Journal of Neuro-Ophthalmology, June 2004, Volume 24, Issue 2

Vasculopathies Affecting the Eye

The retinal arteries and veins may be involved in isolation or as the result of a systemic vasculitis. This article emphasizes neurologic diseases in which the ocular vasculature is affected.

STATE OF THE ART Vasculopathies Affecting the Eye Judith E. A. Warner, MD Abstract: The retinal arteries and veins may be involved in isolation or as the result of a systemic vasculitis. This article emphasizes neurologic diseases in which the ocular vasculature is affected. ( JNeuro- Ophthalmol 2004; 24: 164- 169) Vasculopathies that involve the eye may be the result of infectious, hereditary, inflammatory, neoplastic, hypoxic/ ischemic, or idiopathic disorders. In some cases, the vasculopathies are isolated to the eye; in other cases, the involvement is system- wide ( Table 1). INFECTIOUS VASCULOPATHIES In most infectious vasculopathies, the association be­tween infection and vasculopathy is speculative. There are few ophthalmoscopic features of the infectious or para­infectious retinal vasculitides that enable distinction. His­tory and laboratory testing are usually necessary to confirm a diagnosis. Human immunodeficiency virus ( HlV)- associated vasculopathy is often included among infectious vasculo­pathies but its vascular manifestations may not be mediated by infection. Patients are usually asymptomatic but may have color or contrast sensitivity deficits. On routine exami­nation, they are found to have cotton- wool spots and intra-retinal hemorrhages in the posterior pole, believed to be a manifestation of microvasculopathy of the retina. The cot­ton- wool spots differ from those seen in diabetes in being more linear, often taking on a boomerang shape ( 1) ( Fig. 1). Lesions resolve spontaneously, usually within two months ( 2). Although the prevalence of HIV- associated vasculop­athy increases with decreasing CD4 counts, it can be seen in Department of Ophthalmology and Visual Sciences, University of Utah Health Sciences Center, Salt Lake City, Utah. Address correspondence to Judith E. A. Warner, Department of Oph­thalmology and Visual Sciences, John A. Moran Eye Center, 50 North Medical Drive, Salt Lake City, UT 84132; E- mail: Judith. warner@ hsc. utah. edu Supported in part by a grant from Research to Prevent Blindness, Inc., New York, New York, to the Department of Ophthalmology and Visual Sciences, University of Utah. Modified from an oral presentation delivered at the 28th Annual Meet­ing of the North American Neuro- Ophfhalmology Society, Copper Moun­tain, Colorado, February 12, 2002. patients whose counts are more than 100 cells/ mm3, a level at which cytomegalovirus ( CMV) retinitis is unlikely. Therefore, the practice in HIV centers is to perform re­peated examination on patients who have cotton- wool spots and CD4 counts more than 100 cells/ mm3 ( 3). If the abnormal fundus findings are a result of CMV retinitis, they will worsen within two to three weeks. If they are caused by HIV- associated vasculopathy, the original cotton- wool spots will resolve, although new spots may develop. HIV- associated vasculopathy may be related to the propensity of the virus to infect endothelial cells. Elevated levels of endothelin- 1 immunoreactivity have been found, possibly causing vasoconstrictor activity ( 4). One interest­ing study ( 5) correlated the presence of HIV- associated retinal vasculopathy with HMPAO- SPECT evidence of re­duced cerebral perfusion. The association was not corre­lated with acquired immune deficiency syndrome staging. The authors speculated that this reduced perfusion might explain neuropsychologic abnormalities experienced by patients with HIV- 1 disease ( 5). When hemorrhages are ex­tensive, anemia should be considered an explanation for the cotton- wool spots. HEREDITARY VASCULOPATHIES In 1988, Grand et al ( 6) described a kindred of pa­tients with variable expression of an inherited cerebroreti-nal vasculopathy. These patients had subtle changes of the vasculature of the posterior pole most suggestive of parafoveal telangiectasia. Vision was relatively preserved, although preretinal hemorrhages occurred late in the dis­ease. On fluorescein angiography, the foveal avascular zone was enlarged with capillary obliteration. Pathologi­cally, there were multiple scattered microinfarctions, but no abnormalities of the retinal capillaries were discovered. Of 18 presumably affected individuals, 10 had brain masses, eight in the frontoparietal region. The masses were typi­cally confined to the white matter and were histologically characterized by vascular abnormalities and coagulation necrosis. The vascular abnormalities were found in the me­dium and small arteries, and consisted of fibrinoid necrosis of vessel walls. Perivascular adventitial fibrosis was promi­nent. Since 1988, several cases have been described with similar features ( 7,8). In most cases, a familial feature is evident. 164 J Neuro- Ophthalmol, Vol. 24, No. 2, 2004 Vasculopathies Affecting the Eye JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 FIG. 1. HIV- associated vasculopathy. Note the boomer­ang- shaped cotton- wool spots. ( Courtesy of Paul Zimmer­man, MD.) In 1997, Jen et al ( 9) described a family with heredi­tary endotheliopathy including retinopathy ( Fig. 2), ne­phropathy, and stroke. In 1998, a Dutch family with heredi­tary vascular retinopathy associated with Raynaud phenomenon and migraine was described by Terwindt et al ( 10). In 2001, Ophoff et al ( 11) were able to show that these three disparate families had linkage to chromosome 3p21.1- 21.3. Of the various features of the three diseases, the retinopathy was most tightly linked to the same region. Further elucidation of the gene and its encoded protein may be very interesting. INFLAMMATORY VASCULOPATHIES Inflammatory choriocapillaropathies such as mul­tiple evanescent white dot syndrome, acute posterior multifocal placoid pigment epitheliopathy ( APMPPE), multifocal choroiditis, and acute idiopathic blind spot en­largement all manifest focal areas of retinal dysfunction and a weak correlation between funduscopic abnormalities and visual dysfunction. Some observers believe that areas of hy-pofluorescence seen on indocyanine green angiography suggest a vascular abnormality in the choroidal circulation ( 12). In some cases, fluorescein angiography shows retinal vascular staining consistent with vasculitis. APMPPE has been reported in several patients who also have Wegener granulomatosis ( 13) or other autoimmune diseases. APMPPE has also been frequently associated with central nervous system manifestations, including headache, vasculitis, stroke, and sagittal sinus thrombosis ( 14,15). There is a case report of a young woman who developed bilateral central retinal vein occlusions one month after presentation with APMPPE ( 16). Retinal venous sheathing is an infrequent but well-recognized phenomenon in multiple sclerosis ( MS). A care­ful study from Liverpool in 1996 ( 17) documented the course of retinal venous sheathing in 23 patients with MS folio wed- up over six months. Six of the patients had venous abnormalities, including diffuse or focal sheathing or focal perivenous hemorrhages. One patient had arterial sheath­ing. For the most part, the venous sheathing/ staining was static over six months, despite ongoing disease activity on enhanced magnetic resonance imaging ( MRI) scans. Two patients showed resolution of retinal angiographic fluores­cein leakage over the course of the study. The relationship between retinal vascular abnormalities and the disease course of MS remains to be elucidated. NEOPLASTIC VASCULOPATHIES Neoplasms and their treatments are notorious for pro­ducing vasculopathies via hypercoagulable states, radiation injury, or toxic chemotherapeutic regimens. Mild micro­vascular occlusive changes are seen commonly in associa­tion with leukemia. Plasma cell dyscrasias such as multiple myeloma, Waldenstrom macroglobulinemia, and systemic amyloidosis are associated with a variety of ophthalmic manifestations. There is an interesting report ( 18) of a plasma cell dyscrasia resulting in systemic deposition of light chains in the kidney and the eye. In this case, the pa­tient presented with constitutional symptoms, bilateral re­cent carpal tunnel surgery, and severe retinal nonperfusion. The patient had bilateral intraretinal hemorrhages, cotton­wool spots, and neovascularization of the discs. Fluorescein angiography showed capillary nonperfusion, but no venous stasis was reported. Specific staining for light chains re­vealed extensive deposition in the blood vessels of various biopsy specimens. Testing for hyperviscosity, including cryoglobulins, cryofibrinogen, quantitative immunoglobu­lins, and serum viscosity, was negative. The well- described carcinoma- associated retinopa­thy ( CAR) and melanoma- associated retinopathy ( MAR) frequently show severe retinal vascular attenuation. There have been several reports of presumed paraneoplastic ret­inopathies with diffuse retinal vessel staining on fluores­cein angiography, particularly involving veins ( 19,20). Although treatment with corticosteroids resulted in im­provement in the vasculitic features, there was no improve­ment in vision. One patient had melanoma- associated reti­nal bipolar cell antibodies in his IgG serum fractions ( 19); the other patient had small cell lung cancer and serum reac­tivity to the 62kd ( rather than the typical 23kd) band of bo­vine retinal homogenate ( 20). Retinal vasculitis is rare in the CAR/ MAR syndromes, and its presence does not seem to be the major pathologic change. However, vasculitis as a neoplastic and paraneoplastic phenomenon occurs in a wide variety of cancers. 165 JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 Warner TABLE 1. Vasculopathies affecting the eye Hereditary Retinitis pigmentosa- associated ( 28) Cerebroretinal vasculopathy with brain masses ( Grand syndrome) ( 6,7,8) Hereditary endotheliopathy with retinopathy, nephropathy, and stroke ( HERNS) ( 9) Hereditary vascular retinopathy with migraine and Raynaud phenomenon ( 10) Inherited retinal arteriolar tortuosity ( 29) Amyloidosis ( 30) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy CADASIL ( 31) Inflammatory Birdshot retinochoroidopathy ( 32) Sarcoidosis ( 33) Multiple sclerosis ( 17) Multiple evanescent white dot syndrome Acute posterior multifocal placoid pigment epitheliopathy ( 14,15) Acute idiopathic blind spot enlargement ( 34) Behcet disease ( 35,36) Wegener granulomatosis ( 13) Inflammatory bowel disease ( 37,38) Giant cell arteritis ( 39) Systemic lupus erythematosus ( 40) Rheumatoid arthritis ( 41,42) Polyarteritis nodosa ( 43) Churg- Strauss syndrome ( 44,45) Infectious Human immunodeficiency virus ( 1- 5) Herpes viruses Progressive outer retinal necrosis ( 46,47) Vasculopathy of herpes zoster ophthalmicus ( 48) Tuberculosis ( 49) Lyme disease ( 50) Cat- scratch disease ( 51) Leptospirosis ( 52) Cytomegalovirus ( 53,54) Cryptococcosis ( 55) Rubella ( 56) Measles/ SSPE ( 57) Wuchereria bancrofti ( filariasis) ( 58) Neoplastic Acute lymphocytic leukemia ( 59) Hairy cell leukemia ( 60) Systemic light chain disease ( 18) Hyperimmunoglobulin D ( 61) Carcinoma- associated retinopathy ( 20) Melanoma- associated retinopathy ( 19) 166 TABLE 1. Continued Hypoxic/ Ischemic Ocular ischemic syndrome ( 62,63) Exfoliation syndrome ( 21,64) Takayasu arteritis ( 65,66) Toxic Ergot alkaloids ( 67) Cranial/ orbital irradiation ( 68,69) Idiopathic Eales disease ( 27) Idiopathic polypoidal choroidal vasculopathy ( 70) Idiopathic retinal vasculitis, aneurysms, and neuro- retinitis ( 71) Parafoveal telangiectasia ( 72) Idiopathic recurrent branch retinal artery occlusions ( 26) Susac syndrome ( 22- 25) HYPOXIC/ ISCHEMIC VASCULOPATHIES Neovascularization is an abnormal vascular prolif­eration in response to hypoxia. It is a well- recognized late effect of ocular ischemic syndrome caused by carotid dis­ease, diabetes, hypertension, or after central retinal vein oc­clusion. Neovascular vessels can occur in various structures of the eye, including retina, optic nerve head, and iris. Iris vasculopathy is a feature of exfoliation syndrome. In this case, the stimulus for micro- neovascularization appears to be deposition of exfoliation material in vessels progressing from the adventitia to the endothelium, resulting in oblit­eration of the lumen and consequent anterior chamber hyp­oxia ( 21). IDIOPATHIC VASCULOPATHIES Among the idiopathic vasculopathies is Susac syn­drome, or retinocochleocerebral microangiopathy of the brain and retina. Originally reported by Susac in 1979 ( 22), and later elaborated by O'Halloran ( 23), among others, it is a perplexing condition typically affecting young women. Patients have multiple, usually bilateral, branch retinal ar­tery occlusions ( Fig. 3), hearing loss attributed to cochlear arterial occlusion, and central nervous system abnormali­ties characterized as encephalopathy, memory loss, and headache. MRIs usually show lesions within the corpus cal-losum and cerebral gray matter. The CSF shows elevated protein and often mononuclear cells. Brain biopsies have shown microinfarcts, some with evidence of perivascular inflammatory infiltrates. Petty et al ( 24) found sparse peri-arteriolar inflammatory cells on muscle biopsies in three of five patients. In one specimen, swollen vascular endo­thelium nearly occluded some small arterioles. The disease can remain active for several months to several years, and may remit spontaneously. However, a recently re- © 2004 Lippincott Williams & Wilkins Vasculopathies Affecting the Eye JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 FIG. 2. Hereditary endotheliopathy including retinopathy, nephropathy, and stroke. Fluorescein angiogram shows parafoveal telangiectasia, microaneurysms, and capillary dropout. ( Courtesy of R. W. Baloh, MD.) ported case documented recrudescence after a hiatus of 18 years ( 25). In 1986, Gass et al ( 26) reported a small series of pa­tients with idiopathic recurrent branch retinal artery occlu­sions. There were nine patients, seven of whom were men, with recurrent arterial occlusions, no uveitis, and in whom systemic evaluation was unrevealing. There was no evi­dence of embolic material. Again, the features on fluores­cein angiography were retinal arterial/ venous staining with FIG. 3. Susac syndrome. Fluorescein angiogram shows multiple branch retinal artery occlusions. ( Courtesy of H. O'Halloran, MD.) FIG. 4. Eales disease. Fluorescein angiogram shows hyper-fluorescence of peripheral veins. ( Courtesy of Paul S. Bern­stein, MD, PhD.) capillary non- perfusion. Three patients ( one woman and two men) had auditory complaints ( auditory hallucinations 1, tinnitus 2). Perhaps they represent a forme fruste of Su­sac syndrome. Eales disease is a noninflammatory occlusive disor­der of the retinal vasculature that causes recurrent hemor­rhages in the retina and vitreous and ischemic changes in the eye. Most patients are men in the fourth decade of life. It may represent a tissue response to bacterial or tubercular antigens. Central nervous system manifestations were re­ported in six of 17 patients ( 27). Fluorescein angiography shows peripheral non- perfusion and retinal venous staining ( Fig. 4), which appears to be a step along the path towards neovascularization, hemorrhages, and progressive visual loss. REFERENCES 1. Jaworski C. Morphology of the HIV versus the diabetic cotton wool spot. Optom Vis Sci 2000; 77: 60CM1. 2. Kuppermann BD, Petty JG, Richman DD, et al. Correlation be­tween CD4+ Counts and prevalence of cytomegalovirus retinitis and human immunodeficiency virus- related noninfectious retinal vasculopathy in patients with acquired immunodeficiency syn­drome. Am J Ophthalmol 1993; 115: 575- 82. 3. Kuppermann BD. Noncytomegalovirus- related chorio- retinal manifestations of the acquired immunodeficiency syndrome. Semin Ophthalmol 1995; 10: 125- 41. 4. Rolinski B, Geier SA, Sadri I, et al. Endothelin- 1 immunoreactivity in plasma is elevated in HIV- 1 infected patients with retinal mi­croangiopathic syndrome. Clin Investig 1994; 72: 288- 93. 5. Geier SA, Schielke E, Tatsch K, et al. Brain HMPAO- SPECT and ocular microangiopathic syndrome in HIV- 1- infected patients. AIDS 1993; 7: 1589- 94. 6. Grand MG, Kaine J, Fulling K, et al. Cerebroretinal vasculopathy: A new hereditary syndrome. Ophthalmology 1988; 95: 64- 59. 167 JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 Warner 7. Weil S, Reifenberger G, Dudel C, et al. Cerebroretinal vasculopathy mimicking a brain tumor: A case of a rare hereditary syndrome. Neurology 1999; 53: 629- 31. 8. Niedermayer I, Reiche W, Graf N, et al. Cerebroretinal vasculopa­thy and leukoencephalopathy mimicking a brain tumor. Report of two early- onset cases with Fanconi's anemia- like phenotypes sug­gesting an autosomal- recessive inheritance pattern. Clin Neuro-pathol 2000; 19: 285- 95. 9. Jen J, Cohen AH, Yue Q, et al: Hereditary endotheliopathy with retinopathy, nephropathy and stroke ( HERNS). Neurology 1997; 49: 1322- 1330. 10. Terwindt GM, Haan J, Ophoff RA, et al: Clinical and genetic analy­sis of a large Dutch family with autosomal dominant vascular reti­nopathy, migraine and Raynaud's phenomenon. Brain 1998; 121: 303- 316. 11. Ophoff RA, DeYoung J, Service SK, et al. Hereditary vascular ret­inopathy, cerebroretinal vasculopathy, and hereditary endotheli­opathy with retinopathy, nephropathy, and stroke map to a single locus on chromosome. Am J Hum Genet 2001; 69: 447- 53. 12. Cimino L, Auer C, Herbort CP. Sensitivity of indocyanine green angiography for the follow- up of active inflammatory choriocapil-laropathies. OculImmunolInflamm 2000; 8: 275- 83. 13. Kinyoun JL. APMPPE associated with Wegener's granulomatosis. Retina 2000; 20: 19- 20. 14. Comu S, Verstraeten T, Rinkoff JS, et al. Neurological manifesta­tions of acute posterior multifocal placoid pigment epitheliopathy. Stroke 1996; 27: 996- 1001. 15. O'Halloran HS, Berger JR, Lee WB, etal. Acute multifocal placoid pigment epitheliopathy and central nervous system involvement: nine new cases and a review of the literature. Ophthalmology 2001; 108: 861- 8. 16. Allee SD, Marks SJ. Acute posterior multifocal placoid pigment epitheliopathy with bilateral central retinal vein occlusion. Am J Ophthalmol 1998; 126: 309- 12. 17. Birch MK, Barbosa S, Blumhardt LD, et al. Retinal Venous Sheath­ing and the blood- retinal barrier in multiple sclerosis. Arch Ophthal­mol 1996; 114: 34- 9. 18. EnzenauerRJ, StockJG, EnzenauerRW, etal. Retinal vasculopathy associated with systemic light chain deposition disease. Retina 1990; 10: 115- 8. 19. Remulla JFC, Pineda R, Gaudio AR, et al: Cutaneous melanoma associated retinopathy with retinal periphlebitis. Arch Ophthalmol 1995; 113: 854- 5. 20. Suzuki T, Obara Y, Sato Y, et al: Cancer- associated retinopathy with presumed vasculitis. Am J Ophthalmol 1996; 122: 125- 7. 21. Helbig H, Schlotzer- Schrehardt U, Noske W, et al: Anterior-chamber hypoxia and iris vasculopathy in pseudoexfoliation syn­drome. Geriatr J Ophthalmol 1994; 3: 148- 53. 22. Susac JO, Hardman JM, Selhorst JB. Microangiopathy of the brain and retina. Neurology 1979; 29: 313- 6. 23. O'Halloran HS, Pearson PA, Lee WB, et al. Microangiopathy of the brain, retina and cochlea ( Susac syndrome): A report of five cases and a review of the literature. Ophthalmology 1998; 105: 1038^ 14. 24. Petty GW, Engel AG, Younge BR, et al. Retinocochleocerebral Vasculopathy. Medicine 1998; 77: 12- 40. 25. Petty GW, Matteson EL, Younge BR, et al: Recurrence of Susac syndrome ( retinocochleocerebral vasculopathy) after remission of 18 years. Mayo Clin Proc 2001; 76: 958- 60. 26. Gass JD, Tiedeman J, Thomas MA, et al: Idiopathic recurrent branch retinal arterial occlusion. Ophthalmology 1986; 93: 1148- 57. 27. White RH. The etiology and neurologic complications of retinal vasculitis. Brain 1961; 84: 262- 73. 28. Fogle JA, Welch RB, Green WR. Retinitis pigmentosa and exuda­tive vasculopathy. Arch Ophthalmol 1978; 96: 696- 702. 29. Sears J, Gilman J, Sternberg P Jr. Inherited retinal arteriolar tortu­osity with retinal hemorrhages. Arch Ophthalmol 1998; 116: 1185- 8. 30. Noble KG. Bilateral multifocal retinal arteriolar sheathing as the only ocular finding in hereditary amyloidosis. Am J Ophthalmol 1998; 125: 111- 3. 31. Robinson W, Galetta SL, McCluskey L, et al. Retinal findings in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ( cadasil). Surv Ophthalmol. 2001; 45: 445- 8. 32. Cassoux N, Lehoang P. Birdshot retinochoroidopathy ( in French). Ann Med Interne ( Paris). 2000; 151: lS45- 7. 33. Verougstraete C, Snyers B, Leys A, et al. : Multiple arterial ectasias in patients with sarcoidosis and uveitis. Am J Ophthalmol 2001; 131: 223- 31. 34. Volpe NJ, Rizzo JF 3rd, Lessell S. Acute idiopathic blind spot en­largement syndrome: a review of 27 new cases. Arch Ophthalmol 2001; 119: 59- 63. 35. Dominguez LN, Irvine AR. Fundus changes in Behcet's disease. Trans Am Ophthalmol Soc 1997; 95: 367- 86. 36. el Belhadji M, Hamdani M, Laouissi N, et al. Ophfhalmological involvement in Behcet disease. Apropos of 520 cases ( in French). JFr Ophtalmol 1997; 20: 592- 8. 37. Ruby AJ, Jampol LM. Crohn's disease and retinal vascular disease. Am J Ophthalmol 199015; 110: 349- 53. 38. Salmon JF, Ursell PG, Frith P. Neovascular glaucoma as a compli­cation of retinal vasculitis in Crohn disease. Am J Ophthalmol. 2000; 130: 528- 30. 39. Hayreh SS, Podhajsky PA, Zimmerman B. Occult giant cell arteri­tis: ocular manifestations. Am J Ophthalmol 1998; 125: 521- 6. 40. Read RW, Chong LP, Rao NA. Occlusive retinal vasculitis associ­ated with systemic lupus erythematosus. Arch Ophthalmol 2000; 118: 588- 9. No abstract available. 41. George RK, Walton RC, Whitcup SM, et al. Primary retinal vascu­litis. Systemic associations and diagnostic evaluation. Ophthalmol­ogy 1996; 103: 384- 9. 42. Giordano N, D'Ettorre M, Biasi G, et al. Retinal vasculitis in rheu­matoid arthritis: an angiographic study. Clin Exp Rheumatol. 1990: 8: 121- 5. 43. Akova YA, Jabbur NS, Foster CS. Ocular presentation of poly­arteritis nodosa. Clinical course and management with steroid and cytotoxic therapy. Ophthalmology 1993; 100: 1775- 81. 44. Dagi LR, Currie J. Branch retinal artery occlusion in the Churg- Strauss syndrome. J Clin Neuroophthalmol 1985; 5: 229- 37. 45. Takanashi T, Uchida S, Arita M, et al. Orbital inflammatory pseu­dotumor and ischemic vasculitis in Churg- Strauss syndrome: report of two cases and review of the literature. Ophthalmology 2001: 108: 1129- 33. 46. Oshitari K, Arimoto H, Suzuki S, et al. Rapidly progressive outer retinal necrosis in a patient with acquired immunodeficiency syn­drome ( in Japanese). Nippon Ganka Gakkai Zasshi 1994; 98: 1141- 6. 47. Kashiwase M, Sata T, Yamauchi Y, et al. Progressive outer retinal necrosis caused by herpes simplex virus type 1 in a patient with acquired immunodeficiency syndrome. Ophthalmology 2000: 107: 790^ 1. 48. Wilson CA, Wander AH, Choromokos EA. Central retinal artery obstruction in herpes zoster ophthalmicus and cerebral vasculopa­thy. Ann Ophthalmol 1990; 22: 347- 51. 49. Gupta A, Gupta V, Arora S, et al. PCR- positive tubercular retinal vasculitis: clinical characteristics and management. Retina 2001; 21: 435- 44. 50. Mikkila HO, Seppala IJ, Viljanen MK, et al. The expanding clinical spectrum of ocular lyme borreliosis. Ophthalmology 2000: 107: 581- 7. 51. Soheilian M, Markomichelakis N, Foster CS. Intermediate uveitis and retinal vasculitis as manifestations of cat scratch disease. Am J Ophthalmol 1996; 122: 582^ 1. 52. Martins MG, Matos KT, da Silva MV, et al. Ocular manifestations in the acute phase of leptospirosis. Ocul Immunol Inflamm 1998; 6: 75- 9. 53. Digre KB, Blodi CF, Bale JF. Cytomegalovirus infection in a healthy adult associated with recurrent branch retinal artery occlu­sion. Retina 1987; 7: 230- 2. 54. Rodrigues MM, Palestine A, Nussenblatt R, et al. Unilateral cyto­megalovirus retinochoroiditis and bilateral cytoid bodies in a 168 © 2004 Lippincott Williams & Wilkins Vasculopathies Affecting the Eye JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 bisexual man with the acquired immunodeficiency syndrome. Oph­thalmology 19S4; 91( lSupp\): 1511- S2. 55. Saran BR, Pomilla PV. Retinal vascular nonperfusion and retinal neovascularization as a consequence of cytomegalovirus retinitis and cryptococcal choroiditis. Retina 1996; 16: 510- 2. 56. Riikonen RS. Retinal vasculitis caused by rubella. Neuropediatrics 1995; 26: 174- 6. 57. Salmon JF, Pan EL, Murray AD. Visual loss with dancing extremi­ties and mental disturbances. Surv Ophthalmol 1991; 35: 299- 306. 58. Gupta A, Agarwal A, Dogra MR. Retinal involvement in Wucheria bancrofti filariasis. Acta Ophthalmol ( Copenh). 1992; 70: 832- 5. 59. Wiznia RA, Rose A, Levy AL. Occlusive microvascular retinopa­thy with optic disc and retinal neovascularization in acute lympho­cytic leukemia. Retina 1994; 14: 253- 5. 60. Di Maria A, Redaelli C, Canevari A, et al. Unilateral retinal vascu­litis associated with hairy cell leukaemia: immunogenetic study. Ophthalmologica 1998; 212: 355- 7. 61. Kumano Y, Nagato T, Kurihara K, et al. : Hyperimmunoglobuline-mia D in idiopathic retinal vasculitis. Graefes Arch Clin Exp Oph­thalmol 1997; 235: 372- 8. 62. Biousse V. Carotid disease and the eye. Curr Opin Ophthalmol 1997; 8: 16- 26. Review. 63. Dhooge M, de Laey JJ. The ocular ischemic syndrome. Bull Soc Beige Ophtalmol 1989; 231: 1- 13. 64. Ritch R, Schlotzer- Schrehardt U. Exfoliation syndrome. Surv Oph­thalmol 2001; 45: 265- 315. 65. Baba T, Itakura K, Tanaka R, et al. Importance of fluorescein an­giographic study in evaluating early retinal changes in Takayasu disease. Jpn J Ophthalmol 1999; 43: 546- 52. 66. Karam EZ, Muci- Mendoza R, Hedges TR 3rd. Retinal findings in Takayasu's arteritis. Acta OphthalmolScand 1999; 77: 209- 13. 67. Mindel JS, Rubenstein AE, Franklin B. Ocular ergotamine tartrate toxicity during treatment of Vacor- induced orthostatic hypotension. Am J Ophthalmol 1981; 92: 492- 6. 68. Brown GC, Shields JA, Sanborn G, et al. Radiation retinopathy. Ophthalmology 1982; 89: 1494- 501. 69. Brown GC, Shields JA, Sanborn G, et al. Radiation optic neuropa­thy. Ophthalmology 1982; 89: 1489- 93. 70. Yannuzzi LA, Sorenson J, Spaide RF, et al. Idiopathic polypoidal choroidal vasculopathy ( IPCV). Retina 1990; 10: 1- 8. 71. Chang TS, Aylward GW, Davis JL, et al. Idiopathic retinal vascu­litis, aneurysms, and neuro- retinitis. Retinal Vasculitis Study. Oph­thalmology 1995; 102: 1089- 97. 72. Hutton WL, Snyder WB, Fuller D, et al. Focal parafoveal retinal telangiectasis. Arch Ophthalmol 1978; 96: 1362- 7. 169