Peripheral
Retinal Neovascularization in Sarcoidosis George
K.
Asdourian, MD; Morton F. Goldberg, MD; Bruce J. Busse, OP
Three black patients with peripheral retinal sea fan neovascularization were found to have sarcoidosis. The periphlebitic process may be the cause of stasis, hypoxia, and a secondary vasoproliferative stimulus. We noted the peculiar finding of a vessel passing through the neovascular tissue into the peripheral retina. This feature may help in the differential diagnosis.
Ocular
lesions are common in pa¬ tients with sarcoidosis. The le¬ sion most often found is anterior uve¬ itis, which occurs in 33% to 55% of the cases.1-2 Sarcoidosis patients frequent¬ ly have fundus changes, although these are usually overshadowed by the concomitant anterior uveitis. Be¬ cause of this, the true incidence of the various fundus lesions has not been well evaluated. Occasionally, the fun¬ dus lesions may be the exclusive ocu¬ lar manifestation of sarcoidosis.3 Gould and Kaufman4 noted that one third of all reported patients with posterior segment sarcoidosis had no apparent uveitis. The following lesions are described as constituting the retinopathy of sarcoidosis:3 chorioretinal spots, can¬ dle wax spots, retinal periphlebitis, macular edema, and optic nerve ede-
Submitted for publication Sept 6, 1974. From the Sickle Cell Eye Clinic, University of Illinois Eye and Ear Infirmary, Chicago. Reprint requests to University of Illinois, Department of Ophthalmology, 1855 W Taylor St, Chicago, IL 60612 (Dr. Goldberg).
ma. Other fundus changes in these patients include chorioretinal granu¬ lomas, chorioretinitis, large granulo¬ mas of the optic nerve, optic nerve atrophy, vitreous opacities, and pre¬ retinal infiltrates.4 Hemorrhagic changes in the retina and the vit¬ reous, although rare, have been re¬ ported.59 These hemorrhagic changes are usually ascribed to either new blood vessels arising over sarcoid granulomas of the optic disc,610 or to vein occlusions due to the periphlebitic process.* Retinitis prolif¬ erane has not been adequately docu¬ mented in a case of sarcoidosis, except by the fluorescein angiograph¬ ie studies of Algvere.11
We encountered three cases of sar¬ coidosis with peripheral retinal neo¬ vascularization, and believe this find¬ ing may be of importance especially in black patients. REPORT OF CASES
21-year-old black man came University of Illinois Eye and Ear Infirmary on July 9,1973, with a history of gradual loss of vision in the left eye during Case 1.—A
to the
the past several months. There was no his¬ tory of trauma. Examination revealed vit¬ reous hemorrhage in the left eye and "sea fan" peripheral neovascularization in the right eye. He was referred to the Sickle Cell Eye Clinic (SCEC) with the provision¬ al diagnosis of proliferative sickle reti¬
nopathy.
Ophthalmic examination at the SCEC revealed visual acuity to be 20/25 in the right eye and hand motions with good light projection in the left eye. Results of exter-
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nal and slit lamp examination of both eyes normal except for red blood cells in the anterior vitreous of the left eye. There was no conjunctival sickling sign12 and no iris atrophy.13 Intraocular pressure and gonioscopy were normal in both eyes. Ophthalmoscopy revealed old and new vitreous hemorrhage in the left eye, ob¬ scuring any retinal details. The right fun¬ dus had a normal disc and macula, but there were many sheathed veins (Fig 1), especially at the inferior fundus, with many occluded venules. A few round, whit¬ ish, opaque waxy lesions were seen along the veins representing the candle wax drippings described by Walsh44 and Franceschetti and Babel15 (Fig 2). Areas of pig¬ mented chorioretinal scarring were also noted at the temporal periphery. Occupy¬ ing the whole upper nasal equatorial region was an extensive fan-shaped neo¬ vascularization very similar to the neo¬ vascular sea fan described in cases of pro¬ liferative sickle retinopathy18 (Fig 3 and 4). The neovascularization, with its fibrous mantle, protruded into the vitreous cavity. Fluorescein angiography demonstrated perfusion of the neovascular tissue from multiple feeder vessels and profuse leak¬ age of dye from these abnormal vessels (Fig 5). Anterior to the neovascularization, the retina was avascular, similar to the fundus condition seen in sickle retinop¬ athy. There were extensive areas of capil¬ lary-free zones. An interesting and un¬ usual finding of fluorescein angiography was the presence of a vessel passing through the neovascular tuft into the area of avascular retina (Fig 5). An initial hemoglobin electrophoresis re¬ vealed AA hemoglobin. The patient was admitted to the hospital for systemic eval¬ uation. Physical examination found him to were
Fig 1.—Right fundus showing peri¬ sheathing (case 1).
venous
Fig 2.—Right fundus showing character¬ wax drippings (case 1).
istic candle
Fig 3.—Right fundus showing neovascularization at 12-o'clock (case 1).
sea
fan
position
Fig 4.—Right fundus showing sea fan neovascularization with its fibrous tissue mantle at 3-o'clock position (case 1). Fig 5.—Fluorescein angiography of sea fan neovascularization in right fundus. Note profuse leakage of dye and two vessels (arrows) passing through neovascular tuft into area of avascular retina (case 1).
Fig 6.—Left fundus sea fan neovascular tuft occupying upper temporal quadrant. Note perivenous sheathing (curved arrow) and vessel (straight arrow) passing through neovascular tissue into anterior retina (case 1).
Fig 7.—Fluorescein angiography of neovascularization in Fig 6. Note leakage of dye and several vessels (arrows) passing through neovascularization into area of avascular retina
(case 1).
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postprandial blood glu¬ mg/100 ml; serum cholesterol, 111 mg/100 ml; serum glutamic oxaloacetic transaminase, 43 international units (IU); serum glutamic pyruvic transaminase, 54 henry units; lactic dehydrogenase, 53 IU; prothrombin time, 12.4 seconds (normal, 11.4 seconds); partial thromboplastin time, 44.8 seconds (normal, 30 to 45 seconds); se¬ rum bilirubin, 0.9 mg/100 ml; serum cal¬ cium, 4.7 mEq/liter; and serum phos¬ phorus, 2.6 mEq/liter. Findings of the serologie test for syphilis were nega¬ tive; glucose-6-phosphate dehydrogenase screening results were negative, and the leukocyte alkaline phosphatase value was 39/100 neut (normal, 40-100 neut). Serum total protein level was 7.4 gm/100 ml with albumin, 56.6%; alpha I, 3.3%; alpha II, 11.0%; beta, 12.1%; and gamma, 17.0%. The IgG value was 1,200 mg/100 ml (normal, 1,100 ± 400 mg/100 ml); IgA, 380 mg/100 ml (normal, 182 ± 92 mg/100 ml); IgM, 310 mg/100 ml (normal, 88 ± 44 mg/100 ml); and IgD, 4 mg/100 ml (normal, 1 to 40 mg/100 ml). Complement B1C/BIB globulin was 180 mg/liter (normal, 143 ± 46 mg/liter). Transferrin value was 215 mg/100 ml (normal, 200 to 400 mg/100 ml). Lupus erythematosus preparation was negative three times. The purified protein derivative test was negative, and comple¬ ment-fixation tests for histoplasmosis, blastomycosis, and coccidioidomycosis gave negative results. A bone marrow aspiration from the right posterior iliac crest resulted in nor¬ mal findings; no leukemic process was evi¬ dent. A chest roentgenogram revealed right paratracheal lymphadenopathy with bilateral hilar lymphadenopathy consistent with sarcoidosis. Pulmonary function test values: Two-hour cose, 77
Fig 8.—Left fundus. Fluorescein angiog¬ raphy reveals sea fan neovascularization at 9-o'clock position. Arrow indicates ves¬ sel passing through neovascularization into area of avascular retina (case 2).
Fig 9.—Left fundus. Late phase fluores¬ cein angiography reveals profuse leakage of dye from neovascular tissue at 9o'clock position (case 2).
Fig 10.—Right fundus. Fluorescein angiography reveals two sea fan vascularizations at 12-o'clock meridian. Arrow indicates vessel passing through vascularization into area of avascular retina (case 3). a thin young black man in no acute dis¬ tress. The blood pressure was 120/70 mm
be
Hg; there was generalized lymphadenopathy with multiple nontender submandibu¬ lar, cervical, axillary, and inguinal lymph nodes. The lungs were clear and resonant, and there was no hepatosplenomegaly. Findings of the neurologic examination were
normal.
Laboratory studies revealed a hematocrit reading of 46% and hemoglobin value of 15.9 gm/100 ml. The white blood cell
neoneo¬
count was 5,100/cu mm. The differential cell count showed 59% neutrophils, 17%
lymphocytes, 18% monocytes, and 6% eo¬ sinophils. The platelets were adequate. Re¬ peated hemoglobin electrophoresis demon¬ strated an AA pattern with A, 96.6%; A2, 2.6%; and F, 0.8%. Urine was normal. A test for Bence Jones protein gave negative results. Multiple blood chemistry studies revealed no abnormalities except for dif¬ fusely elevated IgA and IgM proteins. Blood chemistry studies gave the following
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results were within normal limits. A sub¬ mandibular lymph node biopsy revealed noncaseating granuloma consistent with the diagnosis of sarcoidosis. The neovascular tissue was treated with argon laser photocoagulation. After three treatment sessions, during which 2,400 burns of 100µ beam diameter at 200 mv for 0.2-second durations were applied, fluores¬ cein angiography revealed nonperf usion of the treated vascular tissue. Six months after the last photocoagula¬ tion, a new sea fan neovascularization pro¬ truding into the vitreous was noted at the 3-o'clock meridian of the previously treated area. Fluorescein angiography demonstrated that this neovascular tuft obtained its blood supply from the choroid. More details about this finding are re¬
ported separately." During follow-up, the hemorrhage from the left eye gradually cleared and a total retinal detachment
was
noted. A
neo-
vascular tuft appeared in the upper tempo¬ ral quadrant (Fig 6). Fluorescein angiogra¬ phy revealed perfusion of this neovascular sea fan with profuse leakage (Fig 7). The finding of a vessel passing through the sea fan into the anterior avascular ret¬ ina was also noted here (Fig 7). Multiple nonperf used capillary beds were also pres¬ ent.
Detachment surgery is scheduled for this patient. Case 2.—A 47-year-old black man had AA hemoglobin and systemic sarcoidosis proved by lymph node biopsy in 1966. He was treated with systemic prednisone ad¬ ministered intermittently at the 2.5 to 5.0 mg/day level and did well on this regimen. He had no history of high blood pressure and his recorded blood pressure during this time was 110/80 mm Hg. The patient did not have ocular symptoms. On ocular ex¬ amination, the right eye and the anterior segment of the left eye were normal. Ophthalmoscopy of the left eye revealed, in the 9-o'clock position, a fan-shaped neo¬ vascularization very similar to the sea fan described in cases of proliferative sickle retinopathy.46 Fluorescein angiography demonstrated perfusion of the neovascular tissue and profuse leakage of dye from these abnormal vessels (Fig 8 and 9). Ante¬ rior to the neovascularization, the retina was avascular, similar to the fundus condi¬ tion seen in sickle retinopathy. A vessel passing through the neovascular tuft into the area of avascular retina was also evi¬ dent (Fig 8). Case 3.—A 30-year-old black woman had AA hemoglobin and systemic sarcoidosis proved by lymph node biopsy in 1974. She had no history of hypertension or diabetes and results of her glucose tolerance test were normal, as were all serologie tests. The patient was seen at the Eye and Ear Infirmary with a history of recurrent at¬ tacks of redness and blurring of vision in both eyes. Ophthalmic examination re¬ vealed visual acuity to be 20/30 in both eyes. Intraocular pressure in both eyes was 12 mm Hg by applanation. Results of ex¬ ternal and slit lamp examination of both eyes revealed mild circumcorneal flush, mutton fat keratic precipitates on the en¬ dothelial surface of the corneas, +2 flare and cells in the anterior chambers, and posterior synechias. Ophthalmoscopy of the right eye revealed a normal disc with abnormal vessels arising from its inferior surface. There were sheathed veins at the lower nasal quadrant. At the 9- and 12o'clock equatorial meridians, fan-shaped neovascularizations were evident. Ophthal¬ moscopy of the left eye gave normal re¬ sults. Fluorescein angiography demon¬ strated perfusion of the neovascular
Fig 11.—Right fundus. Fluorescein angiography reveals two sea fan vascularizations at 9-o'clock meridian. Arrow indicates vessel passing through vascularization into area of avascular retina (case 3). tissues and leakage of dye from all the neovascular tissues including the ones over the disc (Fig 10 and 11). A vessel passing through the equatorial neovascular tufts was also evident.
COMMENT
Peripheral retinal neovasculariza¬ tion has not been considered to be a prominent feature of sarcoid ret¬ inopathy, possibly because of rare oc¬ currence, peripheral location in the fundus, or difficulty in detection due to anterior uveitis or vitreous hemor¬ rhage. All clinical sarcoidosis patients who have a clear fundus view should undergo careful fundus examination with scierai depression, since early detection and treatment of these neo¬ vascular tufts may prevent major vit¬ hemorrhage. Peripheral retinal
reous
neovasculariza¬ tion has been found in many diseases characterized by sluggish blood flow, vascular occlusions, stasis, and hypoxia, with production of a resultant, presumed vasoformative stimulus.18 Such disease entities include sickle cell anemia, sickle cell hemoglobin C disease,16 sickle thalassemia,19 he¬ moglobin C trait,20 macroglobuline-
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neoneo¬
mia,21-22 polycythemia,23 chronic myelogenous leukemia,24·25 Eales disease,
central and branch retinal vein occlu¬ sion, diabetes, and others. A similar mechanism may apply to neovasculari¬ zation in sarcoidosis, since the peri¬ vascular infiltration of the retinal vessels with sarcoid granulomas and accompanying changes may compress (or occlude) the vessel lumen and lead to sluggish blood flow, stasis, and hypoxia of the retina, with concomitant elaboration of a putative vasoformative stimulus. The ophthalmoscopic and fluores¬ cein angiographie pattern of the neovascularizations reported here, as well as of those reported in another case of sarcoidosis41 and in two cases of chronic myelogenous leukemia,24·25 is similar to the sea fan configuration described in the different sickle cell retinopathies. This similarity may lead the ophthalmologist to an incor¬ rect clinical diagnosis, especially if the neovascularization occurs in black patients and is accompanied by pe¬ ripheral vascular occlusions and chorioretinal scars similar to those of sickle retinopathies. Hemoglobin elec¬ trophoresis is mandatory; if it shows
AA pattern, an intensive systemic and biochemical investigation is nec¬ essary to reach the correct diagnosis. On careful examination of the fluo¬ rescein angiograms, one or more un¬ usual vessels can be seen passing through the neovascular tuft into the peripheral avascular zone (Fig 5 and 7). It is not possible to say if these vessels are arterial or venous. We have seen this phenomenon in only two of more than 50 patients with an
proliferative sickle cell retinopathy whose neovascular fans end abruptly at the junction of vascular and avascular zones. In the fluorescein
an¬
giogram of the peripheral sarcoid neovascularization studied by Algvere,11 this finding is also evident. A vessel passing through the neovas¬ cularization into the anterior retina was also evident in the angio¬ grams of patients with chronic myelogenous leukemia24 25 and hemoglobin
C trait retinopathy.19 Although the
importance of this finding is not clear, its occurrence mainly in neovasculari-
zations other than those due to sickling may represent a useful ophthal¬ moscopic and angiographie sign in differential diagnosis of the retinal sea fan. This work was supported in part by National and by Institutes of Health contract 72 2956 grant IP HL 15168-03 from the National Heart and Lung Institute.
References 1. Duke-Elder S, Perkins ES: Diseases of the uveal tract, in Duke-Elder S (ed): System of Ophthal 9: St. Louis, CV Mosby Co, 1966, p 5. 2. James DG: Ocular sarcoidosis. Am J Med 26:331-339, 1959. 3. Chumbley LC, Kearns TP: Retinopathy in sarcoidosis. Trans Am Ophthalmol Soc 69:307\x=req-\ 320, 1971. 4. Gould HL, Kaufman HE: Sarcoid of the fundus. Arch Ophthalmol 65:453-456, 1961. 5. Dow DS: Ocular sarcoidosis: Report of a case characterized by vitreous and retinal hemorrhages, extensive periphlebitis, anterior uveitis and secondary glaucoma with multiple system involvement. Am J Ophthalmol 59:93-97, 1965. 6. Goldberg S, Newell FW: Sarcoidosis with retinal involvement: Report of two cases. Arch Ophthalmol 32:93-96, 1944. 7. Cross AG: Ocular sarcoidosis. Trans Ophthalmol Soc UK 75:181, 1955. 8. Hudelo A, Hudelo J: Manifestation ocularies au cours de six cas de sarcodose de Besnier-Boeck-Schaumann. Bull Soc Ophtalmol Fr, 62:21, 1962. 9. Geeraets WJ, McNeer KW, Maxey EF, et
al:
Retinopathy
in sarcoidosis. Acta
Ophthalmol
40:492-514, 1962. 10. Laties AM, Scheie HG: Evolution of mul-
tiple small tumors of sarcoid granuloma of the optic disc. Am J Ophthalmol 74:60-68, 1972. 11. Algvere P: Fluorescein studies of retinal vasculitis in sarcoidosis: Report of a case. Acta Ophthalmol 48:1129-1139, 1970. 12. Paton D: The conjunctival sign of sickle cell disease. Arch Ophthalmol 68:627-632, 1962. 13. Galinos S, Rabb MF, Goldberg MF, et al: Hemoglobin SC disease and iris atrophy. Am J Ophthalmol 75:421-425, 1973. 14. Walsh FB: Ocular importance of sarcoid. Arch Ophthalmol 21:421-438, 1939.
15. Franceschetti A, Babel J: La chorioretinit\l=e'\ en "taches de bougie" manifestation de la maladie de Besnier-Boeck. Ophthalmologica 118:701\x=req-\ 710, 1949. 16. Welch RB, Goldberg MF: Sickle cell hemoglobin and its relation to fundus abnormality. Arch Ophthalmol 75:353-362, 1966. 17. Galinos SO, Asdourian GK, Woolf MB, et al: Choroido-vitreal neovascularization after argon laser photocoagulation. Arch Ophthalmol 93:524-530, 1975.
Downloaded From: http://archopht.jamanetwork.com/ by a University of Calgary User on 05/28/2015
18. Wise GN: Factors influencing retinal new vessel formation. Am J Ophthalmol 52:637-650, 1961. 19. Goldberg MF, Charache S, Acacio I: Ophthalmologic manifestations of sickle cell thalassemia. Arch Intern Med 128:33-39, 1971. 20. Moschandreou M, Galinos S, Valenzuela R, et al: Retinopathy in hemoglobin C trait (AC hemoglobinopathy). Am J Ophthalmol 77:465-471, 1974. 21. Anderson
B, Samuelson A: A case of hyperglobulinemia with pronounced eye changes and acrocyanosis. Acta Med Scand 117:248-260, 1944. 22. Carr RE, Henkind P: Retinal findings associated with serum hyperviscosity. Am J Ophthalmol 56:23-31, 1963. 23. Nagy F: Changes in the fundus caused by polycythemia. Br J Ophthalmol 34:380-384, 1950. 24. Frank RN, Ryan SJ: Peripheral retinal neovascularization with chronic myelogenous leukemia. Arch Ophthalmol 87:585-589, 1972. 25. Morse PH, McCready JL: Peripheral retinal neovascularization in chronic myelocytic leukemia. Am J Ophthalmol 72:975-978, 1971.
Retinal Neovascularization in Sarcoidosis George
K.
Asdourian, MD; Morton F. Goldberg, MD; Bruce J. Busse, OP
Three black patients with peripheral retinal sea fan neovascularization were found to have sarcoidosis. The periphlebitic process may be the cause of stasis, hypoxia, and a secondary vasoproliferative stimulus. We noted the peculiar finding of a vessel passing through the neovascular tissue into the peripheral retina. This feature may help in the differential diagnosis.
Ocular
lesions are common in pa¬ tients with sarcoidosis. The le¬ sion most often found is anterior uve¬ itis, which occurs in 33% to 55% of the cases.1-2 Sarcoidosis patients frequent¬ ly have fundus changes, although these are usually overshadowed by the concomitant anterior uveitis. Be¬ cause of this, the true incidence of the various fundus lesions has not been well evaluated. Occasionally, the fun¬ dus lesions may be the exclusive ocu¬ lar manifestation of sarcoidosis.3 Gould and Kaufman4 noted that one third of all reported patients with posterior segment sarcoidosis had no apparent uveitis. The following lesions are described as constituting the retinopathy of sarcoidosis:3 chorioretinal spots, can¬ dle wax spots, retinal periphlebitis, macular edema, and optic nerve ede-
Submitted for publication Sept 6, 1974. From the Sickle Cell Eye Clinic, University of Illinois Eye and Ear Infirmary, Chicago. Reprint requests to University of Illinois, Department of Ophthalmology, 1855 W Taylor St, Chicago, IL 60612 (Dr. Goldberg).
ma. Other fundus changes in these patients include chorioretinal granu¬ lomas, chorioretinitis, large granulo¬ mas of the optic nerve, optic nerve atrophy, vitreous opacities, and pre¬ retinal infiltrates.4 Hemorrhagic changes in the retina and the vit¬ reous, although rare, have been re¬ ported.59 These hemorrhagic changes are usually ascribed to either new blood vessels arising over sarcoid granulomas of the optic disc,610 or to vein occlusions due to the periphlebitic process.* Retinitis prolif¬ erane has not been adequately docu¬ mented in a case of sarcoidosis, except by the fluorescein angiograph¬ ie studies of Algvere.11
We encountered three cases of sar¬ coidosis with peripheral retinal neo¬ vascularization, and believe this find¬ ing may be of importance especially in black patients. REPORT OF CASES
21-year-old black man came University of Illinois Eye and Ear Infirmary on July 9,1973, with a history of gradual loss of vision in the left eye during Case 1.—A
to the
the past several months. There was no his¬ tory of trauma. Examination revealed vit¬ reous hemorrhage in the left eye and "sea fan" peripheral neovascularization in the right eye. He was referred to the Sickle Cell Eye Clinic (SCEC) with the provision¬ al diagnosis of proliferative sickle reti¬
nopathy.
Ophthalmic examination at the SCEC revealed visual acuity to be 20/25 in the right eye and hand motions with good light projection in the left eye. Results of exter-
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nal and slit lamp examination of both eyes normal except for red blood cells in the anterior vitreous of the left eye. There was no conjunctival sickling sign12 and no iris atrophy.13 Intraocular pressure and gonioscopy were normal in both eyes. Ophthalmoscopy revealed old and new vitreous hemorrhage in the left eye, ob¬ scuring any retinal details. The right fun¬ dus had a normal disc and macula, but there were many sheathed veins (Fig 1), especially at the inferior fundus, with many occluded venules. A few round, whit¬ ish, opaque waxy lesions were seen along the veins representing the candle wax drippings described by Walsh44 and Franceschetti and Babel15 (Fig 2). Areas of pig¬ mented chorioretinal scarring were also noted at the temporal periphery. Occupy¬ ing the whole upper nasal equatorial region was an extensive fan-shaped neo¬ vascularization very similar to the neo¬ vascular sea fan described in cases of pro¬ liferative sickle retinopathy18 (Fig 3 and 4). The neovascularization, with its fibrous mantle, protruded into the vitreous cavity. Fluorescein angiography demonstrated perfusion of the neovascular tissue from multiple feeder vessels and profuse leak¬ age of dye from these abnormal vessels (Fig 5). Anterior to the neovascularization, the retina was avascular, similar to the fundus condition seen in sickle retinop¬ athy. There were extensive areas of capil¬ lary-free zones. An interesting and un¬ usual finding of fluorescein angiography was the presence of a vessel passing through the neovascular tuft into the area of avascular retina (Fig 5). An initial hemoglobin electrophoresis re¬ vealed AA hemoglobin. The patient was admitted to the hospital for systemic eval¬ uation. Physical examination found him to were
Fig 1.—Right fundus showing peri¬ sheathing (case 1).
venous
Fig 2.—Right fundus showing character¬ wax drippings (case 1).
istic candle
Fig 3.—Right fundus showing neovascularization at 12-o'clock (case 1).
sea
fan
position
Fig 4.—Right fundus showing sea fan neovascularization with its fibrous tissue mantle at 3-o'clock position (case 1). Fig 5.—Fluorescein angiography of sea fan neovascularization in right fundus. Note profuse leakage of dye and two vessels (arrows) passing through neovascular tuft into area of avascular retina (case 1).
Fig 6.—Left fundus sea fan neovascular tuft occupying upper temporal quadrant. Note perivenous sheathing (curved arrow) and vessel (straight arrow) passing through neovascular tissue into anterior retina (case 1).
Fig 7.—Fluorescein angiography of neovascularization in Fig 6. Note leakage of dye and several vessels (arrows) passing through neovascularization into area of avascular retina
(case 1).
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postprandial blood glu¬ mg/100 ml; serum cholesterol, 111 mg/100 ml; serum glutamic oxaloacetic transaminase, 43 international units (IU); serum glutamic pyruvic transaminase, 54 henry units; lactic dehydrogenase, 53 IU; prothrombin time, 12.4 seconds (normal, 11.4 seconds); partial thromboplastin time, 44.8 seconds (normal, 30 to 45 seconds); se¬ rum bilirubin, 0.9 mg/100 ml; serum cal¬ cium, 4.7 mEq/liter; and serum phos¬ phorus, 2.6 mEq/liter. Findings of the serologie test for syphilis were nega¬ tive; glucose-6-phosphate dehydrogenase screening results were negative, and the leukocyte alkaline phosphatase value was 39/100 neut (normal, 40-100 neut). Serum total protein level was 7.4 gm/100 ml with albumin, 56.6%; alpha I, 3.3%; alpha II, 11.0%; beta, 12.1%; and gamma, 17.0%. The IgG value was 1,200 mg/100 ml (normal, 1,100 ± 400 mg/100 ml); IgA, 380 mg/100 ml (normal, 182 ± 92 mg/100 ml); IgM, 310 mg/100 ml (normal, 88 ± 44 mg/100 ml); and IgD, 4 mg/100 ml (normal, 1 to 40 mg/100 ml). Complement B1C/BIB globulin was 180 mg/liter (normal, 143 ± 46 mg/liter). Transferrin value was 215 mg/100 ml (normal, 200 to 400 mg/100 ml). Lupus erythematosus preparation was negative three times. The purified protein derivative test was negative, and comple¬ ment-fixation tests for histoplasmosis, blastomycosis, and coccidioidomycosis gave negative results. A bone marrow aspiration from the right posterior iliac crest resulted in nor¬ mal findings; no leukemic process was evi¬ dent. A chest roentgenogram revealed right paratracheal lymphadenopathy with bilateral hilar lymphadenopathy consistent with sarcoidosis. Pulmonary function test values: Two-hour cose, 77
Fig 8.—Left fundus. Fluorescein angiog¬ raphy reveals sea fan neovascularization at 9-o'clock position. Arrow indicates ves¬ sel passing through neovascularization into area of avascular retina (case 2).
Fig 9.—Left fundus. Late phase fluores¬ cein angiography reveals profuse leakage of dye from neovascular tissue at 9o'clock position (case 2).
Fig 10.—Right fundus. Fluorescein angiography reveals two sea fan vascularizations at 12-o'clock meridian. Arrow indicates vessel passing through vascularization into area of avascular retina (case 3). a thin young black man in no acute dis¬ tress. The blood pressure was 120/70 mm
be
Hg; there was generalized lymphadenopathy with multiple nontender submandibu¬ lar, cervical, axillary, and inguinal lymph nodes. The lungs were clear and resonant, and there was no hepatosplenomegaly. Findings of the neurologic examination were
normal.
Laboratory studies revealed a hematocrit reading of 46% and hemoglobin value of 15.9 gm/100 ml. The white blood cell
neoneo¬
count was 5,100/cu mm. The differential cell count showed 59% neutrophils, 17%
lymphocytes, 18% monocytes, and 6% eo¬ sinophils. The platelets were adequate. Re¬ peated hemoglobin electrophoresis demon¬ strated an AA pattern with A, 96.6%; A2, 2.6%; and F, 0.8%. Urine was normal. A test for Bence Jones protein gave negative results. Multiple blood chemistry studies revealed no abnormalities except for dif¬ fusely elevated IgA and IgM proteins. Blood chemistry studies gave the following
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results were within normal limits. A sub¬ mandibular lymph node biopsy revealed noncaseating granuloma consistent with the diagnosis of sarcoidosis. The neovascular tissue was treated with argon laser photocoagulation. After three treatment sessions, during which 2,400 burns of 100µ beam diameter at 200 mv for 0.2-second durations were applied, fluores¬ cein angiography revealed nonperf usion of the treated vascular tissue. Six months after the last photocoagula¬ tion, a new sea fan neovascularization pro¬ truding into the vitreous was noted at the 3-o'clock meridian of the previously treated area. Fluorescein angiography demonstrated that this neovascular tuft obtained its blood supply from the choroid. More details about this finding are re¬
ported separately." During follow-up, the hemorrhage from the left eye gradually cleared and a total retinal detachment
was
noted. A
neo-
vascular tuft appeared in the upper tempo¬ ral quadrant (Fig 6). Fluorescein angiogra¬ phy revealed perfusion of this neovascular sea fan with profuse leakage (Fig 7). The finding of a vessel passing through the sea fan into the anterior avascular ret¬ ina was also noted here (Fig 7). Multiple nonperf used capillary beds were also pres¬ ent.
Detachment surgery is scheduled for this patient. Case 2.—A 47-year-old black man had AA hemoglobin and systemic sarcoidosis proved by lymph node biopsy in 1966. He was treated with systemic prednisone ad¬ ministered intermittently at the 2.5 to 5.0 mg/day level and did well on this regimen. He had no history of high blood pressure and his recorded blood pressure during this time was 110/80 mm Hg. The patient did not have ocular symptoms. On ocular ex¬ amination, the right eye and the anterior segment of the left eye were normal. Ophthalmoscopy of the left eye revealed, in the 9-o'clock position, a fan-shaped neo¬ vascularization very similar to the sea fan described in cases of proliferative sickle retinopathy.46 Fluorescein angiography demonstrated perfusion of the neovascular tissue and profuse leakage of dye from these abnormal vessels (Fig 8 and 9). Ante¬ rior to the neovascularization, the retina was avascular, similar to the fundus condi¬ tion seen in sickle retinopathy. A vessel passing through the neovascular tuft into the area of avascular retina was also evi¬ dent (Fig 8). Case 3.—A 30-year-old black woman had AA hemoglobin and systemic sarcoidosis proved by lymph node biopsy in 1974. She had no history of hypertension or diabetes and results of her glucose tolerance test were normal, as were all serologie tests. The patient was seen at the Eye and Ear Infirmary with a history of recurrent at¬ tacks of redness and blurring of vision in both eyes. Ophthalmic examination re¬ vealed visual acuity to be 20/30 in both eyes. Intraocular pressure in both eyes was 12 mm Hg by applanation. Results of ex¬ ternal and slit lamp examination of both eyes revealed mild circumcorneal flush, mutton fat keratic precipitates on the en¬ dothelial surface of the corneas, +2 flare and cells in the anterior chambers, and posterior synechias. Ophthalmoscopy of the right eye revealed a normal disc with abnormal vessels arising from its inferior surface. There were sheathed veins at the lower nasal quadrant. At the 9- and 12o'clock equatorial meridians, fan-shaped neovascularizations were evident. Ophthal¬ moscopy of the left eye gave normal re¬ sults. Fluorescein angiography demon¬ strated perfusion of the neovascular
Fig 11.—Right fundus. Fluorescein angiography reveals two sea fan vascularizations at 9-o'clock meridian. Arrow indicates vessel passing through vascularization into area of avascular retina (case 3). tissues and leakage of dye from all the neovascular tissues including the ones over the disc (Fig 10 and 11). A vessel passing through the equatorial neovascular tufts was also evident.
COMMENT
Peripheral retinal neovasculariza¬ tion has not been considered to be a prominent feature of sarcoid ret¬ inopathy, possibly because of rare oc¬ currence, peripheral location in the fundus, or difficulty in detection due to anterior uveitis or vitreous hemor¬ rhage. All clinical sarcoidosis patients who have a clear fundus view should undergo careful fundus examination with scierai depression, since early detection and treatment of these neo¬ vascular tufts may prevent major vit¬ hemorrhage. Peripheral retinal
reous
neovasculariza¬ tion has been found in many diseases characterized by sluggish blood flow, vascular occlusions, stasis, and hypoxia, with production of a resultant, presumed vasoformative stimulus.18 Such disease entities include sickle cell anemia, sickle cell hemoglobin C disease,16 sickle thalassemia,19 he¬ moglobin C trait,20 macroglobuline-
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neoneo¬
mia,21-22 polycythemia,23 chronic myelogenous leukemia,24·25 Eales disease,
central and branch retinal vein occlu¬ sion, diabetes, and others. A similar mechanism may apply to neovasculari¬ zation in sarcoidosis, since the peri¬ vascular infiltration of the retinal vessels with sarcoid granulomas and accompanying changes may compress (or occlude) the vessel lumen and lead to sluggish blood flow, stasis, and hypoxia of the retina, with concomitant elaboration of a putative vasoformative stimulus. The ophthalmoscopic and fluores¬ cein angiographie pattern of the neovascularizations reported here, as well as of those reported in another case of sarcoidosis41 and in two cases of chronic myelogenous leukemia,24·25 is similar to the sea fan configuration described in the different sickle cell retinopathies. This similarity may lead the ophthalmologist to an incor¬ rect clinical diagnosis, especially if the neovascularization occurs in black patients and is accompanied by pe¬ ripheral vascular occlusions and chorioretinal scars similar to those of sickle retinopathies. Hemoglobin elec¬ trophoresis is mandatory; if it shows
AA pattern, an intensive systemic and biochemical investigation is nec¬ essary to reach the correct diagnosis. On careful examination of the fluo¬ rescein angiograms, one or more un¬ usual vessels can be seen passing through the neovascular tuft into the peripheral avascular zone (Fig 5 and 7). It is not possible to say if these vessels are arterial or venous. We have seen this phenomenon in only two of more than 50 patients with an
proliferative sickle cell retinopathy whose neovascular fans end abruptly at the junction of vascular and avascular zones. In the fluorescein
an¬
giogram of the peripheral sarcoid neovascularization studied by Algvere,11 this finding is also evident. A vessel passing through the neovas¬ cularization into the anterior retina was also evident in the angio¬ grams of patients with chronic myelogenous leukemia24 25 and hemoglobin
C trait retinopathy.19 Although the
importance of this finding is not clear, its occurrence mainly in neovasculari-
zations other than those due to sickling may represent a useful ophthal¬ moscopic and angiographie sign in differential diagnosis of the retinal sea fan. This work was supported in part by National and by Institutes of Health contract 72 2956 grant IP HL 15168-03 from the National Heart and Lung Institute.
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