Luis E. Pablo

Axonal loss in the retinal nerve fiber layer in patients with multiple sclerosis

Objective To quantify axonal loss in the retinal nerve fiber layer (RNFL) in patients with multiple sclerosis (MS), with and without a history of optic neuritis, by means of ocular imaging technologies. Methods This cross-sectional study enrolled 50 patients with MS and 25 age- and sex-matched healthy controls. All patients underwent neurologic assessment and a complete ophthalmic examination that included visual acuity, visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (GDx) and visual evoked potentials (VEPs). Visual parameters and RNFL measurements were evaluated in MS eyes with a prior optic neuritis episode (MS-ON), with no prior episode (MS-NON) and control subjects. Results There were significant differences (p < 0.05, analysis of variance) between MS-ON (n = 25 eyes) and healthy eyes (n = 25 eyes) for all RNFL parameters measured by OCT and GDx. Significant differences between MS-NON (n = 75 eyes) and healthy eyes were also found for most of these parameters. RNFL thickness in the temporal quadrant was the parameter with the greatest differences between groups (71.79 μm in healthy eyes, 60.29 μm in MS-NON and 53.92 μm in MS-ON, p < 0.0005). Although there was a highly significant but moderate correlation between RNFL thickness and duration of the disease, no correlation was observed between RNFL thickness and neurologic impairment (Expanded Disability Status Scale). Conclusions Axonal loss was detected not only in MS eyes with a previous acute optic neuritis, but also in MS eyes with no known optic neuritis episode. Structural abnormalities correlate with functional assessments of the optic nerve.

Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study

BACKGROUND Most patients with multiple sclerosis without previous optic neuritis have thinner retinal layers than healthy controls. We assessed the role of peripapillary retinal nerve fibre layer (pRNFL) thickness and macular volume in eyes with no history of optic neuritis as a biomarker of disability worsening in a cohort of patients with multiple sclerosis who had at least one eye without optic neuritis available. METHODS In this multicentre, cohort study, we collected data about patients (age ≥16 years old) with clinically isolated syndrome, relapsing-remitting multiple sclerosis, and progressive multiple sclerosis. Patients were recruited from centres in Spain, Italy, France, Germany, Czech Republic, Netherlands, Canada, and the USA, with the first cohort starting in 2008 and the latest cohort starting in 2013. We assessed disability worsening using the Expanded Disability Status Scale (EDSS). The pRNFL thickness and macular volume were assessed once at study entry (baseline) by optical coherence tomography (OCT) and was calculated as the mean value of both eyes without optic neuritis for patients without a history of optic neuritis or the value of the non-optic neuritis eye for patients with previous unilateral optic neuritis. Researchers who did the OCT at baseline were masked to EDSS results and the researchers assessing disability with EDSS were masked to OCT results. We estimated the association of pRNFL thickness or macular volume at baseline in eyes without optic neuritis with the risk of subsequent disability worsening by use of proportional hazards models that included OCT metrics and age, disease duration, disability, presence of previous unilateral optic neuritis, and use of disease-modifying therapies as covariates. FINDINGS 879 patients with clinically isolated syndrome (n=74), relapsing-remitting multiple sclerosis (n=664), or progressive multiple sclerosis (n=141) were included in the primary analyses. Disability worsening occurred in 252 (29%) of 879 patients with multiple sclerosis after a median follow-up of 2·0 years (range 0·5-5 years). Patients with a pRNFL of less than or equal to 87 μm or less than or equal to 88 μm (measured with Spectralis or Cirrus OCT devices) had double the risk of disability worsening at any time after the first and up to the third years of follow-up (hazard ratio 2·06, 95% CI 1·36-3·11; p=0·001), and the risk was increased by nearly four times after the third and up to the fifth years of follow-up (3·81, 1·63-8·91; p=0·002). We did not identify meaningful associations for macular volume. INTERPRETATION Our results provide evidence of the usefulness of monitoring pRNFL thickness by OCT for prediction of the risk of disability worsening with time in patients with multiple sclerosis. FUNDING Instituto de Salud Carlos III.

Ability and reproducibility of Fourier-domain optical coherence tomography to detect retinal nerve fiber layer atrophy in Parkinson's disease.

PURPOSE To evaluate and compare the ability of 3 protocols of Fourier-domain optical coherence tomography (OCT) to detect retinal thinning and retinal nerve fiber layer (RNFL) atrophy in patients with Parkinsons disease (PD) compared with healthy subjects. To test the intrasession reproducibility of RNFL thickness measurements in patients with PD and healthy subjects using the Cirrus (Carl Zeiss Meditec Inc., Dublin, CA) and Spectralis (Heidelberg Engineering, Inc., Heidelberg, Germany) OCT devices. DESIGN Observational, cross-sectional study. PARTICIPANTS Patients with PD (n = 75) and age-matched healthy subjects (n = 75) were enrolled. METHODS All subjects underwent three 360-degree circular scans centered on the optic disc by the same experienced examiner using the Cirrus OCT instrument, the classic glaucoma application, and the new Nsite Axonal Analytics of the Spectralis OCT instrument. MAIN OUTCOME MEASURES Differences between the eyes of healthy subjects and the eyes of patients with PD were compared using the 3 protocols. The relationship between measurements provided by each OCT protocol was evaluated. Repeatability was studied by intraclass correlation coefficients and coefficients of variation. RESULTS Retinal nerve fiber layer atrophy was detected in eyes of patients with PD (P = 0.025, P=0.042, and P < 0.001) with the 3 protocols used, but the Nsite Axonal Analytics of the Spectralis OCT device was the most sensitive for detecting subclinical defects. In eyes of patients with PD, RNFL thickness measurements determined by the OCT devices were correlated, but they were significantly different between the Cirrus and Spectralis devices (P = 0.038). Reproducibility was good with all 3 protocols but better using the Glaucoma application of the Spectralis OCT device. CONCLUSIONS Fourier-domain OCT can be considered a valid and reproducible device for detecting subclinical RNFL atrophy in patients with PD, especially the Nsite Axonal Analytics of the Spectralis device. Retinal nerve fiber layer thickness measurements differed significantly between the Cirrus and Spectralis devices despite a high correlation of the measurements between the 2 instruments.

Retinal layer segmentation in patients with multiple sclerosis using spectral domain optical coherence tomography.

PURPOSE To evaluate the thickness of the 10 retinal layers in the paramacular area of patients with multiple sclerosis (MS) compared with healthy subjects using the new segmentation technology of spectral domain optical coherence tomography (OCT). To examine which layer has better sensitivity for detecting neurodegeneration in patients with MS. DESIGN Observational, cross-sectional study. PARTICIPANTS Patients with MS (n = 204) and age-matched healthy subjects (n = 138). METHODS The Spectralis OCT system (Heidelberg Engineering, Inc., Heidelberg, Germany) was used to obtain automated segmentation of all retinal layers in a parafoveal scan in 1 randomly selected eye of each participant, using the new segmentation application prototype. MAIN OUTCOME MEASURES The thicknesses of 512 parafoveal points in the 10 retinal layers were obtained in each eye, and the mean thickness of each layer was calculated and compared between patients with MS and healthy subjects. The analysis was repeated, comparing patients with MS with and without previous optic neuritis. Correlation analysis was performed to evaluate the association between each retinal layer mean thickness, duration of disease, and functional disability in patients with MS. A logistic regression analysis was performed to determine which layer provided better sensitivity for detecting neurodegeneration in patients with MS. RESULTS All retinal layers, except the inner limiting membrane, were thinner in patients with MS compared with healthy subjects (P < 0.05). Greater effects were observed in the inner retinal layers (nerve fiber, ganglion cells, inner plexiform, and inner nuclear layers) of eyes with previous optic neuritis (P < 0.05). The retinal nerve fiber layer and ganglion cell layer thicknesses were inversely correlated with the functional disability score in patients with MS. The ganglion cell layer and inner plexiform layer thicknesses could predict axonal damage in patients with MS. CONCLUSIONS Analysis based on the segmentation technology of the Spectralis OCT revealed retinal layer atrophy in patients with MS, especially of the inner layers. Reduction of the ganglion cell and inner plexiform layers predicted greater axonal damage in patients with MS.

Fluorophotometric Study of the Effect of the Glaukos Trabecular Microbypass Stent on Aqueous Humor Dynamics

PURPOSE. To evaluate the changes in aqueous humor dynamics and the efficacy and safety of the iStent (Glaukos Corp., Laguna Hills, CA), in combination with cataract surgery. METHODS. This investigation was a prospective, randomized, clinical study in patients with open-angle glaucoma or ocular hypertension who were undergoing cataract surgery. Aqueous flow (F) and trabecular outflow facility (C(T)) were measured by fluorophotometry before surgery and at months 1, 6, and 12 in both groups. RESULTS. Thirty-three eyes of 33 patients were randomized to either two stents and cataract surgery (n = 17, group 1) or cataract surgery alone (n = 16, group 2). Before surgery, F and C(T) were similar in groups 1 and 2 (1.78 +/- 0.44 and 1.74 +/- 0.82 microL/min, P = 0.18; 0.12 +/- 0.03 and 0.13 +/- 0.06 microL/min/mm Hg, P = 0.71, respectively). After surgery, there were no changes of note in F, however, C(T) increased in both groups. At 1 year, C(T) was 0.45 +/- 0.27 microL/min/mm Hg in group 1 and 0.19 +/- 0.05 microL/min/mm Hg in group 2 (P = 0.02), which represented increases of 275% and 46%, respectively. Mean IOP reduction was also greater in group 1 than in group 2 (6.6 +/- 3.0 mm Hg vs. 3.9 +/- 2.7 mm Hg; P = 0.002). The mean number of medications was significantly lower in group 1 than in group 2 (0.0 vs. 0.7 +/- 1.0, respectively; P = 0.007). CONCLUSIONS. Compared with cataract surgery alone, implantation of the iStent concomitant with cataract extraction significantly increased trabecular outflow facility, reduced IOP, and reduced the number of medications at 1 year. Longer follow-up is needed to assess the long-term effect on outflow facility. (ClinicalTrials.gov number, NCT00326066.).

Distribution of retinal layer atrophy in patients with Parkinson disease and association with disease severity and duration.

PURPOSE To evaluate the thickness of the 10 retinal layers in the paramacular area of Parkinson disease patients using a new segmentation technology of optical coherence tomography (OCT) to examine whether the thickness of specific layers predicts neurodegeneration or Parkinson disease severity. DESIGN Observational prospective study. METHODS Parkinson disease patients (n = 129) and age-matched healthy subjects (n = 129) were enrolled. The Spectralis OCT system was used to automatically segment all retinal layers in a parafoveal scan using the new segmentation application prototype. Mean thickness of each layer was calculated and compared between Parkinson disease patients and healthy subjects, and between Parkinson disease patients with disease durations of less than or at least 10 years. A correlation analysis was performed to evaluate the association between retinal layer thickness, duration of disease, and Parkinson disease severity. Logistic regression analysis was performed to determine the most sensitive layer for predicting axonal atrophy. RESULTS Parkinson disease patients showed statistically significant reduced thickness in the retinal nerve fiber, ganglion cell, inner plexiform, and outer plexiform layers and increased thickness in the inner nuclear layer compared with healthy subjects (P < .05). The inner retinal layers were more affected in Parkinson disease patients with long disease duration. The ganglion cell layer thickness was inversely correlated with disease duration and Parkinson disease severity, and was predictive of axonal damage in Parkinson disease patients. CONCLUSIONS The segmentation application of the Spectralis OCT revealed retinal layer atrophy in Parkinson disease patients, especially in the inner layers of patients with long disease duration. Ganglion cell layer reduction was associated with increased axonal damage.

Retinal thinning and correlation with functional disability in patients with Parkinson's disease

Aims To determine whether there is an association between retinal thinning and functional rating scales in patients with Parkinsons disease (PD). Materials and methods Patients with PD (n=153) and controls (n=242) underwent evaluations of the macula and retinal nerve fibre layer (RNFL) using two new-generation Fourier domain optical coherence tomography (OCT) devices (Cirrus, Carl Zeiss Meditec, Dublin, California, USA; Spectralis, Heidelberg Engineering, Heidelberg, Germany). PD severity was assessed using the Schwab-England Activities of Daily Living scale, the Unified Parkinson Disease Rating Scale, the Hoehn and Yahr (HY) scale. Retinal and RNFL thicknesses were compared between patients and controls. Correlations between structural parameters and the scores of the neurologic scales were evaluated. Results RNFL parameters were significantly reduced in patients with PD, especially when using the Spectralis OCT device. All macular parameters, except for foveal thickness, differed significantly between controls and patients with PD (p<0.001). HY scores were significantly and inversely correlated with all macular parameters when measured with the Spectralis OCT device (p<0.05) and with RNFL thickness when measured with the Cirrus OCT device (nasal quadrant, sectors 2 and 5). Conclusions The neurodegeneration caused by PD can be detected using Fourier domain OCT. RNFL and macular thicknesses correlate with PD severity.

Electrophysiology and Optical Coherence Tomography to Evaluate Parkinson Disease Severity

PURPOSE To evaluate correlations between visual evoked potentials (VEP), pattern electroretinogram (PERG), and macular and retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) and the severity of Parkinson disease (PD). METHODS Forty-six PD patients and 33 age and sex-matched healthy controls were enrolled, and underwent VEP, PERG, and OCT measurements of macular and RNFL thicknesses, and evaluation of PD severity using the Hoehn and Yahr scale to measure PD symptom progression, the Schwab and England Activities of Daily Living Scale (SE-ADL) to evaluate patient quality of life (QOL), and disease duration. Logistical regression was performed to analyze which measures, if any, could predict PD symptom progression or effect on QOL. RESULTS Visual functional parameters (best corrected visual acuity, mean deviation of visual field, PERG positive (P) component at 50 ms -P50- and negative (N) component at 95 ms -N95- component amplitude, and PERG P50 component latency) and structural parameters (OCT measurements of RNFL and retinal thickness) were decreased in PD patients compared with healthy controls. OCT measurements were significantly negatively correlated with the Hoehn and Yahr scale, and significantly positively correlated with the SE-ADL scale. Based on logistical regression analysis, fovea thickness provided by OCT equipment predicted PD severity, and QOL and amplitude of the PERG N95 component predicted a lower SE-ADL score. CONCLUSIONS Patients with greater damage in the RNFL tend to have lower QOL and more severe PD symptoms. Foveal thicknesses and the PERG N95 component provide good biomarkers for predicting QOL and disease severity.

Use of Fourier-domain OCT to detect retinal nerve fiber layer degeneration in Parkinson’s disease patients

PurposeTo demonstrate axonal loss in the retinal nerve fiber layer (RNFL) of patients with Parkinson’s disease (PD) and to evaluate the ability of Fourier-domain optical coherence tomography (OCT) to detect RNFL degeneration and retinal thinning in these patients.MethodsPD patients (n=100) and healthy subjects (n=100) were included in the study and underwent visual acuity, color vision, and OCT examinations using two next-generation Fourier-domain devices (Spectralis and Cirrus). Differences in the RNFL thicknesses were compared between patients and controls.ResultsRNFL thicknesses were significantly reduced in PD patients compared with healthy subjects, especially those obtained using the Spectralis OCT, in the inferotemporal quadrant (155.6±16.5 μm in healthy eyes vs 142.1±24.9 μm in patients, P=0.040) and in the superotemporal quadrant (142.6±20.9 μm in healthy eyes vs 132.77±18.6 μm in PD patients, P=0.046). Significant differences were observed between controls and patients in relation to mean macular thickness (P=0.031), foveal thickness (P=0.030), and inferior outer thickness (P=0.019).ConclusionPD is associated with RNFL loss and retinal thinning, which is detectable by Fourier-domain OCT measurements.

Sub‐clinical atrophy of the retinal nerve fibre layer in multiple sclerosis

Acta Ophthalmol. 2010: 88: 748–752