Macular function in tilted disc syndrome

Tilted disc syndrome can cause visual field defects due to an optic disc anomaly. Recent electrophysiological findings demonstrate reduced central outer retinal function with ophthalmoscopically normal maculae. We measured macular sensitivity with the microperimeter and performed psychophysical assessment of mesopic rod and cone luminance temporal sensitivity (critical fusion frequency)in a 52-year-old male patient with tilted disc syndrome and ophthalmoscopically normal maculae. We found a marked reduction of sensitivity in the central 20 degrees and reduced rod- and cone-mediated mesopic visual function. Our findings extend previous electrophysiological data that suggest an outer retinal involvement of cone pathways and present a case with rod and cone impairment mediated via the magnocellular pathway in uncomplicated tilted disc syndrome.

Ocular refractive and biometric characteristics in patients with tilted disc syndrome

BACKGROUND Tilted disc syndrome (TDS) is associated with characteristic ocular findings. The purpose of this study was to evaluate the ocular, refractive, and biometric characteristics in patients with TDS. METHODS This case-control study included 41 eyes of 25 patients who had established TDS and 40 eyes of 20 healthy control subjects. All participants underwent a complete ocular examination, including refraction and analysis using Fourier transformation, slit lamp biomicroscopy, pachymetry, keratometry, and ocular biometry. Corneal topography examinations were performed in the syndrome group only. RESULTS There were no significant differences in spherical equivalent (P = 0.13) and total astigmatism (P = 0.37) between groups. However, mean best spectacle-corrected visual acuity (Log Mar) was significantly worse in TDS patients (P = 0.003). The lenticular astigmatism was greater in the syndrome group, whereas the corneal component was greater in controls (P = 0.059 and P = 0.028, respectively). The measured biometric features were the same in both groups, except for the lens thickness and lens-axial length factor, which were greater in the TDS group (P = 0.007 and P = 0.055, respectively). CONCLUSIONS Clinically significant lenticular astigmatism, more oblique corneal astigmatism, and thicker lenses were characteristic findings in patients with TDS.

Ocular refractive and biometric characteristics in patients with tilted disc syndrome

Purpose: To evaluate the ocular refractive and biometric characteristics in patients with tilted disc syndrome (TDS). Methods: This case-control study comprised 41 eyes of 25 patients with established TDS and forty eyes of 20 age- and sex-matched healthy control subjects. All had a complete ocular examination including refraction and analysis using Fourier transformation, slit lamp biomicroscopy, pachymetry keratometry, and ocular biometry. Corneal topography examinations were performed in the syndrome group only. Results: There were no significant differences in spherical equivalent (p = 0.334) and total astigmatism (p= 0.246) between groups. However, mean best spectacular corrected visual acuity was significantly worse in TDS patients (P < 0.001). The lenticular astigmatism was significantly greater in the syndrome group, while the corneal component was greater in the controls (p = 0.004 and p = 0.002, respectively). The measured biometric features were the same in both groups, except for the lens thickness, relative lens position, and lens-axial length factor which were greater in the TDS group (p = 0.002, p = 0.015, and p = 0.025, respectively). Conclusions: Clinically significant lenticular astigmatism, more oblique corneal astigmatism, and thicker lens were characteristic findings in patients with TDS.

Drusen do disco óptico e tilted disc

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Refractive errors associated with tilted optic discs:a prospective study

Purpose: Tilted disc syndrome has been described to be associated with obliquely directed long axis of the disc, oblique direction of vessels, retinal pigment epithelial conus, hypoplasia of retina, visual field defects and myopic astigmatism. This prospective study looks at corneal astigmatism in eyes with a tilted optic disc. Refractive errors in these eyes were also analyzed. Methods: Patients with tilted optic discs were identified prospectively by clinical evaluation (BI, VK). All the patients with obliquely directed long axis of the disc, oblique direction of vessels and retinal pigment epithelial conus were included in the study. Best corrected visual acuity, slit-lamp examination, optic disc measurements, keratometry and refraction were recorded. Results: Twenty four patients (41 eyes) were recruited for the study. Eighteen (75%) patients had bilateral tilted optic discs. Eighteen patients (75%) were females and six (25%) were males. The mean age was 62 years(range 9 – 86 years). 76% of the patients were myopic and 24% hypermetropic. The mean spherical equivalent was –7.49 dioptres (SD 1.7D, range +6D to -17D). The mean corneal astigmatism was 1.09D (SD 0.9D, range 0.25D to 3.80D). The 6 patients who had unilateral, untilted discs were used as a control group to compare their mean corneal astigmatism (1.32 D) with the rest. Student "t" test was performed. ("p" = 0.49). Conclusions: In our study, tilted disc syndrome was found to be largely bilateral and more commonly seen in females. Myopia was the commonest refractive error associated with this clinical condition. However, 24% of patients in this series were hypermetropic. No correlation between the tilting of the optic disc and significant corneal astigmatism was noted as previously reported.

Molecular genetics of primary open angle glaucoma and exfoliation syndrome

Glaucoma is the second leading cause of blindness worldwide. It is a group of optic neuropathies, characterized by progressive optic nerve degeneration, excavation of the optic disc due to apoptosis of retinal ganglion cells and corresponding visual field defects. Open angle glaucoma (OAG) is a subtype of glaucoma, classified according to the age of onset into juvenile and adult- forms with a cut-off point of 40 years of age. The prevalence of OAG is 1-2% of the population over 40 years and increases with age. During the last decade several candidate loci and three candidate genes, myocilin (MYOC), optineurin (OPTN) and WD40-repeat 36 (WDR36), for OAG have been identified. Exfoliation syndrome (XFS), age, elevated intraocular pressure and genetic predisposition are known risk factors for OAG. XFS is characterized by accumulation of grayish scales of fibrillogranular extracellular material in the anterior segment of the eye. XFS is overall the most common identifiable cause of glaucoma (exfoliation glaucoma, XFG). In the past year, three single nucleotide polymorphisms (SNPs) on the lysyl oxidase like 1 (LOXL1) gene have been associated with XFS and XFG in several populations. This thesis describes the first molecular genetic studies of OAG and XFS/XFG in the Finnish population. The role of the MYOC and OPTN genes and fourteen candidate loci was investigated in eight Finnish glaucoma families. Both candidate genes and loci were excluded in families, further confirming the heterogeneous nature of OAG. To investigate the genetic basis of glaucoma in a large Finnish family with juvenile and adult onset OAG, we analysed the MYOC gene in family members. Glaucoma associated mutation (Thr377Met) was identified in the MYOC gene segregating with the disease in the family. This finding has great significance for the family and encourages investigating the MYOC gene also in other Finnish OAG families. In order to identify the genetic susceptibility loci for XFS, we carried out a genome-wide scan in the extended Finnish XFS family. This scan produced promising candidate locus on chromosomal region 18q12.1-21.33 and several additional putative susceptibility loci for XFS. This locus on chromosome 18 provides a solid starting point for the fine-scale mapping studies, which are needed to identify variants conferring susceptibility to XFS in the region. A case-control and family-based association study and family-based linkage study was performed to evaluate whether SNPs in the LOXL1 gene contain a risk for XFS, XFG or POAG in the Finnish patients. A significant association between the LOXL1 gene SNPs and XFS and XFG was confirmed in the Finnish population. However, no association was detected with POAG. Probably also other genetic and environmental factors are involved in the pathogenesis of XFS and XFG.

Intradural lumbar disc herniation: report of five cases with literature review

Introduction: Intradural lumbar disc herniations are uncommon presentations of a relatively frequent pathology, representing less than 1% of all lumbar disc hernias. They show specific features concerning their clinical diagnosis, with a higher incidence of cauda equina syndrome, and their surgical treatment requires a transdural approach. Methods: In this article, we describe five cases of this pathology and review the literature as well as some considerations about the difficulties in the preoperative diagnostic issues and the surgical technique. Conclusion: We concluded that for intradural disc herniations the diagnosis is mainly intraoperative, and the surgical technique has some special aspects. © 2012 Springer-Verlag Berlin Heidelberg.

Frontonasal dysplasia, callosal agenesis, basal encephalocele, and eye anomalies syndrome with a partial 21q22.3 deletion

We describe a girl with a phenotype characterized by frontonasal dysplasia, callosal agenesis, basal encephalocele, and eye anomalies who presents a 46,XX,r(21) karyotype. Array-comparative genomic hybridization using the Afflymetrix 100K DNA oligoarray set showed an interstitial deletion 21q22.3 of approximately 219?kb. Conventional karyotype of both parents was normal, and it was not possible to perform the molecular studies. In this report we raise the hypothesis that the deleted genes located at 21q22.3 could account to the phenotype. (C) 2012 Wiley Periodicals, Inc.

Cell therapy for intervertebral disc repair: advancing cell therapy from bench to clinics

Intervertebral disc (IVD) degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encouraging results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium "Where Science meets Clinics", sponsored by the AO Foundation and held in Davos, Switzerland, from September 5-7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imaging methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neuro-genesis. Discogenic pain, originating from "black discs" or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects.

Clinical manifestation of Fuchs uveitis syndrome in childhood

PURPOSE The aim of this study was to describe clinical signs and complications of Fuchs uveitis syndrome (FUS) with onset in childhood. METHODS Ophthalmologic findings and complications in patients with FUS becoming manifest before the age of 16 years were analyzed in a retrospective study at a tertiary referral uveitis center. Inclusion criteria were the presence of pathognomonic FUS findings at any time point and exclusion of any systemic immune-mediated or infectious disease. RESULTS A total of 23 patients (male = 16, female = 7) with juvenile FUS (unilateral n = 20, bilateral n = 3 patients) were included in the study. Mean ages at uveitis and FUS diagnosis were 12.0 ± 4.2 and 22.7 ± 10.7 years, respectively. In six patients, inflammation was noted at age ≤ 7 years. The following inflammatory signs were observed in a total of 26 eyes: ≤ 1+ anterior chamber cell grade (n = 26), vitreous cells (n = 24), fine keratic precipitates (KPs; n = 23), stellate KPs (n = 11), mutton-fat KPs (n = 23), diffuse (n = 24) or inferior (n = 8) distribution of KPs, Koeppe nodules (n = 10), and iris heterochromia (n = 14). A representative subgroup of patients (n = 5) is shown who presented with non-specific clinical signs in the beginning and in whom typical FUS signs became manifest only at a later stage. Secondary complications such as cataract (n = 19), ocular hypertension (n = 3), or glaucomatous disc damage (n = 2) were found after a mean uveitis duration of 11.6, 19.5, and 20.3 years, respectively. CONCLUSION FUS may begin in early childhood, and the characteristic findings may not be present at onset of disease. The diagnosis is often delayed for years, occasionally with the consequence of overtreatment with anti-inflammatory drugs.

Label-free immunoassay for porcine circovirus type 2 based on excessively tilted fiber grating modified with staphylococcal protein A

Using excessively tilted fiber grating (Ex-TFG) inscribed in standard single mode fiber, we developed a novel label-free immunoassay for specific detection of porcine circovirus type 2 (PCV2), which is a minim animal virus. Staphylococcal protein A (SPA) was used to modify the silanized fiber surface thus forming a SPA layer, which would greatly enhance the proportion of anti-PCV2 monoclonal antibody (MAb) bioactivity, thus improving the effectiveness of specific adsorption and binding events between anti-PCV2 MAbs and PCV2 antigens. Immunoassay experiments were carried out by monitoring the resonance wavelength shift of the proposed sensor under different PCV2 titer levels. Anti-PCV2 MAbs were thoroughly dissociated from the SPA layer by treatment with urea, and recombined to the SPA layer on the sensor surface for repeated immunoassay of PCV2. The specificity of the immunosensor was inspected by detecting porcine reproductive and respiratory syndrome virus (PRRSV) first, and PCV2 subsequently. The results showed a limit of detection (LOD) for the PCV2 immunosensor of ~9.371TCID50/mL, for a saturation value of ~4.801×103TCID50/mL, with good repeatability and excellent specificity.

Ocular manifestations of microcephaly with or without chorioretinopathy, lymphedema or intellectual disability (MCLID) syndrome associated with mutations in KIF11

Purpose Microcephaly with or without chorioretinopathy, lymphedema or intellectual disability (MCLID) is an autosomal dominant condition. Mutations in KIF11 have been found to be causative in approximately 75% of cases. This study describes the ocular phenotype in patients with confirmed KIF11 mutations. Methods Standard ophthalmic examination and investigation including visual acuity, refraction and fundus examination was carried out in all patients. Fundus autofluorescence imaging (FAF) was performed in three patients, and four patients underwent spectral domain optical coherence tomography (OCT). Flash electroretinography (ERG) was performed in seven patients, and five underwent additional pattern electroretinography (PERG). Results The patients ranged in age from 2 to 10 years. Most presented with visual acuity loss. Fundus examination revealed lacunae of chorioretinal atrophy. Pigmentary macular changes and optic disc pallor were present in three of seven patients. Fundus autofluorescence demonstrated hypoautofluorescence at the macula in two of three patients. The lacunae of chorioretinal atrophy were hypoautofluorescent. The OCT showed atrophic maculae in three of four patients. Follow-up in one patient showed no deterioration of the vision over a 9-year period. The lesions appear not to be progressive on the follow-up imaging. Electrophysiology showed generalized rod and cone dysfunction and severe macular dysfunction. Inner retinal dysfunction was evident in three of seven patients. Conclusions Patients with KIF11 mutations show a specific ocular phenotype with variable expressivity and intrafamilial variability. Macular atrophy and dysfunction have not been consistently documented before. The fundus lesions appear non-progressive. The findings assist in providing an accurate diagnosis and thus improving the management and follow-up of patients with this syndrome.

Quantitative electroencephalographic comodulation : an investigation of patterns in chronic fatigue syndrome

Introduction. This is a pilot study of quantitative electro-encephalographic (QEEG) comodulation analysis, which is used to assist in identifying regional brain differences in those people suffering from chronic fatigue syndrome (CFS) compared to a normative database. The QEEG comodulation analysis examines spatial-temporal cross-correlation of spectral estimates in the resting dominant frequency band. A pattern shown by Sterman and Kaiser (2001) and referred to as the anterior posterior dissociation (APD) discloses a significant reduction in shared functional modulation between frontal and centro-parietal areas of the cortex. This research attempts to examine whether this pattern is evident in CFS. Method. Eleven adult participants, diagnosed by a physician as having CFS, were involved in QEEG data collection. Nineteen-channel cap recordings were made in five conditions: eyes-closed baseline, eyes-open, reading task one, math computations task two, and a second eyes-closed baseline. Results. Four of the 11 participants showed an anterior posterior dissociation pattern for the eyes-closed resting dominant frequency. However, seven of the 11 participants did not show this pattern. Examination of the mean 8-12 Hz amplitudes across three cortical regions (frontal, central and parietal) indicated a trend of higher overall alpha levels in the parietal region in CFS patients who showed the APD pattern compared to those who did not have this pattern. All patients showing the pattern were free of medication, while 71% of those absent of the pattern were using antidepressant medications. Conclusions. Although the sample is small, it is suggested that this method of evaluating the disorder holds promise. The fact that this pattern was not consistently represented in the CFS sample could be explained by the possibility of subtypes of CFS, or perhaps co-morbid conditions. Further, the use of antidepressant medications may mask the pattern by altering the temporal characteristics of the EEG. The results of this pilot study indicate that further research is warranted to verify that the pattern holds across the wider population of CFS sufferers.