Neuro-ophthalmic manifestations of diabetes.
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Brain Diseases↗
Biomedical subjects
A A Sadun
Publications and source records attributed to A A Sadun.
Immunolocalization of IL-1beta and IL-6 in optic nerves of patients with AIDS.
PURPOSE: Immunohistochemical procedures were employed to test the hypothesis that cytokines such as interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) are involved in AIDS-related optic neuropathy and to determine the primary cell types involved. METHODS: Fixed sections of six human HIV-1 infected optic nerves were immunostained for the presence of IL-1beta and IL-6, using horseradish peroxidase and diaminobenzidine as markers. RESULTS: IL-1beta and IL-6 were found in astrocytes, macrophages, microglia, and endothelial cells. The great majority of astrocytes demonstrated strong immunoreactivity. CONCLUSION: Our findings support the premise that IL-1beta and IL-6 are significant pro-inflammatory mediators in AIDS-related optic neuropathy. This finding supports the theory that HIV infection stimulates the release of IL-1beta and IL-6 in astrocytes, macrophages, and endothelial cells in the optic nerve which ultimately leads to demyelination, astrogliosis, and neuronal destruction.
Acquired Immunodeficiency Syndrome↗
Microvascular changes in the retrobulbar optic nerve in idiopathic intracranial hypertension.
PURPOSE: To examine the microvascular changes in the retrobulbar optic nerve in idiopathic intracranial hypertension (PTC). METHODS: Both optic nerves from a 29-year-old man with a two year history of PTC were examined histologically and morphometrically. A semi-automated image analysis system and paraphenylenediamine (PPD) stain were employed to resolve sufficiently the microvascular images for counts and measurement. RESULTS: There were 150 vessels distributed in the optic nerves which revealed the following: The average lumen of the vessels in outer sectors were larger than those of the inner sector vessels (168.17 microns 2 vs. 46.99 microns 2; p = 0.0338; OD; and 251.96 microns 2 vs. 130.02 microns 2; p = 0.029; OS) while in the normal control optic nerve the outer and inner area lumens were reversed in size-differential, but this did not show a statistical difference. The thickness of the PTC optic nerve vessel walls in the outer sectors was also greater than that of the walls in the inner sectors (4.95 microns vs. 2.67 microns; p = 0.013; OD and 5.25 microns vs. 3.34 microns; p = 0.019; OS); the same measurements in the normal optic nerve showed a reversed ratio, which was opposite that of the experimental group and but not statistically different. CONCLUSION: This pattern of microvascular changes is consistent with the selective axonal loss in the peripheral area of each optic nerve as much more severe than that in the inner sectors.
Adult↗
Clearing the cornea with nerve growth factor.
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Administration, Topical↗
A histopathologic and morphometric differentiation of nerves in optic nerve hypoplasia and Leber hereditary optic neuropathy.
OBJECTIVES: To characterize and quantitate optic nerve histopathologic and morphometric differences between optic nerve hypoplasia (ONH) as an early and congenital form of intrinsic axonal loss and Leber hereditary optic neuropathy (LHON) as a late and acquired form of intrinsic axonal loss. MATERIALS AND METHODS: Optic nerves from 3 sources were examined: a 42-year-old healthy woman (control), a 53-year-old woman with ONH diagnosed postmortem, and a 74-year-old woman with LHON. The optic nerves were processed, embedded, and stained with a 1% solution of paraphenylene diamine. Histopathologic and morphometric analyses were performed via light microscopy and a semiautomatic computer image analysis system. RESULTS: The ONH showed severe axonal depletion without degenerated profiles in an inferonasal sector, with only a small superotemporal sector having a near normal appearance. The LHON revealed general axonal depletion centrally, fibrocytic scarring, scattered "degeneration dust," and evidence of minimal inflammation, with residual axons limited to superior and temporal peripheral clusters. Morphometric analysis revealed total fiber populations of 98,000 in the ONH optic nerve and 48,000 in the LHON optic nerve, representing 90% and 95% reductions, respectively, compared with the control optic nerve (1.2 million fibers). CONCLUSIONS: Optic nerve hypoplasia and LHON present 2 distinguishable and distinctive patterns of nerve fiber distribution and axonal dropout. The lack of degenerated axons in ONH indicates that any axonal death probably occurred through apoptosis during development. In LHON, degenerated axons and minimal grade of inflammation were obvious, implicating a more "active" pathologic process. This study describes distinctions between these 2 optic neuropathies.
Adult↗
Image enhancement improves reading performance in age-related macular degeneration patients.
We wanted to determine whether the 2- to 4-fold increases in reading speed found for patients with age-related macular degeneration (ARMD) when reading filtered text, presented one word at a time in the middle of the display would also be found when filtered text was scrolled across the screen. Reading speeds for filtered text that compensates for an observer's reduced contrast sensitivity function (CSF) were compared with the reading speeds for unfiltered text, when continuous, non-repeating text was scrolled across the display. The reading speeds of the ARMD observers tested were 1.7-4.5-times faster when reading filtered text, than when reading unfiltered text that was scrolled across the screen. The largest increments, over a 4-fold increase, were obtained in those subjects with the lowest unfiltered reading rates and the greatest loss of central vision. This study illustrates the usefulness of individualized text filtering for image enhancement in digitally based viewing devices to provide low vision remediation.
Aged↗
The role of copper on ethambutol's antimicrobial action and implications for ethambutol-induced optic neuropathy.
The principal side effect of the antimycobacterial agent ethambutol (EMB) is an optic neuropathy with clinical features very similar to a mitochondrial hereditary optic neuropathy (Leber's). The mechanism of EMB-induced optic neuropathy may be EMB's chelation of copper, thereby precluding normal cytochrome c oxidase activity and mitochondrial metabolism in the optic nerve. Before attempting to use therapeutic copper to replenish endogenous stores in an attempt to preclude EMB-induced optic neuropathy, we wished to determine whether EMB is still effective against mycobacteria in the presence of copper. EMB and copper, alone and in combination, were tested against six strains of Mycobacterium tuberculosis and five strains of Mycobacterium avium using a radiometric broth macrodilution assay. Copper did not effect EMB's antimicrobial actions against either species of mycobacteria. This in vitro study suggests that if copper were given to patients to prevent EMB-induced optic neuropathy, it would not compromise EMB's bacteriostatic properties.
Antitubercular Agents↗
Comparison of visual function in fellow eyes after bilateral nonarteritic anterior ischemic optic neuropathy.
PURPOSE: Although previous studies have examined the risk of bilaterality of nonarteritic ischemic optic neuropathy (NAION), none have compared extensively the extent of visual loss between fellow eyes. The authors examined cases of bilateral NAION to determine the extent of vision loss in the second eye compared with that in the first eye. METHODS: Thirty-one cases of bilateral NAION were reviewed. Variables included age, gender, and the presence of comorbid disease. Visual function was assessed by Snellen visual acuity, color vision, and pattern and mean deviation of the visual fields. RESULTS: No correlation was detected between the extent or pattern of visual loss in fellow eyes. No significant difference in visual function existed between first and second eyes for the patients overall. Patients who retained better visual function in the second eye were significantly older than those who retained better visual function in the first eye (visual acuity, P = 0.0005; color vision, P = 0.07; mean deviation, P = 0.02). In patients older than 50 years of age (25 of 31 cases), the second eye had significantly better visual acuity (P = 0.04) and less Humphrey visual field mean deviation (P = 0.04) than the first eye. CONCLUSION: Visual function in the second eye correlated poorly with that of the first eye. Older patients with bilateral NAION retained better visual function in the second eye than in the first eye. For younger patients, the extent of visual loss in the second eye could not be predicted based on the visual loss in the first eye.
Adult↗
An immunohistochemical study of TNF-alpha in optic nerves from AIDS patients.
PURPOSE: Both in vitro and in vivo studies have implicated a role for tumor necrosis factor (TNF-alpha) in the pathology of demyelinating diseases. The purpose of this study was to address the hypothesis that TNF-alpha is a mediator of AIDS-related optic nerve injury and to determine the cell types involved in the proliferation of TNF-alpha in the AIDS optic nerve. METHODS: Ten optic nerves from seven patients with AIDS, and three from persons who were HIV negative were stained, using the indirect immunoperoxidase method. Six of the ten AIDS optic nerves were positive for cytomegalovirus (CMV), but the remainder did not have abnormal fundus findings. RESULTS: In all the optic nerves from AIDS patients with or without CMV retinitis, the vast majority of astrocytes stained strongly for TNF-alpha. Microglial cells (MPS-derived macrophages) varied from not staining to staining strongly positive for TNF-alpha. However, oligodendrocytes were not labeled positively for TNF-alpha. Some endothelial cells also stained for TNF-alpha. Examination of normal optic nerves and controls did not reveal any cell type that stained positively for TNF-alpha. CONCLUSIONS: The present study supports the contention that TNF-alpha is a major mediator of AIDS-associated optic neuropathy. HIV infection induces the production of TNF-alpha in macrophages and astrocytes, which probably causes demyelination and other neuronal damage.
Acquired Immunodeficiency Syndrome↗
Pentoxifylline suppression of TNF-alpha mediated axonal degeneration in the rabbit optic nerve.
In AIDS patients, axonal degeneration in the optic nerve occurs as a histopathological manifestation of the optic neuropathy. Direct infection of neurons by HIV is unlikely, and the axonal injury may be an indirect effect mediated by cytotoxic factors such as tumor necrosis factor-alpha (TNF-alpha) which we have previously demonstrated to cause axonal degeneration in the rabbit optic nerve. To test the suppressive effects of pentoxifylline in preventing TNF-alpha-mediated axonal degeneration, we applied pentoxifylline to an established rabbit model that demonstrates an AIDS-like optic neuropathy using intravitreal TNF-alpha injections. Degenerated axonal profiles were numerous in control rabbit optic nerve (mean 1879) and reduced in rabbits receiving the medium dose of pentoxifylline (300 mg PO BID, mean 439, p < 0.001) and the highest dose of pentoxifylline (600 mg PO BID, mean 120, p < 0.007). High dose pentoxifylline reduced TNF-alpha-induced axonal losses to less than 10% that seen without pentoxifylline pretreatment. Lower doses of pentoxifylline had a lesser but significant protective effect. Our results suggest that TNF-alpha-mediated axonal degeneration can be suppressed by high doses of pentoxifylline. Pentoxifylline may therefore be useful in AIDS patients demonstrating neurological or neuro-ophthalmological symptoms.
Animals↗
Apoptotic photoreceptor cell death after traumatic retinal detachment in humans.
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Apoptosis↗
Rapid growth of an optic nerve ganglioglioma in a patient with neurofibromatosis 1.
BACKGROUND: Optic nerve gangliogliomas are extremely rate tumors of the central nervous system composed of elements of glial and neuronal origin. The clinical and biologic behavior of gangliogliomas depends on the glial component. Pilocytic gangliogliomas generally have a low growth rate and good ultimate prognosis. No definitive relation has yet been established between gangliogliomas and neurofibromatosis type 1. METHODS: The authors describe the clinical, histologic, and immunohistochemical features of an optic nerve ganglioglioma with several atypical findings. A review of the literature is provided. RESULTS: An optic nerve glioma was diagnosed in a 16-year-old patient who had signs of neurofibromatosis type 1; the atypical clinical course involved a rapid progression of symptoms with a significant increase in tumor size. The tumor was removed surgically and found to be a ganglioglioma composed of pilocytic glial cells (immunoperoxidase-positive for glial fibrillary acid protein) and neurons (immunoperoxidase-positive for neuron specific enolase, synaptophysin, and neurofilament). A focal astrocytic area showed increased cellularity, several mitotic figures, and an elevated labeling index with Ki-67 immunoperoxidase staining. CONCLUSION: Optic nerve gangliogliomas are rare tumors that cannot be distinguished clinically from pilocytic astrocytomas. Although these tumors usually grow slowly, careful follow-up is advised. The atypical histologic features are considered to be a manifestation of rapid local growth rather than a harbinger of malignant behavior. The authors' findings suggest that gangliogliomas may be included in the diagnostic criteria for neurofibromatosis type 1.
Adolescent↗
Leber hereditary optic neuropathy.
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Aged↗
Tumor necrosis factor-alpha (TNF-alpha)-induced optic neuropathy in rabbits.
Both in vitro and in vivo studies have implicated a role for tumor necrosis factor-alpha (TNF alpha) in various demyelinating diseases, including HIV-related encephalopathy. To investigate whether intravitreal TNF alpha can induce optic nerve axonal damage in a rabbit eye model, fifteen rabbit eyes were initially injected with TNF alpha (final concentrations: 2U, 20U, and 200U respectively) and studied at varying time intervals for up to 24 weeks post-injection, using light and electron microscopy. Control optic nerves (no injection or diluent injection only) had normal myelinated axons and glia; the myelinated regions, neural retina, retinal glia and vasculature of control retinas were normal. In TNF alpha-exposed optic nerves, intact, degenerating and demyelinated axons were interspersed. Astrogliosis was present, particularly from 8 weeks p.i. and was noted up to 24 weeks. Oligodendrocytes were not severely affected in TNF alpha-exposed optic nerves, and activated macrophages or microglia were not obvious. Axonal degeneration was visible among the more superficial myelinated fibers in TNF alpha-exposed retinas however the neural retina glia were unaffected. These observations suggest that the axonal degeneration induced in TNF alpha-exposed rabbit optic nerves over a 24 week period was most likely related to direct effects of TNF alpha on optic nerve axons, and not primarily due to anterograde degeneration from retinal lesions. In-so-far as neurological pathology in general, and optic nerve degeneration in particular, has been described in AIDS, and TNF alpha levels may be elevated in this disease, it is of great clinical significance that TNF alpha has the capacity to mediate neuronal or axonal injury. If so, strategies to block or inhibit TNF alpha can be pursued for treatment for the neurological symptoms of AIDS.
Animals↗
Preliminary morphometric study of tumor necrosis factor-alpha (TNF alpha)-induced rabbit optic neuropathy.
Intravitreal injections of tumor necrosis factor-alpha (TNF alpha) induce morphological changes in the optic nerve suggesting a primary TNF alpha-induced optic neuropathy. A preliminary morphometric analysis of axonal loss and degeneration in optic nerves of a TNF alpha rabbit eye model was conducted. Fifteen rabbits were injected in one eye only with TNF alpha (final doses: 2 U, 20 U and 200 U respectively), and optic nerve cross-sections were examined using a semi-automated image analysis system, at varying time intervals for up to 24 weeks post-injection. Control optic nerves (uninjected or injected with diluent only) were also assessed. Intact, degenerating and demyelinated axons were visible in TNF alpha-exposed optic nerves. Considerable variation was observed between TNF alpha-exposed optic nerves, however the intact axon density consistently decreased in the 200 U TNF alpha group, although not in the 2 U and 20 U groups. Overall, TNF alpha-exposed optic nerves had significantly more degenerating profiles compared to control optic nerves. These observations suggest a dose-dependent axonal loss and degeneration associated with the morphological changes induced in rabbit optic nerves following intravitreal injection of TNF alpha.
Animals↗
The anterior visual pathways--Part II.
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Eye↗
Idiopathic intracranial hypertension. Lack of histologic evidence for cerebral edema.
OBJECTIVE: To study brain histologic features in two cases of idiopathic intracranial hypertension (pseudotumor cerebri) at autopsy. DESIGN: Formaldehyde solution-fixed sections of cerebral white matter in two cases and structures of the sensory visual system in one case were analyzed. SETTING: University medical center. PATIENTS: Two patients with idiopathic intracranial hypertension who died unexpectedly. MAIN OUTCOME MEASURE: Histologic study of cerebral white matter in the two patients. RESULTS: We did not find histologic evidence of any type of cerebral edema in our patients. Review of a portion of the material from a previous report is also consistent with this conclusion. CONCLUSION: If patients with idiopathic intracranial hypertension have histologically apparent cerebral edema, it is not a consistent finding.
Adult↗