Heterogeneous Pattern of Retinal Nerve Fiber Layer in Multiple Sclerosis. High Resolution Optical Coherence Tomography: Potential and Limitations

BACKGROUND: Recently the reduction of the retinal nerve fibre layer (RNFL) was suggested to be associated with diffuse axonal damage in the whole CNS of multiple sclerosis (MS) patients. However, several points are still under discussion. (1) Is high resolution optical coherence tomography (OCT) required to detect the partly very subtle RNFL changes seen in MS patients? (2) Can a reduction of RNFL be detected in all MS patients, even in early disease courses and in all MS subtypes? (3) Does an optic neuritis (ON) or focal lesions along the visual pathways, which are both very common in MS, limit the predication of diffuse axonal degeneration in the whole CNS? The purpose of our study was to determine the baseline characteristics of clinical definite relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients with high resolution OCT technique. METHODOLOGY: Forty-two RRMS and 17 SPMS patients with and without history of uni- or bilateral ON, and 59 age- and sex-matched healthy controls were analysed prospectively with the high resolution spectral-domain OCT device (SD-OCT) using the Spectralis 3.5mm circle scan protocol with locked reference images and eye tracking mode. Furthermore we performed tests for visual and contrast acuity and sensitivity (ETDRS, Sloan and Pelli-Robson-charts), for color vision (Lanthony D-15), the Humphrey visual field and visual evoked potential testing (VEP). PRINCIPAL FINDINGS: All 4 groups (RRMS and SPMS with or without ON) showed significantly reduced RNFL globally, or at least in one of the peripapillary sectors compared to age-/sex-matched healthy controls. In patients with previous ON additional RNFL reduction was found. However, in many RRMS patients the RNFL was found within normal range. We found no correlation between RNFL reduction and disease duration (range 9-540 months). CONCLUSIONS: RNFL baseline characteristics of RRMS and SPMS are heterogeneous (range from normal to markedly reduced levels)

Evaluation of ranibizumab-induced changes in high-resolution optical coherence tomographic retinal morphology and their impact on visual function

To evaluate the effects of intravitreal ranibizumab on retinal function and morphology and to identify a correlation between anatomy and function by using spectral domain optical coherence tomography (SDOCT). Twenty-three patients affected by neovascular AMD received three injections of ranibizumab in three consecutive months and were monitored by assessment of best corrected visual acuity (BCVA), central retinal sensitivity (CRS) and morphologic changes at the level of the retina and the retinal pigment epithelium (RPE). The morphologic changes, identified by SDOCT segmentation, were mean retinal thickness (MRT), central retinal thickness (CRT), and the pathologic area (lesion area) of the RPE. BCVA increased from a mean 60.1 +/- 8.7 letters at baseline to 67.0 +/- 10.9 at month 3 (P = 0.0003). The CRS at the 0 degrees position increased from 2.8 +/- 3.1 dB at baseline to 4.0 +/- 5.7 at week 1, remaining stable until month 3. Absolute scotoma size decreased continuously from baseline to month 3, in a mean of 5.3 +/- 5.8 to 3.6 +/- 4.0 test point locations. By SDOCT, MRT decreased from 308.6 +/- 25.9 microm at baseline to 268.4 +/- 22.4 microm at month 3 (P = 0.0001). CRT was 365.8 +/- 84.9 and 254.9 +/- 95.1 microm at month 3 (P = 0.0002). The mean RPE lesion area was 6.0 +/- 3.0 mm(2) at baseline, which decreased to 5.0 +/- 3.1 mm(2) at month 3 (P = 0.115). The only significant correlation was identified between the lesion area and CRS. In ranibizumab therapy, the condition of the RPE lesion may be more relevant for visual function than the usual OCT parameters, retinal thickness

Human macula investigated in vivo with polarization-sensitive optical coherence tomography. Invest Ophthalmol Vis Sci.

PURPOSE. To investigate a depolarizing layer that is visible in polarization-sensitive optical coherence tomography (PS-OCT) images of the retina. To identify this layer and characterize its depolarizing effect quantitatively. METHODS. Ten healthy human subjects (mean age, 31 Ϯ 8 years) and two patients with RPE diseases participated in the study. The macular region of one eye of each subject was investigated with a phase-resolved PS-OCT system. The instrument measured backscattered intensity (standard OCT), phase retardation, and (cumulative) birefringent axis orientation, simultaneously. For a quantification of the depolarizing layer, plots of the distributions of retardation and axis orientation within and above this layer were analyzed. RESULTS. A polarization-scrambling layer (PSL) was observed at the posterior boundary of the retina in PS-OCT images of all volunteers. It was identified in PS-OCT images by determining random retardation and axis orientation in a transverse direction. Measurements in patients with neurosensory retinal detachment, retinal pigment epithelium (RPE) detachment, and RPE atrophy suggest that the PSL is the RPE. The statistical analysis provided objective discrimination of the RPE from the other retinal structures. CONCLUSIONS. PS-OCT represents a powerful tool for increasing image contrast in ocular tissues. The observed polarizationscrambling nature of the RPE may be used in diseased eyes to locate the RPE or remains of the RPE definitively in OCT images. (Invest Ophthalmol Vis Sci. 2006;47:5487-5494

RNFL thickness in MS-associated acute optic neuritis using SD-OCT: critical interpretation and limitations

PURPOSE: Axonal loss is considered a key prognostic factor in diagnosing and monitoring the progress of multiple sclerosis (MS). The purpose of our research was to determine whether the measurement of retinal nerve fibre layer thickness (RNFLT) as measured with high-resolution spectral-domain optical coherence tomography (SD-OCT) differs between optic nerve injury following acute optic neuritis (ON) or following unregistered subclinical axonal damage in patients with MS.METHODS: High-resolution SD-OCT measurements of RNFLT were initially carried out in the acute phase of ON and again after 3 months, in 25 patients with clinical definite MS and 25 sex- and age-matched healthy controls, all at the University Eye Hospital, Vienna.RESULTS: Conventional OCT-based RNFLT analysis correctly identified all three patients with initial RNFL swelling. However, only two of three acute ON eyes with a history of ON were registered with RNFLT decrease in seven peripapillary sectors (PPs). The remaining have only been revealed using RNFLT symmetry comparison. Two of 22 (9%) first-episode ON eyes were labelled as pathologic. The number and metric RNFL values of pathologically labelled PPs remained unchanged after 3 months. Our age- and sex-match-based measurement model, with patients with MS being plotted individually and towards the fellow eye, identified all acute ON eyes (with a history of prior ON) with RNFLT reduction in 11 PPs. A global RNFL loss was registered in 36.4% (eight of 22 eyes). However, in 72%, or 16 of 22 ON eyes presenting with first episode of acute ON, a segmental RNFL loss was initially registered in 39 PPs upon baseline examination. The number of PPs with identified axonal decrease increased to a total of 48 PPs within the observational period.CONCLUSIONS: Spectral-domain optical coherence tomography imaging of identical scanning locations, combined with an optimized scan centring around the optic disc, offers the technological potential of detecting prior, subtle, clinically unregistered optic nerve injury within MS individuals. Significant discrepancy in RNFLT to the potential ON eye may be achieved by comparing OCT metrics with the fellow eye and a sufficient number of age and sex-matched controls.</p

Comparing retinal thickness measurements from Cirrus spectral domain- and Stratus time domain-optical coherence tomography

The purpose of this study was to compare retinal measurements obtained using spectral domain-optical coherence tomography with measurements obtained using time domain-optical coherence tomography. Three hundred and seventy subjects were recruited at three university-based and one community-based retina practice for a cross-sectional observational study. For each subject, one eye was enrolled as the study eye. A Stratus Fast Macular scan was performed, and a Cirrus 200 x 200 Macular Cube scan was performed. Both instruments segment the acquired images to generate retinal thickness values and report averages measured in nine subfields defined by the Early Treatment Diabetic Retinopathy Study. These average values were compared with each other quantitatively using linear regression and Bland-Altman plots. Of the recruited subjects, 283 had acceptable images taken on the same day with both the Cirrus and Stratus devices. Mean differences between the instruments were noted in all subfields for all disease categories and ranged from 29 microm (outer superior subfield) to 54 microm (central subfield). Differences between time domain and spectral domain measurements of retinal thickness depend on pathology and location. Comparisons across instruments should be made with caution

Segmental reduction of RNFL.

<p>*p<0.05; **p<0.005; ***p<0.0001.</p

Global reduction of RNFL.

<p>*p<0.05; **p<0.005; ***p<0.0001.</p