Sohan Singh Hayreh

Nocturnal Arterial Hypotension and Its Role in Optic Nerve Head and Ocular Ischemic Disorders

We measured 24-hour ambulatory blood pressure monitoring and diurnal curve of the intraocular pressure in 166 white patients with anterior ischemic optic neuropathy, normal-tension glaucoma, primary open-angle glaucoma, and other optic nerve head disorders. Hourly average blood pressure data analyses showed a significant (P < .0001) decrease in mean systolic (26%) and diastolic (33%) blood pressure measurements at night. A significantly (P = .0028) lower nighttime mean diastolic blood pressure and a significantly (P = .0044) greater mean percentage decrease in diastolic blood pressure were noted in normal-tension glaucoma than in anterior ischemic optic neuropathy. Patients with arterial hypertension taking oral hypotensive therapy showed a significant association between progressive visual field deterioration and nocturnal hypotension, particularly in anterior ischemic optic neuropathy. Intraocular pressure showed no significant correlation with visual field deterioration in any of these conditions. Our findings suggest that nocturnal hypotension, in the presence of other vascular risk factors, may reduce the optic nerve head blood flow below a critical level, and thereby may play a role in the pathogenesis of anterior ischemic optic neuropathy and glaucomatous optic neuropathy; that is, nocturnal hypotension may be the final insult in a multifactorial situation. The same mechanisms may be true of a number of other ocular ischemic disorders. This finding opens a new dimension in the understanding and management of these visually disabling diseases.

Blood supply of the optic nerve head and its role in optic atrophy, glaucoma, and oedema of the optic disc.

The blood supply of the optic disc is an important and a fascinating subject in ophthalmology. Since the time of Haller (I754) and Zinn (I755) it has remained the centre of controversy. The literature on the subject has recently been reviewed in detail by Hayreh (i963a), Fransois and Neetens (I966), and Bonamour, Bregeat, Bonnet, and Juge (I968). The recent introduction of fluorescence angiography has made a significant contribution to the subject because it enables us to study the microcirculation in vivo.

Scleritis and episcleritis.

The data from 159 patients (217 eyes) with episscleritis and 207 patients (301 eyes) with scleritis have been investigated in detail and the results analysed with the help of a computer. Of these patients, 91 per cent were followed-up during a period of one to eight years. A new classification is presented which is as follows: Episcleritis (217 eyes) Simple episcleritis (170 eyes) Nodular episcleritis (47 eyes) Scleritis (301 eyes) Diffuse anterior scleritis (119 eyes) Nodular anterior scleritis (134 eyes) Necrotizing scleritis (42 eyes). Of these, 13 were regarded as scleromalacia perforans. Posterior scleritis (6 eyes) The diagnosis is based on an exact clinical examination which is fully described. Episcleritis has been shown to be a benign recurring condition, a mild keratitis being the only occasional complication. Episcleritis does not progress to scleritis, except in the case of herpes zoster which sometimes starts as an episcleritis with the vesicular stage of the eruption, to reappear three months later as a scleritis in the same site. No clear conclusions could be drawn as to the aetiology of episcleritis.

Ischemic optic neuropathy

Ischemic optic neuropathy is one of the major causes of blindness or seriously impaired vision, yet there is disagreement as to its pathogenesis, clinical features and especially its management. This is because ischemic optic neuropathy is not one disease but a spectrum of several different types, each with its own etiology, pathogenesis, clinical features and management. They cannot be lumped together. Ischemic optic neuropathy is primarily of two types: anterior (AION) and posterior (PION), involving the optic nerve head (ONH) and the rest of the optic nerve respectively. Furthermore, both AION and PION have different subtypes. AION comprises arteritic (A-AION - due to giant cell arteritis) and, non-arteritic (NA-AION - due to causes other than giant cell arteritis); NA-AION can be further classified into classical NA-AION and incipient NA-AION. PION consists of arteritic (A-PION - due to giant cell arteritis), non-arteritic (NA-PION - due to causes other than giant cell arteritis), and surgical (a complication of several systemic surgical procedures). Thus, ischemic optic neuropathy consists of six distinct types of clinical entities. NA-AION is by far the most common type and one of the most prevalent and visually crippling diseases in the middle-aged and elderly. A-AION, though less common, is an ocular emergency and requires early diagnosis and immediate treatment with systemic high dose corticosteroids to prevent further visual loss, which is entirely preventable. Controversy exists regarding the pathogenesis, clinical features and especially management of the various types of ischemic optic neuropathy because there are multiple misconceptions about its many fundamental aspects. Recently emerging information on the various factors that influence the optic nerve circulation, and also the various systemic and local risk factors which play important roles in the development of various types of ischemic optic neuropathy have given us a better understanding of their pathogeneses, clinical features and management. This knowledge should help us not only to manage them better but also to reduce their incidence. For example, clinically, the evidence that about 40% of NA-AION eyes experience spontaneous improvement in visual acuity and that systemic steroid therapy during early stages in both NA-AION and NA-PION has a significant beneficial effect for visual outcome are encouraging developments. This review discusses the current concepts on various issues related to various types of ischemic optic neuropathy.

Incidence of Various Types of Retinal Vein Occlusion and Their Recurrence and Demographic Characteristics

We analyzed data on 1,108 patients (1,229 eyes) with various types of retinal vein occlusion. Retinal vein occlusion was classified into six distinct clinical types: (I) nonischemic and (II) ischemic central retinal vein occlusion, (III) nonischemic and (IV) ischemic hemicentral retinal vein occlusion, and (V) major and (VI) macular branch retinal vein occlusion. Retinal vein occlusion occurred more often in men than women. The age range of patients was between 14 and 92 years, with 570 of 1,108 patients (51%) 65 years or older; however, 99 of 620 (16%), 15 of 154 (10%), and 17 of 375 (5%) of the patients with central, hemicentral, and branch retinal vein occlusion, respectively, were younger than 45 years. The cumulative probability of developing a second episode of the same or a different type of retinal vein occlusion in the same eye was 0.9% within two years and 2.5% within four years, and in the fellow eye was 7.7% and 11.9%, respectively. The cumulative probability of conversion of nonischemic to ischemic central retinal vein occlusion at six months and 18 months was 13.2% and 18.6%, respectively, in persons 65 years of age or older and 6.7% and 8.1%, respectively, in persons 45 to 64 years of age.

Systemic Diseases Associated With Nonarteritic Anterior Ischemic Optic Neuropathy

PURPOSE We investigated, in nonarteritic anterior ischemic optic neuropathy, the prevalence of various systemic diseases before or at its onset and the incidence of subsequent morbidity and mortality. METHODS We investigated prospectively the presence of systemic diseases before or at the onset of nonarteritic anterior ischemic optic neuropathy in 406 patients. The information was obtained by complete medical history and physical examination. The prevalence rates of systemic diseases in young, middle-aged, and elderly groups were compared with those in the general population. We also analyzed the influence of systemic diseases on subsequent morbidity and mortality. RESULTS Compared with the prevalences reported in the general population, our patients in each of the three age groups showed a significantly higher prevalence of arterial hypertension (P < or = .02), diabetes mellitus (P < .01), and gastrointestinal ulcer (P < or = .02). Also, middle-aged and elderly patients showed a significantly higher prevalence of ischemic heart disease (P < .01) and thyroid disease (P < .01). Middle-aged patients had significantly higher rates of chronic obstructive pulmonary disease and cerebrovascular disease (P < or = .01). After onset of anterior ischemic optic neuropathy, patients with both arterial hypertension and diabetes mellitus had a significantly higher incidence of cerebrovascular disease (P < .01). CONCLUSIONS Nonarteritic anterior ischemic optic neuropathy is a multifactorial disease in which some systemic diseases may act as predisposing factors and others as precipitating factors. Patients with anterior ischemic optic neuropathy show no significant increase in mortality, but those with both arterial hypertension and diabetes mellitus have significantly (P < .01) increased incidence of cerebrovascular disease.

Central Retinal Artery Occlusion and Retinal Tolerance Time

Transient central retinal artery occlusion (CRAO) was produced in 63 eyes of rhesus monkeys by lateral orbitotomy and temporary clamping of the central retinal artery (CRA) for between 15 and 270 minutes. Thirty-three eyes were examined at regular intervals for 12 to 22 weeks. Color fundus photography, fluorescein fundus angiography, electroretinography (ERG) and visual evoked response (VER) were performed before and during clamping of the CRA as well as periodically after unclamping. All the eyes were examined by light and/or electron microscopy. This study revealed that the retina suffered irreparable damage after ischemia of 105 minutes, but recovered well after ischemia of 97 minutes. As a general rule, the monkey retina can tolerate up to 100 minutes of ischemia but not more.

Giant Cell Arteritis: Validity and Reliability of Various Diagnostic Criteria

PURPOSE To ascertain the validity, reliability, sensitivity, and specificity of various signs and symptoms of and diagnostic tests for early diagnosis of giant cell arteritis. METHODS From 1973 to 1994, we studied 363 patients who had temporal artery biopsy for suspected giant cell arteritis. All patients underwent detailed clinical evaluation and had erythrocyte sedimentation rates determined; since 1985, 223 patients had their C-reactive protein values estimated. Erythrocyte sedimentation rate and C-reactive protein levels were also estimated in 749 and 138 control subjects, respectively. Signs and symptoms of giant cell arteritis, erythrocyte sedimentation rate, and C-reactive protein levels among patients with positive and negative biopsies were compared. RESULTS Of the 363 patients, temporal artery biopsy was positive in 106 and negative in 257. The odds of a positive biopsy were 9.0 times greater with jaw claudication (P < .0001), 3.4 times greater with neck pain (P = .0085), 2.0 times greater with an erythrocyte sedimentation rate of 47 to 107 mm/hour (P = .0454), 3.2 times greater with C-reactive protein above 2.45 mg/dl (P = .0208), and 2.0 times greater for age 75 years or more (P = .0105). CONCLUSIONS Clinical criteria most strongly suggestive of giant cell arteritis include jaw claudication, C-reactive protein above 2.45 mg/dl, neck pain, and an erythrocyte sedimentation rate of 47 mm/hour or more, in that order. C-reactive protein was more sensitive (100%) than erythrocyte sedimentation rate (92%) for detection of giant cell arteritis; erythrocyte sedimentation rate combined with C-reactive protein gave the best specificity (97%).

Classification of Central Retinal Vein Occlusion

Our prospective clinical study of 360 eyes with central retinal vein occlusion (CRVO) and our experimental studies on CRVO in 54 eyes of rhesus monkeys have shown that CRVO consists of the following two distinct entities: (1) Nonischemic CRVO in which there is essentially a stasis of retinal venous circulation; we call it venous stasis retinopathy (VSR). (2) Ischemic CRVO: We call this hemorrhagic retinopathy (HR). Our prospective clinical studies have revealed that it is absolutely essential to differentiate CRVO into VSR and HR because of their very different prognoses and management. VSR is a benign and self-limited condition, while HR is a severe, potentially blinding disorder. Lumping the two types of CRVO together as one disease has caused much confusion concerning the prognosis and management of CRVO. The basis of such a classification and differential diagnosis of VSR and HR is discussed at length.

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.