Inhibition of experimental diabetic cataract by topical administration of RS-verapamil hydrochloride.

AIM: To investigate the efficacy of verapamil eye drops for inhibition of diabetic cataract in rats. METHODS: Diabetes was induced in 69 male Sprague-Dawley rats by an intraperitoneal injection of streptozotocin (65 mg/kg body weight). One group (DV) of animals was treated by instillation of one drop of 0.2% RS-verapamil hydrochloride in both eyes three times daily for 8 weeks. The placebo treated group (D) received the vehicle solution only. After 8 weeks the lenses were removed, inspected, and photographed using bright and dark field illumination. The transmission of He-Ne laser light was measured in the optical axis of each lens in order to determine the turbidity coefficient (t) as a measure of central lens opacity. Following digital image analysis, the integrated density as a measure of central and mid-peripheral opacities was determined. RESULTS: Lenses of both groups developed peripheral cortical opacities not affecting the optical axis. Advanced and paracentral cortical opacities were present in 10 (16.7%) of the placebo treated lenses (D) and two (3.8%) of the verapamil treated lenses (DV). Complete corticonuclear cataract developed in four (6.7%) of the lenses from group D but none of the lenses from group DV. The mean lens turbidity t was determined to be 0.019 (SEM 0.002) mm(-1) (n = 52) in the verapamil treated diabetic rats (DV) and 0.042 (0.008) mm(-1) (n = 60) in the placebo treated group (D). This difference was statistically significant (p = 0.0054). The mean integrated density was 274.91 (22.5) in group D (n = 60) and 196.28 (20.7) in group DV (n = 37). This difference was also significant (p = 0.0037). CONCLUSION: Verapamil eye drops 0.2% administered three times daily are effective in inhibiting the progression of lens opacities in streptozotocin diabetic rats.

Anatomy of the orbital apex and cavernous sinus on high-resolution magnetic resonance images.

Diseases of the orbital apex and cavernous sinus usually present with involvement of multiple cranial nerves, corresponding to the complex anatomy of the region. In nontraumatic disorders, magnetic resonance imaging is the diagnostic modality of choice. However, its capabilities can be fully used only with thorough knowledge of the complicated topographic relationships in this region. This article describes the imaging anatomy of the cranio-orbital junction and adjacent subarachnoid spaces. High-resolution magnetic resonance images of normal subjects are presented, and the results are compared with findings reported in the literature. The following anatomic structures can be visualized on high-resolution magnetic resonance images: extraocular muscles and corresponding connective tissue, major orbital and cerebral arteries, ophthalmic veins, cavernous sinus, and all sensory and motor cranial nerves of the eye along their intraorbital and intracranial course.

High-resolution magnetic resonance imaging of the orbital connective tissue system.

A complex system of connective-tissue septa within the orbit has previously been described in serial histologic sections. The present study describes the anatomy of the orbital connective tissue system on high-resolution magnetic resonance (MR) images in vivo. Five volunteers aged 26 to 35 year underwent magnetic resonance imaging of the orbit on a 1 Tesla unit (Impact, Siemens, Germany). T1-weighted coronal images were obtained using a surface coil. Anatomical structures on the MR images were identified by comparison with corresponding histologic sections. On MR images of the anterior orbit, the levator aponeurosis, Lockwood ligament, transverse intermuscular ligament, common sheath, check ligaments, Tenon capsule, intermuscular septa, and palpebral ligaments can be seen. In the mid- and posterior orbit, the intermuscular orbital septa, especially the superolateral septum, the superior ophthalmic vein hammock, and septa of the radial connective tissue system are visualized. High-resolution magnetic resonance imaging is capable of delineating the major septa of the orbital connective tissue system.

Effectiveness of eye drops protective against ultraviolet radiation.

BACKGROUND: To test the effectiveness of commercially available ultraviolet (UV)-protective eye drops (8-hydroxy-1-methylchinolinium methylsulphate) which are recommended for protection against both solar and artificial UV radiation. METHODS: The spectral transmission in the wavelength range from 250 to 500 nm was investigated in 1-nm steps using a high-resolution double monochromator with holographic gratings of 2,400 lines/mm and a 1,000-watt halogen lamp as light source. The transmission spectrum was measured for different values of the layer thickness. RESULTS: The transmission of a liquid layer of about 10 microns, which corresponds to the thickness of the human tear film, shows a cut-off at 290 nm with a transmission of about 25-50% at shorter wavelengths. For wavelengths longer than 290 nm the transmission is higher than 90%. The threshold time ratio for keratitis formation with and without eye drops is above 0.93 considering solar radiation on the earth's surface and above 0.65 considering radiation from arc-welding, respectively. DISCUSSION: The transmission spectrum of the eye drops under realistic conditions does not show a protective effect against solar UV radiation. However, there exists reduction of UVC radiation in the spectral range typical of artificial UV sources such as arc-welding. We cannot recommend the application of these eye drops as an UV-protective aid against eye damage by solar UV radiation.

Is Whitnall's ligament responsible for the curved course of the levator palpebrae superioris muscle?

BACKGROUND AND PURPOSE: The levator palpebrae superioris (LPS) muscle courses anteriosuperiorly to culminate cranial to the posteriosuperior surface of the globe from where it courses anterioinferiorly to the trasal plate. Whitnall's superior transverse ligament (STL) has been suggested to suspend the LPS at its culmination. If this was the case, one would expect the STL to be located near the culmination of the LPS. In order to elucidate this functional aspect of the STL, the spatial relation of the STL of the LPS muscle is investigated in this study. METHODS: Surface coil MRI in an oblique sagittal plane along the optic nerve was performed in 6 orbits from 3 human cadavers in which the STL was marked with synthetic material. RESULTS: The MR images showed that in human cadaver specimens the STL is situated in the anterior descending portion of the LPS. CONCLUSION: This result suggests that the STL does not suspend the LPS at its culmination and is therefore not responsible for the curved course of the muscle.

Choristoma of the optic nerve: neuroimaging characteristics and association with spinal cord lipoma.

A 54-year-old patient presented with amaurosis of the right eye that resulted from a dysontogenetic tumor of the right optic nerve. The tumor involved the intraorbital, intracanalicular and intracerebral portion of the right optic nerve, without involvement of the chiasm. Although the patient had refused further diagnostic surgical exploration, we show that it is possible to establish the diagnosis of choristoma of the optic nerve by means of modern neuroimaging techniques based on computed tomography and magnetic resonance imaging. It appears from neuroimaging that choristomata of the optic nerve and spinal cord lipomas represent different manifestations of the same type of tumor. The neuroimaging characteristics of both kinds of tumors are discussed.

Ocular pharmacokinetics of verapamil in rabbits.

Previously, it had been demonstrated that cataract in diabetic rats can be prevented by systemical administration of the calcium channel blocker verapamil. In addition to that, 0.125% verapamil eye drops were found to significantly reduce the intraocular pressure in ocular hypertensive human subjects. The purpose of this study was to investigate the ocular penetration and elimination of verapamil after topical administration of the drug in rabbits. Two drops of a 0.125% aqueous solution of RS-verapamil hydrochloride (corresponding to a total dose of 125 microg RS-verapamil hydrochloride) were administered into the conjunctival sac. Aqueous humor and blood samples were taken at different times after administration and analysed for drug concentration by combined gas chromatography-mass spectroscopy. Following the instillation of 0.125% verapamil eye drops in a total dose of 125 microg RS-verapamil, mean (+/- SEM) aqueous humor peak levels of 1607 +/- 272 ng/ml were achieved after 20 min. Mean half-life for the elimination from the aqueous humor was 33 min. Topical application of verapamil produced very low serum peak concentrations (10.5 +/- 1.3 ng/ml). The results of our study demonstrate that topically administered verapamil readily penetrates into the anterior chamber leading to aqueous humor drug levels in the microM range without producing serum levels that are high enough to cause cardiovascular side effects.

Dynamic magnetic resonance imaging of the levator palpebrae superioris muscle.

The relationship between upper lid elevation (h) and shortening (s) of the levator palpebrae superioris muscle (LPS) has an influence on the dose-response relationship in ptosis surgery. In order to investigate the relationship between upper lid elevation and shortening of the LPS, parasagittal T1-weighted MR images of the orbit were obtained in healthy subjects with the eye in down- and upgaze. The position of the upper lid margin and the length of the LPS were measured in the images in down- and upgaze and the amount of h and s was determined. For a mean (+/- SD) vertical upper lid elevation of 15 +/- 1 mm, the mean (+/- SD) shortening of the LPS muscle was 21 +/- 3 mm (n = 4). The mean ratio of his was calculated to be 1:1.4, which means that the levator muscle must contract by 1.4 cm in order to achieve a lid elevation of 1 cm. Therefore, the force of the LPS which is necessary to lift the upper eyelid can be smaller than the lid-closing force. This strongly suggests a physiological mechanism which reduces the muscle force necessary for lifting the upper eyelid.

Collagen fibrils in the human corneal stroma: structure and aging.

PURPOSE: Transparency and biomechanical properties of the cornea depend on the structure and organization of collagen fibrils. The authors determined diameter, axial period, and lateral molecular spacing of collagen fibrils in human corneal stroma as a function of age. METHODS: Seventeen normal human corneas were investigated in their native state by means of small-angle and wide-angle x-ray scattering. RESULTS: The mean radius of collagen fibrils, the axial period of collagen fibrils, and the lateral intermolecular Bragg spacing were found to be age dependent. The authors determined fibril radii of 16.1 +/- 0.5 nm in persons older than 65 years of age (n = 10) and 15.4 +/- 0.5 nm (mean +/- SD) in persons younger than 65 years (n = 7) (P < 0.022). The related age-dependent values were 66.4 +/- 0.7 nm (> 65 years) and 65.2 +/- 0.8 nm (< 65 years) for the axial period (P < 0.006) and 1.515 +/- 0.010 nm (> 65 years) and 1.499 +/- 0.013 nm (< 65 years) for the intermolecular Bragg spacing (P < 0.022). CONCLUSIONS: Aging is related to a three-dimensional growth of collagen fibrils in the human corneal stroma. The age-related growth of the fibril diameter was mostly a result of an increased number of collagen molecules and, in addition, to some expansion of the intermolecular Bragg spacing probably resulting from glycation-induced cross-linking. The observed expansion of the fibrils in an axial direction may result from reduction of the molecular tilting angle within collagen fibrils. The observed alterations of the collagen framework may have implications for refractive surgery and ocular tonometry achieved through related changes in the biomechanical properties of the cornea.

High resolution magnetic resonance imaging of neurovascular orbital anatomy.

PURPOSE: This study describes the magnetic resonance imaging (MRI) anatomy of the blood vessels and nerves of the orbit to provide a morphological basis for the interpretation of clinical findings. METHODS: Seven volunteers aged 29 to 54 years underwent high-resolution MRI of the orbit on a 1 Tesla unit (Impact, Siemens, Germany). T1-weighted oblique-sagittal, coronal, and axial images were obtained using a surface coil. Anatomic structures on the magnetic resonance images were identified by comparison with corresponding histologic sections of the orbit. RESULTS: The ophthalmic artery and most of its branches (central retinal artery, posterior ciliary arteries, lacrimal artery, anterior and posterior ethmoidal arteries, supratrochlear artery, supraorbital artery, dorsal nasal artery) are visualized. The superior ophthalmic vein, the lacrimal vein, the medial ophthalmic vein, the inferior ophthalmic vein, the medial and lateral collateral veins, and the vorticose veins are also delineated. Furthermore, branches of the oculomotor nerve, the abducens nerve, the frontal nerve, the nasociliary nerve, the lacrimal nerve and the infraorbital nerve are identified in the magnetic resonance images. CONCLUSION: High-resolution MRI is capable of delineating the orbital arteries, veins, and nerves. This is mainly based on two principles. First, blood vessels appear mostly dark on magnetic resonance images because of the signal void of flowing blood. Second, the bright background of the orbital fat on T1-weighted magnetic resonance images accounts for the good soft-tissue contrast in the orbit. With improved MRI technology and reduced imaging time, high-resolution-MRI may be applied routinely for diagnostic purposes.

Collagen fibril orientation in the human corneal stroma and its implication in keratoconus.

PURPOSE: The kind and the degree of preferred collagen fibril orientation in normal human corneal stroma were investigated as important qualities of the cornea with respect to its mechanical properties and, hence, to refractive surgery. To determine whether this information is relevant to corneal disease, the authors investigated collagen fibril orientation in several corneas with keratoconus. METHODS: By means of low-angle x-ray scattering, 17 normal human corneas and four corneas of eyes with keratoconus were investigated. RESULTS: Collagen fibrils in the normal human corneal stroma showed two preferred orientations orthogonal to each other. These were the horizontal and the vertical directions. The authors defined a degree of orientation gamma, determined to be gamma = 0.49 +/- 0.10 (mean +/- SD). This means that the excess of the preferentially oriented fibrils in relation to the total number of fibrils was approximately 49%. It follows from this value that approximately two thirds of the fibrils (66%) were within in a 45 degrees sector (+/-22.5 degrees) around the horizontal and vertical meridians, whereas approximately one third (34%) is oriented in the oblique sectors in between. No statistically significant variation of gamma within a central 7 mm zone could be detected in normal corneas. The orthogonal arrangement of the collagen fibrils was, however, profoundly altered in keratoconus, in which nonorthogonal orientations were found inside the apical scar. CONCLUSIONS: The normal human corneal stroma shows a considerable degree of structural anisotropy. It is characterized by two preferred collagen fibril orientations orthogonal to each other. Alteration of the regular orthogonal arrangement of the fibrils in keratoconus may be related to the biomechanical instability of the tissue.

High-resolution magnetic resonance imaging of the normal extraocular musculature.

PURPOSE: Magnetic resonance imaging (MRI) of the extraocular muscles has attracted growing interest for the evaluation of complex motility disorders. However, little information is available on the high-resolution MRI anatomy of the normal extraocular muscles and their connective tissue system. The study describes the imaging anatomy of the recti and oblique muscles and the levator palpebrae superioris muscle. METHODS: MRI of the orbit at 1 tesla was performed in four normal volunteers using a surface coil. RESULTS: Many anatomical details such as Zinn's tendinous annulus, the trochlea, the superior oblique tendon, the intermuscular septa, the check ligaments, Lockwood's ligament and the common sheath between the superior rectus muscle and the levator muscle were visualised. A striking imaging feature was the curved path of both the recti muscles and the levator palpebrae muscle. The inferior oblique muscle also showed a marked curvature in the region of Lockwood's ligament. CONCLUSIONS: High-resolution MRI is capable of demonstrating the anatomy of the extraocular musculature and parts of its connective tissue system. The curved path of the extraocular muscles can be explained by the configuration of the orbital connective tissue system which couples each extraocular muscle with the adjacent orbital wall. We discuss the clinical implications of our findings and review previous radiological studies regarding the functional anatomy of the extraocular muscles.

Mechanisms in retinal vasculogenesis: an analysis of the spatial branching site correlation.

Starting from fractal dimension calculations of retinal vessel patterns, different growth models and related mechanisms have been suggested to simulate retinal vasculogenesis. A comprehensive view of this topic does not exist. In order to elucidate this question the spatial correlation of the vessel branching sites of the embryonic vessel pattern has been studied. During development of the retinal vasculature within the nerve fiber layer a modification of the branching characteristics can be observed. This result supports theories which suggest a close relation between the vessel propagation and the structure and surface characteristics of the invading vascular cells and the retinal tissue. Arterio-venous differentiation, however, may be dominated by diffusion processes.

Corneal vascularisation and its relation to the physical properties of the tissue: a fractal analysis.

Various pathological conditions may cause vascularisation of the normally avascular and transparent cornea. The purpose of this study was to investigate the fractal geometry of corneal vascularisation and relate it to different growth models which may have implications for the understanding of fundamental processes involved in vasculogenesis. Photographs of 12 cases of severe superficial corneal vascularisation were obtained from accidentally alkali burned eyes long after the acute inflammatory reaction was over. The fractal dimension of these vessel patterns was calculated by means of the density-density-correlation function method to be D = 1.893 +/- 0.044 (m +/- sd) (n = 12). It is in excellent agreement with percolation models. The results suggest the importance of the surface characteristics of the invading cells as well as that of the extracellular matrix and the related interaction between them.

Hereditary vitreoretinal dystrophy associated with peripheral neuropathy.

Autosomal dominant inherited vitreoretinal dystrophy has been reported to occur as isolated ocular disease (Wagner's disease) or in combination with systemic manifestations (e.g., Stickler's syndrome). We examined five members of one family (three generations) and found vitreoretinal dystrophy and non-ocular signs in a mother and her two children. In the mother we also observed tractional detachment of the macula. In addition to routine ophthalmological examinations, we performed electrophysiological tests (ERG, EOG), adaptometry and magnetic resonance imaging of the head. Neurological examination revealed peripheral neuropathy in the mother and her children. We had no evidence that the neuropathy had a toxic or metabolic origin, and other genetically determined neuropathies were unlikely based on the clinical picture, MRI, and laboratory tests. Therefore, the neuropathy might be either a hitherto unrecognized feature of a variant of Stickler's syndrome or part of a yet unclassified hereditary vitreoretinal dystrophy with systemic involvement.

Proton relaxation times of the vitreous body in hereditary vitreoretinal dystrophy.

We performed proton magnetic resonance imaging of the vitreous body in a 37-year-old mother and her 14-year-old son who suffered from autosomal dominant vitreoretinal dystrophy. Both showed the characteristic signs of the disease including premature liquefaction of the vitreous. Magnetic resonance imaging at 1.5 T using a standard head coil yielded a shortened mean (+/- SD) transverse proton relaxation time (T2) of the vitreous in our patients (T2 = 311 +/- 22 ms) in comparison with 8 eyes of normal volunteers (T2 = 546 +/- 157 ms). The longitudinal proton relaxation time (T1) showed a tendency towards lower values in the patients (T1 = 2,928 +/- 207 ms) but was not significantly decreased when compared with normal volunteers (T1 = 3,257 +/- 307 ms). The decrease in the T2 times in our patients is in accordance with previous in vitro studies of artificial vitreous liquefaction in bovine eyes and provides information on the mechanism of vitreous liquefaction in vitreoretinal dystrophy.

Nuclear magnetic resonance spectroscopy. Principles and applications in neuroophthalmology.

Magnetic resonance spectroscopy is a valuable method for the non-invasive investigation of metabolic processes and can now be combined with conventional magnetic resonance imaging in patients. This article gives a brief introduction into the principles and physiological and clinical applications of in vivo proton magnetic resonance spectroscopy, surveys experiences in healthy volunteers and presents exemplary results in patients suffering from cortical blindness or visual field defects. The causes of visual loss include brain trauma, cerebral ischemia, and brain tumors. In traumatic, ischemic and neoplastic lesions, an important spectral finding is an elevated lactate resonance which has been explained by increased anaerobic glycolysis of ischemic brain tissue and macrophages invading necrotic tissue. In our investigations using a clinical spectroscopy protocol on a 1.5 T MR system, a significant lactate signal was absent in spectra obtained from the visual cortex of normal volunteers, even during photic stimulation with a stroboscope. Other spectral changes in the patients include a decreased N-acetyl-aspartate resonance which indicates a decreased number of viable neurons in the examined brain region.

Spectral transmission of the optical media of the human eye with respect to keratitis and cataract formation.

The spectral transmissions of cornea, aqueous humour, lens and vitreous humour of human eyes were measured in the range from 250 nm to 800 nm in 1 nm steps using a high resolution double monochromator. Cornea and lens are good cut off filters; 1% transmission was measured in various cornea samples between 291 and 298 nm, and in different lenses between 389 and 414 nm. Aqueous humour and vitreous humour showed high transparency (80%) at lambda > 320 nm. The wavelength range of keratitis effective irradiance was found to be completely within the wavelength range of absorption of the cornea, that of cataract effective irradiance was found to be at the short wavelength end partly outside the wavelength range of absorption of the lens. It may therefore be supposed that the action spectrum of cataract obtained by animal experiments is applicable to the human eye only with certain reservations.