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Arteriolar Occlusive Diseases of the Macula
Arteriolar Occlusive Diseases of the Macula LEE M. JAMPOL, MD
Abstract: Occlusion of retinal precapillary arterioles may be related to vascular endothelial damage, embolization, vasculitis, and other factors. Following acute retinal precapillary arteriolar occlusion in the macular area, inhibition of axoplasmic transport results in the formation of cotton-wool patches. A variable loss of retinal function occurs. During the subacute phase, reperfusion of the vascular bed is usually seen with a gradual fading of the cotton-wool patch. In the chronic phase, the only sign of the infarction may be a loss of inner retinal substance with an irregularity of the light reflex from the internal limiting membrane, the retinal depression sign. The characteristics of retinal precapillary arteriolar occlusions are reviewed and specific features of hypertensive retinopathy, talc retinopathy, and sickle cell retinopathy are discussed. [Key words: axoplasmic transport, cotton-wool patch, hypertension, ischemia, precapillary arteriole, sickle cell retinopathy, talc retinopathy.] Ophthalmology
90:534-539, 1983
Closure of retinal capillaries with loss of function is a common occurrence in ophthalmology. This can be seen as a chronic relentless process in patients with diabetes mellitus or following acute vascular occlusions as seen in patients with central retinal artery occlusion. Extensive capillary loss in the posterior pole is also seen in patients with central retinal vein occlusion and branch retinal vein occlusion. This report describes a group of diseases characterized by closure of retinal precapillary arterioles in the posterior pole (Table 1). Although the mechanism of arteriolar closure varies from disease to disease, the ophthalmoscopic picture seen in these patients is similar because of the similarity of the anatomic site of closure. The acute, subacute, and chronic appearances of the retina following precapillary arteriolar occlusion are discussed and specific features of patients with hypertensive retinopathy, talc retinopathy, and sickle cell retinopathy are described. From the Department of Ophthalmology, University of Illinois College of Medicine, Chicago, Illinois. Supported in part by Grant PHS HL 15168 from The National Heart, Lung and Blood Institute, and Grant PHS EY 02214 and Core Grant EY 1792 from the National Eye Institute, National Institutes of Health, Bethesda, Maryland. Presented at the Eighty·Seventh Annual Meeting of the American Academy of Ophthalmology, San Francisco, California, October 30-Novernber 5, 1982. Reprint requests to Lee M. Jarnpol, MD 1855 W. Taylor Street, Chicago, IL 60612.
534
ACUTE CLOSURE OF THE RETINAL PRECAPILLARY ARTERIOLE Closure of the retinal precapillary arteriole may be related to embolization (eg, talc retinopathy), vasculitis, (eg, lupus erythematosus), blockage by abnormal erythrocytes (sickle cell retinopathy), or abnormalities of the vascular endothelium (hypertension, diabetes mellitus, radiation retinopathy, and others). With occlusion ofthe retinal precapillary arteriole, the distal capillary bed is not perfused normally and the retina becomes ischemic. If fluorescein angiography is performed at the proper moment, a dark line corresponding to the occluded precapillary arteriole may be seen (Figs 1, 2). Microaneurysmal dilatation of the adjacent retinal capillary bed occurs. Leakage of fluorescein from these adjacent capillaries may result in diffuse staining of the area of ischemia. The local ischemia inhibits orthograde and retrograde axoplasmic transport with the formation of cotton-wool patches! (Fig 3). These patches may be seen on either side of the area of ischemia (ie, toward or away from the disc) or, if the lesion is small, the cotton-wool patch may occupy the entire area of ischemia. In the acute phase, loss of function in the area of occlusion may be symptomatic. However, depending upon the location and size of the lesion the patient may also be asymptomatic. If sensitive testing is used (such as static perimetry),2 a scotoma often can be demonstrated in the area of ischemia. However, despite an obvious vascular
0161-6420/83/0500/0534/$1.10 © American Academy of Ophthalmology
JAM POL • ARTERIOLAR OCCLUSIVE DISEASES
Table 1. Arteriolar Occlusive Diseases of The Macula 1. 2. 3. 4. 5. 6. 7. 8.
Hypertension Embolic retinopathies (eg, talc) Sickle cell disease Radiation retinopathy Acquired diseases of connective tissue (eg, lupus erythematosus) Diabetes mellitus Chronic granulocytic leukemia Others
occlusion in the macular area, visual acuity, color vision testing, Amsler grid testing, and kinetic perimetry may be completely normal. On the other hand, these tests may reveal abnormalities (eg, central and paracentral scotomas). When the capillary closure involves the fovea, it mayor may not be associated with measurable loss of central visual acuity. The whitening of the retina in the area of the cottonwool patch corresponds to an accumulation of axonal organelles at the margins of the ischemic area. Histopathologically, these swollen axons have been called cytoid bodies. The accumulation of the organelles can be demonstrated on both the proximal and distal margins of the areas of ischemia. 1
SUBACUTE CHANGES This phase, usually occurring days to weeks after the occlusion, is characterized by gradual fading of the cotton-wool patches. Reperfusion of the precapillary arte-
rioles and the dependent vascular bed can usually be demonstrated; on rare occasions, however, there may be permanent nonperfusion. Remodeling of the vascular bed may occur with abnormally tortuous capillaries. The density of the capillaries may also be diminished. Some return of visual function may be seen if the fovea had been involved and visual acuity had been impaired initially. On the other hand, permanent visual loss is not uncommon. Again, careful perimetry will usually reveal residual functional abnormality in the area of ischemia.
CHRONIC CHANGES This stage of retinal precapillary arteriolar occlusion has not received adequate attention in the past. Dr. Michael Goldbaum has described in detail the "retinal depression sign.,,2 If large areas of the inner retina are infarcted, for example, following central retinal artery occlusion, a diffuse loss of inner retinal substance is seen; this may be apparent only by increased transparency of the retina in the chronic phase. However, with local retinal infarctions (varying from less than one to several disc diameters in size) the loss of inner retinal elements results in local areas of concavity, which can be detected ophthalmoscopically (Fig 4). Observation with the direct ophthalmoscope, indirect ophthalmoscope, or the fundus camera reveals a darkening of the area of involvement, particularly in young patients and patients with darkly pigmented fundi. If the "depressed" lesion is small, there actually may be a focusing of the light rays, causing a small central bright reflex.
Figs lA-B. A, fluorescein angiogram of monkey with talc retinopathy. Precapillary arterioles are obstructed and are visible as dark lines (arrows). B, photograph shows cotton-wool patches in regions ofretinal ischemia. (Reprinted from Arch Ophthalmol 1981; 99:1275 with permission.)
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OPHTHALMOLOGY • MAY 1983 • VOLUME 90 • NUMBER 5
Fig 2. Patient with hemoglobin SC disease. Fluorescein angiogram demonstrates occluded arterioles.
Fig 3. Photograph of area seen in Figure 2. Axoplasmic accumulation along edge of ischemic area results in cotton-wool patch (arrows).
Retinal depression signs are not obvious unless they are looked for specifically. In patients with hypertension, embolization, and the other entities described in this review, they are common and are important signs of previous retinal ischemia. The retinal depression sign becomes particularly important because fluorescein an-
giography at this time may reveal a normal capillary bed. On the other hand, residual abnormalities including thinning out of the capillary bed, abnormally tortuous capillaries, venous loops, or rarely nonperfusion may be seen.
HYPERTENSIVE RETINOPATHY
Fig 4. Multiple retinal depression signs in patient with sickle cell disease (arrows and others).
536
Hypertension is a common cause of posterior pole and macular arteriolar occlusion. Cotton-wool spots are often present (Fig 5). Although primates with hypertensive retinopathy have been studied3 and material on humans has been collected,4,5 the exact mechanism of the retinal precapillary arteriolar occlusion still remains uncertain~ Direct damage to the vascular endothelium in the precapillary arteriole is an important factor however. This damage also causes hemorrhages in the nerve fiber layer. Vascular leakage is often associated with retinal exudation, retinal edema, and in severe cases, macular star formation. Disc edema may also be present. With control of the blood pressure, resolution of the cotton-wool patchs and retinal hemorrhages is seen (Fig 6); however, retinal depression signs often remain. Figure 7 demonstrates a patient initially seen with a controlled blood pressure but multiple retinal depression signs. At this time there was no evidence ofaxoplasmic stasis. The patient discontinued his antihypertensive medications and was subsequently seen with multiple fresh cotton-wool patches around the foveal area (Fig 8). The old depression signs were still visible. Sometimes hypertensive retinopathy may be associated with obstruction of larger arterioles. 5 Nonperfu-
JAMPOL • ARTERIOLAR OCCLUSIVE DISEASES
Fig 5. Acute cotton-wool patch and macular star formation in patient with uncontrolled hypertension.
Fig 6. Same eye pictured in Figure 5. Blood pressure has been controlled. Cotton-wool patches are gone but depression signs remain.
Fig 7. Multiple depression signs in patient with hypertension. (Reprinted from Ophthalmology 1982; 89: 1140 with permission.)
Fig 8. Same eye seen in Figure 7. Blood pressure is now poorly controlled and acute cotton-wool patches have appeared. (Reprinted from Ophthalmology 1982; 89:1140 with permission.)
sion of the dependent capillary bed is visible around the damaged arteriole. However, with control of the blood pressure, subsequent remodeling and reperfusion of the vasculature may be seen despite permanent nonperfusion of the large arteriole.
TALC RETINOPATHY The mechanism of precapillary arteriolar occlusion in patients with talc retinopathy is more apparent. 6 Drug 537
OPHTHALMOLOGY • MAY 1983 • VOLUME 90 • NUMBER 5
abusers crush oral medications containing talc as a filler and inject them intravenously. After a prolonged period of injections, talc particles pass through collateral vessels in the lungs and enter the systemic circulation. The talc crystals then embolize to the eye, where they obstruct precapillary arterioles. Vascular closure in the peripheral retina may be associated with neovascularization. 7 Vascular closure in the macular area results in areas of retinal ischemia (Fig I). The talc can be recognized in the posterior pole as multiple glistening crystals usually surrounding the foveal area and along the temporal raphe (Fig 9). Areas of precapillary arteriolar occlusion, capillary nonperfusion, microaneurysmal dilatation of the vascular bed, tortuosity and irregular capillaries and other changes are apparent in the macular area of these patients. 7-9 We have created an animal model of talc retinopathy with chronic intravenous injections in rhesus monkeys.6 We were able to demonstrate occlusion of precapillary arterioles with the secondary formation of cotton-wool patches. Leakage of the vascular bed was invariably present. With termination of the injections the cotton-wool patches disappeared. Trypsin digestion studies confirmed occlusion of precapillary arterioles by the talc crystals. 10 Patients and monkeys with talc embolization have normal electroretinograms.6,8 However, focal foveal electroretinography may be abnormal. 8 In severe cases, scotomas are easily demonstrated using the Amsler grid or kinetic perimetry. However, these tests often show normal findings.
SICKLE CELL RETINOPATHY Patients with sickle cell disease are well known to develop peripheral retinal vascular nonperfusion. Recently, however, attention has focused on macular changes in these patients. II Precapillary arteriolar occlusions in the posterior pole and macular area are common (Figs 2, 3, 10). It is unclear whether the mechanism of closure is obstruction by irreversibly sickled cells, sick-
Fig 10. Patient with sickle cell disease demonstrates area of cottonwool patch formation (arrows) from small retinal arteriolar occlusions.
ling of the cells in the precapillary arteriole, or a backup from log-jamming of erythrocytes in the capillary bed. Careful fluorescein angiography demonstrates abnormalities of the macular vasculature in at least 20 to 30% of patients with sickle cell disease. 12,13 Although these patients occasionally present with central retinal artery or major branch retinal artery occlusion, more commonly perimacular precapillary arteriolar occlusions are seen with the formation of cotton-wool patches. The evolution of the cotton-wool patches through the acute, subacute, and chronic phases has been demonstrated,12-14 and retinal depression signs are seen frequently in these patients, Remodeling of the vasculature in the macular area has been demonstrated by fluorescein angiography. 14
OTHER ARTERIOLAR OCCLUSIVE DISEASES IN THE MACULA
Fig 9. Talc crystals in macular area of drug abuser.
538
Patients with radiation retinopathy may develop macular precapillary arteriolar obliteration with capillary nonperfusion. 15 Microaneurysms, exudation, and other changes similar to diabetic retinopathy are seen. The changes develop months to years following exposure of the retina to radiation. Patients with very high granulocyte counts from chronic granulocytic leukemia may develop occlusion of small vessels in the macular area. 16 Patients with retinal vasculitis from acquired connective tissue diseases, particularly lupus erythematosus, may develop precapillary arteriolar disease. 17 This results in the appearance of multiple cotton-wool patches, sometimes seen as the
JAM POL •
ARTERIOLAR OCCLUSIVE DISEASES
presenting sign of patients with acquired disease of connective tissue, even in the absence of hypertension. Many of these patients do have hypertension, and it seems likely that the hypertension and vasculitis are additive in their effects on the precapillary arteriole. Patients with diabetes mellitus may also show multiple macular arteriolar occlusions with the development of widespread macular ischemia. 18 This variant of diabetic retinopathy is particularly common in patients with juvenile onset diabetes mellitus. It is interesting that the clinical findings are so similar in such a diverse group of diseases as those shown in the Table 1. It is also interesting that the incidence of disc and retinal neovascularization varies greatly from disease to disease. For example, patients with hypertension alone do not develop disc, iris, or retinal neovascularization. Patients with talc retinopathy may develop peripheral retinal neovascularization and occasionally disc or iris neovascularization. On the other hand, patients with sickle cell disease frequently develop peripheral retinal neovascularization, but almost never develop disc or iris neovascularization. Patients with ischemic diabetic maculopathy frequently develop neovascularization of the disc, neovascularization elsewhere, and frequently rubeosis iridis. The differences in the comparative incidence of disc neovascularization, retinal neovascularization, and rubeosis iridis in these different disease processes may be related to the location and the amount of ischemic retina. Despite these differences, however, the macular lesions in these various diseases are very similar.
REFERENCES 1. McLeod D, Marshall J, Kohner EM, Bird AC. The role ofaxoplasmic transport in the pathogenesis of retinal cotton-wool spots. Br J OphthalmoI1977; 61:177-91.
2. Goldbaum MH. Retinal depression sign indicating a small retinal infarct. Am J Ophthalmol 1978; 86:45-55. 3. Garner A, Ashton N, Tripathi R, et al. Pathogenesis of hypertensive retinopathy; an experimental study in the monkey. Br J Ophthalmol 1975; 59:3-44. 4. Ashton N. The eye in malignant hypertension. Trans Am Acad OphthalmolOtolaryngol 1972; 76:17-40. 5. Tso MOM, Jampol LM. Pathophysiology of hypertensive retinopathy. Ophthalmology 1982; 89:1132-45. 6. Jampol LM, Setogawa T, Rednam KRV, Tso MOM. Talc retinopathy in primates. A model of ischemic retinopathy: I. Clinical studies. Arch Ophthalmol 1981; 99:1273-80. 7. Kresca LJ, Goldberg MF, Jampol LM. Talc emboli and retinal neovascularization in a drug abuser. Am J Ophthalmol 1979; 87:334-9. 8. Friberg TR, Gragoudas ES, Regan CDJ. Talc emboli and macular ischemia in intravenous drug abuse. Arch Ophthalmol1979; 97:108991. 9. Tse DT, Ober RR. Talc retinopathy. Am J Ophthalmol1980; 90:62440. 10. Kaga N, Tso MOM, Jampol LM, et al. Talc retinopathy in primates: a model of ischemic retinopathy. II. A histopathologic study. Arch Ophthalmol 1982; 100:1644-8. 11. Goldberg MF, Galinos S, Lee CB, et al. Macular ischemia and infarction in sickling. Invest Ophthalmol 1973; 12:633-5. 12. Stevens TS, Busse B, Lee CB, et al. Sickling hemoglobinopathies; macular and perimacular vascular abnormalities. Arch Ophthalmol 1974; 92:455-63. 13. Asdourian GK, Nagpal KC, Busse B, et al. Macular and peri macular vascular remodelling in sickling haemoglobinopathies. Br J Ophthalmol 1976; 60:431-53. 14. Goldberg MF. Retinal vaso-occlusion in sickling hemoglobinopathies, Birth Defects 1976; 12:475-515. 15. Irvine AR, Alvarado JA, Wara WM, et aI. Radiation retinopathy: an experimental model for the ischemic-proliferative retinopathies. Trans Am Ophthalmol Soc 1981; 79:103-22. 16. Jampol LM, Rabb MF. Peripheral retinal occlusive disease. In: Yannuzzi LA, Gitter KA, Schatz H (eds). The Macula: A Comprehensive Text and Atlas. Baltimore: Williams and Wilkins, 1979; 103-17. 17. Jampol LM, Rabb MF: Vasoocclusive diseases of the posterior pole. Int Ophthalmol Clin 1981; 21(3):201-13. 18. Bresnick GH, de Venecia G, Myers FL, et al. Retinal ischemia in diabetic retinopathy. Arch Ophthalmol 1975; 93: 1300-1 O.
539
Abstract: Occlusion of retinal precapillary arterioles may be related to vascular endothelial damage, embolization, vasculitis, and other factors. Following acute retinal precapillary arteriolar occlusion in the macular area, inhibition of axoplasmic transport results in the formation of cotton-wool patches. A variable loss of retinal function occurs. During the subacute phase, reperfusion of the vascular bed is usually seen with a gradual fading of the cotton-wool patch. In the chronic phase, the only sign of the infarction may be a loss of inner retinal substance with an irregularity of the light reflex from the internal limiting membrane, the retinal depression sign. The characteristics of retinal precapillary arteriolar occlusions are reviewed and specific features of hypertensive retinopathy, talc retinopathy, and sickle cell retinopathy are discussed. [Key words: axoplasmic transport, cotton-wool patch, hypertension, ischemia, precapillary arteriole, sickle cell retinopathy, talc retinopathy.] Ophthalmology
90:534-539, 1983
Closure of retinal capillaries with loss of function is a common occurrence in ophthalmology. This can be seen as a chronic relentless process in patients with diabetes mellitus or following acute vascular occlusions as seen in patients with central retinal artery occlusion. Extensive capillary loss in the posterior pole is also seen in patients with central retinal vein occlusion and branch retinal vein occlusion. This report describes a group of diseases characterized by closure of retinal precapillary arterioles in the posterior pole (Table 1). Although the mechanism of arteriolar closure varies from disease to disease, the ophthalmoscopic picture seen in these patients is similar because of the similarity of the anatomic site of closure. The acute, subacute, and chronic appearances of the retina following precapillary arteriolar occlusion are discussed and specific features of patients with hypertensive retinopathy, talc retinopathy, and sickle cell retinopathy are described. From the Department of Ophthalmology, University of Illinois College of Medicine, Chicago, Illinois. Supported in part by Grant PHS HL 15168 from The National Heart, Lung and Blood Institute, and Grant PHS EY 02214 and Core Grant EY 1792 from the National Eye Institute, National Institutes of Health, Bethesda, Maryland. Presented at the Eighty·Seventh Annual Meeting of the American Academy of Ophthalmology, San Francisco, California, October 30-Novernber 5, 1982. Reprint requests to Lee M. Jarnpol, MD 1855 W. Taylor Street, Chicago, IL 60612.
534
ACUTE CLOSURE OF THE RETINAL PRECAPILLARY ARTERIOLE Closure of the retinal precapillary arteriole may be related to embolization (eg, talc retinopathy), vasculitis, (eg, lupus erythematosus), blockage by abnormal erythrocytes (sickle cell retinopathy), or abnormalities of the vascular endothelium (hypertension, diabetes mellitus, radiation retinopathy, and others). With occlusion ofthe retinal precapillary arteriole, the distal capillary bed is not perfused normally and the retina becomes ischemic. If fluorescein angiography is performed at the proper moment, a dark line corresponding to the occluded precapillary arteriole may be seen (Figs 1, 2). Microaneurysmal dilatation of the adjacent retinal capillary bed occurs. Leakage of fluorescein from these adjacent capillaries may result in diffuse staining of the area of ischemia. The local ischemia inhibits orthograde and retrograde axoplasmic transport with the formation of cotton-wool patches! (Fig 3). These patches may be seen on either side of the area of ischemia (ie, toward or away from the disc) or, if the lesion is small, the cotton-wool patch may occupy the entire area of ischemia. In the acute phase, loss of function in the area of occlusion may be symptomatic. However, depending upon the location and size of the lesion the patient may also be asymptomatic. If sensitive testing is used (such as static perimetry),2 a scotoma often can be demonstrated in the area of ischemia. However, despite an obvious vascular
0161-6420/83/0500/0534/$1.10 © American Academy of Ophthalmology
JAM POL • ARTERIOLAR OCCLUSIVE DISEASES
Table 1. Arteriolar Occlusive Diseases of The Macula 1. 2. 3. 4. 5. 6. 7. 8.
Hypertension Embolic retinopathies (eg, talc) Sickle cell disease Radiation retinopathy Acquired diseases of connective tissue (eg, lupus erythematosus) Diabetes mellitus Chronic granulocytic leukemia Others
occlusion in the macular area, visual acuity, color vision testing, Amsler grid testing, and kinetic perimetry may be completely normal. On the other hand, these tests may reveal abnormalities (eg, central and paracentral scotomas). When the capillary closure involves the fovea, it mayor may not be associated with measurable loss of central visual acuity. The whitening of the retina in the area of the cottonwool patch corresponds to an accumulation of axonal organelles at the margins of the ischemic area. Histopathologically, these swollen axons have been called cytoid bodies. The accumulation of the organelles can be demonstrated on both the proximal and distal margins of the areas of ischemia. 1
SUBACUTE CHANGES This phase, usually occurring days to weeks after the occlusion, is characterized by gradual fading of the cotton-wool patches. Reperfusion of the precapillary arte-
rioles and the dependent vascular bed can usually be demonstrated; on rare occasions, however, there may be permanent nonperfusion. Remodeling of the vascular bed may occur with abnormally tortuous capillaries. The density of the capillaries may also be diminished. Some return of visual function may be seen if the fovea had been involved and visual acuity had been impaired initially. On the other hand, permanent visual loss is not uncommon. Again, careful perimetry will usually reveal residual functional abnormality in the area of ischemia.
CHRONIC CHANGES This stage of retinal precapillary arteriolar occlusion has not received adequate attention in the past. Dr. Michael Goldbaum has described in detail the "retinal depression sign.,,2 If large areas of the inner retina are infarcted, for example, following central retinal artery occlusion, a diffuse loss of inner retinal substance is seen; this may be apparent only by increased transparency of the retina in the chronic phase. However, with local retinal infarctions (varying from less than one to several disc diameters in size) the loss of inner retinal elements results in local areas of concavity, which can be detected ophthalmoscopically (Fig 4). Observation with the direct ophthalmoscope, indirect ophthalmoscope, or the fundus camera reveals a darkening of the area of involvement, particularly in young patients and patients with darkly pigmented fundi. If the "depressed" lesion is small, there actually may be a focusing of the light rays, causing a small central bright reflex.
Figs lA-B. A, fluorescein angiogram of monkey with talc retinopathy. Precapillary arterioles are obstructed and are visible as dark lines (arrows). B, photograph shows cotton-wool patches in regions ofretinal ischemia. (Reprinted from Arch Ophthalmol 1981; 99:1275 with permission.)
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OPHTHALMOLOGY • MAY 1983 • VOLUME 90 • NUMBER 5
Fig 2. Patient with hemoglobin SC disease. Fluorescein angiogram demonstrates occluded arterioles.
Fig 3. Photograph of area seen in Figure 2. Axoplasmic accumulation along edge of ischemic area results in cotton-wool patch (arrows).
Retinal depression signs are not obvious unless they are looked for specifically. In patients with hypertension, embolization, and the other entities described in this review, they are common and are important signs of previous retinal ischemia. The retinal depression sign becomes particularly important because fluorescein an-
giography at this time may reveal a normal capillary bed. On the other hand, residual abnormalities including thinning out of the capillary bed, abnormally tortuous capillaries, venous loops, or rarely nonperfusion may be seen.
HYPERTENSIVE RETINOPATHY
Fig 4. Multiple retinal depression signs in patient with sickle cell disease (arrows and others).
536
Hypertension is a common cause of posterior pole and macular arteriolar occlusion. Cotton-wool spots are often present (Fig 5). Although primates with hypertensive retinopathy have been studied3 and material on humans has been collected,4,5 the exact mechanism of the retinal precapillary arteriolar occlusion still remains uncertain~ Direct damage to the vascular endothelium in the precapillary arteriole is an important factor however. This damage also causes hemorrhages in the nerve fiber layer. Vascular leakage is often associated with retinal exudation, retinal edema, and in severe cases, macular star formation. Disc edema may also be present. With control of the blood pressure, resolution of the cotton-wool patchs and retinal hemorrhages is seen (Fig 6); however, retinal depression signs often remain. Figure 7 demonstrates a patient initially seen with a controlled blood pressure but multiple retinal depression signs. At this time there was no evidence ofaxoplasmic stasis. The patient discontinued his antihypertensive medications and was subsequently seen with multiple fresh cotton-wool patches around the foveal area (Fig 8). The old depression signs were still visible. Sometimes hypertensive retinopathy may be associated with obstruction of larger arterioles. 5 Nonperfu-
JAMPOL • ARTERIOLAR OCCLUSIVE DISEASES
Fig 5. Acute cotton-wool patch and macular star formation in patient with uncontrolled hypertension.
Fig 6. Same eye pictured in Figure 5. Blood pressure has been controlled. Cotton-wool patches are gone but depression signs remain.
Fig 7. Multiple depression signs in patient with hypertension. (Reprinted from Ophthalmology 1982; 89: 1140 with permission.)
Fig 8. Same eye seen in Figure 7. Blood pressure is now poorly controlled and acute cotton-wool patches have appeared. (Reprinted from Ophthalmology 1982; 89:1140 with permission.)
sion of the dependent capillary bed is visible around the damaged arteriole. However, with control of the blood pressure, subsequent remodeling and reperfusion of the vasculature may be seen despite permanent nonperfusion of the large arteriole.
TALC RETINOPATHY The mechanism of precapillary arteriolar occlusion in patients with talc retinopathy is more apparent. 6 Drug 537
OPHTHALMOLOGY • MAY 1983 • VOLUME 90 • NUMBER 5
abusers crush oral medications containing talc as a filler and inject them intravenously. After a prolonged period of injections, talc particles pass through collateral vessels in the lungs and enter the systemic circulation. The talc crystals then embolize to the eye, where they obstruct precapillary arterioles. Vascular closure in the peripheral retina may be associated with neovascularization. 7 Vascular closure in the macular area results in areas of retinal ischemia (Fig I). The talc can be recognized in the posterior pole as multiple glistening crystals usually surrounding the foveal area and along the temporal raphe (Fig 9). Areas of precapillary arteriolar occlusion, capillary nonperfusion, microaneurysmal dilatation of the vascular bed, tortuosity and irregular capillaries and other changes are apparent in the macular area of these patients. 7-9 We have created an animal model of talc retinopathy with chronic intravenous injections in rhesus monkeys.6 We were able to demonstrate occlusion of precapillary arterioles with the secondary formation of cotton-wool patches. Leakage of the vascular bed was invariably present. With termination of the injections the cotton-wool patches disappeared. Trypsin digestion studies confirmed occlusion of precapillary arterioles by the talc crystals. 10 Patients and monkeys with talc embolization have normal electroretinograms.6,8 However, focal foveal electroretinography may be abnormal. 8 In severe cases, scotomas are easily demonstrated using the Amsler grid or kinetic perimetry. However, these tests often show normal findings.
SICKLE CELL RETINOPATHY Patients with sickle cell disease are well known to develop peripheral retinal vascular nonperfusion. Recently, however, attention has focused on macular changes in these patients. II Precapillary arteriolar occlusions in the posterior pole and macular area are common (Figs 2, 3, 10). It is unclear whether the mechanism of closure is obstruction by irreversibly sickled cells, sick-
Fig 10. Patient with sickle cell disease demonstrates area of cottonwool patch formation (arrows) from small retinal arteriolar occlusions.
ling of the cells in the precapillary arteriole, or a backup from log-jamming of erythrocytes in the capillary bed. Careful fluorescein angiography demonstrates abnormalities of the macular vasculature in at least 20 to 30% of patients with sickle cell disease. 12,13 Although these patients occasionally present with central retinal artery or major branch retinal artery occlusion, more commonly perimacular precapillary arteriolar occlusions are seen with the formation of cotton-wool patches. The evolution of the cotton-wool patches through the acute, subacute, and chronic phases has been demonstrated,12-14 and retinal depression signs are seen frequently in these patients, Remodeling of the vasculature in the macular area has been demonstrated by fluorescein angiography. 14
OTHER ARTERIOLAR OCCLUSIVE DISEASES IN THE MACULA
Fig 9. Talc crystals in macular area of drug abuser.
538
Patients with radiation retinopathy may develop macular precapillary arteriolar obliteration with capillary nonperfusion. 15 Microaneurysms, exudation, and other changes similar to diabetic retinopathy are seen. The changes develop months to years following exposure of the retina to radiation. Patients with very high granulocyte counts from chronic granulocytic leukemia may develop occlusion of small vessels in the macular area. 16 Patients with retinal vasculitis from acquired connective tissue diseases, particularly lupus erythematosus, may develop precapillary arteriolar disease. 17 This results in the appearance of multiple cotton-wool patches, sometimes seen as the
JAM POL •
ARTERIOLAR OCCLUSIVE DISEASES
presenting sign of patients with acquired disease of connective tissue, even in the absence of hypertension. Many of these patients do have hypertension, and it seems likely that the hypertension and vasculitis are additive in their effects on the precapillary arteriole. Patients with diabetes mellitus may also show multiple macular arteriolar occlusions with the development of widespread macular ischemia. 18 This variant of diabetic retinopathy is particularly common in patients with juvenile onset diabetes mellitus. It is interesting that the clinical findings are so similar in such a diverse group of diseases as those shown in the Table 1. It is also interesting that the incidence of disc and retinal neovascularization varies greatly from disease to disease. For example, patients with hypertension alone do not develop disc, iris, or retinal neovascularization. Patients with talc retinopathy may develop peripheral retinal neovascularization and occasionally disc or iris neovascularization. On the other hand, patients with sickle cell disease frequently develop peripheral retinal neovascularization, but almost never develop disc or iris neovascularization. Patients with ischemic diabetic maculopathy frequently develop neovascularization of the disc, neovascularization elsewhere, and frequently rubeosis iridis. The differences in the comparative incidence of disc neovascularization, retinal neovascularization, and rubeosis iridis in these different disease processes may be related to the location and the amount of ischemic retina. Despite these differences, however, the macular lesions in these various diseases are very similar.
REFERENCES 1. McLeod D, Marshall J, Kohner EM, Bird AC. The role ofaxoplasmic transport in the pathogenesis of retinal cotton-wool spots. Br J OphthalmoI1977; 61:177-91.
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