Retinal and optic nerve head ischemic disorders and atherosclerosis: role of serotonin

Ischemic disorders of the retina and optic nerve head (OPH) constitute a common cause of visual loss in the middle-aged and elderly population. These disorders have a high association with atherosclerosis. This review has considered the various aspects of atherosclerosis and its role, as well as that of serotonin, in the development of ischemic disorders of the retina and ONH. It is known that when platelets aggregate on an atheromatous plaque, serotonin is one of the agents released. Studies in experimental atherosclerotic monkeys have shown that, although serotonin has no effect on ocular vasculature in normal monkeys, in atherosclerotic monkeys it produces vasopasm of the central retinal artery (CRA) and/or posterior ciliary artery (PCA) in various combinations but not vasopasm of the arterioles in the retina; vasospasm of the CRA and/or PCA(s) can consequently cause transient, complete occlusion or impaired blood flow in these arteries. It is postulated that in some atherosclerotic individuals this mechanism may play an important role in the development of ischemic disorders of the retina and ONH, including amaurosis fugax, (CRA) occlusion and anterior ischemic optic neuropathy, and possibly also glaucomatous optic neuropathy, particularly in normal tension glaucoma. Studies have also shown that dietary treatment of atherosclerosis abolishes or markedly improves the serotonin induced vasoconstriction within a few months. All these considerations may have important implications for our understanding of the pathogenesis and management of these blinding disorders.     

Serotonin-induced constriction of ocular arteries in atherosclerotic monkeys. Implications for ischemic disorders of the retina and optic nerve head

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.     

Medulloepithelioma of the optic nerve head

Medulloepithelioma of the optic nerve is a rare developmental tumor. We describe a 2-year-old boy with profound loss of vision associated with a visible tumor of the optic nerve head in his left eye. A clinically diagnosed retinoblastoma necessitated left eye enucleation. The histopathological diagnosis was malignant medulloepithelioma that was incompletely resected. Further tumor resection was required, and the patient received adjunctive chemotherapy and radiotherapy. Four years after treatment, the patient has neither clinical nor radiological evidence of tumor.     

Progressive growth in melanocytoma of the optic nerve head

The authors describe the method of closure of laparotomic wounds by means of an atraumatic continuous PDS loop suture. Based on evaluation of a group of 166 patients they appreciate the positive aspects of the technique of this suture, in particular the speed, easy implementation and safe closure of laparotomy. As regard the sewing material, they value highly the quality of atraumatic fibres which are firm and do not irritate the tissues.     

Hypoxemia and arterial hypotension at the accident scene in head injury

OBJECTIVE: To quantify the occurrence of arterial hypotension and arterial oxygen desaturation in a series of patients with head trauma rescued by helicopter. DESIGN: Prospective, observational study. MATERIALS AND METHODS: Arterial HbO2 was measured before tracheal intubation at the accident scene in 49 consecutive patients with head injuries. Arterial pressure was measured using a sphygmomanometer. MAIN RESULTS: Mean arterial saturation was 81% (SD 24.24); mean arterial systolic pressure was 112 mm Hg (SD 37.25). Airway obstruction was detected in 22 cases. Twenty-seven patients showed an arterial saturation lower than 90% on the scene, and 12 had a systolic arterial pressure of less than 100 mm Hg. The outcome was significantly worse in cases of hypotension, desaturation, or both. CONCLUSIONS: Hypoxemia and shock are frequent findings on patients at the accident scene. Hypoxemia is more frequently detected and promptly corrected, white arterial hypotension is more difficult to control. Both insults may have a significant impact on outcome.     

Effect of topical timolol on tissue circulation in optic nerve head

OBJECTIVE: The aim of the present study was to determine whether removal of all amalgam restorations might significantly affect mercury levels in plasma and urine and whether the use of rubber dams might reduce patient exposure to mercury during amalgam removal. METHODS: All amalgam restorations were removed from 18 subjects during a single treatment session in which a rubber dam was used and from 10 subjects when a rubber dam was not used. All amalgam restorations were removed by the same dentist using high-speed cutting, water coolant, and high-volume evacuation. The levels of mercury in plasma and urine were analyzed both before and during the subsequent twelve months after amalgam removal. In order to determine whether removal of all amalgam restorations might cause an exposure large enough to significantly increase the mercury levels in two indicator media for mercury exposure, i.e., plasma and urine, and to determine if the removal might cause a significant decrease in the mercury levels found over time, the one-tailed, paired Students' t-test was used. For each individual, the pre-removal levels were compared with both the levels found in plasma on d 1 and in urine on d 10, and also with the levels found 1 y after removal. Furthermore, in order to examine whether the use of rubber dams had any effect on the mercury levels found after removal, the changes in the mercury levels found were compared between the groups using the Wilcoxon-Mann-Whitney rank sum test. RESULTS: After removal of all amalgam restorations, only the non-rubber dam group showed significant increases in the mercury levels found in plasma (p = 0.012) and urine (p = 0.037). However, one year later, the mercury levels in plasma and urine had sunk significantly below the pre-removal levels for both groups. When the changes in the mercury levels found were compared between the groups, the non-rubber dam group showed a significantly higher increase of mercury in plasma than the rubber dam group the day after removal (p = 0.0010). Compared to the pre-removal mercury levels in plasma and urine, the levels found 1 y after removal of all amalgam restorations were on average 52 +/- 23% (range 4-89%) lower in plasma and 76 +/- 21% (range 20-94%) lower in urine. SIGNIFICANCE: The study showed that dental amalgam had a statistically significant impact on the mercury levels found in plasma and urine in the patients tested, and that the use of a rubber dam during removal of all amalgam restorations significantly reduced the peak of mercury in plasma following removal.     

Confocal tomographic angiography of the optic nerve head in patients with glaucoma

BACKGROUND: Essential hypertension is characterized by an impairment of endothelium-dependent vasodilatation. OBJECTIVE: To test whether antihypertensive treatment with the angiotensin converting enzyme inhibitor lisinopril can improve vasodilatation in response to endothelium-dependent agonists in essential hypertensive patients. DESIGN AND METHODS: We studied the effect of acute (6-8 h after dosing), prolonged (1 month) and chronic (12 months) lisinopril treatment on forearm blood flow response (strain-gauge plethysmography) induced in 10 hypertensive patients (aged 43.6 +/- 8.1 years, blood pressure 151.4 +/- 6.8/99.8 +/- 3.3 mmHg) by intrabrachial infusions of 0.15, 0.45, 1.5, 4.5, and 15 microg/100 ml per min acetylcholine and 5, 15, and 50 ng/100 ml per min bradykinin, two endothelium-dependent vasodilators, and 1, 2, and 4 microg/100 ml per min sodium nitroprusside, an endothelium-independent vasodilator. At baseline, vascular response was compared with that of 10 normotensive subjects (aged 42.4 +/- 6.6 years, blood pressure 118.4 +/- 6.1/77.8 +/- 3.4 mmHg). RESULTS: Hypertensive patients had blunted (P < 0.01 or less) vasodilatations in response to infusions of acetylcholine (from 3.7 +/- 0.3 to 18.3 +/- 4.9 ml/100 ml per min) and bradykinin (from 3.7 +/- 0.4 to 15.8 +/- 2.6 ml/100 ml per min) compared with those of controls (from 3.6 +/- 0.3 to 25.3 +/- 5.2 ml/100 ml per min for acetylcholine and from 3.7 +/- 0.3 to 26.9 +/- 4.9 ml/100 ml per min for bradykinin) whereas the responses to infusion of sodium nitroprusside were similar (from 3.6 +/- 0.3 to 18.5 +/- 3.9 and from 3.6 +/- 0.3 to 16.4 +/- 1.8 ml/100 ml per min, respectively). Acute and prolonged lisinopril treatments significantly (P < 0.05 or less) improved vasodilatation in response to infusion of bradykinin (from 3.7 +/- 0.4 to 24.5 +/- 4.9 and from 3.7 +/- 0.3 to 22.1 +/- 4.9 ml/100 ml per min, respectively), but not in response to infusions of acetylcholine and of sodium nitroprusside. Chronic lisinopril treatment increased (P < 0.05) the response to infusions of not only bradykinin (from 3.5 +/- 0.5 to 27.6 +/- 5.3 ml/100 ml per min), but also of acetylcholine (from 3.5 +/- 0.5 to 27.8 +/- 8.0 ml/100 ml per min) and sodium nitroprusside (from 3.4 +/- 0.6 to 25.9 +/- 8.5 ml/100 ml per min). However, when the responses to infusions of acetylcholine and bradykinin were normalized with respect to that to infusion of sodium nitroprusside, only the vasodilatation in response to infusion of bradykinin was shown to have been increased by lisinopril treatment. CONCLUSIONS: Administration of lisinopril to patients with essential hypertension can selectively increase vasodilatation in response to infusion of bradykinin.     

Diagnostic and therapeutic challenges. Lesions of the optic nerve head

Unilateral injection of 10 mg all-trans retinoic acid (in 1 ml of castor oil) into the early pedicle anlage of a male fallow deer resulted in accelerated growth of the cranial appendage, and altered pedicle and first antler shape on the treatment side, whereas pedicle and antler growth on the control side, injected with 1 ml of vehicle solution only, was normal. It is concluded that retinoic acid is able to alter pedicle and first antler morphogenesis, presumably by affecting the positional information of the periosteal cells covering the incipient pedicle.     

Aging changes of the optic nerve head in relation to open angle glaucoma

AIMS: To determine the age related changes in optic nerve head structure in a group of normal subjects and assess the significance of any changes in relation to those found in open angle glaucoma. METHODS: A group of 88 white volunteers and friends and spouses of patients with a normal visual field and normal intraocular pressure was studied. Two different imaging and measurement devices were used (computer assisted planimetry and scanning laser ophthalmoscopy), and the results from each were compared. Measurements were made of the optic disc, optic cup, and neuroretinal rim areas, and the vertical optic disc diameter and cup/disc diameter ratio. RESULTS: Neuroretinal rim area declined at the rate of between 0.28% and 0.39% per year. Vertical optic cup diameter and optic cup area increased with age. The mean cup/disc diameter ratio increased by about 0.1 between the ages of 30 and 70 years. CONCLUSIONS: Age related changes are significant and measurable, and should be taken into account when assessing the glaucoma suspect, and when estimating the rate of progression of glaucomatous optic neuropathy in patients with established disease.     

Perfusion of the juxtapapillary retina and optic nerve head in acute ocular hypertension

Chronically elevated intraocular pressure (IOP) is often associated with glaucomatous optic nerve atrophy. Impaired blood flow may play a role in the pathogenesis of this disease. We present data concerning juxtapapillary retinal and optic nerve-head blood flow during acute increases in IOP. With the combination of a laser Doppler flowmeter and a scanning-laser system (Scanning Laser Doppler Flowmeter, SLDF; Heidelberg Engineering) the perfusion of the retina and the optic nerve head was quantified and visualized. Juxtapapillary retinal and optic nerve-head blood flow was measured simultaneously by SLDF during variations in IOP induced by a suction cup in nine healthy volunteers. The ocular pressure was increased for 2 min to IOP +15 mmHg, then to IOP +30 mmHg, and finally, to IOP +45 mmHg. Ocular perfusion pressure (PP) was calculated as the mean arterial blood pressure minus the IOP. The declines in juxtapapillary retinal flow as expressed in present per 10-mmHg IOP elevation ranged from 3.6% to 14.1% (median 7.4%). Over all measurements we found a significant linear relationship between juxtapapillary retinal blood flow and PP (r = 0.55, P < 0.0001). The observed decrease in optic nerve-head blood flow with increasing IOP was significantly greater as compared with the retinal blood flow decrease (8.4%/10 mmHg versus 7.4%/10 mmHg, P < 0.05). SLDF enables the quantification and visualization of perfused capillaries of the retina and the optic nerve head in high resolution. Acute elevations of IOP led to a decreases in juxtapapillary retinal and optic nerve-head blood flow of 7.4% and 8.4%/ 10-mmHg IOP increase, respectively.     

Autoregulation of human optic nerve head circulation in response to increased intraocular pressure

The following experiments were undertaken to determine if blood flow is maintained by autoregulation in the human optic nerve head when circulation is challenged by elevated intraocular pressure, and to determine if the presence or absence of autoregulation is universal. Laser Doppler flowmetry was used to determine the average velocity, the number of moving erythrocytes, and the volume of flow in the capillary bed of the optic disc. These parameters were measured in 10 subjects at spontaneous levels of intraocular pressure (IOP), and at pressures artificially elevated to 25, 35, 45 and 55 mm Hg with a scleral suction cup. Four subjects (two who showed autoregulation and two who did not) were studied on six additional occasions to determine consistency of the findings. In these same four subjects a second location on the disc was also measured on six occasions to determine if the IOP-effect on blood flow varied by location. Of the 10 subjects initially studied, seven maintained the baseline level of blood flow over the lower part of the range of elevated intraocular pressure (evidence of autoregulation), but showed a decline in flow by the time IOP reached 45 or 55 mm Hg. Two subjects showed a linear decline in blood flow beginning with the smallest increment of elevation of IOP (no autoregulation), and one showed an uninterpretable result. The two individuals who showed the linear decline and two of those who showed efficient autoregulation were remeasured, and each showed consistently the same pattern as before when restudied on six different occasions each. However, at a different location on their discs, autoregulation was manifest in all of these four individuals. When challenged by elevated IOP, the optic nerve head typically maintains a steady-blood flow over a range of IOP, but fails to maintain the same flow by the time IOP reaches 45 or 55 mm Hg. Some disc locations, at least in some individuals, do not show this autoregulation, but exhibit a decline in blood flow linearly related to IOP, even with the modest elevation of IOP.     

Laser scanning tomography of the optic nerve head in ocular hypertension and glaucoma

BACKGROUND: This study evaluated the ability of laser scanning tomography to distinguish between normal and glaucomatous optic nerve heads, and between glaucomatous subjects with and without field loss. METHODS: 57 subjects were classified into three diagnostic groups: subjects with elevated intraocular pressure, normal optic nerve heads, and normal visual fields (n = 10); subjects with glaucomatous optic neuropathy and normal visual fields (n = 30); and subjects with glaucomatous optic neuropathy and repeatable visual field abnormality (n = 17). Three 10 degrees image series were acquired on each subject using the Heidelberg retina tomograph (HRT). From the 14 HRT stereometric variables, three were selected a priori for evaluation: (1) volume above reference (neuroretinal rim volume), (2) third moment in contour (cup shape), and (3) height variation contour (variation in relative nerve fibre layer height at the disc margin). Data were analysed using analysis of covariance, with age as the covariate. RESULTS: Volume above reference, third moment in contour, and mean height contour were significantly different between each of the three diagnostic groups (p < 0.001). Height variation contour showed no significant difference among the three diagnostic groups (p = 0.906). CONCLUSIONS: The HRT variables measuring rim volume, cup shape, and mean nerve fibre layer height distinguished between (1) subjects with elevated intraocular pressures and normal nerve heads, and glaucomatous optic nerve heads, and (2) glaucomatous optic nerve heads with and without repeatable visual field abnormality. This study did not directly assess the ability of the HRT to identify patients at risk of developing glaucoma. It is hypothesised that the greatest potential benefit of laser scanning tomography will be in the documentation of change within an individual over time.     

Role of the splanchnic nerve in hypotension induced by acute obstructive suppurative cholangitis

A model of acute suppurative cholangitis with septicemia but without shock was made in 14 rabbits. Fourty-eight hours afterwards, reoperation was performed with the right major splanchnic nerve and right celiac plexus exposed for monitoring. A catheter with an inflatable rubber bag was inserted into the common bile duct via the duodenum for injection with water into the rubber bag to produce a biliary high pressure of 20 kPa, which was subsequently maintained for 2 hours. The right major splanchnic nerve impulse frequency was found significantly increased (P < 0.01). The study shows that the fall of blood pressure or shock in the early stage of acute obstructive suppurative cholangitis is induced predominantly by acute biliary hypertension, and our findings would be complementary to Reynolds' hypothesis of the production of shock.     

Comparison of methods to evaluate the optic nerve head and nerve fiber layer for glaucomatous change

Depression occurs in 40% to 50% of Parkinson's disease (PD) patients. From research over the last decade, this co-occurrence appears to be more than an emotional reaction to disability. Replacement of the neurotransmitter, dopamine, benefits the PD motor functions, and the neurotransmitter, serotonin, in antidepressants, reduces depressive symptoms. However, identification of the physiological linkage between PD and depression continues to evade research efforts.     

Location of the fovea at the fundus in relation to the optic nerve head

BACKGROUND: Exact determination of the location of the fovea may be difficult, especially in patients suffering from macular pathology. The purpose of this study was to evaluate whether the distance between the optic nerve head and fovea in healthy eyes may be helpful in such patients. PATIENTS AND METHODS: We measured the distance between the center of the optic nerve head and the fovea in 165 healthy eyes in a horizontal and vertical direction. Results were correlated to the refractive status. RESULTS: There was a relatively high deviation between all eyes for the distance between the optic disc and the fovea (15.5 +/- 1.2 degrees [12.8 to 21.3 degrees]). There was a significant relationship between this distance and the refraction (r = 0.353, P < 0.001). Intraindividual deviation between the right and left eyes showed a markedly lower variance (0.67 +/- 0.49 degree [0.05 to 2.3 degrees]). CONCLUSION: The distance between the optic nerve head and the fovea does not allow for meaningful determination of the location of the fovea in eyes in which morphological changes have occurred. However, knowledge of this distance from the other eye of the same patient is helpful.     

Evaluation of coexisting optic nerve head drusen and glaucoma with optical coherence tomography

OBJECTIVE: Optic nerve head drusen often make evaluation of the nerve head difficult to interpret. In addition, visual field defects are known to occur in patients with optic disk drusen, resembling glaucomatous damage. The authors report two cases of coincident optic nerve head drusen and glaucoma, in which the use of optical coherence tomography (OCT) in evaluating the nerve fiber layer was beneficial. PARTICIPANTS: Two patients with both optic nerve head drusen and glaucoma, one with primary open angle glaucoma, the other with pseudoexfoliation glaucoma were evaluated. Both patients had asymmetric optic disk drusen, with clinically visible drusen only in one eye. INTERVENTION: Ophthalmologic examination, color and red-free photography, automated Humphrey visual field testing and OCT were performed. RESULTS: Nerve fiber layer loss as measured by OCT was found to be greater than expected by the appearance of the optic nerve head and red-free photography, with visual fields consistent with findings in case 1. In case 2, visual fields were full, despite nerve fiber layer thinning seen by OCT and red-free photography. CONCLUSIONS: There can be significant nerve fiber layer thinning in patients with both glaucoma and optic disk drusen, despite the appearance of the optic nerve head in these patients. The cup margin may be obscured by the drusen, giving rise to a falsely full-appearing disk. In such cases, OCT may provide a useful means to quantitatively measure the nerve fiber layer thickness and to aid in the management of these patients by detecting nerve fiber layer thinning earlier than would otherwise be possible.     

Open foramen ovale in patients with arterial vascular occlusions of the retina and optic nerve

BACKGROUND: We examined the frequency and significance of persistent foramen ovale (PFO) in patients with ocular circulatory disturbance. PATIENTS AND METHODS: Forty patients with acute arterial occlusions of the posterior bulb segment were investigated by means of transthoracic and transesophageal echocardiography (TEE). The parallel presence of cerebral ischemia was clarified on the basis of existing CCT findings and by additional HMPAO-SPECT investigation. RESULTS: PFO was identified in nine of the patients investigated. The probability of paradoxical embolism arises from further findings: eight of those with PFO (89%) showed echocardiographic signs of right heart strain, indicating previous pulmonary embolism, compared with only three of those without PFO (10%). Five of those with PFO showed a potential source of embolism, two of them with phlebothromboses in their clinical history and three with additional atrial septal aneurysm. Cardiovascular risk factors were prevalent in the group without PFO. Both groups had a mean age of approximately 60 years. Signs of cerebral ischemia were present in the SPECT or CT findings for four of the patients with PFO and nine of those without. CONCLUSIONS: From our findings, it appears highly probable that ocular arterial occlusion is caused by paradoxical embolism. PFO should be taken into account in establishing a diagnosis, including diagnosis in elderly patients.     

Effects of 0.5% apraclonidine on optic nerve head and peripapillary retinal blood flow

AIMS: To examine the effects of 0.5% apraclonidine on optic nerve head (ONH) and peripapillary retinal blood flow by scanning laser Doppler flowmetry (SLDF). METHODS: ONH and peripapillary retinal blood flow of 17 healthy subjects were measured by SLDF before and 1 hour and 3 hours after unilateral administration of 0.5% apraclonidine. The fellow eyes were treated with balanced salt solution and the examiners were masked as to which eye was treated with apraclonidine. On each occasion, three scans were obtained and haemodynamic variables (volume, flow, and velocity) were analysed at eight locations, four in the neural rim and four in the peripapillary retina, avoiding ophthalmoscopically visible vessels. The statistical significance of changes from the baseline value of variables and the differences in the measured quantities between apraclonidine treated eyes and fellow eyes at each time point were evaluated using Wilcoxon signed rank test. RESULTS: The intraocular pressure was reduced significantly in apraclonidine treated eyes by 15.0% (p = 0.001) at 1 hour and 30.0% (p = 0.000) at 3 hours after administration. In the volume, flow, or velocity of ONH and peripapillary retinal blood flow, there were no significant changes from the baseline values at 1 hour and 3 hours after apraclonidine administration in either apraclonidine treated eyes (p > 0.4) or fellow eyes (p > 0.2). Also, no significant differences were found in the measured quantities between apraclonidine treated eyes and fellow eyes at each time point (p > 0.1). CONCLUSION: A single dose of topical apraclonidine 0.5% in healthy subjects does not have adverse effects on the ONH and peripapillary retinal blood flow.