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This is a case report of ‘familial giant cell arteritis’ in three siblings from northwest India. This is the first case report of ‘familial giant cell arteritis’ in a non-Caucasian family.

Purpose To compare the severity of ischemic damage after posterior ciliary artery (PCA) occlusion in old, atherosclerotic, hypertensive monkeys with that in young monkeys. Design Experimental study. Participants Seven eyes of normal, healthy rhesus monkeys and 8 eyes of old, atherosclerotic, hypertensive monkeys. Methods By lateral orbitotomy, all PCAs were cut behind the eyeball in both groups of animals. The fundus and the optic disc were evaluated by repeated ophthalmoscopy, color fundus photography, and fluorescein fundus angiography before and immediately after cutting the PCAs and serially thereafter during the follow-up period. Main Outcome Measures Severity of acute ischemic damage to the choroid, outer retina, and optic nerve head. Results Cutting all the PCAs resulted in the development of ischemic infarction of the choroid, retinal pigment epithelium, outer part of the retina, and optic nerve head within 24 hours in both groups of animals. The severity of the various ischemic fundus and retinal lesions and of the optic disc during the acute phase showed no statistically significant differences between the 2 groups of animals. Fluorescein fundus angiography performed soon after cutting the PCAs showed no filling of the entire choroid and the optic disc in both groups of animals. On follow-up until approximately 3 months in both groups, the white opacity of the infarct in the fundus seen during the acute phase gradually resolved in approximately 2 to 3 weeks, leaving greyish, granular, depigmented fundus, unmasking of the large choroidal vessels, and optic atrophy; fluorescein angiography revealed gradual restoration of the choroidal blood flow and unmasking of the big choroidal vessels. Conclusions The study showed that the severity of ischemic damage after occlusion of all the PCAs was similar in both the young, healthy monkeys and the old, atherosclerotic, hypertensive monkeys. This is in contrast to the findings of our similar study dealing with central retinal artery occlusion, where the young demonstrated much more severe ischemic damage than the old.

The role of photocoagulation in retinal vein occlusion (RVO) has been studied since 1974. The most serious complications of central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) are: (i) visual deterioration, most commonly due to macular edema, and (ii) the development of ocular neovascularization (NV), particularly neovascular glaucoma (NVG), with hazardous consequences for vision and even the eye itself. Before discussing the role of photocoagulation in the management of NV and macular edema in RVO, it is crucial to gain a basic scientific understanding of the following relevant issues: classification of RVO, ocular NV in RVO, and the natural history of macular edema and visual outcome of RVO. These topics are discussed. In CRVO, ocular NV is a complication of ischemic CRVO but not of nonischemic CRVO. Photocoagulation has been advocated to prevent and/or treat the development of ocular NV and NVG. Since NVG is the most dreaded, intractable and blinding complication of ischemic CRVO, the role of photocoagulation and its management are discussed. Findings of three randomized, prospective clinical trials dealing with photocoagulation in ischemic CRVO are discussed. The role of photocoagulation in the management of ocular NV and macular edema in BRVO, and three randomized, prospective clinical trials dealing with those are discussed. Recent advent of intravitreal anti-VEGF and corticosteroid therapies has drastically changed the role of photocoagulation in the management of macular edema and NV in CRVO and BRVO. This is discussed in detail.

OBJECTIVE: To estimate the incidence of acute cerebral ischaemia detected by magnetic resonance imaging (MRI) in acute central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO) and transient monocular vision loss (TMVL). METHODS: Studies reporting the incidence of acute cerebral ischaemia, detected by MRI, within 7 days from diagnosis of acute CRAO, BRAO and TMVL up to January 2019 were systematically searched for on Pubmed, Medline and Cochrane Library. Meta-analysis was performed using random effects model. The primary outcome was the pooled estimate of incidence of acute cerebral ischaemia in CRAO, BRAO and TMVL cohorts including both neurologically symptomatic and asymptomatic patients, expressed as a proportion along with 95% confidence intervals (CIs). The pooled estimate of incidence of asymptomatic acute cerebral ischaemia represented a secondary outcome measure. RESULTS: For the primary outcome, the pooled proportion of acute cerebral ischaemia was 0.30 (CI 0.24–0.36) in the CRAO cohort, and 0.25 (CI 0.16–0.37) in the BRAO cohort, without statistical heterogeneity. The rate of acute cerebral ischaemia was 11.8% in the TMVL cohort. For the secondary outcome, the pooled proportion of asymptomatic acute cerebral ischaemia was 0.22 (CI 0.16–0.28) in the CRAO cohort, 0.29 (CI 0.20–0.41) in the BRAO cohort and 0.08 (CI 0.05–0.15) in the TMVL cohort, with no statistical heterogeneity. CONCLUSIONS: 30% of patients with acute CRAO and 25% of patients with acute BRAO presented an acute cerebral ischaemia on MRI. Such high rates support a care pathway of prompt referral of such patients for neurological evaluation and brain imaging.

ObjectiveThere has long been a great interest in neuroprotection therapy for ischaemic stroke and various types of optic neuropathies. In view of that, I reviewed the literature on the role of neuroprotection for non-arteritic anterior ischaemic optic neuropathy (NA-AION).MethodsThe review is based on a PubMed search of literature about the use of neuroprotectors in stroke and optic neuropathies and about current clinical trials of RPh201 and QPI-1007 in NA-AION.ResultsSeveral neuroprotection agents for ischaemic stroke and various types of optic neuropathies have been evaluated extensively in experimental studies in animals and benefits claimed. However, translation of therapeutic strategies for neuroprotection from experimental research to humans has invariably been fraught with failure. Two currently ongoing studies dealing with neuroprotection by RPh201 and QPI-1007 in NA-AION may have limitations in their rationale and study designs.ConclusionsUnfortunately, in spite of all the experimental and clinical research on neuroprotection agents in NA-AION so far, we have no scientifically proven evidence of neuroprotection agents showing any benefit in the human clinical studies so far.

Optic disc edema in raised intracranial pressure was first described in 1853. Ever since, there has been a plethora of controversial hypotheses to explain its pathogenesis. I have explored the subject comprehensively by doing basic, experimental and clinical studies. My objective was to investigate the fundamentals of the subject, to test the validity of the previous theories, and finally, based on all these studies, to find a logical explanation for the pathogenesis. My studies included the following issues pertinent to the pathogenesis of optic disc edema in raised intracranial pressure: the anatomy and blood supply of the optic nerve, the roles of the sheath of the optic nerve, of the centripetal flow of fluids along the optic nerve, of compression of the central retinal vein, and of acute intracranial hypertension and its associated effects. I found that, contrary to some previous claims, an acute rise of intracranial pressure was not quickly followed by production of optic disc edema. Then, in rhesus monkeys, I produced experimentally chronic intracranial hypertension by slowly increasing in size space-occupying lesions, in different parts of the brain. Those produced raised cerebrospinal fluid pressure (CSFP) and optic disc edema, identical to those seen in patients with elevated CSFP. Having achieved that, I investigated various aspects of optic disc edema by ophthalmoscopy, stereoscopic color fundus photography and fluorescein fundus angiography, and light microscopic, electron microscopic, horseradish peroxidase and axoplasmic transport studies, and evaluated the effect of opening the sheath of the optic nerve on the optic disc edema. This latter study showed that opening the sheath resulted in resolution of optic disc edema on the side of the sheath fenestration, in spite of high intracranial CSFP, proving that a rise of CSFP in the sheath was the essential pre-requisite for the development of optic disc edema. I also investigated optic disc edema with raised CSFP in patients, by evaluating optic disc and fundus changes by stereoscopic fundus photography and fluorescein fundus angiography. Based on the combined information from all the studies discussed above, it is clear that the pathogenesis of optic disc edema in raised intracranial pressure is a mechanical phenomenon. It is primarily due to a rise of CSFP in the optic nerve sheath, which produces axoplasmic flow stasis in the optic nerve fibers in the surface nerve fiber layer and prelaminar region of the optic nerve head. Axoplasmic flow stasis then results in swelling of the nerve fibers, and consequently of the optic disc. Swelling of the nerve fibers and of the optic disc secondarily compresses the fine, low-pressure venules in that region, resulting in venous stasis and fluid leakage; that leads to the accumulation of extracellular fluid. Contrary to the previous theories, the various vascular changes seen in optic disc edema are secondary and not primary. Thus, optic disc edema in raised CSFP is due to a combination of swollen nerve fibers and the accumulation of extracellular fluid. My studies also provided information about the pathogeneses of visual disturbances in raised intracranial pressure.

Purpose To describe a framework for logical, immediate action to manage patients with retinal artery occlusion. Design Literature review and perspective. Methods Review of the literature and the author’s experience. Results Since embolism is the most common factor causing retinal artery occlusion, to manage these patients, immediate evaluation and management of the source of embolism is critical to prevent further episodes. Conclusions The logical, immediate action to manage patients with retinal artery occlusion is evaluation of the carotid artery and heart for embolism, fasting lipid levels and a complete blood count, rather than neurological evaluation, unless, of course, there are neurological symptoms.

To investigate systematically the retinal and optic disk changes in central retinal vein occlusion (CRVO) and their natural history.This study comprised 562 consecutive patients with CRVO (492 nonischemic [NI-CRVO] and 89 ischemic CRVO [I-CRVO] eyes) seen within 3 months of onset. Ophthalmic evaluation at initial and follow-up visits included recording visual acuity, visual fields, and detailed anterior segment and fundus examinations and fluorescein fundus angiography.Retinal and subinternal limiting membrane hemorrhages and optic disk edema in I-CRVO were initially more marked (P0.0001) and took longer to resolve (P0.015) than that in NI-CRVO. Initially, macular edema was more marked in I-CRVO than that in NI-CRVO (P0.0001) but did not significantly differ in resolution time (P = 0.238). Macular retinal epithelial pigment degeneration, serous macular detachment, and retinal perivenous sheathing developed at a higher rate in I-CRVO than that in NI-CRVO (P0.0001). Ischemic CRVO had more retinal venous engorgement than NI-CRVO (P = 0.003). Fluorescein fundus angiography showed significantly more fluorescein leakage, retinal capillary dilatation, capillary obliteration, and broken capillary foveal arcade (P0.0001) in I-CRVO than NI-CRVO. Resolution time of CRVO was longer for I-CRVO than NI-CRVO (P0.0001).Characteristics and natural history of fundus findings in the two types of CRVO are different.

Ocular vascular occlusive disorders collectively constitute the most common cause of visual disability. Before a disease can be managed, it is essential to understand its natural history, so as to be able to assess the likely effectiveness of any intervention. I investigated natural history of visual outcome in prospective studies of 386 eyes with non-arteritic anterior ischemic optic neuropathy (NA-AION), 16 eyes with non-arteritic posterior ischemic optic neuropathy, 697 eyes with central retinal vein occlusion (CRVO), 67 eyes with hemi-CRVO (HCRVO), 216 eyes with branch retinal vein occlusion (BRVO), 260 eyes with central retinal artery occlusion (CRAO), 151 eyes with branch retinal artery occlusion (BRAO) and 61 eyes with cilioretinal artery occlusion (CLRAO). My studies have shown that every one of these disorders consists of multiple distinct clinical sub-categories with different visual findings. When an ocular vascular occlusive disorder is caused by giant cell arteritis, which is an ophthalmic emergency, it would be unethical to do a natural history study of visual outcome in them, because in this case early diagnosis and immediate, intensive high-dose steroid therapy is essential to prevent any further visual loss, not only in the involved eye but also in the fellow, normal eye. In NA-AION in eyes seen ≤2 weeks after the onset, visual acuity (VA) improved in 41% of those with VA 20/70 or worse, and visual field (VF) improved in 26% of those with moderate to severe VF defect. In non-ischemic CRVO eyes with VA 20/70 or worse, VA improved in 47% and in ischemic CRVO in 23%; moderate to severe VF defect improved in 79% in non-ischemic CRVO and in 27% in ischemic CRVO. In HCRVO, overall findings demonstrated that initial VA and VF defect and the final visual outcome were different in non-ischemic from ischemic HCRVO – much better in the former than the latter. In major BRVO, in eyes with initial VA of 20/70 or worse, VA improved in 69%, and moderate to severe VF defect improved in 52%. In macular BRVO with 20/70 or worse initial VA, it improved in 53%, and initial minimal-mild VF defect was stable or improved in 85%. In various types of CRAO there are significant differences in both initial and final VA and VF defects. In CRAO eyes seen within 7 days of onset and initial VA of counting fingers or worse, VA improved in 82% with transient non-arteritic CRAO, 67% with non-arteritic CRAO with cilioretinal artery sparing, 22% with non-arteritic CRAO. Central VF improved in 39% of transient non-arteritic CRAO, 25% of non-arteritic CRAO with cilioretinal artery sparing and 21% of non-arteritic CRAO. Peripheral VF improved in non-arteritic CRAO in 39% and in transient non-arteritic CRAO in 39%. In transient CRAO, finally peripheral VFs were normal in 93%. In non-arteritic CRAO eyes initially 22% had normal peripheral VF and in the rest it improved in 39%. Final VA of 20/40 or better was seen in 89% of permanent BRAO, and in 100% of transient BRAO and non-arteritic CLRAO. In permanent BRAO eyes, among those seen within 7 days of onset, central VF defect improved in 47% and peripheral VF in 52%, and in transient BRAO central and peripheral VFs were normal at follow-up. My studies showed that AION, CRVO, BRVO, CRAO and BRAO, each consist of multiple distinct clinical sub-categories with different visual outcome. Contrary to the prevalent impression, these studies on the natural history of visual outcome have shown that there is a statistically significant spontaneous visual improvement in each category. The factors which influence the visual outcome in various ocular vascular occlusive disorders are discussed.

To investigate the incidence of ocular neovascularization (NV) in central and hemicentral retinal vein occlusion.The study comprised consecutive 912 (673 nonischemic and 239 ischemic) central retinal vein occlusion and 190 (147 nonischemic, 43 ischemic) hemicentral retinal vein occlusion eyes. Ophthalmic evaluation at initial and follow-up visits included recording visual acuity, visual fields, and detailed anterior segment and fundus examinations and fluorescein fundus angiography.In ischemic central retinal vein occlusion, within 6 months from time of onset, the cumulative probability of development of iris NV was 49%, angle NV 37%, NV glaucoma 29%, retinal NV 9%, and disk NV 6%. More severe peripheral retinal hemorrhages were significantly associated with iris NV (P = 0.005), angle NV (P = 0.0004), and NV glaucoma (P = 0.012). Eyes that developed disk NV had more cotton wool spots (P = 0.058) than those without. In ischemic hemicentral retinal vein occlusion, within 12 months of onset, the cumulative probability of development of retinal NV was 29%, disk NV 12%, and iris NV 12%; within 6 months of onset, angle NV was found in 10% and NV glaucoma in 5%. Anterior chamber flare was associated with anterior segment NV and may precede the development of NV. Patients who developed NV were significantly younger, and there was a greater prevalence of NV glaucoma in patients with primary open angle glaucoma.In ischemic central retinal vein occlusion, anterior segment NV is much more common than posterior segment NV, and the cumulative chance of developing anterior segment NV is maximum during the first 6 months. In ischemic hemicentral retinal vein occlusion, posterior segment NV is much more common than anterior segment NV.

Non-arteritic anterior ischemic optic neuropathy (NAAION) is a common, visually disabling disease. However, its pathogenesis and management have been highly controversial. There is a common belief that NA-AION and cerebral ischemic stroke are similar in nature pathogenetically and in management. For example, ophthalmologists and neurologists routinely tend to prescribe aspirin to NAAION patients with the rationale that NA-AION, like stroke, is a thromboembolic disorder and aspirin helps thromboembolic disorders. NA-AION patients who come to consult me usually tell me that their neuro-ophthalmologists and neurologists have stated that NA-AION and cerebral ischemic stroke are similar in nature. This concept has resulted in major controversy on the pathogenesis and management of NA-AION. The evidence shows, however, that NA-AION is pathogenetically a totally different clinical entity from cerebral ischemic stroke. It is well-established that cerebral ischemic stroke is a thromboembolic disorder in most cases. In a smaller number of cases, cerebral ischemic stroke can also be due to hypoperfusion and watershed infarcts when blood pressure drops to a critical level. My studies have shown that NA-AION, unlike most cases of cerebral ischemic stroke, is NOT a thromboembolic disorder, except very rarely [1–3]. Fluorescein fundus angiography provides the crucial information about this, as is evident from the following. The optic nerve head (ONH) is supplied by the posterior ciliary artery [4, 5]. First and foremost, if NA-AION were a thromboembolic disorder, fluorescein fundus angiography during the early stages of the onset of visual loss would invariably show evidence of complete occlusion of the posterior ciliary artery, with no filling of the ONH and the choroid. For example, in arteritic AION, due to giant cell arteritis, where there is complete occlusion of the posterior ciliary artery due to thrombosis [6–8], the ONH and choroid do not fill at all, as shown in Fig. 1. In sharp contrast to that, in my angiographic studies of more than 1,000 eyes with acute, classical NA-AION, no such occlusion was ever seen (except in a rare case when NA-AION was due to embolism to the posterior ciliary artery). Angiography soon after the onset of NA-AION may show only a transient hypoperfusion or non-perfusion of the peripapillary choroid and/or choroidal watershed zones, but these areas eventually fill with fluorescein during angiography, indicating no arterial occlusion and that NA-AION is not a thromboembolic occlusive disorder, as shown in Fig. 2. Fluorescein fundus angiography in Fig. 2 was performed during the day when the patient’s blood pressure was normal, yet it still revealed a transient filling defect in the peripapillary choroid and watershed zone. My 24-hour ambulatory blood pressure monitoring studies in more than 700 patients have shown that in all normal persons, daytime blood pressure is in the normal range, but nevertheless there is always a variable degree of fall in blood pressure during sleep (see Figs. 3, 4). In the eye in Fig. 2, it is hypothesized that prolonged nonfilling of the peripapillary choroid (main source of blood supply to the ONH) and the watershed zone surrounding the ONH during sleep, due to a fall of blood pressure, must have reduced blood flow to the ONH maximally, resulting in S. S. Hayreh Department of Ophthalmology and Visual Sciences, College of Medicine, University of Iowa, Iowa City, IA, USA

Objective To investigate systematically the role of anti–platelet-aggregating drugs or anticoagulants in central retinal vein occlusion (CRVO) and hemi-CRVO. Design Cohort study. Participants Six hundred eighty-six consecutive patients with CRVO (567 patients, 585 eyes) and nonischemic hemi-CRVO (119 patients, 122 eyes). Methods At first visit, all patients had a detailed ophthalmic and medical history (including the use of anti–platelet aggregating drugs or anticoagulants), and comprehensive ophthalmic and retinal evaluation. Visual evaluation was carried out by recording visual acuity, using the Snellen visual acuity chart, and visual fields with a Goldmann perimeter. The same ophthalmic evaluation was performed at each follow-up visit. At the initial visit, CRVO and hemi-CRVO were classified as nonischemic and ischemic. Main Outcome Measures Visual acuity, visual fields, and severity of retinal hemorrhages. Results All 3 types of CRVO, showed a significantly greater severity of retinal hemorrhages among aspirin users than nonusers ( P P = 0.020). Of those whose macular edema resolved, overall cumulative visual acuity outcome also suggested a higher percentage with deterioration among aspirin users, odds ratio for deterioration of 3.62 (95% CI, 0.97–13.54; P = 0.05) for aspirin users relative to nonusers. For the nonischemic CRVO patients with 20/70 or worse visual acuity at the initial visit, after resolution of macular edema, improvement in visual acuity was less likely in the aspirin users than in nonusers (odds ratio, 0.18; 95% CI, 0.04–0.72; P = 0.016). Conclusions Findings of this study indicate that, for patients with CRVO and hemi-CRVO, the use of aspirin, other anti–platelet aggregating agents, or anticoagulants was associated with a worse visual outcome and no apparent benefit. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Purpose of review The aim is to briefly discuss the currently controversial management of nonarteritic anterior ischemic optic neuropathy (NA-AION) and central retinal artery occlusion (CRAO). Recent findings The role of systemic corticosteroid therapy and aspirin in NA-AION and of thrombolysis in CRAO is discussed. Summary NA-AION is a major cause of seriously impaired vision. A recent large prospective study has shown that systemic corticosteroid resulted in a significantly higher probability of improvement in visual acuity (P = 0.001) and visual fields (P = 0.005), compared to an untreated group. In CRAO, the latest prospective study has shown that thrombolytic therapy not only has no beneficial effect but also is harmful.

Dear Editor, I was interested to read the comments by Berdahl and colleagues [1] opposing my conclusion that cerebrospinal fluid pressure (CSFP) has no role to play in optic disc cupping in glaucoma [2]. Unfortunately, the entire basis of their hypothesis that low CSFP causes bowing back of the lamina cribrosa, and consequently glaucomatous optic disc cupping, has several fundamental flaws, which invalidate their hypothesis. The hypothesis is primarily based on the presumption that optic disc cupping in glaucoma is just the reverse of optic disc swelling in raised CSFP; therefore, it should be caused by low CSFP. As I discussed in my editorial [2], that concept is invalid, because optic disc edema in raised CSFP is due to axoplasmic flow stasis [3, 4] and not due to bowing forward of the lamina cribrosa, whereas optic disc cupping in glaucoma has totally different pathogenesis, in which axoplasmic flow plays no role. Therefore, to apply findings from optic disc swelling in raised CSFP to optic disc cupping in glaucoma has no scientific logic at all. In my editorial, my conclusion that low CSFP plays no role in optic disc cupping was based on my studies (since 1961) on optic disc structure [5], the pathogenesis of optic disc swelling in raised CSFP [3, 4, 6, 7], other CSFP studies [8, 9], and the pathogenesis of optic disc cupping in glaucoma [10–16], as well as on the studies of others in the published literature [2]. By contrast, the hypothesis by Berdahl and colleagues [1] that CSFP “may play an important role in the development of POAG and NTG” is drawn from only the following two studies.

Non-arteritic anterior ischemic optic neuropathy (NA- AION) is a common, visually disabling disorder occurring in the middle-aged and elderly, but no age group is immune to it—in two large series the youngest persons with NA- ION were 18 (1) and 13 (2) years old. NA-AION is a multifactorial disease; several risk factors play a role in its development, some acting as predisposing and others as precipitating risk factors, as discussed detail elsewhere (3- 6). Some studies have mentioned thrombophilia (7-12 )a s a risk factor, including one published in this issue of this journal (13). To place the role of thrombophilia in proper perspective, it is essential to discuss two basic issues, i.e., the pathogenesis of NA-AION and whether thrombophilia has any role in that or not. Pathogenesis of NA-AION One often hears and reads that the pathogenesis of NA-AION is unknown, but that is no longer true with our current knowledge of the subject. The pathogenesis of NA-AION is discussed at length elsewhere (4). NA-AION represents a multifactorial acute ischemic disorder of the optic nerve head (ONH) which is supplied by the posterior ciliary artery.

To describe the clinical characteristics and pathogenesis of central retinal vein occlusion (CRVO) associated with cilioretinal artery occlusion (CLRAO).The study included 38 patients (38 eyes) who had CRVO associated with CLRAO and were seen in our clinic from 1974 to 1999. At their first visit to our clinic, all patients provided a detailed ophthalmic and medical history and underwent comprehensive ophthalmic evaluation, color fundus photography, and fluorescein fundus angiography. At each follow-up visit, the same ophthalmic evaluations were performed, except for fluorescein fundus angiography.Of 38 eyes, 30 had nonischemic CRVO, 5 had ischemic CRVO, and 3 had nonischemic hemi-CRVO. Patients with nonischemic CRVO were significantly younger (mean age +/- SD: 45.3 +/- 16.0 years) than those with ischemic CRVO (72.3 +/- 9.2 years; P = 0.001) and those with nonischemic hemi-CRVO (64.7 +/- 7.5 years; P = 0.018). At least one third of the patients gave a definite history of episode(s) of transient visual blurring before the onset of constant blurred vision. Initially, the ophthalmoscopic and fluorescein angiographic findings were similar to those seen in CRVO and hemi-CRVO, except that all these eyes had retinal infarct in the distribution of the cilioretinal artery; its size and site varied widely. Fluorescein angiography typically showed only transient hemodynamic block and not the typical CLRAO. During follow-up, visual acuity improved markedly in nonischemic CRVO (P0.001) and nonischemic hemi-CRVO but deteriorated in ischemic CRVO. Retinopathy resolved spontaneously in 22 eyes with nonischemic CRVO (mean duration +/- SD: 42.0 +/- 101.0 months), in 2 eyes with ischemic CRVO (15.4 +/- 4.5 months), and in 1 eye with nonischemic hemi-CRVO. Retinociliary collaterals developed in 30% of eyes with nonischemic CRVO, in 40% of eyes with ischemic CRVO, and in 66% of eyes with nonischemic hemi-CRVO.CRVO associated with CLRAO constitutes a distinct clinical entity. The pathogenesis of CLRAO in CRVO is due to transient hemodynamic blockage of the cilioretinal artery caused by a sudden sharp rise in intraluminal pressure in the retinal capillary bed (due to CRVO) above the level of that in the cilioretinal artery.

In 1970, based on my experimental and clinical studies, I defined glaucoma as: “a disease wherein the normal balance between the intraocular pressure and the blood pressure in the choroidal vessels supplying the optic disc and retrolaminar part of the optic nerve is disturbed, resulting in vascular insufficiency in the optic disc and retrolaminar part of the optic nerve, and hence in visual field defects and pathological changes in the optic disc and optic nerve.”1 Since the conventional wisdom at that time was that glaucoma was essentially mechanical in nature, caused solely by high intraocular pressure (IOP), this concept was received with marked skepticism. Since then, however, evidence that vascular insufficiency in the optic nerve head (ONH) plays an important role in pathogenesis of glaucomatous optic neuropathy has progressively accumulated; so that now its vasogenic origin is widely accepted.2 To understand the vasogenic mechanism of glaucomatous optic neuropathy, it is crucial to have a good understanding of the following: 1. Blood supply of the ONH. 2. The various factors that influence the ONH circulation. 3. Evaluation of the ONH circulation.

NV: NeovasculationThe eye had 2203 argon laser burns, starting 71 days after onset of ischemic central retinal vein occlusion.(A) Prepanretinal photocoagulation visual field had almost normal perip...

To evaluate whether tobacco smoking may be a risk factor for development of nonarteritic anterior ischemic optic neuropathy (NA-AION).Cohort study.Six hundred twenty-four consecutive patients with NA-AION who fulfilled our inclusion criteria.All patients provided a detailed ocular, medical, and smoking history, and underwent a comprehensive ophthalmic evaluation. For data analysis, patients were divided into current, former, and never smokers. The prevalence for current smoking in the NA-AION patients was compared to the corresponding race-, gender-, age-, and period-matched subgroup of the U.S. population.Association between NA-AION and tobacco smoking.Of the 624 patients, 369 (59.1%) were men, and mean (+/- standard deviation) age was 61.0+/-12.3 years. Of all the patients, 151 (24.2%) were current smokers, 160 (25.6%) former smokers, and 313 (50.2%) had never smoked. The prevalence of smoking in NA-AION patients was not significantly different from the prevalence in the period-matched U.S. population and the period matched Iowa population. In contrast, the prevalence of diabetes mellitus, ischemic heart disease, arterial hypertension, and cerebrovascular disease in NA-AION patients was significantly higher compared to the prevalence of these chronic conditions in the matched U.S. population (P0.0001). There was no significant difference in initial visual acuity (P = 0.97) or the amount of initial visual field loss (P = 0.31) among nonsmokers, former smokers, and current smokers. Current smokers had NA-AION in the first eye at a significantly younger age (57.8+/-11.7 years) than former smokers (64.0+/-10.2 years; P0.0001), and nonsmokers (60.4+/-13.5 years; P = 0.032). Comparison of the distribution of the time to develop NA-AION in the fellow eye showed no significant difference among the 3 groups (log-rank test P = 0.186).Our study showed no association between NA-AION and tobacco smoking.

To investigate systematically the ophthalmoscopic fundus findings associated with central retinal artery occlusion (CRAO).The study included 240 consecutive patients (248 eyes) with CRAO. The eyes underwent detailed fundus evaluation and stereoscopic color fundus photography at initial and follow-up visits. Patients without evidence of giant cell arteritis were advised to have carotid Doppler imaging and echocardiography to determine the source of emboli. CRAO was classified into 3 types: permanent CRAO (175 eyes), permanent CRAO with cilioretinal artery sparing (35 eyes), and transient CRAO (38 eyes). In the three types of CRAO, acute-phase and late-phase changes in the retina, optic disk, and retinal vessels were evaluated.The main findings during the initial examination in our clinic for permanent CRAO were retinal opacity in the posterior pole (58%), cherry-red spot (90%), box-carring (19%), retinal arterial attenuation (32%), and optic disk edema (22%) and pallor (39%). The most frequent findings identified at the late stage, based on survivorship curves, were optic atrophy (91%), retinal arterial attenuation (58%), cilioretinal collaterals (18%), and macular retinal pigment epithelial changes (11%). Compared with permanent CRAO, permanent CRAO with cilioretinal artery sparing was associated with a lower incidence of all macular and optic disk abnormalities. For transient CRAO, the incidence of initial findings varied greatly compared with the other types. Intraarterial emboli were observed in 20% of patients. Carotid Doppler evaluation identified carotid vascular plaques in 67% of patients tested and hemodynamically significant (50%) obstruction in 32%. Four percent of CRAOs presented with simultaneous bilateral onset.The type and incidence of fundus findings at the initial visit and in the late phase of CRAO vary by its type. This study confirms that retinal opacity is predominantly evident in the posterior retina, that optic disk findings at presentation are common, that CRAO associated with normal-appearing retinal vessels and/or optic disk is not rare, and that observation of emboli is infrequent. Clinicians should be aware of the various presentation findings during the acute and late stages of CRAO and its various types. A complete picture of CRAO is provided by combined information of our clinical and experimental studies of CRAO.

We investigated the clinical characteristics, time to resolution and the factors that influence it, and evolutionary pattern of optic disc edema (ODE) in non-arteritic anterior ischemic optic neuropathy (NA-AION). Our study was conducted in 591 consecutive patients (749 eyes) with NA-AION who fulfilled our inclusion criteria. On their first visit to our clinic, all patients had a detailed ophthalmic and medical history, a comprehensive ophthalmic evaluation, and stereoscopic color fundus photography and fluorescein fundus angiography. On each follow-up visit, the same ophthalmic evaluation was performed, except for fluorescein fundus angiography. The effect of steroid therapy on ODE was evaluated in a “patient choice study” in 723 eyes, i.e., patients who voluntarily opted to have (343 eyes) or not have (380 eyes) this therapy. To identify the factors that influence time to ODE resolution, parametric regression models for interval-censored data were fitted by maximum likelihood estimation using an SAS procedure. Our results indicate that the overall median time (25–75th percentile) to spontaneous resolution of ODE from the onset of visual loss was 7.9 (5.8–11.4) weeks. The ODE resolution time was longer in diabetics than in non-diabetics (p = 0.003) in the single factor model. Multi-factor analysis showed that worse initial visual field defects (p < 0.0001) and worse visual acuity (p = 0.04) were associated with a faster resolution of ODE. Those treated with steroid therapy within 2 weeks after onset of NA-AION had significantly (p = 0.0006) faster ODE resolution than untreated cases. Severity of initial visual loss and systemic diseases were identical in steroid treated and untreated patients. A characteristic evolutionary pattern of ODE in NA-AION was observed. In conclusion, our study showed that in NA-AION the time course for resolution of ODE is shorter with greater severity of initial visual field and visual acuity loss, which may relate to the number of axons permanently damaged during the acute stage. Steroid therapy was associated with shorter time to resolution of ODE. Resolution of ODE goes through a characteristic evolutionary process.

To identify the genetic factors associated with familial non-arteritic anterior ischemic optic neuropathy (NA-AION) in a large pedigree.Eleven family members of a single pedigree, including six affected with NA-AION, underwent detailed clinical examinations. The mitochondrial DNA of the proband was sequenced in its entirety in search of disease-causing mutations associated with NA-AION in the pedigree. A control panel comprising 1488 patients suspected of having Leber hereditary optic neuropathy (LHON) and 97 general-population control subjects was screened for the mitochondrial sequence variant identified in the family.Affected family members were all male and exhibited classic features of NA-AION. Their mean age was 50.2 +/- 5.0 years. A total of 23 sequence variations were detected in the mitochondrial genome of the proband, including one novel sequence variation (G4132A, Ala276Thr) in the NADH dehydrogenase subunit 1 gene (ND1). The G4132A mitochondrial variant was detected in six members of a single pedigree with NA-AION. The G4132A variation was not observed in any of the 1585 subjects in the control panel. Moreover, this variant was not identified in over 2469 ethnically diverse individuals previously evaluated through the Human Mitochondrial Genome Database. None of the three major mutations associated with LHON (G3460A, G11778A, T14484C) were identified in the family.The G4132A mitochondrial variation is associated with familial NA-AION in our pedigree.

Purpose To explore associations of lamina cribrosa thickness with axial length and thickness of the posterior sclera in monkeys. Methods Examining histological sections by light microscopy, we measured the thickness of the lamina cribrosa and posterior sclera and axial length. Results The study included 28 animals (28 eyes) with a mean age of 13.3 ± 4.9 years (range: 3–24 years) and mean axial length of 18.9 ± 1.4 mm (range: 17–21 mm) (22 eyes after experimental temporary central retinal artery occlusion; four eyes after a permanent occlusion of the posterior ciliary artery; and two eyes without any intervention). Mean thickness of the lamina cribrosa was 167 ± 30 μm (range: 115–273 μm). Thinner lamina cribrosa thickness was significantly associated with longer axial length (standardized correlation coefficient beta: -0.42; p = 0.026), with thinner sclera at the posterior pole (beta: 0.56; p = 0.002) and with thinner sclera at the disc border (beta: 0.55; p = 0.002). Lamina cribrosa thickness was not significantly related to temporary central retinal artery occlusion (p = 0.14) or to permanent posterior ciliary artery occlusion (p = 0.49) or age (p = 0.46). Conclusions As in humans, lamina cribrosa thickness in non-glaucomatous monkeys got thinner with longer axial length and with thinner posterior sclera. These data may be of interest for studies on the process of emmetropization/myopization in monkeys, and they may be of interest for the studies on the biomechanics of the optic nerve head.

Purpose To investigate systematically various fundus changes in branch retinal arteriolar occlusion (BRAO) and their natural history. Methods The study comprised a cohort of 123 consecutive patients (135 eyes) with BRAO. Ophthalmic evaluation at initial and follow-up visits included recording visual acuity, visual fields, and detailed anterior segment and fundus examinations, and at initial visit fluorescein fundus angiography. Results Probability estimates of retinal infarct still present were 89% 1 week after BRAO onset, 69% after 2 weeks, 67% after 3 weeks, 34% after 1 month, and 13% after 3 months. Optic disk pallor in the involved region developed in 21% within 1 month from onset, in 42% by 2 months, and in 65% by 3 months. Retinal arteriolar attenuation developed in 19% within 1 month from onset, and in 28% by 6 months. Arteriolar sheathing developed in 19% within 1 month and 25% within 12 months. Arteriolar emboli were found in 58%; 65% of those were at initial visit, in BRAO seen within 1 week of onset. Conclusion Most common cause of BRAO is embolism from the heart or carotid arteries; emboli usually get impacted at the arteriolar bifurcation. Migration and disappearance of retinal emboli is a common finding. Evolution of the retinal and optic disk changes is described.

To investigate systematically the retinal changes in branch retinal vein occlusion (BRVO) and their natural history.The study comprised 214 consecutive patients with BRVO (144 major BRVO and 72 macular BRVO eyes) seen within 3 months of onset. Ophthalmic evaluation at initial and follow-up visits included recording visual acuity, visual fields, and detailed anterior segment and fundus examinations and fluorescein fundus angiography.Initially, retinal hemorrhages were moderate to severe in the perifovea and macula in at least 65% in major and 52% in macular BRVO; at the fovea, it was 51% in major and 36% in macular BRVO. Initially, macular edema was more marked in major BRVO than in macular BRVO (P = 0.007). Major BRVO had a significantly higher rate of development of serous macular detachment (P = 0.002), epiretinal membrane (P = 0.008), serous retinal detachment (P = 0.002), perivenous sheathing (P0.0001), optic disk pallor (P0.0001), and lipid deposit (P0.0001) compared with macular BRVO. Retinal and disk neovascularization was seen only in major BRVO. The time to resolution of BRVO was significantly longer for major BRVO compared with macular BRVO (P = 0.0002).Major and macular BRVOs are two distinct clinical entities. Initial and final fundus findings in the two types differ markedly.