Glaucomatous optic nerve atrophy: the circumlinear vessel revisited

Baring of a circumlinear vessel, or gap sign, is a sign of glaucomatous optic neuropathy that can be rapidly assessed during direct ophthalmoscopy. We previously found a significant association between the presence of this sign and the diagnosis and status of visual field defects. In the current study we followed this same group of patients for a mean of 78 months. The rate of agreement between two independent observers for the presence or absence of a circumlinear vessel was 79%, and the intraobserver rate was 71%. The corresponding rates for the presence of a gap sign were 84% and 90%. The presence of baring was significantly associated with development of a visual field defect in the glaucoma suspect group (p = 0.0105). The development of a gap sign in photographs taken approximately 6 years later was significantly associated with clinical progression of the appearance of the disc or the visual field defect (p = 0.0142). We conclude that patients with baring of a circumlinear vessel should be closely monitored for the development or progression of the glaucomatous process.     

Optic nerve head drusen associated with abnormally small optic discs

Summary Using Littmann's method for correcting the magnification of central fundus photographs we evaluated the absolute optic disc size in 26 eyes with visible optic nerve head drusen. The optic nerve head area in these eyes (1.79 + –0.50mm²) was significantly smaller (p<0.001) than normal standard values previously determined (2.89 + –0.76 mm²). The drusen were most commonly located and most densely packed at the upper and lower optic disc border. The coefficients of variation of the method's reproducibility were 0.06 for intraobserver and 0.11 for interobserver determination.The abnormally small optic disc indicating an abnormally small optic nerve scleral canal may inhibit by mechanical compression the axonal flow within the optic nerve fibers. This may ultimately lead to drusen formation. Pseudoneuritis also associated with an abnormally small optic disc may be a preceder of acquired optic nerve head drusen.This study was supported in part by the Deutsche Forschungsgemeinschaft, grant Nr. NA/55-4/1.     

Glaucomatous optic nerve head changes with scanning laser ophthalmoscopy

Purpose: To determine whether there are angiographicdifferences among normal, preperimetric and advanced glaucoma eyes using indocyaninegreen angiography with SLO. This method was chosen because of its sensibility todetect peripapillary capillary vessels.Methods: Scanning laser opthalmoscopy was preformed on normal eyes, preperimetric glaucomas and advanced glaucomas.Material: The authors used a confocal SLO (HeidelbergRetina Angiograph-HRA)Conclusion: Several changes may be seen on peripapillarycapillary vessels at the different glaucomatous stages.Discussion: In normal subjects HRT shows preservation ofthe disc/cup area ratio; indocyanine green angiography shows normalprepapillary plexus pattern on the neuroretinal rim and cup.Subjects on glaucomatous preperimetric stage reveal a decrease in the disc/cuparea ratio as a result of an increase of the cup area secondary to a reductionof the neuroretinal rim area. ICG at this hipertensive stage shows an increasein prepapillary plexus visualization, which may be a consequence of increasedblood flow while autoregulation is still operative.Subjects with advanced glaucoma show prominent decrease in the disc/cuparea ratio as well as marked capillary droupout in ICG angiography.     

Pseudopapilledema associated with abnormally small optic discs

Using Littmann's method for correcting the magnification of central fundus photographs, we determined the absolute size of 35 unselected optic discs with pseudopapilledema. The optic disc area (1.95 +/- 0.33 mm2 (mean and SD)) was significantly (P less than 0.001, Student's t-test ) smaller than standard values of normal unselected optic nerve heads (2.73 +/- 0.76 mm2). There was no cupping in the discs with pseudopapilledema. Coefficients of variation for intraobserver re-evaluation were 0.045, and for interobserver re-evaluation 0.08. The markedly reduced optic disc size coincide with an abnormally small optic nerve scleral canal may inhibit the intraaxoplasmatic flow with secondary swelling of the juxtapapillary optic nerve fibers. This may lead t o prominence and indistinct borders of the optic disc. Pseudopapilledema might be related to optic nerve head drusen, which are also associated with abnormally small optic discs.     

Dominant infantile optic nerve atrophy

The authors present an account of a family with an autosomal dominant infantile atrophy of the optic nerve. In three generations two men and three women were affected. With the clinical picture of simple atrophy of the optic nerve with a different degree of expressivity corresponded functional and fluoroangiographic changes. Disorders of colour vision were within the range of deuteroanomaly, deuteroanopia. The proband suffered also from tritanopia. The disease did not call for amaurotic training.     

Anterior optic nerve blood flow in experimental optic atrophy

This study attempts to establish whether neurogenic optic atrophy induces changes in anterior optic nerve circulation and to determine how noninvasive techniques of measuring blood flow in vivo compare to microsphere distribution. Five cats underwent unilateral optic nerve transection in the orbital apex and a sham procedure in the contralateral eye. Two to three months later, no abnormalities were detected by fluorescein angiography. Laser Doppler measurements demonstrated a 53% decrease in red blood cell speed through the capillaries of the atrophic optic nerve heads in vivo. Optic disk reflectance measurements of anterior optic nerve blood volume in vivo demonstrated a 51% decrease in the estimated blood volume of the capillaries in atrophic optic nerve heads. Flow was calculated on the basis of these noninvasive measurements and demonstrated an average decrease of 74% in optic atrophy. Histologic studies of microsphere distribution demonstrated an average decrease of 80% in flow to the anterior optic nerve in optic atrophy. These results suggest that anterior optic nerve blood flow is significantly reduced in primary neurogenic optic atrophy. This study also demonstrates that the noninvasive measurements of blood flow are substantiated by histologic evaluation of microsphere distribution.     

Ampli-pulse phoresis in patients with partial optic nerve atrophy

A new complex method for treating partial atrophies of the optic nerve unites surgical, physiotherapeutic, and drug effects. One electrode is attached directly to the anterior segment of the optic nerve by a collagen infusion system and the other is fixed at the back of the neck. The involved optic nerve is exposed to sinusoidal modulated currents in the rectified mode, permitting direct drug electrophoresis in parallel with electric stimulation of nerve fibers. The efficiency of the method is two times higher than of standard treatment.     

Bilateral optic nerve atrophy in myotonic dystrophy

PURPOSE: To document a case of bilateral optic atrophy in a patient with myotonic dystrophy. Myotonic dystrophy is an autosomal dominant disorder, genetically resulting from an expansion of an unstable CTG repeat in the 3'-untranslated region of a protein kinase gene (DMPK) on chromosome 19q13.3. METHODS: Case report, clinical examination, fundus photographs, visual fields, visual evoked potentials, electroretinograms, and genetic studies of a 56-year-old woman clinically diagnosed with myotonic dystrophy. RESULTS: The patient experienced decreased vision consisting of light perception with the right eye and 20/25 with the left. Fundus examination showed bilateral pallor of the optic disks. Intraocular pressure was normal. Visual field testing, visual evoked potentials, and electroretinogram were abnormal. A pathologic CTG expansion in the myotonic dystrophy gene was found. CONCLUSIONS: In a patient with myotonic dystrophy, confirmed with genetic molecular diagnosis, bilateral optic atrophy was present. Optic atrophy should be considered a possible complication of myotonic dystrophy.     

Dominant optic atrophy: Culprit mitochondria in the optic nerve

Dominant optic atrophy (DOA) is an inherited mitochondrial disease leading to specific degeneration of retinal ganglion cells (RGCs), thus compromising transmission of visual information from the retina to the brain. Usually, DOA starts during childhood and evolves to poor vision or legal blindness, affecting the central vision, whilst sparing the peripheral visual field. In 20% of cases, DOA presents as syndromic disorder, with secondary symptoms affecting neuronal and muscular functions. Twenty years ago, we demonstrated that heterozygous mutations in OPA1 are the most frequent molecular cause of DOA. Since then, variants in additional genes, whose functions in many instances converge with those of OPA1, have been identified by next generation sequencing. OPA1 encodes a dynamin-related GTPase imported into mitochondria and located to the inner membrane and intermembrane space. The many OPA1 isoforms, resulting from alternative splicing of three exons, form complex homopolymers that structure mitochondrial cristae, and contribute to fusion of the outer membrane, thus shaping the whole mitochondrial network. Moreover, OPA1 is required for oxidative phosphorylation, maintenance of mitochondrial genome, calcium homeostasis and regulation of apoptosis, thus making OPA1 the Swiss army-knife of mitochondria. Understanding DOA pathophysiology requires the understanding of RGC peculiarities with respect to OPA1 functions. Besides the tremendous energy requirements of RGCs to relay visual information from the eye to the brain, these neurons present unique features related to their differential environments in the retina, and to the anatomical transition occurring at the lamina cribrosa, which parallel major adaptations of mitochondrial physiology and shape, in the pre- and post-laminar segments of the optic nerve. Three DOA mouse models, with different Opa1 mutations, have been generated to study intrinsic mechanisms responsible for RGC degeneration, and these have further revealed secondary symptoms related to mitochondrial dysfunctions, mirroring the more severe syndromic phenotypes seen in a subgroup of patients. Metabolomics analyses of cells, mouse organs and patient plasma mutated for OPA1 revealed new unexpected pathophysiological mechanisms related to mitochondrial dysfunction, and biomarkers correlated quantitatively to the severity of the disease. Here, we review and synthesize these data, and propose different approaches for embracing possible therapies to fulfil the unmet clinical needs of this disease, and provide hope to affected DOA patients.     

Anterior optic nerve blood flow decreases in clinical neurogenic optic atrophy

Anterior optic nerve blood flow was studied in nine patients with unilateral neurogenic optic atrophy using noninvasive techniques. Disk reflectometry measurements from temporal sites demonstrated a significant reduction in the index of blood volume in atrophic optic nerves as compared with the contralateral optic nerves (P less than 0.00001). Laser Doppler measurements from the same temporal sites detected a significant reduction in the speed of blood (P less than 0.002). On average, blood volume was decreased by 49% +/- 11% and blood speed by 30% +/- 17%. Combining the results of these two techniques yielded a relative index of blood flow that showed a significant reduction in the atrophic nerves (P less than 0.0001), averaging 64% +/- 14% temporally. Nasally there was less reduction in blood flow. The results correlated well with clinical assessment of the degree of optic nerve damage (rho = 0.92, P less than 0.002). This study demonstrates that clinical neurogenic optic atrophy induces significant reductions in overall anterior optic nerve blood flow that are detected by these noninvasive techniques.     

Electrophysiological diagnosis in partial optic nerve atrophy syndrome

Vision conduction routes were examined in 75 patients with the syndrome of optic nerve partial atrophy by recording the visual evoked potentials, threshold of electric sensitivity emergence, critical frequency of phosphene disappearance, electroretino- and electroneurograms. The findings of these examinations correlated best of all with the clinical picture when visual evoked potentials (latency increase, decrease of the amplitude with atrophy augmentation, interhemispheric asymmetry in chiasmal and retro-chiasmal involvement) or the critical frequency of phosphene disappearance (reliably reduced if a disease was developing) were recorded. Introduction of electrodes with therapeutic and diagnostic purpose permitted assessment of optic nerve function from the electroneurogram amplitude and time parameters.     

Optic disc morphometry in simple optic nerve atrophy

This study was undertaken to evaluate the optic disc changes in eyes with non-glaucomatous optic nerve damage. The intra- and parapapillary region was evaluated morphometrically in 106 eyes of 56 patients with simple optic nerve atrophy (SONA) and in 107 normal eyes of 57 subjects. Colour stereo optic disc diapositives were used. Only one randomly chosen eye per subject and patient was taken for statistical analysis. Characteristics of SONA were: decreased visibility of the parapapillary retinal nerve fibers, diminished retinal vessel diameter, and area with pallor larger than area with cupping. Size and form of the optic disc, neuroretinal rim, peripapillary scleral ring, and zone Alpha and Beta of the parapillary chorioretinal atrophy were not significantly different. Also, distinctness of a tesselated fundus, frequency of optic disc haemorrhages and frequency of bared circumlinear or bared cilioretinal vessels did not differ significantly. These morphologic features are helpful in the diagnosis and differential diagnosis of SONA.