Alex P. Lange

Spectral-domain optical coherence tomography of retinal nerve fiber layer thickness in NMO patients.

Background: Neuromyelitis optica (NMO) is a demyelinating syndrome of the central nervous system. NMO might be underdiagnosed at early stages when patients have not yet developed the full spectrum of disease. The aim of this study was to analyze the retinal nerve fiber layer (RNFL) with optical coherence tomography (OCT) and to compare RNFL measurements between NMO patients, patients with relapsing–remitting multiple sclerosis (RRMS), and healthy controls to determine whether differences in RNFL thickness could be an early diagnostic marker for NMO. Methods: In a cross-sectional study, eyes of 25 NMO patients, 25 RRMS patients, and 50 healthy controls underwent RNFL measurements by OCT. Clinical parameters were collected by history and chart review. Pairwise Wilcoxon rank sum tests with Holm correction were used to compare means of RNFL thickness among 6 groups (NMO, RRMS, and healthy control) of patients [without or with 1 or more episode of optic neuritis (ON)]. The association between RNFL thickness and patient characteristics for NMO group was examined via linear mixed-effects models (adjusting for within-patient intereye correlations and history of ON, where appropriate). Results: Based on the pairwise Wilcoxon rank sum tests with Holm correction, significant differences were found between NMO with 1 episode of ON and non-ON eyes (mean RNFL 63.7 vs 97.0 µm, P < 0.0001), multiple sclerosis (MS) non-ON eyes, and controls (RNFL 93.2 vs 98.4 µm, P = 0.03). No significant differences were found between NMO and MS with 1 attack of ON eyes (RNFL 63.7 vs 73.9 µm, P = 0.46), NMO non-ON eyes and healthy controls (RNFL 97.0 vs 98.4 µm, P = 0.56), and NMO non-ON and MS non-ON (RNFL 97.0 vs 93.2 µm, P = 0.56). For NMO group, RNFL thickness was associated with a history of ON (P < 0.001) but not with disability or disease duration when adjusting for the history of ON (P > 0.1). Conclusions: RNFL in NMO is not different enough to distinguish NMO ON from MS ON eyes, but the intereye difference in RFNL with a history of unilateral ON may be a better diagnostic marker for NMO.

Retinal nerve fiber layer thickness in benign multiple sclerosis.

Background/objective: Retinal nerve fiber layer (RNFL) thickness has been linked to brain atrophy in multiple sclerosis (MS). However, little is known about retinal atrophy in ‘benign’ MS. We compared RNFL thickness in benign MS with healthy controls. Methods: Patients with benign MS (Expanded Disability Status Scale (EDSS) ≤ 3; ≥15 years’ disease duration), identified through the British Columbia MS database, along with age-matched healthy controls, were recruited. RNFL thickness was measured using spectral-domain optical coherence tomography. Analysis of variance (ANOVA) was used to compare groups. The association between RNFL thickness and MS patient characteristics was examined via linear mixed-effects models (adjusting for within-patient inter-eye correlations and history of optic neuritis (ON), where appropriate). Results: Overall, 29 benign MS patients and 29 healthy controls were included, totaling 116 eyes. RNFL thickness was lowest for the benign MS eyes, with and then without a history of ON, followed by healthy controls (mean=73.2 µm, SD ± 0.4; 89.9 µm, SD ± 12.5; 96.7 µm, SD ± 10.4; p<0.02). RNFL thickness was associated with a history of ON (p<0.0001), but not EDSS or disease duration (p>0.1). Conclusions: RNFL thickness was lower in patients with benign MS than healthy controls, regardless of the previous history of ON. However, no association was found between RNFL values and disability or MS disease duration.

Quantifying visual pathway axonal and myelin loss in multiple sclerosis and neuromyelitis optica

Background The optic nerve is frequently injured in multiple sclerosis and neuromyelitis optica, resulting in visual dysfunction, which may be reflected by measures distant from the site of injury. Objective To determine how retinal nerve fiber layer as a measure of axonal health, and macular volume as a measure of neuronal health are related to changes in myelin water fraction in the optic radiations of multiple sclerosis and neuromyelitis optica participants with and without optic neuritis and compared to healthy controls. Methods 12 healthy controls, 42 multiple sclerosis (16 with optic neuritis), and 10 neuromyelitis optica participants (8 with optic neuritis) were included in this study. Optical coherence tomography assessment involved measurements of the segmented macular layers (total macular, ganglion cell layer, inner plexiform layer, and inner nuclear layer volume) and paripapillary retinal nerve fiber layer thickness. The MRI protocol included a 32-echo T2-relaxation GRASE sequence. Average myelin water fraction values were calculated within the optic radiations as a measure of myelin density. Results Multiple sclerosis and neuromyelitis optica eyes with optic neuritis history had lower retinal nerve fiber layer thickness, total macular, ganglion cell and inner plexiform layer volumes compared to eyes without optic neuritis history and controls. Inner nuclear layer volume increased in multiple sclerosis with optic neuritis history (mean = 0.99 mm3, SD = 0.06) compared to those without (mean = 0.97 mm3, SD = 0.06; p = 0.003). Mean myelin water fraction in the optic radiations was significantly lower in demyelinating diseases (neuromyelitis optica: mean = 0.098, SD = 0.01, multiple sclerosis with optic neuritis history: mean = 0.096, SD = 0.01, multiple sclerosis without optic neuritis history: mean = 0.098, SD = 0.02; F3,55 = 3.35, p = 0.03) compared to controls. Positive correlations between MRI and optical coherence tomography measures were also apparent (retinal nerve fiber layer thickness and ganglion cell layer thickness: r = 0.25, p = 0.05, total macular volume and inner plexiform layer volume: r = 0.27, p = 0.04). Conclusions The relationship between reductions in OCT measures of neuro-axonal health in the anterior visual pathway and MRI-based measures of myelin health in the posterior visual pathway suggests that these measures may be linked through bidirectional axonal degeneration.

Time-Domain and Spectral-Domain Optical Coherence Tomography of Retinal Nerve Fiber Layer in MS Patients and Healthy Controls

Objective. The aim of this study was to compare retinal nerve fiber layer thickness (RNFLT) between spectral-domain (SD-) and time-domain optical coherence tomography (TD-OCT) in MS patients and healthy controls (HC). Furthermore, RNFLT between MS eyes with and without optic neuritis (ON) and HC should be explored. Finally, the relationship between RNFLT, disease duration, EDSS, and disease modifying therapy (DMT) should be established. Design. Prospective, cross-sectional study. Participants. 28 MS patients and 35 HC. Methods. Both groups underwent TD- and SD-OCT measurements. RFNLT was correlated between the two machines and between MS eyes with and without ON and HC. Furthermore, RNFLT was correlated to disease duration, EDSS and DMT. Results. A strong correlation (Pearsons r = 0.921, P < 0.001), but a statistically significant difference of 2 μm (P < 0.001), was found between the two devices. RNFLT was significantly different between MS eyes with history of ON (mean RFNLT (SD) 72.21 μm (15.83 μm)), MS eyes without history of ON 93.03 μm (14.25 μm), and HC 99.07 μm (7.23 μm) (P < 0.001). Conclusions. The measurements between different generation of OCT machines are not interchangeable, which should be taken into account if comparing results between different machines and switching OCT machine in longitudinal studies.

Longitudinal Study of Retinal Nerve Fiber Layer Thickness and Macular Volume in Patients With Neuromyelitis Optica Spectrum Disorder.

Background:Neuromyelitis spectrum disorder (NMOSD) is a rare autoimmune disorder previously thought to be a subtype of multiple sclerosis (MS). NMOSD is characterized by episodes of inflammation and damage to astrocytes that primarily results in damage to optic nerve and spinal cord. The objective of this exploratory study was to use optical coherence tomography (OCT) to measure axonal and neuronal health in NMOSD eyes over time. Methods:Nine patients with definite NMOSD were assessed at baseline and follow-up visits (time between visits: 35–55 months). OCT assessment involved a macular volume protocol and a retinal nerve fiber layer (RNFL) thickness scan. Results:The temporal, inferior, nasal, or superior quadrant and the mean global RNFL thickness, macular thickness, and volume of each NMOSD patient was unchanged compared with baseline for each eye separately and both together. There also was no change between the 2 time points for the OCT measures for eyes affected and unaffected by optic neuritis and all eyes together except for a significant change in the temporal RNFL quadrant when all NMOSD eyes were pooled together (mean = 2.88 &mgr;m, SD = 3.7, P = 0.021). Conclusions:Unlike in MS eyes, ongoing RNFL and macular thinning secondary to brain and optic nerve atrophy could not be observed in NMOSD eyes during an observation period of 4 years. This might be an additional marker to distinguish these 2 diseases. However, to confirm this finding, more long-term data are needed to compare these 2 diseases longitudinally.

Corticospinal tract integrity measured using transcranial magnetic stimulation and magnetic resonance imaging in neuromyelitis optica and multiple sclerosis

Background: Both multiple sclerosis (MS) and neuromyelitis optica (NMO) can present with transverse myelitis; however, NMO symptoms are usually more severe and may present with more extensive axonal loss. Transcranial magnetic stimulation (TMS)-based input–output recruitment curves can quantitatively assess the excitability of corticospinal tract pathways and myelin water imaging can quantify the amount of myelin within this same pathway. Objective: To compare differential effects of MS and NMO on TMS recruitment curves and myelin water imaging. Methods: Ten healthy controls, 10 individuals with MS and 10 individuals with NMO completed clinical assessments, a TMS assessment and magnetic resonance imaging scan to measure recruitment curves and myelin water fraction in the corticospinal tract. Results: Individuals with NMO had lower recruitment curve slopes (mean 13.6±6 μV/%) than MS (23.6±11 μV/%) and controls (21.9±9 μV/%, analysis of variance (ANOVA) P=0.05). Corticospinal tract myelin water fraction was lower in individuals with NMO (mean 0.17±0.02) compared to MS (0.19±0.02) and controls (0.20±0.02, ANOVA P=0.0006). Conclusion: Corticospinal pathway damage in individuals with NMO was evident by reduced recruitment curve slope and lower myelin water fraction. These specific measures of corticospinal function and structure may be used to obtain a better understanding and monitor brain injury caused by inflammatory central nervous system disorders.

Bilateral corneal ulceration caused by vitamin a deficiency in eosinophilic gastroenteropathy.

Purpose: Vitamin A deficiency is a very rare condition in the developed world and can lead to a variety of ocular changes from xerosis and xerophthalmia to corneal ulcer and perforation. The treatment of this devastating disease is simple and inexpensive. It is therefore important to recognize and treat accordingly, especially in the event of ulcers unresponsive to treatment or in the presence of severe malnutrition/malabsorption syndromes. The purpose of this case report is to remind physicians of the potentially devastating effects of vitamin A deficiency on the eyes and to demonstrate outcomes after vitamin A treatment. Methods: Single observational case report. Results: A 29-year-old male with known eosinophilic gastroenteropathy was treated with oral steroids for peripheral ulcerative keratitis. Two weeks after resolution, the patient suffered from peripheral ulcerative keratitis in his other eye, with a self-sealing perforation. Vitamin A deficiency was confirmed and successfully treated, leading to subsequent resolution of signs and symptoms. Conclusions: Vitamin A deficiency can be present in patients with malabsorption and malnutrition syndromes and should be considered as cause of corneal ulceration.

Reproducibility of Retinal Nerve Fiber Layer Measurements with Manual and Automated Centration in Healthy Subjects Using Spectralis Spectral-Domain Optical Coherence Tomography

Objective. The aim of this study was to test the reproducibility of the Heidelberg Spectralis SD-OCT and to determine if provided software retest function for follow-up exam is superior to manual centration. Design. Prospective, cross-sectional study. Participants. 20 healthy subjects. Methods. All subjects underwent SD-OCT testing to determine retinal nerve fiber layer (RNFL) measurements sequentially on two different days and with two different centration techniques. Within-subject standard deviation, coefficient of variation, and intraclass correlation coefficient were used to assess reproducibility. Results. RNFL measurements showed high reproducibility, low within-subject standard deviation (1.3), low coefficient of variation (0.63%), and low intra-class correlation coefficient (0.98 (95% CI 0.97–0.99)) in the automated centration and manual centration groups for average RNFL Thickness. Quadrants showed slightly higher variability in the manual group compared to the automated group (within-subject standard deviation 2.5–5.3 versus 1.1–2.4, resp.). Conclusions. SD-OCT provides high-resolution RNFL measurements with high reproducibility and low variability. The re-test function allows for easier recentration for longitudinal examinations with similar results in average RNFL, but less variability in quadrant RNFL. SD-OCT high reproducibility and low variability is a promising fact and should be further evaluated in longitudinal studies of RNFL.

Focal limbal stem cell deficiency associated with soft contact lens wear

OBJECTIVE The aim of this study is to summarize the clinical characteristics of patients with contact lens-associated focal limbal stem cell deficiency (FLSCD) from a tertiary corneal referral centre. DESIGN Retrospective, observational case series in a tertiary care centre. METHODS Patients with contact lens-associated FLCSD were identified in our database. Clinical data were retrieved by chart review. A questionnaire asking for contact lens brand, type, cleaning solution, and duration of contact lens wear was sent to the patients with telephone follow-up. Clinical features and recovery time were identified. RESULTS Twenty-seven eyes of 17 patients were identified with superior corneal whorl-like patches of opaque epithelium, sometimes accompanied by neovascularization. Of the patients, 17/17 used soft contact lenses, with a mean wearing duration of 11.4 hours per day. Patients had been wearing lenses for an average of 18.1 years. Silicone hydrogel lenses were noted in 12/17 cases. LSCD was superior in all 27 eyes, and all of them improved with contact lens wear cessation, preservative-free topical steroids, and preservative-free artificial tears. Visual acuity improved from 20/28 to 20/22 (p < 0.001). CONCLUSIONS Contact lens-associated FLSCD typically presents in the superior cornea with whorl-like epithelial opacities advancing from the limbus. Conservative medical treatment is available and shows a high success rate after a slow recovery.