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Optic Disk Edema With a Macular Star
SURVEY OF OPHTHALMOLOGY VOLUME 43 • NUMBER 3 • NOVEMBER–DECEMBER 1998
CLINICAL CHALLENGES PETER SAVINO, EDITOR
Optic Disk Edema With a Macular Star RANA RAHMAN GHAURI1 AND ANDREW G. LEE, MD2 1
Texas A & M University Health Sciences Center, College Station, and 2Departments of Ophthalmology, Neurology, and Neurosurgery, Baylor College of Medicine, Houston, and The Division of Neurosurgery, M.D. Anderson Cancer Center, University of Texas, Houston, Texas, USA
Comments by Valerie Purvin, MD (In keeping with the format of a clinical pathological conference, the abstract and key words appear at the end of the article.) Case Report. A 13-year-old boy was examined in September 1997 with acute loss of vision in his right eye for 2 weeks. After returning from a trip to Alaska during the last week of July 1997, he had developed a high fever and was ill for several days, then improved. In August 1997, he had recurrent episodes of sweating and a high fever. Subsequently, he developed acute loss of vision in the right eye. Magnetic resonance imaging of the head and complete blood cell count were normal. The patient was taking no medications. He had a number of pets, including a dog, cats, ferrets, birds, a rabbit, and a fish. The patient had no complaints of ocular pain, diplopia, or headaches. He denied any recent tick bite or rash, but admitted having had several cat scratches in the previous few months. Results of physical examination were normal, with no adenopathy, skin lesions, or external eye findings. Neuroophthalmologic examination showed visual acuity of counting fingers at 1 foot OD and 20/20 OS. Pupil examination showed a 5-mm pupil in each eye, a diminished light reaction in the right eye, and a right afferent pupillary defect. Extraocular movements were full. Slit-lamp examination and intraocular pressure measurements were normal in both eyes.
Goldmann perimetry disclosed a central scotoma in the right eye (Fig. 1) and a normal visual field in the left eye. Ophthalmoscopy of the right eye showed optic disk edema, mild vitreous cells, and minimal exudates in the macula (Fig. 2). Ophthalmoscopic findings in the left eye were normal. What is the differential diagnosis? What further studies should be performed?
Comments Comments by Valerie Purvin, MD, Neuro-Ophthalmology Section, Midwest Eye Institute, Indianapolis, Indiana, and Departments of Ophthalmology and Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA A previously healthy 13-year-old boy developed acute unilateral visual loss after two bouts of a febrile illness unassociated with other systemic symptoms or focal neurologic deficits. Examination showed reduced visual acuity in the involved eye, a relative afferent pupillary defect, and marked optic disk swelling. The differential diagnosis of acute unilateral optic neuropathy with disk edema includes compressive/ infiltrative processes, hereditary optic neuropathy, 270
© 1998 by Elsevier Science Inc. All rights reserved.
0039-6257/98/$19.00 PII S0039-6257(98)00038-1
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OPTIC DISK EDEMA WITH MACULAR STAR
Fig. 2. Fundus photograph shows optic disk edema and minimal macular exudate in the right eye. Fig. 1. Goldmann perimetry of right eye shows central scotoma to V4e isopter and an enlarged blind spot with preservation of peripheral isopters (V4e, I4e, I3e, I2e).
and a variety of inflammatory conditions. The abrupt onset, absence of proptosis, and negative neuroimaging speak against any sort of compressive lesion. The most common infiltrative optic neuropathy in childhood is acute leukemia, caused by either cells around the intraorbital optic nerve or, in some cases, an aggregation of malignant cells overlying the optic disk. Visual acuity is usually markedly reduced in the former and relatively normal in the latter.1 The overlying vitreous cells in the present case could potentially be leukemic rather than inflammatory, although the decreased visual acuity speaks against this mechanism. In any case, a complete blood cell count should be obtained to rule out this possibility. Some forms of chronic meningitis (e.g., fungal, tuberculous) may also cause optic neuropathy because of infiltration around the optic nerve. In most cases, other signs and symptoms are present, typically including headache and other cranial nerve palsies. Unilateral optic neuropathy with disk swelling in a teenage boy should also suggest the possibility of Leber hereditary optic neuropathy (LHON). The acute onset, absence of pain, and central scotoma would all be consistent with this form of hereditary optic neuropathy. The optic disk in LHON may have a normal appearance or may exhibit opacification of the peripapillary nerve fiber layer, termed pseudoedema. In some cases such swelling is quite prominent and may easily be mistaken for true disk edema. The characteristic peripapillary microangiography of LHON may further add to the impression of acquired disk edema. In the present case, the central rather than peripheral location of the di-
lated vascular channels and the overlying vitreous cells effectively rule out LHON. The most common cause of acute optic neuropathy in young people is optic neuritis, which may develop in several settings. Optic neuritis may occur as an isolated, idiopathic event, as a sequela to a viral illness or immunization, or as a part of multiple sclerosis. Occasionally, optic neuritis occurs as a manifestation of a systemic infectious/inflammatory disorder such as lupus, sarcoidosis, syphilis, Lyme disease, or brucellosis. Whatever the underlying mechanism, most cases of optic neuritis are associated with prominent eye pain, which may precede the onset of visual loss by several days and is typically exacerbated by eye movement. The absence of pain in the present case speaks against optic neuritis as the cause of visual loss. In addition, both idiopathic isolated optic neuritis and the demyelinating optic neuritis associated with multiple sclerosis are unusual in childhood. When optic neuritis does occur in a child, it is typically bilateral and associated with disk swelling, and it often follows a viral illness. Specific inflammatory disorders that may cause optic neuritis are unlikely in the absence of other systemic or neurologic manifestations, but should be excluded with appropriate laboratory tests, including an antinuclear antibody test, angiotensin-converting enzyme, fluorescent treponemal antibody test, and Lyme titers.
Case Report (Continued) Angiotensin-converting enzyme level, rapid plasma reagin, fluorescent treponemal antibody testing, Lyme titers, and complete blood cell count were normal. Six days later, physical examination disclosed mild lymphadenopathy in the neck. Visual acuity was 20/200 OD and 20/20 OS. Ophthalmoscopy revealed optic disk edema and a florid macular
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star in the right eye (Fig. 3). The left eye remained normal. What tests would you order now?
Comments (Continued) The appearance of a macular star figure is extremely helpful in narrowing the differential diagnosis. Few disorders are associated with lipid deposits with this particular pattern. Florid papilledema, i.e., disk edema secondary to increased intracranial pressure, is occasionally associated with a macular star, but typically it involves both optic disks and does not cause marked optic nerve dysfunction. Hypertensive retinopathy, another potential cause of such macular exudates, is similarly bilateral and in most cases is associated with more widespread retinal exudates, hemorrhages, and cotton wool spots. Occasional cases of anterior ischemic optic neuropathy manifests a macular star as the disk edema resolves, but such disk infarction would be extraordinarily rare in a 13-yearold. In this clinical setting, the appearance of a macular star figure points to a diagnosis of neuroretinitis. Neuroretinitis is an inflammatory disorder of the optic disk that typically presents with acute, painless, unilateral visual loss in a young person.10,19 The initial fundus appearance consists of florid disk edema with surrounding serous retinal detachment extending to the macula. Visual field findings often reflect this pattern of edema, usually manifested as a large central or cecocentral scotoma. That the visual loss is in large part caused by retinal edema rather than optic nerve dysfunction is evidenced by a relative afferent pupillary defect that is small in comparison to the extent of visual loss. (Quantification of the relative afferent pupillary defect is not provided in the
Fig. 3. Fundus photograph shows optic disk edema with macular star figure in the right eye.
GHAURI AND LEE
case under discussion.) In some cases disk edema is segmental rather than diffuse. Within 2 weeks, resorption of disk and retinal edema begins. Faster resorption of the aqueous phase leaves lipid deposits that track along the outer plexiform layer to form the characteristic macular star figure. The diagnosis of neuroretinitis may be suspected at initial examination based on the large amount of disk and surrounding retinal edema, the small degree of relative afferent pupillary defect, and the absence of pain, but the diagnosis can only be confirmed 10 to 14 days later when the star figure appears. The prognosis for visual recovery after an episode of neuroretinitis is excellent, regardless of treatment. More importantly, patients with neuroretinitis are not at increased risk for subsequently developing multiple sclerosis as in “garden variety” optic neuritis. This is presumably because the target tissue in neuroretinitis is disk vasculature rather than neural tissue. Neuroretinitis may be caused by a number of specific infectious conditions, including tuberculosis,11 syphilis,14 mumps,15 toxoplasmosis,13,24 leptospirosis,10 Lyme disease,18 and cat scratch disease (CSD).3,29 Most of these specific causes occur infrequently. In previously published series of neuroretinitis cases, the large majority have been classified as idiopathic. Recent advances in laboratory testing for Bartonella henselae, the agent responsible for CSD, have led to more frequent recognition of cat scratch neuroretinitis.8,16,25,27,31 It is still unclear whether most cases of neuroretinitis previously categorized as idiopathic will turn out to be caused by CSD. Most patients with cat scratch neuroretinitis have a history of exposure to a cat (usually a kitten) and, more specifically, a history of cat scratches. Fleas can act as a vector for the cat scratch organism, and this may explain occasional cases without such a history. Patients often, although not always, experience systemic symptoms in the weeks before visual loss, including fever, chills, headache, malaise, and lymphadenopathy. Ophthalmoscopic features that suggest CSD as opposed to some other cause of neuroretinitis include segmental rather than generalized disk edema, the presence of scattered chorioretinal white lesions, and occasional bilateral involvement (e.g., asymptomatic disk edema or chorioretinal spots in the fellow eye).28 In the present case, none of these features was present, but the history of preceding fevers and cat scratches is sufficiently characteristic that serologic tests for B. henselae should be obtained. Until recently, the diagnosis of CSD was usually based on clinical criteria (regional adenopathy after a cat scratch or bite). More definitive diagnosis depended on demonstration of typical histopathologic changes in material from lymph node biopsy and a
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positive reaction to the cat-scratch antigen skin test. Since the identification of B. henselae as the causative agent, the diagnosis can also be made by culturing the organism from blood, cerebrospinal fluid, or lymph node aspirate. Newer methods that use the polymerase chain reaction technique and DNA hybridization have largely obviated culturing. More recently, serologic tests are increasingly relied on for diagnosis. Immunofluorescent antibody testing has been found to have a sensitivity of 84% and specificity of 96%.30 Enzyme immunoassay testing is reportedly 5 to 10 times more sensitive than the immunofluorescent antibody technique.26
Case Report (Continued) Bartonella henselae titers were elevated for IgG at 4.5 and for IgM at 1.2 (. 1.1 5 positive). What treatment plan should be initiated and what is the probable prognosis of this patient?
Comments (Continued) Most cases of CSD are mild and self-limited even without treatment. Similarly, the prognosis for spontaneous visual recovery is excellent.28 Occasional patients with CSD experience prolonged and/or recurrent fevers and other systemic manifestations.21 Anecdotal reports indicate successful treatment of CSD with a wide variety of antibiotics.22 Treatment failures with a number of agents are also reported. A retrospective study of 268 patients plus review of the literature suggests that the most efficacious agents for the treatment of CSD are rifampin (effective in 84%), ciprofloxacin (84%), intramuscular gentamicin (73%), and trimethoprim-sulfamethoxazole (58%).20 A recent report of seven patients with cat scratch neuroretinitis suggests that a combined regimen of doxycycline (100 mg twice daily) and rifampin (300 mg two or three times daily) given for 4 to 6 weeks may exert a beneficial effect on the disease process; however, no nontreatment control group was used in the study.27
Author’s Discussion A diagnosis of optic disk edema with a macular star (ODEMS) secondary to CSD was made. The patient was treated with doxycycline and made a dramatic improvement to a visual acuity of 20/30 with a minimal residual relative central scotoma in the right eye. The optic disk edema and macular star resolved, and the patient was left with mild optic atrophy in the right eye. We would like to add a few comments to those provided by Dr. Purvin. The vast majority of cases of CSD occur in patients younger than 20 years. Patients may develop a pri-
mary cutaneous lesion 7 to 10 days after inoculation with B. henselae. Between 5 and 50 days after the appearance of the primary lesion, 96% of patients develop lymphadenopathy that spontaneously regresses within 2 to 6 months.2-7 Patients with CSD occasionally (9–14%) present with other findings, including Parinaud’s oculoglandular syndrome, encephalopathy, aseptic meningitis, hepatitis, atypical pneumonia, erythema nodosa, osteomyelitis, and neuroretinitis. The major manifestation is ODEMS in approximately 1.5% of cases of CSD. Patients with CSD-related posterior segment inflammation usually present with sudden vision loss, optic disk swelling, peripapillary and macular exudates, and cells in the vitreous. As discussed by Dr. Purvin, a variety of infectious diseases must be ruled out by appropriate testing. Exposure to cats, sexually transmitted disease, recent skin rashes, tick bites, travel to areas endemic for Lyme disease, recent arthralgias or myalgias, fever, malaise, and lymphadenopathy are important in the history.2–7,9,12–15,17–19 Occasionally, depending on the history, tests such as toxoplasmosis titer, Toxocara titer, purified protein derivative skin testing, and a chest radiograph may be indicated.3,6,7,13–15,18 Although laboratory studies are important in the evaluation of ODEMS, magnetic resonance imaging and lumbar puncture are not usually indicated unless the patient has neurologic symptoms, or unless the features are atypical for infectious or idiopathic ODEMS (e.g., bilateral, lack of improvement, lack of vitreous cells).14 Optic disk edema with a macular star may be mimicked by anterior ischemic optic neuropathy, branch or central retinal vein occlusion, or papilledema.6 These usually can be excluded by clinical history and examination. In most cases of ODEMS associated with CSD, disk edema resolves in 6 to 8 weeks.3,13,23,29 The macular exudates initially progress but then stabilize over several weeks, and then resolve over several months. Patients may, however, have residual macular pigmentary changes,5 and a small subgroup of patients may have a poor visual outcome. Our patient presented with optic disk edema and macular exudate, but progressed rapidly to a full macular star figure. Patients with optic disk edema should be observed closely for the development of ODEMS and evaluated for infectious causes, such as CSD.
References 1. Allen RA, Straatsma BR: Ocular involvement in leukemia and allied disorders. Arch Ophthalmol 66:490–508, 1961 2. American Academy of Pediatrics, in Peter G (ed): 1997 Red Book: Report of the Committee on Infectious Diseases. Elk Grove Village, IL, American Academy of Pediatrics, 1997, ed 24, pp 165–166
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3. Bar S, Segal M, Shapira R, Savir H: Neuroretinitis associated with cat scratch disease (letter). Am J Ophthalmol 110:703– 705, 1990 4. Bass JW, Vincent JM, Person DA: The expanding spectrum of Bartonella infections. II. Cat-scratch disease. Pediatr Infect Dis J 16:163–179, 1997 5. Bogue CW, Wise JD, Gray GF, Edwards KM: Antibiotic therapy for cat-scratch disease? JAMA 268:813–816, 1989 6. Brazis PW, Lee AG: Optic disk edema with a macular star. Mayo Clin Proc 71:1162–1166, 1996 7. Carithers HA: Cat-scratch disease. An overview based on a study of 1200 patients. Am J Dis Child 139:1124–1133, 1985 8. Chrousos GA, Drack AV, Young M, et al: Neuroretinitis in cat scratch disease. J Clin Neuro-Ophthalmol 19:92–94, 1990 9. Collip PJ: Cat-scratch disease therapy (letter). Am J Dis Child 143:1261, 1989 10. Dreyer DF, Hopen G, Gass DM, et al: Leber’s idiopathic stellate neuroretinitis. Arch Ophthalmol 102:1140, 1984 11. Duke-Elder S, Dobree JH: Diseases of the retina, in DukeElder S (ed): System of Ophthalmology, Vol 10. St Louis, CV Mosby, 1967, pp 246–248 12. Fish RH, Hogan RN, Nightingale SD, Anand R: Peripapillary angiomatosis associated with cat-scratch neuroretinitis (letter). Arch Ophthalmol 110:323, 1992 13. Fish RH, Hoskins JC, Kline LB: Toxoplasmosis neuroretinitis. Ophthalmology 100:1177–1182, 1993 14. Folk JC, Weingeist TA, Corbett JJ, et al: Syphilitic neuroretinitis. Am J Ophthalmol 95:480–486, 1983 15. Foster RE, Lowder CY, Meisler DM, et al: Mumps neuroretinitis in an adolescent. Am J Ophthalmol 110:91–93, 1990 16. Golnik KC, Marota ME, Fanous MM, et al: Ophthalmic manifestations of Rochalimaea species. Am J Ophthalmol 118: 145–151, 1994 17. Holley HP Jr: Successful treatment of cat-scratch disease with ciprofloxacin. JAMA 265:1563–1565, 1991 18. Lesser RL, Kornmehl EW, Pachner AR, Kattah J, Hedges TR III, Newman NM, et al: Neuro-ophthalmologic manifestations of Lyme disease. Ophthalmology 97:699–706, 1990 19. Maitland CG, Miller NR: Neuroretinitis. Arch Ophthalmol 102:1146–1150, 1984 20. Margileth AM: Antibiotic therapy for cat scratch disease:
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21. 22. 23. 24. 25.
26. 27. 28. 29. 30. 31.
Clinical study of therapeutic outcome in 268 patients and a review of the literature. Pediatr Infect Dis J 11:474–478, 1992 Margileth AM, Wear DJ, English CK: Systemic cat scratch disease: Report of 23 patients with prolonged or recurrent severe bacterial infection. J Infect Dis 155:390–402, 1987 Maurin M, Gasquet S, Ducco C, Raoult D: MICs of 28 antibiotic compounds for 14 Bartonella (formerly Rochalimaea) isolates. Antimicrob Agents Chemother 39:2387–2391, 1995 McCrary B, Cockerham W, Pierce P: Neuroretinitis in catscratch disease associated with the macular star (letter). Pediatr Infect Dis J 13:838–839, 1994 Moreno RJ, Weisman J, Waller S: Neuroretinitis: an unusual presentation of ocular toxoplasmosis. Ann Ophthalmol 24: 68–70, 1992 Newsom R, Martin T, Wasilauskas B: Cat scratch disease diagnosed serologically using an enzyme immunoassay in a patient with neuroretinitis. Arch Ophthalmol 114:493–494, 1996 Patnaik M, Schwartzman WA, Barka NE, et al: Possible role of Rochalimaea henselae in pathogenesis of AIDS encephalopathy. Lancet Oct 17, 340–371, 1992 Reed JB, Scales DK, Wong MR, et al: Bartonella henselae neuroretinitis in cat scratch disease. Ophthalmology 105:459– 466, 1998 Sawyer R: Cat scratch neuroretinitis: Differential diagnosis and management (abstract). Ophthalmology 101 (Suppl): 87, 1994 Ulrich CG, Waecker NJ Jr, Meister SJ, et al: Cat scratch disease associated with neuroretinitis in a 6-year-old girl. Ophthalmology 99:246–249, 1992 Zangwill KM, Hamilton DH, Perkins BA, et al: Cat scratch disease in Connecticut: Epidemiology, risk factors, and evaluation of a new diagnostic test. N Engl J Med 329:8–13, 1993 Zhao X, Ge B: Treatment of papillo-retinitis and uveitis with cat scratch disease by combination of TCM and modern drugs. J Trad Chin Med 11:184–186, 1991
Reprint address: Andrew G. Lee, MD, 6501 Fannin Street, NC 200, Baylor College of Medicine, Houston, TX 77030, USA.
Abstract. A 13-year-old boy presented with acute loss of vision in his right eye of 2 weeks’ duration. He had a high fever and was ill for several days, then improved but suffered recurrent episodes of sweating and a high fever. Ophthalmoscopy of the right eye showed optic disk edema, mild vitreous cells, and minimal exudates in the macula. Bartonella henselae titers were positive. A diagnosis of optic disk edema with a macular star secondary to cat-scratch disease was made. The patient was treated with doxycycline and made a dramatic improvement to visual acuity of 20/30 with a minimal residual relative central scotoma. The optic disk edema and macular star resolved, and the patient was left with mild optic atrophy in the right eye. (Surv Ophthalmol 43:270–274, 1998. © 1998 by Elsevier Science Inc. All rights reserved.) Key words. cat-scratch disease
•
Bartonella henselae
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optic disk edema • macular star
CLINICAL CHALLENGES PETER SAVINO, EDITOR
Optic Disk Edema With a Macular Star RANA RAHMAN GHAURI1 AND ANDREW G. LEE, MD2 1
Texas A & M University Health Sciences Center, College Station, and 2Departments of Ophthalmology, Neurology, and Neurosurgery, Baylor College of Medicine, Houston, and The Division of Neurosurgery, M.D. Anderson Cancer Center, University of Texas, Houston, Texas, USA
Comments by Valerie Purvin, MD (In keeping with the format of a clinical pathological conference, the abstract and key words appear at the end of the article.) Case Report. A 13-year-old boy was examined in September 1997 with acute loss of vision in his right eye for 2 weeks. After returning from a trip to Alaska during the last week of July 1997, he had developed a high fever and was ill for several days, then improved. In August 1997, he had recurrent episodes of sweating and a high fever. Subsequently, he developed acute loss of vision in the right eye. Magnetic resonance imaging of the head and complete blood cell count were normal. The patient was taking no medications. He had a number of pets, including a dog, cats, ferrets, birds, a rabbit, and a fish. The patient had no complaints of ocular pain, diplopia, or headaches. He denied any recent tick bite or rash, but admitted having had several cat scratches in the previous few months. Results of physical examination were normal, with no adenopathy, skin lesions, or external eye findings. Neuroophthalmologic examination showed visual acuity of counting fingers at 1 foot OD and 20/20 OS. Pupil examination showed a 5-mm pupil in each eye, a diminished light reaction in the right eye, and a right afferent pupillary defect. Extraocular movements were full. Slit-lamp examination and intraocular pressure measurements were normal in both eyes.
Goldmann perimetry disclosed a central scotoma in the right eye (Fig. 1) and a normal visual field in the left eye. Ophthalmoscopy of the right eye showed optic disk edema, mild vitreous cells, and minimal exudates in the macula (Fig. 2). Ophthalmoscopic findings in the left eye were normal. What is the differential diagnosis? What further studies should be performed?
Comments Comments by Valerie Purvin, MD, Neuro-Ophthalmology Section, Midwest Eye Institute, Indianapolis, Indiana, and Departments of Ophthalmology and Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA A previously healthy 13-year-old boy developed acute unilateral visual loss after two bouts of a febrile illness unassociated with other systemic symptoms or focal neurologic deficits. Examination showed reduced visual acuity in the involved eye, a relative afferent pupillary defect, and marked optic disk swelling. The differential diagnosis of acute unilateral optic neuropathy with disk edema includes compressive/ infiltrative processes, hereditary optic neuropathy, 270
© 1998 by Elsevier Science Inc. All rights reserved.
0039-6257/98/$19.00 PII S0039-6257(98)00038-1
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Fig. 2. Fundus photograph shows optic disk edema and minimal macular exudate in the right eye. Fig. 1. Goldmann perimetry of right eye shows central scotoma to V4e isopter and an enlarged blind spot with preservation of peripheral isopters (V4e, I4e, I3e, I2e).
and a variety of inflammatory conditions. The abrupt onset, absence of proptosis, and negative neuroimaging speak against any sort of compressive lesion. The most common infiltrative optic neuropathy in childhood is acute leukemia, caused by either cells around the intraorbital optic nerve or, in some cases, an aggregation of malignant cells overlying the optic disk. Visual acuity is usually markedly reduced in the former and relatively normal in the latter.1 The overlying vitreous cells in the present case could potentially be leukemic rather than inflammatory, although the decreased visual acuity speaks against this mechanism. In any case, a complete blood cell count should be obtained to rule out this possibility. Some forms of chronic meningitis (e.g., fungal, tuberculous) may also cause optic neuropathy because of infiltration around the optic nerve. In most cases, other signs and symptoms are present, typically including headache and other cranial nerve palsies. Unilateral optic neuropathy with disk swelling in a teenage boy should also suggest the possibility of Leber hereditary optic neuropathy (LHON). The acute onset, absence of pain, and central scotoma would all be consistent with this form of hereditary optic neuropathy. The optic disk in LHON may have a normal appearance or may exhibit opacification of the peripapillary nerve fiber layer, termed pseudoedema. In some cases such swelling is quite prominent and may easily be mistaken for true disk edema. The characteristic peripapillary microangiography of LHON may further add to the impression of acquired disk edema. In the present case, the central rather than peripheral location of the di-
lated vascular channels and the overlying vitreous cells effectively rule out LHON. The most common cause of acute optic neuropathy in young people is optic neuritis, which may develop in several settings. Optic neuritis may occur as an isolated, idiopathic event, as a sequela to a viral illness or immunization, or as a part of multiple sclerosis. Occasionally, optic neuritis occurs as a manifestation of a systemic infectious/inflammatory disorder such as lupus, sarcoidosis, syphilis, Lyme disease, or brucellosis. Whatever the underlying mechanism, most cases of optic neuritis are associated with prominent eye pain, which may precede the onset of visual loss by several days and is typically exacerbated by eye movement. The absence of pain in the present case speaks against optic neuritis as the cause of visual loss. In addition, both idiopathic isolated optic neuritis and the demyelinating optic neuritis associated with multiple sclerosis are unusual in childhood. When optic neuritis does occur in a child, it is typically bilateral and associated with disk swelling, and it often follows a viral illness. Specific inflammatory disorders that may cause optic neuritis are unlikely in the absence of other systemic or neurologic manifestations, but should be excluded with appropriate laboratory tests, including an antinuclear antibody test, angiotensin-converting enzyme, fluorescent treponemal antibody test, and Lyme titers.
Case Report (Continued) Angiotensin-converting enzyme level, rapid plasma reagin, fluorescent treponemal antibody testing, Lyme titers, and complete blood cell count were normal. Six days later, physical examination disclosed mild lymphadenopathy in the neck. Visual acuity was 20/200 OD and 20/20 OS. Ophthalmoscopy revealed optic disk edema and a florid macular
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star in the right eye (Fig. 3). The left eye remained normal. What tests would you order now?
Comments (Continued) The appearance of a macular star figure is extremely helpful in narrowing the differential diagnosis. Few disorders are associated with lipid deposits with this particular pattern. Florid papilledema, i.e., disk edema secondary to increased intracranial pressure, is occasionally associated with a macular star, but typically it involves both optic disks and does not cause marked optic nerve dysfunction. Hypertensive retinopathy, another potential cause of such macular exudates, is similarly bilateral and in most cases is associated with more widespread retinal exudates, hemorrhages, and cotton wool spots. Occasional cases of anterior ischemic optic neuropathy manifests a macular star as the disk edema resolves, but such disk infarction would be extraordinarily rare in a 13-yearold. In this clinical setting, the appearance of a macular star figure points to a diagnosis of neuroretinitis. Neuroretinitis is an inflammatory disorder of the optic disk that typically presents with acute, painless, unilateral visual loss in a young person.10,19 The initial fundus appearance consists of florid disk edema with surrounding serous retinal detachment extending to the macula. Visual field findings often reflect this pattern of edema, usually manifested as a large central or cecocentral scotoma. That the visual loss is in large part caused by retinal edema rather than optic nerve dysfunction is evidenced by a relative afferent pupillary defect that is small in comparison to the extent of visual loss. (Quantification of the relative afferent pupillary defect is not provided in the
Fig. 3. Fundus photograph shows optic disk edema with macular star figure in the right eye.
GHAURI AND LEE
case under discussion.) In some cases disk edema is segmental rather than diffuse. Within 2 weeks, resorption of disk and retinal edema begins. Faster resorption of the aqueous phase leaves lipid deposits that track along the outer plexiform layer to form the characteristic macular star figure. The diagnosis of neuroretinitis may be suspected at initial examination based on the large amount of disk and surrounding retinal edema, the small degree of relative afferent pupillary defect, and the absence of pain, but the diagnosis can only be confirmed 10 to 14 days later when the star figure appears. The prognosis for visual recovery after an episode of neuroretinitis is excellent, regardless of treatment. More importantly, patients with neuroretinitis are not at increased risk for subsequently developing multiple sclerosis as in “garden variety” optic neuritis. This is presumably because the target tissue in neuroretinitis is disk vasculature rather than neural tissue. Neuroretinitis may be caused by a number of specific infectious conditions, including tuberculosis,11 syphilis,14 mumps,15 toxoplasmosis,13,24 leptospirosis,10 Lyme disease,18 and cat scratch disease (CSD).3,29 Most of these specific causes occur infrequently. In previously published series of neuroretinitis cases, the large majority have been classified as idiopathic. Recent advances in laboratory testing for Bartonella henselae, the agent responsible for CSD, have led to more frequent recognition of cat scratch neuroretinitis.8,16,25,27,31 It is still unclear whether most cases of neuroretinitis previously categorized as idiopathic will turn out to be caused by CSD. Most patients with cat scratch neuroretinitis have a history of exposure to a cat (usually a kitten) and, more specifically, a history of cat scratches. Fleas can act as a vector for the cat scratch organism, and this may explain occasional cases without such a history. Patients often, although not always, experience systemic symptoms in the weeks before visual loss, including fever, chills, headache, malaise, and lymphadenopathy. Ophthalmoscopic features that suggest CSD as opposed to some other cause of neuroretinitis include segmental rather than generalized disk edema, the presence of scattered chorioretinal white lesions, and occasional bilateral involvement (e.g., asymptomatic disk edema or chorioretinal spots in the fellow eye).28 In the present case, none of these features was present, but the history of preceding fevers and cat scratches is sufficiently characteristic that serologic tests for B. henselae should be obtained. Until recently, the diagnosis of CSD was usually based on clinical criteria (regional adenopathy after a cat scratch or bite). More definitive diagnosis depended on demonstration of typical histopathologic changes in material from lymph node biopsy and a
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positive reaction to the cat-scratch antigen skin test. Since the identification of B. henselae as the causative agent, the diagnosis can also be made by culturing the organism from blood, cerebrospinal fluid, or lymph node aspirate. Newer methods that use the polymerase chain reaction technique and DNA hybridization have largely obviated culturing. More recently, serologic tests are increasingly relied on for diagnosis. Immunofluorescent antibody testing has been found to have a sensitivity of 84% and specificity of 96%.30 Enzyme immunoassay testing is reportedly 5 to 10 times more sensitive than the immunofluorescent antibody technique.26
Case Report (Continued) Bartonella henselae titers were elevated for IgG at 4.5 and for IgM at 1.2 (. 1.1 5 positive). What treatment plan should be initiated and what is the probable prognosis of this patient?
Comments (Continued) Most cases of CSD are mild and self-limited even without treatment. Similarly, the prognosis for spontaneous visual recovery is excellent.28 Occasional patients with CSD experience prolonged and/or recurrent fevers and other systemic manifestations.21 Anecdotal reports indicate successful treatment of CSD with a wide variety of antibiotics.22 Treatment failures with a number of agents are also reported. A retrospective study of 268 patients plus review of the literature suggests that the most efficacious agents for the treatment of CSD are rifampin (effective in 84%), ciprofloxacin (84%), intramuscular gentamicin (73%), and trimethoprim-sulfamethoxazole (58%).20 A recent report of seven patients with cat scratch neuroretinitis suggests that a combined regimen of doxycycline (100 mg twice daily) and rifampin (300 mg two or three times daily) given for 4 to 6 weeks may exert a beneficial effect on the disease process; however, no nontreatment control group was used in the study.27
Author’s Discussion A diagnosis of optic disk edema with a macular star (ODEMS) secondary to CSD was made. The patient was treated with doxycycline and made a dramatic improvement to a visual acuity of 20/30 with a minimal residual relative central scotoma in the right eye. The optic disk edema and macular star resolved, and the patient was left with mild optic atrophy in the right eye. We would like to add a few comments to those provided by Dr. Purvin. The vast majority of cases of CSD occur in patients younger than 20 years. Patients may develop a pri-
mary cutaneous lesion 7 to 10 days after inoculation with B. henselae. Between 5 and 50 days after the appearance of the primary lesion, 96% of patients develop lymphadenopathy that spontaneously regresses within 2 to 6 months.2-7 Patients with CSD occasionally (9–14%) present with other findings, including Parinaud’s oculoglandular syndrome, encephalopathy, aseptic meningitis, hepatitis, atypical pneumonia, erythema nodosa, osteomyelitis, and neuroretinitis. The major manifestation is ODEMS in approximately 1.5% of cases of CSD. Patients with CSD-related posterior segment inflammation usually present with sudden vision loss, optic disk swelling, peripapillary and macular exudates, and cells in the vitreous. As discussed by Dr. Purvin, a variety of infectious diseases must be ruled out by appropriate testing. Exposure to cats, sexually transmitted disease, recent skin rashes, tick bites, travel to areas endemic for Lyme disease, recent arthralgias or myalgias, fever, malaise, and lymphadenopathy are important in the history.2–7,9,12–15,17–19 Occasionally, depending on the history, tests such as toxoplasmosis titer, Toxocara titer, purified protein derivative skin testing, and a chest radiograph may be indicated.3,6,7,13–15,18 Although laboratory studies are important in the evaluation of ODEMS, magnetic resonance imaging and lumbar puncture are not usually indicated unless the patient has neurologic symptoms, or unless the features are atypical for infectious or idiopathic ODEMS (e.g., bilateral, lack of improvement, lack of vitreous cells).14 Optic disk edema with a macular star may be mimicked by anterior ischemic optic neuropathy, branch or central retinal vein occlusion, or papilledema.6 These usually can be excluded by clinical history and examination. In most cases of ODEMS associated with CSD, disk edema resolves in 6 to 8 weeks.3,13,23,29 The macular exudates initially progress but then stabilize over several weeks, and then resolve over several months. Patients may, however, have residual macular pigmentary changes,5 and a small subgroup of patients may have a poor visual outcome. Our patient presented with optic disk edema and macular exudate, but progressed rapidly to a full macular star figure. Patients with optic disk edema should be observed closely for the development of ODEMS and evaluated for infectious causes, such as CSD.
References 1. Allen RA, Straatsma BR: Ocular involvement in leukemia and allied disorders. Arch Ophthalmol 66:490–508, 1961 2. American Academy of Pediatrics, in Peter G (ed): 1997 Red Book: Report of the Committee on Infectious Diseases. Elk Grove Village, IL, American Academy of Pediatrics, 1997, ed 24, pp 165–166
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3. Bar S, Segal M, Shapira R, Savir H: Neuroretinitis associated with cat scratch disease (letter). Am J Ophthalmol 110:703– 705, 1990 4. Bass JW, Vincent JM, Person DA: The expanding spectrum of Bartonella infections. II. Cat-scratch disease. Pediatr Infect Dis J 16:163–179, 1997 5. Bogue CW, Wise JD, Gray GF, Edwards KM: Antibiotic therapy for cat-scratch disease? JAMA 268:813–816, 1989 6. Brazis PW, Lee AG: Optic disk edema with a macular star. Mayo Clin Proc 71:1162–1166, 1996 7. Carithers HA: Cat-scratch disease. An overview based on a study of 1200 patients. Am J Dis Child 139:1124–1133, 1985 8. Chrousos GA, Drack AV, Young M, et al: Neuroretinitis in cat scratch disease. J Clin Neuro-Ophthalmol 19:92–94, 1990 9. Collip PJ: Cat-scratch disease therapy (letter). Am J Dis Child 143:1261, 1989 10. Dreyer DF, Hopen G, Gass DM, et al: Leber’s idiopathic stellate neuroretinitis. Arch Ophthalmol 102:1140, 1984 11. Duke-Elder S, Dobree JH: Diseases of the retina, in DukeElder S (ed): System of Ophthalmology, Vol 10. St Louis, CV Mosby, 1967, pp 246–248 12. Fish RH, Hogan RN, Nightingale SD, Anand R: Peripapillary angiomatosis associated with cat-scratch neuroretinitis (letter). Arch Ophthalmol 110:323, 1992 13. Fish RH, Hoskins JC, Kline LB: Toxoplasmosis neuroretinitis. Ophthalmology 100:1177–1182, 1993 14. Folk JC, Weingeist TA, Corbett JJ, et al: Syphilitic neuroretinitis. Am J Ophthalmol 95:480–486, 1983 15. Foster RE, Lowder CY, Meisler DM, et al: Mumps neuroretinitis in an adolescent. Am J Ophthalmol 110:91–93, 1990 16. Golnik KC, Marota ME, Fanous MM, et al: Ophthalmic manifestations of Rochalimaea species. Am J Ophthalmol 118: 145–151, 1994 17. Holley HP Jr: Successful treatment of cat-scratch disease with ciprofloxacin. JAMA 265:1563–1565, 1991 18. Lesser RL, Kornmehl EW, Pachner AR, Kattah J, Hedges TR III, Newman NM, et al: Neuro-ophthalmologic manifestations of Lyme disease. Ophthalmology 97:699–706, 1990 19. Maitland CG, Miller NR: Neuroretinitis. Arch Ophthalmol 102:1146–1150, 1984 20. Margileth AM: Antibiotic therapy for cat scratch disease:
GHAURI AND LEE
21. 22. 23. 24. 25.
26. 27. 28. 29. 30. 31.
Clinical study of therapeutic outcome in 268 patients and a review of the literature. Pediatr Infect Dis J 11:474–478, 1992 Margileth AM, Wear DJ, English CK: Systemic cat scratch disease: Report of 23 patients with prolonged or recurrent severe bacterial infection. J Infect Dis 155:390–402, 1987 Maurin M, Gasquet S, Ducco C, Raoult D: MICs of 28 antibiotic compounds for 14 Bartonella (formerly Rochalimaea) isolates. Antimicrob Agents Chemother 39:2387–2391, 1995 McCrary B, Cockerham W, Pierce P: Neuroretinitis in catscratch disease associated with the macular star (letter). Pediatr Infect Dis J 13:838–839, 1994 Moreno RJ, Weisman J, Waller S: Neuroretinitis: an unusual presentation of ocular toxoplasmosis. Ann Ophthalmol 24: 68–70, 1992 Newsom R, Martin T, Wasilauskas B: Cat scratch disease diagnosed serologically using an enzyme immunoassay in a patient with neuroretinitis. Arch Ophthalmol 114:493–494, 1996 Patnaik M, Schwartzman WA, Barka NE, et al: Possible role of Rochalimaea henselae in pathogenesis of AIDS encephalopathy. Lancet Oct 17, 340–371, 1992 Reed JB, Scales DK, Wong MR, et al: Bartonella henselae neuroretinitis in cat scratch disease. Ophthalmology 105:459– 466, 1998 Sawyer R: Cat scratch neuroretinitis: Differential diagnosis and management (abstract). Ophthalmology 101 (Suppl): 87, 1994 Ulrich CG, Waecker NJ Jr, Meister SJ, et al: Cat scratch disease associated with neuroretinitis in a 6-year-old girl. Ophthalmology 99:246–249, 1992 Zangwill KM, Hamilton DH, Perkins BA, et al: Cat scratch disease in Connecticut: Epidemiology, risk factors, and evaluation of a new diagnostic test. N Engl J Med 329:8–13, 1993 Zhao X, Ge B: Treatment of papillo-retinitis and uveitis with cat scratch disease by combination of TCM and modern drugs. J Trad Chin Med 11:184–186, 1991
Reprint address: Andrew G. Lee, MD, 6501 Fannin Street, NC 200, Baylor College of Medicine, Houston, TX 77030, USA.
Abstract. A 13-year-old boy presented with acute loss of vision in his right eye of 2 weeks’ duration. He had a high fever and was ill for several days, then improved but suffered recurrent episodes of sweating and a high fever. Ophthalmoscopy of the right eye showed optic disk edema, mild vitreous cells, and minimal exudates in the macula. Bartonella henselae titers were positive. A diagnosis of optic disk edema with a macular star secondary to cat-scratch disease was made. The patient was treated with doxycycline and made a dramatic improvement to visual acuity of 20/30 with a minimal residual relative central scotoma. The optic disk edema and macular star resolved, and the patient was left with mild optic atrophy in the right eye. (Surv Ophthalmol 43:270–274, 1998. © 1998 by Elsevier Science Inc. All rights reserved.) Key words. cat-scratch disease
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Bartonella henselae
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optic disk edema • macular star