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PubMed2003

Optic neuritis: correlation of pain and magnetic resonance imaging.

PURPOSE: To demonstrate whether the magnetic resonance imaging (MRI) localization of the abnormal enhancement of the optic nerve can be related to the pain or pattern of visual field loss associated with acute optic neuritis. DESIGN: Retrospective observational series and MRI review from a referral neuro-ophthalmology service. PARTICIPANTS: Seventy-three women and 23 men with acute optic neuritis who had high resolution gadolinium-enhanced fat-suppressed MRI within twenty days of the onset of visual loss. METHODS: The presence of eye or other fifth cranial nerve (V(1)) pain, and pain with eye movement ipsilateral to the affected optic nerve or no eye pain was recorded. The neuroradiologist reviewed the MRI, masked to the affected eye, and recorded the length and segment (orbital, canalicular, intracranial, or combination of segments) of abnormal optic nerve enhancement. The presenting visual field defects were characterized as diffuse, central, arcuate, nasal or temporal. MAIN OUTCOME MEASURES: The types of pain and patterns of field loss were correlated with the segments of optic nerve enhancement in the affected eye. RESULTS: Five patients had nerves that did not enhance and were excluded from the outcome analysis. In the 91 patients with abnormal enhancement, 70 experienced eye/V(1) pain, 67 had pain with eye movement and 17 patients had no pain. Enhancement of the orbital optic nerve occurred in 66 patients, 93.9% who had eye/V(1) pain and 92.4% who had pain with eye movement. In the 25 patients with enhancement of the canalicular, intracranial or both segments, without orbital involvement, 32% had eye/V(1) pain and 24% had pain with eye movement. No pain occurred in 3% with enhancement of the orbital segment and in 60% with enhancement of the other optic nerve segments. The length of enhancement moderately correlated with eye/V(1) pain (r = 0.49, P = 0.01) and pain with eye movement (r = 0.37, P = 0.01). Patients with enhancement longer than 10 mm had pain five times (P = 0.004) more frequent than did those with enhancement <or=10 mm. There was no significant specific pattern of field loss associated with a particular location of enhancement, except temporal field loss occurred in 25% of intracranial lesions (P = 0.04). CONCLUSION: When optic neuritis involved the orbital segment of the optic nerve, eye or other V(1) distribution pain (94.3% vs. 32%) and pain with eye movement (91.4% vs. 24%) were significantly more frequent. In contrast, pain was absent 20 times more often when the orbital segment was not involved (60% vs. 3%). Except for temporal field loss in eyes with intracranial nerve lesions, no pattern of visual field loss appeared to correlate with the location or length of abnormal optic nerve enhancement.

Acute Disease↗
PubMed1996

Magnetic resonance imaging in patients with unexplained optic neuropathy.

PURPOSE: To investigate the anatomic relation between the optic nerve and the adjacent intracranial internal carotid artery (ICA) in patients with unexplained optic neuropathy. METHODS: Coronal magnetic resonance images (MRIs) of 20 patients with unexplained optic neuropathy and 20 age-matched controls were evaluated with digitizing software. RESULTS: The distance between the optic nerve and ICA was significantly less on the side ipsilateral to the atrophic optic nerve than either the study group's contralateral optic nerve-ICA distance (P<0.001) or the control group's optic nerve-ICA distance (P<0.001). The diameter of the atrophic optic nerves was significantly less than either the diameter of the study group's contralateral normal nerves (P=0.008) or the control group's nerves (P<0.001). There was no significant difference between the diameters of the ICA flow voids adjacent to the atrophic optic nerves versus either the study group's contralateral ICA flow voids (P=0.91) or the control group's ICA flow voids (P=0.74). CONCLUSIONS: The authors speculate that the intimate relation between the optic nerve and adjacent ICA may be important in the development of unexplained optic neuropathy. The ICA need not appear abnormal in MRIs.

Aged↗
PubMed2002

Contrast-enhanced MRI in acute optic neuritis: relationship to visual performance.

The location and extent of an abnormal signal on MRI of the optic nerve affected by optic neuritis are said to correlate with the severity of initial visual loss and recovery. We used gadolinium-enhanced fat-suppressed MRI to show abnormal enhancement of the optic nerve to determine the sensitivity of this modality in acute optic neuritis and whether the abnormal enhancement correlates with presenting visual deficits or recovery. A total of 107 patients, 93 with follow-up (68 steroid treated), were included; 101 patients had enhancement of the affected optic nerve and no unaffected nerve enhanced. The baseline visual performance was similar between nerves with and without enhancement. Optic nerves with enhancement in the optic canal had poorer colour vision (P = 0.04) and nerves with all segments involved had worse threshold perimetry (P = 0.001) and colour vision (P = 0.008). Nerves with enhancement >10 mm had worse threshold perimetry (P = 0.004), while nerves with enhancing segments >17 mm had poorer baseline visual acuity (P = 0.02), threshold perimetry (P = 0.009) and colour vision (P = 0.01). For all parameters of vision, recovery was similar regardless of location or length of abnormal enhancement. Abnormal contrast enhancement of the optic nerve is a sensitive (94%) finding in acute optic neuritis and is absent in unaffected or previously affected optic nerves. Although lesions involving the canal or longer segments of optic nerve have worse starting vision, the location and length of enhancement are not predictive of recovery.

Adult↗
PubMedDate not supplied

Optic nerve damage in highly myopic eyes with chronic open-angle glaucoma.

PURPOSE: To compare the amount of optic nerve damage in relation to intraocular pressure in highly myopic eyes with chronic open-angle glaucoma versus non-highly myopic eyes with chronic open-angle glaucoma. METHODS: The comparative clinical observational study included 1841 eyes of 1100 patients with chronic open-angle glaucoma. The highly myopic study group consisted of 25 eyes with a myopic refractive error equal to or higher than -8 diopters. It was subdivided into eyes with an optic disc size larger than 2.7 mm2 and eyes with an optic disc smaller than 2.7 mm2. The control group included the remaining, non-highly myopic eyes (n=1816). For all patients, a morphometric analysis of color stereo optic disc photographs was performed. Main outcome measures were morphometric optic disc measurements and intraocular pressure. RESULTS: In the highly myopic, large-optic-disc study group compared with the control group, maximal and minimal intraocular pressure readings were significantly (p<0.05) lower and neuroretinal rim area corrected for optic disc size was slightly (p=0.16) smaller. Comparing the total highly myopic study group with a control group adjusted for optic disc area, neuroretinal rim area was significantly (p=0.039) smaller in the study group with no significant difference in intraocular pressure measurements between the groups. CONCLUSIONS: At a given intraocular pressure in chronic open-angle glaucoma, optic nerve damage may be more pronounced in highly myopic eyes with large optic discs than in non-highly myopic eyes. This may suggest a higher susceptibility for glaucomatous optic nerve fiber loss in highly myopic eyes than in non-highly myopic eyes.

Chronic Disease↗
PubMed1999

Optic nerve and peripapillary choroidal microvasculature of the rat eye.

PURPOSE: To investigate the three-dimensional microvascular anatomy of the optic nerve and peripapillary choroid in the rat eye. METHODS: Gross vascular anatomy of the posterior eye segment of Wistar rats was studied in serial microsections with a light microscope. The optic nerve and peripapillary choroidal vessels were sequentially microdissected, using methylmethacrylate corrosion microvascular castings, and were examined with a scanning electron microscope to determine the three-dimensional relationships of the vessels. RESULTS: The posterior ciliary artery traveled along the inferior side of the optic nerve sheath, directly entered the optic nerve head, and divided into three branches: the central retinal artery and medial and lateral long posterior ciliary arteries, which provided several short branches to the choroid. The optic nerve head vasculature was consistently nourished by a recurrent arteriole from the central retinal artery and an arteriole from the choroidal artery at the peripapillary choroid. The central retinal vein flowed into a venous anastomosis along the optic disc border of the peripapillary choroid. Capillaries within the optic nerve drained into the central retinal vein, the marginal venous anastomosis of the peripapillary choroid, and the pial veins, all of which flowed into the posterior ciliary veins along the optic nerve sheath. CONCLUSIONS: The findings illustrate vascular anatomic differences in optic nerve and peripapillary choroidal microcirculation between rat and human. In rats, the peripapillary choroid plays a significant role in both blood supply and venous drainage of the optic nerve head. The central retinal artery also contributes to the optic nerve head circulation.

Animals↗
PubMed2003

Characteristics of optic disc changes in Taiwanese patients with primary angle-closure glaucoma.

BACKGROUND AND PURPOSE: Primary angle-closure glaucoma (PACG) is the predominant form of glaucoma among Asians. Although numerous studies have been done to describe the characteristic optic disc changes in patients with primary open angle glaucoma (POAG) which is the predominant form of glaucoma among Western populations, few studies have evaluated the optic disc changes in patients with PACG. The aim of this study was to elucidate the characteristic intrapapillary and parapapillary disc changes in PACG in a cross-sectional study and to develop a practical approach to the detection of glaucomatous optic disc changes in PACG by ophthalmoscopic examination. METHODS: A total of 103 eyes in 103 PACG patients were studied. Forty one eyes of 41 age- and sex-matched healthy subjects served as controls. Three glaucoma-trained subspecialists examined stereophotographs of optic discs to evaluate the intrapapillary and parapapillary changes. The differences in PACG and control group eyes were compared. RESULTS: Concentric steep enlargement of the optic disc was found in 99 PACG eyes (96%). Local notching was noted in only 3 eyes, and vertically oval-shaped cupping of the optic disc in only 1 eye. Disc hemorrhage was not detected in any eye. Parapapillary atrophy of the alpha zone involving both temporal and nasal side of the optic disc and parapapillary atrophy of beta zone were significantly more frequent in the PACG group. The presence of an alpha zone or a beta zone simultaneously involving both the temporal and nasal side of the optic disc was associated with more severe optic nerve head damage. CONCLUSIONS: The intrapapillary change in the PACG group eyes reflected the development of cupping in PACG patients with small and compact optic discs. The parapapillary atrophy paralleled the intrapapillary optic disc cupping in eyes of the PACG group.

Case-Control Studies↗
PubMed2006

[A case of anterior ischemic optic neuropathy associated with Vogt-Koyanagi-Harada disease].

BACKGROUND: Although optic disc swelling is one of the common findings of Vogt-Koyanagi-Harada (VKH) disease, severe visual field loss from optic disc involvement is not common. We report a case of severe visual field contraction from optic disc involvement in VKH disease. CASE REPORT: A 51-year-old woman was diagnosed as having VKH disease and was treated with intravenous pulse methylprednisolone. Exudative retinal detachments disappeared and visual acuity improved, but optic disc swelling was persistent in both eyes. Ten weeks after VKH disease onset, she claimed acute visual field loss in the right eye. Marked optic disc swelling with peripapillary hemorrhages and severe visual field loss were observed in the right eye. Fluorescein angiography showed filling delay and late leakage of the optic disc in the right eye. One month later, right optic disc swelling disappeared, but visual field loss remained. In addition, 5.5 months later, the left optic disc swelled further, and the left visual field was markedly contracted. Hyperbaric oxygen therapy was added. The swelling in the left optic disc gradually decreased and disappeared in one month, but the visual field loss remained. CONCLUSIONS: The optic disc involvement with irreversible visual field loss in this case is thought to be due to anterior ischemic optic neuropathy, which may be a possible complication of VKH disease.

Female↗
PubMed1998

Descriptive information of topographic parameters computed at the optic nerve head with the Heidelberg retina tomograph.

PURPOSE: To analyze the frequency distribution and descriptive information of topometric data obtained with the Heidelberg Retina Tomograph (HRT) in a normal population. METHODS: Topographic measurements of the optic disc were acquired and evaluated using the HRT in 225 subjects between 12 and 90 years of age. After randomly selecting one eye per subject, the frequency distributions, mean values, minima, maxima, and first, fifth, fiftieth, ninety-fifth, and ninety-ninth percentiles were evaluated for topographic parameters computed by the HRT. The influence of age, intraocular pressure (IOP), disc size, and disc shape on optic disc topometric data was analyzed. A principal component analysis of the topometric parameters was performed. The frequency distributions, mean values, minima, maxima, and first, fifth, fiftieth, ninety-fifth, and ninety-ninth percentiles of the interocular difference in topographic parameters were evaluated. RESULTS: All topographic parameters showed a unimodal but not necessarily normal distribution. None of the parameters showed a relevant correlation with age, IOP (in the normal range), and overall shape of the anterior optic nerve, but a few parameters showed a clinically significant correlation with disc size. A principal component analysis identified four relevant factors (optic nerve cup, retinal nerve fiber layer, optic disc size, and optic nerve cup shape) in the entire data set of optic nerve topometric data. The absolute value of all interocular differences in topographic parameters showed an asymmetric but unimodal distribution. CONCLUSION: The mathematical description of the optic nerve cup shape provides information on optic nerve head topography independently from cupping, nerve fiber layer thickness, and disc size. Potentially, quantification of further aspects in optic nerve head topography might improve the discriminatory power of computerized quantitative optic nerve head analysis.

Adolescent↗
PubMed1991

Relationship of retinotopic ordering of axons in the optic pathway to the formation of visual maps in central targets.

We examined in rats the relationship between the ordering of retinal axons in the optic pathway and the formation of a retinotopically organized projection to their primary target, the contralateral superior colliculus (SC). We have previously found that axons labeled by focal injections of 1,1'-dioctadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) made in temporal or nasal retina of perinatal rats commonly mistarget along the medial-lateral and rostral-caudal axes of the SC. By postnatal day (P) 11-12, the retinocollicular projection attains an adult-like topography. Incorrectly targeted axons or axon segments are removed; axons that persist terminate in the topographically appropriate part of the SC (Simon and O'Leary: Dev Biol 137:125, 1990). In the present study, we made similar DiI injections, covering less than 2% of the retinal area, in peripheral temporal, nasal, superior, or inferior retina, in rats of two age groups, embryonic day (E) 21 to P (postnatal day) 2 and P11-P17. Whole mounts of retina, optic nerve and tract, and SC, and cross sections of the optic nerve, were examined. In E21-P2 rats, retinal axons labeled from each retinal site are diffusely distributed in the SC, and poorly ordered in the optic pathway. In retina, labeled axons travel in fascicles directly from the injection site to the optic disc, but neighbor relationships begin to degrade as fascicles split and mix. Retinotopic order is virtually lost in the optic nerve; axons labeled from each injection site disperse throughout its cross-sectional area, but the labeled axons tend to be concentrated toward a specific half of the nerve depending upon their retinal origin. This slight tendency toward retinotopic order increases in the optic tract, but axons are still poorly ordered as they leave the tract and enter the SC. Targeting errors along the medial-lateral axis of the SC, but apparently not along its rostral-caudal axis, are related to the positioning of axons across the width of the optic tract. In P11-P17 rats, axons labeled from each injection site arborize only in a small, topographically correct part of the SC. However, the distributions of labeled retinal axons observed in whole mounts of the retina and optic pathway have a degree of disorder similar to those in E21-P2 rats. Further, the scatter of labeled axons in optic nerve cross sections is comparable in both age groups. Therefore, the emergence of topographic order in the retinocollicular projection is not accompanied by an emergence of a retinotopic ordering of axons in the optic nerve.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2006

Colorectal tumors and hepatic metastases differ in their optical properties-relevance for dosimetry in laser-induced interstitial thermotherapy.

BACKGROUND AND OBJECTIVES: The therapeutic application of laser light is a promising alternative to surgical resection of colorectal liver metastases. The extent of tumor destruction achieved by this strategy depends primarily on light distribution in the target tissue. Knowledge about optical properties is necessary to predict light distribution in the tissue for careful irradiation planning. The aim of this study was to compare the optical behavior of healthy colon tissue with that of colorectal carcinomas and their hepatic metastases in the native and coagulated state in order to test the effect of malignant degeneration, metastasis, and thermal coagulation on optical parameters. MATERIALS AND METHODS: Ninety tissue samples were taken from patients with a colorectal carcinoma and concomitant liver metastases: healthy colon tissue (n = 30); colon carcinoma (n = 30); liver metastases (n = 30). Optical properties were measured according to the single integrating sphere principle in the native state and after thermal coagulation in the wavelength range of 800-1,100 nm and analyzed by inverse Monte Carlo simulation. RESULTS: The highest optical penetration depth for all tissue types was obtained at the end of the spectral range investigated. The highest penetration depths of 4.13 mm (healthy colon), 7.47 mm (colon carcinoma tissue), and 4.08 (liver metastases) were at 1,060 nm, although the values decreased significantly after thermal coagulation. Comparing healthy colon-to-colon carcinoma always revealed a significantly lower absorption and scattering coefficient in the tumor tissue. This resulted in a higher optical penetration depth of the laser light in the colon carcinoma tissue (P < 0.05). A direct comparison disclosed no agreement between the optical properties of the primary tumor and the liver metastases. In the native state, colon carcinoma tissue had a lower scattering coefficient (P < 0.05), higher anisotropy factor, and optical penetration depth than liver metastases (P < 0.05). The absorption coefficient did not differ significantly. The differences in the native state were equalized by tissue coagulation. CONCLUSIONS: Colon carcinoma tissue has a higher optical penetration depth than healthy colon tissue, which speaks in favor of tumor selectivity for interstitial laser application, since large treatment volumes can be obtained in the tumor. The lack of agreement between primary tumors and their concomitant liver metastases indicates a modification of optical behavior through metastasis. Thermal coagulation of tissue leads to changes in the optical properties, which are clearly less pronounced in carcinoma tissue. The data obtained in this study clearly show that an individual irradiation schedule is necessary for effective and safe dosimetry in laser-induced thermotherapy (LITT).

Adenocarcinoma↗
PubMed1998

Putative role of calpain in the pathophysiology of experimental optic neuritis.

Since myelin proteins are degraded in autoimmune demyelinating diseases such as optic neuritis, proteinases are believed to participate in myelinolysis. Calpain (calcium activated neutral proteinase) degrades myelin proteins at physiological pH and is found in glial and inflammatory cells involved in demyelination. To examine the putative role of calpain in myelinolysis, the activity and expression (translational and transcriptional) of this enzyme and endogenous inhibitor, calpastatin were examined in optic nerves of Lewis rats with experimental allergic encephalomyelitis (EAE), an animal model of optic neuritis. Calpain activity was examined via Western blotting by measuring the extent of myelin protein degradation and calpain-specific fodrin proteolysis in optic nerves from controls versus rats with experimental optic neuritis. RT-PCR studies demonstrated no significant change in millicalpain, microcalpain, or calpastatin expression at the mRNA level in optic nerves from animals with experimental optic neuritis compared to controls. However, myelin associated glycoprotein (MAG) levels were decreased by 25.5% while calpain translational expression and calpain-autolyzed fodrin levels were increased by 72.1% and 462.8% respectively, in experimental optic neuritis compared to controls. Translational expression of calpastatin isoforms (80, 68 and 55 KD) was not significantly different in rats with experimental optic neuritis compared to controls. Thus, increased activity and translational expression of calpain in experimental optic neuritis suggests this proteinase may participate in the degradation of myelin and cytoskeletal proteins in demyelinating diseases such as optic neuritis.

Animals↗
PubMed1995

Transcranial optical path length in infants by near-infrared phase-shift spectroscopy.

BACKGROUND: Near-infrared spectroscopy (NIRS) is an emerging technique for noninvasive, bedside monitoring of cerebral oxygenation and blood flow. Traditionally, it has relied on the Beer's Law relationship in which the concentration of light-absorbing oxygen-carrying pigments is proportional to their light absorbance, and inversely proportional to an optical path length (a measure of the distance traveled by photons passing through the tissue). In practice, NIRS has been based upon assumptions that mean transcranial optical path length, the average optical path length for a given patient, is constant among patients and independent of the wavelength of light used. OBJECTIVE: The objective of our study was to measure mean optical transcranial path length in infants as a step in allowing quantitation of cerebral oxygenation. METHODS: We measured mean transcranial optical path length in 34 infants, aged 1 day to 3 years, using amplitude-modulated phase-shift spectroscopy at 754 nm and 816 nm. Optical transcranial path lengths (mean +/- SEM) were 8.6 +/- 0.9 cm, 11.1 +/- 0.9 cm, and 11.3 +/- 0.9 cm at 754 nm, and 8.8 +/- 0.9 cm, 11.2 +/- 0.8 cm, and 11.1 +/- 0.9 cm at 816 nm, using emitter-detector separations of 1.8, 2.5, and 3.0 cm, respectively. Optical path length increased as emitter-detector separation, head circumference, or age increased. Variance in the ratio of mean optical path lengths at the two different wavelengths exceeded that accounted for by variation in repeated measures alone (p < 0.001), suggesting that optical path length is also not independent of wavelength. CONCLUSIONS: NIRS instrument emitter-detector geometry, subject age, head size, and wavelength used each influence optical path length. Quantitative NIRS measurements in clinical use may require concurrent measurement of both absorbance and optical path length at each wavelength, or use of newer measures that are not based upon Beer's Law assumptions.

Child, Preschool↗
PubMed1986

Retinal topography in the optic tract of adult goldfish.

The present study was aimed at determining how transformations in fiber order establish a retinal topography in the optic tract of adult Carassius auratus. Horseradish peroxidase was applied to the optic nerve or retina, and the pathways of labeled axons originating from retinal annuli or wedges were analysed in reconstructed serial-sections and wholeamounts of the optic pathway. The age-related fiber order of the optic tract involves a rotation of the optic pathway that begins near the chiasm, continues through the optic tract as it wraps around the brain, and extends through the brachia. The relative order of laminae, in which each lamina is composed of age-related axons, is maintained in the optic pathway. The laminae add systematically onto the optic tract in a mediolateral direction with the oldest lamina forming the medial margin. Retinal sector order in the optic tract is established by the rearrangement of axons from each lamina. These rearrangements begin at the chiasm and, in part, involve transposition of axons originating from the ventrotemporal and dorsonasal sectors of the retina. The transformations achieve a fiber order in the optic tract that is appropriate for entry into the tectum. It is proposed that the final retinal topography of the optic tract is determined by the combined influences of selective affinities along the neural axis and substrate guidance mechanisms, the latter being mediated largely by the oldest axons of the fasciculus medialis tractus opticus.

Animals↗
PubMed2006

Determining whether delayed nonarteritic ischemic optic neuropathy associated with cataract extraction is a true entity.

PURPOSE: To evaluate cases of delayed nonarteritic anterior and posterior ischemic optic neuropathy after cataract extraction and to evaluate the need for centralized prospective reporting of nonarteritic ischemic optic neuropathy after cataract extraction. SETTING: Neuro-ophthalmology Clinics, University of Colorado Health Sciences Center and Denver Veterans Affairs Medical Center, Denver, Colorado, USA. METHODS: A retrospective review of all patients referred to the Neuro-ophthalmology Divisions, University of Colorado Health Sciences Center and Denver Veterans Affairs Medical Center, from January 2001 to October 2005 was performed. All patients with a diagnosis of nonarteritic anterior or posterior ischemic optic neuropathy were identified. Patients with ischemic optic neuropathy that occurred between 2 months and 12 months after cataract extraction were selected for evaluation. RESULTS: Six eyes with nonarteritic ischemic optic neuropathy that occurred 2 to 6 months after cataract extraction in 4 patients (2 bilateral nonarteritic ischemic optic neuropathy) and 1 eye with nonarteritic ischemic optic neuropathy that occurred after 6 months in 1 patient were identified. One patient had nonarteritic ischemic optic neuropathy in 1 eye 3 months after cataract extraction and 4 years later had nonarteritic ischemic optic neuropathy in the fellow eye 5 months after cataract extraction. Follow-up after the last cataract extraction was 1 to 3 years for all patients. CONCLUSIONS: Although an association between cataract extraction and delayed nonarteritic anterior and posterior ischemic optic neuropathy has been suggested, current data do not support a causal relationship. In addition, the window of postoperative susceptibility for delayed ischemic optic neuropathy after cataract extraction is unclear.

Aged↗
PubMed2005

Two-dimensional and 3-dimensional optical coherence tomographic imaging of the airway, lung, and pleura.

BACKGROUND: Methods for obtaining real-time in vivo histologic resolution by means of noninvasive endoscopic optical imaging would be a major advance for thoracic surgical diagnostics and treatment. Optical coherence tomography is a rapidly evolving technology based on near-infrared interferometry that might provide these capabilities. The purpose of this study is to investigate the feasibility of real-time 2- and 3-dimensional optical coherence tomographic imaging of airway, pleural, and subpleural lung tissues in normal, inflammatory, and malignant animal models and patients with known or suspected airway malignancy. METHODS: Freshly excised lungs and pleural tissue obtained from rabbits with inhalation lung injury and induced empyema, metastatic sarcomas, and pleural sarcomas and from patients with airway disease were imaged by using 2- and 3-dimensional optical coherence tomography with a prototype superluminescent diode optical coherence tomographic system constructed in our laboratory. Lungs and pleural tissue were subsequently processed for standard hematoxylin and eosin histology for comparison with optical coherence tomography. RESULTS: Optical coherence tomographic imaging achieved an ex vivo resolution of 10 microm and an in vivo resolution of about 30 microm with a depth penetration of 1 to 2 mm with 2- and 3- dimensional reconstruction capabilities. Tumors as small as 500 microm were detectable with optical coherence tomography. The acquired images closely matched histologic images, demonstrating details at the level of mucosal layers, glands, alveoli, and respiratory bronchioles. CONCLUSIONS: Optical coherence tomography with near-infrared interferometric methods enables near real-time in vivo near-histologic resolution optical imaging. With further advances, optical coherence tomography has the potential for real-time accurate and early pleural and subpleural diagnostics by using small-diameter flexible fiberoptic endoscopic probes for a wide range of thoracic surgical applications.

Animals↗
PubMed2005

Optic neuropathies--importance of spatial distribution of mitochondria as well as function.

Optic neuropathies such as Leber's hereditary optic neuropathy, dominant optic atrophy and toxic amblyopia are an important cause of irreversible visual failure. Although they are associated with a defect of mitochondrial energy production, their pathogenesis is poorly understood. A common feature to all these disorders is relatively selective degeneration of the papillomacular bundle of retinal ganglion cells resulting central or caecocentral visual field defects. The striking similarity in the pattern of clinical involvement seen with these disparate disorders suggests a common pathway in their aetiology. The existing hypothesis that the optic nerve head has higher energy demands than other tissues making it uniquely dependent on oxidative phosporylation is not satisfactory. First, other ocular tissues such as photoreceptors, which are more dependent on oxidative phosporylation are not affected. Second, other mitochondrial disorders, which have a greater impact on mitochondrial energy function, do not affect the optic nerve. The optic nerve head has certain unique ultra structural features. Ganglion cell axons exit the eye through a perforated collagen plate, the lamina cribrosa. There is a sharp discontinuity in the density of mitochondria at the optic nerve head, with a very high concentration in the prelaminar nerve fibre layer and low concentration behind the lamina. This has previously been attributed to a mechanical hold up of axoplasmic flow, which has itself been proposed as a factor in the pathogenesis of a number of optic neuropathies. More recent evidence shows that mitochondrial distribution reflects the different energy requirements of the unmyelinated prelaminar axons in comparison to the myelinated retrolaminar axons. The heterogeous distribution of mitochondria is actively maintained to support conduction through the optic nerve head. We propose that factors that disrupt the heterogeneous distribution of mitochondria can result in ganglion cell death. Evidence for this comes from studies of cultured cells with the dominant optic atrophy mutation in which mitochondrial distribution is altered and from some forms of hereditary spastic paraparesis which are associated with optic atrophy. The responsible mutations do not affect ATP production until late in the disease but do affect mitochondrial arrangement, again showing that mitochondrial distribution as well as energy production by individual mitochondria may be important in the pathogenesis of ganglion cell death. Greater understanding of the factors localising mitochondria within the ganglion cell axon in particular the interaction with cytoskeleton is required to formulate new treatments. Boosting energy production alone may not be an effective treatment.

Animals↗
PubMed2006

Detection and prognostic significance of optic disc hemorrhages during the Ocular Hypertension Treatment Study.

PURPOSE: To compare the rates of detection of optic disc hemorrhages by clinical examination and by review of optic disc photographs at the Optic Disc Reading Center (ODRC), to assess the incidence of and the predictive factors for disc hemorrhages in the annual disc photographs of the Ocular Hypertension Treatment Study (OHTS), and to determine whether optic disc hemorrhages predict the development of primary open-angle glaucoma (POAG) in the OHTS. DESIGN: Cohort study. PARTICIPANTS: Three thousand two hundred thirty-six eyes of 1618 participants. METHODS: Both eyes of participants were examined for optic disc hemorrhages every 6 months by clinical examination, with dilated fundus examinations every 12 months, and by annual review of stereoscopic disc photographs at the ODRC. MAIN OUTCOME MEASURES: Incidence of optic disc hemorrhages and POAG end points. RESULTS: Median follow-up was 96.3 months. Stereophotography-confirmed glaucomatous optic disc hemorrhages were detected in 128 eyes of 123 participants before the POAG end point. Twenty-one cases (16%) were detected by both clinical examination and review of photographs, and 107 cases (84%) were detected only by review of photographs (P<0.0001). Baseline factors associated with disc hemorrhages were older age, thinner corneas, larger vertical cup-to-disc ratio, larger pattern standard deviation index on perimetry, family history of glaucoma, and smoking status. The occurrence of a disc hemorrhage increased the risk of developing POAG 6-fold in a univariate analysis (P<0.001; 95% confidence interval, 3.6-10.1) and 3.7-fold in a multivariate analysis that included baseline factors predictive of POAG (P<0.001; 95% confidence interval, 2.1-6.6). The 96-month cumulative incidence of POAG in the eyes without optic disc hemorrhage was 5.2%, compared with 13.6% in the eyes with optic disc hemorrhage. In eyes with a disc hemorrhage in which a POAG end point developed, the median time between the 2 events was 13 months. CONCLUSIONS: Review of stereophotographs was more sensitive at detecting optic disc hemorrhage than clinical examination. The occurrence of an optic disc hemorrhage was associated with an increased risk of developing a POAG end point in participants in the OHTS. However, most eyes (86.7%) in which a disc hemorrhage developed have not experienced a POAG end point to date.

Cohort Studies↗
PubMed1999

Physiology of perfusion as it relates to the optic nerve head.

Blood flow in the optic nerve has been demonstrated to be autoregulated, and, thus, within certain limits, to be independent of the local perfusion pressure. As in the brain, a close coupling of neuronal activity and optic nerve head blood flow has been demonstrated. A number of regulatory systems and factors participate in the regulation of vascular tone in various organs, including the optic nerve. Metabolic and myogenic mechanisms keep local perfusion constant or adapted to the local metabolic needs. Such mechanisms seem to be involved in the regulation of optic nerve blood flow as well. In contrast, neuronal blood flow regulation is of minor importance in the optic nerve. Many of the regulatory modalities induce a response of vascular smooth muscle cells through stimulation of factors produced by the endothelial cell layer. Indeed, endothelial factors are of utmost importance in the regulation of optic nerve blood flow. The facts that there is a basal formation of nitric oxide, which leads to an active dilation of the ocular vasculature, and that endothelin-1 decreases blood flow to the anterior optic nerve in a dose-dependent manner suggest that alterations in these regulatory mechanisms might be relevant for optic nerve blood flow alterations as they relate to glaucomatous optic neuropathy. It is hoped that a detailed knowledge of blood flow regulation in the optic nerve might initiate new treatment modalities in optic neuropathies that are hemodynamic and vascular in nature.

Animals↗