Ophthalmologies!. Basel 177: 140 145 (1978)
Retinal Ischemia (Capillary Nonperfusion) and Retinal Neovascularization in Patients with Diabetic Retinopathy1 .S'. Merin, /. Ber and M. Ivry Department of Ophthalmology. Hadassah University Hospital. Jerusalem
Materials and Methods 253 consecutive patients with diabetic retino pathy attending the Retinopathy Clinic of the Hadassah Eye Department were examined and referred for fluorescein angiography. The methods of angiography used were previously described \Merin el til., 1978]. After exclusion of patients with hazy media and uncooperative patients. 138 patients with good fluorescein angiograms of the 1 Supported in part by the Swiss Fund for Re search in Ophthalmology (Dr. Merin). Part of this study served as an MD thesis for the Hebrew University of Jerusalem (Dr. Her).
macular area remained and are the subject of this study. Of these, 71 were men and 67 were women. Most patients had only one eye photographed.
Results
Most areas of CNP were surrounded by additional pathology in the form of micro aneurysms, dilated and tortuous capillaries, or arteriovenous shunts (fig. 1). Some pa tients had severe capillary pathology in most of the examined retina (fig. 2, 3). Abnor mally dilated arterioles and venules were seen crossing areas of CNP. Their thickness varied, with caliber variations prominent and increased leakage into their walls (fig. 4). The areas of CNP could be seen affecting any part of the capillary bed but often these were noted as based on an existing large vessel, so that this vessel (arteriole or venule) served as a boundary for one side of the area of CNP (fig. 3, 5). 36 of 142 eyes (25.3%) had neovascu larization in the photographed macular area. The neovascularization was usually within or on the border of an area of CNP (fig. 3, 4. 6, 7).
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In a previous study [Merin el al., 1978] the high ineidenee of eapillary nonperfusion (CNP), as detected by fluorescein angiog raphy in patients with diabetic retinopathy, was noted. It was shown there that systemic hypertension does not have a substantial ef fect on the presence of CNP. The purpose of the present study was to seek the relationship of capillary nonper fusion to other intraretinal microvascular abnormalities (IRMA) and to the develop ment of retinal neovascularization in pa tients with diabetic retinopathy.
Retinal Ischemia and Retinal Neovascularization
141
Table I. The anatomical relationship of neo vascularization (NV) to areas of CNP in 36 eyes
NV within or on border of CNP area NV away from CNP area NV without visible CNP area Relationship not clear
Eyes, n
%
26 5 3 2
72.2 13.9 8.3 5.6 p 0.001
Table II. The relationship of size of CNP and neovascularization (NV) in 93 patients with CNP1 Total area of CNP, d.d.
NV present
NV absent
Less than 1 1-2 2-3 More than 3 Not clear
6 7 3 16 1
31 15 8 5 1 p< 0.001 p 3 d.d.). Patients with hypertension had more neo vascularization than normotensive patients but the difference was not statistically sig nificant. Neovascularization was found in 15.4% of normotensives, 24.6% of hyper tensives and 26.8% of patients with border line hypertension.
143
Merin/Ber/Ivry
144
Summary 138 diabetic retinopathy patients with good fluorescein angiograms of the macular areas were studied. Areas of capillary nonperfusion (CNP) were surrounded by other capillary abnormalities and were often based on a larger retinal vessel. A statistically highly significant anatomical rela tionship was found between CNP and neovascular ization. In addition, the frequency of neovascu larization increased with the increase in size of CNP.
Zusammenfassung 138 Patienten mit einer diabetischen Retino pathie und gutem Fluoreszenzangiogramm der Makula wurden untersucht. Avaskuläre Kapillar-
gebicte waren umgeben von anderen Kapillar anomalien und lagen häufig über einem grösseren retinalen Gefäss. Zwischen avaskulären Arealen und Gefässneubildungcn wurde eine statistisch hochsignifikante anatomische Beziehung gefunden. Zusätzlich stieg die Häufigkeit der Gefässneubildungen mit der Grössenzunahme der avasku lären Areale an.
Résumé Etude de 138 patients souffrant d'une rétino pathie diabétique et pour lesquels les auteurs dis posaient de bons angiogrammes fluorescéiniques de la macula. Des zones capillaires avasculaires étaient entourées par d'autres anomalies capil laires et se trouvaient souvent au-dessus d'un grand vaisseau rétinien. Une relation anatomique statistiquement, hautement significative, a été notée entre la présence de zones avasculaires et la néo vascularisation. De plus, la fréquence des néo vascularisations augmentait avec l'étendue des zones avasculaires.
References Ashton, N.: Studies of the retinal capillaries in relation to diabetic and other retinopathies. Br. J. Ophthal. 47: 521-538 (1963). Ashton, N.: Pathophysiology of retinal cotton wool spots. Br. mcd. Bull. 26: 143-150 (1970). Ashton. N.; Dollcry, C. T.: Henkind. P.; Hill, D. W.; Paterson, J. W.; Ramalho, P. S., and Shakib, M.: Focal retinal ischaemia, ophthal moscopic circulatory and ultra-structural changes. Br. J. Ophthal. 50: 283-384 (1966). Davis. M. D.: The natural course of diabetic ret inopathy. Symposium on DR. Trans. Am. Acad. Ophthal. Oto-lar. 721: 237-241 (1968). • Davis. M. D.: Definition, classification, and course of DR; in Lynn, Snyder Vaiser Diabetic retino pathy, pp. 7-33 (Gruñe & Stratton, New York 1974). Gass, J. D. M.: A fluorescein angiographic study of macular dysfunction secondary to retinal vascular diseases. III. Hypertensive retinopathy. Archs Ophthal. 80: 569-582 (1968).
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cularization was seen without CNP. It could be that the CNP is present, but in another region, which was not photographed, but it could also be that the area of CNP revas cularized after the development of CNP. It was claimed that areas of CNP are found more frequently near arteries [Ashton et al., 1966; Gass, 1968; Ashton, 1970] while the density of retinal capillaries is greater near veins. These facts do not ex plain our finding that the area of CNP was often bounded by either an arteriole or a venule. It is possible that this was caused by a swelling of the nerve axons in the ischemic area which displaced the vessel, as was seen in histological specimens [Ashton et al., 1966; Ashton, 1970]. However, the arte rioles bounding areas of CNP did not look displaced. Another explanation could be that areas of CNP develop near arteries as a result of occlusion of primary or second ary feeding arterioles as suggested by Gass [1968].
Goldberg, M. F.: The role of ischaemia in the production of vascular retinopathies; in Lynn. Snyder and Vaiscr Diabetic retinopathy, pp. 47-63 (Gruñe & Stratton. New York 1974). Kohner. E. M.; Dollery, C. T.; Paterson. J. W.. and Oakley, N. W.: Arterial fluorescein studies in DR. Diabetes 16: 1-10 (1967). Kohner, E. M.; Shilling, J. S., and Hamilton, A. M.: The role of avascular retina in new vessel for mation. Metab. Ophthal. /: 15-23 (1976). Little. H. L.: Retinal NV in diabetes mellitus and the role of fluorescein angiography in argon laser photocoagulation; in Lynn, Snyder and Vaiser Diabetic retinopathy, pp. 133-144 (Gru ñe & Stratton, New York 1974).
145
Little. H. L.: The role of abnormal hemorrheodynamics in the pathogenesis of diabetic retino pathy. Trans. Am. ophthal. Soc. 74: 573-636 (1976). Merin. S.; Ber, L, and Ivry, M.: Retinal ischemia (capillary nonperfusion) in diabetic retinopathy of patients with and without systemic hyper tension. Ophthalmologica 177: 76-81 (1978). Michaelson, 1. C.: Retinal circulation in man and animals (Thomas. Springfield 1954).
Prof. S. Merin. Department of Ophthalmology, POB 499. Jerusalem (Israel)
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Retinal Ischemia and Retinal Neovascularization
Retinal Ischemia (Capillary Nonperfusion) and Retinal Neovascularization in Patients with Diabetic Retinopathy1 .S'. Merin, /. Ber and M. Ivry Department of Ophthalmology. Hadassah University Hospital. Jerusalem
Materials and Methods 253 consecutive patients with diabetic retino pathy attending the Retinopathy Clinic of the Hadassah Eye Department were examined and referred for fluorescein angiography. The methods of angiography used were previously described \Merin el til., 1978]. After exclusion of patients with hazy media and uncooperative patients. 138 patients with good fluorescein angiograms of the 1 Supported in part by the Swiss Fund for Re search in Ophthalmology (Dr. Merin). Part of this study served as an MD thesis for the Hebrew University of Jerusalem (Dr. Her).
macular area remained and are the subject of this study. Of these, 71 were men and 67 were women. Most patients had only one eye photographed.
Results
Most areas of CNP were surrounded by additional pathology in the form of micro aneurysms, dilated and tortuous capillaries, or arteriovenous shunts (fig. 1). Some pa tients had severe capillary pathology in most of the examined retina (fig. 2, 3). Abnor mally dilated arterioles and venules were seen crossing areas of CNP. Their thickness varied, with caliber variations prominent and increased leakage into their walls (fig. 4). The areas of CNP could be seen affecting any part of the capillary bed but often these were noted as based on an existing large vessel, so that this vessel (arteriole or venule) served as a boundary for one side of the area of CNP (fig. 3, 5). 36 of 142 eyes (25.3%) had neovascu larization in the photographed macular area. The neovascularization was usually within or on the border of an area of CNP (fig. 3, 4. 6, 7).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 9:36:08 AM
In a previous study [Merin el al., 1978] the high ineidenee of eapillary nonperfusion (CNP), as detected by fluorescein angiog raphy in patients with diabetic retinopathy, was noted. It was shown there that systemic hypertension does not have a substantial ef fect on the presence of CNP. The purpose of the present study was to seek the relationship of capillary nonper fusion to other intraretinal microvascular abnormalities (IRMA) and to the develop ment of retinal neovascularization in pa tients with diabetic retinopathy.
Retinal Ischemia and Retinal Neovascularization
141
Table I. The anatomical relationship of neo vascularization (NV) to areas of CNP in 36 eyes
NV within or on border of CNP area NV away from CNP area NV without visible CNP area Relationship not clear
Eyes, n
%
26 5 3 2
72.2 13.9 8.3 5.6 p 0.001
Table II. The relationship of size of CNP and neovascularization (NV) in 93 patients with CNP1 Total area of CNP, d.d.
NV present
NV absent
Less than 1 1-2 2-3 More than 3 Not clear
6 7 3 16 1
31 15 8 5 1 p< 0.001 p 3 d.d.). Patients with hypertension had more neo vascularization than normotensive patients but the difference was not statistically sig nificant. Neovascularization was found in 15.4% of normotensives, 24.6% of hyper tensives and 26.8% of patients with border line hypertension.
143
Merin/Ber/Ivry
144
Summary 138 diabetic retinopathy patients with good fluorescein angiograms of the macular areas were studied. Areas of capillary nonperfusion (CNP) were surrounded by other capillary abnormalities and were often based on a larger retinal vessel. A statistically highly significant anatomical rela tionship was found between CNP and neovascular ization. In addition, the frequency of neovascu larization increased with the increase in size of CNP.
Zusammenfassung 138 Patienten mit einer diabetischen Retino pathie und gutem Fluoreszenzangiogramm der Makula wurden untersucht. Avaskuläre Kapillar-
gebicte waren umgeben von anderen Kapillar anomalien und lagen häufig über einem grösseren retinalen Gefäss. Zwischen avaskulären Arealen und Gefässneubildungcn wurde eine statistisch hochsignifikante anatomische Beziehung gefunden. Zusätzlich stieg die Häufigkeit der Gefässneubildungen mit der Grössenzunahme der avasku lären Areale an.
Résumé Etude de 138 patients souffrant d'une rétino pathie diabétique et pour lesquels les auteurs dis posaient de bons angiogrammes fluorescéiniques de la macula. Des zones capillaires avasculaires étaient entourées par d'autres anomalies capil laires et se trouvaient souvent au-dessus d'un grand vaisseau rétinien. Une relation anatomique statistiquement, hautement significative, a été notée entre la présence de zones avasculaires et la néo vascularisation. De plus, la fréquence des néo vascularisations augmentait avec l'étendue des zones avasculaires.
References Ashton, N.: Studies of the retinal capillaries in relation to diabetic and other retinopathies. Br. J. Ophthal. 47: 521-538 (1963). Ashton, N.: Pathophysiology of retinal cotton wool spots. Br. mcd. Bull. 26: 143-150 (1970). Ashton. N.; Dollcry, C. T.: Henkind. P.; Hill, D. W.; Paterson, J. W.; Ramalho, P. S., and Shakib, M.: Focal retinal ischaemia, ophthal moscopic circulatory and ultra-structural changes. Br. J. Ophthal. 50: 283-384 (1966). Davis. M. D.: The natural course of diabetic ret inopathy. Symposium on DR. Trans. Am. Acad. Ophthal. Oto-lar. 721: 237-241 (1968). • Davis. M. D.: Definition, classification, and course of DR; in Lynn, Snyder Vaiser Diabetic retino pathy, pp. 7-33 (Gruñe & Stratton, New York 1974). Gass, J. D. M.: A fluorescein angiographic study of macular dysfunction secondary to retinal vascular diseases. III. Hypertensive retinopathy. Archs Ophthal. 80: 569-582 (1968).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 9:36:08 AM
cularization was seen without CNP. It could be that the CNP is present, but in another region, which was not photographed, but it could also be that the area of CNP revas cularized after the development of CNP. It was claimed that areas of CNP are found more frequently near arteries [Ashton et al., 1966; Gass, 1968; Ashton, 1970] while the density of retinal capillaries is greater near veins. These facts do not ex plain our finding that the area of CNP was often bounded by either an arteriole or a venule. It is possible that this was caused by a swelling of the nerve axons in the ischemic area which displaced the vessel, as was seen in histological specimens [Ashton et al., 1966; Ashton, 1970]. However, the arte rioles bounding areas of CNP did not look displaced. Another explanation could be that areas of CNP develop near arteries as a result of occlusion of primary or second ary feeding arterioles as suggested by Gass [1968].
Goldberg, M. F.: The role of ischaemia in the production of vascular retinopathies; in Lynn. Snyder and Vaiscr Diabetic retinopathy, pp. 47-63 (Gruñe & Stratton. New York 1974). Kohner. E. M.; Dollery, C. T.; Paterson. J. W.. and Oakley, N. W.: Arterial fluorescein studies in DR. Diabetes 16: 1-10 (1967). Kohner, E. M.; Shilling, J. S., and Hamilton, A. M.: The role of avascular retina in new vessel for mation. Metab. Ophthal. /: 15-23 (1976). Little. H. L.: Retinal NV in diabetes mellitus and the role of fluorescein angiography in argon laser photocoagulation; in Lynn, Snyder and Vaiser Diabetic retinopathy, pp. 133-144 (Gru ñe & Stratton, New York 1974).
145
Little. H. L.: The role of abnormal hemorrheodynamics in the pathogenesis of diabetic retino pathy. Trans. Am. ophthal. Soc. 74: 573-636 (1976). Merin. S.; Ber, L, and Ivry, M.: Retinal ischemia (capillary nonperfusion) in diabetic retinopathy of patients with and without systemic hyper tension. Ophthalmologica 177: 76-81 (1978). Michaelson, 1. C.: Retinal circulation in man and animals (Thomas. Springfield 1954).
Prof. S. Merin. Department of Ophthalmology, POB 499. Jerusalem (Israel)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 9:36:08 AM
Retinal Ischemia and Retinal Neovascularization
