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Precocious invasion of the optic stalk by transient retinopetal axons.

This study demonstrates that the fetal optic nerve contains a conspicuous population of transient retinopetal axons. Implants of the carbocyanine dye, DiI, were made into the retina or diencephalon of fetal ferrets to label the retinopetal axons retrogradely or anterogradely, respectively, and sections were immunostained for beta-tubulin to label the early differentiating axons in the optic nerve. Dye implants into the optic nerve head, but not the retinal periphery, retrogradely labeled somata in the ventrolateral diencephalon, provided the implants were made before embryonic day (E) 30. When dye implants were made into the ventrolateral diencephalon, these same retinopetal axons were anterogradely labeled, coursing through the optic nerve but never invading the retina. The axons course as 2-5 fascicles from their cells of origin and turn laterally to enter the optic nerve where it joins the future hypothalamus. The retinopetal cells can be retrogradely labeled as early as E20, before optic axons have left the retina. The optic nerve and fiber layer are immunoreactive for beta-tubulin on E24 and thereafter, whereas on E20 and E22, they are immunonegative. Yet at these early embryonic ages, immunopositive fascicles of axons course from the diencephalon into the optic stalk, confirming the precocious nature of the retinopetal projection. Implants of dye made into the future optic nerve head at these very early stages also retrogradely label retinopetal cells in the future chiasmatic region. These cells are distributed primarily on the side ipsilateral to the midline, but a few can be found contralateral to it. Both these, as well as the retinopetal axons arising from the ventrolateral diencephalon, may serve a transient guidance function for later developing optic axons.

Afferent Pathways↗

Hyaluronic acid in the normal and glaucomatous optic nerve.

Eighteen normal human eye-bank eyes (age: 18-81 years), five fetal eyes (16-24 weeks), 11 primary open-angle glaucoma (POAG) eyes (age: 76-89 years), and two Schnabel's cavernous optic atrophy eyes were examined using a biotinylated-hyaluronan binding protein to study the changes in the distribution of hyaluronic acid (HA) in the fetal, adult and glaucomatous optic nerve head. The vitreous body served as a positive control. Sections treated with Streptomyces hyaluronidase were used to confirm specificity. Monoclonal antibodies to myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) were used as additional controls. In fetal optic nerve, HA was localized in blood vessels, peripapillary sclera and the pial septae in the retrolaminar nerve. No staining was associated with axons. Staining for MBP was negative. In adults, HA was found surrounding the myelin sheaths in the retrolaminar nerve; staining decreased with age. In contrast, HA staining in myelinated peripheral nerves (e.g. ciliaries) remained unchanged with age. HA also was localized to the adventitia of arteries and veins throughout the posterior segment. Compared to age-matched normal eyes, HA staining was virtually absent around myelin sheaths of the retrolaminar nerve in POAG eyes. Similar changes were not found in other HA positive structures. In Schnabel's cavernous optic atrophy. HA was present in increased amount in the atrophic area, but virtually absent in the remaining retrolaminar nerve. HA staining was invariably positive in vitreous, and Streptomyces hyaluronidase treated sections were negative. In adults, staining of MBP was associated with the myelin sheath in the retrolaminar nerve. In contrast to HA, staining of MBP was unchanged with age and in POAG. In Schnabel's atrophy, MBP staining disappeared only in the atrophic area. HA in the retrolaminar optic nerve appears to be associate with the space-filling matrix between myelin sheaths. HA is not present in the axon bundles prior to myelination of the optic nerve. HA in the retrolaminar optic nerve appears to decrease with age and is further reduced in POAG; however, corresponding changes are not found in MBP or in peripheral nerves. Perhaps, decreased amounts of HA is related to a higher susceptibility to elevated intraocular pressure or to optic nerve atrophy. In Schnabel's cavernous optic atrophy, HA is present in increased amount only in the atrophic area while MBP is markedly decreased, suggesting in situ production of HA in areas of optic nerve atrophy.

Adolescent↗

Surgically verified case of optic sheath nerve meningocele: case report with review of the literature.

Optic sheath meningocele is rare; only approximately 31 cases have been reported. The term optic sheath meningocele has recently been proposed by Garrity and Forbes to describe primary CSF cysts of the optic nerve sheath, without apical mass or malformation of the cranio-orbital junction. Presenting symptoms are often related to involvement of the optic nerve, with a slow or rapid decrease of visual acuity. CT and MRI studies reveal a tubular-cystic enlargement of the optic nerve/optic sheath complex (on/onsc), with thickening of the optic nerve. Radiological differential diagnosis should include optic nerve tumors such as gliomas, meningiomas, and arachnoid cysts involving the optic nerve sheath. Up to now, it seems that early surgical management by means of optic nerve/optic nerve sheath decompression affords an improvement of visual function with minimal morbidity in patients who present a rapid decrease of visual acuity within 3-6 months. We present an additional case and discuss the clinical, radiological, and operative features of this pathological condition of the optic nerve sheath.

Adolescent↗

Unilateral adult malignant optic nerve glioma.

INTRODUCTION: Adult malignant optic nerve gliomas are rare and rapidly fatal visual pathway tumours. They represent a clinical entity different from the more common childhood benign optic nerve gliomas, which are frequently associated with neurofibromatosis I. CASE REPORT: A 61-year-old woman presented with rapidly progressing right vision loss, lower altitudinal visual field defect and papilloedema. MRI showed intraorbital and intracranial swelling of the right optic nerve. Resection of the intracranial part of the right optic nerve up to the chiasm revealed anaplastic astrocytoma grade III. Within 1 year, the patient died of leptomeningeal metastasis despite radiotherapy. Clinical and MRI evaluation of the left eye and optic nerve were normal at all times. DISCUSSION: Unilateral adult malignant glioma of the optic nerve is exceptional. The final diagnosis was only confirmed by optic nerve biopsy. In the literature, only one patient has been reported with a unilateral tumour manifestation; he was lost to follow-up 3 months later. All other cases were bilateral. To date, 44 case reports of adult malignant optic nerve glioma have been published, either malignant astrocytoma or glioblastoma. These tumours can mimic optic neuritis in their initial presentation. The diagnosis is seldom made before craniotomy. On MRI images, malignant glioma cannot be distinguished from optic nerve enlargement due to other causes. Although radiotherapy appears to prolong life expectancy, all presently available treatment options (radiation, surgery, radio-chemotherapy) are of limited value. Most patients go blind and die within 1 or 2 years.

Fatal Outcome↗

Traumatic optic neuropathy.

Knowledge concerning the pathophysiologic mechanisms of traumatic optic neuropathy is limited. The optic nerve is a tract of the brain. Therefore, the cellular and biochemical pathophysiology of brain and spinal cord trauma and ischemia provide insight into mechanisms that may operate in traumatic optic neuropathy. The dosage of methylprednisolone (30 mg/kg/6 hours) which was successful in the National Acute Spinal Cord Injury Study 2 (NASCIS 2) evolved from the unique pharmacology of corticosteroids as antioxidants. The management of traumatic optic neuropathy rests on an accurate diagnosis which begins with a comprehensive clinical assessment and appropriate neuroimaging. The results of medical and surgical strategies for treating this injury have not been demonstrated to be better than those achieved without treatment. The spinal cord is a mixed grey and white matter tract of the brain in contrast to the optic nerve which is a pure white matter tract. The treatment success seen with methylprednisolone in the NASCIS 2 study may not generalize to the treatment of traumatic optic neuropathy. Conversely, if the treatment does generalize to the optic nerve, NASCIS 2 data suggests that treatment must be started within eight hours of injury, making traumatic optic neuropathy one of the true ophthalmic emergencies. Given the uncertainties in the treatment, ophthalmologists involved in the management of traumatic optic neuropathy are encouraged to participate in the collaborative study of traumatic optic neuropathy.

Administration, Topical↗

Radiation optic neuropathy after megavoltage external-beam irradiation: analysis of time-dose factors.

PURPOSE: To investigate the risk of radiation-induced optic neuropathy according to total radiotherapy dose and fraction size, based on both retrospective and prospectively collected data. METHODS AND MATERIALS: Between October 1964 and May 1989, 215 optic nerves in 131 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 21 years). The clinical end point was visual acuity of 20/100 or worse as a result of optic nerve injury. RESULTS: Anterior ischemic optic neuropathy developed in five nerves (at mean and median times of 32 and 30 months, respectively, and a range of 2-4 years). Retrobulbar optic neuropathy developed in 12 nerves (at mean and median times of 47 and 28 months, respectively, and a range of 1-14 years). No injuries were observed in 106 optic nerves that received a total dose of < 59 Gy. Among nerves that received doses of > or = 60 Gy, the dose per fraction was more important than the total dose in producing optic neuropathy. The 15-year actuarial risk of optic neuropathy after doses of > or = 60 Gy was 11% when treatment was administered in fraction sizes of < 1.9 Gy, compared with 47% when given in fraction sizes of > or = 1.9 Gy. The data also suggest an increased risk of optic nerve injury with increasing age. CONCLUSION: As there is no effective treatment of radiation-induced optic neuropathy, efforts should be directed at its prevention by minimizing the total dose, paying attention to the dose per fraction to the nerve, and using reduced-field techniques where appropriate to limit the volume of tissues that receive high-dose irradiation.

Adolescent↗

Optic gliomas in neurofibromatosis type 1: role of visual evoked potentials.

Optic gliomas occur in 15% of patients with neurofibromatosis type 1 (NF 1) and are a significant cause of morbidity. Of these tumors, 20-30% become symptomatic, usually before age 10 years. Previous studies have suggested that visual evoked potentials (VEPs) are a sensitive method for the detection of asymptomatic optic gliomas. Because routine neuroimaging of children with NF 1 is currently not recommended, the role of pattern-shift VEPs (PS VEPs) as a screening test for optic gliomas was evaluated. PS VEPs were performed on 10 children with NF 1 and optic gliomas and 20 children with NF 1 and normal visual pathways (as defined on MRI). PS VEPs had 90% sensitivity for detecting optic gliomas, with an increase in sensitivity to 100% when hemifield stimulation was used. The specificity of the test was 60%. Four of 20 children without optic gliomas had thickened optic nerves on computed tomography which represented dural ectasia with normal visual pathways on MRI; PS VEPs were normal in these patients. The efficacy of PS VEPs as a routine screen for optic gliomas is limited by the age at which children will cooperate with the test procedure and the high incidence of false-positive results; however, VEPs do provide a useful adjunct to routine clinical ophthalmologic assessment in the detection of optic gliomas in children with NF 1. Abnormal test results provide a stronger indication for neuroimaging. The early detection of optic gliomas allows for close monitoring of tumor progression and earlier intervention prior to significant visual loss.

Adolescent↗

Mitochondrial dysfunction as a cause of optic neuropathies.

Mitochondria are increasingly recognized as central players in the life and death of cells and especially of neurons. The energy-dependence of retinal ganglion cells (RGC) and their axons, which form the optic nerve, is singularly skewed. In fact, while mitochondria are very abundant in the initial, unmyelinated part of the axons anterior to the lamina cribrosa, their number suddenly decreases as the myelin sheath begins more posteriorly. The vascular system also presents different blood-brain barrier properties anterior and posterior to the lamina, possibly reflecting the different metabolic needs of the optic nerve head (unmyelinated) and of the retrobulbar optic nerve (myelinated). Mitochondrial biogenesis occurs within the cellular somata of RGC in the retina. It needs the coordinated interaction of nuclear and mitochondrial genomes. Mitochondria are then transported down the axons and distributed where they are needed. These locations are along the unmyelinated portion of the nerve, under the nodes of Ranvier in the retrobulbar nerve, and at the synaptic terminals. Efficient transportation of mitochondria depends on multiple factors, including their own energy production, the integrity of the cytoskeleton and its protein components (tubulin, etc.), and adequate myelination of the axons. Any dysfunction of these systems may be of pathological relevance for optic neuropathies with primary or secondary involvement of mitochondria. Leber's hereditary optic neuropathy (LHON) is the paradigm of mitochondrial optic neuropathies where a primary role for mitochondrial dysfunction is certified by maternal inheritance and association with specific mutations in the mitochondrial DNA (mtDNA). Clinical phenocopies of this pathology are represented by the wide array of optic neuropathies associated with vitamin depletion, toxic exposures, alcohol and tobacco abuse, and use of certain drugs. Moreover, the recent identification of mutations in the nuclear gene OPA1 as the causative factor in dominant optic atrophy (DOA, Kjer's type) brought the unexpected finding that this gene encodes for a mitochondrial protein, suggesting that DOA and LHON may be linked by similar pathogenesis. Polymorphisms in this very same gene may be associated with normal tension glaucoma (NTG), which might be considered a genetically determined optic neuropathy that again shows similarities with both LHON and DOA. Exciting new developments come from first examples of mitochondrial optic neuropathies in animal models that are genetically determined or are the result of ingenious engineering of mitochondrial gene expression, or from biochemical manipulations of the respiratory complexes. Even more exciting is the first successful attempt to correct the LHON-related complex I dysfunction by the allotopic nuclear expression of the recoded mitochondrial gene. There is hope that the genetic complexities, biochemical dysfunctions, and integrated anatomical-physiological cellular relationships will soon be precisely delineated and that promising therapeutic and prophylactic strategies will be proposed.

Animals↗

Management of optic neuritis.

To improve understanding and effectiveness of therapy in optic nerve disease, various causes of so-called optic neuritis should be identified when possible. The clinical characteristics of demyelinating optic neuropathy can be contrasted with those of ischemic optic neuropathy, nutritional optic neuropathy, true optic nerve inflammation (e.g., luetic), optic nerve infiltration with tumor, and compression neuropathy caused by adjacent tumor. Radiologic studies and other means of investigating patients with optic neuritis are reviewed. Arguments in favor of, and against, treatment of presumed demyelinating optic neuritis are presented along with representative corticosteroid treatment regimens. The natural tendency toward spontaneous improvement of optic neuritis makes the effect of treatment difficult to assess.

Adrenocorticotropic Hormone↗

First application of extremely high-resolution magnetic resonance imaging to study microscopic features of normal and LHON human optic nerve.

PURPOSE: To apply new methods in magnetic resonance imaging (MRI) in resolving the histoarchitecture of the human optic nerve obtained from normal individuals and a Leber's hereditary optic neuropathy (LHON) case. DESIGN: Small case series--clinicopathologic correlation. METHOD: Three optic nerves were obtained from two normal subjects, aged 69 and 70, and a LHON/3460 patient, aged 75. The posterior pole of the eye with attached optic nerves was fixed in buffered paraformaldehyde and placed into a 10-mm quartz tube. Images were acquired in a Bruker AMX500 12 Tesla microimaging system. The three-dimensional data were acquired with 512 x 256 x 256 points, yielding a final isotopic resolution of 30 microm. RESULTS: The sclera, choroids, and retina were easily distinguished. The nerve fiber layer was seen to enter the optic disc and traverse the lamina cribrosa (LC). The resolution of the image of the optic nerve head was such that the LC was visualized as multiple stacked plates. The fibers emerged from glial columns in the LC as distinct fascicles and could be made out to change appearance as they became myelinated and expanded in the more posterior nerve. The ophthalmic artery and vein were visualized, as were the optic nerve arachnoid and dural sheaths. In the Leber's case, the LC plates seemed collapsed or compressed. The axonal bundles were atrophic and the pial-collagen septae markedly thickened. The entire nerve had shrunk, creating space under the arachnoid, down and around the central ophthalmic artery and vein. CONCLUSIONS: These results demonstrate the feasibility of using extremely high-resolution magnetic resonance imaging (microMRI) to examine the three-dimensional (30 microm) images of the human optic nerve. Several atrophic lesions, normally visible only by histopathologic examination, were visualized in the Leber's optic nerve. microMRI may eventually permit the in vivo visualization of lesions in or about the optic nerve.

Aged↗

Enhancement and demyelination of the intraorbital optic nerve. Fat suppression magnetic resonance imaging.

Conventional spin-echo magnetic resonance imaging (MRI) of intraorbital optic neuritis is hampered by the adjacent high signal and chemical shift artifact of orbital fat. Frequency-selective saturation pulse MRI reduces these problems and was used to determine its utility in evaluation of intraorbital optic neuritis. Eight consecutive patients with optic neuritis underwent MRI within 1 week of the onset of visual loss. Conventional MRI with T1, proton density, and T2 weighting and frequency-selective saturation pulse MRI with T1, proton density, and T2 weighting were performed. After administration of intravenous gadopentetate dimeglumine, T1-weighted conventional and frequency-selective saturation pulse MRI were performed. Frequency-selective saturation pulse MRI showed gadopentetate dimeglumine enhancement in the intraorbital optic nerve in 7 patients and the intracranial optic nerve in 3 patients. Conventional MRI failed to show optic nerve gadopentetate dimeglumine enhancement in patients with intraorbital lesions, but did show intracranial lesions. Frequency-selective saturation pulse MRI showed bilateral optic nerve enhancement in 3 patients with unilateral visual signs and symptoms. Proton density and T2-weighted conventional MRI of the brain showed no convincing signal aberrations in the optic nerves. In the MRI evaluation of intraorbital optic neuritis: (1) frequency-selective saturation pulse fat suppression MRI is superior to T1-weighted conventional MRI in the detection of gadopentetate dimeglumine enhancement; (2) frequency-selective saturation pulse proton density and T2-weighted MRI is superior to proton density and T2-weighted conventional MRI; (3) frequency-selective saturation pulse MRI showed gadopentetate dimeglumine enhancement as well as proton density/T2-weighted signal aberration in exactly the same portion of the intraorbital optic nerve.

Adult↗

Focal narrowing of retinal arterioles in optic nerve atrophy.

PURPOSE: To investigate the occurrence of focal narrowing of retinal arterioles in optic neuropathies. PATIENTS AND METHODS: Color stereo optic disc photographs of patients with primary open-angle glaucoma (n = 114), pseudoexfoliative glaucoma (n = 41), normal-pressure glaucoma (n = 54), ocular hypertension (n = 45), nonarteritic anterior ischemic optic neuropathy (n = 20), descending optic nerve atrophy (n = 60), and control subjects (n = 100) were morphometrically examined in a masked fashion. Focal narrowing of the retinal arterioles was estimated on a scale ranging from 0 to 6. RESULTS: In the control subjects, focal vessel narrowing was significantly and positively correlated with age (P < 0.05). It occurred significantly more often and was more pronounced in eyes with optic neuropathies than in the normal eyes when matched for age. In the eyes with glaucoma, focal narrowing of the arterioles was significantly (P < 0.01) correlated with the degree of optic nerve damage. In addition to a tendency toward a more marked vessel narrowing in the eyes with normal-pressure glaucoma, it did not vary significantly between the various glaucoma types and other optic neuropathies. It was independent of an enlarged parapapillary chorioretinal atrophy. DISCUSSION: Similar to general constriction, focal narrowing of the retinal arterioles is found more frequently and is more marked in eyes with glaucomatous or nonglaucomatous optic nerve damage than in normal eyes. It is correlated with the degree of optic nerve damage, and is typical for optic nerve atrophy, but not pathognomonic for glaucoma.

Adolescent↗

Are optic disc drusen inherited?

OBJECTIVE: To conduct family studies of the incidence of optic disc drusen and related optic disc anomalies among relatives of those affected. DESIGN: Retrospective case series with prospective examination of patients and their relatives using B-scan ultrasonography and color photography. PARTICIPANTS: A total of 27 relatives of 7 probands with bilateral optic disc drusen were examined. MAIN OUTCOME MEASURES: Presence of optic disc drusen on clinical examination or B-scan ultrasonography and presence of related anomalies, including absence of optic disc cup and presence of anomalous vasculature. RESULTS: Only 1 of 27 relatives had optic disc drusen (3.7%). Thirty of 53 eyes had anomalous vessels (57%), and 26 eyes had no optic cup (49%). CONCLUSION: The primary pathology of optic disc drusen is likely to be an inherited dysplasia of the optic disc and its blood supply, which predisposes to the formation of optic disc drusen.

Adolescent↗

Optic neuritis in chronic relapsing experimental allergic encephalomyelitis in Biozzi ABH mice: demyelination and fast axonal transport changes in disease.

The encephalitogenicity of optic nerve tissue was demonstrated in Biozzi ABH (H-2(dq1)) mice. Acute experimental allergic encephalomyelitis (EAE) occurred in 11/14 animals and 4/5 exhibited relapse. The involvement of the optic nerve in spinal cord homogenate induced chronic relapsing EAE (CREAE) was demonstrated by mononuclear cell infiltration and myelin degradation in the optic nerve prior to and during clinical disease. During the relapse phase gross pathological assessment revealed swollen and translucent plaques on the optic nerves. Advanced lesions showed widespread demyelination, astrocytic gliosis and fibrotic changes of the blood vessels. Physiologically, the fast axonal transport of proteins from the retina to the optic nerve and superior colliculus was significantly decreased during relapse. The association of inflammation and demyelination with physiological deficit in the optic nerve highlights the usefulness of this model in the study of multiple sclerosis in which acute monosymptomatic unilateral optic neuritis is a common manifestation. Furthermore, the novel induction of CREAE with optic nerve homogenate suggests that optic neuritis is a common significant role in the pathophysiology and progression of neurological disease in CREAE which may be relevant to studies of optic neuritis in multiple sclerosis.

Animals↗

Organization of retinal ganglion cell axons in the optic fiber layer and nerve of fetal ferrets.

Previous authors have hypothesized that retinotopic projections may be influenced by 'preordering' of the axons as they grow towards their targets. In some nonmammalian species, axons are reorganized at or near the optic nerve head to establish a retinotopic order. Data are ambiguous concerning the retinotopy of the mammalian retinal nerve fiber layer and whether fibers become reorganized at the optic nerve head. We have examined this question in fetal and newborn ferrets (Mustela putorius furo) by comparing the arrangement of axons in the retinal nerve fiber layer with that in the optic nerve. Dil or DiA crystals were implanted into fixed tissue in the innermost layers of the retinal periphery, or at a location midway between the periphery and the optic nerve head. Fluorescence labelling was examined in 100-200 microns Vibratome sections, or the eyecup and nerve were photooxidized and 1-2 microns longitudinal or transverse sections were examined. Regardless of fetal age, eccentricity or quadrant of the implant site, a segregation of labelled peripheral axons from unlabelled central ones was not detected within the nerve fiber layer. Axons coursed into the nerve head along the margin of their retinal quadrant of origin, often entering the optic nerve as a radial wedge, thus preserving a rough map of retinal circumference. However, peripheral axons were in no way restricted to the peripheral (nor central) portions of the nerve head or nerve, indicating that the optic axons do not establish a map of retinal eccentricity. Our results demonstrate that (1) the nerve fiber layer is retinotopic only with respect to circumferential position and (2) optic axons are not actively reorganized to establish a retinotopic ordering at the nerve head. The present results suggest that any degree of order present within the optic nerve is a passive consequence of combining the fascicles of the retinal nerve fiber layer; optic axons are not instructed to establish, nor constrained to maintain, a retinotopic order within the optic nerve.

Animals↗

Detection of changes of the optic disc in glaucomatous eyes: clinical examination and image analysis with the Topcon Imagenet system.

PURPOSE: This study was designed to evaluate the clinical agreement in the detection of optic disc changes and the ability of computerized image analysis to detect glaucomatous deterioration of the optic disc. METHODS: Pairs of stereophotographs of 35 glaucomatous optic discs taken 5 years apart and of 5 glaucomatous discs photographed twice on the same day. Two glaucoma specialists examined the pairs of stereophotographs (35 cases and 5 controls) in a masked manner and judged whether the optic disc showed changes in the optic disc compatible with progression of glaucomatous damage. The stereophotographs of the five optic discs photographed twice on the same day (which by definition did not change) and of five cases judged to have deteriorated by both glaucoma specialists were analyzed by computerized image analysis with the Topcon ImageNet system. Intra- and inter-observer agreement in the detection of optic disc changes (evaluated using kappa statistic), and changes in the rim area to disc area ratio (evaluated using descriptive statistics and paired t-test). RESULTS: Intra-observer agreement had a kappa value of 0.75 for observer 1 and 0.60 for the observer 2. Inter-observer agreement between the glaucoma specialists had a kappa value of 0.60. The image analyzer did not discriminate between controls and cases with clinically apparent glaucomatous change of the optic disc. CONCLUSION: Clinical agreement in detecting changes in the optic disc was moderate to substantial. Computerized image analysis with the Topcon ImageNet system appeared not to be useful in detecting glaucomatous changes of the optic disc.

Disease Progression↗

[3-dimensional topography of the optic papilla with laser scanning tomography: clinical correlation of cluster analysis].

BACKGROUND The evaluation of optic disc topography is essential for the clinical diagnosis of primary open angle glaucoma. The purpose of this study was (1) to establish a computerized cluster formation of optic nerve head topography based on quantitative three-dimensional parameter values and (2) to describe the resulting clusters according to morphological appearance and visual fields. PATIENTS AND METHODS 337 optic nerve heads (glaucomatous optic neuropathy (n = 99), glaucoma suspects (n = 159), normals (n = 79) were analyzed using laser scanning tomography. A hierarchical cluster analysis was performed based on standardized variables (optic disc area, rim area, area-ratio, cup depth, cup steepness, height variations along the contour-line). Visual fields were tested by computerized static threshold perimetry. RESULTS A seven cluster solution met the optimizing criteria. The characteristic morphology of the clusters can be described as "normal" (N), "normal, large" (NL), "supernormal" (SN), "pseudonormal" (PN), "glaucoma-like-flat" (GF), "glaucoma-like-steep" (GS) and "macropapillary" (M). Visual fields were normal in 180 eyes. 99 eyes had glaucomatous field defects, 58 eyes revealed isolated relative scotomas < 10 db. Presence and degree of visual field defects varied within the automatically classified optic disc groups considerably. Visual field defects were found in 7.7% (SN), 8.3% (N), 18.8% (NL), 33.3% (M), 37% (PN), 64.7% (GF) and 83.3% (GS) respectively. Pseudonormal discs were characterized by a flattening of the height variations along the disc border. CONCLUSIONS (1) Optic nerve heads may be automatically classified based upon a combination of three-dimensional topographic variables. (2) Analysis of optic disc topography and computerized perimetry are supplementary tools in the evaluation of the glaucoma patient. Visual field defects may be present within any cluster. However, the likelyness of the presence of visual field defects differs considerably among the topometrically defined groups of optic nerve heads. Functional damage is to be expected in association with reduced height variations along the disc border, a small rim area and a steep cupping of the optic nerve head.

Cluster Analysis↗

Optic nerve regeneration in adult fish and apolipoprotein A-I.

Fish optic nerves, unlike mammalian optic nerves, are endowed with a high capacity to regenerate. Injury to fish optic nerves causes pronounced changes in the composition of pulse-labeled substances derived from the surrounding non-neuronal cells. The most prominent of these injury-induced changes is in a 28-kilodalton (kDa) polypeptide whose level increases after injury, as revealed by one-dimensional gel electrophoresis and autoradiography. The present study identified as apolipoprotein A-I (apo-A-I) a polypeptide of 28 kDa in media conditioned by regenerating fish optic nerves. The level of this polypeptide increased after injury by approximately 35%. Apo-A-I was isolated by gel-permeation chromatography from delipidated high-density lipoproteins (HDL) that had been obtained from carp plasma by sequential ultracentrifugation. Further identification of the purified protein as apo-A-I was based on its molecular mass (28 kDa) as determined by gel electrophoresis, amino acid composition, and microheterogeneity studies. The isolated protein was further analyzed by immunoblots of two-dimensional gels and was found to contain six isoforms. Western blot analysis using antibodies directed against the isolated plasma protein showed that the 28-kDa polypeptide in the preparation of soluble substances derived from the fish optic nerves (conditioned media, CM) cross-reacted immunologically with the isolated fish plasma apo-A-I. Immunoblots of two-dimensional gels revealed the presence of three apo-A-I isoforms in the CM of regenerating fish optic nerves (pIs: 6.49, 6.64, and 6.73). At least some of the apo-A-I found in the CM is derived from the nerve, as was shown by pulse labeling with [35S]methionine, followed by immunoprecipitation. The apo-A-I immunoactive polypeptides in the CM of the fish optic nerve were found in high molecular-weight, putative HDL-like particles. Immunocytochemical staining revealed that apo-A-I immunoreactive sites were present in the fish optic nerves. Higher labeling was found in injured nerves (between the site of injury and the brain) than in non-injured nerves. The accumulation of apo-A-I in nerves that are capable of regenerating may be similar to that of apo-E in sciatic nerves of mammals (a regenerative system); in contrast, although its synthesis is increased, apo-A-I does not accumulate in avian optic nerves nor does apo-E in rat optic nerves (two nonregenerative systems).

Animals↗