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Peripheral Retinal Neovascularization in Sarcoidosis and Sickle Cell Anemia
PERIPHERAL IN
RETINAL
NEOVASCULARIZATION
SARCOIDOSIS AND
SICKLE
C E L L
ANEMIA
JOHN C . MADIGAN, J R . , M . D . , EVANGELOS S. GRAGOUDAS,
M.D.,
P E T E R L . S C H W A R T Z , M . D . , AND J A I M E V . L A P U S , M . D .
Boston,
Massachusetts
The retinal neovascularization seen in different sickle cell hemoglobinopathies has been described p r e v i o u s l y . Proliferation of new vessels at the periphery of the retina with similar appearance has been described recently in patients with proven sarcoidosis and normal hemoglobin electrophoresis. The purpose of this report is to present a patient with sarcoidosis and sickle cell anemia who developed new vessels at the retinal periphery. Since the two diseases are not mutually exclusive, both should be considered in the differential diagnosis of black patients with peripheral retinal neovascularization. 1-6
7,8
CASE REPORT
A 30-year-old black woman with a diagnosis of homozygous sickle cell (Hb SS) disease since age 8 was admitted here in 1971, in sickling crisis. Her past history was characterized by episodes of joint and extremity pain, a pregnancy at age 19 with successful delivery of a male infant with sickle cell trait (Hb AS), hepatitis during pregnancy of unknown type, and an uneventful cholecystectomy at age 21. She had had a blood transfusion once, at age 8 years. Hematologic evaluation at that time revealed Hb SS disease by cellulose acetate strip, as well as 10% Hb F by alkali denaturation, and 2.8% Hb A by starch block, all characteristic of Hb SS disease. A bilateral parotitis of unknown etiology was also noted and gradually resolved. The patient gave a history of intermittent diplopia and an ocular examination was performed. Visual acuity was R.E.: 6/6 2
From the Fluorescein Angiography Laboratory, Massachusetts Eye and Ear Infirmary (Drs. Gragoudas, Lapus, and Madigan) and the Department of Retina Research, Eye Research Institute of Retina Foundation (Drs. Gragoudas and Schwartz), Boston, Massachusetts. This study was supported by Public Health Service research grant EY-00227 from the National Eye Institute, National Institutes of Health. Reprint requests to E. S. Gragoudas, M.D., Eye Research Institute of Retina Foundation, 20 Stamford St., Boston MA 02114.
(20/20) and L.E.: 6/9 (20/30). An exophoria of 15 to 30 diopters was noted but the patient had stereopsis of 100 seconds of arc. Anterior segment and ophthalmoscopic examinations were normal with no evidence of sickle retinopathy. She was frequently admitted for joint, abdominal, and chest pain that required multiple transfusions. She developed congestive heart failure, controlled with 0.25 mg of digoxin daily, and multiple episodes of small pulmonary emboli. In addition, the patient had another male infant with Hb AS in June 1971. In early 1974, the patient was admitted to another hospital and bilateral hilar adenopathy consistent with sarcoid was noted. Results of an immunodeficiency examination were negative, including normal complement, gamma globulin, and absence of anergy. On March 17, 1975, the patient was readmitted here with dyspnea and chest pain. Evaluation on this and subsequent admissions revealed bilateral hilar adenopathy consistent with sarcoid on chest x-ray and chest tomography. Second strength purified protein derivative (PPD) was negative. Cultures of sputum, urine, and liver biopsy material were negative for mycobacteria. Antibodies to hepatitis associated antigen were nondetectable. Urine was negative for Bence Jones protein, and cold agglutinin titer was 1:2. Immunoglobulin electrophoresis revealed normal Ig A and Ig M, with moderately increased Ig G. Upper gastrointestinal series, intravenous cholangiogram, intravenous pyelogram, nephrotomograms, and a renal angiogram were normal. Serologic test for syphilis was nonreactive. On May 31, a liver biopsy specimen revealed multiple noncaseating granulomas, marked sludging of sickled red cells in the sinusoids, hemosiderin deposition in the Kupfer cells, and negative stains for acidfast and fungal organisms (Fig. 1). These findings were characteristic of both sarcoidosis and Hb SS disease. Cardiopulmonary evaluation in June, including pulmonary function tests and cardiac catheterization (left side of the heart), revealed pulmonary vascular obstructive disease caused by congestive heart failure and sickling. She continued to have episodes of chest and joint pain complicated by hypoxemia. In November, pulmonary function tests revealed the additional finding of decreased diffusion capacity thought to be caused by interstitial infiltration by sarcoidosis. At that time the patient complained of intermittent blurring of vision, and an eye examination was performed. Visual acuity was R.E.: 6/6 (20/20), and L.E.: 6/7.5 (20/25), and intraocular pressure was 15 mm Hg in both eyes. Extraocular movements were full without nystagmus or diplopia, and pupil and ante-
387
388
AMERICAN JOURNAL OF OPHTHALMOLOGY
MARCH, 1977
Fig. 1 (Madigan and associates). Liver biopsy. Top, Noncaseating granuloma typical of sarcoidosis (arrow). Bottom, Same specimen has sickled erythrocytes obstructing liver sinusoids (arrow). rior segment examinations were normal. The palpebral portions of the lacrimal glands were described as nodular, and the Hertel exophthalmometer readings were R.E.: 15, and L.E.: 12, with a92-mm base. Tangent screen fields were full to a 3-mm white object at 1 meter. Indirect ophthalmoscopy with scleral depression revealed several white elevated nodules in the temporal periphery, thought initially to represent active sarcoid uveitis. The left fundus was normal. Skull series revealed a coarse, textured calvarium consistent with Hb SS disease, and orbit-
al polytomography revealed normal optic canals and bony orbits with some increased soft tissue density in the right orbit. Orbital ultrasonography revealed an enlarged right lateral rectus muscle and lacrimal gland consistent with sarcoid. Fluorescein angiography revealed the lesions in the right temporal periphery to represent foci of neovascularization with associated distal retinal ischemia, without signs of active inflammation (Fig. 2). Because of the deterioration in her pulmonary disease and the possibility of ocular sarcoidosis, the
VOL. 83, NO. 3
RETINAL NEOVASCULARIZATION
Fig. 2 (Madigan and associates). Fluorescein angiography of the temporal periphery of the right eye demonstrates the presence of new vessels and distal ischemic retina.
patient received 40 mg of oral prednisone daily. However, she continued to have painful crises complicated by the development of narcotic dependence, and her pulmonary status failed to show significant improvement after two months on corticosteroids. On Feb. 7, 1976, ophthalmic follow-up revealed that visual acuity was R.E.: 6/7.5 (20/25), and L.E.: 6/7.5 (20/25). Intraocular pressures were 18 mm Hg, and the Hertel exophthalmometer readings were R.E.: 17, and L.E.: 16, with a 94-mm base. Slit-lamp examination was again normal with no signs of active or old uveitis. The vitreous body was free of cells and the neovascular lesions in the right eye appeared unchanged. Because of the lack of improvement in her pulmonary status and the absence of signs of sarcoid uveitis, corticosteroids were discontinued. She has never experienced aplastic crises, renal failure, osteomyelitis, or neurologic problems, and her hematocrit reading generally ranged from 20 to 30%. The patient was referred here where repeat ophthalmoscopy and fluorescein angiography on Feb. 18, 1976, confirmed the presence of the neovascular lesion (Figs. 3 and 4). In addition several ghost vessels were seen in the left far temporal periphery and several small erosions were noted inferiorly near the ora serrata in both eyes. Ghost vessels in the right eye were passing through the area of neovascularization into the area of distal ischemic retina but did not perfuse with fluorescein (Figs. 3 and 4). No angioid streaks or pigmentary changes such as "black sunbursts" or "salmon patches" were noted, and macular capillary perfusion was normal. On Feb. 20, focal laser photocoagulation of the lesion was performed using an argon laser with 239 applications of 0.2 second's duration, 500-u.diameter spot size, and 200 to 350 mW of power (Fig. 5).
389
Fig. 3 (Madigan and associates). Fundus picture showing white fibrovascular areas and ghost vessels extending beyond area of neovascularization into ischemic area.
Follow-up fluorescein angiography on March 12 showed successful obliteration of the neovascular lesion (Fig. 6). In addition, angioscopy of both peripheral fundi revealed an area of retinal ischemia in the left far temporal periphery without neovascularization. At follow-up ophthalmic examination one month after treatment and after cessation of all corticosteroids visual acuity was 6/12 (20/40) with cycloplegic retinoscopy of R.E.: +.50 + . 5 0 x 45, L.E.: +.50 +.50 x 150. The patient had no ocular symptoms. A small variable exotropia with full extraocular movements and stereopsis of 200 sec-
Fig. 4 (Madigan and associates). Fluorescein angiography shows leakage of new vessels and no filling of ghost vessels.
390
AMERICAN JOURNAL OF OPHTHALMOLOGY
MARCH, 1977
ticularly in populations with access to medical care, is the treatment of the systemic disease with multiple transfusions over extended periods. This results in alteration of the hemoglobin pattern, by increasing the H b A concentration, and elevating the hematocrit level, both of which may alter blood viscosity and, presumably, the capacity for vascular occlusion. Another factor, which may also modify atypical H b SS retinopathy, is the possibility of an occult sickle cell thalassemia (Sthal) genotype. T h e small amount of Hb A that may occur in Sthal may go undetected in an initial hemoglobin electrophoresis, and once transfusions of exogenous Hb A have been given, the Sthal genotype is impossible to establish on electrophoretic grounds. 6
Fig. 5 (Madigan and associates). Photocoagulation of feeder vessels and neovascular tufts with argon laser.
onds was present. The palpebral portion of the lacrimal glands was prominent and nodular, but exophthalmometry was normal. The Shirmer test with proparacaine hydrochloride revealed a marked decrease in basal tear production of 1 mm after five minutes. Slit-lamp examination, gonioscopy, biomicroscopy of the fundus and vitreous, and ophthalmoscopy with scleral depression revealed no sign in either eye of anterior or posterior segment inflammation. The vitreous was clear and there was no peripheral uveitis, candle wax drippings, or inflammatory venous sheathing. The neovascular lesion appeared to be obliterated. Follow-up examination two months after treatment showed visual acuity was 6/6 (20/20) and similar findings with no evidence of intraocular influence. The conjunctival vessels showed marked segmentation of the blood columns but no isolated dilated segments. Retinal examination revealed no equatorial "whitewithout-pressure" lesions, although there was extensive peripheral whitening at the ora serrata, as well as condensation of the vitreous base. Her medical management at this time consisted of hypertransfusion, which has kept her hematocrit level at 35%, given her a high Hb A level, and effectively reduced the percentage of endogenous Hb S. She remained asymptomatic on this regimen.
T h e incidence of proliferative retinopathy is higher among patients with Hb S S disease who have a high hemoglobin level, and among those with Sthal disease who have a higher Hb A level. In the light of frequent transfusions in our patient it is not surprising that the black, disk-shaped retinal scars (black sunbursts), tortuosity of veins, and conjunctival vessel anomalies often seen in pa6
DISCUSSION
T h e ocular lesions in sickle cell anemia have been described, and the rarity of peripheral neovascularization in patients with the homozygous (SS) genotype has been stressed. However, a factor that may modify sickle cell retinopathy, par2,4
Fig. 6 (Madigan and associates). Fluorescein angiography demonstrates obliteration of proliferative lesions.
VOL. 8 3 , NO. 3
RETINAL
NEOVASCULARIZATION
tients with Hb S S were lacking while the arteriolar obliteration, peripheral retinal ischemia, arteriovenous shunting, and neovascular proliferation typical of more severe sickle retinopathy, were present. In addition, there was extensive whitening of the retina at the ora serrata and condensation of the vitreous base, as reported in all sickle cell r e t i n o p a t h i e s , although the equatorial white-withoutpressure lesions recently d e s c r i b e d were not present. The neovascular lesions associated with sarcoidosis are usually overshadowed by the coexistent inflammation, and the new vessel formation is thought to be secondary to retinal vascular obstruction by the perivascular infiltration with sarcoid granulomas. Our patient showed no signs of anterior or posterior uveitis but had involvement of the lacrimal glands, right lateral rectus muscle, lungs, liver, and probably parotid glands. T h e possibility of suppression of the inflammatory component during her two months on corticosteroids should be considered although no inflammation was seen before corticosteroid use, or after they were discontinued. This suppression can occur in patients with sarcoidosis and has been observed previously. 2 , 9
4-6
10
7,8
391
SUMMARY
A 30-year-old black woman with biopsy-proven sarcoidosis and sickle cell anemia had peripheral retinal neovascularization. Elevated fibrovascular proliferations and distal retinal ischemia with nonperfused ghost vessels passing through the area of neovascularization were found at the temporal periphery. No signs of intraocular inflammation were present. Both diseases occur in black patients and should always be considered in the presence of peripheral retinal neovascularization.
11,12
7
8
Vessels in neovascular lesions of sarcoidosis pass through the neovascular area into the ischemic retina, and this configuration is rare in proliferative sickle retinopathy. In these patients those vessels were patent on fluorescein angiography, whereas in our patient only nonperfused ghost vessels passed through the area of neovascularization (Fig. 3). Although either sarcoidosis or Hb S S disease could be responsible for neovascularization in our patient, a similar vasoformative factor probably stimulates new vessel proliferation in both diseases. 7
REFERENCES
1. Goldberg, M. F., Charache, S., and Acacio, I.: Ophthalmologic manifestations of sickle cell thalassemia. Arch. Intern. Med. 128:33, 1971. 2. Welch, R. B., and Goldberg, M. F.: Sickle-cell hemoglobin and its relation to fundus abnormality. Arch. Ophthalmol. 75:353, 1966. 3. Galinos, S. O., Asdourian, G. K., Woolf, M. B., Stevens, T. S., Lee, C. B., Goldberg, M. F., Chow, J. C. F., and Busse, B. J.: Spontaneous remodeling of the peripheral retinal vasculature in sickling disorders. Am. J. Ophthalmol. 79:853, 1975. 4. Condon, P. I., and Serjeant, G. R.: Ocular findings in homozygous cell anemia in Jamaica. Am. J. Ophthalmol. 73:533, 1972. 5. : Ocular findings in hemoglobin SC disease in Jamaica. Am. J. Ophthalmol. 74:921, 1972. 6. : Ocular findings in sickle cell thalassemia in Jamaica. Am. J. Ophthalmol. 74:1105, 1972. 7. Algvere, P.: Fluorescein studies of retinal vasculitis in sarcoidosis: report of a case. Acta Ophthalmol. 48:1129, 1970. 8. Asdourian, G. K., Goldberg, M. F., and Busse, B. J.: Peripheral retinal neovascularization in sarcoidosis. Arch. Ophthalmol. 93:787, 1975. 9. Serjeant, G. R., Serjeant, B. E., and Condon, P. I.: The conjunctival sign in sickle cell anemia. J.A.M.A. 219:1428, 1972. 10. Nagpal, K. C , Huamonte, F., Constantaras, A., Asdourian, G., Goldberg, F., and Busse, B.: Migratory white-without-pressure retinal lesions. Arch. Ophthalmol. 94:576, 1976. 11. Chumbley, L. C , and Kearns, T. P.: Retinopathy in sarcoidosis. Trans. Am. Ophthalmol. Soc. 69:307, 1971. 12. Gould, H. L., and Kaufman, H. E.: Sarcoid of the fundus. Arch. Ophthalmol. 65:453, 1961.
RETINAL
NEOVASCULARIZATION
SARCOIDOSIS AND
SICKLE
C E L L
ANEMIA
JOHN C . MADIGAN, J R . , M . D . , EVANGELOS S. GRAGOUDAS,
M.D.,
P E T E R L . S C H W A R T Z , M . D . , AND J A I M E V . L A P U S , M . D .
Boston,
Massachusetts
The retinal neovascularization seen in different sickle cell hemoglobinopathies has been described p r e v i o u s l y . Proliferation of new vessels at the periphery of the retina with similar appearance has been described recently in patients with proven sarcoidosis and normal hemoglobin electrophoresis. The purpose of this report is to present a patient with sarcoidosis and sickle cell anemia who developed new vessels at the retinal periphery. Since the two diseases are not mutually exclusive, both should be considered in the differential diagnosis of black patients with peripheral retinal neovascularization. 1-6
7,8
CASE REPORT
A 30-year-old black woman with a diagnosis of homozygous sickle cell (Hb SS) disease since age 8 was admitted here in 1971, in sickling crisis. Her past history was characterized by episodes of joint and extremity pain, a pregnancy at age 19 with successful delivery of a male infant with sickle cell trait (Hb AS), hepatitis during pregnancy of unknown type, and an uneventful cholecystectomy at age 21. She had had a blood transfusion once, at age 8 years. Hematologic evaluation at that time revealed Hb SS disease by cellulose acetate strip, as well as 10% Hb F by alkali denaturation, and 2.8% Hb A by starch block, all characteristic of Hb SS disease. A bilateral parotitis of unknown etiology was also noted and gradually resolved. The patient gave a history of intermittent diplopia and an ocular examination was performed. Visual acuity was R.E.: 6/6 2
From the Fluorescein Angiography Laboratory, Massachusetts Eye and Ear Infirmary (Drs. Gragoudas, Lapus, and Madigan) and the Department of Retina Research, Eye Research Institute of Retina Foundation (Drs. Gragoudas and Schwartz), Boston, Massachusetts. This study was supported by Public Health Service research grant EY-00227 from the National Eye Institute, National Institutes of Health. Reprint requests to E. S. Gragoudas, M.D., Eye Research Institute of Retina Foundation, 20 Stamford St., Boston MA 02114.
(20/20) and L.E.: 6/9 (20/30). An exophoria of 15 to 30 diopters was noted but the patient had stereopsis of 100 seconds of arc. Anterior segment and ophthalmoscopic examinations were normal with no evidence of sickle retinopathy. She was frequently admitted for joint, abdominal, and chest pain that required multiple transfusions. She developed congestive heart failure, controlled with 0.25 mg of digoxin daily, and multiple episodes of small pulmonary emboli. In addition, the patient had another male infant with Hb AS in June 1971. In early 1974, the patient was admitted to another hospital and bilateral hilar adenopathy consistent with sarcoid was noted. Results of an immunodeficiency examination were negative, including normal complement, gamma globulin, and absence of anergy. On March 17, 1975, the patient was readmitted here with dyspnea and chest pain. Evaluation on this and subsequent admissions revealed bilateral hilar adenopathy consistent with sarcoid on chest x-ray and chest tomography. Second strength purified protein derivative (PPD) was negative. Cultures of sputum, urine, and liver biopsy material were negative for mycobacteria. Antibodies to hepatitis associated antigen were nondetectable. Urine was negative for Bence Jones protein, and cold agglutinin titer was 1:2. Immunoglobulin electrophoresis revealed normal Ig A and Ig M, with moderately increased Ig G. Upper gastrointestinal series, intravenous cholangiogram, intravenous pyelogram, nephrotomograms, and a renal angiogram were normal. Serologic test for syphilis was nonreactive. On May 31, a liver biopsy specimen revealed multiple noncaseating granulomas, marked sludging of sickled red cells in the sinusoids, hemosiderin deposition in the Kupfer cells, and negative stains for acidfast and fungal organisms (Fig. 1). These findings were characteristic of both sarcoidosis and Hb SS disease. Cardiopulmonary evaluation in June, including pulmonary function tests and cardiac catheterization (left side of the heart), revealed pulmonary vascular obstructive disease caused by congestive heart failure and sickling. She continued to have episodes of chest and joint pain complicated by hypoxemia. In November, pulmonary function tests revealed the additional finding of decreased diffusion capacity thought to be caused by interstitial infiltration by sarcoidosis. At that time the patient complained of intermittent blurring of vision, and an eye examination was performed. Visual acuity was R.E.: 6/6 (20/20), and L.E.: 6/7.5 (20/25), and intraocular pressure was 15 mm Hg in both eyes. Extraocular movements were full without nystagmus or diplopia, and pupil and ante-
387
388
AMERICAN JOURNAL OF OPHTHALMOLOGY
MARCH, 1977
Fig. 1 (Madigan and associates). Liver biopsy. Top, Noncaseating granuloma typical of sarcoidosis (arrow). Bottom, Same specimen has sickled erythrocytes obstructing liver sinusoids (arrow). rior segment examinations were normal. The palpebral portions of the lacrimal glands were described as nodular, and the Hertel exophthalmometer readings were R.E.: 15, and L.E.: 12, with a92-mm base. Tangent screen fields were full to a 3-mm white object at 1 meter. Indirect ophthalmoscopy with scleral depression revealed several white elevated nodules in the temporal periphery, thought initially to represent active sarcoid uveitis. The left fundus was normal. Skull series revealed a coarse, textured calvarium consistent with Hb SS disease, and orbit-
al polytomography revealed normal optic canals and bony orbits with some increased soft tissue density in the right orbit. Orbital ultrasonography revealed an enlarged right lateral rectus muscle and lacrimal gland consistent with sarcoid. Fluorescein angiography revealed the lesions in the right temporal periphery to represent foci of neovascularization with associated distal retinal ischemia, without signs of active inflammation (Fig. 2). Because of the deterioration in her pulmonary disease and the possibility of ocular sarcoidosis, the
VOL. 83, NO. 3
RETINAL NEOVASCULARIZATION
Fig. 2 (Madigan and associates). Fluorescein angiography of the temporal periphery of the right eye demonstrates the presence of new vessels and distal ischemic retina.
patient received 40 mg of oral prednisone daily. However, she continued to have painful crises complicated by the development of narcotic dependence, and her pulmonary status failed to show significant improvement after two months on corticosteroids. On Feb. 7, 1976, ophthalmic follow-up revealed that visual acuity was R.E.: 6/7.5 (20/25), and L.E.: 6/7.5 (20/25). Intraocular pressures were 18 mm Hg, and the Hertel exophthalmometer readings were R.E.: 17, and L.E.: 16, with a 94-mm base. Slit-lamp examination was again normal with no signs of active or old uveitis. The vitreous body was free of cells and the neovascular lesions in the right eye appeared unchanged. Because of the lack of improvement in her pulmonary status and the absence of signs of sarcoid uveitis, corticosteroids were discontinued. She has never experienced aplastic crises, renal failure, osteomyelitis, or neurologic problems, and her hematocrit reading generally ranged from 20 to 30%. The patient was referred here where repeat ophthalmoscopy and fluorescein angiography on Feb. 18, 1976, confirmed the presence of the neovascular lesion (Figs. 3 and 4). In addition several ghost vessels were seen in the left far temporal periphery and several small erosions were noted inferiorly near the ora serrata in both eyes. Ghost vessels in the right eye were passing through the area of neovascularization into the area of distal ischemic retina but did not perfuse with fluorescein (Figs. 3 and 4). No angioid streaks or pigmentary changes such as "black sunbursts" or "salmon patches" were noted, and macular capillary perfusion was normal. On Feb. 20, focal laser photocoagulation of the lesion was performed using an argon laser with 239 applications of 0.2 second's duration, 500-u.diameter spot size, and 200 to 350 mW of power (Fig. 5).
389
Fig. 3 (Madigan and associates). Fundus picture showing white fibrovascular areas and ghost vessels extending beyond area of neovascularization into ischemic area.
Follow-up fluorescein angiography on March 12 showed successful obliteration of the neovascular lesion (Fig. 6). In addition, angioscopy of both peripheral fundi revealed an area of retinal ischemia in the left far temporal periphery without neovascularization. At follow-up ophthalmic examination one month after treatment and after cessation of all corticosteroids visual acuity was 6/12 (20/40) with cycloplegic retinoscopy of R.E.: +.50 + . 5 0 x 45, L.E.: +.50 +.50 x 150. The patient had no ocular symptoms. A small variable exotropia with full extraocular movements and stereopsis of 200 sec-
Fig. 4 (Madigan and associates). Fluorescein angiography shows leakage of new vessels and no filling of ghost vessels.
390
AMERICAN JOURNAL OF OPHTHALMOLOGY
MARCH, 1977
ticularly in populations with access to medical care, is the treatment of the systemic disease with multiple transfusions over extended periods. This results in alteration of the hemoglobin pattern, by increasing the H b A concentration, and elevating the hematocrit level, both of which may alter blood viscosity and, presumably, the capacity for vascular occlusion. Another factor, which may also modify atypical H b SS retinopathy, is the possibility of an occult sickle cell thalassemia (Sthal) genotype. T h e small amount of Hb A that may occur in Sthal may go undetected in an initial hemoglobin electrophoresis, and once transfusions of exogenous Hb A have been given, the Sthal genotype is impossible to establish on electrophoretic grounds. 6
Fig. 5 (Madigan and associates). Photocoagulation of feeder vessels and neovascular tufts with argon laser.
onds was present. The palpebral portion of the lacrimal glands was prominent and nodular, but exophthalmometry was normal. The Shirmer test with proparacaine hydrochloride revealed a marked decrease in basal tear production of 1 mm after five minutes. Slit-lamp examination, gonioscopy, biomicroscopy of the fundus and vitreous, and ophthalmoscopy with scleral depression revealed no sign in either eye of anterior or posterior segment inflammation. The vitreous was clear and there was no peripheral uveitis, candle wax drippings, or inflammatory venous sheathing. The neovascular lesion appeared to be obliterated. Follow-up examination two months after treatment showed visual acuity was 6/6 (20/20) and similar findings with no evidence of intraocular influence. The conjunctival vessels showed marked segmentation of the blood columns but no isolated dilated segments. Retinal examination revealed no equatorial "whitewithout-pressure" lesions, although there was extensive peripheral whitening at the ora serrata, as well as condensation of the vitreous base. Her medical management at this time consisted of hypertransfusion, which has kept her hematocrit level at 35%, given her a high Hb A level, and effectively reduced the percentage of endogenous Hb S. She remained asymptomatic on this regimen.
T h e incidence of proliferative retinopathy is higher among patients with Hb S S disease who have a high hemoglobin level, and among those with Sthal disease who have a higher Hb A level. In the light of frequent transfusions in our patient it is not surprising that the black, disk-shaped retinal scars (black sunbursts), tortuosity of veins, and conjunctival vessel anomalies often seen in pa6
DISCUSSION
T h e ocular lesions in sickle cell anemia have been described, and the rarity of peripheral neovascularization in patients with the homozygous (SS) genotype has been stressed. However, a factor that may modify sickle cell retinopathy, par2,4
Fig. 6 (Madigan and associates). Fluorescein angiography demonstrates obliteration of proliferative lesions.
VOL. 8 3 , NO. 3
RETINAL
NEOVASCULARIZATION
tients with Hb S S were lacking while the arteriolar obliteration, peripheral retinal ischemia, arteriovenous shunting, and neovascular proliferation typical of more severe sickle retinopathy, were present. In addition, there was extensive whitening of the retina at the ora serrata and condensation of the vitreous base, as reported in all sickle cell r e t i n o p a t h i e s , although the equatorial white-withoutpressure lesions recently d e s c r i b e d were not present. The neovascular lesions associated with sarcoidosis are usually overshadowed by the coexistent inflammation, and the new vessel formation is thought to be secondary to retinal vascular obstruction by the perivascular infiltration with sarcoid granulomas. Our patient showed no signs of anterior or posterior uveitis but had involvement of the lacrimal glands, right lateral rectus muscle, lungs, liver, and probably parotid glands. T h e possibility of suppression of the inflammatory component during her two months on corticosteroids should be considered although no inflammation was seen before corticosteroid use, or after they were discontinued. This suppression can occur in patients with sarcoidosis and has been observed previously. 2 , 9
4-6
10
7,8
391
SUMMARY
A 30-year-old black woman with biopsy-proven sarcoidosis and sickle cell anemia had peripheral retinal neovascularization. Elevated fibrovascular proliferations and distal retinal ischemia with nonperfused ghost vessels passing through the area of neovascularization were found at the temporal periphery. No signs of intraocular inflammation were present. Both diseases occur in black patients and should always be considered in the presence of peripheral retinal neovascularization.
11,12
7
8
Vessels in neovascular lesions of sarcoidosis pass through the neovascular area into the ischemic retina, and this configuration is rare in proliferative sickle retinopathy. In these patients those vessels were patent on fluorescein angiography, whereas in our patient only nonperfused ghost vessels passed through the area of neovascularization (Fig. 3). Although either sarcoidosis or Hb S S disease could be responsible for neovascularization in our patient, a similar vasoformative factor probably stimulates new vessel proliferation in both diseases. 7
REFERENCES
1. Goldberg, M. F., Charache, S., and Acacio, I.: Ophthalmologic manifestations of sickle cell thalassemia. Arch. Intern. Med. 128:33, 1971. 2. Welch, R. B., and Goldberg, M. F.: Sickle-cell hemoglobin and its relation to fundus abnormality. Arch. Ophthalmol. 75:353, 1966. 3. Galinos, S. O., Asdourian, G. K., Woolf, M. B., Stevens, T. S., Lee, C. B., Goldberg, M. F., Chow, J. C. F., and Busse, B. J.: Spontaneous remodeling of the peripheral retinal vasculature in sickling disorders. Am. J. Ophthalmol. 79:853, 1975. 4. Condon, P. I., and Serjeant, G. R.: Ocular findings in homozygous cell anemia in Jamaica. Am. J. Ophthalmol. 73:533, 1972. 5. : Ocular findings in hemoglobin SC disease in Jamaica. Am. J. Ophthalmol. 74:921, 1972. 6. : Ocular findings in sickle cell thalassemia in Jamaica. Am. J. Ophthalmol. 74:1105, 1972. 7. Algvere, P.: Fluorescein studies of retinal vasculitis in sarcoidosis: report of a case. Acta Ophthalmol. 48:1129, 1970. 8. Asdourian, G. K., Goldberg, M. F., and Busse, B. J.: Peripheral retinal neovascularization in sarcoidosis. Arch. Ophthalmol. 93:787, 1975. 9. Serjeant, G. R., Serjeant, B. E., and Condon, P. I.: The conjunctival sign in sickle cell anemia. J.A.M.A. 219:1428, 1972. 10. Nagpal, K. C , Huamonte, F., Constantaras, A., Asdourian, G., Goldberg, F., and Busse, B.: Migratory white-without-pressure retinal lesions. Arch. Ophthalmol. 94:576, 1976. 11. Chumbley, L. C , and Kearns, T. P.: Retinopathy in sarcoidosis. Trans. Am. Ophthalmol. Soc. 69:307, 1971. 12. Gould, H. L., and Kaufman, H. E.: Sarcoid of the fundus. Arch. Ophthalmol. 65:453, 1961.