The effects of protease inhibitors on histidine decarboxylase activities and assay of enzyme in various rat tissues.

Histidine decarboxylase (L-histidine carboxy-lyase, EC 4.1.1.22) of an extract of rat stomach was inactivated by a pancreatic extract. This inactivation was prevented by the protease inhibitors leupeptin, antipan, chymostatin, pepstatin, Trasylol and phenylmethanesulfonyl fluoride. Leupeptin, antipain, chymostatin and pepstatin together and phenylmethanesulfonyl fluoride alone prevented complete inactivation of the enzyme, while Trasylol had a weak protective effect. The inactivation and protection of histidine decarboxylase purified from whole fetal rats were similar to those of the stomach enzyme: both enzymes were strongly inactivated by trypsin and chymotrypsin, but not by elatase or carboxypeptidase Y. The histidine decarboxylase activities of various rat tissues were assayed in the presence of protease inhibitors: activity was highest in mast cells followed by the whole bodies of fetal rats and the stomach, while the activities were lower in decreasing order in the brain, spleen, lung and liver. Heart and kidney had no activity.

Intravenous nicardipine in cats increases optic nerve head but not retinal blood flow.

The effect of intravenously injected nicardipine on retinal and optic nerve head (ONH) blood flow was studied in 27 cats using laser Doppler velocimetry and flowmetry, respectively. A dose of 20 micrograms/kg of nicardipine had little effect on retinal blood flow. A dose of 100 micrograms/kg, however, produced a significant transient decrease in flow. By contrast, both doses produced a significant increase in ONH blood flow despite a significant decrease of the mean arterial blood pressure. Measurements of the partial pressure of oxygen (PO2) with an oxygen-sensitive microelectrode, whose tip was placed in the vitreous just in front of the optic disc, showed a significant increase in the PO2 that paralleled the increase in ONH blood flow. These results demonstrate, for the first time to the authors' knowledge, a pharmacologically induced increase in ONH blood flow and suggest that nicardipine could have a beneficial effect on ONH tissue.

Flicker evoked increase in optic nerve head blood flow in anesthetized cats.

The effect of diffuse luminance flicker stimulation of a large area (approximately 30 degrees diameter) on red blood cell flux (F) in the optic nerve head was measured in the anesthetized cat. F increased markedly during sustained flicker. The F-response to the initiation and cessation of the stimulation was found to occur within a few seconds. Upon sustained stimulation, the increase in F reached a plateau within approximately 2 min. Its level depended upon the intensity, frequency and wavelength of the stimulation and the state of adaptation of the retina. This stimulus offers a new and powerful means of investigating blood flow regulation in the optic nerve head (ONH).

Indocyanine green angiographic findings in Vogt-Koyanagi-Harada disease.

PURPOSE: To report the indocyanine green angiographic findings associated with Vogt-Koyanagi-Harada disease and compare them with fluorescein angiographic findings and monochromatic scanning laser images. METHODS: In a prospective study, indocyanine green angiography, by scanning laser ophthalmoscopy or infrared fundus photography, was performed in ten consecutive patients (20 eyes) with Vogt-Koyanagi-Harada disease during the acute stage before and recovery stage after corticosteroid treatment. Findings were compared with fluorescein angiographic features and monochromatic scanning laser imaging. RESULTS: During the acute stage of the disease, indocyanine green angiography disclosed a dark background in the early phase and multiple, non-uniform hypofluorescent lesions in the midphases. Lesions were more numerous and extensive than areas either of serous retinal detachment on monochromatic scanning laser imaging or of punctate hyperfluorescence on fluorescein angiography. During the recovery stage, the abnormal dark background on indocyanine green angiography at initial examination resolved, with choroidal vessels visible in all cases, but nonuniform hypofluorescent lesions persisted in most eyes. Fluorescein angiography disclosed hypofluorescent patchy areas, and confocal infrared laser imaging showed some bright reflective lesions in three patients with especially severe clinical symptoms. On final examination after an average of 17.7 months, both angiographies still disclosed abnormal findings in these three patients. CONCLUSIONS: Indocyanine green angiographic findings suggest that choroidal inflammation may cause a transient choroidal circulatory disturbance during the acute stage of Vogt-Koyanagi-Harada disease. In more severe cases, this dysfunction may secondarily damage the retinal pigment epithelium.

Chronic ocular ischemia associated with the Eisenmenger's syndrome.

We studied the ocular findings of two adult patients with the Eisenmenger's syndrome who had atrial septal defects that were diagnosed before the age of 10 years but not operated on and pulmonary hypertension. Both eyes of these patients showed microaneurysms, multiple small blot hemorrhages, or capillary dilation in the temporal peripheral fundus. Multiple microaneurysms and retinal collaterals were confirmed by fluorescein angiography. One of the patients developed bilateral rubeosis iridis with slow progression. These retinal lesions and the rubeosis iridis are probably related to chronic ocular ischemia caused by chronic systemic hypoxia.

Skin test with varicella-zoster virus antigen for ophthalmic herpes zoster.

We assessed delayed dermal hypersensitivity to varicella-zoster virus by a varicella skin test in 12 patients (nine women and three men ranging in age from 27 to 85 years) with ophthalmic herpes zoster during the acute stage and in a group of 27 healthy controls (15 women and 12 men ranging in age from 18 to 58 years). Of the 27 healthy individuals, 25 had positive skin test reactions whereas only one of the 12 patients with ophthalmic herpes zoster had a positive skin test reaction within two weeks after the onset of the eruption, suggesting that cellular immunity to varicella-zoster virus antigens is impaired in the development of ophthalmic herpes zoster. Our study also showed that the varicella skin test is a convenient way to diagnose ophthalmic herpes zoster during the acute stage of the disease.

Survey of complications of indocyanine green angiography in Japan.

PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.

Rebreathing into a bag increases human retinal macular blood velocity.

AIMS: The effect of rebreathing into a bag (RB) on retinal macular blood velocity was evaluated in healthy volunteers. METHODS: Ten normal volunteers, whose ages ranged from 17 to 34 years, performed RB over 135 to 260 seconds (mean (SD) 193 (38) seconds) while retinal macular blood velocity was determined non-invasively using the blue field simulation technique. RESULTS: Leucocyte velocity significantly increased (p < 0.05) at 2 minutes and at the end of RB by 53% (42%) and 92% (65%), respectively (95% confidence interval of the mean (CIM)). All subjects observed an increase in the density of leucocytes. At the end of RB, mean systolic brachial arterial pressure and heart rate were significantly increased by 24% (11%) and 37% (15%) respectively (p < 0.01). At 2 minutes, end tidal oxygen concentration in the exhaled air was 47% (8%) (95% CIM) below and carbon dioxide was 41% (16%) above baseline (p < 0.001). The RB produces a large increase in macular leucocyte velocity, suggesting an increase in blood flow. CONCLUSION: Although RB has some systemic risk due to hypoxia and hypercapnia, RB for a short period of 1 or 2 minutes might be of help in the treatment of retinal arterial obstructive diseases in young patients without cardiovascular disorders if other treatments do not show any beneficial effects.

Real time fixation point monitoring system for photocoagulation of juxtafoveal neovascularisation.

BACKGROUND/AIMS: A new real time monitoring system has been developed to locate the fixation point during juxtafoveal laser photocoagulation. METHOD: The red diode laser beam is combined coaxially with the illumination beam to image a cross in the focal plane of the slit lamp, which allows projection of a red cross onto the patient's fundus. 27 patients with juxtafoveal choroidal neovascularisation were treated by photocoagulation using this system. RESULTS: 13 (48%) patients whose visual acuity ranged from 20/200 to 20/40 answered that it was easier to keep the focus on the cross target image than on the aiming beam. The patient maintained stable fixation throughout the treatment. The laser treatment was completed without foveal damage near the fixation point in all patients. CONCLUSION: The real time fixation monitoring system should allow surgeons to treat juxtafoveal lesions with laser photocoagulation more safely and accurately.

Transient hyperopia with lens swelling at initial therapy in diabetes.

The clinical courses of 10 eyes of five diabetic patients who exhibited bilateral transient hyperopia (maximum: 1:1-4.9 dioptres, spherical equivalent) after initiation of strict control of diabetes with or without insulin are reported. The hyperopia occurred within a few days after abrupt decrease in plasma glucose, progressed to maximum at days 7-14, and regressed gradually over 1 month thereafter. Transient cycloplegia had no effect on refractive error. During hyperopia, there were no significant changes in axial length or corneal curvature. However, thickened lens, decreased anterior chamber depth, and transient cataract were observed to significant degrees. It is suggested that the transient hyperopia, with lens swelling and opacity, was caused by decreased lens refractive index following water influx.

Comparative study of intraocular lens implantation through 3.0 mm temporal clear corneal and superior scleral tunnel self-sealing incisions.

PURPOSE: To compare the clinical outcome of phacoemulsification and foldable silicone intraocular lens (IOL) implantation through a 3.0 mm temporal clear corneal incision and 3.0 mm superior scleral tunnel incision. SETTING: Department of Ophthalmology, Yodogawa Christian Hospital, Osaka, Japan. METHODS: Eighty cataractous eyes of 78 patients with pre-existing against-the-rule (ATR) astigmatism were recruited for this prospective, randomized study. The patients were assigned to one of the two groups. Data on uncorrected and corrected visual acuities, keratometry, flare intensity measurement, and central cornea endothelial cell count were evaluated preoperatively and at 2 days, 1 week, and 1 and 3 months postoperatively. RESULTS: Although the pre-existing keratometric cylinder decreased in the temporal clear corneal incision group and increased in the superior scleral tunnel incision group, the amount of cylinder shift was not significantly different. Mean scalar shift of keratometric cylinder in the corneal incision group was 1.19 diopters (D) at 2 days postoperatively, 0.86 D at 1 week, and 0.56 D at 3 months and in the scleral incision group, 1.09 D at 2 days, 0.76 D at 1 week, and 0.65 D at 3 months. Eighty percent of the eyes in each group achieved an uncorrected visual acuity of 20/40 or better from the second day postoperatively. No statistically significant difference in visual rehabilitation or other parameters was noted between the groups throughout the study. Complications including corneal endothelial cell loss and wound incompetence requiring suturing were observed in the temporal clear corneal incision group. CONCLUSIONS: Both incisions offered satisfactory clinical results, but the superior scleral tunnel incision resulted in fewer complications. Minimal corneal keratometric change induced by a 3.0 mm incision was not related to uncorrected visual rehabilitation.

Extraction of fluorescent dot traces from a scanning laser ophthalmoscope image sequence by spatio-temporal image analysis: Gabor filter and radon transform filtering.

The scanning laser ophthalmoscope (SLO) allows the tracking of fluorescent dot motion, thereby enabling the flow velocities in perimacular capillaries to be directly measured. These can serve as an important index of local retinal soundness or reflect the whole body circulation status in disorders such as diabetes. Although it is possible to perceive moving fluorescent dots with the human eye, they are so faint and unstable that it is difficult to detect them by conventional digital still-image processing methods. To solve this problem, we generated spatio-temporal images of the fluorescent dots in a capillary and applied Gabor filters tuned to the direction of the traces in order to detect them. Finally, by discriminating and integrating the output using two levels of threshold, we were able to extract their traces. Because the medium-size Gabor filter requires a considerable amount of time for two-dimensional convolution calculation, we prove that there is a certain equivalence between the Gabor filter, the radon transform, and the Hough transform. In the light of this, we propose a form of radon transform filtering that includes a radon transform Gabor filter as a very long Gabor filter. This allows a whole trace to be detected in a single step with a one-dimensional convolution, thereby shortening the processing time. In an experiment, 60% of the traces could be detected without error, which is sufficient to allow the mean flow velocity in a capillary to be measured.

The effect of nipradilol, an alpha-beta blocker, on retinal blood flow in healthy volunteers.

PURPOSE: To study the effects of topically applied nipradilol, an alpha-beta blocker recently developed in Japan as an ocular hypotensive drug, on retinal blood flow (RBF) in healthy volunteers. METHODS: Seven healthy volunteers (mean age, 33 years) underwent measurement of RBF using a newly developed stabilized laser Doppler velocimetry system. In a double-blind trial, retinal arterial blood flow, intraocular pressure (IOP), and blood pressure (BP) were measured before and after the instillation of nipradilol or saline every hour for 5 hours. RESULTS: Retinal arterial blood flow and the diameter of the retinal artery significantly (p< 0.05) increased at 4 hours after instillation in nipradilol-treated eyes. Retinal blood velocity did not change significantly. Nipradilol evoked a significant (p< 0.05) bilateral decrease in IOP. Mean BP decreased significantly (p< 0.05) 3 hours after instillation. Ocular perfusion pressure (OPP), calculated from the mean BP and IOP, did not change significantly during the study. CONCLUSION: Topical nipradilol significantly increased retinal arterial blood flow in healthy volunteers, not through a secondary effect dependent on a change in OPP, but likely through the vasodilatory action of the drug.

Effects of intravenous cilostazol on optic nerve head and choroidal blood flow in anesthetized cats.

Cilostazol is one of a number of anti-platelet agents used for the treatment of thrombotic disorders, such as chronic arterial obstruction, and is a vasodilator as well. In the present study, cilostazol was intravenously administered to seven anesthetized cats, and the optic nerve head (ONH) and choroidal blood flows were continuously monitored in a noninvasive method using laser Doppler flowmetry. The systemic blood pressure dropped significantly by 4+/-4% (p<0.05) with cilostazol 0.03 microg/kg/min, although there were no significant changes in ONH and choroidal blood flows. When the drug was given at 0.1 microg/kg/min, ONH blood flow remained significantly higher than the baseline, 54+/-37% (p<0.05) at maximum, immediately after the start of administration. Soon after the start of the infusion, a significant decrease, 17+/-10% (p<0.05) at maximum, in choroidal blood flow occurred, but this was followed by a significant increase, 35+/-27% (p<0.05) at maximum. At that time, the systemic blood pressure dropped significantly by 14+/-6% (p<0.05). These findings indicate that an intravenous administration of cilostazol increases both ONH and choroidal blood flows, suggesting the potential usefulness of cilostazol for both prophylactic and therapeutic management of ophthalmic circulatory disorders.

Role of nitric oxide in mediating retinal blood flow regulation in cats.

The role of nitric oxide (NO) was evaluated in mediating control of retinal blood flow in the anesthetized cat. This was done under resting conditions and as a function of decreases in perfusion pressure. The retinal blood flow was calculated by measuring blood velocity with laser Doppler velocimetry (LDV) and retinal blood vessel diameter with image analysis. Graded decreases in perfusion pressure were obtained by increasing intraocular pressure (IOP). Following intravenous administration of 30 mg/kg NG-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, the arterial blood pressure increased under resting conditions by 34+/-3% (n = 7), the blood vessel diameter decreased by 18+/-2%, and retinal blood flow significantly declined by 27+/-6% (n = 6). Irrespective of the presence or absence of L-NAME (30 mg/kg), stepwise reductions in perfusion pressure that reached a level that was 35% of the baseline value had no significant effect on retinal blood flow. These results suggest that, under resting conditions, retinal blood flow decreases in response to a putative fall in NO levels. However, NO does not appear to be involved in mediating the autoregulatory response to a decrease in perfusion pressure.

Liposomal prostaglandin E1 enhances optic nerve head blood flow in cats.

We investigated the effects of intravenous administration of prostaglandin E1 (PGE1) and lipo-prostaglandin E1 (lipo-PGE1), on optic nerve head blood flow (ONHBF) using ten anesthetized cats. Changes in relative ONHBF were noninvasively and continuously measured with fundus camera-based laser Doppler flowmetry. The blood pressure (BP) decreased significantly by 6 +/- 5 (mean +/- SD)% and 8 +/- 4%, respectively, after PGE1 (30, 100 ng/kg/min) administration, but at either of these concentrations there were no significant changes in ONHBF. On the other hand, with lipo-PGE1 (10 ng/kg/min), the BP remained unchanged, but ONHBF increased significantly by 61 +/- 49%. A larger dose of lipo-PGE1 (30 ng/kg/min) had opposite effects because the BP decreased significantly by 14 +/- 4% after administration, and the ONHBF remained unchanged (i.e., 67 +/- 102%). In all cases, there were no changes in IOP. With 10 ng lipo-PGE1, the large increase in ONHBF can be accounted for by vasodilation since perfusion pressure was unchanged. The inability of 30 ng lipo-PGE1 to affect ONHBF could be ascribed to the decrease in BP resulting in decreased ocular circulation. These results suggest that, in humans, lipo-PGE1 may also increase ONHBF provided that it is used at doses that do not produce large decreases in BP.

Effects of endothelin-1 on optic nerve head blood flow in cats.

We determined the effects of endothelin-1 on optic nerve head (ONH) blood flow in anesthetized cats. Endothelin-1 (50-2500 pmol) injected into the vitreous produced a dose-related and sustained decrease (22 +/- 6% by 500 pmol and 36 +/- 11% by 2500 pmol) in the ONH blood flow. Blood pressure (BP) and heart rate (HR) remained, however, unchanged. In contrast, intravenous (i.v.) injected endothelin-1 (0.004-0.4 nmol kg-1) produced a dose-related and short-lasting increase in the ONH blood flow; its maximum increase by 0.4 nmol kg-1 was 135 +/- 34%. Endothelin-1, at 0.4 nmol kg-1, i.v., produced a transient decrease followed by a more sustained increase in BP, but had no remarkable effect on HR. The increase in ONH blood flow by i.v. injection of endothelin-1 was abolished by N(G)-nitro-L-arginine methyl ester (L-NAME, 5 mg kg-1 min-1, i.v.). The suppression of blood flow by L-NAME was reversed by the addition of L-arginine (50 mg kg-1 min-1). Pressor responses to endothelin-1 (0.4 nmol kg-1, i.v.) were augmented in the presence of L-NAME, but reversed in combination with L-arginine. These findings suggest that i.v. injection of endothelin-1 causes NO release from endothelial cells which increases ONH blood flow, whereas intravitreal injection of endothelin-1 decreases ONH blood flow by its vasoconstrictive effect. Different populations of ET receptors on vascular smooth muscles or endothelial cells would reflect the opposing effects of endothelin-1.

Effect of hyperbaric oxygen on ophthalmic artery blood velocity in patients with diabetic neuropathy.

To assess the relationship between blood flow and the complications of diabetes mellitus, we investigated the changes in the velocity of blood flow in the ophthalmic artery before and after hyperbaric oxygen therapy (HBO), one of the treatments for diabetic neuropathy. Color Doppler imaging was used before and after HBO. Seven diabetic neuropathy patients, 3 diabetics without neuropathy, and 7 normal, control subjects were enrolled. The patients were subjected to breathing 100% oxygen at 2.0 atmosphere absolute (ATA) for 1 hour. Hyperbaric oxygen therapy resulted in an average decrease in blood velocity by 15.0 +/- 9.0% (mean +/- SD) in normal subjects and 10.7 +/- 8.6% in diabetics without neuropathy. Blood velocity returned to the baseline level 4 hours after discontinuation of HBO. In contrast, blood velocity increased by 20.6 +/- 9.5% in diabetic patients with neuropathy irregardless of the severity of the diabetic retinopathy. The resistance index of the ophthalmic artery was not changed during HBO in the group with diabetic neuropathy, indicating that other mechanisms may be implicated, leading to the compensatory changes of blood flow. These results suggest that the increase in the blood velocity in the ophthalmic artery after HBO in diabetic neuropathy patients could be attributed to an imbalance in autonomic nervous function.

Clinicopathological report of retinitis pigmentosa with vitamin E deficiency caused by mutation of the alpha-tocopherol transfer protein gene.

PURPOSE: To discuss the clinicopathological findings in a patient with retinitis pigmentosa (RP) accompanied by a vitamin E deficiency caused by an H101Q mutation in the alpha-tocopherol transfer protein (alpha-TTP) gene. CASE: The clinical course of this patient was followed by conventional ophthalmological examinations over a 3-year period. After the patient died from pancreatic cancer, the eyes were obtained, and examined by light and electron microscopy. OBSERVATIONS: The patient complained of night blindness subsequent to adult-onset ataxia, although the ataxia was very mild. His visual acuity was 0.6 OU, and ophthalmoscopy revealed RP sine pigmento. Ring scotomas were detected, and the electroretinography, electro-oculography, and dark-adaptation were altered. Fluorescein angiography showed granular hyperfluorescence around the macula. No progression of the visual and neurological symptoms was observed during the 10 years he was taking oral vitamin E. Histopathological examination revealed the loss of the outer and inner segments of the photoreceptors in the area corresponding to the ring scotoma, as well as a disorganization and shortening of the outer segments in the peripheral retina. CONCLUSIONS: We conclude that the clinical and pathological findings in the eyes of this patient having RP with vitamin E deficiency caused by an H101Q mutation are similar to those of common autosomal recessive RP. However, special attention is required in making a diagnosis of RP with vitamin E deficiency because RP with vitamin E deficiency is medically treatable. The mild Friedreich-type ataxia accompanying the RP may be helpful in identifying this disease.

Two-year follow-up study comparing primary vitrectomy with scleral buckling for macula-off rhegmatogenous retinal detachment.

PURPOSE: To compare the anatomic and visual outcomes achieved by scleral buckling and primary vitrectomy for the repair of macula-off rhegmatogenous retinal detachment. METHODS: The records were reviewed for a consecutive series of 167 patients (167 eyes) who were initially treated with scleral buckling or pars plana vitrectomy for primary macula-off retinal detachment. Patients were treated between January 1993 and December 1996. After adjustments for preoperative characteristics, data from 102 cases (55 scleral buckle cases and 47 primary vitrectomy cases) were used for the final comparison. There had been a minimum follow-up period of 24 months. RESULTS: No significant differences in single-procedure reattachment incidence (91%), final success incidence (100%) and incidence of postoperative proliferative vitreoretinopathy development (4%) were observed between the two treatment groups. Preoperative visual acuity, preoperative intraocular pressure, and duration of macular detachment were the three best predictors of postoperative visual recovery in both groups. Favorable overall visual recovery was obtained postoperatively, with no significant differences between the two groups throughout the follow-up period. However, in the eyes with poor preoperative visual acuity (<0.1), ocular hypotony (intraocular pressure <7 mm Hg), or prolonged macular detachment (more than 7 days), visual recovery in the primary vitrectomy group was significantly better (P <.05) than in the scleral buckle group from the first postoperative month. CONCLUSION: Both procedures achieved favorable anatomic and visual outcomes in the majority of patients with primary macula-off retinal detachment. Primary vitrectomy may be more effective than scleral buckling for achieving early visual rehabilitation in cases complicated by poor preoperative vision, ocular hypotony, and prolonged macular detachment.