The temporal evolution of structural and functional measures after acute optic neuritis.

BACKGROUND: In this prospective case series, we aimed to characterise the temporal evolution of functional and structural measures in the afferent visual pathway of patients with acute optic neuritis (ON). METHODS: Fifty patients with ON were followed over 12 months. Testing with spectral-domain optical coherence tomography, Early Treatment Diabetic Retinopathy Study logarithm of the minimum angle of resolution (LogMAR) visual acuity and Humphrey perimetry central 30-2 threshold (SITA strategy) was performed at baseline, 3, 6 and 12 months after symptom onset. The main outcome measure was mean peripapillary retinal nerve fibre layer (RNFL) thickness in ON eyes. Secondary outcomes included mean ganglion cell layer (GCL) thickness, LogMAR visual acuity, and Humphrey perimetry measured visual field mean deviation (VFMD). Survival analyses were performed to Kaplan-Meier curves and variables in the models were tested using the log-rank test. RESULTS: Over 12 months, RNFL and GCL values progressively declined in ON eyes, and intereye differences were significantly different across all time points. When functional recovery was defined as a VFMD better than -5.00 dB in ON eyes, the mean recovery time for the entire cohort was 3 months (survival was 48%, SE=0.09, 95% CI 0.30 to 0.64). There were significant differences in cumulative recovery when comparisons were made between genders: 3 months after symptom onset there was a higher percentage cumulative recovery for female (75%) versus male (25%) patients. CONCLUSIONS: Structural and functional measures evolve over time in patients with ON. There may be sex-specific differences in recovery after an acute ON event.

Sex-specific differences in retinal nerve fiber layer thinning after acute optic neuritis.

OBJECTIVE: The primary objective of this study was to explore the potential influence of gender on recovery from optic neuritis (ON) by determining whether differences in retinal nerve fiber layer (RNFL) thickness can be detected between men and women 6 months after an ON event. METHODS: In this prospective cohort study, 39 men and 105 women with acute ON underwent repeat visual and optical coherence tomography (OCT) testing. The main outcome measures were change in RNFL measurements for male and female patients 6 months after ON. RESULTS: Men were older (mean age = 39 years) than women (35 years) (p = 0.05) in this study, and more men (62%) than women (41%) had a diagnosis of relapsing-remitting multiple sclerosis (MS) (p = 0.02). Because age and MS subtype were 2 significant covariates, both variables were controlled for in multiple regression analyses. Other covariates controlled for in the multivariate regression included disease duration (years), use of disease-modifying therapy (yes/no), and use of high-dose corticosteroids for acute ON (yes/no). After 6 months, mean RNFL values were lower in men (74 µm) than women (91 µm) (p < 0.001). Men showed more apparent change in RNFL thickness in their ON eyes from baseline to 6 months after ON than women (p = 0.003). CONCLUSIONS: There may be differences in recovery between men and women after ON, which can be difficult to detect with conventional visual testing. Our findings raise interesting questions about the potential influence of gender in MS, which may be explored in future studies.

Exploring the Association between Retinal Nerve Fiber Layer Thickness and Initial Magnetic Resonance Imaging Findings in Patients with Acute Optic Neuritis.

Background. Recent studies have shown that OCT-measured retinal nerve fiber layer (RNFL) values may represent a marker for axonal damage in the anterior visual pathway of optic neuritis (ON) and multiple sclerosis (MS) patients. The goal of this study was to determine the link between RNFL values and initial magnetic resonance imaging (MRI) evidence of central nervous system (CNS) inflammation in patients with acute ON. Methods. Fifty patients who experienced ON as a clinically isolated syndrome (CIS) were followed for a mean period of 34 months with OCT testing. RNFL values in affected (ON) eyes and clinically unaffected (non-ON) eyes were compared between patients with MRI evidence of white matter lesions and those with normal baseline MRI findings, over a two year period. Findings. Twenty-one patients (42%) developed clinically definite MS (CDMS) during the study. After two years, temporal RNFL values were thinner (P = .07) in ON patients with MRI lesions at baseline, but the results were not significant. Conclusions. There is no association between RNFL values and baseline MRI status in ON patients at risk for future CDMS over a two year period.

Using retinal architecture to help characterize multiple sclerosis patients.

OBJECTIVE: We compared retinal nerve fibre layer (RNFL) thickness and visual function in a heterogeneous multiple sclerosis (MS) cohort to determine whether optical coherence tomography (OCT) may complement the existing methods used to characterize MS patients. DESIGN: Cross-sectional cohort study. PARTICIPANTS: One hundred and ninety-three patients with optic neuritis (ON) as a clinically isolated syndrome (CIS) (n = 63), relapsing-remitting MS (RRMS) (n = 108), secondary progressive MS (SPMS) (n = 13), and primary progressive MS (PPMS) (n = 9). METHODS: All patients underwent standardized ophthalmic, neurological, and OCT testing at a single academic institution. RESULTS: RNFL values were reduced in PPMS (94.3 µm), RRMS (99.6 µm), and SPMS eyes (84.7 µm) relative to CIS eyes (105.7 µm) (p<0.0001). RNFL values were lower in eyes with recurrent ON (64.2 µm) relative to eyes affected by a single ON event (86.3 µm) (p<0.0001). The strongest correlation between RNFL thickness and neurological disability occurred in RRMS patients (r = -0.51, p < 0.0001). RNFL thickness correlated with visual field sensitivity for CIS (r = 0.23, p < 0.01) and RRMS (r = 0.22, p < 0.01) patients. Simple linear regression showed that every 10 µm decrease in RNFL correlated with a 5.8 decibel decrease in visual field sensitivity (adjusted R2 = 0.35, p < 0.0001) for RNFL values less than 75 µm. CONCLUSIONS: There were robust correlations between RNFL thickness and visual function, particularly in ON eyes. OCT may complement the existing tools used to characterize MS patients, but further studies are needed.

Differences in retinal nerve fiber layer atrophy between multiple sclerosis subtypes.

OBJECTIVES: To determine whether retinal nerve fiber layer (RNFL) atrophy in the afferent visual pathway may complement existing tools used to describe and characterize differences across MS subtypes. METHODS: Optical coherence tomography-measured RNFL values were compared over two years in 35 patients (70 eyes) with optic neuritis (ON) as a clinically isolated syndrome (CIS); 39 patients (78 eyes) with relapsing remitting MS (RRMS); and 7 patients (14 eyes) with secondary progressive MS (SPMS). RESULTS: RNFL comparisons involving eyes without ON yielded greater differences between MS subtypes than ON-affected eyes. Overall RNFL values in non-affected eyes were reduced in SPMS patients (83.4 microm), relative to CIS (101.2 microm) (p=0.0009), and RRMS patients (103.7 microm) (p=0.001); and temporal RNFL atrophy was greater in RRMS (64.4 microm) eyes as compared to CIS eyes (73.2 microm) (p=0.02). In ON-affected eyes, RNFL atrophy was greater in SPMS patients (39.5 microm) than CIS patients (58.1 microm) (p=0.03), and in RRMS patients (48.2 microm) relative to CIS patients (p=0.05). RNFL values did not change significantly for any MS subtype during the two-year duration of the study. INTERPRETATION: RNFL thickness may represent a structural marker, which can help distinguish MS subtypes, because the extent of atrophy is commensurate with disease progression. RNFL comparisons between non-affected eyes revealed greater differences between CIS, RRMS, and SPMS patients relative to ON-affected eyes, because the impact of prior ON may supplant the effects of disease subtype.

Retinal nerve fiber layer and future risk of multiple sclerosis.

BACKGROUND: Optical coherence tomography (OCT)--measured retinal nerve fiber layer (RNFL) values may represent a surrogate biomarker for axonal integrity in multiple sclerosis (MS). The purpose of this study was to determine whether RNFL measurements obtained within two years of an optic neuritis (ON) event distinguish patients at increased risk of developing clinically-definite MS (CDMS). METHODS: Fifty consecutively sampled patients who experienced a single ON event were followed prospectively for a mean period of 34 months with OCT testing. Values of RNFL in clinically-affected and non-affected eyes were compared between patients who developed CDMS and those that did not develop MS after ON. FINDINGS: Twenty-one patients (42%) developed CDMS during the course of the study, with a mean conversion time of 27 months. Mean RNFL values were thinner in the clinically-affected eyes of non-MS patients than CDMS eyes after one year (p = 0.0462) due to more severe ON events in the former. By year two, CDMS patients manifested more recurrent ON events and RNFL thinning than non-MS patients. Temporal RNFL values were thinner in the non-affected eyes of CDMS patients with a trend towards significance (p = 0.1302). INTERPRETATION: Our results indicate that RNFL thickness does not reliably distinguish patients at higher risk of converting to CDMS after ON. The severity of ON has a greater effect on RNFL thickness than risk of CDMS at one year. The CDMS patients demonstrate progressive RNFL thinning likely due to recurrent sub-clinical ON events, which may help differentiate them from non-MS patients over time.

Tranexamic acid in the treatment of pediatric traumatic hyphema.

BACKGROUND: This study was undertaken to determine whether a difference exists in treatment outcome between patients treated with tranexamic acid (TEA) plus topical steroids and those treated with topical steroids alone. METHODS: A retrospective cohort study was conducted to compare treatment results for children with traumatic hyphema treated with TEA and topical steroids versus topical steroids alone. Patients were identified from a chart review of the Children's Hospital of Eastern Ontario eye clinic and the Queen's Department of Ophthalmology emergency eye clinic for charts coded "traumatic hyphema." The primary outcomes measured included visual acuity, rebleed rate, intraocular pressure, and time to hyphema resolution. Covariates were hyphema grade, the need for medications to lower intraocular pressure, and the presence of associated ocular traumatic complications. Analysis was performed with both bivariate analysis and multivariate models. RESULTS: Two hundred and fifteen patients with traumatic hyphema were included in our study. One hundred and thirty-seven patients (63.1%) received TEA plus topical steroids, and the remaining 78 patients received topical steroids alone. There was no significant difference in rebleed rate between the TEA plus topical steroid group (1.6%) and the steroid-alone group (2.6%, p = 0.60). INTERPRETATION: Patients with traumatic hyphema treated with TEA plus topical steroids did not have a significantly lower incidence of rebleed than those treated with topical steroids alone.

Quantifying axonal loss after optic neuritis with optical coherence tomography.

OBJECTIVE: To determine to what degree changes in retinal nerve fiber layer (RNFL) thickness after optic neuritis (ON) correlate with either visual recovery or impairment. METHODS: ON can cause visible defects within the RNFL, which can be quantified using optical coherence tomography (OCT). It may be possible to predict visual recovery by measuring RNFL loss after ON. Fifty-four patients underwent repeated evaluations with optical coherence tomography and standardized ophthalmic testing after ON. Regression analyses were used to determine the relationship between RNFL thickness and visual function. RESULTS: Thinning of the RNFL was seen in the majority of patients (74%), and it tended to occur within 3 to 6 months of ON. The average RNFL value was thinner (p<0.0001) in the affected (78 microm) compared with the unaffected eye (100 microm). Patients with incomplete visual recovery demonstrated greater RNFL loss after ON. Regression analyses demonstrated a threshold of RNFL thickness (75 microm), below which RNFL measurements predicted persistent visual dysfunction. INTERPRETATION: Determination of RNFL thickness may predict visual recovery after ON, and lower RNFL values correlate with impaired visual function. Optical coherence tomography may have a potential role as a surrogate marker for axonal integrity within the optic nerve among patients with ON.