Ophthalmologic findings in a large pedigree of 11778/Haplogroup J Leber hereditary optic neuropathy

Sadun, Federico; Negri, Anna Maria De; Carelli, Valerio; Salomão, Solange Rios; Berezovsky, Adriana; Andrade, Rafael; Moraes, Maria Nathália; Passos, Angelo Ferreira; Belfort, Rubens; Rosa, Arlon Bastos Da; Quirós, Peter A.; Sadun, Alfredo A.

doi:10.1016/j.ajo.2003.08.010

Cited by 78 publications

(61 citation statements)

References 25 publications

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“…[19][20][21][22][23][24][25] Ortiz et al 21 studied the optic disc Table 5 A comparison of sectoral parameter measurements between whole normal eyes and eyes with compressive optic neuropathy appearance of seven patients with LHON with stereoscopic fundus photography. They described that all the patients showed increased disc cupping with C/D ratios of 0.7-0.9 and that six of them displayed the shallow cupping.…”

Section: Hrt Parameters In Optic Neuropathiesmentioning

confidence: 99%

Evaluation of optic nerve head configuration in various types of optic neuropathy with Heidelberg Retina Tomograph

Nagai-Kusuhara

Nakamura

Kanamori

et al. 2007

Eye

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Purpose To test whether Heidelberg Retina Tomograph (HRT) is applicable to assess the optic nerve head (ONH) configuration of the atrophic phase of non-glaucomatous optic neuropathy when a default set of the reference plane is used. Methods Ten eyes with non-arteritic anterior ischaemic optic neuropathy (NAION), 17 eyes with Leber's hereditary optic neuropathy (LHON), 40 eyes with compressive optic neuropathy (CON) owing to chiasmal tumour, and 241 eyes of control individuals were examined with HRT using the default reference plane. The global values of HRT parameters were evaluated among the groups of patients and controls. The sectoral measurements of the eyes with LHON and CON were compared with controls. To eliminate the influence of disc size and age on HRT measurements, eyes with disc area-and age-matched normal controls were used for comparison with eyes with NAION and LHON. Results Cup parameters in eyes with NAION were similar to those in controls. The retinal nerve fibre layer (RNFL) thickness was significantly thinner in eyes with NAION than that of controls. The eyes with LHON had significantly larger cup parameters, smaller rim volume, and thinner mean RNFL thickness than controls. Eyes with CON had significantly larger rim area and smaller cup parameters but similar RNFL thickness compared with controls. Conclusions When the default reference plane is used, HRT can measure the ONH configuration in eyes with NAION and LHON as expected. However, caution must be made to interpret the parameters obtained from the eyes with CON.

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Section: Hrt Parameters In Optic Neuropathiesmentioning

confidence: 99%

Evaluation of optic nerve head configuration in various types of optic neuropathy with Heidelberg Retina Tomograph

Nagai-Kusuhara

Nakamura

Kanamori

et al. 2007

Eye

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“…This extended LHON family has been characterized in a number of clinical studies. [20][21][22][23][24][25][26] One proband, displaying milder neurodegenerative changes in the optic nerves, died at the age of 59 years from acute myocardial infarction. His younger brother, showing more severe neurodegenerative changes in the optic nerves died at the age of 52 years, also from an acute myocardial infarct.…”

Section: Postmortem Control Tissues (Lhon and Controls)mentioning

confidence: 99%

Mathematically Modeling the Involvement of Axons in Leber's Hereditary Optic Neuropathy

Pan

Ross‐Cisneros

Carelli

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Leber's hereditary optic neuropathy (LHON), a mitochondrial disease, has clinical manifestations that reflect the initial preferential involvement of the papillomacular bundle (PMB). The present study seeks to predict the order of axonal loss in LHON optic nerves using the Nerve Fiber Layer Stress Index (NFL-S I ), which is a novel mathematical model. METHODS.Optic nerves were obtained postmortem from four molecularly characterized LHON patients with varying degrees of neurodegenerative changes and three age-matched controls. Tissues were cut in cross-section and stained with pphenylenediamine to visualize myelin. Light microscopic images were captured in 32 regions of each optic nerve. Control and LHON tissues were evaluated by measuring axonal dimensions to generate an axonal diameter distribution map. LHON tissues were further evaluated by determining regions of total axonal depletion. RESULTS.A size gradient was evident in the control optic nerves, with average axonal diameter increasing progressively from the temporal to nasal borders. LHON optic nerves showed an orderly loss of axons, starting inferotemporally, progressing centrally, and sparing the superonasal region until the end. Values generated from the NFL-S I equation fit a linear regression curve (R 2 ¼ 0.97; P < 0.001).CONCLUSIONS. The quantitative histopathologic data from this study revealed that the PMB is most susceptible in LHON, supporting clinical findings seen early in the course of disease onset. The present study also showed that the subsequent progression of axonal loss within the optic nerve can be predicted precisely with the NFL-S I equation. The results presented provided further insight into the pathophysiology of LHON. (Invest Ophthalmol Vis Sci. 2012;53:7608-7617)

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“…6,[13][14][15] This study adhered to the tenets of the Declaration of Helsinki regarding the ethical principles for medical research involving human subjects and institutional review board approval was obtained. All patients gave informed consent and patient confidentiality was maintained throughout the study.…”

Section: Methodsmentioning

confidence: 99%

“…Based on the pedigree and the clinical status, we classified 46/74 individuals as ''unaffected mutation carriers'' (from herein carriers) defined by the presence of homoplasmic 11,778/ND4 mutation with no visual symptoms. [13][14][15] We also classified 14/74 individuals as ''LHON affected'' (affected) who carried the homoplasmic 11,778/ND4 mutation and suffered significant vision loss or blindness. [13][14][15] Finally, we classified 14/74 individuals as ''off pedigree'' (controls) as being a family member not belonging to the maternal lineage, thus not carrying the 11,778/ND4 mutation and with no visual complaints.…”

Section: Methodsmentioning

confidence: 99%

“…[13][14][15] We also classified 14/74 individuals as ''LHON affected'' (affected) who carried the homoplasmic 11,778/ND4 mutation and suffered significant vision loss or blindness. [13][14][15] Finally, we classified 14/74 individuals as ''off pedigree'' (controls) as being a family member not belonging to the maternal lineage, thus not carrying the 11,778/ND4 mutation and with no visual complaints. [13][14][15] Among carriers, 21/46 were male and 25/46 female.…”

Section: Methodsmentioning

confidence: 99%

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Neuron-Specific Enolase Is Elevated in Asymptomatic Carriers of Leber's Hereditary Optic Neuropathy

Yee

Ross‐Cisneros

Lee

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Neuron-specific enolase (NSE) is a biomarker for neuronal stress. Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease affecting retinal ganglion cells (RGC). These RGCs and their axons in the retinal nerve fiber layer (RNFL) and optic nerve head may show subclinical pathology in unaffected mutation carriers, or undergo cell death in affected patients. We hypothesize that increased levels of blood NSE may characterize LHON carriers as a biomarker of ongoing RGC stress.METHODS. Serum was obtained from 74 members of a Brazilian pedigree with LHON carrying the homoplasmic 11778/ND4 mitochondrial DNA mutation. Classified by symptoms and psychophysical metrics, 46/74 patients were unaffected mutation ''carriers,'' 14/74 were ''affected,'' and 14/74 were ''off-pedigree'' controls. Serum NSE levels were determined by ELISA specific for the c subunit of NSE.RESULTS. Serum NSE concentrations in carriers (27.17 6 39.82 lg/L) were significantly higher than affected (5.66 6 4.19 lg/ L; P ¼ 0.050) and off-pedigree controls (6.20 6 2.35 lg/L; P ¼ 0.047). Of the 14/46 (30.4 %) carriers with significantly elevated NSE levels (mean ¼ 75.8 6 42.3 lg/L), 9/14 (64.3%) were male. Furthermore, NSE levels were nearly three times greater in asymptomatic male carriers (40.65 6 51.21 lg/L) than in asymptomatic female carriers (15.85 6 22.27 lg/L; P ¼ 0.034).CONCLUSIONS. Serum NSE levels are higher in LHON carriers compared with affected and off-pedigree individuals. A subgroup of mostly male carriers had significantly elevated serum NSE levels. Thus, male carriers are at higher risk for LHON-related neuronal stress. (Invest Ophthalmol Vis Sci.

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Ophthalmologic findings in a large pedigree of 11778/Haplogroup J Leber hereditary optic neuropathy

Cited by 78 publications

References 25 publications

Evaluation of optic nerve head configuration in various types of optic neuropathy with Heidelberg Retina Tomograph

Evaluation of optic nerve head configuration in various types of optic neuropathy with Heidelberg Retina Tomograph

Mathematically Modeling the Involvement of Axons in Leber's Hereditary Optic Neuropathy

Neuron-Specific Enolase Is Elevated in Asymptomatic Carriers of Leber's Hereditary Optic Neuropathy

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