INDOCYANINE GREEN ANGIOGRAPHIC FINDINGS OF HYPERTENSIVE CHOROIDOPATHY Miwako Kawashima, MD, PHD, Masami Nakajima, MD, PHD, Akiyuki Kawamura, MD, PHD
Purpose: To evaluate fundus lesions in patients with malignant hypertension with indocyanine green angiography (ICGA). Methods: Cases of hypertensive choroidopathy were followed prospectively with ICGA, fluorescein angiography (FA), and optical coherence tomography (OCT). Results: In Case 1, a 34-year-old man had a 10-day history of blurred vision in both eyes. Visual acuity was 0.2 in the right eye and 0.01 in the left eye. Blood pressure (BP) was 270/178 mmHg, and laboratory tests disclosed severe renal dysfunction. In Case 2, a 31-year-old man had noticed blurred vision in both eyes. Visual acuity was 1.2 in the right eye and 1.0 in the left eye. BP was 272/180 mmHg. Marked optic edema, retinal hemorrhage, cotton-wool patches, and Elschnig spots were seen in both cases. FA showed poorly perfused choroid in the early phase and fluorescein dye leakage from the optic disk. OCT demonstrated serous retinal detachment in both cases. ICGA revealed Elschnig spots corresponding to the patchy choroidal filling defect. ICGA demonstrated a larger area of choroidal filling defect than FA. In Case 1, ICGA revealed dye leakage from large choroidal vessels. These OCT and ICGA findings reduced after early systemic treatment for malignant hypertension. Conclusion: Hypofluorescent spots in the choroid thought to be choriocapillaris occlusion and choroidal vessel damage recover as result of early treatment for malignant hypertension. ICGA is useful to reveal the disturbance of choroidal circulation in hypertensive choroidopathy. RETINAL CASES & BRIEF REPORTS 2:154 –157, 2008
From the Department of Ophthalmology, Nihon University School of Medicine, Tokyo, Japan.
indocyanine green (ICG) angiography clearly depicts the choroidal vasculature. This modality would presumably be useful for visualizing choroidal circulation in hypertensive choroidopathy, although few studies have been conducted.2 We used ICG angiography to investigate the choroidal blood flow disorders associated with hypertensive choroidopathy.
H
ypertensive choroidopathy, associated with nephropathy, preeclampsia, or malignant hypertension, is ophthalmoscopically characterized by serous retinal detachment or Elschnig spots. Experimental hypertension studies have shown hypertensive choroidopathy to be caused by ischemia and infarction of choroidal vessels.1 Because of the retinal pigment epithelium, it has been difficult to evaluate choroidal blood flow and vascular disorders of hypertensive choroidopathy by fluorescein angiography. However,
Case Reports Case 1 A 34-year-old man had reduced vision in the left eye for 4 months. For 10 days before presenting to the Department of Ophthalmology at Nihon University Itabashi Hospital (Tokyo, Japan), he had visual impairment in both eyes. Hypertension had been diagnosed 2 years previously, but he had not been given antihypertensive therapy. He had no history of ocular disorders. At the first examination, corrected visual acuity was 20/100 in the right
Presented at the annual meeting of the Association for Research in Vision and Ophthalmology; Ft. Lauderdale, FL; May 2, 2006. Reprint requests: Masami Nakajima, MD, Department of Ophthalmology, Nihon University, School of Medicine, 30-1, Ohyaguchikami-machi, Itabashi-ku, Tokyo 173-8610 Japan; e-mail: [email protected]
154
ICG ANGIOGRAPHIC FINDINGS OF HYPERTENSIVE CHOROIDOPATHY
Fig. 1. Case 1. Fundus photograph of the left eye (A) shows papilledema, hemorrhage, and soft exudates. Elschnig spots are apparent (arrows) around the center of the ocular fundus. Optical coherence tomography shows marked serous retinal detachment (arrow) (B).
Fig. 2. Case 1. Indocyanine green angiography shows numerous hypofluorescent spots over the entire ocular fundus in the early phase (A). Choroidal vessels have staining in the late phase (B). Three months after the start of antihypertensive therapy, the hypofluorescent spots are smaller (arrowheads). Some hypofluorescent spots persist (arrows). Choroidal circulation is improved in the early phase (C). The choroidal vessel staining in the temporal portion of the left eye is no longer detectable (D).
155
Fig. 3. Case 1. Fundus photograph of the left eye (A) after antihypertensive therapy. Papilledema has improved, serous retinal detachment has resolved, and a hard exudate is visible in the macula. The Elschnig spots have mostly disappeared. Optical coherence tomography shows absorption of subretinal fluid. (B).
156
RETINAL CASES & BRIEF REPORTSℜ
●
2008
●
VOLUME 2
●
NUMBER 2
rescent spots were seen in the peripheral choroid. Goldmann perimetry showed an enlarged Marriotte blind spot in both eyes and relative scotoma in the left eye, but there was no difference between right and left eyes in flicker values or color vision examination results. Peritoneal dialysis was introduced starting on day 22 of the illness. Three months later, blood pressure was well controlled at 124/77 mmHg, and corrected visual acuity had improved to 20/16 in the right eye and 20/30 in the left eye. Ophthalmoscopy confirmed papilledema to have improved and serous retinal detachment to have disappeared and revealed a hard exudate that had become apparent in the macular region (Fig. 3A). The Elschnig spots had mostly disappeared or decreased in size. Optical coherence tomography showed absorption of subretinal fluid and deposition of a hard exudate in the inner retinal layer (Fig. 3B). ICG angiography showed spots with reduced hypofluorescence in the ocular fundus and improved choroidal circulation (Fig. 2C). In addition, the choroidal vessel staining in the temporal portion of the left eye was no longer detectable (Fig. 2D).
Case 2
Fig. 4. Case 2. Indocyanine green angiography shows hypofluorescent spots (arrows) over the entire ocular fundus in the early phase (A). Choroidal vessels have staining (arrow) in the late phase (B).
eye and 20/2000 in the left eye. Slit-lamp examination results were unremarkable. In the ocular fundus of both eyes, papilledema, hemorrhage, and soft exudates were seen, and serous retinal detachment was apparent in the macular region (Fig. 1A). Elschnig spots were confirmed around the center of the ocular fundus in both eyes. Optical coherence tomography confirmed marked serous retinal detachment in both eyes (Fig. 1B). Blood pressure was 270/178 mmHg, and chest roentgenography showed cardiac dilatation and pulmonary congestion. Laboratory investigations confirmed severe renal dysfunction: hemoglobin level, 8.9 g/dL; urea nitrogen level, 88 mg/dL; and creatinine level, 13 mg/dL. Malignant hypertension was diagnosed, and antihypertensive therapy was initiated. On day 13 of the illness, fluorescein angiography and ICG angiography were performed using a fundus camera (TRC-50LX; Topcon, Tokyo, Japan). For ICG angiography, the patient was given an intravenous injection of 25 mg of ICG (Ophthagreen; Santen Pharmaceutical, Osaka, Japan) diluted in 5 mL of distilled water. Fluorescein angiography confirmed prominent fluorescent dye leakage in both optic disks and hypofluorescent spots, equivalent to Elschnig spots. ICG angiography showed numerous hypofluorescent spots over the entire ocular fundus in the early phase of angiography (Fig. 2A). In the late phase, choroidal vessels had staining in the temporal portion of the left eye (Fig. 2B). Besides the Elschnig spots detected by ophthalmoscopy, several hypofluo-
A 31-year-old man presented to our clinic with a complaint of blurred vision in both eyes. Hypertension had been diagnosed 2 years previously, but he had not been treated with antihypertensive medication. He had no history of ocular disorders. Corrected visual acuity was 20/16 in the right eye and 20/20 in the left eye. Slit-lamp examination findings were unremarkable. In the ocular fundus of both eyes, papilledema, hemorrhage, and soft exudates were seen. Elschnig spots and whitish changes in choroidal vessels were confirmed around the center of the ocular fundus bilaterally. Optical coherence tomography confirmed marked serous retinal detachment in the left eye. Blood pressure was 272/180 mmHg, and chest roentgenography showed cardiac dilatation and pulmonary congestion. Laboratory investigations disclosed a urea nitrogen level of 15.8 mg/dL and a creatinine level of 1.48 mg/dL. Aggressive antihypertensive therapy was promptly initiated. On day 5 of the illness, fluorescein angiography and ICG angiography were performed. ICG angiography showed numerous hypofluorescent spots over the entire ocular fundus in the early phase (Fig. 4A). In the late phase of angiography, several choroidal vessels had staining over the entire ocular fundus (Fig. 4B). Three months later, blood pressure was controlled at 166/107 mmHg, and corrected visual acuity had improved to 20/16 in both eyes. ICG angiography revealed that there were fewer hypofluorescent spots in the ocular fundus. Staining of choroidal vessels in the late phase was no longer detectable.
Discussion The ocular findings associated with systemic hypertension include retinopathy, choroidopathy, and papilledema, and as was the case for our patients, choroidopathy is often seen in young individuals with acute hypertension.3 Choroidal vessels lack autoregulation, and because of the lack of a blood– ocular barrier, malignant hypertension results in leakage of angiotensin from choroidal vessels, leading to contraction of these vessels and thus choroidal ischemia.4 Persistent ischemia breaks down the blood–retinal barrier, causing serous retinal detachment and outer retinal layer damage. In both of our cases, optical coherence to-
157
ICG ANGIOGRAPHIC FINDINGS OF HYPERTENSIVE CHOROIDOPATHY
mography confirmed resolution of serous retinal detachment and retinal edema after adequate blood pressure control was achieved. In both cases, blood pressure was controlled before irreversible retinal pigment epithelium damage due to breakdown of the blood–retinal barrier. Successful blood pressure management could contribute to prompt resolution of serous retinal detachment and to visual improvement. Elschnig spots are considered to represent infarction of the choriocapillaris or small choroidal arterioles, and ICG angiography confirmed the presence of these spots. Although hypofluorescent spots in the choroid appeared to reflect choriocapillaris occlusion, rapid improvement of the patients’ systemic conditions could have contributed to the observed decrease in hypofluorescent spots and improved choroidal circulation. In both of our patients, more hypofluorescent spots in the choroid were detected by ICG angiography than by fluorescein angiography. ICG angiography showed staining of medium-sized and large choroidal vessels. This new finding was thought to be attributable to damage to the endothelial cells of choroidal vessels and to have resolved with adequate
blood pressure control. We considered the possibility of irreversible change involving vascular endothelial cells in the absence of antihypertensive therapy. Kishi et al1 conducted a study on experimental hypertensive choroidopathy and reported that chronic ischemia occluded the choriocapillaris and small choroidal arterioles. The ICG angiographic findings for our patients confirmed similar changes. Key words: Elschnig spot, hypertensive choroidopathy, indocyanine green angiography. References 1.
2.
3.
4.
Kishi S, Tso MO, Hayreh SS. Fundus lesions in malignant hypertension. I. A pathologic study of experimental hypertensive choroidopathy. Arch Ophthalmol 1985;103:1189–1197. MacCumber MW, Flower RW, Langham ME. Ischemic hypertensive choroidopathy. Fluorescein angiography, indocyanine green videoangiography, and measurement of pulsatile blood flow. Arch Ophthalmol 1993;111:704–705. de Venecia G, Jampol LM. The eye in accelerated hypertension. II. Localized serous detachments of the retina in patients. Arch Ophthalmol 1984;102:68–73. Hayreh SS, Servais GE, Virdi PS. Fundus lesions in malignant hypertension. VI. Hypertensive choroidopathy. Ophthalmology 1986;93:1383–1400.
Purpose: To evaluate fundus lesions in patients with malignant hypertension with indocyanine green angiography (ICGA). Methods: Cases of hypertensive choroidopathy were followed prospectively with ICGA, fluorescein angiography (FA), and optical coherence tomography (OCT). Results: In Case 1, a 34-year-old man had a 10-day history of blurred vision in both eyes. Visual acuity was 0.2 in the right eye and 0.01 in the left eye. Blood pressure (BP) was 270/178 mmHg, and laboratory tests disclosed severe renal dysfunction. In Case 2, a 31-year-old man had noticed blurred vision in both eyes. Visual acuity was 1.2 in the right eye and 1.0 in the left eye. BP was 272/180 mmHg. Marked optic edema, retinal hemorrhage, cotton-wool patches, and Elschnig spots were seen in both cases. FA showed poorly perfused choroid in the early phase and fluorescein dye leakage from the optic disk. OCT demonstrated serous retinal detachment in both cases. ICGA revealed Elschnig spots corresponding to the patchy choroidal filling defect. ICGA demonstrated a larger area of choroidal filling defect than FA. In Case 1, ICGA revealed dye leakage from large choroidal vessels. These OCT and ICGA findings reduced after early systemic treatment for malignant hypertension. Conclusion: Hypofluorescent spots in the choroid thought to be choriocapillaris occlusion and choroidal vessel damage recover as result of early treatment for malignant hypertension. ICGA is useful to reveal the disturbance of choroidal circulation in hypertensive choroidopathy. RETINAL CASES & BRIEF REPORTS 2:154 –157, 2008
From the Department of Ophthalmology, Nihon University School of Medicine, Tokyo, Japan.
indocyanine green (ICG) angiography clearly depicts the choroidal vasculature. This modality would presumably be useful for visualizing choroidal circulation in hypertensive choroidopathy, although few studies have been conducted.2 We used ICG angiography to investigate the choroidal blood flow disorders associated with hypertensive choroidopathy.
H
ypertensive choroidopathy, associated with nephropathy, preeclampsia, or malignant hypertension, is ophthalmoscopically characterized by serous retinal detachment or Elschnig spots. Experimental hypertension studies have shown hypertensive choroidopathy to be caused by ischemia and infarction of choroidal vessels.1 Because of the retinal pigment epithelium, it has been difficult to evaluate choroidal blood flow and vascular disorders of hypertensive choroidopathy by fluorescein angiography. However,
Case Reports Case 1 A 34-year-old man had reduced vision in the left eye for 4 months. For 10 days before presenting to the Department of Ophthalmology at Nihon University Itabashi Hospital (Tokyo, Japan), he had visual impairment in both eyes. Hypertension had been diagnosed 2 years previously, but he had not been given antihypertensive therapy. He had no history of ocular disorders. At the first examination, corrected visual acuity was 20/100 in the right
Presented at the annual meeting of the Association for Research in Vision and Ophthalmology; Ft. Lauderdale, FL; May 2, 2006. Reprint requests: Masami Nakajima, MD, Department of Ophthalmology, Nihon University, School of Medicine, 30-1, Ohyaguchikami-machi, Itabashi-ku, Tokyo 173-8610 Japan; e-mail: [email protected]
154
ICG ANGIOGRAPHIC FINDINGS OF HYPERTENSIVE CHOROIDOPATHY
Fig. 1. Case 1. Fundus photograph of the left eye (A) shows papilledema, hemorrhage, and soft exudates. Elschnig spots are apparent (arrows) around the center of the ocular fundus. Optical coherence tomography shows marked serous retinal detachment (arrow) (B).
Fig. 2. Case 1. Indocyanine green angiography shows numerous hypofluorescent spots over the entire ocular fundus in the early phase (A). Choroidal vessels have staining in the late phase (B). Three months after the start of antihypertensive therapy, the hypofluorescent spots are smaller (arrowheads). Some hypofluorescent spots persist (arrows). Choroidal circulation is improved in the early phase (C). The choroidal vessel staining in the temporal portion of the left eye is no longer detectable (D).
155
Fig. 3. Case 1. Fundus photograph of the left eye (A) after antihypertensive therapy. Papilledema has improved, serous retinal detachment has resolved, and a hard exudate is visible in the macula. The Elschnig spots have mostly disappeared. Optical coherence tomography shows absorption of subretinal fluid. (B).
156
RETINAL CASES & BRIEF REPORTSℜ
●
2008
●
VOLUME 2
●
NUMBER 2
rescent spots were seen in the peripheral choroid. Goldmann perimetry showed an enlarged Marriotte blind spot in both eyes and relative scotoma in the left eye, but there was no difference between right and left eyes in flicker values or color vision examination results. Peritoneal dialysis was introduced starting on day 22 of the illness. Three months later, blood pressure was well controlled at 124/77 mmHg, and corrected visual acuity had improved to 20/16 in the right eye and 20/30 in the left eye. Ophthalmoscopy confirmed papilledema to have improved and serous retinal detachment to have disappeared and revealed a hard exudate that had become apparent in the macular region (Fig. 3A). The Elschnig spots had mostly disappeared or decreased in size. Optical coherence tomography showed absorption of subretinal fluid and deposition of a hard exudate in the inner retinal layer (Fig. 3B). ICG angiography showed spots with reduced hypofluorescence in the ocular fundus and improved choroidal circulation (Fig. 2C). In addition, the choroidal vessel staining in the temporal portion of the left eye was no longer detectable (Fig. 2D).
Case 2
Fig. 4. Case 2. Indocyanine green angiography shows hypofluorescent spots (arrows) over the entire ocular fundus in the early phase (A). Choroidal vessels have staining (arrow) in the late phase (B).
eye and 20/2000 in the left eye. Slit-lamp examination results were unremarkable. In the ocular fundus of both eyes, papilledema, hemorrhage, and soft exudates were seen, and serous retinal detachment was apparent in the macular region (Fig. 1A). Elschnig spots were confirmed around the center of the ocular fundus in both eyes. Optical coherence tomography confirmed marked serous retinal detachment in both eyes (Fig. 1B). Blood pressure was 270/178 mmHg, and chest roentgenography showed cardiac dilatation and pulmonary congestion. Laboratory investigations confirmed severe renal dysfunction: hemoglobin level, 8.9 g/dL; urea nitrogen level, 88 mg/dL; and creatinine level, 13 mg/dL. Malignant hypertension was diagnosed, and antihypertensive therapy was initiated. On day 13 of the illness, fluorescein angiography and ICG angiography were performed using a fundus camera (TRC-50LX; Topcon, Tokyo, Japan). For ICG angiography, the patient was given an intravenous injection of 25 mg of ICG (Ophthagreen; Santen Pharmaceutical, Osaka, Japan) diluted in 5 mL of distilled water. Fluorescein angiography confirmed prominent fluorescent dye leakage in both optic disks and hypofluorescent spots, equivalent to Elschnig spots. ICG angiography showed numerous hypofluorescent spots over the entire ocular fundus in the early phase of angiography (Fig. 2A). In the late phase, choroidal vessels had staining in the temporal portion of the left eye (Fig. 2B). Besides the Elschnig spots detected by ophthalmoscopy, several hypofluo-
A 31-year-old man presented to our clinic with a complaint of blurred vision in both eyes. Hypertension had been diagnosed 2 years previously, but he had not been treated with antihypertensive medication. He had no history of ocular disorders. Corrected visual acuity was 20/16 in the right eye and 20/20 in the left eye. Slit-lamp examination findings were unremarkable. In the ocular fundus of both eyes, papilledema, hemorrhage, and soft exudates were seen. Elschnig spots and whitish changes in choroidal vessels were confirmed around the center of the ocular fundus bilaterally. Optical coherence tomography confirmed marked serous retinal detachment in the left eye. Blood pressure was 272/180 mmHg, and chest roentgenography showed cardiac dilatation and pulmonary congestion. Laboratory investigations disclosed a urea nitrogen level of 15.8 mg/dL and a creatinine level of 1.48 mg/dL. Aggressive antihypertensive therapy was promptly initiated. On day 5 of the illness, fluorescein angiography and ICG angiography were performed. ICG angiography showed numerous hypofluorescent spots over the entire ocular fundus in the early phase (Fig. 4A). In the late phase of angiography, several choroidal vessels had staining over the entire ocular fundus (Fig. 4B). Three months later, blood pressure was controlled at 166/107 mmHg, and corrected visual acuity had improved to 20/16 in both eyes. ICG angiography revealed that there were fewer hypofluorescent spots in the ocular fundus. Staining of choroidal vessels in the late phase was no longer detectable.
Discussion The ocular findings associated with systemic hypertension include retinopathy, choroidopathy, and papilledema, and as was the case for our patients, choroidopathy is often seen in young individuals with acute hypertension.3 Choroidal vessels lack autoregulation, and because of the lack of a blood– ocular barrier, malignant hypertension results in leakage of angiotensin from choroidal vessels, leading to contraction of these vessels and thus choroidal ischemia.4 Persistent ischemia breaks down the blood–retinal barrier, causing serous retinal detachment and outer retinal layer damage. In both of our cases, optical coherence to-
157
ICG ANGIOGRAPHIC FINDINGS OF HYPERTENSIVE CHOROIDOPATHY
mography confirmed resolution of serous retinal detachment and retinal edema after adequate blood pressure control was achieved. In both cases, blood pressure was controlled before irreversible retinal pigment epithelium damage due to breakdown of the blood–retinal barrier. Successful blood pressure management could contribute to prompt resolution of serous retinal detachment and to visual improvement. Elschnig spots are considered to represent infarction of the choriocapillaris or small choroidal arterioles, and ICG angiography confirmed the presence of these spots. Although hypofluorescent spots in the choroid appeared to reflect choriocapillaris occlusion, rapid improvement of the patients’ systemic conditions could have contributed to the observed decrease in hypofluorescent spots and improved choroidal circulation. In both of our patients, more hypofluorescent spots in the choroid were detected by ICG angiography than by fluorescein angiography. ICG angiography showed staining of medium-sized and large choroidal vessels. This new finding was thought to be attributable to damage to the endothelial cells of choroidal vessels and to have resolved with adequate
blood pressure control. We considered the possibility of irreversible change involving vascular endothelial cells in the absence of antihypertensive therapy. Kishi et al1 conducted a study on experimental hypertensive choroidopathy and reported that chronic ischemia occluded the choriocapillaris and small choroidal arterioles. The ICG angiographic findings for our patients confirmed similar changes. Key words: Elschnig spot, hypertensive choroidopathy, indocyanine green angiography. References 1.
2.
3.
4.
Kishi S, Tso MO, Hayreh SS. Fundus lesions in malignant hypertension. I. A pathologic study of experimental hypertensive choroidopathy. Arch Ophthalmol 1985;103:1189–1197. MacCumber MW, Flower RW, Langham ME. Ischemic hypertensive choroidopathy. Fluorescein angiography, indocyanine green videoangiography, and measurement of pulsatile blood flow. Arch Ophthalmol 1993;111:704–705. de Venecia G, Jampol LM. The eye in accelerated hypertension. II. Localized serous detachments of the retina in patients. Arch Ophthalmol 1984;102:68–73. Hayreh SS, Servais GE, Virdi PS. Fundus lesions in malignant hypertension. VI. Hypertensive choroidopathy. Ophthalmology 1986;93:1383–1400.
