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Biomedical subjects

A A Sadun

Publications and source records attributed to A A Sadun.

At least 19 recordsLinked to original sources
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

AIDS-related optic neuropathy: a histological, virological and ultrastructural study.

BACKGROUND: Clinical and histopathological evidence of optic nerve axonal loss has been reported in AIDS patients without retinitis. The study was carried out to investigate the possible involvement of HIV-infected cells in the development of optic nerve degeneration. METHODS: Optic nerves were obtained from eight AIDS patients and four normal controls. These nerves were morphologically and immunohistochemically analyzed. Additionally, using PCR amplification techniques, the retina and optic nerve samples obtained from three HIV-seropositive patients and one control were examined for the presence of HIV and cytomegalovirus antigens. RESULTS: We noted various stages of axonal degeneration in the optic nerves obtained from AIDS patients in whom there was an absence of retinal findings. Characteristic glial changes involving hypertrophic astrocytes, vacuolated oligodendrocytes, and mononuclear phagocyte series cells were also seen in the AIDS optic nerves. HIV DNA was present in at least four of five optic nerves but in only one of five retinas. Control specimens were each negative for all cytomegalovirus and HIV antigens. CONCLUSIONS: Degeneration in the optic nerve may be mediated by HIV-infected macrophages rather than by direct viral infection of neurons. Axonal degeneration due to AIDS at the level of the optic nerve can occur independently of retinal infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Review of the visual system in Parkinson's disease.

In an era when the prevalence of Parkinson's disease (PD) is increasing because our population is aging, eye care professionals need to become aware of the visual changes experienced by PD patients. This paper reviews the visual pathophysiology of PD and the results of the lack of dopamine on the retina and visual cortex. It also discusses the impact of PD on the oculomotor system and the visual sensory pathways with the consequent effects on reading, balance, and driving abilities of PD patients. Further research on the visual system and PD may provide improved means for early diagnostic testing as well as the possibility of vision rehabilitation for treatment of visual performance impairments.

Dopamine↗