Neuropatía óptica en un caso de paquimeningitis hipertrófica idiopática recurrente sin respuesta a esteroides e inmunosupresores / Optic neuropathy in a case of recurrent idiopathic hypertrophic pachymeningitis unresponsive to steroids and immunosuppressants

CASO CLÍNICO: Mujer de 38 años con pérdida visual en ojo izquierdo y papiledema bilateral. La resonancia magnética nuclear (RMN) mostraba engrosamiento de la duramadre y la presión intracraneal estaba elevada. Se descartó enfermedad infecciosa, tumoral y autoinmune. DISCUSIÓN: La respuesta inicial a corticoides fue satisfactoria con desaparición del edema de disco óptico, mejoría de la agudeza visual y mejoría radiológica. Después de un año sin tratamiento presentó un nuevo brote, desarrollando una neuropatía óptica izquierda con pérdida irreversible de visión a pesar del retratamiento con corticoides y azatioprina

CASE REPORT: A 38-year-old female patient with bilateral papilledema who presented with loss of vision in her left eye. The Magnetic Resonance Imagining (MRI) showed thickening of the dura mater, and the intracranial pressure was elevated. A cancer, infectious, and autoimmune origin was ruled out. DISCUSSION: The initial response to high doses of corticoids was satisfactory, with disappearance of the optic disc enema, with visual acuity and an improvement in the MRI. However, after one year without treatment she had a new outbreak of the disease. Despite renewed treatment with corticoids and azathioprine, the patient developed a left optic neuropathy and irreversible visual loss

Dietary omega-3 fatty acids, other fat intake, genetic susceptibility, and progression to incident geographic atrophy.

OBJECTIVE: To investigate associations between dietary omega-3 fatty acids and other fat intake, genes related to age-related macular degeneration (AMD), and progression to geographic atrophy (GA). DESIGN: Observational analysis of a prospective cohort. PARTICIPANTS: A total of 2531 individuals from the Age-Related Eye Disease Study, among which 525 eyes progressed to GA and 4165 eyes did not. METHODS: Eyes without advanced AMD at baseline were evaluated for progression to GA. Behavioral data, including smoking and body mass index measurements, were collected at baseline using questionnaires. Dietary data were collected from food frequency questionnaires (FFQs) at baseline. Omega-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]), omega-6 fatty acids, monounsaturated, saturated, polyunsaturated, and total fat were adjusted for sex and calories and divided into quintiles (Q). Eight single nucleotide polymorphisms in 7 genes (CFH, ARMS2/HTRA1, CFB, C2, C3, CFI, and LIPC) were genotyped. Cox proportional hazards models were used to test for associations between incident GA and intake of dietary lipids and interaction effects between dietary fat intake and genetic variation on risk of GA. MAIN OUTCOME MEASURES: Associations between dietary fat intake reported from FFQs, genetic variants, and incident GA. RESULTS: Increased intake of DHA was significantly associated with reduced risk of progression to GA in models with behavioral factors (model A) plus genetic variants (model B) (P trend = 0.01 and 0.03, respectively). Total omega-3 long chain polyunsaturated (DHA + EPA) fatty acid intake was significantly associated with reduced risk of progression in model B (P trend = 0.02). Monounsaturated fat was associated with increased risk in model A (P trend = 0.05). DHA intake was significantly associated with reduced risk of incident GA among those with the ARMS2/HTRA1 homozygous risk genotype (hazard ratio [HR] Q5 vs Q1, 0.4; P = 0.002; P for interaction between gene and fat intake = 0.05). DHA was not associated with reduced risk of GA among those with the homozygous ARMS2/HTRA1 nonrisk genotype (HR, 1.0; P = 0.90). CONCLUSIONS: Increased self-reported dietary intake of omega-3 fatty acids is associated with reduced risk of GA and may modify genetic susceptibility for progression to GA. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Mutant NADH dehydrogenase subunit 4 gene delivery to mitochondria by targeting sequence-modified adeno-associated virus induces visual loss and optic atrophy in mice.

PURPOSE: Although mutated G11778A NADH ubiquinone oxidoreductase subunit 4 (ND4) mitochondrial DNA (mtDNA) is firmly linked to the blindness of Leber hereditary optic neuropathy (LHON), a bona fide animal model system with mutated mtDNA complex I subunits that would enable probing the pathogenesis of optic neuropathy and testing potential avenues for therapy has yet to be developed. METHODS: The mutant human ND4 gene with a guanine to adenine transition at position 11778 with an attached FLAG epitope under control of the mitochondrial heavy strand promoter (HSP) was inserted into a modified self-complementary (sc) adeno-associated virus (AAV) backbone. The HSP-ND4FLAG was directed toward the mitochondria by adding the 23 amino acid cytochrome oxidase subunit 8 (COX8) presequence fused in frame to the N-terminus of green fluorescent protein (GFP) into the AAV2 capsid open reading frame. The packaged scAAV-HSP mutant ND4 was injected into the vitreous cavity of normal mice (OD). Contralateral eyes received scAAV-GFP (OS). Translocation and integration of mutant human ND4 in mouse mitochondria were assessed with PCR, reverse transcription-polymerase chain reaction (RT-PCR), sequencing, immunoblotting, and immunohistochemistry. Visual function was monitored with serial pattern electroretinography (PERG) and in vivo structure with spectral domain optical coherence tomography (OCT). Animals were euthanized at 1 year and processed for light and transmission electron microscopy. RESULTS: The PCR products of the mitochondrial and nuclear DNA extracted from infected retinas and optic nerves gave the expected 500 base pair bands. RT-PCR confirmed transcription of the mutant human ND4 DNA in mice. DNA sequencing confirmed that the PCR and RT-PCR products were mutant human ND4 (OD only). Immunoblotting revealed the expression of mutant ND4FLAG (OD only). Pattern electroretinograms showed a significant decrement in retinal ganglion cell function OD relative to OS at 1 month and 6 months after AAV injections. Spectral domain optical coherence tomography showed optic disc edema starting at 1 month post injection followed by optic nerve head atrophy with marked thinning of the inner retina at 1 year. Histopathology of optic nerve cross sections revealed reductions in the optic nerve diameters of OD versus OS where transmission electron microscopy revealed significant loss of optic nerve axons in mutant ND4 injected eyes where some remaining axons were still in various stages of irreversible degeneration with electron dense aggregation. Electron lucent mitochondria accumulated in swollen axons where fusion of mitochondria was also evident. CONCLUSIONS: Due to the UGA codon at amino acid 16, mutant G11778A ND4 was translated only in the mitochondria where its expression led to significant loss of visual function, loss of retinal ganglion cells, and optic nerve degeneration recapitulating the hallmarks of human LHON.

A case of optic nerve atrophy with severe disc cupping after methanol poisoning.

We report a rare case of optic nerve atrophy with severe disc cupping resulting from methanol poisoning. A 30-year-old man presented to the hospital complaining of decreased visual acuity in both eyes a day after drinking alcohol containing methanol. His initial visual acuity allowed for only visualizing hand motion and not corrected in either eye. Initial intraocular pressure was within normal limits in both eyes. Initial fundus examination showed optic disc swelling in both eyes. Four years later, he visited our hospital for an eye evaluation. Visual acuity in both eyes still only allowed for visualizing hand motion. No nystagmus was observed in either eye during the optokinetic nystagmus test, and no waves were found in a visual evoked potential test. No specific change was noted on brain magnetic resonance imaging. On fundus examination, there was disc pallor in both eyes and disc cupping with a high cup/disc (C/D) ratio above 0.9 in the left eye. C/D ratio of the right eye was 0.5. Methanol poisoning may induce glaucomatous disc cupping in the late stage as well as optic atrophy. One possible mechanism of disc cupping is ganglion cell loss due to acute demyelination of the retrobulbar optic nerve. This report is the first photographic evidence of methanol induced optic disc cupping in Korea.

Neurological disorders associated with cassava diet: a review of putative etiological mechanisms.

Tropical ataxic neuropathy (TAN) and epidemic spastic paraparesis (konzo) are two neurological disorders associated with the consumption of cassava (Manihot esculenta) in several African countries. TAN is characterized by sensory polyneuropathy, sensory ataxia, bilateral optic atrophy and bilateral sensori-neural deafness. It occurs in elderly individuals subsisting on a monotonous cassava diet with minimal protein supplementation. Konzo is a syndrome of symmetrical spastic paraparesis with a predilection for children and young women and invariably associated with consumption of inadequately processed bitter cassava roots with minimal protein supplementation. Despite numerous epidemiological, clinical and biochemical studies aimed at elucidating the etiological mechanisms of these disorders, their etiologies remain unknown, and there is no known treatment. The diseases continue to be prevalent in endemic areas, causing significant disability and increased mortality. A fresh appraisal of the putative etiologic mechanisms proposed for these intriguing and enigmatic syndromes is presented in this paper. Evidences against a causal role for cyanide intoxication are discussed, and evidences implicating thiamine deficiency as a unifying etiological mechanism for these neurological syndromes are presented. It is concluded that urgent research is needed to evaluate thiamine status and implement a therapeutic trial of thiamine in these debilitating neurological disorders.

Taurine deficiency damages photoreceptors and retinal ganglion cells in vigabatrin-treated neonatal rats.

The anti-epileptic drug vigabatrin induces an irreversible constriction of the visual field, but is still widely used to treat infantile spasms and some forms of epilepsy. We recently reported that vigabatrin-induced cone damage is due to a taurine deficiency. However, optic atrophy and thus retinal ganglion cell degeneration was also reported in children treated for infantile spasms. We here show in neonatal rats treated from postnatal days 4 to 29 that the vigabatrin treatment triggers not only cone photoreceptor damage, disorganisation of the photoreceptor layer and gliosis but also retinal ganglion cell loss. Furthermore, we demonstrate in these neonatal rats that taurine supplementation partially prevents these retinal lesions and in particular the retinal ganglion cell loss. These results provide the first evidence of retinal ganglion cell neuroprotection by taurine. They further confirm that taurine supplementation should be administered with the vigabatrin treatment for infantile spasms or epilepsy.

Morphological changes in the visual pathway induced by experimental glaucoma in Japanese monkeys.

Glaucoma, an optic neuropathy, is the leading cause of world blindness. In this condition, the damage extends from the retina to the visual center in the brain, although the primary region of damage is thought to be the optic nerve head (ONH), with the lateral geniculate nucleus (LGN) being secondarily affected. We investigated time-dependent alterations in the ONH, the optic nerve (ON), and the LGN after intraocular pressure (IOP) elevation in Japanese monkeys (a species more similar to humans than other macaque species). Nine Japanese monkeys, each with an experimental glaucomatous left eye, and two naive monkeys were studied. Ocular-testing sessions (including IOP measurement and fundus photography) were held weekly. Eyes and brains were enucleated at 2-48 weeks after IOP elevation, and alterations in ONs and LGN were evaluated. The IOP of the treated eyes was monitored periodically and found to be elevated continuously throughout the observation period in each monkey. The ONH of the glaucomatous eyes exhibited time-dependent deep cupping and thinning of the rim area from 2 weeks after the IOP elevation. Loss of axons and a decrease in the area of ON were first observed at 4 and 28 weeks, respectively. Neuronal loss was first observed at 2 weeks in layers 1 and 2 of LGN [magnocellular (M)-layer] and at 12 weeks in layers 3-6 of LGN [parvocellular (P)-layer]. Neuronal shrinkage was first observed at 2 weeks in all layers in LGN. These findings indicate that in Japanese monkeys, damage to neurons in LGN can be detected in the early phase (first few weeks) after an IOP elevation, as can damage to ONH.

Psychiatric symptoms in a patient with Wolfram syndrome caused by a combination of thalamic deficit and endocrinological pathologies.

DIDMOAD or Wolfram syndrome is a hereditary disorder characterized by early onset diabetes and optic atrophy. Besides these features, a variety of other symptoms have been described including psychiatrical abnormalities leading to hospitalization in about 25% of all patients. To our knowledge, until now, a detailed characterization of these psychiatric symptoms does not exist. Here we describe a 21-year-old male patient with deficits of frontal lobe function, such as impaired impulse control and learning deficits. Magnetic resonance imaging (MRI) of the brain showed a bilateral optic atrophy, but no signs of frontal brain atrophy. Neuropsychological tests revealed performance deficits in complex planning (e.g., Tower of London). Also his capacities in memorizing logically connected information after a short and delayed period of time were significantly reduced. Since histopathological studies did not reveal frontal brain abnormalities, but did show thalamic neuronal loss and gliosis, we interpret our findings as representative of thalamic dysfunction. In addition, hypoglycaemia seemed to trigger rapid mood swings. As soon as blood glucose levels improved, the patient stabilized emotionally and assaultive behaviour disappeared while the cognitive deficits remained unchanged.

Optic nerve hydropic axonal degeneration and blocked retrograde axoplasmic transport: histopathologic features in human high-pressure secondary glaucoma.

OBJECTIVE: To describe histopathologic features of anterior optic nerves of 12 eyes enucleated for sustained high ocular pressure from iris-ciliary body melanomas in 10 and choroidal melanomas with chronic angle closure in 2. METHODS: In this retrospective study, we analyzed cases indexed in 2 eye pathology laboratories and reviewed the pertinent literature. Cases were identified from diagnostic indexes; microscopic study of slides stained with hematoxylin-eosin and Verhoeff-van Gieson, Mallory trichrome, periodic acid-Schiff, alcian blue, or colloidal iron for acid mucopolysaccharide; review of available clinical documentation; and analysis of features and photography. The main outcome measures were description of optic nerve heads, prelaminar atrophy, laminar posterior bowing, locations and density of hydropic axonal degeneration, blocked retrograde axoplasmic transport, posterior atrophy, and optic nerve disorganization with glial proliferation. RESULTS: Hydropic axonal degeneration was present in front of, within, and posterior to the lamina cribrosa in all 12 eyes. This degeneration extended diffusely and posteriorly from the peripheral lamina and was most dense centrally in 10 eyes. Retrolaminar changes compatible with blockage of retrograde axoplasmic transport were seen in 9 eyes. Posterior atrophy with disorganization and glial proliferation was seen in 10 eyes. No eye had classic glaucomatous atrophic cupping. CONCLUSIONS: Diffuse and centrally intense hydropic axonal degeneration and central blocked retrograde axoplasmic transport explain loss of central acuity, generalized contraction of visual field, and generalized optic atrophy without glaucomatous cupping in eyes with prolonged high-pressure secondary glaucoma.

[Irrigation therapy as a method of intensive care of ophthalmopathology in the posterior eye segment in children].

Presented in the paper are data of a comparative analysis of efficiency of different methods of administration of drugs in neuritis and partial atrophy of the optic nerve. New techniques of application and fixation of irrigation systems in the retrobulbar and Tenon's space are described. Experimental and clinical data proving advantages of the new method of administration of drugs by an automatic pulse doser in the treatment of inflammatory diseases of the optic nerve are represented. The use of such intensive intermittent technique of administration of drugs in Tenon's space performed at the preliminary stage before electrostimulation of the optic nerve made the procedure by far more effective and ensured better treatment results.

[Primary intraocular lymphoma with unusual clinical presentation and poor outcome]. / Primäres intraokuläres Lymphom mit untypischer Klinik und ungünstigem Verlauf.

BACKGROUND: Primary intraocular lymphoma is a distinct subset of primary non-Hodgkin's lymphoma of the CNS. In general, the primary non-Hodgkin's lymphoma of the CNS is rare, accounting for 1 % of all non-Hodgkin's lymphomas and less than 1 % of all intraocular tumors. HISTORY AND SIGNS: A 70-year-old man was hospitalized in June 2002 because of acute loss of vision on his left eye. A severe vitreous hemorrhage was observed. Ultrasound showed solid subretinal lesions at the posterior fundus. Diagnostic vitreous surgery including a biopsy was performed. An intraocular malignant B-cell lymphoma was determined by immunohistochemistry. General screening revealed no further manifestations of the lymphoma. THERAPY AND OUTCOME: The patient initially refused any therapy until a painful secondary neovascular glaucoma with complete loss of visual function developed, thus prompting us to perform an enucleation. The following immunohistochemical examination confirmed the initial diagnosis. A chemotherapy with high-dose methotrexate and leucovorin rescue was initiated. CONCLUSIONS: Primary intraocular lymphoma can present as diffuse uveitis refractory to corticosteroids. Diagnosis can be difficult and is often delayed.

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.

Correlation between optic disc atrophy and aetiology: anterior ischaemic optic neuropathy vs optic neuritis.

BACKGROUND: The morphologic features of swollen disc in the acute stage of optic neuritis and anterior ischaemic optic neuropathy (AION) have been extensively investigated in contrast to the morphologic features of optic disc atrophy after these events. OBJECTIVE: : A prospective study to evaluate the morphologic features of optic disc atrophy 6 months or more after optic neuritis and nonarteritic AION. PATIENTS AND METHODS: A total of 35 optic discs after nonarteritic AION (n=27) and 24 after optic neuritis (n=19) in otherwise healthy subjects have been evaluated by direct fundoscopic examination with a +90 diopters lens and optic disc photography. The average age of patients at the onset of AION was 57.8 years (range: 38-80) and at the onset of optic neuritis was 32.6 (range: 19-46). The female:male ratio was 18 : 17 in the former and 15 : 9 in the latter. The evaluated parameters included: degree of rim pallor (0 to +3), location of rim pallor, height of rim above the retina, depth and width of cup, peripapillary retinal artery to vein (A : V) ratio, and peripapillary pigment epithelial atrophy. A comparison was made also with 17 age-matched normal discs of 17 patients. Statistical significance was calculated with chi(2) and Fisher's exact test. RESULTS: Most of the discs after AION were paler (+2: 70%, +3: 26%) than after optic neuritis (normal colour: 8%, +1: 58%, P< or =0.007). Rim segmental involvement after AION was usually either superior 'altitudinal' (53%) or inferior 'altitudinal' (29%), whereas after optic neuritis, it was usually either temporal-central (papillomacular) (42%) or diffuse temporal (42%, P<0.0001). Discs had lower A : V ratio (1 : 3, 40%) after AION compared with optic neuritis (1 : 3, 8%) (P=0.007). There were no significant differences between the two groups in height of the rim, cupping, and peripapillary atrophy. CONCLUSIONS: : A combination of the degree of rim pallor, location of rim pallor, and A : V ratio may be of value in assessing the aetiology of optic disc atrophy when no previous clinical data are available and a compressive lesion has been ruled out.

[Ampli-pulse phoresis in patients with partial optic nerve atrophy]. / Primenenie amplipul's-foreza u patsientov s chastichnoi atrofiei zritel'nogo nerva.

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.

Correlation of the peripapillary atrophy area with optic disc cupping and disc hemorrhage.

PURPOSE: To investigate the association of the peripapillary atrophy area with disc cupping area and disc hemorrhage in subjects who underwent ocular examination as part of a routine physical examination. METHODS: We reviewed plain color fundus photographs taken of 12,140 eyes of 6,070 subjects as part of a routine health examination. The refractive error in these eyes was not known. Using a computerized image analysis system, we measured the area of peripapillary atrophy (zone beta), the optic disc, and optic disc cupping by means of planimetry in 8,842 eyes of 4,421 subjects with fundus images of good quality. RESULTS: The ratio of cup area to disc area was significantly greater in eyes with peripapillary atrophy (0.36 + 0.09) than in eyes without peripapillary atrophy (0.34 + 0.07), and the ratio of peripapillary atrophy area to disc area was significantly greater in eyes with disc hemorrhage (0.26 + 0.34) than in those without disc hemorrhage (0.09 + 0.18). Moreover, in eyes with peripapillary atrophy, the ratio of cup area to disc area was significantly larger in eyes with disc hemorrhage (0.48 + 0.08) than in those without disc hemorrhage (0.36 + 0.09). These results remained statistically unchanged even after "glaucomatous" eyes were excluded from the study. CONCLUSION: Peripapillary atrophy appears to be associated with a higher degree of cupping of the optic disc and disc hemorrhage, and the results suggest an association between peripapillary atrophy and glaucomatous optic neuropathy.

Essential iris atrophy, pigment dispersion, and glaucoma in DBA/2J mice.

PURPOSE: To characterize ocular abnormalities associated with iris atrophy in DBA/2J mice and to determine whether mice of this strain develop elevated intraocular pressure (IOP) and glaucoma. METHODS: Different approaches, including slit-lamp biomicroscopy, ophthalmoscopic examination, ultrasound backscatter microscopy, and histology were used to examine the eyes of DBA/2J mice ranging from 2 to 30 months old. IOP was measured in DBA/2J mice of different ages. RESULTS: DBA/2J mice were found to develop pigment dispersion, iris transillumination, iris atrophy, anterior synechias, and elevated IOP. IOP was elevated in most mice by the age of 9 months. These changes were followed by the death of retinal ganglion cells, optic nerve atrophy, and optic nerve cupping. The prevalence and severity of these lesions increased with age. Optic nerve atrophy and optic nerve cupping was present in the majority of mice by the age of 22 months. CONCLUSIONS: DBA/2J mice develop a progressive form of secondary angle-closure glaucoma that appears to be initiated by iris atrophy and the associated formation of synechias. This mouse strain represents a useful model to evaluate mechanisms of pressure-related ganglion cell death and optic nerve atrophy, and to evaluate strategies for neuroprotection.

Optic disc morphology in "age-related atrophic glaucoma".

BACKGROUND: This study was performed in order to evaluate whether, in primary open-angle glaucoma (POAG), patients with a different degree of fundus tessellation vary in optic disc morphology and level of intraocular pressure. METHODS: Color stereo optic disc photographs of 562 patients with POAG and a myopic refractive error of less than -8 diopters were morphometrically examined. According to the degree of fundus tessellation, the total group was divided into a tessellated subgroup (n = 256) and a nontessellated subgroup (n = 306), both matched for neuroretinal rim area and refractive error. RESULTS: In the tessellated subgroup, as compared to the nontessellated subgroup, the mean maximal intraocular pressure values were significantly lower, the parapapillary atrophy was significantly larger, the optic cup was significantly more shallow, frequency of disc hemorrhages was lower, the mean visual field defect was significantly more marked, and patient age was significantly higher. Within the whole study group, the degree of fundus tessellation increased significantly (P < 0.005) with decreasing mean maximal intraocular pressure, decreasing optic cup depth, and increasing degree of parapapillary atrophy. In the subgroups with the highest degree of fundus tessellation, parapapillary atrophy was the greatest and the mean maximal intraocular pressure was the lowest compared to other subgroups. CONCLUSION: At the low-pressure end of POAG, marked fundus tessellation is associated with large parapapillary atrophy, shallow disc cupping, mostly concentric emaciation of the neuroretinal rim, and high patient age. The results suggest a distinct subtype of POAG in older patients with relatively low intraocular pressure leading to a mainly diffuse atrophy of the optic nerve.

Optic disc morphology in juvenile primary open-angle glaucoma.

BACKGROUND: The aim of the study was to evaluate whether, in primary open-angle glaucoma (POAG), patients younger than 40 years differ in optic disc morphology from patients older than 40 years. METHODS: Out of a total group of 419 patients with POAG, we formed and compared two subgroups, one consisting of 37 patients with an age of less than 40 years, the other composed of 382 patients with an age equal to or more than 40 years. Both subgroups were matched for neuroretinal rim area. We examined the optic disc morphometrically using stereo disc photographs. RESULTS: The younger subgroup, as compared to the older subgroup, showed deeper and steeper optic disc cupping, concentric emaciation of the neuroretinal rim, a significantly smaller area of parapapillary atrophy, and significantly higher maximal and minimal intraocular pressure measurements (P < 0.001). The size and shape of the optic disc and the diameter of the retinal vessels at the optic disc border did not vary significantly. CONCLUSIONS: In POAG, patients younger than 40 years differ in optic disc morphology from patients older than 40 years. The younger patients with POAG have high minimal and maximal intraocular pressure readings and an optic disc morphology with deep and steep cupping, concentric loss of neuroretinal rim, and an almost unremarkable parapapillary atrophy. POAG in patients under 40 represents chronic high-pressure open-angle glaucoma with mainly diffuse optic nerve damage.

Direct clinico-histological correlation of parapapillary chorioretinal atrophy.

Parapapillary chorioretinal atrophy is a morphological feature of glaucomatous optic nerve damage since it occurs more often and is larger in glaucomatous eyes than in normal eyes. This study was undertaken to find the histological correlation. Optic disc photographs and histological sections through the optic disc of 21 human eyes enucleated because of malignant uveal melanoma were morphometrically evaluated. Seventeen eyes had normal intraocular pressure and four eyes showed elevated intraocular pressure and glaucomatous optic disc cupping. Ophthalmoscopically, the parapillary chorioretinal atrophy was divided into zone 'alpha', located peripherally and characterised by irregular hypopigmentation and hyperpigmentation, and zone 'beta' located close to the optic disc border and showing visible sclera and visible large choroidal vessels. Histologically, zones 'A' and 'B' were differentiated. Zone 'A' peripheral to zone 'B' showed irregularities in the retinal pigment epithelium. It consisted of an unequal distribution of melanin granules and partial atrophy of cells. In zone 'B' adjacent to the optic disc, Bruch's membrane was bared of retinal pigment epithelium cells and the photoreceptors were markedly reduced in density or were completely missing. In a direct clinical histological comparison, zone 'A' correlated significantly with zone 'alpha' (r = 0.66; p < 0.01), and zone 'B' correlated with zone 'beta' (r = 0.99; p < 0.0001). Zone 'A', 'B', 'alpha' and 'beta' were larger in the four glaucomatous eyes than in the normal ones. The findings indicate that zone 'beta' represents histologically a complete loss of retinal pigment epithelium cells and an incomplete loss of adjacent photoreceptors. Zone 'alpha' may be the histological correlate of irregularities in the retinal pigment epithelium.