F L U O R E S C E I N PATTERN O F T H E CHORIOCAPILLARIS IN T H E NEONATAL RHESUS MONKEY H E N R Y D. P E R R Y , M.D.,
R O B E R T V. H A T F I E L D , B.A., Washington,
Recent angiographic 1 - 6 and anatomic 7 , 8 studies suggest that the vascular pattern of the choriocapillaris is segmental in arrangement. The segmental pattern is based on individual units called lobules, 3 each of which is supplied by a choroidal arteriole and drained by a choroidal venule. Most investigators believe each lob ule of the choriocapillaris is supplied by a central arteriole and drained by circum ferential venules. 1 ' 4 - 6 , 9 - 1 1 The study of the choroidal circulation by fluorescein angiography has been made difficult by the natural barrier filter of the retinal pigment epithelium (RPE). In human albinos, in whom the barrier is least, nystagmus and poor fixation make sharp angiographic pictures difficult to obtain. Since neonatal rhesus monkeys have little pigment in the RPE and choroid, they provide unique subjects in which to study the choroidal circulation
AND M A R K O. M. T S O ,
M.D.
D.C.
and delineate the pattern of the chorio capillaris. In this report we review the sequence of accumulation of pigment in the RPE and submacular choroid in the neonatal period as well as the patterns of filling of the choroidal vasculature by fluorescein. From these data we propose a scheme for the circulatory dynamics of the chorio capillaris in the normal neonatal rhesus monkey. M A T E R I A L AND M E T H O D S
From the Registry of Ophthalmic Pathology, Armed Forces Institute of Pathology, and the De partment of Ophthalmology, George Washington University Medical Center (Dr. Tso), Washington, D.C. This work was supported in part by U.S. Public Health Service Research grants EY-01903 and EY-01163 and training grant EY-00032 from the National Eye Institute, National Institutes of Health, Bethesda, Maryland. In conducting the research described in this re port, the investigators adhered to the "Guide for Laboratory Animal Facilities and Care" as promul gated by the Committee on the Guide for Laboratory Animal Facilities and Care of the Institute of Labo ratory Animal Resources, National Academy of Sciences-National Research Council. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of De fense. Reprint requests to Mark O. M. Tso, M.D., Uni versity of Illinois Eye and Ear Infirmary, 1855 W. Taylor St., Chicago, IL 60612.
We studied seven neonatal rhesus mon keys during the first 12 weeks of life by serial fundus photography and fluoresce in angiography by means of the Zeiss Fundus Flash II with Spectrotech filters. Anesthesia was obtained with a combina tion of 10.05 ml of ketamine hydrochloride and a titration of 1:4 dilution of pentobarbital, 65 mg/ml. The eyes were dilated with 10% phenylephrine hydrochloride and 0.5% tropicamide, one drop in each eye one half hour before photogra phy. Color fundus photographs were taken before each angiogram. We injected 0.1 ml of 10% fluorescein into the greater saphenous vein. We obtained 23 angiograms over a 12-week period, 14 in the first six weeks and nine in the second six weeks. Two eyes were enucleated at 2 weeks and 12 weeks of age, respectively, and fixed in 2% glutaraldehyde solution. The tissues were embedded in Epon, sec tioned at 2 (X, and stained with toluidine blue for light microscopy. RESULTS
Fundus pigmentation—From birth to approximately six weeks, the fundus was bright red and had clearly visible retinal
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Fig. 1 (Perry, Hatfield, and Tso). Fundus photo graph of macular area in 2-week-old rhesus mon key showing a generalized lack of pigmentation. The retinal and choroidal vessels are distinct, and there is no delineation of the macula.
choroidal vessels (Fig. 1). There was no well-demarcated macular (foveal)* area, and pigmentation of the macula was ab sent. During the ensuing weeks, increas ing pigmentation of the fundus resulted in a mottled appearance, obscuring the choroidal vessels. After 6 months of age the fundus developed a dark, brownishgreen color and a well-demarcated macu la, typical of the adult rhesus monkey (Fig. 2). Histopathologic examination of the foveal area in 2-week-old and 3month-old rhesus monkeys demonstrated clearly the increased pigmentation of the RPE and the choroid that developed dur ing this neonatal period (Fig. 3). Fluorescein angiography—Fluorescein angiograms in neonatal rhesus monkeys demonstrated a consistent circulatory pat tern for the choroid.' We observed two distinct patterns of filling, an initial phase *Following the recommendations suggested by Yanoff and Fine, the term "macula" will be used for clinical matters, while the equivalent term "fovea" will be used for anatomic descriptions.
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and a recirculation of dye both appearing ahead of the retinal phase. The transit time through the choroidal circulation was from 1.8 to 2.3 seconds. The pattern of the fluorescein angio grams is illustrated by atypical series taken from a 2-week-old rhesus monkey. Fluorescein is first seen entering the large choroidal arteries via the short posterior ciliary arteries 4.4 seconds after injection (Fig. 4). At 4.8 seconds, as the retinal arterial phase appeared, fluorescent puffs of varying sizes were noted along the choroidal arteries, representing the filling of choroidal arterioles. The puffs were larger on the nasal side of the macula than on the temporal side (Fig. 5). At 5.2 sec onds, the late retinal arterial phase, the choroidal fluorescence became more ho mogeneous as each puff became larger and appeared as an individual lobule (Fig. 6). The lobules measured 150 to 300 ma. in diameter. Subsequently the centers of the nasal lobules became hypofluorescent and were surrounded by the fluores-
Fig. 2 (Perry, Hatfield, and Tso). Fundus photo graph of macular area in the same rhesus monkey six months later showing a deeply pigmented fundus. The choroidal vessels are obscured, and a welldemarcated macula is present.
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i^V-v •_•-• s-t'*f*«-/fl»'|2sC;
Fig. 3 (Perry, Hatfield, and Tso). Photomicrograph of the macular area in a 2-week-old rhesus (left) and 12-week-old rhesus (right). Increased pigmentation of the retinal pigment epithelium and choroid is evident in the older monkey. Both sections are parafoveolar (x440, toluidine blue).
cent borders of the lobules. Temporal to the macula, the lobules were hyperfluorescent, in contrast to those nasally. At 5.6 seconds a diffuse "fishnet" pattern ap peared across the choroid (Fig. 7). This pattern was made u p of polygonal lobules of varying size having perimeters that
were hyperfluorescent (venules) and cen ters that were hypofluorescent. At this time, the retina was in the arteriovenous phase. At 6.0 seconds, in the venous phase of the retinal circulation and in the late venous phase of the choroidal circu lation, the fishnet pattern faded nasally,
Fig. 4 (Perry, Hatfield, and Tso). (Phase 2). Fluorescein angiogram of left macular area in 2-week-old rhesus monkey. Early filling of cho roidal vessels from the short poster ior ciliary arteries at 4.4 seconds after injection.
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Fig. 5 (Perry, Hatfield, and Tso). (Phase 2). Retinal arterial phase ap pears at 4.8 seconds, and fluores cent puffs of varying size (arrows) are noted along the choroidal arter ies; they are larger on the nasal side of the macula than the temporal side.
Fig. 6 (Perry, Hatfield, and Tso). (Phase 3). In the late retinal phase, 5.2 seconds after injection, the cho roidal fluorescence is more homoge neous, as most of the lobules are full of dye. Some early emptying of lobules is noted on the nasal side of the macula (arrow).
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that dye was seen in the interstitial tissues of the choroid. We noted hyperfluorescence of the lobules and a diffuse back ground haze that was not apparent in the earlier angiograms (Fig. 11). The back ground haze was present only after the initial transit of dye. The pattern of flow was noted to be more uniform but still followed the same sequence as described for the initial transit. DISCUSSION
Fig. 7 (Perry, Hatfleld, and Tso). (Phase A). In the retinal arteriovenous phase and the choroidal ve nous phase at 5.6 seconds, the lobules show hypofluorescent centers and hyperflourescept borders, producing a diffuse fishnet appearance.
yet remained distinct in the areas just temporal to the macula (Fig. 8). At 6.4 seconds, in the late venous phase of the retinal circulation, all choroidal fluores cence disappeared. This was in striking contrast to the retinal vessels and espe cially to their fine capiljaries (Fig. 9). Another neonatal rhesus monkey showed a stage comparable to that in Fig. 5, but at a slightly later time. A distinct gradation of filling of the lobules was noted. In the latter angiogram the overall pattern was that of sharply outlined fluorescein lobules in the central macular region (Fig. 10). The filling pattern of the choroid in the macular region was not uniform but segmental. The nasal macula usually filled before the temporal side. This resulted in the presence of various stages in the same photograph (Figs. 5-8, and 10), but each individual area showed the same sequen tial pattern of filling. This segmental flow in the macular region was reproducible and seen in all angiograms. It was not until the recirculation phase
In the neonatal rhesus monkey there is an excellent opportunity to study the cho roidal circulation. The relative lack of pigment in the RPE provides excellent visibility of the choroid while still main taining the physical boundary between the retinal and choroidal circulations. Al though the transit time is rapid, a recircu lation phase allows for further study of the fluorescein patterns. For the sake of clarity, the early circula tion in the choroid may be divided into five phases, according to the appearance of the fluorescein angiogram:
Fig. 8 (Perry, Hatfleld, and Tso). In the retinal venous phase and the late choroidal venous phase at 6.0 seconds, the choriocapillaris shows a fishnet pattern temporally (arrows) and the absence of back ground fluorescence nasally.
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Fig. 9 (Perry, Hatfield, and Tso). In the late venous phase of the retina at 6.4 seconds, the choroidal circulation is virtually devoid of fluorescence, providing striking contrast for the retinal vessels, espe cially the fine capillaries.
1. Choroidal arterial phase—This stage represents fluorescein entering the large choroidal vessels via the short posterior ciliary arteries. At approximately 4.4 sec onds after injection, fluorescein fills the large choroidal vessel while both the choriocapillaris and retinal circulation are devoid of dye (Fig. 4). 2. Choroidal arteriolar phase—This stage represents early filling of the lob ules of the choriocapillaris by centrally feeding arterioles. At 4.8 seconds, fluores cent puffs of varying sizes appear, simu lating microaneurysms in appearance. These fluorescent puffs are larger in the nasal macular region than in the temporal macular region. At this stage the retinal arteries are filling with dye (Fig. 5). 3. Choroidal arteriolar-venular (com plete filling phase)—This stage represents complete filling of the lobules of the choriocapillaris. At 5.2 seconds, the cho
roidal fluorescence becomes more ho mogeneous as each lobule fills with dye during the late retinal arterial phase (Fig. 6). 4. Venular phase—This stage repre sents emptying of the lobules centrally and filling of the circumferentially orient ed draining venules at 5.6 seconds (Fig. 7). Evidence of this stage is also apparent in Figure 6 in the nasal macular region. The retinal circulation is in the midvenous phase. 5. Venous phase—This stage repre sents complete draining of fluorescein from the choroid (Fig. 8). This stage was observed only during the initial transit of dye. The retinal vasculature is in the venous stage. The choroidal circulation, and espe cially the circulatory dynamics of the choriocapillaris, have received much at tention recently. 3 - 1 0 No longer is the cho-
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Fig. 10 (Perry, Hatfield, and Tso). Early arterial phase of retina and arteriolar phase of the choroidal ar teries, illustrating a distinct grada tion of fluorescence in the lobules. This stage is slightly later than Fig ure 5 and shows early filling of the lobules temporal to the macula (phase 2, arrows) and complete fill ing in the nasal and central macula; the hypofluorescing venules pro vide contrast for the full lobules (circles).
roidal circulation thought of as a morass of interconnecting channels. Through an atomic studies and fluorescein angiography, a definite pattern of flow can be delineated. The basic anatomic and func tional unit responsible for this pattern is the lobule. Controversy exists with re spect to the circulatory patterns in the individual lobules in different regions of the retina. It has been suggested that the lobules fill from the periphery and are drained centrally in the equatorial and peripheral retina, 7 but our data and those of others 3 ' 8,9 studying the posterior pole suggest the contrary. It is possible that the pattern of flow is different in the periph ery but this appears unlikely. In our study, the choroid in the nasal macular region tended to fill with dye before the temporal macular region. For example, the nasal region would be in the venular phase, while the temporal macu lar region would be in the arterial phase.
Fig. 11 (Perry, Hatfield, and Tso). Arterial phase of retina and late arteriolar phase of choroid. The lobules are hyperfluorescing and represent a transi tion between phase 2 and phase 3. Inferiorly there is a merging of the fluorescence, giving a typical phase 3 background fluorescence.
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This segmental pattern contrasts with the retinal circulation, in which the arterial and venous phases never appear simulta neously. This definitive separation of ar terial and venous phases in the retina is probably due to the fact that the retinal circulation is supplied by a single source, the central retinal artery. On the other hand, segmental flow in the choroid re flects the multiple posterior ciliary arter ies supplying the choriocapillaris. In adult humans and in mature rhesus monkeys a diffuse background fluores cence appears following the initial transit of dye into the choroid. In the neonatal rhesus this was not observed. One might speculate that in neonatal rhesus mon keys the endothelial cells in the chorio capillaris are less permeable to sodium fluorescein, thus preventing diffusion of dye on the initial transit. The choriocapillaris was found to have a consistent and distinct pattern of dye transfer based upon individual lobules supplied by central arterioles and drained by surrounding venules. From analyzing one lobule, the reproducible phases of flow could easily be determined. This highly structured anatomic and physio logic pattern is more in keeping with the high flow rate and the rapid transit time observed in the choroid. It is most unlike ly that the choroidal circulation consists of a morass of interconnecting channels, considering its rapid blood flow.8 Perhaps by studying the choriocapil laris in the light of its segmental blood supply and unit structure, we will gain a better understanding of various entities such as nonspecific chorioretinitis, abiotrophies, and dystrophies of retinal pig ment epithelium.
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SUMMARY
Seven neonatal rhesus monkeys were studied by serial fundus photography and fluorescein angiography at weekly inter vals during the first 12 weeks of life. The neonatal rhesus showed little pigmenta tion of the fundus during the first six weeks of life. The fluorescein angiograms showed a definite sequential as well as segmental filling pattern at the level of the choriocapillaris. This filling pattern was based on individual units called lobules. In addition there was a segmental flow in the macula; that is, the nasal macula filled before the temporal macula. REFERENCES 1. Dollery, C. T., Henkind, P., Kohner, E. M., and Paterson, J. W.: Effect of raised intraocular pressure on the retinal and choroidal circulation. Invest. Ophthalmol. 7:191, 1968. 2. Hyvarinen, L., Maumenee, A. E., George, T., and Weinstein, G. W.: Fluorescein angiography of the choriocapillaris, Am. J. Ophthalmol. 67:653, 1969. 3. Hayreh, S. S.: Vascular pattern of the chorioca pillaris. Exp. Eye Res. 19:101, 1974. 4. : Recent advances in fluorescein fundus angiography. Rr. J. Ophthalmol. 58:391, 1974. 5. Amalric, P.: Progress to the knowledge of the choroidal vasculature with the aid of new tech niques for fluorescein angiography. Rull. Hellenic Ophthalmol. S o c , suppl. 45, 1975. 6. Ernest, J. T., Stern, W. H., and Archer, D. B.: Submacular choroidal circulation. Am. J. Ophthal mol. 81:574, 1976. 7. Krey, H. F.: Segmental vascular patterns of the choriocapillaris. Am. J. Ophthalmol. 80:198, 1975. 8. Torczynski, E., and Tso, M. O. M.: The archi tecture of the choriocapillaris at the posterior pole. Am. J. Ophthalmol. 81:428, 1976. 9. Hayreh, S. S.: The choriocapillaris. Albrecht von Graefe's Arch. Klin. Ophthalmol. 192:164, 1975. 10. Weiter, J. J., and Ernest, J. T.: Anatomy of the choroidal vasculature. Am. J. Ophthalmol. 78:583, 1974. 11. Yanoff, M., and Fine, B. S.: Ocular Pathology: A Text and Atlas. Hagerstown, Harper & Row, 1975, p. 104.
R O B E R T V. H A T F I E L D , B.A., Washington,
Recent angiographic 1 - 6 and anatomic 7 , 8 studies suggest that the vascular pattern of the choriocapillaris is segmental in arrangement. The segmental pattern is based on individual units called lobules, 3 each of which is supplied by a choroidal arteriole and drained by a choroidal venule. Most investigators believe each lob ule of the choriocapillaris is supplied by a central arteriole and drained by circum ferential venules. 1 ' 4 - 6 , 9 - 1 1 The study of the choroidal circulation by fluorescein angiography has been made difficult by the natural barrier filter of the retinal pigment epithelium (RPE). In human albinos, in whom the barrier is least, nystagmus and poor fixation make sharp angiographic pictures difficult to obtain. Since neonatal rhesus monkeys have little pigment in the RPE and choroid, they provide unique subjects in which to study the choroidal circulation
AND M A R K O. M. T S O ,
M.D.
D.C.
and delineate the pattern of the chorio capillaris. In this report we review the sequence of accumulation of pigment in the RPE and submacular choroid in the neonatal period as well as the patterns of filling of the choroidal vasculature by fluorescein. From these data we propose a scheme for the circulatory dynamics of the chorio capillaris in the normal neonatal rhesus monkey. M A T E R I A L AND M E T H O D S
From the Registry of Ophthalmic Pathology, Armed Forces Institute of Pathology, and the De partment of Ophthalmology, George Washington University Medical Center (Dr. Tso), Washington, D.C. This work was supported in part by U.S. Public Health Service Research grants EY-01903 and EY-01163 and training grant EY-00032 from the National Eye Institute, National Institutes of Health, Bethesda, Maryland. In conducting the research described in this re port, the investigators adhered to the "Guide for Laboratory Animal Facilities and Care" as promul gated by the Committee on the Guide for Laboratory Animal Facilities and Care of the Institute of Labo ratory Animal Resources, National Academy of Sciences-National Research Council. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of De fense. Reprint requests to Mark O. M. Tso, M.D., Uni versity of Illinois Eye and Ear Infirmary, 1855 W. Taylor St., Chicago, IL 60612.
We studied seven neonatal rhesus mon keys during the first 12 weeks of life by serial fundus photography and fluoresce in angiography by means of the Zeiss Fundus Flash II with Spectrotech filters. Anesthesia was obtained with a combina tion of 10.05 ml of ketamine hydrochloride and a titration of 1:4 dilution of pentobarbital, 65 mg/ml. The eyes were dilated with 10% phenylephrine hydrochloride and 0.5% tropicamide, one drop in each eye one half hour before photogra phy. Color fundus photographs were taken before each angiogram. We injected 0.1 ml of 10% fluorescein into the greater saphenous vein. We obtained 23 angiograms over a 12-week period, 14 in the first six weeks and nine in the second six weeks. Two eyes were enucleated at 2 weeks and 12 weeks of age, respectively, and fixed in 2% glutaraldehyde solution. The tissues were embedded in Epon, sec tioned at 2 (X, and stained with toluidine blue for light microscopy. RESULTS
Fundus pigmentation—From birth to approximately six weeks, the fundus was bright red and had clearly visible retinal
197
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Fig. 1 (Perry, Hatfield, and Tso). Fundus photo graph of macular area in 2-week-old rhesus mon key showing a generalized lack of pigmentation. The retinal and choroidal vessels are distinct, and there is no delineation of the macula.
choroidal vessels (Fig. 1). There was no well-demarcated macular (foveal)* area, and pigmentation of the macula was ab sent. During the ensuing weeks, increas ing pigmentation of the fundus resulted in a mottled appearance, obscuring the choroidal vessels. After 6 months of age the fundus developed a dark, brownishgreen color and a well-demarcated macu la, typical of the adult rhesus monkey (Fig. 2). Histopathologic examination of the foveal area in 2-week-old and 3month-old rhesus monkeys demonstrated clearly the increased pigmentation of the RPE and the choroid that developed dur ing this neonatal period (Fig. 3). Fluorescein angiography—Fluorescein angiograms in neonatal rhesus monkeys demonstrated a consistent circulatory pat tern for the choroid.' We observed two distinct patterns of filling, an initial phase *Following the recommendations suggested by Yanoff and Fine, the term "macula" will be used for clinical matters, while the equivalent term "fovea" will be used for anatomic descriptions.
AUGUST, 1977
and a recirculation of dye both appearing ahead of the retinal phase. The transit time through the choroidal circulation was from 1.8 to 2.3 seconds. The pattern of the fluorescein angio grams is illustrated by atypical series taken from a 2-week-old rhesus monkey. Fluorescein is first seen entering the large choroidal arteries via the short posterior ciliary arteries 4.4 seconds after injection (Fig. 4). At 4.8 seconds, as the retinal arterial phase appeared, fluorescent puffs of varying sizes were noted along the choroidal arteries, representing the filling of choroidal arterioles. The puffs were larger on the nasal side of the macula than on the temporal side (Fig. 5). At 5.2 sec onds, the late retinal arterial phase, the choroidal fluorescence became more ho mogeneous as each puff became larger and appeared as an individual lobule (Fig. 6). The lobules measured 150 to 300 ma. in diameter. Subsequently the centers of the nasal lobules became hypofluorescent and were surrounded by the fluores-
Fig. 2 (Perry, Hatfield, and Tso). Fundus photo graph of macular area in the same rhesus monkey six months later showing a deeply pigmented fundus. The choroidal vessels are obscured, and a welldemarcated macula is present.
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Fig. 3 (Perry, Hatfield, and Tso). Photomicrograph of the macular area in a 2-week-old rhesus (left) and 12-week-old rhesus (right). Increased pigmentation of the retinal pigment epithelium and choroid is evident in the older monkey. Both sections are parafoveolar (x440, toluidine blue).
cent borders of the lobules. Temporal to the macula, the lobules were hyperfluorescent, in contrast to those nasally. At 5.6 seconds a diffuse "fishnet" pattern ap peared across the choroid (Fig. 7). This pattern was made u p of polygonal lobules of varying size having perimeters that
were hyperfluorescent (venules) and cen ters that were hypofluorescent. At this time, the retina was in the arteriovenous phase. At 6.0 seconds, in the venous phase of the retinal circulation and in the late venous phase of the choroidal circu lation, the fishnet pattern faded nasally,
Fig. 4 (Perry, Hatfield, and Tso). (Phase 2). Fluorescein angiogram of left macular area in 2-week-old rhesus monkey. Early filling of cho roidal vessels from the short poster ior ciliary arteries at 4.4 seconds after injection.
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Fig. 5 (Perry, Hatfield, and Tso). (Phase 2). Retinal arterial phase ap pears at 4.8 seconds, and fluores cent puffs of varying size (arrows) are noted along the choroidal arter ies; they are larger on the nasal side of the macula than the temporal side.
Fig. 6 (Perry, Hatfield, and Tso). (Phase 3). In the late retinal phase, 5.2 seconds after injection, the cho roidal fluorescence is more homoge neous, as most of the lobules are full of dye. Some early emptying of lobules is noted on the nasal side of the macula (arrow).
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that dye was seen in the interstitial tissues of the choroid. We noted hyperfluorescence of the lobules and a diffuse back ground haze that was not apparent in the earlier angiograms (Fig. 11). The back ground haze was present only after the initial transit of dye. The pattern of flow was noted to be more uniform but still followed the same sequence as described for the initial transit. DISCUSSION
Fig. 7 (Perry, Hatfleld, and Tso). (Phase A). In the retinal arteriovenous phase and the choroidal ve nous phase at 5.6 seconds, the lobules show hypofluorescent centers and hyperflourescept borders, producing a diffuse fishnet appearance.
yet remained distinct in the areas just temporal to the macula (Fig. 8). At 6.4 seconds, in the late venous phase of the retinal circulation, all choroidal fluores cence disappeared. This was in striking contrast to the retinal vessels and espe cially to their fine capiljaries (Fig. 9). Another neonatal rhesus monkey showed a stage comparable to that in Fig. 5, but at a slightly later time. A distinct gradation of filling of the lobules was noted. In the latter angiogram the overall pattern was that of sharply outlined fluorescein lobules in the central macular region (Fig. 10). The filling pattern of the choroid in the macular region was not uniform but segmental. The nasal macula usually filled before the temporal side. This resulted in the presence of various stages in the same photograph (Figs. 5-8, and 10), but each individual area showed the same sequen tial pattern of filling. This segmental flow in the macular region was reproducible and seen in all angiograms. It was not until the recirculation phase
In the neonatal rhesus monkey there is an excellent opportunity to study the cho roidal circulation. The relative lack of pigment in the RPE provides excellent visibility of the choroid while still main taining the physical boundary between the retinal and choroidal circulations. Al though the transit time is rapid, a recircu lation phase allows for further study of the fluorescein patterns. For the sake of clarity, the early circula tion in the choroid may be divided into five phases, according to the appearance of the fluorescein angiogram:
Fig. 8 (Perry, Hatfleld, and Tso). In the retinal venous phase and the late choroidal venous phase at 6.0 seconds, the choriocapillaris shows a fishnet pattern temporally (arrows) and the absence of back ground fluorescence nasally.
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Fig. 9 (Perry, Hatfield, and Tso). In the late venous phase of the retina at 6.4 seconds, the choroidal circulation is virtually devoid of fluorescence, providing striking contrast for the retinal vessels, espe cially the fine capillaries.
1. Choroidal arterial phase—This stage represents fluorescein entering the large choroidal vessels via the short posterior ciliary arteries. At approximately 4.4 sec onds after injection, fluorescein fills the large choroidal vessel while both the choriocapillaris and retinal circulation are devoid of dye (Fig. 4). 2. Choroidal arteriolar phase—This stage represents early filling of the lob ules of the choriocapillaris by centrally feeding arterioles. At 4.8 seconds, fluores cent puffs of varying sizes appear, simu lating microaneurysms in appearance. These fluorescent puffs are larger in the nasal macular region than in the temporal macular region. At this stage the retinal arteries are filling with dye (Fig. 5). 3. Choroidal arteriolar-venular (com plete filling phase)—This stage represents complete filling of the lobules of the choriocapillaris. At 5.2 seconds, the cho
roidal fluorescence becomes more ho mogeneous as each lobule fills with dye during the late retinal arterial phase (Fig. 6). 4. Venular phase—This stage repre sents emptying of the lobules centrally and filling of the circumferentially orient ed draining venules at 5.6 seconds (Fig. 7). Evidence of this stage is also apparent in Figure 6 in the nasal macular region. The retinal circulation is in the midvenous phase. 5. Venous phase—This stage repre sents complete draining of fluorescein from the choroid (Fig. 8). This stage was observed only during the initial transit of dye. The retinal vasculature is in the venous stage. The choroidal circulation, and espe cially the circulatory dynamics of the choriocapillaris, have received much at tention recently. 3 - 1 0 No longer is the cho-
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Fig. 10 (Perry, Hatfield, and Tso). Early arterial phase of retina and arteriolar phase of the choroidal ar teries, illustrating a distinct grada tion of fluorescence in the lobules. This stage is slightly later than Fig ure 5 and shows early filling of the lobules temporal to the macula (phase 2, arrows) and complete fill ing in the nasal and central macula; the hypofluorescing venules pro vide contrast for the full lobules (circles).
roidal circulation thought of as a morass of interconnecting channels. Through an atomic studies and fluorescein angiography, a definite pattern of flow can be delineated. The basic anatomic and func tional unit responsible for this pattern is the lobule. Controversy exists with re spect to the circulatory patterns in the individual lobules in different regions of the retina. It has been suggested that the lobules fill from the periphery and are drained centrally in the equatorial and peripheral retina, 7 but our data and those of others 3 ' 8,9 studying the posterior pole suggest the contrary. It is possible that the pattern of flow is different in the periph ery but this appears unlikely. In our study, the choroid in the nasal macular region tended to fill with dye before the temporal macular region. For example, the nasal region would be in the venular phase, while the temporal macu lar region would be in the arterial phase.
Fig. 11 (Perry, Hatfield, and Tso). Arterial phase of retina and late arteriolar phase of choroid. The lobules are hyperfluorescing and represent a transi tion between phase 2 and phase 3. Inferiorly there is a merging of the fluorescence, giving a typical phase 3 background fluorescence.
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AMERICAN JOURNAL OF OPHTHALMOLOGY
This segmental pattern contrasts with the retinal circulation, in which the arterial and venous phases never appear simulta neously. This definitive separation of ar terial and venous phases in the retina is probably due to the fact that the retinal circulation is supplied by a single source, the central retinal artery. On the other hand, segmental flow in the choroid re flects the multiple posterior ciliary arter ies supplying the choriocapillaris. In adult humans and in mature rhesus monkeys a diffuse background fluores cence appears following the initial transit of dye into the choroid. In the neonatal rhesus this was not observed. One might speculate that in neonatal rhesus mon keys the endothelial cells in the chorio capillaris are less permeable to sodium fluorescein, thus preventing diffusion of dye on the initial transit. The choriocapillaris was found to have a consistent and distinct pattern of dye transfer based upon individual lobules supplied by central arterioles and drained by surrounding venules. From analyzing one lobule, the reproducible phases of flow could easily be determined. This highly structured anatomic and physio logic pattern is more in keeping with the high flow rate and the rapid transit time observed in the choroid. It is most unlike ly that the choroidal circulation consists of a morass of interconnecting channels, considering its rapid blood flow.8 Perhaps by studying the choriocapil laris in the light of its segmental blood supply and unit structure, we will gain a better understanding of various entities such as nonspecific chorioretinitis, abiotrophies, and dystrophies of retinal pig ment epithelium.
AUGUST, 1977
SUMMARY
Seven neonatal rhesus monkeys were studied by serial fundus photography and fluorescein angiography at weekly inter vals during the first 12 weeks of life. The neonatal rhesus showed little pigmenta tion of the fundus during the first six weeks of life. The fluorescein angiograms showed a definite sequential as well as segmental filling pattern at the level of the choriocapillaris. This filling pattern was based on individual units called lobules. In addition there was a segmental flow in the macula; that is, the nasal macula filled before the temporal macula. REFERENCES 1. Dollery, C. T., Henkind, P., Kohner, E. M., and Paterson, J. W.: Effect of raised intraocular pressure on the retinal and choroidal circulation. Invest. Ophthalmol. 7:191, 1968. 2. Hyvarinen, L., Maumenee, A. E., George, T., and Weinstein, G. W.: Fluorescein angiography of the choriocapillaris, Am. J. Ophthalmol. 67:653, 1969. 3. Hayreh, S. S.: Vascular pattern of the chorioca pillaris. Exp. Eye Res. 19:101, 1974. 4. : Recent advances in fluorescein fundus angiography. Rr. J. Ophthalmol. 58:391, 1974. 5. Amalric, P.: Progress to the knowledge of the choroidal vasculature with the aid of new tech niques for fluorescein angiography. Rull. Hellenic Ophthalmol. S o c , suppl. 45, 1975. 6. Ernest, J. T., Stern, W. H., and Archer, D. B.: Submacular choroidal circulation. Am. J. Ophthal mol. 81:574, 1976. 7. Krey, H. F.: Segmental vascular patterns of the choriocapillaris. Am. J. Ophthalmol. 80:198, 1975. 8. Torczynski, E., and Tso, M. O. M.: The archi tecture of the choriocapillaris at the posterior pole. Am. J. Ophthalmol. 81:428, 1976. 9. Hayreh, S. S.: The choriocapillaris. Albrecht von Graefe's Arch. Klin. Ophthalmol. 192:164, 1975. 10. Weiter, J. J., and Ernest, J. T.: Anatomy of the choroidal vasculature. Am. J. Ophthalmol. 78:583, 1974. 11. Yanoff, M., and Fine, B. S.: Ocular Pathology: A Text and Atlas. Hagerstown, Harper & Row, 1975, p. 104.
