A Comparison of Rates of Change in Neuroretinal Rim Area and Retinal Nerve Fiber Layer Thickness in Progressive Glaucoma

PURPOSE. To evaluate and compare rates of change in neuro-retinal rim area (RA) and retinal nerve fiber layer thickness (RNFLT) measurements in glaucoma patients, those with suspected glaucoma, and normal subjects observed over time. METHODS. In this observational cohort study, patients recruited from two longitudinal studies (Diagnostic Innovations in Glaucoma Study-DIGS and African Descent and Evaluation Study-ADAGES) were observed with standard achromatic perimetry (SAP), optic disc stereophotographs, confocal scanning laser ophthalmoscopy (HRT-3; Heidelberg Engineering, Heidelberg, Germany), and scanning laser polarimetry (GDx-VCC; Carl Zeiss Meditec, Inc., Dublin, CA). Glaucoma progression was determined by the Guided Progression Analysis software for standard automated perimetry [SAP] and by masked assessment of serial optic disc stereophotographs by expert graders. Random-coefficients models were used to evaluate rates of change in average RNFLT and global RA measurements and their relationship with glaucoma progression. RESULTS. At baseline, 194 (31%) eyes were glaucomatous, 347 (55%) had suspected glaucoma, and 88 (14%) were normal. Forty-six (9%) eyes showed progression by SAP and/or stereophotographs, during an average follow-up of 3.3 (+/-0.7) years. The average rate of decline for RNFLT measurements was significantly higher in the progressing group than in the non-progressing group (-0.65 vs. -0.11 mu m/y, respectively; P < 0.001), whereas RA decline was not significantly different between these groups (-0.0058 vs. -0.0073 mm(2)/y, respectively; P = 0.727). The areas under the receiver operating characteristic (ROC) curves used to discriminate progressing versus nonprogressing eyes were 0.811 and 0.507 for the rates of change in the RNFLT and RA, respectively (P < 0.001). CONCLUSIONS. The ability to discriminate eyes with progressing glaucoma by SAP and/or stereophotographs from stable eyes was significantly greater for RNFLT than for RA measurements. (Invest Ophthalmol Vis Sci. 2010;51:3531-3539) DOI: 10.1167/iovs.09-4350

Agreement for Detecting Glaucoma Progression with the GDx Guided Progression Analysis, Automated Perimetry, and Optic Disc Photography

Purpose: To evaluate the ability of the GDx Variable Corneal Compensation (VCC) Guided Progression Analysis (GPA) software for detecting glaucomatous progression. Design: Observational cohort study. Participants: The study included 453 eyes from 252 individuals followed for an average of 46 +/- 14 months as part of the Diagnostic Innovations in Glaucoma Study. At baseline, 29% of the eyes were classified as glaucomatous, 67% of the eyes were classified as suspects, and 5% of the eyes were classified as healthy. Methods: Images were obtained annually with the GDx VCC and analyzed for progression using the Fast Mode of the GDx GPA software. Progression using conventional methods was determined by the GPA software for standard automated achromatic perimetry (SAP) and by masked assessment of optic disc stereophotographs by expert graders. Main Outcome Measures: Sensitivity, specificity, and likelihood ratios (LRs) for detection of glaucoma progression using the GDx GPA were calculated with SAP and optic disc stereophotographs used as reference standards. Agreement among the different methods was reported using the AC(1) coefficient. Results: Thirty-four of the 431 glaucoma and glaucoma suspect eyes (8%) showed progression by SAP or optic disc stereophotographs. The GDx GPA detected 17 of these eyes for a sensitivity of 50%. Fourteen eyes showed progression only by the GDx GPA with a specificity of 96%. Positive and negative LRs were 12.5 and 0.5, respectively. None of the healthy eyes showed progression by the GDx GPA, with a specificity of 100% in this group. Inter-method agreement (AC1 coefficient and 95% confidence intervals) for non-progressing and progressing eyes was 0.96 (0.94-0.97) and 0.44 (0.28-0.61), respectively. Conclusions: The GDx GPA detected glaucoma progression in a significant number of cases showing progression by conventional methods, with high specificity and high positive LRs. Estimates of the accuracy for detecting progression suggest that the GDx GPA could be used to complement clinical evaluation in the detection of longitudinal change in glaucoma. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2010; 117: 462-470 (C) 2010 by the American Academy of Ophthalmology.

Scanning laser polarimetry with enhanced corneal compensation for detection of axonal loss in band atrophy of the optic nerve

PURPOSE: To compare the abilities of scanning laser polarimetry (SLP) with enhanced corneal compensation (ECC) and variable corneal compensation (VCC) modes for detection of retinal nerve fiber layer (RNFL) loss in eyes with band atrophy (BA) of the optic nerve. DESIGN. Cross-sectional study. METHODS: Thirty-seven eyes from 37 patients with BA and temporal visual field defect from chiasmal compression and 40 eyes from 40 healthy subjects were studied. Subjects underwent standard automated perimetry and RNFL measurements using an SLP device equipped with VCC and ECC. Receiver operating characteristic (ROC) curves were calculated for each parameter. Pearson correlation coefficients were obtained to evaluate the relationship between RNFL thickness parameters and severity of visual field loss, as assessed by the temporal mean defect. RESULTS: All RNFL thickness parameters were significantly lower in eyes with BA compared with normal eyes with both compensation modes. However, no statistically significant differences were observed in the areas under the ROC curves for the different parameters between GDx VCC and ECC (Carl Zeiss Meditec, Inc, Dublin, California, USA). Structure-function relationships also were similar for both compensation modes. CONCLUSIONS: No significant differences were found between the diagnostic accuracy of GDx ECC and that of VCC for detection of BA of the optic nerve. The use of GDx ECC does not seem to provide a better evaluation of RNFL loss on the temporal and nasal sectors of the peripapillary retina in subjects with BA of the optic nerve.

Neuroprotection for optic nerve disorders.

The concept that optic nerve fiber loss might be reduced by neuroprotection arose in the mid 1990s. The subsequent research effort, focused mainly on rodent models, has not yet transformed into a successful clinical trial, but provides mechanistic understanding of retinal ganglion cell death and points to potential therapeutic strategies. This review highlights advances made over the last year. In excitotoxicity and axotomy models retinal ganglion cell death has been shown to result from a complex interaction between retinal neurons and Müller glia, which release toxic molecules including tumor necrosis factor alpha. This counteracts neuroprotection by neurotrophins such as nerve growth factor, which bind to p75NTR receptors on Müller glia stimulating the toxic release. Another negative effect against neurotrophin-mediated protection involves the action of LINGO-1 at trkB brain-derived neurotrophic factor (BDNF) receptors, and BDNF neuroprotection is enhanced by an antagonist to LINGO-1. As an alternative to pharmacotherapy, retinal defences can be stimulated by exposure to infrared radiation. The mechanisms involved in glaucoma and other optic nerve disorders are being clarified in rodent models, focusing on retrograde degeneration following axonal damage, excitotoxicity and inflammatory/autoimmune mechanisms. Neuroprotective strategies are being refined in the light of the mechanistic understanding.

Effect of hormone replacement therapy on retinal and optic nerve head blood flow and topography in postmenopausal women, and retinal tissue perfusion in ovariectomized rats

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Analysis and Testing of a Novel Oadm Based on FBG and Machzehnder Interferometer

A novel optical add-drop multiplexer (OADM) based on the Mach-Zelauler interferometer (MZI) and the fiber Bragg grating (FBG) is proposed for the first tittle to the authors ' knowledge. In the structure, the Mach-Zehnder interferometer acts as an optical switch. The principle of the OADM is analyzed in this paper. The OADM can add/drop one of the multi-input channels or pass the channel directly by adjusting the difference of the two arms of the interferometer. The channel isolation is more than 20 dB

Loss of nerve fiber layer in HIV positive patients and comparative patterns in a series of cases in Bucaramanga, Colombia

Objective: The objective of this study is to conduct a description of the features of optic neuropathy associated with Human Immunodeficiency Virus in relation to their possible incidence within our population, regarding that there is no data in our population in terms of frequency of this pathology (1,2). Methodology: Descriptive cross-sectional study of a clinical series of patients infected with human immunodeficiency virus, but AIDS, and the thickness of optic nerve´s layer of fibers studied with OCT technology (optical coherence tomography), patients were cited once captured. OCT was performed by the same observer, by taking 3 shots and picking the one with better reliability. Patients were given personally to the Ophthalmologic Foundation of Santander to conduct the review called OCT (optical coherence tomography). Results: In terms of viral load variable, we found a clear correlation in which validates the hypothesis that lower viral load means a thicker layer of fibers finding statistically significant differences for the 6 hours in right eye and 12 and 6 hours in left eye. Comparison between the known nomogram of fiber layer thickness for the population of Bucaramanga, Santander and thickness found in our sample, we note a clear decrease in the upper and lower quadrants, specifically in 7 hours and 11 hours, being more important in 7 hours, showing statistically significant differences. Conclusions: The pattern  of thinning of the nerve fiber layer in HIV positive patients without AIDS, and antiretroviral treatment type HAART, showed a statistically significant thinning targeted at 7 hours and 11 hours, being higher in first. Viral load figures have a direct relation with loss fiber layer, showing a statistically significant difference for the 6 and 12 hours.

Retinal nerve fiber layer analysis using GDx® in 49 patients with chronic phase DUSN

To describe retinal nerve fiber layer changes in late-stage diffuse unilateral subacute neuroretinitis eyes and compare these results with healthy eyes observed through nerve fiber analyzer (GDx®). Methods: This is a retrospective case-control study in which 49 eyes in late-stage diffuse unilateral subacute neuroretinitis were examined from May/97 to December/ 01. First, eyes with diffuse unilateral subacute neuroretinitis and healthy contralateral eyes (Control Group I) were statistically matched. Subsequently, eyes with diffuse unilateral subacute neuroretinitis were compared with eyes of healthy patients (Control Group II). Results: Eyes from Control Groups I and II had higher relative frequency of “within normal limits” status. Eyes from the diffuse unilateral subacute neuroretinitis (DUSN) Group had higher frequency of “outside normal limits” and “borderline” status. Control Groups I and II had absolute values different from the DUSN Group regarding all parameters (p<0.05), except for Symmetry in Control Groups I and II, Average thickness and Superior Integral in control group II. Conclusion: Patients with late-stage diffuse unilateral subacute neuroretinitis presented presumed decrease in nerve fiber layer thickness shown by GDx®. Retinal zones with larger vascular support and larger amount of nerve fibers presented higher decrease in the delay of the reflected light measured by the nerve fiber analyzer

Heterodyne Interferometry Applied to the Characterization of Acousto-Electro-Optic Light Modulators

When the electro-optic and acousto-optic effects are combined into a single device, the resulting acousto-electro-optic (AEO) modulator shows improved flexibility to overcome some limitations of the individual modulators or their cascade combinations. By using optical interferometry, it is possible to investigate the AEO modulator behavior as a function of this applied voltage. By this way, a lithium niobate AEO modulator is positioned in one of the arms of a Mach-Zehnder interferometer and operates at 62 MHz frequency, which constitutes the intermediate frequency of the heterodyne interferometer. Operating the AEO modulator in the acousto-optic small diffraction efficiency regime, the photodetected signal amplitude and phase are analyzed, and the induced phase shift, transmission curve and linearity response are obtained. The experimental results show good agreement with that expected from the coupled-mode theory. The possibility of linear control of the optical phase shift by the external voltage, from 0 to 2 p radians, is demonstrated.

Microsurgical Anatomy of the Optic Radiation and Related Fibers in 3-Dimensional Images

BACKGROUND: The fiber dissection technique provides unique 3-dimensional anatomic knowledge of the white matter. OBJECTIVE: To examine the optic radiation anatomy and its important relationship with the temporal stem and to discuss its findings in relation to the approaches to temporal lobe lesions. METHODS: We studied 40 cerebral hemispheres of 20 brains that had been fixed in formalin solution for 40 days. After removal of the arachnoid membrane, the hemispheres were frozen, and the Klingler technique was used for dissection under magnification. Stereoscopic 3-dimensional images of the dissection were obtained for illustration. RESULTS: The optic radiations are located deep within the superior and middle temporal gyri, always above the inferior temporal sulcus. The mean distance between the cortical surface and the lateral edge of the optic radiation was 21 mm. Its fibers are divided into 3 bundles after their origin. The mean distance between the anterior tip of the temporal horn and the Meyer loop was 4.5 mm, between the temporal pole and the anterior border of the Meyer loop was 28.4 mm, and between the limen insulae and the Meyer loop was 10.7 mm. The mean distance between the lateral geniculate body and the lateral margin of the central bundle of the optic radiation was 17.4 mm. CONCLUSION: The white matter fiber dissection reveals the tridimensional intrinsic architecture of the brain, and its knowledge regarding the temporal lobe is particularly important for the neurosurgeon, mostly because of the complexity of the optic radiation and related fibers.

Retinal nerve fiber evaluation in neuro-ophthalmic diseases of the anterior visual pathway

Retinal nerve fiber evaluation is important in the diagnosis and management of several diseases of the anterior visual pathway. In this report we review the clinical findings and the current techonologies avalilable to analyse the retinal nerve fiber layer. We furthermore review the main findings in several disease of the anterior visual pathways including inflammatory, ischemic, toxics, hereditary, compressive and traumatic optic neuropathies as well as lesion of the optic chiasm, optic tract and lateral geniculate body.

Quantification of Retinal Neural Loss in Patients with Neuromyelitis Optica and Multiple Sclerosis with or without Optic Neuritis Using Fourier-Domain Optical Coherence Tomography

PURPOSE. We compared retinal nerve fiber layer (RNFL) and macular thickness measurements in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) with or without a history of optic neuritis, and in controls using Fourier-domain (FD) optical coherence tomography (OCT). METHODS. Patients with MS (n = 60), NMO (n = 33), longitudinal extensive transverse myelitis (LETM, n = 28) and healthy controls (n = 41) underwent ophthalmic examination, including automated perimetry, and FD-OCT RNFL and macular thickness measurements. Five groups of eyes were compared: MS with or without previous optic neuritis, NMO, LETM, and controls. Correlation between OCT and visual field (VF) findings was investigated. RESULTS. With regard to most parameters, RNFL and macular thickness measurements were significantly smaller in eyes of each group of patients compared to controls. MS eyes with optic neuritis did not differ significantly from MS eyes without optic neuritis, but measurements were smaller in NMO eyes than in all other groups. RNFL (but not macular thickness) measurements were significantly smaller in LETM eyes than in controls. While OCT abnormalities were correlated significantly with VF loss in NMO/LETM and MS, the correlation was much stronger in the former. CONCLUSIONS. Although FD-OCT RNFL and macular thickness measurements can reveal subclinical or optic neuritis-related abnormalities in NMO-spectrum and MS patients, abnormalities are predominant in the macula of MS patients and in RFNL measurements in NMO patients. The correlation between OCT and VF abnormalities was stronger in NMO than in MS, suggesting the two conditions differ regarding structural and functional damage. (ClinicalTrials.gov number, NCT01024985.) Invest Ophthalmol Vis Sci. 2012;53:3959-3966) DOI:10.1167/iovs.11-9324

Nerve fiber layer in glaucomatous hemifield loss: a case-control study with time- and spectral-domain optical coherence tomography

Purpose: To evaluate the retinal nerve fiber layer measurements with time-domain (TD) and spectral-domain (SD) optical coherence tomography (OCT), and to test the diagnostic ability of both technologies in glaucomatous patients with asymmetric visual hemifield loss. Methods: 36 patients with primary open-angle glaucoma with visual field loss in one hemifield (affected) and absent loss in the other (non-affected), and 36 age-matched healthy controls had the study eye imaged with Stratus-OCT (Carl Zeiss Meditec Inc., Dublin, California, USA) and 3 D OCT-1000 (Topcon, Tokyo, Japan). Peripapillary retinal nerve fiber layer measurements and normative classification were recorded. Total deviation values were averaged in each hemifield (hemifield mean deviation) for each subject. Visual field and retinal nerve fiber layer "asymmetry indexes" were calculated as the ratio between affected versus non-affected hemifields and corresponding hemiretinas. Results: Retinal nerve fiber layer measurements in non-affected hemifields (mean [SD] 87.0 [17.1] mu m and 84.3 [20.2] mu m, for TD and SD-OCT, respectively) were thinner than in controls (119.0 [12.2] mu m and 117.0 [17.7] mu m, P<0.001). The optical coherence tomography normative database classified 42% and 67% of hemiretinas corresponding to non-affected hemifields as abnormal in TD and SD-OCT, respectively (P=0.01). Retinal nerve fiber layer measurements were consistently thicker with TD compared to SD-OCT. Retinal nerve fiber layer thickness asymmetry index was similar in TD (0.76 [0.17]) and SD-OCT (0.79 [0.12]) and significantly greater than the visual field asymmetry index (0.36 [0.20], P<0.001). Conclusions: Normal hemifields of glaucoma patients had thinner retinal nerve fiber layer than healthy eyes, as measured by TD and SD-OCT. Retinal nerve fiber layer measurements were thicker with TD than SD-OCT. SD-OCT detected abnormal retinal nerve fiber layer thickness more often than TD-OCT.

Thermal excitations of optical nanofibers measured with a fiber-integrated Fabry-Pérot cavity

Efficient coupling of light to quantum emitters, such as atoms, molecules or quantum dots, is one of the great challenges in current research. The interaction can be strongly enhanced by coupling the emitter to the eva-nescent field of subwavelength dielectric waveguides that offer strong lateral confinement of the guided light. In this context subwavelength diameter optical nanofibers as part of a tapered optical fiber (TOF) have proven to be powerful tool which also provide an efficient transfer of the light from the interaction region to an optical bus, that is to say, from the nanofiber to an optical fiber. rnAnother approach towards enhancing light–matter interaction is to employ an optical resonator in which the light is circulating and thus passes the emitters many times. Here, both approaches are combined by experi-mentally realizing a microresonator with an integrated nanofiber waist. This is achieved by building a fiber-integrated Fabry-Pérot type resonator from two fiber Bragg grating mirrors with a stop-band near the cesium D2-line wavelength. The characteristics of this resonator fulfill the requirements of nonlinear optics, optical sensing, and cavity quantum electrodynamics in the strong-coupling regime. Together with its advantageous features, such as a constant high coupling strength over a large volume, tunability, high transmission outside the mirror stop band, and a monolithic design, this resonator is a promising tool for experiments with nanofiber-coupled atomic ensembles in the strong-coupling regime. rnThe resonator's high sensitivity to the optical properties of the nanofiber provides a probe for changes of phys-ical parameters that affect the guided optical mode, e.g., the temperature via the thermo-optic effect of silica. Utilizing this detection scheme, the thermalization dynamics due to far-field heat radiation of a nanofiber is studied over a large temperature range. This investigation provides, for the first time, a measurement of the total radiated power of an object with a diameter smaller than all absorption lengths in the thermal spectrum at the level of a single object of deterministic shape and material. The results show excellent agreement with an ab initio thermodynamic model that considers heat radiation as a volumetric effect and that takes the emitter shape and size relative to the emission wavelength into account. Modeling and investigating the thermalization of microscopic objects with arbitrary shape from first principles is of fundamental interest and has important applications, such as heat management in nano-devices or radiative forcing of aerosols in Earth's climate system. rnUsing a similar method, the effect of the TOF's mechanical modes on the polarization and phase of the fiber-guided light is studied. The measurement results show that in typical TOFs these quantities exhibit high-frequency thermal fluctuations. They originate from high-Q torsional oscillations that couple to the nanofiber-guided light via the strain-optic effect. An ab-initio opto-mechanical model of the TOF is developed that provides an accurate quantitative prediction for the mode spectrum and the mechanically induced polarization and phase fluctuations. These high-frequency fluctuations may limit the ultimate ideality of fiber-coupling into photonic structures. Furthermore, first estimations show that they may currently limit the storage time of nanofiber-based atom traps. The model, on the other hand, provides a method to design TOFs with tailored mechanical properties in order to meet experimental requirements. rn

Microcystic macular edema: retrograde maculopathy caused by optic neuropathy

PURPOSE To investigate retrograde axonal degeneration for its potential to cause microcystic macular edema (MME), a maculopathy that has been previously described in patients with demyelinating disease. To identify risk factors for MME and to expand the anatomic knowledge on MME. DESIGN Retrospective case series. PARTICIPANTS We included 117 consecutive patients and 180 eyes with confirmed optic neuropathy of variable etiology. Patients with glaucoma were excluded. METHODS We determined age, sex, visual acuity, etiology of optic neuropathy, and the temporal and spatial characteristics of MME. Eyes with MME were compared with eyes with optic neuropathy alone and to healthy fellow eyes. With retinal layer segmentation we quantitatively measured the intraretinal anatomy. MAIN OUTCOME MEASURES Demographic data, distribution of MME in the retina, and thickness of retinal layers were analyzed. RESULTS We found MME in 16 eyes (8.8%) from 9 patients, none of whom had multiple sclerosis or neuromyelitis optica. The MME was restricted to the inner nuclear layer (INL) and had a characteristic perifoveal circular distribution. Compared with healthy controls, MME was associated with significant thinning of the ganglion cell layer and nerve fiber layer, as well as a thickening of the INL and the deeper retinal layers. Youth is a significant risk factor for MME. CONCLUSIONS Microcystic macular edema is not specific for demyelinating disease. It is a sign of optic neuropathy irrespective of its etiology. The distinctive intraretinal anatomy suggests that MME is caused by retrograde degeneration of the inner retinal layers, resulting in impaired fluid resorption in the macula.