal specialist for identification and management of the retinal lesion. Given the nature of her persistent visual complaint, an additional referral was made to neuro-ophthalmology to rule out neurologic etiologies. Routine blood screening and neuroimaging studies were obtained and showed no abnormalities or intracranial/orbital lesions of any kind. The retinal specialist agreed with our findings and ordered some blood work to rule out systemic infectious, inflammatory, and collagen vascular diseases. The patient returned to the office 4 weeks after the initial onset of symptoms. Although the visual acuity, symptoms, and external findings remained unaltered, biomicroscopy uncovered a grade 1 iritis. Examination of the posterior pole found enlarged areas of subretinal edema O.D. (see Figure 1). The patient was started on a topical regimen of atropine 1% twice a day and topical prednisolone acetate 1% 4 times a day O.D. to quell discomfort and to arrest the local inflammatory response. A follow-up examination was scheduled for 1 week. The patient returned to the office, as scheduled, 1 week after the discovery of the new signs. All findings were consistent with previous data from acuity and neurologic testing to intraocular pressure and anterior segment findings. Examination of the posterior pole found stable but unregressed areas of subretinal edema O.D. The patient was instructed to continue the regimen of topical atropine 1% twice a day and topical prednisolone acetate 1% 4 times a day O.D. A follow-up reassessment was scheduled for 4 weeks. Figure 1 Subretinal edema O.D. at 4 weeks. Twelve weeks after the onset of the initial symptoms, the patient was no longer taking drops, the photopsia persisted, and a grade 1 afferent pupillary defect (APD) was detected O.D. Anteriorly, the mild iritis persisted, and posteriorly, retinal pigment epithelium (RPE) changes with retinal and subretinal atrophy, corresponding to the affected area, were noted (see Figure 2). Because the patient remained relatively comfortable, no alteration of the therapy was implemented. Following an extensive and protracted workup, after a total of 18 weeks from the time the symptoms were first reported, the retinal specialist returned the diagnosis of AZOOR. (The result of an ERG, if performed at the retina clinic, was not available to us.) The patient was followedup at 6- to 8-week intervals by the retinal specialist and at 3-month intervals by our office over the next 6 months, then by our office at 4- to 6-month intervals. At 31 months, although all symptoms had subsided, the RPE changes superior-nasally with their corresponding infero-temporal field defects remained O.D. (see Figure 3). No choroidal neovascularization developed, and no additional retinal treatment was offered or is currently indicated according to the standard of care. Figure 2 RPE changes with atrophy superior nasally O.D. at 3 months.

3 24 Optometry, Vol 81, No 1, January 2010 Figure 3 Persistent visual field defect O.D. at 31 months.

4 Ibironke and Gurwood Clinical Care 25 Discussion Gass et al. 1 completed a prospective and retrospective study in 51 AZOOR patients (90 eyes). That study and others have identified many of the characteristic clinical findings common to AZOOR patients. 1-3,5,7,9,10 Most patients are myopic, young, white women. 1,3,5,7 Many (55% to 88%) complain of photopsia characterized as lights, lines, floaters, bursts, or sparkles without headaches. 1-3,7,8 The photopsia is typically experienced weeks before or after the onset of visual field loss in areas corresponding to the affected retina; it may be constant or intermittent, lasting for short periods. 1 Patients also often complain of their scotomata, describing dark blind spots in their field. Although photopsia and scotomata are usually only present in one eye, bilateral presentations have been documented to occur in 39% of cases. 1,4 Corrected visual acuities are often 20/40 or better in 76% to 82% of the patients 1,3,11 (see Table 1). At onset, a majority of the patients have little or no fundoscopic involvement. 1-5,7-9 However, visual fields can contain enlarged blind spots, ring scotomas, concentric contractions, arcuate defects, and even multiple isolated scotomas. 1-3,5,6,8,9 The central field is often spared. 1,6,12,13 There may be a delayed involvement of the other eye with asymmetry of signs and symptoms. 1,6,8 There may be a history of some event, such as viral-like illness or headache, days to weeks before the onset of the severe symptoms in up to 40% to 50% of cases. 1,5,7 Several weeks after the initial presentation of signs and symptoms, up to 25% of the patients show enough retinal involvement to produce an afferent pupillary defect. 1,2,7 In fact, most patients progress to vitritis with perivascular exudates and/or sheathing. 1,2 Three quarters of affected individuals will show stabilization of their visual field loss within 2 to 6 months of the initial event. 1,3,10 Visual improvement is more likely in eyes with normal-appearing fundi that present without vitritis in the acute phase. However, even in these individuals, improvement may never be complete, with residual visual field defects remaining even after the disease has become inactive. 1,2 Other associated fundus changes include cystoid macular edema, RPE changes, and narrowing of retinal vessels. 1,2 Interestingly, the retinal pigment epithelial atrophy and migration into the overlying neurosensory retina are similar in appearance and pathogenesis to the changes observed in retinitis pigmentosa (RP). 1 Some patients (31%) have recurrences up to 2 to 3 years later. 1 These recurrences may be in the initially affected eye, in the fellow eye, or in both. 1,10,14 Etiology The mechanisms causing the RPE malfunction and their relationship with the initiating events are still unknown. 7,10 However, several factors currently are under investigation. AZOOR has been found to have associations with herpes simplex dermatitis, central nervous system abnormalities, herpes zoster ophthalmicus, viral-like illnesses, immunizations, tick Table 1 Presentation of AZOOR in the acute phase Patient characteristics Symptoms Laterality Corrected visual acuity Signs Young, healthy, myopic, white women Photopsia Loss of vision in 1 or more zones of visual field Unilateral or bilateral 20/40 or better Visual field defects with little or no funduscopic involvement Abnormal ERG findings bites, migraines, the periods during and/or immediately after pregnancy, and Candida famata. 1,4,5,7,15,16 AZOOR has also been loosely associated with autoimmune diseases, various hormones, bacteria, viruses, and histoplasma capsulatum. 1,5,7,10 A viral theory to explain the etiology of AZOOR proposes that viruses that have the capability of causing vitreoretinal sequellae are suspected to gain access to the retina via the optic disc and/or ora serrata. This is postulated as a mechanism because of the characteristic visual field loss: enlarged blind spot and loss of field in the periphery. 1,2,5,10 These 2 areas have photoreceptor cells in close contact with the globe s circulation. It is theorized that an offending organism gains entry via these portals and spreads from cell to cell. 1,5 Cells infected by the virus become deactivated by the host s immune response causing an acute loss of retinal function. 1,5,12 The fundus appears as if it is unaffected in the beginning, as the immune response deactivates retinal cell function without initially causing inflammation, apoptosis, or necrosis. 1,7 However, all patients gradually show fundus changes as the acute phase of infection transitions into the later, more advanced stages of the disease. 1,2,4,8,15 Patients who are less fortunate develop early inflammation in the vitreous, perivascular exudates, and optic nerve edema, leading to acute and permanent cell death and compromise. 1 The amount of inflammation observed within the vitreous body is proportional to the area of the affected retina because inflammation is in response to dying or dead photoreceptor cells. In the later phases, narrowing blood vessels may be observed secondary to declining oxygen consumption within the affected areas. 1,2 Patients with widespread areas of compromise will have a relative afferent pupillary defect. 2 An interesting characteristic of AZOOR is its propensity to affect myopes. 1,7 The disease is shown to most commonly strike those with 2 diopters of myopia or more. 1 This is thought to occur because larger eyes may have increased susceptibility at the suspected routes of entry (ora and disc). 1 Autoimmune diseases are also known to share association with AZOOR. Some patients (28%) either have or will have an autoimmune disease during AZOOR s acute phase. 1,15 Interestingly, it has been postulated 1,5 that if

5 26 Optometry, Vol 81, No 1, January 2010 Table 2 Differential diagnosis of AZOOR Disease Multiple evanescent white dot syndrome (MEWDS) Serpignous choroidopathy Acute posterior multifocal placoid pigment epitheliopathy (AMPEE) Multifocal choroiditis and panuveitis (MCP) Punctate inner choroidopathy (PIC) Cancer associated retinopathy (CAR) Acute annular outer retinopathy Retinitis pigmentosa (RP) Diffuse unilateral subacute neuroretinitis (DUSN) Features Benign; rare recurrences; acute; unilateral; young women; white dots at the level of RPE; blind spot enlargement with visual field loss; regression in weeks; granular macular appearance; visual acuity improves. Visual acuity is affected; bilateral; may recur; acute yellow-white subretinal patches with indistinct borders; old scars are bordered; white men and women; between 30 and 60 years of age; neovascularization may develop. Young men and women; very large white lesions; bilateral; acute; vitreous cells; vision returns to normal in 2 to 6 weeks. Young women; anterior and posterior chamber inflammation; recurrences, no subretinal scarring; enlarged blind spot; fair prognosis; multiple foci of choroiditis. White spots in acute phase; no vitreous inflammation; little or no scarring; no recurrences; enlarged blind spot; normal ERG. Slower course of visual field loss; nyctalopia over months to years; history of cancer or melanoma. No age or sex association; no vitreous inflammation; has an evanescent white intraretinal ring (possibly an immunity ring) that separates normal retinal from abnormal retina. RPE changes; no associated history of rapid onset vision loss; night vision decreases; abnormal ERG; optic disc pallor; decreased color vision. Unilateral vision loss; in children and young adults; caused by a nematode; optic nerve edema, deep-white retinal lesion; optic atrophy and RPE changes after the acute phase. autoimmune diseases are precipitators, one would expect to find more cases of bilateral, symmetric involvement of both eyes. Further, one would also predict that oral and topical steroids would provide rapid improvement and that circulating retinal antibodies should also be easily detectable. 1,5 However, despite these suppositions, with AZOOR, this is not the case. 1,5,6 Diagnosis and treatment When a retinal disease cannot be definitively distinguished by its appearance alone, other tests are required. The diagnostic study of choice in suspected cases of AZOOR, and tapetoretinal diseases in general, is the ERG. 1,4,9,17 An ERG waveform shows the summation of electrical potential by all retinal cells. The potential is measured by a contact lens electrode in conjunction with a skin reference electrode placed on the patient s forehead. Scotopic functions are rod responses measured after a period of dark adaptation, whereas photopic functions are cone responses measured after light adaptation. 17 A full-field ERG measures the overall rod and cone responses from the entire retina. The focal and multifocal ERGs are used to detect local retinal dysfunction; however, these 2 techniques mostly assess only light-adapted cone activities because dark adaptation is difficult to maintain during these techniques. 17 ERGs assess the level of function of the outer retinal layers and the photoreceptors. This is especially helpful when retinal tissue manifestations are not yet apparent. 1,6,8,9,15,18 In AZOOR, the scotopic function, photopic function, or both are reduced in affected eyes. The abnormalities in the ERG findings are known to be variable and directly correlated to the degree of visual field loss. This makes full-field ERGs useful tools in diagnosing AZOOR, especially when the amount of retina involved is large. 1,9 Multifocal ERGs can also be used; however, they are only sensitive to cone dysfunction. This selectivity may fail to detect abnormalities in patients with only rod dysfunction. 1,9,17 Because the outer retinal layer dysfunction in AZOOR is often permanent, ERGs are also useful for monitoring progress. 7,8 Nishio et al. 11 also found scanning laser ophthalmoscopy to be useful in localizing retinal damage in AZOOR because changing the laser wavelength can show retinal lesions and the underlying unaffected choroidal layer. Visual field studies are needed in conjunction with ERGs to quantify the visual field loss and monitor the disease s progression. If progression is noted after the 2- to 6-month stabilization period, other pathologies may need to be investigated. 1,3,10 Fluorescein angiography can also be useful in detecting the early alterations of AZOOR. The test can exhibit hyperfluorescence and the redistribution of melanin in patients that later experience RP-like changes. 1,6 Differential diagnosis AZOOR is classified into the category of heterogeneous groups of retinopathies of unknown etiology. 8,10,15 These

6 Ibironke and Gurwood Clinical Care 27 retinopathies may represent a continuum of one disease process 1,2,5-7,10,13,15 because they seem to have similar presentations and features, although some argue that unique characteristics and etiologic links point to separate entities. 10,13 Other retinopathies that should be considered given the described constellation of signs and symptoms include multiple evanescent white dot syndrome (MEWDS), acute annular outer retinopathy (AAOR), acute idiopathic blind spot enlargement syndrome (AIBSES), acute macular neuroretinopathy (AMN), multifocal inner choroiditis (Krill s disease), recurrent multifocal choroiditis and panuveitis (MCP), punctate inner choroidopathy (PIC), and the acute posterior multifocal placoid pigment epitheliopathy (AMPEE) (see Table 2). 1,10,12,15,19-21 Because some AZOOR patients present with vitritis and retinal perivascular exudation and because of proposed systemic associations, consideration must be given to adding studies that rule out sarcoid, Behcet s disease, rheumatoid vasculitis, and nonspecific causes of uveitis. 1 Management There are no proven treatments for AZOOR. 1,7 It is a selflimiting condition. However, if there are associated systemic illnesses discovered, they must be addressed and managed. The role of systemic and topical medications in the treatment of this ocular disease is still unclear, as only the vitritis regresses when treated with topical agents. 10 In patients in whom the inflammation is solely anterior, the benefits of topical cycloplegic and anti-inflammatory preparations are anecdotal and analgesic at best. 4,7 Although the retinal losses and visual field losses are typically permanent, the overall prognosis is generally good, 1,3,7,18 as the disease stabilizes in most instances before disabling central losses occur. Conclusion Understanding AZOOR and its presentation allows for timely referral and diagnosis along with testing for associated systemic conditions. Knowledge of the entity allows for effective communication regarding the disease s course and treatment options. References 1. Gass JD, Agarwal A, Scott IU. Acute zonal occult outer retinopathy: a long-term follow-up. Am J Ophthalmol 2002;134: Gass JD, Stern C. Acute annular outer retinopathy as a variant of the acute zonal occult outer retinopathy. Am J Ophthalmol 1995;119: Lee AG, Prager TC. Acute zonal occult outer retinopathy. Acta Ophthalmol Scand 1996;74: Jacobson DM. Acute zonal occult outer retinopathy and central nervous system inflammation. J Neuro-Ophthalmol 1996;16(3): Gass JD. Are acute zonal occult outer retinopathy and the white spot syndromes (AZOOR Complex) specific autoimmune diseases? Am J Ophthalmol 2003;135(3): Gass JD. Stereoscopic atlas of macular disease: diagnosis and treatment, 4th ed. St. Louis: CV Mosby; 1997: Holz FG, Kim RY, Schwartz SD, et al. Acute zonal occult outer retinopathy (AZOOR) associated with multifocal choroidopathy. Eye 1994;8: Jacobson SSG, Morales DS, Sun XK, et al. Pattern of retinal dysfunction in acute occult zonal outer retinopathy. Ophthalmology 1995;102: Arai M, Nao-i N, Sawada A, et al. Multifocal electroretinogram indicates visual field loss in acute zonal occult outer retinopathy. Am J Ophthalmol 1998;126(3): Jampol LM, Becker KG. White Spot syndromes of the retina: A hypothesis based on the common genetic hypothesis of autoimmune/inflammatory disease. Am J Ophthalmol 2003;135(3): Nishio M, Suzuki T, Chikuda M, et al. Scanning laser ophthalmoscopic findings in a patient with acute zonal occult outer retinopathy. Am J Ophthalmol 1998;125: Gass JD. The acute zonal outer retinopathies. Am J Ophthalmol 2000; 130(5): Gass JD. Overlap among acute idiopathic blind spot enlargement syndrome and other conditions. Arch Ophthalmol 2001;119: Lombardo J. Multiple evanescent white dot syndrome and acute zonal occult outer retinopathies. Optomy Vis Sci 2003;80(10): Jampol LM, Wiredu AMEWDS. MFC, PIC, AMN, AIBSE, and AZOOR: one disease or many? Retina 1995;15(5): Carrasco L, Ramos M, Galisteo R, et al. Isolation of Candida famata from a patient with Acute Zonal Occult Outer Retinopathy. J Clin Microbiol 2005;43(2): Lam BL. Electrophysiology of vision: clinical testing and applications. Boca Raton: Taylor & Francis; 2005: Gass JD. Acute zonal occult outer retinopathy. Donders lecturedthe Netherlands Ophthalmological Society, Maastricht, Holland, June 19, J Clin Neurol Ophthalmol 1993;13: Arbet TP. Multiple evanescent white dot syndrome. J Am Optometric Assoc 1997;68(12): Reddy CV, Brown J, Folk JC, et al. Enlarged blind spots in chorioretinal inflammatory disorders. Ophthalmology 1996;103: Fekrat S, Wilkinson CP, Chang B, et al. Acute annular outer retinopathy: report of four cases. Am J Ophthalmol 2000;130: