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Bilateral Acute Retinal Necrosis
BILATERAL ACUTE RETINAL NECROSIS FRANCIS
W.
PRICE,
JR., M.D., AND T. F.
SCHLAEGEL,
JR., M.D.
Indianapolis, Indiana
Bilateral acute retinal necrosis begins as a symmetrical and confluent retinal swelling with hemorrhages. It develops into necrosis and sloughing of the retina into the vitreous. This disease process appears to be secondary to an obliterative vasculitis of the retina, and it is accompanied by an anterior uveitis. Destruction of the retina is rapid, lasting only a few weeks in each eye. 1•2 We describe a patient who had complete retinal destruction in one of the two eyes involved. No systemic abnormalities were found in this case and no cause was identified. CASE REPORT A 20-year-old woman had a three-week history of soreness in the back of her mouth that gradually spread to include the whole left side of her face, as well as a left frontal headache for one week, and progressive blurring in the left eye for three days. Examination on Sept. 3, 1978, showed tenderness over the left frontal, temporal, maxillary, and orbital areas, as well as the ascending ramus of the mandible. She had a low-grade fever up to 37.8°C. No signs of infection or ulceration were found. Results of her neurologic examination were normal except for redness of the conjunctiva and a dilated and fixed pupil in the left eye. Ophthalmoscopic examination of the left eye showed disk edema, venous engorgement, and peripheral retinal hemorrhages. The working diagnosis was a Facial infection, possibly secondary to a sinusitis with secondary venous thrombosis in the left eye. She was treated with penicillin. Laboratory examination included the following: x-rays of her skull, sinuses, and chest; computed axial tomography with and without contrast; blood cultures; urine cultures and cerebral
From the Department of Ophthalmology, Indiana University Medical Center, Indianapolis, Indiana. This study was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York. Reprint requests to Francis W. Price, jr., M.D., Department of Ophthalmology, Indiana University Medical Center, lloo W. Michigan St., Indianapolis, IN 46223.
spinal fluid cultures for bacteria and fungi; all results were negative. She had an erythrocyte sedimentation rate of 13 mm/hr, a hemoglobin of 14.4 g/dl, a white blood cell count of 9,3OO/mm3 , and a red blood cell count of 4.9 x 1()6/mm3. Her spinal tap suggested a viral, or nonspecific low grade inflammation with a normal opening pressure, a red blood cell count of 34/mm 3 ; and a white blood cell count of 14,OOO/mm 3 with a differential of 79% lymphocytes and 21% polymorphonuclear leukocytes. The protein level was 30 mg/loo ml and the glucose was 55 mg/loo ml with a blood glucose level of 117 mg/loo m!' She was transferred here where she was seen on Sept. 8, 1978. On examination, her best corrected visual acuity was R.E.: 6/4.5 (20/15) and L.E.: light perception. Results of external and biomicroscopic examinations were normal in the right eye and no follicles or papillae were seen in either eye. The conjunctiva on the left was +2 hyperemic, the pupil was fixed at 7 mOl, and biomicroscopic examination showed signs of an anterior uveitis with 1.5 fine, medium, and greasy keratic precipitates, 2 flare, 3.5 cells," no synechiae, and no cells in the vitreous. Intraocular pressure was R.E.: 8 mm Hg and L.E.: 14 mm Hg. Results of ophthalmoscopic examination of the right eye were normal (Fig. 1). Ophthalmoscopic examination of the left eye showed hemorrhages in all quadrants, edema of both the retina and the nerve head, and dilated and irregular vessels. The
Fig. 1 (Price and Schlaegel). Kodachrome of the right eye on Sept. 8, 1978, showing a normal fundus.
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Fig. 2 (Price and Sehlal·gel). Two views of the right eye on Sept. 20. 197H. Left. A Kodachrome. Right, A Huoresceiu angiogram in the late venous phase showing a mild dilation of the vessels and tortuositv of the
veins not present on Sept. H, 197H. The posterior pole is otherwise normal.
fluorescein angiography of the left eye showed a diffuse leakage of all re-tinal vessels with obliteration of flow in some. 1\0 c-ause for her vasculitis could be found and no treatment was given. The obliterative nature seemed to be ximilar to that reported in Behcet's disease,' although there was no history of ulcerative lesions, arthralgias, phlebitis, or erythema uorlosurn. Her history was noncontributory with respec-t to immunizations, travel, recent upper respiratory trac-t infection, and toxic or chemical exposures. She had a normal full-term infant in May 1978. She had had frequent sore throats during her pregnancy. On Sept. 19, 1978, she hegan to have supraorhital pain on the right. Visual acuity decreased to R.E.: 6/6 (20/20) and L.E.: 110 light perception. The anterior cham her was still quiet on the right, whereas that on the left showed an increased reaction, as well as retrolental and anterior vitreous cells. Ophthalmoscopic examination of the right eye revealed a mild increase in haze and dilation of some veins (Fig. 2). Fluorescein angiography also showed the increased vessel size, as well as peripheral arteritis (Fig. 3). We treated her for Behcet' s disease because the vasculitis was spreading to the right eye. She was given 10 mg of chloramburil daily as reported by Mamo." By Oct, 2, 1978 (two weeks after the onset of symptoms in the right eye), her visual acuity had decreased to hand movements at 4 feet. She was given 300 mg of prednisone and 15 grains of aspirin every morning as a last attempt to reverse the vasculitis. There was now a full blown anterior uveitis in the right eye with +2 fine, medium, and greasy keratic prec-ipitates, 3 flare, 3.5 c-ells, and no svueehiae. Cells were prese-nt in the vitreous. She had diffusl' retinal hemorrhages and edema in the right eye (Fig. 4), and fluorescein angiography revealed a
severe ob literative vasculitis with little perfusion more than three to four disk diameters from the disk (Fig. 5). Hemorrhages in the left eye were dearing, leaving white glioti« vessels. On Oct. 18, 1978, visual acuity in the right eye was still hand movements at 4 feet. The anterior ohambcr examination showed no change, and the fundus and fluorescein examinations showed essen-
Fig. 3 (Price and Schlaegel), Right eye, Sept. 20, 197H. Fluorescein angiogram of a peripheral inferotemporal arteriole sho\\'iug leakage and late staining with dilation. Earlier frames showed the dilation to he irregular.
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Fig. 4 (Price and Schlaegel). Right eye, Oct. 2, 1978. Left, Kodachrome now shows abrupt vessel dilation in an inferior temporal arteriole (large arrow), macular edema, and multiple hemorrhages (small arrows). The light spot at the above site of dilation appears to be a thrombus secondary to the inflammatory reaction. Right, Kodachrome of a more temporal and inferior view of the fundus showing more blotlike hemorrhages and abrupt vessel dilation characteristic of peripheral vessel occlusion. tially the same intensity of inflammation. Tlie left eye now had a funnel-shaped detachment of necrotic retina. Because the intensity of the reaction in the right eye had not decreased, the chlorambucil was
Fig. 5 (Price and Schlaegel), Fluorescein angiography shows the obliterative nature of this process. Compare the large arrow here to the one in Figure 4. The small arrows mark an arteriovenous anastomosis that has formed across the macula, apparently in response to the disease process; it was not present on the earlier fluorescein angiogram from Sept. 18, 1978 (Fig. 2).
discontinued and 100 mg of cyclophosphamide twice daily was started. By Nov. 1, 1978, she had light perception only in the right eye. The anterior chamber on the right showed no change, and she had necrotic retinas with retinal detachments bilaterally (Fig. 6). The cyclophosphamide was stopped, her prednisone was tapered, and she continued taking the aspirin.
Fig. 6 (Price and Schlaegel). Fluorescein angiogram of the right eye on Nov. 1, 1978 shows diffuse leakage from the disk and from the few vessels that have remained patent. . .
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Follow-up examination has shown a gradual decrease in her inflammatory process, but no other significant change. Since first seen in the uveitis clinic, the patient was extensively examined for any systemic abnormality, but none was found. Despite the marked vasculitic changes in her retinas, neither neurologic or renal changes were noted during the entire time. Erythrocyte sedimentation rates on Sept. 8, Oct. 5, and Nov. 8, 1978, were 12, 12, and 16 mm/hr, respectively. The purified protein derivative intermediate strength skin test was nonreactive, and that of streptokinase was 12.5 mm of induration. The VORL test and fluorescent treponemal antibodyabsorption was nonreactive. Enzyme-linked immunosorbent assays for Toxocara and Ascaris were negative, as were the rheumatoid latex agglutination. Antinuclear antibodies were not detected at a titer of 1:40. Her thyroxin level was normal at 10.1 I-l/dl and her blood cell count showed a hemoglobin of 15.0 g/dl and a white blood cell count of 9,OOO/mm3 with a differential of 1% bands, 52% polymorphonuclear cells, 43% lymphocytes, and 2% mononuclear cells. The indirect hemagglutination toxoplasmosis titer was 1:8. The cytomegalovirus titer of her serum was 1:32, but without change on repeat titers, and culture of the buffy coat for any viruses was negative. Her HLA profile was All, A24, B7, B15, and CW3. She was positive for W6 and negative for the other known A, B, and C antigens including B5. Her blood was also checked for clotting abnormalities or evidence of any intravascular abnormalities, and results of the following tests were all within the normal limits: prothrombin time, 12.0 seconds; partial thromboplastin time, 22.5 seconds; fibrinogen, 280 mgjmm", thrombin time, 26.1 seconds; platelet aggregation with epinephrine, 95% at four minutes; platelet adhesiveness, 71%; antithrombin III, 42.8 mg/dl, duke bleeding time, one minute; C 3 compliment, 165 mg/dl, C 4 compliment, 39 mg/dl; cryoglobulins, negative; serum protein electrophoresis: albumin, 47.2%; alpha-s, 4.8%; alpha-s, 10.7%; beta, 13.5%; gamma, 23.8%. The serum immunoglobulins were increased with IgM, 2.50 mg/rnrn" (normal, l.15:!: 0.26); IgA, 3.30 mgjmm" (normal, 1.69 :!: 0.80); and IgG, 16.00 mg/mm" (normal, 9.76 :!: 2.18). Her initial blood cell count on Sept. 8, 1978, showed some spherocytes and macrocytes, but these were not noted on subsequent testing. On March 20, 1979, she still had visual acuity of light perception in the right eye and none in the left. Her applanation pressures were 0 mm Hg bilaterally. Ophthalmoscopic examination showed only a small area of viable retina in the superior periphery (Fig. 7). DISCUSSION
Our case appears to be another example of bilateral acute retinal necrosis as reported by Young and Bird.! The disease
MARCH, 1980
Fig. 7 (Price and Schlaegel). Fundus drawing of the right eye March 20, 1979, The posterior pole is now bare retinal pigment epithelium with onlv a few strands of white retina over it. Superiorly th~re is a small area of attached retina. The rest of the peripheral retina is detached and atrophic. Inferiorly, there are some large vessels that originate anteriorly. Vitreous haze is nearly gone at this point.
process here is similar, although our patient's age of 21 years is much younger than their four cases ranging from 57 to 63 years of age. Willers on, Aaberg, and Heeser" also reported two cases of a fulminant retinal vase-occlusive disease that destroyed the retina bilaterally in each patient just as in our case (their patients were 65 and 30 years of age). One of their patients displayed systemic manifestations of Behcet's disease including aphthous ulcers and iridocyclitis with hypopyon. Their second patient had iridocyclitis and a history of vulvar sores. Willerson's first patient was treated with isoniazid, chlorambucil, and prednisone. Although it was suggested that antimetabolite treatment may have led to a quiescence of the retinal vasculitis, one eye progressed from an apparently minimally involved state to a diffuse vasculitis of the retina on this treatment. The sec-
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ond patient was treated with corticosteroids topically, subconjunctivally, and orally, as well as with pooled transfer factor. none of which changed the course of her disease. All four of these eyes apparently ended with visual acuity of light perception at best. Young and Bird, 1 however, only treated their four patients with corticosteroids (two also were treated with an antibiotic). Four of these eight eyes retained visual acuity of 6/12 (20/40) to 6/60 (20/200). The one woman in their study was the only patient to end up with bilateral blindness, but even her vasculitis may have decreased on the corticosteroid treatment. However, they suggested that treatment did not appear to alter the course of the disease. Whether it did, or whether their patients did not manifest the extent of the disease as in our patient and Willerson's is unknown. The end result in all of these cases appears to be a vitreous contraction from the inflammatory process with traction on the necrotic retina causing either or both a traction retinal detachment and a rhegmatogenous retinal detachment. These detachments sometimes occurred after the inflammation had resolved and they invariably proved to be impossible to repair if attempted. As previously noted, our patient showed no decrease in her vasculitis with corticosteroids or chlorambucil, although she was not given the full dose of 20 mg per day as sometimes used by Mamo.P It is interesting in our case that such a severe vasculitis of the retina could develop without any hematologic changes suggestive of a more diffuse vasculitis in the body or neurologic changes suggestive of a vasculitis in the central nervous system. Only one of the previously reported cases gives any evidence of systemic involvement'' and two others had increased sedimentation rates with one of these having
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evidence of ankylosing spondylitis on xrays. 1 Whatever the causal agent, it would appear to be specific for the retina with some involvement and inflammation of the uveal tract as well. All cases, except one, appear to have been in patients with an apparently normal immunologic status before treatment. Evidence for Behcet's disease in our patient is circumstantial at best. Her retinal changes with obliterative vasculitis and low-grade fever during her beginning attack are consistent with those described by Mamo and Baghdassarian." Emotional stress, chronic sore throats for one year before onset. and being in the 20- to 3O-year age group are also noted to be associated with Behcet's disease." However, our patient lacked the other more common signs and symptoms of Behcet's disease needed to make a diagnosis. Herpes virus infections have been noted to have a similar appearance to bilateral acute retinal necrosis.I'" but such cases seldom occur beyond infancy. The possibility of herpes and cytomegalovirus infections as the cause of bilateral acute retinal necrosis were discussed at length in the previously mentioned reports. However, we cannot attribute a firm diagnosis of this condition to any virus. The terminology that has developed in published reports regarding these cases is potentially confusing. We have chosen the terminology used by Young and Bird;' bilateral acute retinal necrosis, because it aptly describes the overall nature of these reported cases, stresses the devastating potential of the process, and supplies an easily remembered acronym. (BARN). Willerson, Aaberg, and Reeser" chose necrotizing vaso-occlusive retinitis which describes the local vascular reaction. Finally, Bloom and associates'' have recently described three cases of acute retinal necrosis that were secondary to
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blunt trauma, had no vaso-occlusive component, and were self-limiting processes without the marked inflammation and vitreous contraction present in the cases discussed here. SUMMARY
A 20-year-old woman lost all useful vision over a 2 112-month period as a result of a necrotizing and occlusive vasculitis of the retina. Treatment with prednisone, immunosuppressants, and aspirin was unsuccessful. No systemic manifestations of the disease were found and no cause was discovered. Kodachromes and fluorescein angiograms showed the progression in one eye from normal to near total retinal necrosis. The process began with a mild venous dilation and peripheral arteritis that progressed into an obliterative vasculitis with abrupt vessel dilation, hemorrhages, and retinal swelling. This was followed by necrosis and sloughing of the
MARCH, 1980
retina into the vitreous. Vitreous contraction and necrotic retina produced unrepairable retinal detachments. REFERENCES 1. Young, N. J., and Bird, A. C.: Bilateral acute retinal necrosis. Br. J. Ophthalmol. 62:581, 1978. 2. Willerson, D., jr., Aaberg, T. M., and Reeser, F. H.: Necrotizing vase-occlusive retinitis. Am. J. Ophthalmol. 84:209, 1977. 3. Schlaegel, T. F., jr.: Symptoms and signs of uveitis. In Duane, T. (ed.): Clinical Ophthalmology, vol. 4. Hagerstown, Harper and Row, Publishers, Inc., 1976, chap. 32. 4. Shikano, S., and Shimizu, K.: Atlas of Fluorescence Fundus Angiography. Philadelphia, W. B. Saunders Co., 1968, p. 136. 5. Mamo, J. G.: Treatment of Behcet's disease with chlorambucil. Arch. Ophthalrnol. 94:580, 1976. 6. Mamo, J. G., and Baghdassarian, A.: Behcet's disease. Arch. Ophthalmol. 71:38, 1964. 7. Cogan, D. G., Kuwabara, T., Young, G. F., and Knox, D. L.: Herpes simplex in the newborn. Int. Ophthalmol. Clin. 12:2, 191, 1972. 8. Minckler, D. S., McLean, E. B., Shaw, C. M., and Hendriksen, A.: Herpes virus hominis encephalitis and retinitis. Arch. Ophthalmol. 94:89, 1976. 9. Bloome, M. A., Ruiz, R. S., Russo, C. E., and Salmonson, P. C.: Acute retinal necrosis. Ann Ophthalmol. 1l:723, 1979.
W.
PRICE,
JR., M.D., AND T. F.
SCHLAEGEL,
JR., M.D.
Indianapolis, Indiana
Bilateral acute retinal necrosis begins as a symmetrical and confluent retinal swelling with hemorrhages. It develops into necrosis and sloughing of the retina into the vitreous. This disease process appears to be secondary to an obliterative vasculitis of the retina, and it is accompanied by an anterior uveitis. Destruction of the retina is rapid, lasting only a few weeks in each eye. 1•2 We describe a patient who had complete retinal destruction in one of the two eyes involved. No systemic abnormalities were found in this case and no cause was identified. CASE REPORT A 20-year-old woman had a three-week history of soreness in the back of her mouth that gradually spread to include the whole left side of her face, as well as a left frontal headache for one week, and progressive blurring in the left eye for three days. Examination on Sept. 3, 1978, showed tenderness over the left frontal, temporal, maxillary, and orbital areas, as well as the ascending ramus of the mandible. She had a low-grade fever up to 37.8°C. No signs of infection or ulceration were found. Results of her neurologic examination were normal except for redness of the conjunctiva and a dilated and fixed pupil in the left eye. Ophthalmoscopic examination of the left eye showed disk edema, venous engorgement, and peripheral retinal hemorrhages. The working diagnosis was a Facial infection, possibly secondary to a sinusitis with secondary venous thrombosis in the left eye. She was treated with penicillin. Laboratory examination included the following: x-rays of her skull, sinuses, and chest; computed axial tomography with and without contrast; blood cultures; urine cultures and cerebral
From the Department of Ophthalmology, Indiana University Medical Center, Indianapolis, Indiana. This study was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York. Reprint requests to Francis W. Price, jr., M.D., Department of Ophthalmology, Indiana University Medical Center, lloo W. Michigan St., Indianapolis, IN 46223.
spinal fluid cultures for bacteria and fungi; all results were negative. She had an erythrocyte sedimentation rate of 13 mm/hr, a hemoglobin of 14.4 g/dl, a white blood cell count of 9,3OO/mm3 , and a red blood cell count of 4.9 x 1()6/mm3. Her spinal tap suggested a viral, or nonspecific low grade inflammation with a normal opening pressure, a red blood cell count of 34/mm 3 ; and a white blood cell count of 14,OOO/mm 3 with a differential of 79% lymphocytes and 21% polymorphonuclear leukocytes. The protein level was 30 mg/loo ml and the glucose was 55 mg/loo ml with a blood glucose level of 117 mg/loo m!' She was transferred here where she was seen on Sept. 8, 1978. On examination, her best corrected visual acuity was R.E.: 6/4.5 (20/15) and L.E.: light perception. Results of external and biomicroscopic examinations were normal in the right eye and no follicles or papillae were seen in either eye. The conjunctiva on the left was +2 hyperemic, the pupil was fixed at 7 mOl, and biomicroscopic examination showed signs of an anterior uveitis with 1.5 fine, medium, and greasy keratic precipitates, 2 flare, 3.5 cells," no synechiae, and no cells in the vitreous. Intraocular pressure was R.E.: 8 mm Hg and L.E.: 14 mm Hg. Results of ophthalmoscopic examination of the right eye were normal (Fig. 1). Ophthalmoscopic examination of the left eye showed hemorrhages in all quadrants, edema of both the retina and the nerve head, and dilated and irregular vessels. The
Fig. 1 (Price and Schlaegel). Kodachrome of the right eye on Sept. 8, 1978, showing a normal fundus.
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Fig. 2 (Price and Sehlal·gel). Two views of the right eye on Sept. 20. 197H. Left. A Kodachrome. Right, A Huoresceiu angiogram in the late venous phase showing a mild dilation of the vessels and tortuositv of the
veins not present on Sept. H, 197H. The posterior pole is otherwise normal.
fluorescein angiography of the left eye showed a diffuse leakage of all re-tinal vessels with obliteration of flow in some. 1\0 c-ause for her vasculitis could be found and no treatment was given. The obliterative nature seemed to be ximilar to that reported in Behcet's disease,' although there was no history of ulcerative lesions, arthralgias, phlebitis, or erythema uorlosurn. Her history was noncontributory with respec-t to immunizations, travel, recent upper respiratory trac-t infection, and toxic or chemical exposures. She had a normal full-term infant in May 1978. She had had frequent sore throats during her pregnancy. On Sept. 19, 1978, she hegan to have supraorhital pain on the right. Visual acuity decreased to R.E.: 6/6 (20/20) and L.E.: 110 light perception. The anterior cham her was still quiet on the right, whereas that on the left showed an increased reaction, as well as retrolental and anterior vitreous cells. Ophthalmoscopic examination of the right eye revealed a mild increase in haze and dilation of some veins (Fig. 2). Fluorescein angiography also showed the increased vessel size, as well as peripheral arteritis (Fig. 3). We treated her for Behcet' s disease because the vasculitis was spreading to the right eye. She was given 10 mg of chloramburil daily as reported by Mamo." By Oct, 2, 1978 (two weeks after the onset of symptoms in the right eye), her visual acuity had decreased to hand movements at 4 feet. She was given 300 mg of prednisone and 15 grains of aspirin every morning as a last attempt to reverse the vasculitis. There was now a full blown anterior uveitis in the right eye with +2 fine, medium, and greasy keratic prec-ipitates, 3 flare, 3.5 c-ells, and no svueehiae. Cells were prese-nt in the vitreous. She had diffusl' retinal hemorrhages and edema in the right eye (Fig. 4), and fluorescein angiography revealed a
severe ob literative vasculitis with little perfusion more than three to four disk diameters from the disk (Fig. 5). Hemorrhages in the left eye were dearing, leaving white glioti« vessels. On Oct. 18, 1978, visual acuity in the right eye was still hand movements at 4 feet. The anterior ohambcr examination showed no change, and the fundus and fluorescein examinations showed essen-
Fig. 3 (Price and Schlaegel), Right eye, Sept. 20, 197H. Fluorescein angiogram of a peripheral inferotemporal arteriole sho\\'iug leakage and late staining with dilation. Earlier frames showed the dilation to he irregular.
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Fig. 4 (Price and Schlaegel). Right eye, Oct. 2, 1978. Left, Kodachrome now shows abrupt vessel dilation in an inferior temporal arteriole (large arrow), macular edema, and multiple hemorrhages (small arrows). The light spot at the above site of dilation appears to be a thrombus secondary to the inflammatory reaction. Right, Kodachrome of a more temporal and inferior view of the fundus showing more blotlike hemorrhages and abrupt vessel dilation characteristic of peripheral vessel occlusion. tially the same intensity of inflammation. Tlie left eye now had a funnel-shaped detachment of necrotic retina. Because the intensity of the reaction in the right eye had not decreased, the chlorambucil was
Fig. 5 (Price and Schlaegel), Fluorescein angiography shows the obliterative nature of this process. Compare the large arrow here to the one in Figure 4. The small arrows mark an arteriovenous anastomosis that has formed across the macula, apparently in response to the disease process; it was not present on the earlier fluorescein angiogram from Sept. 18, 1978 (Fig. 2).
discontinued and 100 mg of cyclophosphamide twice daily was started. By Nov. 1, 1978, she had light perception only in the right eye. The anterior chamber on the right showed no change, and she had necrotic retinas with retinal detachments bilaterally (Fig. 6). The cyclophosphamide was stopped, her prednisone was tapered, and she continued taking the aspirin.
Fig. 6 (Price and Schlaegel). Fluorescein angiogram of the right eye on Nov. 1, 1978 shows diffuse leakage from the disk and from the few vessels that have remained patent. . .
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Follow-up examination has shown a gradual decrease in her inflammatory process, but no other significant change. Since first seen in the uveitis clinic, the patient was extensively examined for any systemic abnormality, but none was found. Despite the marked vasculitic changes in her retinas, neither neurologic or renal changes were noted during the entire time. Erythrocyte sedimentation rates on Sept. 8, Oct. 5, and Nov. 8, 1978, were 12, 12, and 16 mm/hr, respectively. The purified protein derivative intermediate strength skin test was nonreactive, and that of streptokinase was 12.5 mm of induration. The VORL test and fluorescent treponemal antibodyabsorption was nonreactive. Enzyme-linked immunosorbent assays for Toxocara and Ascaris were negative, as were the rheumatoid latex agglutination. Antinuclear antibodies were not detected at a titer of 1:40. Her thyroxin level was normal at 10.1 I-l/dl and her blood cell count showed a hemoglobin of 15.0 g/dl and a white blood cell count of 9,OOO/mm3 with a differential of 1% bands, 52% polymorphonuclear cells, 43% lymphocytes, and 2% mononuclear cells. The indirect hemagglutination toxoplasmosis titer was 1:8. The cytomegalovirus titer of her serum was 1:32, but without change on repeat titers, and culture of the buffy coat for any viruses was negative. Her HLA profile was All, A24, B7, B15, and CW3. She was positive for W6 and negative for the other known A, B, and C antigens including B5. Her blood was also checked for clotting abnormalities or evidence of any intravascular abnormalities, and results of the following tests were all within the normal limits: prothrombin time, 12.0 seconds; partial thromboplastin time, 22.5 seconds; fibrinogen, 280 mgjmm", thrombin time, 26.1 seconds; platelet aggregation with epinephrine, 95% at four minutes; platelet adhesiveness, 71%; antithrombin III, 42.8 mg/dl, duke bleeding time, one minute; C 3 compliment, 165 mg/dl, C 4 compliment, 39 mg/dl; cryoglobulins, negative; serum protein electrophoresis: albumin, 47.2%; alpha-s, 4.8%; alpha-s, 10.7%; beta, 13.5%; gamma, 23.8%. The serum immunoglobulins were increased with IgM, 2.50 mg/rnrn" (normal, l.15:!: 0.26); IgA, 3.30 mgjmm" (normal, 1.69 :!: 0.80); and IgG, 16.00 mg/mm" (normal, 9.76 :!: 2.18). Her initial blood cell count on Sept. 8, 1978, showed some spherocytes and macrocytes, but these were not noted on subsequent testing. On March 20, 1979, she still had visual acuity of light perception in the right eye and none in the left. Her applanation pressures were 0 mm Hg bilaterally. Ophthalmoscopic examination showed only a small area of viable retina in the superior periphery (Fig. 7). DISCUSSION
Our case appears to be another example of bilateral acute retinal necrosis as reported by Young and Bird.! The disease
MARCH, 1980
Fig. 7 (Price and Schlaegel). Fundus drawing of the right eye March 20, 1979, The posterior pole is now bare retinal pigment epithelium with onlv a few strands of white retina over it. Superiorly th~re is a small area of attached retina. The rest of the peripheral retina is detached and atrophic. Inferiorly, there are some large vessels that originate anteriorly. Vitreous haze is nearly gone at this point.
process here is similar, although our patient's age of 21 years is much younger than their four cases ranging from 57 to 63 years of age. Willers on, Aaberg, and Heeser" also reported two cases of a fulminant retinal vase-occlusive disease that destroyed the retina bilaterally in each patient just as in our case (their patients were 65 and 30 years of age). One of their patients displayed systemic manifestations of Behcet's disease including aphthous ulcers and iridocyclitis with hypopyon. Their second patient had iridocyclitis and a history of vulvar sores. Willerson's first patient was treated with isoniazid, chlorambucil, and prednisone. Although it was suggested that antimetabolite treatment may have led to a quiescence of the retinal vasculitis, one eye progressed from an apparently minimally involved state to a diffuse vasculitis of the retina on this treatment. The sec-
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ond patient was treated with corticosteroids topically, subconjunctivally, and orally, as well as with pooled transfer factor. none of which changed the course of her disease. All four of these eyes apparently ended with visual acuity of light perception at best. Young and Bird, 1 however, only treated their four patients with corticosteroids (two also were treated with an antibiotic). Four of these eight eyes retained visual acuity of 6/12 (20/40) to 6/60 (20/200). The one woman in their study was the only patient to end up with bilateral blindness, but even her vasculitis may have decreased on the corticosteroid treatment. However, they suggested that treatment did not appear to alter the course of the disease. Whether it did, or whether their patients did not manifest the extent of the disease as in our patient and Willerson's is unknown. The end result in all of these cases appears to be a vitreous contraction from the inflammatory process with traction on the necrotic retina causing either or both a traction retinal detachment and a rhegmatogenous retinal detachment. These detachments sometimes occurred after the inflammation had resolved and they invariably proved to be impossible to repair if attempted. As previously noted, our patient showed no decrease in her vasculitis with corticosteroids or chlorambucil, although she was not given the full dose of 20 mg per day as sometimes used by Mamo.P It is interesting in our case that such a severe vasculitis of the retina could develop without any hematologic changes suggestive of a more diffuse vasculitis in the body or neurologic changes suggestive of a vasculitis in the central nervous system. Only one of the previously reported cases gives any evidence of systemic involvement'' and two others had increased sedimentation rates with one of these having
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evidence of ankylosing spondylitis on xrays. 1 Whatever the causal agent, it would appear to be specific for the retina with some involvement and inflammation of the uveal tract as well. All cases, except one, appear to have been in patients with an apparently normal immunologic status before treatment. Evidence for Behcet's disease in our patient is circumstantial at best. Her retinal changes with obliterative vasculitis and low-grade fever during her beginning attack are consistent with those described by Mamo and Baghdassarian." Emotional stress, chronic sore throats for one year before onset. and being in the 20- to 3O-year age group are also noted to be associated with Behcet's disease." However, our patient lacked the other more common signs and symptoms of Behcet's disease needed to make a diagnosis. Herpes virus infections have been noted to have a similar appearance to bilateral acute retinal necrosis.I'" but such cases seldom occur beyond infancy. The possibility of herpes and cytomegalovirus infections as the cause of bilateral acute retinal necrosis were discussed at length in the previously mentioned reports. However, we cannot attribute a firm diagnosis of this condition to any virus. The terminology that has developed in published reports regarding these cases is potentially confusing. We have chosen the terminology used by Young and Bird;' bilateral acute retinal necrosis, because it aptly describes the overall nature of these reported cases, stresses the devastating potential of the process, and supplies an easily remembered acronym. (BARN). Willerson, Aaberg, and Reeser" chose necrotizing vaso-occlusive retinitis which describes the local vascular reaction. Finally, Bloom and associates'' have recently described three cases of acute retinal necrosis that were secondary to
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blunt trauma, had no vaso-occlusive component, and were self-limiting processes without the marked inflammation and vitreous contraction present in the cases discussed here. SUMMARY
A 20-year-old woman lost all useful vision over a 2 112-month period as a result of a necrotizing and occlusive vasculitis of the retina. Treatment with prednisone, immunosuppressants, and aspirin was unsuccessful. No systemic manifestations of the disease were found and no cause was discovered. Kodachromes and fluorescein angiograms showed the progression in one eye from normal to near total retinal necrosis. The process began with a mild venous dilation and peripheral arteritis that progressed into an obliterative vasculitis with abrupt vessel dilation, hemorrhages, and retinal swelling. This was followed by necrosis and sloughing of the
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retina into the vitreous. Vitreous contraction and necrotic retina produced unrepairable retinal detachments. REFERENCES 1. Young, N. J., and Bird, A. C.: Bilateral acute retinal necrosis. Br. J. Ophthalmol. 62:581, 1978. 2. Willerson, D., jr., Aaberg, T. M., and Reeser, F. H.: Necrotizing vase-occlusive retinitis. Am. J. Ophthalmol. 84:209, 1977. 3. Schlaegel, T. F., jr.: Symptoms and signs of uveitis. In Duane, T. (ed.): Clinical Ophthalmology, vol. 4. Hagerstown, Harper and Row, Publishers, Inc., 1976, chap. 32. 4. Shikano, S., and Shimizu, K.: Atlas of Fluorescence Fundus Angiography. Philadelphia, W. B. Saunders Co., 1968, p. 136. 5. Mamo, J. G.: Treatment of Behcet's disease with chlorambucil. Arch. Ophthalrnol. 94:580, 1976. 6. Mamo, J. G., and Baghdassarian, A.: Behcet's disease. Arch. Ophthalmol. 71:38, 1964. 7. Cogan, D. G., Kuwabara, T., Young, G. F., and Knox, D. L.: Herpes simplex in the newborn. Int. Ophthalmol. Clin. 12:2, 191, 1972. 8. Minckler, D. S., McLean, E. B., Shaw, C. M., and Hendriksen, A.: Herpes virus hominis encephalitis and retinitis. Arch. Ophthalmol. 94:89, 1976. 9. Bloome, M. A., Ruiz, R. S., Russo, C. E., and Salmonson, P. C.: Acute retinal necrosis. Ann Ophthalmol. 1l:723, 1979.