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.

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 MR imaging anatomy of the orbit. Correlation with comparative cryosectional anatomy.

High resolution MR imaging of the orbit enables visualization of anatomic details in the orbit, including important blood vessels, muscles, nerves and connective tissue structures. The best resolution of anatomic details currently is obtained by using surface coils and T1-weighted spin echo sequences. Some examples of clinical applications demonstrate that a detailed knowledge of orbital imaging anatomy is a prerequisite for successful interpretation of clinical MR images. Additionally, this noninvasive diagnostic technique may be used for anatomical in vivo studies.

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.

Functional anatomy of the levator palpebrae superioris muscle and its connective tissue system.

AIMS/BACKGROUND: The connective tissue system of the levator palpebrae superioris muscle (LPS) consists of the septa surrounding its muscle sheath, the superior transverse ligament (STL) commonly referred to as 'Whitnall's ligament' and the common sheath which is the fascia between the LPS and the superior rectus muscle (SRM). The anterior band-like component of the common sheath is called transverse superior fascial expansion (TSFE) of the SRM and LPS. It mainly extends from the connective tissue of the trochlea to the fascia of the lacrimal gland. A detailed description of the relation between the LPS and its connective tissue is presented. Furthermore, the course of the LPS in the orbit is described. The study was conducted to provide a morphological basis for biomechanical and clinical considerations regarding ptosis surgery. METHODS: Postmortem dissections were performed in 16 orbits from eight cadavers. The microscopical anatomy was demonstrated in six formalin preserved orbits from six cadavers which had been sectioned in the frontal and sagittal plane and stained with haematoxylin and azophloxin. Surface coil magnetic resonance imaging in the sagittal and coronal plane was performed in five orbits from five normal volunteers using a T1 weighted spin echo sequence. RESULTS: The STL and the TSFE surround the LPS to form a fascial sleeve around the muscle which has attachments to the medial and lateral orbital wall. The TSFE, which is thicker than the STL, blends with Tenon's capsule. The STL and the fascial sheath of the LPS muscle are suspended from the orbital roof by a framework of radial connective tissue septa. MR images show that the TSFE is located between the anterior third of the superior rectus muscle and the segment of the LPS muscle where it changes its course from upwards to downwards. In this area, the LPS reaches its highest point in the orbit (culmination point). The culmination point is located a few millimetres posterior to the equator and superior to the globe. CONCLUSION: Whitnall's ligament can be considered to consist of two distinct parts--the TSFE inferior to the LPS and the STL superior to the LPS. Since the medial and lateral main attachments of Whitnall's ligament are situated inferior to the level of the culmination point of the LPS, the ligament itself is unlikely to suspend the levator muscle. However, a suspension of the LPS may be achieved by the radial connective tissue septa of the superior orbit. The TSFE in connection with the globe may have an additional supporting function. The elasticity of Whitnall's ligament and its connections with highly elastic structures including Tenon's capsule, may provide the morphological substrate for the previously proposed passive (that is, without orbicularis action) lowering of the lid during downward saccades.

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.

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.

[Orbital decompression in endocrine orbitopathy: advantages and disadvantages of different methods]. / Orbita-Dekompression bei endokriner Orbitopathie: Vor- und Nachteile verschiedener Methoden.

Based on the disease activity score, current indications for orbital decompression are described. After that, all contemporary decompression techniques are mentioned and their advantages and disadvantages are described. Transpalpebral fat resection is also included. Results (reduction of proptosis, complications) are presented for the coronal and transconjunctival (swinging eyelid and transcaruncular orbitotomy) approach used by the author and discussed in comparison with other methods.

[Orbital decompression in graves disease: indications, techniques, results and complications]. / Die Orbitadekompression bei endokriner Orbitopathie: Indikationen, Techniken, Ergebnisse und Komplikationen.

BACKGROUND: The surgical rehabilitation of patients with Graves disease involves orbital decompression and various lid and extraocular muscle procedures. METHODS: We have reviewed the literature and include a presentation of our own results. RESULTS: The indications for orbital decompression include not only functional reasons (optic neuropathy, keratopathy, glaucoma, pain) but also aesthetic and psychosocial reasons without visual problems. Current techniques for orbital decompression (bone versus fat removal) are described and discussed. Results demonstrating a mean reduction of proptosis (4 - 6 mm) and complications (mainly diplopia in 3 - 12 %) are presented for coronal and transconjunctival approaches and compared with other methods. CONCLUSION: Current techniques of orbital decompression are effective and safe and are therefore increasingly used not only for functional but also for aesthetic or "rehabilitative" indications.

[Xerophthalmia in liver cirrhosis. Correct diagnosis after 15 years]. / Xerophthalmie bei Leberzirrhose. Richtige Diagnose nach 15 Jahren.

The clinical features of xerophthalmia are described in a 60-year-old patient, who was known to have alcoholic cirrhosis. In this patient, vitamin A deficiency, which presumably had been overlooked for 15 years, was confirmed by determination of the serum vitamin A level. After substitutive vitamin A therapy, superficial punctate keratitis and conjunctival xerosis disappeared completely. Although xerophthalmia has only sporadically been described in developed countries, we point out that the possibility of a vitamin A deficiency should also be considered in cases of recurrent conjunctival and corneal lesions.

Retinal phakomata associated with cerebral astrocytoma. An incomplete form of Bourneville-Pringle disease?

We report on a 21-year-old, male patient with unilateral retinal phakomata associated with histologically proved cerebral astrocytoma. The patient had presented with bilateral loss of vision and a left-sided hemiparesis. Ophthalmoscopy showed bilateral optic nerve atrophy, multiple punched-out areas of depigmentation and astrocytic hamartomata in the right eye. Despite the absence of classic signs of Bourneville-Pringle disease such as adenoma sebaceum, epilepsy and mental retardation, a strongly presumptive diagnosis of tuberous sclerosis could be made. This unusual case demonstrates that retinal phakomata can be the solely visible manifestation of Bourneville-Pringle disease.

Localized hypertrichosis associated with periorbital neurofibroma: clinical findings and differential diagnosis.

BACKGROUND: Congenital localized hypertrichosis in the periorbital region is an uncommon finding. The authors report two patients with hypertrichosis and cutaneous hyperpigmentation overlying a periorbital neurofibroma. METHODS: In addition to a complete ophthalmic and systemic examination, the patients underwent computed tomography of the head and biopsy of the tumor. RESULTS: Case 1 previously had received a diagnosis of neurofibromatosis type I. On examination, hyperpigmentation, hypertrichosis, and swelling in the right supraorbital region were noted. A computed tomographic scan showed a tumor in the same region. The tumor was removed, and a plexiform neurofibroma was diagnosed. Case 2 was admitted with hyperpigmentation, hypertrichosis, and swelling of the left half of her face. Other signs of neurofibromatosis were absent. A computed tomographic scan showed a tumor, which was underlying the skin changes. Results of histologic examination of the biopsy specimen showed a plexiform neurofibroma. CONCLUSION: Neurofibroma-associated hypertrichosis should be considered in the differential diagnosis of congenital localized hypertrichosis.

Orbital involvement in Waldenström's macroglobulinemia: ultrasound, computed tomography and magnetic resonance findings.

A case of orbital involvement in Waldenström's macroglobulinemia is presented. Orbital echography, computed tomography (CT) and magnetic resonance imaging (MRI) were performed and revealed a retrobulbar mass of the right orbit. Ultrasonography suggested a lymphoid orbital tumor. A CT scan was nonspecific, but helpful in exactly locating the tumor and excluding bony lesions. Signal intensity patterns of MRI were characterized by a low intensity on T1- and T2-weighted images. A marked enhancement of the tumor was evident after intravenous injection of a paramagnetic contrast agent (gadolinium-DTPA). Although the definite diagnosis could only be established by means of an ultrasound-guided fine-needle aspiration biopsy, MRI in connection with the history of our patient strongly suggested a diagnosis of orbital lymphoma in Waldenström's disease.

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.

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.

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.

Corneal edema induced by cold.

We report on a patient, who regularly developed reversible corneal edema of the right eye after cold stress. Cycling tours in cold weather and windy conditions seemed to precipitate the edema. After a provocation test, we also observed transient, corneal edema. A few reports in the literature suggested that Raynaud's disease or trigeminal neuropathy might be responsible for cold-induced corneal opacification. None of these conditions was present in our patient, as proved by laboratory tests and magnetic resonance imaging. We found that contact lenses were an effective prophylaxis against corneal edema.