Papillomacular Bundle Research Articles

VITREOMACULAR TRACTION SYNDROME

To evaluate the relationship between preoperative structure and surgical outcome in eyes with macular edema caused by vitreomacular traction (VMT).A retrospective review of 24 eyes of 24 patients with macular edema due to VMT who underwent vitrectomy to relieve macular traction is presented. The diagnosis of VMT was based on findings of clinical examination and optical coherence tomography (OCT). Preoperative and postoperative best-corrected visual acuity was converted to logarithm of the minimal angle of resolution visual acuity for analysis. Patients with a minimum of 6 months of follow-up were included.Eyes were categorized into one of the three groups based on the relationship of the posterior hyaloid to the retina: Group 1 (11 eyes) had focal vitreofoveal hyaloidal attachment with perifoveal separation; Group 2 (6 eyes) had vitreoretinal hyaloidal attachment to the macula and papillomacular bundle; and Group 3 (7 eyes) had broad vitreofoveal attachment with a fine epiretinal membrane over the posterior pole. Mean postoperative follow-up was 9.8 months (range, 6-15 months). Twenty-one eyes (87.5%) had at least 1 line of improvement in visual acuity (logMAR). Improvement in vision was significantly greater in the eyes in Group 1 (2.82 +/- 1.47 lines) than in those in Group 2 (0.83 +/- 1.17 lines; P = 0.004) or Group 3 (1.29 +/- 0.49 lines; P = 0.036). Visual outcome correlated with symptom duration (P = 0.024), VMT category (Group 1, 2, or 3; P = 0.013), and preoperative central macular thickness (CMT) by OCT (P = 0.007). A decrease in mean CMT was also significantly correlated with VMT configuration (Group 1, 2, or 3; P = 0.041).Visual outcome after vitrectomy for VMT is correlated with preoperative vitreomacular structure, duration of symptoms, and preoperative CMT.

Alcoholic Optic Neuropathy: Another Complication of Alcohol Abuse

Back to table of contents Previous article Next article LETTERFull AccessAlcoholic Optic Neuropathy: Another Complication of Alcohol AbuseThomas Paparrigopoulos M.D.Elias Tzavellas M.D.Dimitris Karaiskos M.D.Ioannis Liappas M.D.,Thomas Paparrigopoulos M.D.Search for more papers by this authorElias Tzavellas M.D.Search for more papers by this authorDimitris Karaiskos M.D.Search for more papers by this authorIoannis Liappas M.D.Search for more papers by this author,Published Online:1 Jul 2008AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Alcohol affects both the central and the peripheral nervous system; hence, cognitive dysfunction as well as sensory and motor peripheral neuropathy are frequent complications of chronic abuse. 1 However, symptoms of cranial nerve neuropathy are not routinely examined in alcohol abusing patients. To emphasize the necessity of such an assessment, we report on a man who abused alcohol and presented with progressive visual loss attributed to optic nerve neuropathy. Case Report A 55-year-old man was admitted to the clinic for alcohol detoxification. He smoked one pack of cigarettes per day for many years and heavily abused alcohol for 15 years, which he had reduced over the last 2 years. Clinical examination revealed numbness and weakness, particularly of the lower limbs, diminished tendon reflexes, and progressive painless blurring of central vision bilaterally; these symptoms, developed over the last 2 years and had seriously compromised his daily functioning. A motor and sensory nerve conduction study showed slowed motor conduction and low-amplitude response to sensory stimuli, mostly on the right. Visual fields testing revealed an infero-temporal and central defect in the right eye and a superonasal, inferior, and central defect in the left. Humphrey 10–2 static perimetry showed bilateral caecocentral scotomas. Visual acuity was 8/10 in the right and 5/10 in the left eye. Color vision was normal. Intraocular pressure was 15 mmHg in both eyes and anterior segments were normal. Funduscopy findings were unremarkable. Blood count, serum vitamin B 12 and folate levels were normal, but macrocytosis was present (MCV: 104fl.); also, transaminases were elevated. Following alcohol withdrawal and a 6-month vitamin supplementation (vitamins C, E, B complex, folate, taken both orally and intramuscularly), peripheral neuropathy considerably improved but optic neuropathy remained refractory to treatment. Discussion Tobacco-alcohol amblyopia was often described prior to World War II in patients with heavy tobacco and ethanol consumption. At the present time, tobacco-alcohol amblyopia is either far less common or is seldom checked for and reported. 2 – 3 It is characterized by subacute or gradual loss of central vision, decreased visual acuity, and dyschromatopsia. Fundi may appear normal, with few abnormalities on detailed examination; temporal atrophy of the optic disk may become evident at later stages. Metabolic optic neuropathies are characterized by specific loss of the nerve fiber layer in the papillomacular bundle. 2 – 4 They are etiologically distinguished from hereditary-degenerative neuropathies, neuropathies due to nutritional deficiencies (e.g., thiamine, vitamin B 12 and folic acid deficiency), and neuropathies caused by various toxic agents (e.g., ethambutol and cyanide). Impairment of mitochondrial oxidative phosphorylation has been proposed as the common underlying pathophysiological mechanism. 5 In tobacco-alcohol amblyopia, gradual accumulation of formic acid, malnutrition, thiamine depletion, poor B 12 absorption in the presence of ethanol, and a number of toxic tobacco ingredients, particularly cyanide, act synergistically to the development of neuropathy. Vitamin and nutritional deficiencies are considered especially important factors for its development and recovery is purportedly complete with abstinence from alcohol and smoking and vitamin supplementation. 3 – 5The present case, the first reported in the literature, does not fulfill the characteristic tobacco-alcohol amblyopia criteria, in that dyschromatopsia, an essential component of tobacco-alcohol amblyopia, is absent and no recovery of vision loss was recorded following sobriety from alcohol and tobacco and protracted vitamin treatment. These findings point to the possibility of a nonreversible atypical form of optic nerve neuropathy due to alcohol abuse.Athens University Medical School, Department of Psychiatry, Drug and Alcohol Addiction Clinic, Eginition Hospital, Athens, GreeceReferences1 . McIntosh C, Chick J: Alcohol and the nervous system. J Neurol Neurosurg Psychiatry 2004; 75:iii16–21Google Scholar2 . Behbehani R, Sergott RC, Savino PJ: Tobacco-alcohol amblyopia: a maculopathy? Br J Ophthalmol 2005; 89:1543–1544Google Scholar3 . Kesler A, Pianka P: Toxic optic neuropathy. Curr Neurol Neurosci Rep 2003; 3:410–414Google Scholar4 . Sadun AA: Metabolic optic neuropathies. Semin Ophthalmol 2002; 17:29–32Google Scholar5 . Carelli V, Ross-Cisneros FN, Sadun AA: Optic nerve degeneration and mitochondrial dysfunction: genetic and acquired optic neuropathies. Neurochem Int 2002; 40:573–584Google Scholar FiguresReferencesCited byDetailsCited ByAcute Motor Axonal Neuropathy: A Severe Complication of Alcohol AbuseSevki Sahin, M.D.Nilgun CinarM.D.,Gulbuz SezginM.D.,Sunay Ayalp, M.D.Sibel KarsidagM.D.,1 October 2010 | The Journal of Neuropsychiatry and Clinical Neurosciences, Vol. 22, No. 4Current World LiteratureCurrent Opinion in Neurology, Vol. 23, No. 1 Volume 20Issue 3 Summer, 2008Pages 368-369 Metrics PDF download History Published online 1 July 2008 Published in print 1 July 2008

Intravitreal bevacizumab for treatment of peripapillary subretinal neovascularization.

To describe the effects of intravitreal bevacizumab treatment for peripapillary subretinal neovascularization. A patient with an idiopathic peripapillary subretinal neovascular membrane in the papillomacular bundle, which led to subretinal hard exudate deposits in the fovea and decreased visual acuity, was treated with a single intravitreal injection of 0.04 mL (1 mg) of bevacizumab. Main outcomes consisted of visual acuity, fluorescein (FA) and indocyanine green (ICG) angiography, and optical coherence tomography (OCT). One week after the treatment the patient had less blurred vision and metamorphopsia but visual acuity was unchanged. At the 1 month visit the visual acuity improved and reduced leakage of the membrane was shown by FA and ICG. OCT demonstrated a reduction of the macular edema. At 14 months follow-up visit the membrane was not detectable with FA and ICG and only isolated remnants of the exudates were still present. OCT showed resolution of the macular edema and a residual hard exudate localized nasally to the fovea. Treatment of peripapillary subretinal neovascular membrane with a single intravitreal injection of bevacizumab was effective and well-tolerated without recurrence of the neovascularization after a 14-month period. Visual acuity improved and retinal edema and exudation disappeared. The authors did not observe ocular or systemic side effects. In this view intravitreal injection of bevacizumab should be evaluated as a potentially effective therapy for peripapillary subretinal neovascularization, in particular for its extension in the papillomacular bundle.

Reduced Retinal Nerve Fiber Layer Thickness of the Papillomacular Bundle and Congenital Pit of the Optic Nerve Head

A 32-year-old healthy woman with a history of poor visual acuity of the left eye was found to have a temporal optic nerve head pit, with no leakage on fluorescein angiography. Visual field showed a caecocentral scotoma, more profound at the location related to the pit. Optical coherence tomography showed the characteristics of the optic pit and excluded signs of previous macular detachment; Moreover, it disclosed a significantly reduced retinal nerve fiber layer thickness at the papillomacular bundle. Thus, reduction of the papillomacular bundle is an additional cause of poor visual acuity in cases of optic pit.

Surgical Management of Optic Disc Pit Associated Maculopathy

To report the surgical outcome in seven cases of optic disc pit associated maculopathy. This was a retrospective case-note analysis of presenting features, pre- and postoperative visual acuities, surgical procedures, complications, and follow-up. The principal treatment in all the cases was pars plana vitrectomy, posterior hyaloid peel, endolaser to the papillomacular bundle temporal to the disc, and internal tamponade with gas or silicone oil. Of the four male and three female patients, two were children. All the patients had posterior hyaloid peeling during the vitrectomy and endolaser. Six patients had intraocular gas tamponade and one had silicone oil. Four patients needed a second surgical procedure to obtain a satisfactory anatomic and visual outcome. Postoperatively, four patients had an improvement of 2 or more Snellen lines. One patient with a history of multiple surgeries developed high intraocular pressure postoperatively and cataract. The mean follow-up period was 9.1 months. Serous retinopathy associated with optic disc pit responds well to early vitrectomy, endolaser, and internal tamponade. Silicone oil was effective in one refractory case. Cumulative data are required to define the management of this condition.

Male Prevalence of Acquired Color Vision Defects in Asymptomatic Carriers of Leber’s Hereditary Optic Neuropathy

Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease resulting in loss of central vision and dyschromatopsia, caused by mitochondrial DNA point mutations. However, only a subset of the mutation carriers becomes affected, with a higher penetrance in males. This study was conducted to investigate chromatic losses in asymptomatic carriers of the LHON mutation. Monocular chromatic discrimination was studied with the Cambridge Colour Test (CCT; Cambridge Research Systems, Ltd., Rochester, UK) along the protan, deutan, and tritan cone isolation axes in 46 LHON carriers (15 men) belonging to the same LHON maternal lineage and 74 age-matched control subjects (39 men). Inclusion criteria were absence of ophthalmic complaints and clear ocular media. A detailed neuro-ophthalmic examination was performed in all the LHON carriers. The differences in threshold between carriers and control subjects were significant for the three cone isolation axes at P < 0.0001. Sixty-five percent of the carriers had abnormal protan and/or deutan thresholds; some of those with higher thresholds also had elevated tritan thresholds (13%). The male thresholds were higher and more frequent than those of the women for the protan and deutan axes (ANOVA; P < 0.05), but not for tritan thresholds. In the most severe losses, the women had instances of diffuse defect whereas all the men displayed a red-green defect. Male LHON asymptomatic carriers had color vision losses with the red-green pattern of dyschromatopsia typical of patients affected with LHON, which includes elevation of tritan thresholds as well. This predominantly parvocellular (red-green) impairment is compatible with the histopathology of LHON, which affects mostly the papillomacular bundle. In contrast with male losses, female losses were less frequent and severe. These gender differences are relevant to understanding LHON pathophysiology, suggesting that hormonal factors may be of great importance.

Relationship between Retinal Nerve Fiber Layer and Visual Field Sensitivity as Measured by Optical Coherence Tomography in Chiasmal Compression

To investigate the spatial relationship between retinal nerve fiber layer (RNFL) thickness measured with optical coherence tomography (OCT) and visual field sensitivity (VFS) measured by standard automated perimetry (SAP) in chiasmal compression. Twenty-six patients with chiasmal compression were enrolled. RNFL thickness was measured with the StratusOCT and VFS with SAP (Humphrey Field Analyzer; both from Carl Zeiss Meditec, Dublin, CA). Relationships between RNFL thickness (in clock hours, hemifields, and sectors) and VFS (zones were divided into hemifields, quadrants, and sectors based on a validated visual field map) expressed in a decibel scale and 1/lambert (L) were evaluated by linear and nonlinear regression. Coefficients of determination (R(2)) were calculated by using a multivariate model. Average RNFL thickness correlated strongly with pattern standard deviation (PSD; R = 0.622) and mean deviation (MD; R = 0.413). The four strongest correlations were between the 8 o'clock OCT position (temporal disc), with the temporal hemifield (R = -0.813), the superotemporal quadrant (R = -0.847), the inferotemporal quadrant (R = -0.855), and the field sector representing the papillomacular bundle (R = -0.809). Coefficients of determination improved significantly in all sectors when time since surgery was included in the regression model-most notably, average thickness and 1/L (R(2) = 0.35-0.49), the decibels (R(2) = 0.31-0.47), and the temporal sector (R(2) = 0.44-0.57). This is the first study to compare the structure-function correlation of RNFL measured by OCT with SAP in patients with chiasmal compression. RNFL is topographically related globally and sectorally to decreased SAP, with the temporal sectors showing the strongest correlations. The correlation between RNFL and VFS strengthens as the time from surgical intervention increases.

Macular hole surgery complicated by accidental massive subretinal indocyanine green, and retinal tear

To report a case of macular hole (MH) surgery complicated by accidental massive subretinal indocyanine green (ICG), and a retinal tear through the papillomacular bundle. A 64-year-old woman complained of one-year history of poor vision in her left eye (LE) and of one month in her right (RE). Dilated fundus examination, fluorescein angiography, and optical coherence tomography (OCT) demonstrated a bilateral full-thickness MH with cystic changes and no posterior vitreous detachment RE and a full-thickness hole with significant surrounding retinal edema and cystic changes LE. A vitrectomy and posterior vitreous mechanical detachment were performed to close the MH RE. Approximately 0.3 ml of 0.5% ICG was applied to stain the internal limiting membrane (ILM). The assistant surgical nurse at the beginning of the instillation pushed the ICG syringe's embolus with too much force into the vitreous cavity with a 20-gauge cannula. Subretinal ICG was accidentally introduced through the macular hole, and an iatrogenic macular retinal tear though the papillomacular bundle was created. Infusion was resumed immediately, and ICG was removed from the vitreous cavity, and the ILM was removed in a circular fashion in the usual manner. The eye was left with 14% perfluoropropane gas. Fundus examination and OCT performed after the intraocular gas was reabsorbed one month after the surgery revealed that the macular hole was completely closed with choroidal hypereflectivity due to RPE and choriocapillaris atrophy. Best-corrected visual acuity was 20/150 with a closed macular hole and ICG still present in the subretinal space seven months after surgery. Our anatomic and functional results were poor with retinal and retinal pigment epithelium (RPE) atrophy, and a visual acuity of 20/150. Subretinal ICG and contact of ICG with the RPE should be avoided, and precautions should be taken when using intravitreous ICG to stain the ILM. Further studies are necessary to determine ICG safety in vitreoretinal surgery.

Successful Management of Melanocytoma-Associated Choroidal Neovascularization with Photodynamic Therapy

To report the efficacy of photodynamic therapy in treatment of choroidal neovascular membrane (CNV) associated with melanocytoma of the optic disc. A middle-aged man with visual acuity of 20/200 in right eye was treated with photodynamic therapy for juxtafoveal classic CNV overlying the papillomacular bundle. CNV was secondary to ocular melanocytoma, a rare event. At the 6-month follow-up, a scarred CNV with final visual acuity of 20/30 was noted clinically and angiographically. Tomography revealed high reflective scar tissue with flat macula and microperimetry showed restoration of retinal sensitivity over the papillomacular bundle. Photodynamic therapy effectively resolved CNV that involved papillomacular bundle (secondary to melanocytoma) and restored retinal function in papillomacular bundle.

MORPHOMETRIC EXAMINATION OF HUMAN AND MONKEY RETINAL GANGLION CELLS WITHIN THE PAPILLOMACULAR AREA

To examine the morphology of the retinal ganglion cells (RGCs) in the lesser characterized area lying between the optic disk and the macula that consists of the central papillomacular area (PMA) and the arcuate papillomacular bundle (PMB). Nineteen human and 10 monkey (Macaca fascicularis) retinas obtained after death were used in the study. Perikaryal, axonal, and dendritic silhouettes were examined by postvital application of the fluorescent dye DiI, which specifically labeled RGCs when placed onto the optic fiber layer. The retinas were freed from surrounding tissue, prepared as flat mounts on a nitrocellulose filter, and fixed overnight in 4% paraformaldehyde. DiI diffuses along the membranes of ganglion cell axons, thereby completely labeling them, their cell bodies, and dendrites, which enables the RGCs to be examined with fluorescence microscopy. In both species, midget cells represented most of the RGCs within the PMA (96.15%) and possessed small, umbrella-like dendrites oriented toward the deeper retinal layers. Parasol cells were less abundant in both species and had small, typical symmetric dendrites. Also along the PMB, midget cells represented most cells (91.52%), whereas only 8.47% could be categorized as parasol cells. In both species, parasol cells of the PMB extended dendrites, which were oriented perpendicular to the axons. The data show that the PMA and PMB mainly contain small midget cells of typical morphology and size but with atypically oriented dendrites, which are only characteristic for this retinal area.

Leber’s hereditary optic neuropathy and vitamin B12 deficiency

Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON. A case series was observed. Three patients who developed bilateral optic neuropathy are presented. All patients had a primary LHON mutation in their mtDNA, but also a subnormal vitamin B12 serum level at the time of presentation. The clinical picture of optic neuropathy associated with vitamin B12 deficiency shows similarity to that of LHON. Both involve the nerve fibres of the papillomacular bundle. The present case reports suggest that optic neuropathy in patients carrying a primary LHON mtDNA mutation may be precipitated by vitamin B12 deficiency. Therefore, known carriers should take care to have an adequate dietary intake of vitamin B12 and malabsorption syndromes like those occurring in familial pernicious anaemia or after gastric surgery should be excluded.

Association Between Localized Visual Field Losses and Thickness Deviation of the Nerve Fiber Layer in Glaucoma

To perform a correlation between morphology and function by studying local perimetric field losses and thickness reduction of the nerve layer in corresponding areas. Forty-seven patients with "preperimetric" open-angle glaucoma, 95 patients with "perimetric" open-angle glaucoma, and 75 control subjects had perimetric (Octopus) and polarimetric measurements. Criteria for exclusion: optic discs larger than 4 mm, media opacities, polarimetric hourglass pattern in the macular image. Thickness values of the retinal nerve fiber layer were determined in 14 upper and 14 lower sectors (10 degrees each) as well as nasally and temporally (40 degrees each) as provided from the GDx (software version 4000). The healthy control subjects served to determine age-corrected thickness deviation in all sectors. Analyses were calculated in eight nerve fiber bundle related areas. Due to non-linear relationships between perimetric defects and corresponding thickness deviation non-parametric tests were used. Localized visual field defects in the present perimetric patients were highest in upper and lower visual field areas abutting the nasal meridian. Thickness loss of nerve fiber layer however was highest in more circumferential upper and lower nerve fiber bundles. Correlations between local mean defects and deviation of the retinal nerve fiber layer thickness from normals showed a clear association for corresponding areas. The correlation coefficients were significant (P < 0.01) for all arcuate superior and inferior visual field zones except horizontally and not for the area of the lower nasal step. The present correspondence map indicates that focal perimetric defects can be identified best polarimetrically if they occur in the arcuate bundles of the visual field. A lack of correspondence was observed in the area of the papillo-macular bundle.

Idiopathic Bilateral Optic Atrophy in the Rhesus Macaque

To document the existence of idiopathic bilateral optic atrophy (BOA) in rhesus macaque monkeys and to characterize the structural and functional consequences of this condition. In vivo assessment of retinal and optic nerve structure included fundus biomicroscopy and stereophotography. Functional analyses included transient pattern-reversal electroretinography (PERG) and full-field flash ERG, with both white flashes while dark adapted and red flashes on a blue background used to assess the photopic negative response (PhNR). Also measured were visual evoked cortical potentials (VEPs) and multifocal (mf)ERGs, with both a standard fast and slowed (7F) stimulation sequence. Post mortem histologic evaluation was performed on a subset of five animals with BOA and compared with data from 22 healthy normal animals. Blood tests, including vitamin E, B(12), folate, lead, and complete blood cell count with differential were obtained on the four animals that remained alive. Animals with BOA showed temporal pallor of the optic nerve head and thinning of the retinal nerve fiber layer (RNFL) between the temporal vascular arcades (i.e., of the papillomacular bundle). Severity of optic atrophy and RNFL loss varied between animals from mild to severe, but was similar in the two eyes of each animal. Functional changes included greater loss of the PERG N95, compared with the P50 component and substantial reduction of mfERG high-frequency components. The mfERG low-frequency components were slightly larger than normal. None of the full-field flash ERG amplitudes (a-wave, b-wave, oscillatory potentials, or PhNR) was significantly different from normal. There were no consistent abnormalities found in the results of any blood test. Histologic findings included axonal loss and gliosis limited to the temporal optic nerve, reduction of nuclei within the retinal ganglion cell layer, and thinning of the temporal retinal RNFL. The existence of BOA in nonhuman primates warrants caution on the part of investigators who use these animals in experimental models of ophthalmic disease.

STRATUSOCT and multifocal ERG in unilateral acute idiopathic maculopathy

Unilateral acute idiopathic maculopathy (UAIM) is a rare entity, in which an inflammatory process involves the macular retinal pigment epithelium (RPE) and outer retina. It represents a wide spectrum of ocular findings not consistently present in all patients, which may lead to difficulties in the recognition of the condition. This observational case report presents the third-generation optical coherence tomography (StratusOCT) and multifocal electroretinogram (mfERG) findings in a 31-year-old woman with UAIM in the acute phase as well as two months later, and discusses the role of StratusOCT in the diagnosis. In the acute phase, StratusOCT demonstrated abnormal heterogeneous hyperreflectivity and thickening at the level of the outer retina and RPE in the foveal region. Two months after the initial presentation, StratusOCT examination showed a subfoveal area of homogeneous hyperreflectivity that extended from the RPE to the outer retinal layers with posterior shadowing, and sparse points of hyperreflectivity at several different levels of the neurosensory retina, including its superficial layers. The foveal retinal thickness during the acute phase was thicken compared with that after resolution. Seven days after the initial evaluation, mfERG showed severely reduced N1-P1 amplitudes with normal latencies in the region corresponding to the affected area of the papillomacular bundle and fovea. Two months later, mfERG results were normal. StratusOCT provided valuable information, allowing for the exclusion of other disorders that might mimic UAIM. mfERG findings were consistent with transient outer retinal dysfunction as the cause of visual loss. We are unaware of previous reports of UAIM studied by these methods and could find no reference to them in a computerized search using MEDLINE.

Photodynamic therapy in symptomatic parafoveal telangiectasia secondary to Osler−Rendu−Weber disease

Editor, O sler Rendu Weber disease is an autosomal-dominant hereditary haemorrhagic telangiectasia (HHT) leading to arteriovenous malformations in the skin, mucosa and viscera (Osler 1901). While mucosal complications may cause epistaxis and gastrointestinal bleeding, additional visceral involvement frequently concerns the lung, liver or brain. The diagnosis of HHT is based on three of four criteria: epistaxis, telangiectasia, visceral lesions and appropriate family history. Frequent ocular abnormalities include conjunctival telangiectasia causing bloody tears. Retinal malformation include visceral angiodysplasia such as arteriovenous fistula, angiectasia, phlebectasia and angioma (Vase & Vase 1979; Brant et al. 1989; Mahmoud et al. 2002). We performed photodynamic therapy (PDT) to treat choroidal neovascularization (CNV) that occurred secondary to parafoveal telangiectasia in a patient with HHT. A 76-year-old woman complained of decreased visual acuity (VA) of 20/60 with metamorphopsia in the left eye. Hereditary haemorrhagic telangiectasia had been diagnosed 10 years earlier due to telangiectasia located at her tongue, distal fingers and conjunctiva (Fig. 1A, B). Although epistaxis occurred frequently, no surgery was required. On fundus examination in both eyes, the retinal vessels appeared well perfused (Fig. 1C, D). However, the macula in the left eye showed a significant oedema with subretinal lipid exudates superiorly and temporally (Fig. 1D). Fluorescein angiography disclosed parafoveal telangiectasia in both eyes (Fig. 1E, F), whereas an additional occult CNV caused a severe leakage temporal to the macula in the left eye (Fig. 1F). Optical coherence tomography in the left eye showed a neuroretinal elevation of 480 mm. Our patient had no additional retinal disease including venous occlusion, hypertensive or diabetic retinopathy. After the patient had signed informed consent, one PDT session was performed. One year after PDT the metamorphopsia disappeared and the subject’s VA stabilized at 20/125. Some subtle exudates and retinal pigment epithelium (RPE) defects maintained temporal to the macula (Fig. 2A). Fluorescein angiography showed a mild atrophy of the choriocapillaris in the area of the PDT application; however, there was no persisting leakage or oedema (Fig. 2B). Optical coherence tomography disclosed no subretinal fluid and a retinal thickness of 240 mm. The tumour growth factor-beta (TGF-b) binding protein endoglin was recently identified as causing HHT with pulmonary arteriovenous malformations. While a corresponding candidate gene for endoglin is localized at 9q33–34 (McAllister et al. 1994), additional genetic studies have demonstrated the pivotal role of TGF-b signalling during angiogenesis. Knockout mice for endoglin, endothelial-specific deletion of the TGF-b-type 2 receptor (TbR2) or activin receptor-like-kinase-5 (ALK-5) failed to differentiate vascular smooth muscle cells as well as endothelial cells, inducing fragile and dilated blood vessels (Carvalho et al. 2004). The prevalence of ocular abnormalities in HHT is approximately 35% for extraocular lesions (conjunctival telangiectasia) and only 10% for retinal vascular malformations (Brant et al. 1989). Although this retrospective analysis observed intraocular findings, the authors questioned the coherence of HHT in selected cases. A great variety of retinal malformations may occur, including telangiectatic vessels at the optic disc or papillomacular bundle, and beading of retinal vessels. Retinal parafoveal telangiectasia, as presented in our HHT patient, has not yet been described in detail. Our HHT patient clearly presented typical findings of parafoveal telangiectasia in both eyes. Whether the idiopathic parafoveal telangiectasia was part of the underlying disease or just coincidental remains speculative as overall retinal involvement in HHT is very rare. However, the presence of telangiectasia in other mucosa and viscera structures supports this assumption. The unilateral symptomatic alteration was associated with severe leakage and oedema corresponding from an adjacent occult CNV in the left eye. Photodynamic therapy reduced the leakage and exudation significantly, maintaining stable VA for our patient. Novel treatment modalities such as intravitreal triamcinolone or antivascular endothelial-growth-factors (anti-VEGF) are currently under investigation in proliferative disease. Further research is necessary to determine the influence of endoglin in the pathogenesis of parafoveal telangiectasia in order to evaluate a possible treatment approach by anti-TGF-b in vascular disease such as HHT.

Myelinated retinal nerve fibres loss in Leber's hereditary optic neuropathy

Editor, A 40-year-old man presented with bilateral, rapid, painless visual loss. He had a history of right eye anisometropic amblyopia. No cigarette smoking or alcohol abuse was declared. He had two maternal uncles with similar histories of bilateral visual loss. No genetic counselling had been carried out previously. His best corrected visual acuity (VA) was counting fingers with − 8.75 D in the right eye, and 20/60 with − 1.5 D in the left eye. Fundus examination showed normal optic discs with myelinated retinal nerve fibres (MRNF) in the right eye (Fig. 1). Right fundus at first examination. Peripapillary myelinated retinal nerve fibres, particularly at the inferior temporal border. Humphrey 24–2 static visual field testing revealed bilateral central scotoma. Normal optic disc perfusion was found at fluorescein angiography. Blood biology, biochemistry and cerebral MRI were also normal. Polymerase chain reaction (PCR) studies of the patient's leucocytes revealed a homoplasmic G11-778-A mutation of mitochondrial DNA mtDNA (one of the most common mutations responsible for Leber's hereditary optic neuropathy [LHON]). A Ubiquinone® trial failed to stop bilateral visual deterioration and the scotoma size increased bilaterally. On examination 2 years later, VA was hand motion in both eyes, there was bilateral optic atrophy and the right eye MNRF had disappeared (Fig. 2). Fundi 2 years later. (A) The right fundus shows loss of myelinated retinal nerve fibres, partial loss of papillomacular bundle and optic disc atrophy. (B) The left fundus shows optic disc atrophy. (C) Red-free photograph of the right fundus shows atrophy of retinal nerve fibres and loss of myelin. Myelinated retinal nerve fibres is a benign, developmental abnormality found on routine examination in about 1% of ophthalmic patients. It can be associated with ipsilateral myopia, strabismus and amblyopia (Buys et al. 1993). It occurs when myelinization of the optic nerve (probably issued from heterotopic oligodendrocytes) continues beyond the lamina cribrosa to involve the retinal nerve fibres. It usually remains unchanged, although MNRF may disappear after damage of the retinal ganglion cells. Several causes have been reported, namely, retinal artery occlusion, diabetic retinopathy (Gentile et al. 2002), radiotherapy for choroidal melanoma (Mashayekhi et al. 2003), chronic glaucoma (Lopez Sanchez et al. 2002), optic neuritis (Sharpe & Sanders 1975), and compression of the anterior optic pathway from the inner layer (central or branch retinal artery occlusion) (Bachmann 1922; Teich 1987), to the lateral geniculate body (Gentile et al. 2002). As far as we know, loss of MNRF has not been previously reported in LHON. In this disease, the retinal ganglion cell damage is produced by intracellular mitochondrial respiratory insufficiency (Kerrison et al. 1995).

Potential Applications of Optical Coherence Tomography in Posterior Segment Trauma

To describe potential clinical applications of optical coherence tomography (OCT) in diagnosis and surgical timing in eyes with posterior segment trauma. In a noncomparative study, 7 consecutive patients who had open-globe or closed-globe injury and were found to have posterior abnormality that could also be detected by OCT are described. All patients had documented OCT abnormalities in the posterior segment. In one patient with a penetrating injury, two metal foreign bodies were located in the posterior segment, one in the vitreous compartment coupled with inflammatory reaction and localized posterior vitreous detachment and the other embedded in the retina. In a second patient with a penetrating injury, OCT revealed the appearance of posterior vitreous detachment 5 days after injury. A closed-globe injury in one patient resulted in anterior optic neuropathy, manifested as disc edema and thickening of the circumpapillary retinal nerve fiber layer. The other patients had received blunt trauma and were found to have either full-thickness macular holes (2 patients), retinal pigment epithelium detachment at the papillomacular bundle site (1 patient), or macular edema (1 patient). OCT may serve as an important adjunct imaging device in evaluation of injuries to the posterior segment, qualitatively and quantitatively. It has potential in diagnosing subtle key abnormalities and in follow-up of these injuries.

Correlation of optical coherence tomography findings with visual acuity and macular lesions in patients with X-linked retinoschisis

To evaluate and correlate findings obtained by optical coherence tomography (OCT) imaging with visual acuity (VA) and macular lesions in patients with X-linked retinoschisis (XLRS). Prospective comparative case series. Thirty-one patients with confirmed XLRS. Best-corrected VA was determined using Early Treatment Diabetic Retinopathy Study charts, and a dilated funduscopic examination was performed on all patients. For all patients, the macula in each eye was OCT imaged. A correlation between VA, macular presentation, and OCT images was determined. Analysis of findings on OCT images, including foveal thickness and the area of macular cystic-appearing lesions, and their correlation with VA. Twenty-five patients with funduscopically evident cystic-appearing macular lesions demonstrated cysticlike spaces on OCT images. No statistically significant correlation was observed between the macular area of the cysticlike spaces, foveal thickness, and VA. Three patients with no funduscopic or OCT evidence of foveal cysts demonstrated thinning of the fovea on OCT images and more extensive reduction of their VA. Retinal papillomacular bundle nerve fiber layer thickness on OCT images showed no significant difference between control and patient groups. In XLRS patients with cystic-appearing macular lesions, there was a lack of correlation between VA, foveal thickness, and cystic area. The anatomical appearance of smaller perifoveal cysts on OCT imaging was most consistent with their location being primarily within the inner nuclear layer of the retina. In older patients, macular cysts were no longer apparent clinically or by OCT imaging, and foveal thickness was reduced. The findings on OCT images are consistent with the hypothesis of a primary Muller cell defect in patients with XLRS.

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.

Retinal nerve fiber layer evaluation by optical coherence tomography in unaffected carriers with Leber's hereditary optic neuropathy mutations

To study retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in unaffected carriers with Leber's hereditary optic neuropathy (LHON) mutations. Cross-sectional study. Sixty-six unaffected carriers (44 females and 22 males) were analyzed and compared with an age-matched control group of 70 patients (40 females and 30 males). The statistical analysis was performed after grouping both the patients and the control group on the basis of gender and, for unaffected carriers only, mitochondrial DNA mutation. The Fast RNFL Thickness (3.4) scan acquisition protocol was used. Retinal nerve fiber layer thickness as measured by OCT. With respect to the control group, unaffected male carriers showed a thicker RNFL in the temporal and inferior quadrants and in the 360 degrees average measurement (P = 0.025, P = 0.03, and P = 0.018, respectively). These differences reached statistical significance in subjects carrying the 11778 mutation, whereas only a trend was detected in those with the 3460 mutation. Unaffected female carriers had an increased thickness in the temporal quadrant when compared with the control group (P = 0.003) and no differences in the other measurements. The increase in temporal sectors was statistically significant in females with the 11778 mutation, whereas a trend was detected in those with the 3460 mutation. A thickening of the temporal fibers was detected in all subgroups of unaffected carriers. This is the first evidence indicating the preferential involvement of the papillomacular bundle in subclinical LHON. This notion previously was based on the early loss of fibers from the temporal quadrant in acute LHON and the selective loss of small-caliber fibers at histopathology. Our study also revealed that males have a more diffuse involvement than females.