Argon laser panretinal photocoagulation in ischemic central retinal vein occlusion. A 10-year prospective study.

We conducted a prospective, planned study of argon laser panretinal photocoagulation (PRP) in ischemic central retinal vein occlusion (CRVO) over a 10-year period in 123 eyes. On comparing the lasered eyes versus the nonlasered eyes, there was no statistically significant difference between the two groups in the incidence of development of angle neovascularization (NV), neovascular glaucoma (NVG), retinal and/or optic disc NV, or vitreous hemorrhage, or in visual acuity. Our study, however, did show a statistically significant (P = 0.04) difference in the incidence of iris NV between the two groups, with iris NV less prevalent in the laser group than in the nonlaser group, but only when the PRP was performed within 90 days after the onset of CRVO. The other parameter which showed a statistically significant difference between the two groups was the peripheral visual fields-the laser group suffered a significantly (P less than or equal to 0.03) greater loss than the non-laser group. We discuss the implications of these findings in light of the natural history of ischemic CRVO and of ocular NV. Since the original rationale for advocating PRP in ischemic CRVO was the proven beneficial effect of PRP on ocular NV in proliferative diabetic retinopathy, we also discuss the disparities in the disease process between ischemic CRVO and proliferative diabetic retinopathy and in their responses to PRP.

Retinal arteriolar changes in malignant arterial hypertension.

Experimental renovascular malignant arterial hypertension was produced by modified Goldblatt's procedures, in 60 rhesus monkeys, and various retinal arteriolar changes in hypertensive retinopathy were studied in detail (by serial ophthalmoscopy, and stereoscopic color fundus photography and fluorescein fundus angiography on long-term follow-up). The retinal arteriolar changes, in ophthalmoscopically visible arterioles, consisted of arteriolar sclerosis and associated changes, e.g., increased arteriolar tortuosity, arteriolar narrowing and in some animals occlusion and sheathing of the fine arterioles; we could find no evidence of localized or generalized 'spasm' in these retinal arterioles. Eyes in animals with accelerated arterial hypertension revealed focal dilatation and leakage of the retinal precapillary terminal arterioles (resulting in development of focal intraretinal periarteriolar transudates), and also occlusion of the terminal retinal arterioles (producing cotton-wool spots and associated intraretinal microvascular abnormalities). We discuss the controversial subjects of narrowing (particularly 'spasm') of ophthalmoscopically visible retinal arterioles and of fibrinoid necrosis in malignant hypertension.

Cotton-wool spots (inner retinal ischemic spots) in malignant arterial hypertension.

We produced experimental renovascular malignant arterial hypertension by modified Goldblatt's procedures, in 60 rhesus monkeys. Hypertensive retinopathy was studied in detail (by ophthalmoscopy, and stereoscopic color fundus photography and fluorescein fundus angiography on long-term follow-up). Cotton-wool spots (CWSs) were found to be an important, early retinal lesion. On ophthalmoscopy, they had a characteristic appearance. Fluorescein fundus angiography of these lesions revealed focal retinal capillary nonperfusion. The CWSs usually lasted for over 3 weeks and resolved within 6 weeks, leaving permanent obliteration of the retinal capillaries in their distribution, secondary intraretinal microvascular abnormalities, and retinal nerve fiber loss. We discuss pathogenesis and other features of CWSs. There is overwhelming evidence that CWSs are due to occlusion of the terminal retinal arterioles, resulting in acute focal inner retinal ischemia; hence the scientifically valid term for them would be 'inner retinal ischemic spots'.

Retinal lipid deposits in malignant arterial hypertension.

In 60 rhesus monkeys with experimental renovascular malignant arterial hypertension (25 one-kidney and 35 two-kidney model animals), we studied the so-called 'hard exudates' or white retinal deposits in detail (by ophthalmoscopy, and stereoscopic color fundus photography and fluorescein fundus angiography, on long-term follow-up). Some manifestation of hypertensive retinopathy developed in 19 one-kidney and 19 two-kidney animals, and white deposits formed in 14 and 5 monkeys, respectively. The onset of white deposits showed no correlation to severity of arterial hypertension or of retinopathy. All eyes with white deposits had antecedent macular or retinal edema. The deposits were everchanging, taking months or even more than a year to resolve. Our study suggests that in hypertensive retinopathy the white retinal deposits are most probably the result of exudative and/or neural degenerative processes. All the available pieces of evidence indicate that it is more appropriate to call the white deposits 'lipid deposits' than 'hard exudates'.

Macular lesions in malignant arterial hypertension.

We produced experimental renovascular malignant arterial hypertension by a modified Goldblatt's procedure in 60 rhesus monkeys (25 one-kidney model and 35 two-kidney model), and studied various macular lesions by detailed serial ophthalmoscopy, and stereoscopic color fundus photography and fluorescein fundus angiography on a long-term follow-up. The various lesions which developed in the macular region included retinal edema, cystic retinal changes, serous retinal detachment, retinal pigment epithelial changes (initially acute focal and later degenerative lesions), and lipid deposits. In addition to these, the usual retinal lesions associated with hypertensive retinopathy, e.g., focal intraretinal periarteriolar transudates, cotton-wool spots and retinal hemorrhages, were also frequently seen in the macular retina. Findings on the various lesions are described in detail, and the pathogenesis of macular edema in malignant arterial hypertension is discussed.

Retinal hemorrhages in malignant arterial hypertension.

We conducted a detailed investigation into retinal hemorrhages in renovascular malignant arterial hypertension experimentally produced in rhesus monkeys. The hypertension was produced by modified Goldblatt's procedures in 60 rhesus monkeys and hypertensive fundus changes were studied by ophthalmoscopy, stereoscopic color fundus photography and fluorescein fundus angiography. Our study revealed that, in hypertensive retinopathy due to malignant hypertension, retinal hemorrhages usually did not constitute either one of the earliest or one of the most conspicuous retinal lesions, but, on the contrary, were a minor feature of the retinopathy. Neither the time of onset of retinal hemorrhages nor their peak severity showed any significant correlation with the level of the arterial hypertension. The hemorrhages were usually situated in the nerve fiber layer, and could be located anywhere in the fundus but were usually found in the distribution of the radial peripapillary retinal capillaries. There was no association between the presence of retinal hemorrhages and retinal venous changes; the latter were seen only in a minority of animals and consisted of retinal venous stasis, venous collaterals and arteriovenous shunts.

Anterior ischemic optic neuropathy. IX. Cup-to-disc ratio and its role in pathogenesis.

The optic disc appearance in the normal fellow eye of 126 patients with nonarteritic anterior ischemic optic neuropathy (n-AION) was compared with the discs in 23 patients with arteritic AION (a-AION) and 122 normal subjects. The number of discs with no cup was significantly greater (P less than 0.001) and the number of discs with a large cup was significantly fewer (P less than 0.001) in the n-AION group compared to the other two groups. No significant differences were found in cup size between the a-AION and normal groups. The pathogenesis of n-AION appears to be multifactorial. There is overwhelming evidence that ischemia is the primary factor. The size of the optic disc also plays a role, probably through a compressive effect at the level of the lamina cribrosa on axons subjected to ischemia. In contrast, a-AION occurs from posterior ciliary artery occlusion and disc size is not a factor.

Fundus lesions in malignant hypertension. VI. Hypertensive choroidopathy.

Experimental renovascular malignant arterial hypertension was produced, by modified Goldblatt's procedures, in 60 rhesus monkeys, and hypertensive fundus changes were studied in detail (by serial ophthalmoscopy and fluorescein fundus angiography in all monkeys on a long-term follow-up, and pathologically in 29 eyes). In hypertensive choroidopathy, retinal pigment epithelial (RPE) lesions and serous retinal detachment (RD) were the classic ophthalmoscopic lesions, whereas fluorescein fundus angiography and histopathologic studies revealed marked abnormalities in the choroidal vascular bed, in addition to the changes in the RPE. The RPE lesions could be subdivided into initial acute focal lesions (due to focal RPE infarction), and degenerative lesions, which developed later and were progressive in nature, maximally involving the macular and peripheral regions of the fundus. The RD developed most commonly in the posterior pole and infrequently involved the peripheral retina. The choroidal vascular bed showed impaired circulation and extensive occlusive and ischemic changes. These studies revealed that hypertensive choroidopathy is as important a fundus change as hypertensive retinopathy. The pathogenesis of hypertensive choroidopathy is discussed in detail; the evidence indicates that it is due to choroidal ischemia, and that hypertensive choroidopathy and retinopathy are two independent and unrelated manifestations of renovascular malignant hypertension.

Relative afferent pupillary defect in central retinal vein occlusion.

In a prospective study, 120 patients with unilateral central retinal vein occlusion (CRVO) were investigated to determine the role of the relative afferent pupillary defect (RAPD) in differentiating ischemic from nonischemic CRVO. In 87 patients with nonischemic CRVO, 90% had a RAPD 0.3 log units or less and none had a RAPD larger than 0.9 log units. In contrast, in 33 patients with ischemic CRVO 91% had a RAPD of 1.2 log units or more, and none had a RAPD smaller than 0.6 log units. Thus, this simple, quick, and inexpensive test has proved to be a highly sensitive and reliable indicator in the differential diagnosis of the two types of CRVO.

Fundus lesions in malignant hypertension. III. Arterial blood pressure, biochemical, and fundus changes.

Malignant (accelerated) renovascular arterial hypertension was produced in 57 adult rhesus monkeys by clamping the renal artery (one-kidney model in 25 animals and two-kidney model in 32). The animals were investigated before renal artery clamping and serially thereafter by recording systolic arterial blood pressure (BP), biochemical changes, and changes in the fundus of the eye; the latter was evaluated by ophthalmoscopy, stereoscopic color fundus photography, and fluorescein fundus angiography. All of the animals developed arterial hypertension. The data on BP, biochemical, and fundus findings were analyzed and correlated. The findings of this study clearly showed that the various fundus lesions seen in these hypertensive animals fall into three distinct categories: (1) hypertensive retinopathy, (2) hypertensive choroidopathy, and (3) hypertensive optic neuropathy. The appearance of the retinopathy was significantly earlier than that of the choroidopathy or optic neuropathy (P less than 0.01), but the difference between the times of appearance of the choroidopathy and neuropathy was not significant. There was no significance in the order in which the three types of fundus changes reached their maximum severity. There was no significant difference between the mean BPs when the retinopathy, choroidopathy, or optic neuropathy first appeared, nor between the BPs at the time of their appearance and at the time when they were most marked. In monkeys of the one-kidney model, the rise in BP developed significantly (P = 0.01) faster and the fundus lesions appeared significantly (P = 0.00001) earlier than in those with the two-kidney model.

Fundus lesions in malignant hypertension. IV. Focal intraretinal periarteriolar transudates.

Experimental renovascular malignant arterial hypertension was produced in 57 rhesus monkeys by a modified Goldblatt's procedure and their eyes were studied by serial ophthalmoscopy, by stereoscopic color fundus photography, and by fluorescein fundus angiography over a period of months or years. A very common, and one of the earliest, lesions in hypertensive retinopathy was focal intraretinal periarteriolar transudates (FIPTs). In the past, FIPTs have been described erroneously as "cotton-wool spots." The two types of lesions differ very much in shape, size, color, location, fluorescein fundus angiographic pattern, resolution pattern, life cycle, and pathogenesis. FIPTs, on ophthalmoscopy, usually are pinpoint to pinhead size, round or oval, dull white in color, and situated in deeper layers of the retina and beside the major retinal arteries and their main branches. On fluorescein angiography, FIPTs show multiple punctate foci of fluorescein leakage from dilated precapillary retinal arterioles, and there is no focal retinal capillary obliteration. They usually last for two to three weeks, and on resolution leave no ophthalmoscopic, angiographic, or microvascular abnormality. Cotton-wool spots are seen in a variety of retinopathies; FIPTs, however, are a specific retinal lesion of malignant arterial hypertension only. They develop due to breakdown of blood-retinal barrier in pre-capillary retinal arterioles, due to dilatation of the arterioles from failure of autoregulation (caused by severe rise of blood pressure).

Fundus lesions in malignant hypertension. V. Hypertensive optic neuropathy.

We produced experimental renovascular arterial hypertension in 57 rhesus monkeys by modified Goldblatt's procedures. Hypertensive fundus changes were studied in detail by serial ophthalmoscopy and fluorescein fundus angiography in all animals on a long-term follow-up, and pathologically in 23 eyes. Initial evidence of hypertensive optic neuropathy was optic disc edema which developed at the median blood pressure (BP) of 190 mmHg (normal BP, 120 mmHg). On follow-up, mild to marked pallor of the optic disc developed. The optic disc changes were correlated with BP and other fundus changes. Pathogenesis of hypertensive optic neuropathy, which has been highly controversial so far, is discussed at length in the light of the findings of the present study and other recent evidence. All the available clinical and pathologic findings in the present study indicate that hypertensive optic neuropathy represents a form of anterior ischemic optic neuropathy, and that hypertensive optic neuropathy is a distinct entity. A caution is given against a precipitous reduction of BP in patients with hypertensive optic neuropathy because that may cause complete, permanent blindness.