Contrast sensitivity following focal laser photocoagulation in clinically significant macular oedema due to diabetic retinopathy.

PURPOSE: To evaluate the influence of focal aser photocoagulation on contrast sensitivity in diabetic patients with clinically significant macular oedema (CSMO). METHODS: A prospective non-comparative interventional study was performed on a group of patients with CSMO at Dr Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, a tertiary eye care centre. Thirteen diabetc patients (14 eyes) with CSMO and no history of prior photocoagulation were recruited for this study. Direct focal photocoagulation of all leaking microaneurysms was performed using an argon green laser (514 nm). A contact lens was used as a slit lamp delivery system. Evaluation of the best corrected Snellen visual acuity, contrast senstivity, slit lamp biomicroscopy, macular status on direct ophthalmoscopy and fluorescein angiography was carried out 1 month and 3 months after laser photocoagulation. RESULTS: Following direct focal laser photocoagulation, focal CSMO resolved completely in all but one eye, 4-8 weeks later, as seen on slit lamp biomicroscopy and/or fluorescein angiography. Post-treatment, visual acuity remained stationary in eight eyes, improved by one line in three eyes, by two lines in two eyes and by three lines in one eye. The mean +/- SD pretreatment and post-treatment decimal visual acuities were 0.49+/-0.30 and 0.59+/-0.28, respectively. The mean +/- SD pre-laser contrast sensitivity score was 121.3+/-83.6, which increased significantly to a mean +/- SD of 151.6+/-80.5 fo lowing direct focal photocoagulation. CONCLUSION: Focal argon laser photocoagulation in CSMO in diabetics helps in improving the contrast sensitivity and stabilizes the visual acuity. The changes in contrast sensitivity and visual acuity are independent of each other.

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.

Anterior segment ischemia after recession of various recti. An experimental study.

In 40 normal adult cynomolgus monkey eyes, recession of various recti in different combinations was done to evaluate their effects on the anterior segment. These procedures were done as primary, secondary, tertiary, and fourth procedures (each separated by several weeks or months), ultimately involving all four recti in the eyes. In 11 eyes, posterior ciliary arteries (PCAs) were occluded to determine its effects on the anterior segment. All eyes were examined by slit lamp, color photography, and fluorescein angiography of the anterior segment, and tonometry, before surgery and serially thereafter during the follow-up period. These studies showed that recession of two or three recti simultaneously in different combinations produced no serious permanent anterior segment changes, although initially in some of the eyes there was transient mild-to-moderate anterior segment ischemia. Recession of four recti simultaneously as a primary procedure produced serious permanent ocular and anterior segment changes; however, when this was done as a secondary or tertiary procedure after previous recessions of three or four recti, anterior segment changes were much fewer and milder than when it was a primary procedure. Occlusion of all the posterior ciliary arteries in itself produced no important changes in the anterior segment, but when combined with simultaneous recession of both the horizontal recti, it produced serious anterior segment changes. In the light of these findings, the pattern of arterial blood supply of the anterior segment is discussed.

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.

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.

Effects of pilocarpine, timolol, epifrin and thymoxamine on iris vessels in rhesus monkeys.

In 24 normal eyes of healthy adult rhesus monkeys, the effects of 1% Pilocarpine, 0.5% Timolol, 0.5% levo-epinephrine (Epifrin) and 0.5% Thymoxamine were tested on the iris vessels, intraocular pressure and pupil size. Fluorescein iris angiography and applanation tonometry were performed on the eyes before the use of any drug, and then 2-4 h after topical instillation of each drug; all drugs were used in all the eyes, an interval of one week being left after the use of each drug. The findings of this study suggest that Pilocarpine and Timolol produced vasodilation. Epifrin and Thymoxamine seemed to have no appreciable effect. Pilocarpine produced miosis while other drugs had no significant effect on pupil size. Pilocarpine, Timolol and Epifrin each produced a significant fall in the intraocular pressure. The mechanisms of vascular changes are discussed. The various limitations of fluorescein iris angiography in such a study are stressed.

Ocular neovascularization with retinal vascular occlusion. I. Association with experimental retinal vein occlusion.

Experimental occlusion of both major temporal retinal veins simultaneously (in six eyes of cynomolgus monkeys) and of the central retinal vein (in one rhesus monkey) produced a fall in intraocular pressure (hypotensive effect) and neovascularization (NV) of the iris and, less frequently, of the optic disc (vasogenic effect). The retinal changes (severity and extent of retinopathy, retinal capillary leakage, and onset and extent of retinal capillary obliteration) were correlated with the pattern of ocular NV and hypotony. No direct correlation was seen between the retinal capillary obliteration and the hypotensive or vasogenic effect. However, a correlation was found between the retinal vascular leakage and the development of ocular NV and hypotony. The pathogeneses of ocular NV and hypotony in retinal vein occlusion are discussed in light of the findings of this study.

Follow-up results of occlusion and pleoptic treatment.

Fifty cases of amblyopia, including some cases of eccentric fixation, which had previously been successfully treated by various therapies (conventional occlusion, red filter occlusion and pleoptics) were followed up from 12 to 68 months. Fifteen cases (30%) deteriorated to pretreatment level during the follow up. Deterioration was found to be greater in cases over the age of 15 years and in cases who did not follow the instructions given to them after cessation of therapy.