Surgical management of dysthyroid optic neuropathy: A systematic review.

OBJECTIVE: There is currently no recommendation on the optimal surgical management for dysthyroid optic neuropathy (DON). The aim of this study is to systematically review the surgical management of DON and its outcome on visual acuity (VA). DATA SOURCES: MEDLINE, Cochrane Library, and clinicaltrials.gov REVIEW METHODS: A systematic review of studies about the surgical management of DON was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Articles were included if preoperative and postoperative VA in logMAR (Logarithm of the Minimum Angle of Resolution) were available. RESULTS: Fifteen articles were included in the study accounting for 669 orbits. The mean VA improvement was of 0.44 logMAR overall, 0.41 logMAR for 1-wall, 0.41 logMAR for 2-wall, and 0.55 logMAR for 3-wall decompressions. The mean reduction in exophthalmos was 4.9 mm overall, 4.3 mm for 1-wall, 4.54 mm for 2-wall, and 6.02 for 3-wall decompressions. The mean new onset diplopia (NOD) rate was 19.84% overall, 19,12% for 1-wall, 20.75% for 2-wall, and 19.83% for 3-wall decompressions. CONCLUSION: The results are limited due to the high number of biases in the included studies. It seems that 3-wall decompression offers the best VA improvement and proptosis reduction although also the highest NOD and complications rate. Two-wall balanced decompression or 1-wall inferomedial decompression seems to be effective with less morbidity.

Anatomy and evaluation of the optic nerve head / Anatomia e avaliação da cabeça do nervo óptico

ABSTRACT Evaluation of the optic disc is important for the correct diagnosis and follow-up of optic neuropathies, especially glaucoma. The characteristics of the optic disc depend on various factors, including demographic and population aspects, and analysis of these characteristics may vary according to the methods used. The size and format of the neural rim along with the nerve fiber layer are important to the clinician's judgment regarding the susceptibility of the subject to develop glaucoma. In this study, we reviewed the literature to summarize the main methods and its characteristics in the evaluation of the optic nerve head.

RESUMO A avaliação do disco óptico é de suma importância para o diagnostico correto e acompanhamento de neuropatias ópticas, especialmente o glaucoma. Características do disco óptico dependem de uma grande variedade de fatores, incluindo aspectos demográficos e populacionais, e também podem variar de acordo com os métodos usados. Tamanho e formato da rima neurorretiniana junto com a camada de fibras nervosas são importantes ao julgamento clinico a respeito da susceptibilidade do paciente desenvolver glaucoma. Nesse estudo, nós revisamos a literatura para resumir os principais métodos e suas características para a avaliação da cabeça do nervo óptico.

Advanced Therapy and Clinical Trials to Treat Patients with Optic Nerve Diseases.

Optic nerve diseases include a wide variety of pathogenic conditions triggering injury or dysfunction of the optic nerves that lead to visual impairment or blindness in one or both eyes. Despite their pathogenic variety, most of them proceed through common mechanisms that allow them to investigate together. Nevertheless, roles of the cells, tissues, genes, growth factors, and proteins, and all underlying pathophysiological mechanisms need to be studied fully for better management of each optic nerve disease. This review presents a collection of information regarding ongoing and completed clinical trials (CT) of advanced therapies that deliver stem cell and gene therapy treatments as drugs to patients with optic nerve diseases as well as successes and failures achieved in treating these patients in the last few years. These drugs seem safe from creating neurotoxicity. It describes outcomes of a bibliographic search for stem cell therapy, gene therapy, and neuroprotection-based CT registered in the International ClinicalTrials.gov, the European EudraCT, and the Spanish REEC database, and related papers published in the PUBMED database by applying different search terminologies. This review overall informs the patients of optic neurodiseases that advanced therapies are progressing successfully in search of effective and safe treatments for them.

Iridochorioretinal coloboma associated with buried optic nerve drusen: a case report / Coloboma irido-coriorretiniano associado a drusas enterradas do nervo óptico: Relato de caso

ABSTRACT Improper closure of the embryonic fissure results in ocular coloboma. Optic nerve head drusen are hyaline deposits located anterior to the lamina cribosa that grow and calcify over time. It is rarely associated with ocular coloboma, with only two cases reported. We present a patient with an irido-chorioretinal coloboma, poorly defined optic nerve limits in the right eye, and increased papillary vascular ramification and peripapillary atrophy in the left eye, without any visible drusen. Fundus autofluorescence, high-resolution optical coherence tomography, and B-scan ultrasonography confirmed the diagnosis of bilateral buried optic nerve head drusen. The association between irido-chorioretinal colobomas and optic nerve drusen in the absence of a systemic disease is exceptional. Our case demonstrates that multimodal imaging is important to correctly diagnose buried optic nerve head drusen.

RESUMO O coloboma ocular é o resultado de um fechamento impróprio da fissura embrionária. As drusas da cabeça do nervo óptico são depósitos hialinos localizados anteriormente à lâmina cribosa que crescem e se calcificam com o tempo. A associação de ambos é rara, com apenas dois casos descritos na literatura. Apresentamos um paciente com coloboma irido-coriorretiniano e limites do nervo óptico mal definidos em seu olho direito, e aumento da ramificação vascular papilar e atrofia peripapilar em seu olho esquerdo, sem drusas visíveis. Autofluorescência de fundo, tomografia de coerência óptica de alta resolução e ultrassonografia B-scan foram realizadas confirmando o diagnóstico de drusas enterradas bilaterais da cabeça do nervo óptico. A associação entre colobomas irido-coriorretinianos com drusas do nervo óptico na ausência de doença sistêmica é excepcional. Nosso caso demonstra a importância da imagem multimodal para o diagnóstico correto de drusas enterradas de cabeça do nervo óptico.

Pattern reversal visual evoked potentials (prVEPs) in autosomal recessive hereditary spastic paraplegia with thin corpus callosum (ARHSPTCC) patients with SPG 11 mutations in Saudi Arabia, cross section hospital base study.

OBJECTIVE: To retrospectively report prVEPs in SPG11 ARHSP-TCC. BACKGROUND: ARHSPTCC is characterized by a thin corpus callosum, progressive spastic paraparesis, cognitive decline,and axonal neuropathy by SPG11 mutations. Additionally, seizures, cerebellar ataxia, speech and swallowing problems, extrapyramidal signs, and skeletal deformities may occur. Neuroradiological findings include thinning of the anterior corpus callosum (TCC), periventricular white matter changes, and cortical atrophy. Electromyography and nerve conduction studies may reveal axonal neuropathy or anterior horn involvement. However, optic nerve involvement and prVEPs have not been well described. DESIGN/METHODS: Routine prVEPs were performed in 11 subjects with genetically confirmed (Athena Diagnostic USA) SPG11 ARHSPTCC. Independent stimulation of each eye with a full-field checkerboard pattern reverse stimulation technique was performed. Repetitive waveforms were averaged and the P-100 was recorded. RESULTS: Eleven subjects aged 20 to 37 years were studied, 5 were female. Nine were from consanguineous parents. Nine had a family history and 3 pairs were siblings. Nine had TCC, 8 had diffuse brain atrophy and 1 had cerebellum and brainstem atrophy. Additionally, 9 had bilaterally abnormal prVEPs. The mean P100 latency of the left eye was 129.45 ms±19.47, and a mean amplitude of 7 µV±2.33, while the right had a mean P100 of 127.72 ms±12.69, and mean amplitude of 6.74 µV±2.84. CONCLUSIONS: Abnormal prVEPs occurred in 81.82% of our subjects with significantly prolonged P100 bilateral responses. This indicates that the visual pathway is affected in patients with SPG11 ARHSPTCC. However, no specific mutation was predominant. prVEPs should be considered in the routine evaluation for spastic paraparesis.

Color vision in anterior ischemic optic neuropathy.

PURPOSE: The non-arteritic form of anterior ischemic optic neuropathy (AION) is the most common acute optic neuropathy among individuals over the age of fifty, yet little is known about how the disorder affects color vision. We tested the hypothesis that color vision correlates with visual acuity in patients with non-arteritic AION. We also evaluated the patterns of visual field loss in a subgroup of patients who manifested relative sparing of color vision. OBSERVATIONS: Records of forty-five patients with non-arteritic AION who had been evaluated at Duke University over a consecutive four-year period were reviewed retrospectively. Statistical analysis of the relationship between color vision and visual acuity was carried out using a linear regression model. Color vision tended to correlate with acuity with respect to visual acuities between 20/16 and 20/63. However, nine patients were identified in whom color vision was relatively spared in comparison with acuity. Most of the affected eyes in this subgroup had a distinctive pattern of visual field loss consisting of a dense, steep-walled cecocentral defect centered below the horizontal meridian. CONCLUSIONS AND IMPORTANCE: In patients with non-arteritic AION, color vision tends to correlate with visual acuity for acuities better than 20/70. Sparing of color vision relative to acuity, a heretofore unreported finding in AION, occurs in approximately 15% of cases. Sparing of color vision reflects damage to foveal projections coupled with preservation of extrafoveal macular projections. The results of color vision testing in patients with non-arteritic AION help to differentiate this condition from other optic neuropathies such as optic neuritis.

Six-month results of suprachoroidal adipose tissue-derived mesenchymal stem cell implantation in patients with optic atrophy: a phase 1/2 study.

PURPOSE: This prospective clinical case series aimed to investigate the safety and efficacy of suprachoroidal adipose tissue-derived mesenchymal stem cell (ADMSC) implantation in patients with optic nerve diseases. METHODS: This prospective, single-center, phase 1/2 study enrolled 4 eyes of 4 patients with optic atrophy of various reasons who underwent suprachoroidal implantation of ADMSCs. The best-corrected visual acuity (BCVA) in the study was HM at 1 m. The worse eye of the patient was operated. Patients were evaluated on the first day, first week, first month, third and sixth months postoperatively. BCVA, anterior segment and fundus examination, color photography, optical coherence tomography (OCT) and visual field examination were carried out at each visit. Fundus fluorescein angiography and multifocal electroretinography (mfERG) recordings were performed at the end of the first, third and sixth months and anytime if necessary during the follow-up. RESULTS: All 4 patients completed the six-month follow-up. None of them had any systemic or ocular complications. All of the patients experienced visual acuity improvement, visual field improvement and improvement in the mfERG recordings. We found choroidal thickening in OCT of the 4 patients. CONCLUSION: Even though the sample size is small, the improvements were still encouraging. Stem cell treatment with suprachoroidal implantation of ADMSCs seems to be safe and effective in the treatment for optic nerve diseases that currently have no curative treatment options.

Glial Cells and Retinal Nerve Fibers Morphology in the Optic Nerves of Streptozotocin-induced Hyperglycemic Rats.

PURPOSE: This study analyzes the structures of optic nerve elements, i.e., glial cells and nerve fibers, in an STZ-induced hyperglycemic animal model. Morphological changes in glial elements of the optic nerve in hyperglycemic and normoglycemic animals were compared. METHODS: Transmission electron microscopy, histochemistry, immunohistochemistry, and morphometry were used in this study. RESULTS: Hyperglycemia increased the numbers of inner mesaxons and axons with degenerative profiles. Furthermore, it led to both an increase in the amount of debris and in the numbers of secondary lysosomic vesicles in glial cytoplasm. Hyperglycemia also led to a decrease in glial fibrillary acidic protein expression and an increase in periodic acid-Schiff-positive deposits in the optic nerves of hyperglycemic animals. CONCLUSION: We conclude that the damage to the structural elements observed in our animal models contributes to the pathogenesis of optic neuropathy in the early stages of diabetes.

Evaluation of a Relative Afferent Pupillary Defect using the RAPDx® Device Before and After Treatment in Patients with Optic Nerve Disease.

We evaluated the amplitude and latency scores in the RAPDx® device together with other ophthalmic examinations, before and after treatment in four patients with optic nerve disease. In all patients, the visual acuity (VA) and visual field (VF) after treatment was resolved. Both scores after treatment were lower, with reduced laterality-based differences in VA and critical flicker fusion frequency (CFF). Even after treatment, 3 patients had laterality-based differences in circumpapillary retinal nerve fiber layer thickness (cpRFNLT). Both scores for evaluation of RAPD by RAPDx® correlated with subjective examinations and were useful for evaluation of the efficacy of treatment.

Neuro-ophthalmological findings in TAFRO syndrome in a patient from South America, a variant of multicentric Castleman's disease.

BACKGROUND: To report the neuro-ophthalmological findings in the TAFRO syndrome in a South American patient. METHODS: This is a case report of a patient with TAFRO syndrome. RESULTS: We present the case of a 66-year-old woman with TAFRO syndrome and multicentric Castleman disease, who developed ophthalmic manifestations, as a rare complication, including optic disk edema and serous retinal detachment, which improved with conventional therapy. CONCLUSIONS: The optic disk edema could be present as a neuro-ophthalmological finding in TAFRO syndrome. To the best of our knowledge, this is the first report on the ophthalmic manifestations in the TAFRO syndrome.

The diagnostic accuracy of chromatic pupillary light responses in diseases of the outer and inner retina.

PURPOSE: To compare the chromatic pupillary light responses (PLR) in healthy subjects with those from patients with diseases of the outer or inner retina under various stimulus conditions, and to ascertain the parameters required to optimally distinguish between disease and control groups. METHODS: Fifteen patients with retinitis pigmentosa (RP), 19 patients with optic nerve disease (ON), and 16 healthy subjects were enrolled in this prospective study. ON included optic neuritis (NNO) and non-arteritic anterior ischemic optic neuropathy (NAION). For each subject, the PLR was recorded, to red, yellow, green, and blue stimuli for durations of 4 and 12 s, and for stimulus intensities of 4 lx and 28 lx. RESULTS: Comparison between control and RP or ON patient results showed that responses after stimulus onset were significantly different for most stimulus conditions, but the post-stimulus amplitudes at 3 s and 7 s after light extinction were not. On the other hand, the difference between the ON and RP groups was significant only for post-stimuli time-points and only for blue stimuli. Differences between responses to blue and red were significantly different, predominantly at post stimulus time-points. A ROC analysis revealed that the maximal constriction amplitudes to a 4 lx, 4 s yellow stimulus are significantly different in ON vs RP patients, and the responses to a 4 s, 28 lx blue stimulus at 7 s post-stimulus are significantly different in controls vs ON vs RP patients with a high specificity. CONCLUSIONS: Pupillary light responses to blue light in healthy, RP, and ON subjects are significantly different from one another. The optimal stimuli for future protocols was found to be a 4 s blue stimulus at 28 lx, and a 4 s yellow stimulus at 4 lx.

The status and progress of morning glory syndrome / 中华眼底病杂志

Morning glory syndrome (MGS) is a congenital optic disc anomaly. The characteristic ophthalmoscopic findings consist of a generally enlarged, funnel-shaped and excavated optic disc, surrounded by an elevated annulus of chorioretinal pigment disturbance, with a central glial tuft, multiple narrow branches of retina vessels radiating from the disc. There are peripheral non-perfusion retinal areas in most cases. The pathogenesis of MGS remains unclear. MGS might be associated with many ocular and systemic abnormalities, involving facial, central nervous, cerebrovascular and endocrine systems. Persistent hyperplastic primary vitreous and retinal detachments (RD) are the most common ocular complications of MGS. The mechanism RD in MGS is unclear. Vitrectomy with long-acting gas or silicone tamponade and photocoagulation around the breaks or the enlarged disc might be efficient for rhegmatogenous RD of MGS. Early diagnosis is crucial for recognition and treatment of the ocular and systemic complications, and maintenance of the visual function.

The status and progress of morning glory syndrome / 中华眼底病杂志

Morning glory syndrome (MGS) is a congenital optic disc anomaly. The characteristic ophthalmoscopic findings consist of a generally enlarged, funnel-shaped and excavated optic disc, surrounded by an elevated annulus of chorioretinal pigment disturbance, with a central glial tuft, multiple narrow branches of retina vessels radiating from the disc. There are peripheral non-perfusion retinal areas in most cases. The pathogenesis of MGS remains unclear. MGS might be associated with many ocular and systemic abnormalities, involving facial, central nervous, cerebrovascular and endocrine systems. Persistent hyperplastic primary vitreous and retinal detachments (RD) are the most common ocular complications of MGS. The mechanism RD in MGS is unclear. Vitrectomy with long-acting gas or silicone tamponade and photocoagulation around the breaks or the enlarged disc might be efficient for rhegmatogenous RD of MGS. Early diagnosis is crucial for recognition and treatment of the ocular and systemic complications, and maintenance of the visual function.

Evaluation of Relative Afferent Pupillary Defect Using RAPDx Device in Patients with Optic Nerve Disease.

We previously reported the standard values of the amplitude and latency scores in the RAPDx device for evaluating relative afferent pupillary defect (RAPD). Here, we evaluated RAPD in patients with optic nerve disease by using these standard values. Twenty-eight patients with current or previous optic nerve disease were enrolled in this study. Additionally, the data of 84 healthy subjects from our previous report were used as control data. We measured the amplitude and latency scores using RAPDx. We then compared their mean values and the percentages of individuals with standard values within a certain range between the optic nerve disease group and healthy group. Additionally, we evaluated their correlation with visual acuity and the critical flicker fusion frequency in the optic nerve disease group. Both parameters were significantly higher in the optic nerve disease group than in the control group (p < 0.0001). The detection rate of RAPD when using the standard value of amplitude score was 75%. Additionally, both parameters showed a significant correlation with laterality-based differences in visual acuity and critical flicker fusion frequency values in the optic nerve disease group (r = 0.59-0.75, p < 0.001). The amplitude and latency scores determined using RAPDx are useful in evaluating RAPD, particularly the standard value of the amplitude score.

Pseudo-Foster Kennedy Syndrome as a Rare Presentation of Vitamin B12 Deficiency.

INTRODUCTION: Pseudo-Foster Kennedy syndrome is a triad consisting of ipsilateral optic atrophy, contralateral optic disc edema, and ipsilateral anosmia in the absence of an intracranial mass. Vitamin B12 plays an important role in DNA synthesis, and its deficiency causes peripheral neuropathy, myeloneuropathy, and, very rarely, optic neuropathy. CASE PRESENTATION: In this study, we describe a 34-year-old male who presented with progressive loss of visual acuity and field. Fundoscopy showed optic disc edema with telangiectasia in the right eye, while the left eye had optic disc atrophy. We ruled out nearly all possible and common causes of optic neuropathy, and vitamin B12 deficiency was finally diagnosed. After treatment with vitamin B12, the patient improved. CONCLUSIONS: Demyelinating disease, anterior ischemic optic neuropathy, non-arteritic anterior ischemic optic neuropathy, autoimmune disease, and hereditary optic neuropathy could cause optic neuropathy. Normal CBC parameters and the absence of clinical manifestations of vitamin B12 deficiency could not rule out its diagnosis. Careful physical examinations and history-taking with a classical approach led us to the diagnosis of vitamin B12 deficiency and its treatment.

Utility of optical coherence tomography in the evaluation of monocular visual loss related to retinal ischemia.

We report four patients with monocular visual loss for whom optical coherence tomography (OCT) was helpful in distinguishing the sequelae of retinal artery occlusion from those of primary optic neuropathy. Determinations of the peripapillary retinal nerve fiber layer (RNFL) thickness as well as macular retinal layer thicknesses and architecture were used. The major findings in our patients show that changes in the inner retinal layers (including ganglion cell and inner plexiform layer) with disruption of normal macular architecture supports a diagnosis of retinal artery occlusion. Our results support the use of OCT imaging for patients with monocular visual loss of uncertain etiology; macular imaging as well as peripapillary RNFL thickness measurement can be helpful in differentiating primary retinal disease or ischemia from primary disorders of the optic nerve.

Immunization and glaucoma / 中华实验眼科杂志

Glaucoma,the major cause of global irreversible blindness,is a chronic neurodegenerative disease of the optic nerve.Apoptosis of retinal ganglion cells (RGCs) and progressive loss of optic nerve axons results in structural and functional deficits in glaucoma patients.Growing evidence obtained from clinical and experimental studies over the last decade strongly suggests the involvement of the immune system in the neurodegenerative process of glaucoma.This review aims to provide a perspective on the complex interplay of cellular events during glaucomatous neurodegeneration that involves aberrances or dysfunctions of immune system,such as ocular immune privilege,glial activation response,T cell-mediated immune responses,autoantibody-mediated immune responses,complement fixation reaction and aging,oxidative stress.The complex interplay of cellular events amplify the primary injury process and contribute to disease progression by oxidative stress and immune response,ultimately lead to cell death with loss of RGCs.

Expression and function of Delta-like ligand 4 in a rat model of retinopathy of prematurity.

The Delta-like ligand 4/Notch signaling pathway was shown to participate in the process of retinal development and angiogenesis. However, the function of the Delta-like ligand 4/Notch signaling pathway in retinopathy of prematurity requires further study. Retinopathy of prematurity was induced in 5-day-old Sprague-Dawley rats exposed to hyperoxia for 7 days, and then returned to room air. Reverse transcription-PCR and western blot revealed that Delta-like ligand 4 levels decreased at postnatal day 12 and increased at postnatal day 17 in retinopathy of prematurity rats. Flat-mounted adenosine diphosphatase stained retina and hematoxylin-eosin stained retinal tissue slices showed that the clock hour scores and the nuclei counts in retinopathy of prematurity rats were significantly different compared to normal control rats. After retinopathy of prematurity rats were intravitreally injected with Delta-like ligand 4 monoclonal antibody to inhibit the Delta-like ligand 4/Notch signaling pathway, there was a significant increase in the severity of retinal neovascularization (clock hours) in the intravitreally injected eyes. The nuclei count was highly correlated with the clock hour score. These results suggest that Delta-like ligand 4/Notch signaling plays an essential role in the process of physiological and pathological angiogenesis in the retina.

A Case of Posterior Ischemic Optic Neuropathy after Endoscopic Sinus Surgery / 대한이비인후과학회지

Recently, endoscopic sinus surgery (ESS) has been acknowledged as a standard surgical procedure for the treatment of chronic rhinosinusitis. Orbital complications of varying degrees that may occur during ESS have been widely reported. Blindness, one of the major complications that can occur during or immediately after ESS, is mainly attributed to orbital hematoma or direct injury to the optic nerve. In contrast to such direct mechanical trauma caused during ESS, we report a case of acute loss of vision that followed ESS without a definite cause. A postulated mechanism for idiopathic optic neuropathy is that it is ischema resulted from vasospasm in the branches of ophthalmic artery due to topical use of vasoconstrictive agents. Otorhinolaryngologists should be aware that this condition may occur following an uncomplicated ESS procedure. When loss of sight is diagnosed postoperatively, patients should be given prompt ophthalmological consultation and possible causes should be considered.