Effect of intravenous fenoldopam on intraocular pressure in ocular hypertension

Intravenous fenoldopam, a selective dopamine-1 receptor agonist, was compared with placebo in this randomized, double-blind, two-period crossover study to evaluate its effects on intraocular pressure, aqueous dynamics, and macular blood flow in patients with elevated intraocular pressure or primary open-angle glaucoma. Doses of fenoldopam were titrated up to a maximum of 0.5 microgram/kg/min. Intraocular pressure, measured by pneumotonometry, was the primary outcome variable. Other outcomes included macular blood flow assessed by blue field examination, visual field examined by automated perimetry, aqueous outflow facility measured by tonography, and aqueous humor production determined by fluorophotometry. During infusions of fenoldopam, intraocular pressure increased from a mean baseline level of 29.2 mmHg to a mean maximum level of 35.7 mmHg. During the placebo infusions, pressure increased from a mean baseline of 28.4 mmHg to a mean of 29.0 mmHg at the time point that corresponded to the mean maximum intraocular pressure on the day intravenous fenoldopam was administered, to yield a mean difference in pressure between study days of 6.7 mmHg (P < 0.05). There were no apparent changes in macular blood flow, visual fields, or production or outflow of aqueous humor associated with fenoldopam infusion. The increase in intraocular pressure seen in this population of patients with ocular hypertension during infusions of fenoldopam is consistent with fenoldopam-associated increases in intraocular pressure reported in previous studies of healthy volunteers and of patients with accelerated systemic hypertension. These results further suggest that dopamine-1 receptors play a role in the regulation of intraocular pressure.     

Sperm DNA analysis in a Friedreich ataxia premutation carrier suggests both meiotic and mitotic expansion in the FRDA gene

BACKGROUND: Puumala virus infection (nephropathia epidemica) is a disease in the group of hemorrhagic fevers with renal syndrome causing ocular manifestations, e.g. transient myopia and changes in intraocular pressure. PATIENT AND METHODS: Comprehensive and repeated ophthalmic examinations of a previously healthy 35-year-old woman with acute Puumala virus infection were performed. Special attention was paid to ophthalmic A-scan ultrasound measurements and simultaneous blood chemistry tests. RESULTS: The ocular manifestations of this patient's illness included transient myopia, low intraocular pressure, conjunctival hemorrhages and changes of intraocular dimensions. There was forward movement of the anterior diaphragm and thickening of the crystalline lens, which occurred simultaneously with prominent fluctuations in the electrolyte balance, especially potassium. CONCLUSIONS: The observed changes in intraocular dimensions may have been caused by simultaneous fluctuations in electrolyte and osmotic balance, which could explain the myopic shift. The symmetry of the ocular measurements implied a systemic infection as the underlying reason for the ophthalmic symptoms and signs.     

A new type of headache of ocular origin: ophthalmotonic headache. Diagnosis and treatment

INTRODUCTION: In some patients it was seen that chronic headaches disappeared after laser iridectomies had been done to prevent glaucoma, in persons with normal intra-ocular pressure (IOP). OBJECTIVE: To make a study of patients with headache, some of whom were treated with topical beta-blockers (carteolol) and others by Yag-laser iridectomies. The effect on headache and IOP was analyzed. MATERIAL AND METHODS: A survey, ophthalmological examination and headache provocation test were carried out in patients with headaches, and the changes in IOP determined by pharmacologically inducing miosis and mydriasis were recorded. Three treatment groups were formed and the results analyzed statistically. RESULTS: In the 12 patients treated pharmacologically, 62% improved and in 14% the headaches disappeared. In the 16 treated using laser 94% were cured and 6% improved. When both types of treatment were used on 9 patients, 22% improved and 78% were cured. The validity of the ocular pressure curve was checked in the diagnosis of blockage of the pupil. CONCLUSIONS: Some headaches of ocular origin (ophthalmotonic), not previously described, occur due to abrupt changes in intraocular pressure, and improve significantly when the IOP is reduced by beta-blockers or Yag-laser iridectomies are done. A valid provocation tests for diagnosis of this type of headache is described. We consider that blockage of the pupil and/or of the angle of the anterior chamber are possible etiopathogenic mechanisms.     

Postoperative complications of subconjunctival THC-YAG (Holmium) laser sclerostomy

BACKGROUND: The THC-YAG (Holmium) laser is currently being used to create thermal sclerostomies, an alternate method of intraocular pressure control with poorly regulated glaucoma. A significant advantage of this procedure is the ab externo approach, which utilizes a small fiberoptic laser probe that is advanced subconjunctivally to the limbus. Surgical intraocular trauma is minimized, decreasing the amount of scarring and ultimate bleb failure. Complications may be seen with the THC-YAG sclerostomy and include: conjunctival burn, filtration bleb leak, posterior corneal striae, peaked pupil, iris incarceration, infection, hyphema, cataracts and ocular hypotony. METHODS: This paper presents four glaucoma patients, co-managed at the Illinois Eye Institute, who developed complications following THC-YAG laser sclerostomy. A discussion of other possible postoperative complications and their management is included. RESULTS: While the holmium laser has shown positive results in lowering intraocular pressure in patients with uncontrolled refractory glaucoma, complications are inherent in this procedure. The most common are posterior corneal striae, iris incarceration with secondary peaked pupil, and ocular hypotony. Conjunctival burn with secondary filtration bleb leak, limbal pigment deposition and hyphema may also be seen. CONCLUSION: Early diagnosis and treatment of postoperative complications may help in maintaining the long term filtration ability of the sclerostomy.     

Seroneutralization of porcine reproductive and respiratory syndrome virus correlates with antibody response to the GP5 major envelope glycoprotein

PURPOSE: To compare the long-term efficacy and safety of brimonidine 0.2% twice daily with timolol 0.5% twice daily in patients with glaucoma or ocular hypertension. METHODS: Of the 926 patients enrolled in the study, 837 met the protocol entry criteria and received either brimonidine 0.2% twice daily (n = 466) or timolol 0.5% (n = 371) twice daily in each eye for 1 year. RESULTS: Brimonidine and timolol significantly reduced mean intraocular pressure (P < .001) from baseline levels at every scheduled follow-up visit, both at hour 2 (peak) and hour 12 (trough). At weeks 1 and 2 and months 3 and 12, significantly greater mean decreases in intraocular pressure (P < .040) at peak were observed in patients treated with brimonidine than those treated with timolol. The mean intraocular pressure decrease at trough was significantly greater for timolol than for brimonidine at each follow-up visit (P < .001). With the exception of ocular allergy (in 11.5% of patients using brimonidine and less than 1% using timolol), fewer than 3% of patients in either treatment group withdrew from the study prematurely as a result of a specific adverse event. Patients receiving timolol experienced significant decreases in heart rate (P < .001) from baseline at all follow-up visits. No significant changes in heart rate were seen in patients treated with brimonidine. Neither medication produced clinically significant changes in blood pressure. CONCLUSION: Brimonidine is safe and effective in the long-term lowering of intraocular pressure in patients with glaucoma or ocular hypertension, with efficacy comparable to that of timolol but without a notable negative chronotropic effect on the heart.     

Acute renal failure complicating nonfulminant hepatitis A

PURPOSE: To compare the orbital blood flow velocities of patients with long-standing ocular hypertension and patients with primary open-angle glaucoma. METHODS: Twenty patients with ocular hypertension were recruited from our clinic and underwent color Doppler imaging evaluation of their retrobulbar vessels. The blood flow velocities and resistance index of their central retinal artery, temporal short posterior ciliary artery, and ophthalmic artery were compared with those of 20 glaucoma patients individually matched for age and level of the highest untreated intraocular pressure ever recorded. RESULTS: Glaucoma patients had significantly lower peak systolic velocity and end-diastolic velocity than did patients with ocular hypertension in their central retinal artery (p < 0.001). No significant difference between the groups was observed in the other vessels studied. CONCLUSIONS: Glaucoma patients had lower blood flow velocity in the central retinal artery compared with that of ocular hypertension patients of similar age and level of untreated intraocular pressure. This might be important in the development of glaucomatous damage in those patients.     

Time-dependent changes in heart rate and pupil size during desflurane or sevoflurane anesthesia

To better characterize alterations in autonomic function associated with prolonged anesthesia, we tested the hypothesis that the time-dependent effects of sevoflurane and desflurane differ. We studied seven male volunteers, each anesthetized for 8 h with 1.25 minimum alveolar anesthetic concentration desflurane on one study day and with 8 h sevoflurane on another. These volunteers did not undergo surgery and were minimally stimulated during the study. Measurements included blood pressure, heart rate, pupillary size and light reactivity, concentrations of serum catecholamines, and carbon dioxide production. Over time, heart rate and pupil size increased significantly. During 6 of the 14 anesthetics (45%), heart rate at some point exceeded 95 bpm; similarly, pupil size at some time exceeded 5 mm during 8 anesthetics (57%). In contrast, plasma catecholamine concentrations and carbon dioxide production remained unchanged, and blood pressure remained nearly constant. There are thus substantial time-dependent changes in autonomic functions during prolonged anesthesia, even in unstimulated, nonsurgical volunteers, but we could not detect a difference in these changes during desflurane compared with sevoflurane anesthesia. Implications: Pupil size and heart rate changes are used to guide the delivery of anesthesia. In volunteers, pupil size and heart rate increased with increasing duration of constant desflurane or sevoflurane anesthesia. Thus, anesthetic duration alters heart rate and pupil size independent of surgery and changes in anesthetic delivery.     

Effects of brovincamine fumarate on choroidal blood volume in rabbits]

We examined the effects of brovincamine fumarate, a Ca(2+)-channel blocker, on choroidal blood flow. We measured the choroidal blood volume continuously for 1 hour using laser Doppler flowmetry, as well as systemic blood pressure, heart rate, and intraocular pressure in six urethane-anesthetized rabbits after intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine. As a control, ten rabbits receiving no medication were used. All the data were recorded and analyzed using MacLab on a computer. In both the 0.1 mg/kg and 0.5 mg/kg brovincamine-injected groups, the choroidal blood volume decreased significantly after administration, but showed no significant difference from controls. Vascular resistance in the choroid showed a significant increase over the value before administration and over the control group. The heart rate decreased significantly compared to the value before injection and to the control group. The mean blood pressure in both dose groups and the intraocular pressure in the 0.5 mg/kg injected group were significantly higher than the controls. These results indicate that intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine does not cause an increase in the choroidal blood volume in urethane-anesthetized rabbits.     

Lower oesophageal sphincter response to pentagastrin in chagasic patients with megaoesophagus and megacolon

Intraluminal manometric studies were performed in 14 chagasic patients with megaoesophagus, 10 chagasic patients with megacolon, and 15 control subjects. Basal lower oesophageal sphincter pressure was 20.27+/-1.16 mmHg (mean+/-SEM) in controls as compared wtih 15.16+/-1.53 mmHg in chagasics with megaoesophagus and 14.38+/-1.50 mmHg in chagasics with megacolon. Dose-response studies to intravenous pentagastrin showed that the chagasic patients exhibited a lower sensitivity to the stimulant than did the controls, as demonstrated by shifting of the dose-response curve to the right and higher individual values of the dose for half maximal contraction (D50). No difference was noted between the calculated maximal contraction (Vmax) of oesophageal sphincter of controls and chagasics. These data are compatible with the hypothesis of an interaction between pentagastrin and cholinergic nervous excitation on oesophageal sphincteric smooth muscle.     

Topographic disorientation: two cases

BACKGROUND: There are many theories, but the etiology of chronic fatigue syndrome (CFS) remains unknown. Diagnosticians have set guidelines to try to classify the condition, but its clinical definition is one of exclusion rather than defined by specific clinical testing. The primary goal of this investigation was to find a diagnostic key to define CFS. CFS patients and those diagnosed with the sympathetic hypersensitivity condition called fibromyalgia syndrome (FMS) exhibit identical brain single photon emission computerized tomography (SPECT) images. Therefore, this investigation was initiated to see if CFS patients also had denervation hypersensitivity of the sympathetic system. METHODS: A standardized supersensitivity test was performed using an ocular instillation of two drops of 1.0% phenylephrine. Sixty-two subjects (29 CFS patients and 33 normals) participated in the study. Measurements of pupil size were recorded by pupil gauge and flash photography. A pupillary dilation of greater than 2.5 mm would suggest a sympathetic denervation hypersensitivity. RESULTS: For all participants, a small, but statistically significant increase in pupil size was found (mean of 0.788 mm in normals and 0.931 mm in CFS patients). The change in pupil size in the CFS patients and controls showed substantial overlap and was not statistically significant (t = 0.83, p = 0.42, dF = 60). CONCLUSION: In conclusion, the results suggest that a denervation hypersensitivity of the pupil does not occur in CFS patients. The use of 1.0% topical phenylephrine had no diagnostic value in detecting CSF patients vs. normals.     

Buspirone, but not sumatriptan, induces miosis in humans: relevance for a serotoninergic pupil control

BACKGROUND AND OBJECTIVE: Drugs that act on the serotoninergic system have been shown to influence the pupil size. However, the 5-hydroxytryptamine (5-HT) receptor type or subtype that affects pupil diameter has not been defined in humans. With a placebo-controlled, double-blind randomized design, we investigated in healthy volunteers the effect on pupil size of buspirone and sumatriptan, which mainly act on 5-HT1A- and the 5-HT1-like receptors, respectively. METHODS: The pupil area was measured by means of a videopupillometer before and after a single oral administration of placebo or of three different doses of active drugs. Heart rate and arterial blood pressure were recorded after pupil area measurement. RESULTS: Buspirone (5, 10, and 20 mg) caused a dose-dependent miosis. Sumatriptan (50, 100, and 200 mg) did not affect the pupil size. Twenty milligrams of buspirone reduced the mydriasis induced by pretreatment with homatropine eyedrops. A 20 mg dose of buspirone reduced blood pressure without change in heart rate, whereas buspirone, at doses lower than 20 mg, and sumatriptan did not affect heart rate and blood pressure. CONCLUSIONS: This study suggests that buspirone, but not sumatriptan, the selective agonist of 5-HT1-like receptors, causes miosis in humans by activation of 5-HT1A receptors, possibly located in the central nervous system where they inhibit iris sympathetic pathways. Measurement of pupil size seems to provide a valuable and sensitive index of 5-HT1A receptor function in humans.     

Bladder biofeedback for the treatment of refractory sensory urgency in adults

PURPOSE: Constriction of the pupil during phacoemulsification and intraocular lens (IOL) implantation in patients with diabetes mellitus was studied. METHODS: Before surgery a combination of 0.75% cyclopentolate and 2.5% phenylephrine was applied topically to the eyes of 32 patients with diabetes mellitus and 25 age-matched controls. Epinephrine was mixed with buffered saline solution and used during the surgery. The surgical procedure included capsulorhexis, phacoemulsification in the posterior chamber and implantation into the capsular bag of a heparine surface-modified poly(methyl metacrylate) IOL with an optic diameter of 5.0 mm. The durations of phacoemulsification and the whole surgical procedure were recorded. Measurements of the horizontal pupillary diameter were taken before surgery, after phacoemulsification and at the end of the surgery. RESULTS: There was no significant difference in pupil size between controls and the diabetic group before the operation. Surgically induced miosis after phacoemulsification and at the end of operation were significantly more pronounced in the diabetic group than in controls (p < 0.05) (p < 0.05). Phacoemulsification and the entire surgical procedure took significantly longer time when performed in the diabetic eyes (p < 0.05) (p < 0.05). CONCLUSION: We conclude from these data that constriction of the pupil during cataract surgery is more pronounced in diabetic eyes as compared to controls.     

Choice of reference axis in ocular wave-front aberration measurement

The geometrical center of the pupil has often been used as the reference axis in ocular wave-front aberration measurement. However, the geometrical center of the pupil may shift when the pupil size changes under different conditions. In particular, for subjective methods, defining the center of the pupil precisely during the actual measurement is not always practical. Furthermore, the geometrical center of the pupil may not define the chief ray of the ocular optics because of the Stiles-Crawford apodization effect, which has a peak location that often deviates from the geometrical center of the pupil. We present the coefficient transformation table of the Taylor polynomial up to the sixth order with respect to reference axis shift. We illustrate the effect of wave-front aberration change with reference axis shift with experimental data. This type of wave-front aberration change could be a true measurement error if there is an error in defining the reference axis. We also propose using the coaxially sighted corneal reflex as a better reference axis in aberration measurement.     

Laser therapy and angle-closure glaucoma

All forms of primary and secondary pupillary block angle-closure glaucoma result in an increased resistance to aqueous flow at the pupil margin. As the pressure in the posterior chamber increases, the iris bows forward until the trabecular meshwork is occluded and aqueous outflow is interrupted. Most pupillary block glaucomas are ocular urgencies and require immediate medical therapy to lower intraocular pressure. The definitive treatment for pupillary block is laser therapy. By creating a hole in the iris, the pressure in the anterior and posterior chambers is equalized, allowing the angle to remain open. This discussion reviews the indications, contraindications, and techniques involved in the laser management of angle-closure glaucomas.     

Corneal endothelial changes with long-term topical epinephrine therapy

Corneal thicknesses and endothelial cell densities were studied in nine patients with ocular hypertension receiving long-term unilateral topical epinephrine hydrochloride therapy. No difference was noted in corneal thickness in the treated eyes. There was a significant (P less than .02) reduction in endothelial cell count in the treated eyes compared to their untreated fellow controls. Those patients who had the most marked intraocular pressure response to epinephrine also had the greatest endothelial cell loss.     

Changes in the chamber angle following ocular contusions (author's transl)

In a retrospective study, 87 patients were reexamined after hospital treatment of ocular contusion. The relationships between intraocular pressure, outflow facility, and lesions of the anterior chamber angle were analyzed. In 52% of the cases, lesions were demonstrated in the anterior chamber angle; about half of these patients showed extension of 180 degrees or more. There was no statistical correlation between intraocular pressure and outflow facility or the extent of anterior chamber angle lesions, although clinical findings clearly indicated such correlations. Blunt ocular injuries evidently lead to higher intraocular pressure in elderly patients. The latency period also appears to play a role: the longer the period between trauma and examination, the higher the pressure measured in the injured eyes. We found secondary glaucoma in two cases (about 2%). Glaucoma was suspected in six patients (6.5%). There was an apparent risk of glaucoma in four patients (4.3%).     

Pupillographic sleepiness testing in hypersomniacs and normals

BACKGROUND: Pupillary oscillations in darkness are considered to be a sign of sleepiness. The purpose of this pilot study was to ascertain whether pupillary oscillations were more pronounced in patients with hypersomnia than in normals. METHODS: Seven patients (four with sleep apnea syndrome, three with narcolepsy) and seven age-matched controls underwent pupillography for 11 min in complete darkness. The changes in pupil size were analyzed mathematically to determine quantitatively the amount of pupillary instability. RESULTS: Hypersomniacs had much higher amounts of pupillary oscillations in darkness than normals. The differences were significant. Baseline pupil size did not differ significantly between the two groups. CONCLUSION: This study showed that a pupillographic sleepiness test based on the evaluation of spontaneous pupillary changes in darkness is applicable in hypersomniacs and may facilitate therapy control, i.e. diagnostic grading by measuring daytime sleepiness objectively.     

Foot blood-flow at isometric handgrip contraction in patients with an ischaemic disease of the lower extremities and in control subjects

At isometric contraction of forearm muscles, the mean systemic pressure and the foot blood flow are statistically significantly increased. These changes are encountered both in controls and in patients with an ischaemic disease of the lower extremities.     

Enteroviral persistence in eye infections in monkeys (postuveitis syndrome)

Follow-up (5.5 years) of monkeys with a history of acute enterovirus uveitis (AEU) after intraocular infection with ophthalmotropic ECHO 11 and ECHO 19 strains showed progressive changes in the infected eye; destruction of the iris, formation of films in the anterior chamber of the eye, deformation of the pupil, and signs of cataract and glaucoma. A short (1-30 days) stage of active reproduction of infective virus (up to 10(10) TCD50/g tissue in the first days postinfection) was followed by the second very long stage of limited specific multiplication of virus in ocular tissues. The virus was not detected during the second stage, but its components (virusspecific antigen and crystalloid accumulations of virions) were found in ophthalmic and conjunctival tissues; moreover, high levels of neutralizing antibodies were detected in the blood. The results indicate AEU transformed into a stubborn persistent infection of the eye in monkeys. The findings of this follow-up and published reports about many-year follow-up of children with AEU permit us to classify a post-uveitis disease as a special nosological form of a persistent enterovirus infection and denote it as enterovirus post-uveitis syndrome. The main signs of this syndrome are a history of AEU, progressive destructive changes in the anterior segment of the eye, presence of virus components in ocular tissues in remote periods after infection, and high antibody level in the blood.     

Expression of major histocompatibility complex antigens and adhesion molecules in hearts of patients with chronic Chagas' disease

We have previously reported that heart lesions in patients with chronic cardiac Chagas' disease are composed predominantly of granzyme A+, cytolytic CD8+ T lymphocytes. We now pursue this study in the immunopathology of chronic chagasic cardiomyopathy by investigation of the expression of HLA antigens, and adhesion molecules in the hearts of seven chagasic patients with cardiac disease, two asymptomatic chagasic patients, and seven normal controls. Comparative immunohistochemical analyses show that HLA-ABC antigen expression is enhanced on the myocardial cells of chagasic patients with chronic cardiomyopathy, suggesting a possible role for these cells as targets for the CD8+ cytolytic lymphocytes dominant in these lesions. The HLA-DR antigens are not observed on myocardial cells, but are consistently upregulated on the endothelial cells in the hearts of patients with chronic chagasic cardiomyopathy. Intercellular adhesion molecule is expressed by endothelial cells of both chagasic and nonchagasic individuals, but E-selectin was detected only on vessels of hearts from chagasic patients who had chronic cardiomyopathy. Most of the lymphocytes in these lesions express lymphocyte function antigen-1 (LFA-1), CD44, and very late antigen-4, and a few display weak expression of LFA-3. We propose that the expression of these adhesion molecules and major histocompatibility complex antigens by endothelial cells, myocardial cells, and lymphoid cells in these lesions contribute to the pathogenesis of chronic chagasic cardiomyopathy.