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Importance Understanding the natural history of visual outcome in branch retinal vein occlusion (BRVO) is fundamental to its management. Objective To investigate the natural history of visual outcome in major and macular BRVO. Design, Setting, and Participants Observational cohort study at a university-based referral practice from 1973 until 1999. The study comprised 216 consecutive eyes with BRVO (144 eyes with major and 72 eyes with macular BRVO) seen within 3 months of onset. Intervention At first visit, all patients had a detailed ophthalmic and medical history and comprehensive ophthalmic evaluation. Ophthalmic evaluation at initial and follow-up visits included recording best-corrected visual acuity (VA) using the Snellen VA chart and visual fields with a Goldmann perimeter. Main Outcomes and Measures Best-corrected VA and visual field outcome on follow-up. Results The median time to macular edema resolution was 21 months in those with major BRVO and 18 months in those with macular BRVO. Overall, for eyes with initial VA of 20/60 or better, VA improved or remained stable in 75% (95% CI, 63%-86%) for major BRVO and 86% (95% CI, 73%-95%) for macular BRVO. In those with initial VA of 20/70 or worse, VA improved in 69% (95% CI, 56%-80%) for major BRVO and in 53% (95% CI, 27%-79%) for macular BRVO, with median final VA of 20/60 for both BRVO types. Conclusions and Relevance Major and macular BRVOs are 2 distinct clinical entities, and initial visual status and final visual outcome in the 2 types are quite different. Overall, on resolution of macular edema, our study suggests that in both major and macular BRVO, VA and visual fields improved to a variable degree in the majority of eyes without any treatment.

We believe the article by Landau et al 1 has several shortcomings. Landau et al argue that nocturnal arterial hypotension plays no role in the development of anterior ischemic optic neuropathy (AION), while our studies suggest that it is an important precipitating factor for AION. 2 Many risk factors contribute to AION. Some are predisposing factors, and others are precipitating factors. 2,3 When an optic nerve head (ONH) has been rendered vulnerable to ischemia by various predisposing factors, nocturnal hypotension may act as the "last straw" to produce ischemia and AION. 2,3 A similar or even greater degree of nocturnal arterial hypotension in a healthy ONH would have no effect at all. Thus, nocturnal arterial hypotension must be placed in the overall context of the disease process and not in isolation (as Landau et al did). Our disagreements are as follows: The authors state that "The patient with AION typically

Background: Ischemic disorders of the retina and optic nerve head, which constitute a common cause of visual loss, are usually seen in patients with atherosclerosis. Objective: To test the hypothesis that serotonin, which is released when platelets aggregate, may produce vasospasm in atherosclerotic monkeys and, thus, may contribute to the ischemic disorders and that short-term dietary treatment of atherosclerosis causes the propensity to vasospasm to subside. Methods: We studied the response of retinal and posterior ciliary circulation to serotonin in 18 atherosclerotic (25 eyes) and 5 normal (8 eyes) cynomolgus monkeys. The eyes were evaluated by color fundus photography and fluorescein fundus angiography. The eyes were examined under basal conditions and, at a different time, during the intravenous infusion of serotonin. In 6 of the 18 atherosclerotic animals, the evaluation was repeated 5 to 12 months after discontinuing the atherogenic diet (ie, the regression group). Results: Serotonin had no effect in normal monkeys. In 18 atherosclerotic monkeys, serotonin produced transient occlusion or delayed filling of the central retinal artery and/or posterior ciliary artery (PCA) in 9 eyes of 9 animals, involving the central retinal artery in 5, lateral PCA in 8, and medial PCA in 5, in various combinations. In 6 animals (6 eyes) of the regression group, the vasoconstrictor effect of serotonin was abolished completely, except in the medial PCA in 1 eye. Conclusions: Serotonin, in the presence of atherosclerotic lesions, can cause transient, complete occlusion or impaired blood flow in the central retinal artery and/or PCA. We speculate that this mechanism may play a role in the development of ischemic disorders of the retina and optic nerve head. Discontinuing the atherogenic diet abolished or markedly improved the serotonin-induced vasoconstriction within a few months.

Objective: In previous research, experimental occlusion of the posterior ciliary arteries resulted in an infarction of the retinal pigment epithelium and outer retina. A simultaneous occlusion of one or two vortex veins (VVs) appeared to have an ameliorative effect on the retinal infarct based on previous clinical and angiographic observations. The objectives of this report were to evaluate the histopathologic changes of the ischemic retina and to examine the disruption and healing of the blood-retinal barrier under various combinations of ciliary artery and VV occlusions. Methods: Experimental posterior ciliary artery (PCA) occlusion with (n=3) or without (n=3) simultaneous VV occlusion was carried out in six rhesus monkey eyes. The eyes were enucleated over a course of 3 months. The histopathologic changes of the ischemic retina were examined by light and electron microscopy. In addition, the horseradish peroxidase tracer technique was used to study the blood-retinal barrier. Results: Ischemic changes following the occlusion of the PCA consisted of coagulation necrosis of the retinal pigment epithelium and of the outer retinal layers and were less pronounced in eyes with simultaneous VV occlusion. At 6 hours after the insult, the blood-retinal barrier was broken and horseradish peroxidase leaked into the subretinal space (PCA occlusion with one VV occlusion). Three months later, the blood-retinal barrier had re-formed, even in the eyes with severe ischemic injury. Conclusions: The histopathologic changes suggest that the ameliorative effect of simultaneous VV occlusion on the effects of PCA occlusion might be due to reduced perfusion in the choroidal circulation.

To the Editor. —I was very interested to read the expedited publication in the December 1989 issue of theArchivesby Sergott et al 1 claiming that surgical optic nerve sheath decompression improved visual function in patients with "progressive" nonarteritic anterior ischemic optic neuropathy (NA-AION). They hypothesized that in NA-AION, "progressive visual loss after the initial ischemic event could be due to interference with rapid axoplasmic transport produced by [cerebrospinal fluid] CSF pressure within the anatomically restricted confines of the perineural optic nerve space. Drainage of the CSF might allow recovery of fast axoplasmic transport with subsequent improvement in vision." This theory raises some very important issues that need comment before they are accepted as scientifically valid concepts. My comments are based on the following: (1) my prospective studies on NA-AION in more than 600 patients; (2) my studies of the blood supply of the optic nerve head for the

In Reply. —I regret that Drs McLeod and Kohner have tried to refute our experimental study on the pathogenesis of CRVO (Archives96:311-323, 1978) by a superficial and somewhat misguided review of our report and misinterpretation of our and their own findings. Had they read the communication more carefully, it would have become evident that the sole purpose of our study was to investigate the pathogenesis of CRVO and not the mechanism of the development of retinal hemorrhages, which are a nonspecific sign of a large variety of retinopathies. Retinal hemorrhages are seen in both entities of CRVO, ie, venous stasis retinopathy (VSR) and hemorrhagic retinopathy (HR), although they are usually far more extensive in the latter than the former; however, the extent of retinal hemorrhages is not the only criterion for diagnosing HR. I stressed that "Diagnosis of venous stasis retinopathy or hemorrhagic retinopathy is thus arrived at

Temporal arteritis, or giant cell arteritis, is an important disease erroneously considered to be rare because of lack of awareness and recognition of the disease by physicians. According to the authors, their primary aim is to increase physicians' awareness of temporal arteritis and to help them recognize and treat the dreaded disease. This monograph is essentially a review of most of the literature on systemic manifestations of temporal arteritis, with occasional reference to the authors' experiences with the disease. After a historical review, various systemic clinical manifestations of temporal arteritis, eg, myalgia, malaise, anorexia, weight loss, fever, anemia, malignancy-like presentation, cranial and neurological manifestations, aortic arch syndrome, and cardiac disorders are discussed. There is a detailed account of the clinical picture of polymyalgia rheumatica. Whether polymyalgia rheumatica is always a manifestation of temporal arteritis or not is discussed at length; the conclusion is that the question cannot yet be answered

• The ocular toxicity of methyl alcohol has been investigated in six rhesus monkeys. All the animals developed fundus changes within 43 to 171 hours after its ingestion. The only fundus lesion seen was optic disc edema and associated changes, usually of a marked degree. Fluorescein fundus angiography confirmed the findings. The retinal and choroidal circulations, including the retinal capillary bed, were normal. Ophthalmoscopically and angiographically, optic disc edema in methyl alcohol poisoning was Indistinguishable from that seen in raised intracranial pressure, except that no increased intracranial pressure was observed. It is postulated that optic disc edema in methyl alcohol poisoning is due to an axoplasmic flow stasis. ( Arch Ophthalmol 95:1851-1858, 1977)

Sixty-one patients (64 eyes) with central retinal artery occlusion (CRAO) and 41 patients (44 eyes) with branch retinal artery occlusion (BRAO) were studied in detail clinically to find out the pathogenesis of their ocular neovascularization (NV). Ocular NV was seen in 12 eyes (11 patients) with CRAO: iris NV was seen in all 12 eyes, angle NV was seen with neovascular glaucoma (NVG) in ten of them, and no NV was seen in BRAO. Nine of ten patients with CRAO associated with NVG were old, having severe carotid artery disease (CAD) and severe generalized atherosclerotic arterial disease; in the remaining patient, NVG was caused by diabetes mellitus. Severe CAD results in chronic ocular ischemia, which, in turn, produces NV of the iris and angle and NVG; the latter, combined with poor perfusion pressure in the central retinal artery (caused by severe CAD), results in CRAO. Our study showed little evidence that CRAO, per se, is responsible for ocular NV. Various evidence in support of this hypothesis is presented. Our study also showed that the only eyes to recover good vision were those with transient CRAO for up to 11/2 hours, and no treatment helped.

• Four unusual patients had bilateral anterior ischemic optic neuropathy (AION). In all four cases, AION developed in the first eye with the classic presentation. The fellow eye had symptomless optic disc edema (ODE) with no subjective or objective visual loss initially, but the classic AION clinical picture developed later on. The findings indicate that symptomless ODE may precede the visual loss in AION and could constitute the earliest sign of this disease. Since ODE in AION is due to axoplasmic flow stasis that, by itself, does not produce visual loss (this is produced by disruption of visual impulse transmission), this would suggest that mild optic nerve head ischemia interferes with axoplasmic flow without disrupting the visual impulse; however, more severe ischemia would disrupt both. Possible effects of various grades of acute optic nerve head ischemia are discussed.

• Tritiated leucine was Injected intravitreously into the eyes of rhesus monkeys that had developed papilledema secondary to implantation of intracranial balloons. Autoradiographic studies of the optic nerve head showed that six hours after intravitreous injection of the isotope the fast component of axoplasmic transport accumulated in the regions of the lamina choroidalis and lamina scleralis. The slow component arrived at the optic nerve head two to four days after injection, and the swollen axons of the entire optic nerve head were filled with radioactive isotopes. Twelve days after injection of isotope, the axons in the optic nerve head were still diffusely labeled. Disturbance of axoplasmic transport was one of the primary events resulting in swelling of axons in papilledema. The pattern of axoplasmic disturbances in papilledema secondary to raised intracranial pressure was similar to that observed in papilledema secondary to ocular hypotony or increased intraocular pressure. Ocular hypotony, raised intracranial pressure, and increased intraocular pressure appear to share a final common pathway. All these conditions apparently converge into this final common pathway of disturbance of axoplasmic transport to give rise to papilledema. (Arch Ophthalmol95:1458-1462, 1977)

• We developed an animal model that allows the early phases of iris neovascularization to be studied in detail. Three major retinal branch veins were occluded with the argon laser in five eyes of cynomolgus monkeys, after which the eyes were enucleated at various time intervals. We observed three phases of the neovascular process in the iris. The early phase was characterized by vessel dilation and intense uptake of tritiated thymidine in the vascular endothelial cells. In the intermediate phase, prominent new vessels, ectropion uveae, peripheral anterior synechiae, and elevated intraocular pressure developed. Also noted were a decrease in tritiated thymidine uptake of the endothelial cells, a remarkable increase in stromal cell tritiated thymidine activity, and the formation of a neovascular membrane in association with the anterior migration of stromal cells. The late phase was marked by a further reduction of tritiated thymidine uptake and regression of the neovascular membrane.

Optic nerve heads of 21 eyes from 13 rhesus monkeys that had developed papilledema secondary to chronically raised intracranial pressure from balloon implantation in the subarachnoid space were studied by light and electron microscopy. Nine eyes were also examined with the horseradish peroxidase tracer technique. The pathologic changes in the optic nerve head included severe axonal changes and mild interstitial edema. Axonal alteration ranged from axonal swelling to formation of cytoid bodies. Interstitial edema and vascular leakage of horseradish peroxidase were noted in the posterior lamina retinalis, lamina choroidalis and lamina scleralis (prelaminar and lamina cribrosa regions), as well as in the retrolaminar myelinated optic nerve. No intracellular edema of the glial elements was noted. Axonal swelling was so prominent that it appeared to be primarily responsible for the overall swelling of the optic disc observed ophthalmoscopically.

Optic disc edema (ODE) due to chronic intracranial hypertension was produced experimentally in rhesus monkeys. Serial studies of fundus changes at frequent intervals, by routine ophthalmoscopy, steroscopic color photography, and fluorescein angiography, revealed that swelling of the optic disc was the first sign of ODE. Other early signs were striation of nerve fibers on the optic disc margins and peripapillary retina, blurring of the disc margins, hyperemia of the disc and capillary dilation, hemorrhages, and other retinal vascular changes; these usually appeared in that sequence. The classically described signs of early ODE were almost always absent. A normal fluorescein fundus angiogram during the incipient stage did not rule out ODE. Stereoscopic color fundus photography was the most sensitive means of detecting early ODE. Fluorescein angiography did not show changes till edema was of a mild to moderate degree; routine ophthalmoscopy was the least reliable method.

• Photoradiation therapy is a new technique currently under clinical investigation for the treatment of a variety of solid malignant tumors. The technique involves intravenous (IV) administration of hematoporphyrin derivative, a photosensitizing compound that is preferentially retained by malignant cells, and photoactivation of a neoplasm with red light (630 nm) to obtain selective destruction of cancer cells. A modification of this technique was used to treat iris neovascularization produced in a primate model of retinal vein occlusion. Following IV injection of hematoporphyrin derivative, the anterior surface of the iris was exposed to red light for 30 to 45 minutes. In the four eyes treated, there was a marked reduction of fluorescein leakage from the neovascular tissue within 24 hours following treatment. Histologic examination of two eyes demonstrated a selective response of the iris neovascularization to this therapy, with apparent preservation of surrounding tissue.

• A two-trunked central retinal vein (CRV) in the anterior part of the optic nerve may persist as a congenital abnormality in a certain proportion of humans. One of the two trunks, like the CRV, may get occluded in the optic nerve to produce hemi-CRV occlusion (hemi-CRVO). It is shown that hemi-CRVO is a distinct entity, clinically and pathogenetically closely related to CRVO, and unrelated to branch retinal vein occlusion because of fundamental differences between the two. Hemi-CRVO clinically presents as either venous stasis retinopathy (VSR) or as hemorrhagic retinopathy (HR), usually involving one half of the retina, although occasionally it may involve one third to two thirds of the retina. The clinical features of VSR and HR caused by hemi-CRVO are identical to those caused by CRVO. The primary object of this article is to identify hemi-CRVO, a not uncommon condition, and to describe its main clinical features.

• The ocular morphological findings of three methyl alcohol-intoxicated rhesus monkeys with optic disc swelling was investigated with light and electron microscopy in conjunction with intravascular horse radish peroxidase. Alterations observed in the optic nerve head were confined to the axons and consisted of swelling and clustering of the mitochondria, disruption of the neurotubules, the formation of vesicles, and enlargement of the axon segments in the prelaminar region. Swelling of the oligodendroglial cytoplasm in contact with the axons and of the astrocytes was seen in the retrolaminar optic nerve and the intraorbital optic nerve. Alterations were not observed in the retina. It is hypothesized that the alterations in the axons are the result of disrupted axoplasmic flow. Possible mechanisms relating methyl alcohol intoxication to disruption of axoplasmic flow are discussed. ( Arch Ophthalmol 95:1859-1865, 1977)

• Iris circulation was investigated by fluorescein iris angiography in 33 human eyes before and after tenotomy of one or more recti for correction of strabismus. Tenotomy of one or both horizontal recti produced no appreciable circulatory disturbance in the iris, but tenotomy of superior or inferior rectus produced circulatory delay in superior temporal or inferior temporal sectors, respectively, of the iris. When tenotomies of a horizontal and one or two vertical recti were combined, the defect occurred in the region of the vertical rectus only. Blood supply of the nasal half of the iris was usually not disturbed by tenotomy of the vertical and/or medial rectus. The findings indicate that the blood supply of the iris is segmental and suggest that, in strabismus surgery, cutting the two vertical recti along with the lateral rectus may subject the eye to the risk of anterior segment ischemia. In the light of the present findings, physiological anatomy of the blood supply of the iris and role of the major arterial circle of the iris are discussed.

This is one of the publications in the seriesCurrent Ophthalmology Monographsintroduced by Grune & Stratton Inc. This monograph is based on the author's interpretation of the fluorescein fundus angiograms in 247 patients. Included in this study were normal control subjects (50); patients suspected of having glaucoma (87); patients with primary open-angle glaucoma (62); patients with lowtension glaucoma (16); and patients with other types of glaucoma (32). These patients were followed up for periods of up to five years. The author concluded that his study showed the existence of considerable differences between control subjects and patients with chronic open-angle glaucoma in regard to blood flow to the optic nerve and retina. Elevation of intraocular pressure caused retardation of the rate of flow in the retina, optic nerve, and possibly choroid. Perfusion of the optic nerve, as determined by fluorescein fundus angiography, was more severely affected in some cases by

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.

• Accelerated renovascular hypertension produces optic nerve changes ranging from optic disc edema to optic atrophy. To elucidate the pathogenesis of hypertensive optic neuropathy, the optic nerves from 12 monkeys (23 eyes) with accelerated renovascular systemic hypertension were studied by electron and light microscopy. Within 21 months, the animals demonstrated the entire spectrum of pathologic changes. In the optic nerves with optic disc edema, the prelaminar optic nerve exhibited vasoconstriction with subsequent axonal hydropic swelling, axolemma disruption, and glial swelling. In retrolaminar myelinated optic nerve, vasoconstriction was more severe, with endothelial swelling and pericytic degeneration resulting in intramyelinic vacuoles and glial swelling. Optic disc edema appeared to result from axonal hydropic swelling secondary to ischemic infarct, followed by loss of axons and gliosis in the prelaminar optic nerve. The retrolaminar myelinated nerve showed prominent microglial reaction and eventual atrophy of axons and glia. Ischemia seemed to play a major role in hypertensive optic neuropathy, which represents anterior ischemic optic neuropathy.

The pathogenesis of optic disc edema (ODE) in raised intracranial pressure is discussed in the light of recent observations on the subject. The findings indicate that ODE is a mechanical phenomenon. The raised cerebrospinal fluid pressure (CSFP) in the sheath of the optic nerve produces axoplasmic flow stasis in the optic nerve head. This results in swelling of the axons, which manifests as early ODE and secondarily produces the well-known optic disc and retinal vascular changes associated with ODE. The pathogenesis of ODE seen in different conditions without raised CSFP cannot be explained by any single mechanism in spite of the occurrence of axoplasmic flow stasis in most cases, because the stasis in different situations has different mechanisms.

• We measured the pupil cycle time, the relative afferent pupillary defect, and the pattern-reversal visual evoked potential (VEP) in 41 patients with unilateral anterior ischemic optic neuropathy (AION) and 24 patients with unilateral optic neuritis. We speculated that the relative afferent pupillary defect would match the VEP amplitude and that the pupil cycle time would correspond to the VEP latency. We found a correlation between the relative afferent pupillary defect and VEP amplitude in patients with AION, but not in patients with optic neuritis. We also found that the pupil cycle time and VEP latency were weakly correlated, but only in patients with optic neuritis. In these two groups of patients with unilateral optic neuropathy, the most sensitive objective indicator of disease was the relative afferent pupillary defect. The least sensitive indicator was the pupil cycle time.