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Occlusive Retinal Arteriolitis with Neovascularization
OCCLUSIVE RETINAL ARTERIOLITIS W I T H NEOVASCULARIZATION L E E M. J A M P O L , M.D., S H E R W I N J. I S E N B E R G , AND M O R T O N F. G O L D B E R G , M.D. Chicago,
Retinal vasculitis can be seen in associ ation with uveitis or can be a manifesta tion of systemic disease. 1,2 On occasion a primary retinal vasculitis is seen unac companied by uveal inflammation or de tectable systemic disease. 1 - 3 The majority of cases of this idiopathic vasculitis (sometimes referred to as Eales's disease) occur in patients with retinal phlebitis that involves either peripheral venules or the central retinal vein. In some cases, however, the retinal vasculitis involves both the retinal arterioles and venules or rarely involves just the arterioles. This report describes a young woman with a progressive bilateral occlusive retinal arteriolitis, which has shown spontaneous remissions and exacerbations and at pre sent is quiescent without therapy.
M.D.,
Illinois electroencephalogram, and skull x-ray films was normal. The VDRL was nonreactive. The patient was discharged with a diagnosis of right optic atrophy of uncertain cause. The patient had no visual problems until July 17, 1974, when she noted the onset of shadows in front of her left eye. She was still taking the same oral contraceptive agent. Eye evaluation here revealed visual acuity of 20/25 in both eyes. The pupil in each eye was 3 mm wide and briskly reactive to light. The right anterior chamber showed trace flare and cells, and the left anterior chamber had trace flare. This was the only time during the patient's examination that anterior chamber abnormalities were noted. Intraocular pressures were normal. Vis ual field testing in the right eye again showed irregular loss of nasal field. Field testing in the left eye showed irregular constriction of the field superotemporally with inferior and superior arcuate scotomata. No central scotoma could be demonstrated. An examination of the right fundus showed loca lized arteriolar tortuosity and definite evidence of an old superotemporal arteriolar occlusion (Figs. 1 and 2). The blood column in the superonasal arteriole appeared dark suggesting stagnation of blood flow (Fig. 1). There was extensive capillary loss in the
CASE REPORT A 34-year-old white woman was in excellent health until August 1971, when she noted the sud den onset of nasal visual field loss in the right eye, accompanied by a headache. The patient's medical history revealed that she was gravida 6, para 6, and had been using dimethisterone with ethinyl estradiol (Oracon) birth control pills for six years. One year previously she had a urinary tract infection and was noted to have a double ureter on the right. She was also allergic to penicillin. Visual acuity was R.E.: 20/100, and L.E.: 20/20. External examination, slitlamp biomieroscopy, and intraocular pressures by applanation tonometry were normal. Visual field testing in the right eye revealed loss of inferonasal field. The left visual field was normal. Ophthalmoscopic examination of the right eye showed a pale disk. A white line was described in the retina near the superotemporal vein. The left fundus was nor mal. Neurologic evaluation including a brain scan,
From the University of Illinois Eye and Ear Infirmary, Chicago, Illinois. This study was sup ported in part by National Institutes of Health Postdoctoral Fellowship 1-F22-HL00812-01. Reprint requests to Lee M. Jampol, M.D., Kimbrough Army Hospital, Ophthalmology Clinic, Fort Meade, MD 20755.
Fig. 1 (Jampol, Isenberg, and Goldberg). Right eye, July 30. Two areas of marked arteriolar tortuosi ty are present (large arrows). A white line corre sponding to an occluded superotemporal arteriole is seen (small arrows). The blood column in the super onasal arteriole is dark, suggesting sluggish blood flow.
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Fig. 2 (Jampol, Isenberg, and Goldberg). Right eye. Distal segment of occluded siiperotemporal arteriole is seen (arrows).
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Fig. 4 (Jampol, Isenberg, and Goldberg). Early arterial phase of fluorescein angiogram showing filling of neovascularization and absence of normal capillary filling.
superotemporal quadrant with an area of neovascul arization with a sea-fan-like configuration (Fig. 3). This sea fan was fed by a tortuous irregular arteriolar feeder (Fig. 4) originating from the superonasal vessels. Late phase fluorescein angiography showed leakage from the sea fan in the right eye (Fig. 5). The right disk appeared pale but no evidence of active vasculitis was seen in the right eye. Examination of the left eye showed disk edema (Fig. 6). Cotton-wool spots, periarteriolar exudation, and arteriolar sheath ing were present in the peripapillary area and the
Fig. 5 (Jampol, Isenberg, and Goldberg). Right eye. Late phase fluorescein angiogram demonstrates leakage from neovascularization.
Fig. 3 (Jampol, Isenberg, and Goldberg). Right eye. Area of sea fan neovascularization in supero temporal periphery.
midperiphery (Figs. 6-8). Arteriolar blood again appeared dark suggesting sluggish flow (Fig. 8). The retinal veins were slightly dilated and irregular, but there was no venous sheathing or periphlebitis. By fluorescein angiography, three small arterioles in the left eye were occluded (Fig. 9). Late phase angiogra phy showed intense staining of the disk and arteri ole walls (Fig. 10). In a few areas minimal staining of the venular walls was noted as well. The patient was admitted to the hospital and had an extensive medical evaluation. Use of the oral contraceptive agent was permanently discontinued.
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Fig. 6 (Jampol, Isenberg, and Goldberg). Left eye, July 30. Posterior pole. Edematous disk with peripapillary cotton-wool spots and periarteriolar sheathing.
Fig. 7 (Jampol, Isenberg, and Goldberg). Left eye. Periarteriolar sheathing is visible along the supero temporal arteriole. Physical examinations including neurologic, der matologie, and hématologie consultations were nor mal. Brain scan, electroencephalogram, and skull x-ray films with optic foramen views were normal. A chest x-ray film showed some scarring at the base of the right lung consistent with old granulomatous disease. An intermediate strength purified protein derivative (PPD) was positive (20 mm induration) while skin testing for histoplasmosis was negative. Sputum cultures for acid-fast bacilli were negative.
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Fig. 8 (Jampol, Isenberg, and Goldberg). Left eye. Superotemporal quadrant showing periarteriolar "cuffing" (arrows) and slight venous irregularity. The arteriolar blood column is again dark.
Fig. 9 (Jampol, Isenberg, and Goldberg). Left eye, July 30. Fluorescein angiogram demonstrating three occluded arterioles (arrows). Normal results were obtained from liver function tests and chemical analyses of the blood, including glucose, blood urea nitrogen (BUN), creatinine, cal cium, and electrolytes. The VDRL for syphilis and FTA-ABS were nonreactive. Serum protein meas urements including quantitative immunoglobulin determinations were normal. No cryoglobulins were present. An indirect fluorescent antibody test for toxoplasmosis was negative. Urinalysis was normal; the urine contained no Bence Jones proteins. The white blood cell count was 8,300/mm 3 with a normal differential. The hematocrit level was 42%. Hemo-
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Fig. 10 (Jampol, Isenberg, and Goldberg). Left eye. Late-phase fluorescein angiogram shows stain ing of disk and arteriole walls. globin electrophoresis showed hemoglobin AA. The latex fixation, rheumatoid factor, antinuclear factor, and lupus erythematosus preparations were nega tive. The sedimentation rate was elevated (42 mm/hr arid 40 mm/hr on two occasions). A lumbar puncture showed a normal pressure, normal lymphocyte count (1/mm 3 ), and normal glucose and chloride levels. The protein level was 53 mg/100 ml (normal, 10 to 40 mg/100 ml). A cerebrospinal fluid VDRL was nonreactive. A muscle-skin biopsy of the left anterior thigh showed no evidence of vasculitis. In
Fig. 11 (Jampol, Isenberg and Goldberg). Left eye, Sept. 9. Inferonasal arteriole coming off the disk at 7 o'clock is more tortuous with total loss of a branch arteriole. Arteriole coming off the disk at 8 o'clock (highest arrow, Fig. 9) is no longer perfused.
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summary, the only abnormal findings were the ele vated sedimentation rate, a positive PPD, and old pulmonary scarring. The patient was observed but not treated, and there was no change in the findings in the right eye. In the left eye several additional branch arterioles occluded and a remaining arteriole inferonsal to the disk became more tortuous (Fig. 11). There was no loss of central vision or further field loss. Several weeks later the disk edema had resolved and the retinal arteriolitis diminished (Fig. 12). Periarterio lar sheathing disappeared (Fig. 13). We used argon laser photocoagulation to close the sea fan in the right eye by treating the feeding arteriole and then the draining venule. After two treatment sessions, the neovascularization was no longer perfused (Fig. 14). The patient has had no evidence of active retinal vasculitis since December 1974. However, the sedi mentation rate has remained elevated (24 to 33 mm/hr). The antinuclear factor has been repeatedly negative. When she was examined Sept. 12, 1975, a test for hepatitis-associated antigen (Australian anti gen) was negative. Results of serum complement measurements including Clq, C3, C4, and C5 were normal. DISCUSSION
Retinal vasculitis is a manifestation of systemic diseases such as temporal arteritis, Takayashu's disease, polyarteritis, lupus erythematosus, multiple sclerosis, and systemic viral infections. 1 · 2 It has
Fig. 12 (Jampol, Isenberg, and Goldberg). Left eye, Dec. 4. Disk edema is gone. Cotton-wool spots and periarteriolar exudation are no longer visible (compare with Fig. 6).
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Fig. 13 (Jampol, Isenberg, and Goldberg). Left eye, Dec. 4. Superotemporal arteriole is visible (compare with Fig. 7). Sheathing has disappeared.
Fig. 14 (Jampol, Isenberg, and Goldberg). Right eye. Fluorescein angiogram showing absence of perfusion of neovascularization following argon laser photocoagulation (compare with Figs. 4 and 5).
also been associated with tuberculosis, sarcoidosis, syphilis, Behçet's disease, toxoplasmosis, cytomegalic inclusion dis ease, Wegener's granulomatosis, and pe ripheral uveitis (pars planitis). 1 - 4 Most of these cases of vasculitis involve exclu sively or primarily the retinal veins.
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Eales's disease is a vaso-obliterative vas culitis seen usually in young males. 5 - 1 0 The phlebitis in this disease is often bilat eral and can lead to retinal neovascular ization, vitreous hemorrhages, and retinal detachment. Retinal phlebitis usually in volves peripheral retinal venules, but some authors have described the in flammation of the central retinal vein, so-called papillophlebitis. 1 1 - 1 5 Retinal vasculitis can involve primarily or exclu sively the retinal arterioles. 1 · 1 6 - 1 8 Some of these patients have systemic vas cular diseases such as lupus erythematosus. 1 8 , 1 9 Retinal arteriolitis is distin guished from segmental retinal periarteritis 20 where discrete white plaques are deposited along the walls of the retinal arterioles. Two cases recently reported by Karel and colleagues 17 showed an occlusive idiopathic retinal arteriolitis similar to our case. The dis ease in these patients also led to retinal neovascularization. A similar case of reti nal vasculitis has been published. 2 1 Our patient had a progressive oblitera tion of her retinal arterioles from a retinal arteriolitis. An extensive medical evalua tion showed only an elevated sedimenta tion rate and inactive pulmonary disease with no evidence of systemic vascular disease. Repeated evaluations for system ic lupus erythematosus including testing for antinuclear factor, lupus erythemato sus preparations, a muscle-skin biopsy, and serum complement determinations were unrevealing. Although our patient may ultimately show evidence of system ic vascular disease, we have not seen this in the four years since the onset of her ocular problems. The vasculitis of Eales's disease has been attributed to tuberculous infection or allergy to tuberculoprotein. 1 0 Although our patient did have a positive PPD and pulmonary scarring, active tuberculosis was not present. We are uncertain as to what role, if any, the oral contraceptives
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may have had in the development of her ocular symptoms. Oral contraceptives may be associated with retinal vein and artery occlusions and retinal "perivasculitis," 2 2 · 2 3 but this relationship has not been documented. Our patient used oral contraceptives for six years before she developed symptoms in her right eye and another three years before her left eye was involved. Any causative role of the con traceptives is currently speculative. The arteriolitis in our patient led to a superotemporal branch arteriolar occlu sion in her right eye in 1971 with the development of retinal neovasculariz ation. Retinal neovascularization is a fre quent complication of occlusive retinal venous disease, and has been associated with diabetes mellitus, central and branch retinal vein occlusions, retinal phlebitis, sarcoidosis, chronic leukemia, uveitis, and many other diseases. The development of arterial collaterals after retinal arterial occlusion has been report ed in experimental 2 4 ' 2 5 and clinical 26 · 27 situations. However, retinal neovascul arization is rarely associated with retinal arterial disease. 17 Although central retinal artery occlusion can result in neovascul arization of the iris with rubeotic glauco ma, 2 8 - 3 1 Wise, Dollery, and Henkind 3 2 stated that retinal neovascularization does not occur after central retinal artery or branch artery occlusion. However, sickle cell retinopathy, an occlusive disease of the peripheral retinal arterioles, is fre quently characterized by the develop ment of peripheral retinal sea fan neovas cularization. 33 Other occlusive arterial diseases such as carotid artery disease, aortic arch syndromes, and retrolental flbroplasia can lead to ocular ischemia and subsequent retinal neovasculariza tion. 34 · 35 SUMMARY
A 34-year-old white woman who had used oral contraceptives for six years
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showed an occlusive bilateral retinal art eriolitis that resulted in a branch arterio lar occlusion in the right eye and retinal neovascularization. Three years later, we observed active arteriolitis in the left eye with successive occlusion of several branch arterioles. The disease has shown spontaneous remissions and exacerba tions. An extensive medical evaluation revealed only old pulmonary granulomatous disease and an elevated sedimenta tion rate in association with exacerbations of the arteriolitis. REFERENCES 1. Cogan, D. G.: Retinal and papillary vasculitis. In Cant, J. S. (ed.): The William MacKenzie Cente nary Symposium on the Ocular Circulation in Health and Disease. St. Louis, C. V. Mosby, 1969, p. 249. 2. : Ophthalmic Manifestations of System ic Vascular Disease. Philadelphia, W. B. Saunders, 1974, p. 132. 3. Duke-Elder, S., and Dobree, J. H.: Diseases of the Retina. In Duke-Elder, S. (ed.): System of Oph thalmology, vol. 10. St. Louis, C. V. Mosby, 1967, p . 218. 4. Coutu, R. E., Klein, M., Lesseil, S., Friedman, E., and Snider, G. L.: Limited form of Wegener's granulomatosis. J.A.M.A. 233:868, 1975. 5. Donders, P. C.: Eales' disease. Doc. Ophthalmol. 12:1, 1958. 6. Cross, A. G.: Vasculitis retinae. Trans. Ophthalmol. Soc. U. K. 83:133, 1963. 7. : Vasculitis retinae. Prognosis and treat ment. Trans. Ophthalmol. Soc. U. K. 85:11, 1965. 8. Elliott, A. J., and Harris, G. S.: The present status of the diagnosis and treatment of periphlebitis retinae (Eales' disease). Can. J. Ophthalmol. 4:117, 1969. 9. Theodossiadis, G.: Fluorescein angiography in Eales' disease. Am. J. Ophthalmol. 69:271, 1970. 10. Ashton, N.: Pathogenesis and etiology of Eales' disease. In Pandit, Y. K. (ed.): XIX Concilium Ophthalmologicum, vol. 2. Bombay, The Times of India Press, 1962, p . 828. 11. Lyle, T. K., and Wybar, K.: Retinal vasculitis. Br. J. Ophthalmol. 45:778, 1961. 12. Lonn, L. I., and Hoyt, W. F.: Papillophlebitis. A cause of protracted yet benign optic disc edema. Eye Ear Nose Throat Mon. 45:62, 1966. 13. Hayreh, S. S.: Optic disc vasculitis. Br. J. Ophthalmol. 56:652, 1972. 14. Hart, C. D., Sanders, M. D., and Miller, S. J. H.: Benign retinal vasculitis. Br. J. Ophthalmol. 55:721, 1971. 15. Hunter, C. P., and Thompson, H. S.: Papillo phlebitis. In Blodi, F. C. (ed.): Current Concepts in
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Ophthalmology, vol. 4. St. Louis, C. V. Mosby, 1974,' p . 353. 16. Kimura, S. J., Carriker, F. R., and Hogan, M. J.: Retinal vasculitis with intraocular hemor rhage. Arch. Ophthalmol. 56:361, 1956. 17. Karel, I., Votockovâ, J., and Peleska, M.: Fluo rescence angiography in unusual forms of idiopathic retinal vasculitis. Ophthalmologica 168:446, 1974. 18. Pfaffenbach, D. D., and Hollenhorst, R. W.: Microangiopathy of the retinal arterioles. J.A.M.A. 225:480, 1973. 19. Henkind, P.: Fundus lesions in connective tissue disease. Trans. Ophthalmol. Soc. U. K. 94: 785, 1974. 20. Orzalesi, N., and Ricciardi, L.: Segmental retinal periarteritis. Am. J. Ophthalmol. 72:55,1971. 21. Wise, G. N., Dollery, C. T., and Henkind, P. The retinal circulation. New York, Harper and Row, 1971, p . 296. 22. Walsh, F. B., Clark, D. B., Thompson, R. S., and Nicholson, D. H.: Oral contraceptives and neuro-ophthalmologic interest. Arch. Ophthalmol. 74:628, 1965. 23. Radnot, M., and Follmann, P.: Ocular sideeffects of oral contraceptives. Ann. Clin. Res. 5:197, 1973. 24. Henkind, P.: Ballotini occlusion of retinal arteries. Br. J. Ophthalmol. 50:482, 1966. 25. Dollery, C. T., Henkind, P., Paterson, J. W.,
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Ramalho, P. S., and Hill, D. W.: Ophthalmoscopic and circulatory changes in focal retinal ischaemia. Br. J. Ophthalmol. 50:285, 1966. 26. Ball, C. J., and Henkind, P.: Retinal arteriolar collaterals in man. Br. J. Ophthalmol. 51:688,1967. 27. Kornzweig, A. L., Eliasoph, I., and Feldstein, M.: Occlusive disease of retinal vasculature. Arch. Ophthalmol. 71:542, 1964. 28. Perraut, L. W., and Zimmerman, L. E.: The occurrence of glaucoma following occlusion of the central retinal artery. Arch. Ophthalmol. 61:845, 1959. 29. Wolter, J. R., and Phillips, R. L.: Secondary glaucoma following occlusion of the central retinal artery. Am. J. Ophthalmol. 47:335, 1959. 30. : Secondary glaucoma in cranial arteritis. Am. J. Ophthalmol. 59:625, 1965. 31. Smith, J. L.: Unilateral glaucoma in carotid occlusive disease. J.A.M.A. 182:683, 1962. 32. Wise, G. N., Dollery, C. T., and Henkind, P.: The retinal circulation, New York, Harper and Row, 1971, p . 299. 33. Goldberg, M. F.: Classification and pathogenesis of proliferative sickle retinopathy. Am. J. Oph thalmol. 71:649, 1971. 34. Knox, D. L.: Ischémie ocular inflammation. Am. J. Ophthalmol. 60:995, 1965. 35. Patz, A.: Retrolental fibroplasia. Survey Oph thalmol. 14:1, 1969.
Retinal vasculitis can be seen in associ ation with uveitis or can be a manifesta tion of systemic disease. 1,2 On occasion a primary retinal vasculitis is seen unac companied by uveal inflammation or de tectable systemic disease. 1 - 3 The majority of cases of this idiopathic vasculitis (sometimes referred to as Eales's disease) occur in patients with retinal phlebitis that involves either peripheral venules or the central retinal vein. In some cases, however, the retinal vasculitis involves both the retinal arterioles and venules or rarely involves just the arterioles. This report describes a young woman with a progressive bilateral occlusive retinal arteriolitis, which has shown spontaneous remissions and exacerbations and at pre sent is quiescent without therapy.
M.D.,
Illinois electroencephalogram, and skull x-ray films was normal. The VDRL was nonreactive. The patient was discharged with a diagnosis of right optic atrophy of uncertain cause. The patient had no visual problems until July 17, 1974, when she noted the onset of shadows in front of her left eye. She was still taking the same oral contraceptive agent. Eye evaluation here revealed visual acuity of 20/25 in both eyes. The pupil in each eye was 3 mm wide and briskly reactive to light. The right anterior chamber showed trace flare and cells, and the left anterior chamber had trace flare. This was the only time during the patient's examination that anterior chamber abnormalities were noted. Intraocular pressures were normal. Vis ual field testing in the right eye again showed irregular loss of nasal field. Field testing in the left eye showed irregular constriction of the field superotemporally with inferior and superior arcuate scotomata. No central scotoma could be demonstrated. An examination of the right fundus showed loca lized arteriolar tortuosity and definite evidence of an old superotemporal arteriolar occlusion (Figs. 1 and 2). The blood column in the superonasal arteriole appeared dark suggesting stagnation of blood flow (Fig. 1). There was extensive capillary loss in the
CASE REPORT A 34-year-old white woman was in excellent health until August 1971, when she noted the sud den onset of nasal visual field loss in the right eye, accompanied by a headache. The patient's medical history revealed that she was gravida 6, para 6, and had been using dimethisterone with ethinyl estradiol (Oracon) birth control pills for six years. One year previously she had a urinary tract infection and was noted to have a double ureter on the right. She was also allergic to penicillin. Visual acuity was R.E.: 20/100, and L.E.: 20/20. External examination, slitlamp biomieroscopy, and intraocular pressures by applanation tonometry were normal. Visual field testing in the right eye revealed loss of inferonasal field. The left visual field was normal. Ophthalmoscopic examination of the right eye showed a pale disk. A white line was described in the retina near the superotemporal vein. The left fundus was nor mal. Neurologic evaluation including a brain scan,
From the University of Illinois Eye and Ear Infirmary, Chicago, Illinois. This study was sup ported in part by National Institutes of Health Postdoctoral Fellowship 1-F22-HL00812-01. Reprint requests to Lee M. Jampol, M.D., Kimbrough Army Hospital, Ophthalmology Clinic, Fort Meade, MD 20755.
Fig. 1 (Jampol, Isenberg, and Goldberg). Right eye, July 30. Two areas of marked arteriolar tortuosi ty are present (large arrows). A white line corre sponding to an occluded superotemporal arteriole is seen (small arrows). The blood column in the super onasal arteriole is dark, suggesting sluggish blood flow.
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Fig. 2 (Jampol, Isenberg, and Goldberg). Right eye. Distal segment of occluded siiperotemporal arteriole is seen (arrows).
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Fig. 4 (Jampol, Isenberg, and Goldberg). Early arterial phase of fluorescein angiogram showing filling of neovascularization and absence of normal capillary filling.
superotemporal quadrant with an area of neovascul arization with a sea-fan-like configuration (Fig. 3). This sea fan was fed by a tortuous irregular arteriolar feeder (Fig. 4) originating from the superonasal vessels. Late phase fluorescein angiography showed leakage from the sea fan in the right eye (Fig. 5). The right disk appeared pale but no evidence of active vasculitis was seen in the right eye. Examination of the left eye showed disk edema (Fig. 6). Cotton-wool spots, periarteriolar exudation, and arteriolar sheath ing were present in the peripapillary area and the
Fig. 5 (Jampol, Isenberg, and Goldberg). Right eye. Late phase fluorescein angiogram demonstrates leakage from neovascularization.
Fig. 3 (Jampol, Isenberg, and Goldberg). Right eye. Area of sea fan neovascularization in supero temporal periphery.
midperiphery (Figs. 6-8). Arteriolar blood again appeared dark suggesting sluggish flow (Fig. 8). The retinal veins were slightly dilated and irregular, but there was no venous sheathing or periphlebitis. By fluorescein angiography, three small arterioles in the left eye were occluded (Fig. 9). Late phase angiogra phy showed intense staining of the disk and arteri ole walls (Fig. 10). In a few areas minimal staining of the venular walls was noted as well. The patient was admitted to the hospital and had an extensive medical evaluation. Use of the oral contraceptive agent was permanently discontinued.
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Fig. 6 (Jampol, Isenberg, and Goldberg). Left eye, July 30. Posterior pole. Edematous disk with peripapillary cotton-wool spots and periarteriolar sheathing.
Fig. 7 (Jampol, Isenberg, and Goldberg). Left eye. Periarteriolar sheathing is visible along the supero temporal arteriole. Physical examinations including neurologic, der matologie, and hématologie consultations were nor mal. Brain scan, electroencephalogram, and skull x-ray films with optic foramen views were normal. A chest x-ray film showed some scarring at the base of the right lung consistent with old granulomatous disease. An intermediate strength purified protein derivative (PPD) was positive (20 mm induration) while skin testing for histoplasmosis was negative. Sputum cultures for acid-fast bacilli were negative.
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Fig. 8 (Jampol, Isenberg, and Goldberg). Left eye. Superotemporal quadrant showing periarteriolar "cuffing" (arrows) and slight venous irregularity. The arteriolar blood column is again dark.
Fig. 9 (Jampol, Isenberg, and Goldberg). Left eye, July 30. Fluorescein angiogram demonstrating three occluded arterioles (arrows). Normal results were obtained from liver function tests and chemical analyses of the blood, including glucose, blood urea nitrogen (BUN), creatinine, cal cium, and electrolytes. The VDRL for syphilis and FTA-ABS were nonreactive. Serum protein meas urements including quantitative immunoglobulin determinations were normal. No cryoglobulins were present. An indirect fluorescent antibody test for toxoplasmosis was negative. Urinalysis was normal; the urine contained no Bence Jones proteins. The white blood cell count was 8,300/mm 3 with a normal differential. The hematocrit level was 42%. Hemo-
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Fig. 10 (Jampol, Isenberg, and Goldberg). Left eye. Late-phase fluorescein angiogram shows stain ing of disk and arteriole walls. globin electrophoresis showed hemoglobin AA. The latex fixation, rheumatoid factor, antinuclear factor, and lupus erythematosus preparations were nega tive. The sedimentation rate was elevated (42 mm/hr arid 40 mm/hr on two occasions). A lumbar puncture showed a normal pressure, normal lymphocyte count (1/mm 3 ), and normal glucose and chloride levels. The protein level was 53 mg/100 ml (normal, 10 to 40 mg/100 ml). A cerebrospinal fluid VDRL was nonreactive. A muscle-skin biopsy of the left anterior thigh showed no evidence of vasculitis. In
Fig. 11 (Jampol, Isenberg and Goldberg). Left eye, Sept. 9. Inferonasal arteriole coming off the disk at 7 o'clock is more tortuous with total loss of a branch arteriole. Arteriole coming off the disk at 8 o'clock (highest arrow, Fig. 9) is no longer perfused.
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summary, the only abnormal findings were the ele vated sedimentation rate, a positive PPD, and old pulmonary scarring. The patient was observed but not treated, and there was no change in the findings in the right eye. In the left eye several additional branch arterioles occluded and a remaining arteriole inferonsal to the disk became more tortuous (Fig. 11). There was no loss of central vision or further field loss. Several weeks later the disk edema had resolved and the retinal arteriolitis diminished (Fig. 12). Periarterio lar sheathing disappeared (Fig. 13). We used argon laser photocoagulation to close the sea fan in the right eye by treating the feeding arteriole and then the draining venule. After two treatment sessions, the neovascularization was no longer perfused (Fig. 14). The patient has had no evidence of active retinal vasculitis since December 1974. However, the sedi mentation rate has remained elevated (24 to 33 mm/hr). The antinuclear factor has been repeatedly negative. When she was examined Sept. 12, 1975, a test for hepatitis-associated antigen (Australian anti gen) was negative. Results of serum complement measurements including Clq, C3, C4, and C5 were normal. DISCUSSION
Retinal vasculitis is a manifestation of systemic diseases such as temporal arteritis, Takayashu's disease, polyarteritis, lupus erythematosus, multiple sclerosis, and systemic viral infections. 1 · 2 It has
Fig. 12 (Jampol, Isenberg, and Goldberg). Left eye, Dec. 4. Disk edema is gone. Cotton-wool spots and periarteriolar exudation are no longer visible (compare with Fig. 6).
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Fig. 13 (Jampol, Isenberg, and Goldberg). Left eye, Dec. 4. Superotemporal arteriole is visible (compare with Fig. 7). Sheathing has disappeared.
Fig. 14 (Jampol, Isenberg, and Goldberg). Right eye. Fluorescein angiogram showing absence of perfusion of neovascularization following argon laser photocoagulation (compare with Figs. 4 and 5).
also been associated with tuberculosis, sarcoidosis, syphilis, Behçet's disease, toxoplasmosis, cytomegalic inclusion dis ease, Wegener's granulomatosis, and pe ripheral uveitis (pars planitis). 1 - 4 Most of these cases of vasculitis involve exclu sively or primarily the retinal veins.
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Eales's disease is a vaso-obliterative vas culitis seen usually in young males. 5 - 1 0 The phlebitis in this disease is often bilat eral and can lead to retinal neovascular ization, vitreous hemorrhages, and retinal detachment. Retinal phlebitis usually in volves peripheral retinal venules, but some authors have described the in flammation of the central retinal vein, so-called papillophlebitis. 1 1 - 1 5 Retinal vasculitis can involve primarily or exclu sively the retinal arterioles. 1 · 1 6 - 1 8 Some of these patients have systemic vas cular diseases such as lupus erythematosus. 1 8 , 1 9 Retinal arteriolitis is distin guished from segmental retinal periarteritis 20 where discrete white plaques are deposited along the walls of the retinal arterioles. Two cases recently reported by Karel and colleagues 17 showed an occlusive idiopathic retinal arteriolitis similar to our case. The dis ease in these patients also led to retinal neovascularization. A similar case of reti nal vasculitis has been published. 2 1 Our patient had a progressive oblitera tion of her retinal arterioles from a retinal arteriolitis. An extensive medical evalua tion showed only an elevated sedimenta tion rate and inactive pulmonary disease with no evidence of systemic vascular disease. Repeated evaluations for system ic lupus erythematosus including testing for antinuclear factor, lupus erythemato sus preparations, a muscle-skin biopsy, and serum complement determinations were unrevealing. Although our patient may ultimately show evidence of system ic vascular disease, we have not seen this in the four years since the onset of her ocular problems. The vasculitis of Eales's disease has been attributed to tuberculous infection or allergy to tuberculoprotein. 1 0 Although our patient did have a positive PPD and pulmonary scarring, active tuberculosis was not present. We are uncertain as to what role, if any, the oral contraceptives
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may have had in the development of her ocular symptoms. Oral contraceptives may be associated with retinal vein and artery occlusions and retinal "perivasculitis," 2 2 · 2 3 but this relationship has not been documented. Our patient used oral contraceptives for six years before she developed symptoms in her right eye and another three years before her left eye was involved. Any causative role of the con traceptives is currently speculative. The arteriolitis in our patient led to a superotemporal branch arteriolar occlu sion in her right eye in 1971 with the development of retinal neovasculariz ation. Retinal neovascularization is a fre quent complication of occlusive retinal venous disease, and has been associated with diabetes mellitus, central and branch retinal vein occlusions, retinal phlebitis, sarcoidosis, chronic leukemia, uveitis, and many other diseases. The development of arterial collaterals after retinal arterial occlusion has been report ed in experimental 2 4 ' 2 5 and clinical 26 · 27 situations. However, retinal neovascul arization is rarely associated with retinal arterial disease. 17 Although central retinal artery occlusion can result in neovascul arization of the iris with rubeotic glauco ma, 2 8 - 3 1 Wise, Dollery, and Henkind 3 2 stated that retinal neovascularization does not occur after central retinal artery or branch artery occlusion. However, sickle cell retinopathy, an occlusive disease of the peripheral retinal arterioles, is fre quently characterized by the develop ment of peripheral retinal sea fan neovas cularization. 33 Other occlusive arterial diseases such as carotid artery disease, aortic arch syndromes, and retrolental flbroplasia can lead to ocular ischemia and subsequent retinal neovasculariza tion. 34 · 35 SUMMARY
A 34-year-old white woman who had used oral contraceptives for six years
MAY, 1976
showed an occlusive bilateral retinal art eriolitis that resulted in a branch arterio lar occlusion in the right eye and retinal neovascularization. Three years later, we observed active arteriolitis in the left eye with successive occlusion of several branch arterioles. The disease has shown spontaneous remissions and exacerba tions. An extensive medical evaluation revealed only old pulmonary granulomatous disease and an elevated sedimenta tion rate in association with exacerbations of the arteriolitis. REFERENCES 1. Cogan, D. G.: Retinal and papillary vasculitis. In Cant, J. S. (ed.): The William MacKenzie Cente nary Symposium on the Ocular Circulation in Health and Disease. St. Louis, C. V. Mosby, 1969, p. 249. 2. : Ophthalmic Manifestations of System ic Vascular Disease. Philadelphia, W. B. Saunders, 1974, p. 132. 3. Duke-Elder, S., and Dobree, J. H.: Diseases of the Retina. In Duke-Elder, S. (ed.): System of Oph thalmology, vol. 10. St. Louis, C. V. Mosby, 1967, p . 218. 4. Coutu, R. E., Klein, M., Lesseil, S., Friedman, E., and Snider, G. L.: Limited form of Wegener's granulomatosis. J.A.M.A. 233:868, 1975. 5. Donders, P. C.: Eales' disease. Doc. Ophthalmol. 12:1, 1958. 6. Cross, A. G.: Vasculitis retinae. Trans. Ophthalmol. Soc. U. K. 83:133, 1963. 7. : Vasculitis retinae. Prognosis and treat ment. Trans. Ophthalmol. Soc. U. K. 85:11, 1965. 8. Elliott, A. J., and Harris, G. S.: The present status of the diagnosis and treatment of periphlebitis retinae (Eales' disease). Can. J. Ophthalmol. 4:117, 1969. 9. Theodossiadis, G.: Fluorescein angiography in Eales' disease. Am. J. Ophthalmol. 69:271, 1970. 10. Ashton, N.: Pathogenesis and etiology of Eales' disease. In Pandit, Y. K. (ed.): XIX Concilium Ophthalmologicum, vol. 2. Bombay, The Times of India Press, 1962, p . 828. 11. Lyle, T. K., and Wybar, K.: Retinal vasculitis. Br. J. Ophthalmol. 45:778, 1961. 12. Lonn, L. I., and Hoyt, W. F.: Papillophlebitis. A cause of protracted yet benign optic disc edema. Eye Ear Nose Throat Mon. 45:62, 1966. 13. Hayreh, S. S.: Optic disc vasculitis. Br. J. Ophthalmol. 56:652, 1972. 14. Hart, C. D., Sanders, M. D., and Miller, S. J. H.: Benign retinal vasculitis. Br. J. Ophthalmol. 55:721, 1971. 15. Hunter, C. P., and Thompson, H. S.: Papillo phlebitis. In Blodi, F. C. (ed.): Current Concepts in
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Ophthalmology, vol. 4. St. Louis, C. V. Mosby, 1974,' p . 353. 16. Kimura, S. J., Carriker, F. R., and Hogan, M. J.: Retinal vasculitis with intraocular hemor rhage. Arch. Ophthalmol. 56:361, 1956. 17. Karel, I., Votockovâ, J., and Peleska, M.: Fluo rescence angiography in unusual forms of idiopathic retinal vasculitis. Ophthalmologica 168:446, 1974. 18. Pfaffenbach, D. D., and Hollenhorst, R. W.: Microangiopathy of the retinal arterioles. J.A.M.A. 225:480, 1973. 19. Henkind, P.: Fundus lesions in connective tissue disease. Trans. Ophthalmol. Soc. U. K. 94: 785, 1974. 20. Orzalesi, N., and Ricciardi, L.: Segmental retinal periarteritis. Am. J. Ophthalmol. 72:55,1971. 21. Wise, G. N., Dollery, C. T., and Henkind, P. The retinal circulation. New York, Harper and Row, 1971, p . 296. 22. Walsh, F. B., Clark, D. B., Thompson, R. S., and Nicholson, D. H.: Oral contraceptives and neuro-ophthalmologic interest. Arch. Ophthalmol. 74:628, 1965. 23. Radnot, M., and Follmann, P.: Ocular sideeffects of oral contraceptives. Ann. Clin. Res. 5:197, 1973. 24. Henkind, P.: Ballotini occlusion of retinal arteries. Br. J. Ophthalmol. 50:482, 1966. 25. Dollery, C. T., Henkind, P., Paterson, J. W.,
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Ramalho, P. S., and Hill, D. W.: Ophthalmoscopic and circulatory changes in focal retinal ischaemia. Br. J. Ophthalmol. 50:285, 1966. 26. Ball, C. J., and Henkind, P.: Retinal arteriolar collaterals in man. Br. J. Ophthalmol. 51:688,1967. 27. Kornzweig, A. L., Eliasoph, I., and Feldstein, M.: Occlusive disease of retinal vasculature. Arch. Ophthalmol. 71:542, 1964. 28. Perraut, L. W., and Zimmerman, L. E.: The occurrence of glaucoma following occlusion of the central retinal artery. Arch. Ophthalmol. 61:845, 1959. 29. Wolter, J. R., and Phillips, R. L.: Secondary glaucoma following occlusion of the central retinal artery. Am. J. Ophthalmol. 47:335, 1959. 30. : Secondary glaucoma in cranial arteritis. Am. J. Ophthalmol. 59:625, 1965. 31. Smith, J. L.: Unilateral glaucoma in carotid occlusive disease. J.A.M.A. 182:683, 1962. 32. Wise, G. N., Dollery, C. T., and Henkind, P.: The retinal circulation, New York, Harper and Row, 1971, p . 299. 33. Goldberg, M. F.: Classification and pathogenesis of proliferative sickle retinopathy. Am. J. Oph thalmol. 71:649, 1971. 34. Knox, D. L.: Ischémie ocular inflammation. Am. J. Ophthalmol. 60:995, 1965. 35. Patz, A.: Retrolental fibroplasia. Survey Oph thalmol. 14:1, 1969.