Letter Acuity Research Articles

Measuring the rate of progression in Friedreich ataxia: Implications for clinical trial design

Friedreich ataxia is an autosomal recessive neurodegenerative disorder characterized by ataxia of all four limbs, dysarthria, and arreflexia. A variety of measures are currently used to quantify disease progression, including the Friedreich Ataxia Rating Scale, examiner-rated functional disability scales, self-reported activities of daily living and performance measures such as the timed 25-foot walk, 9-hole pegboard test, PATA speech test, and low-contrast letter acuity vision charts. This study examines the rate of disease progression over one and two years in a cohort of 236 Friedreich ataxia patients using these scales and performance measure composites. The Friedreich Ataxia Rating Scale and performance-measure composites captured disease progression, with a greater sensitivity to change over 2 years than over 1 year. The measures differed in their sensitivity to change and in possible bias. These results help to establish norms for progression in FRDA that can be useful in measuring the long-term success of therapeutic agents and defining sample-size calculations for double-blind clinical trials.

61st Annual Meeting of the American Academy of Neurology Seattle, Washington April 25-May 2, 2009

61st Annual Meeting of the American Academy of Neurology Seattle, Washington April 25-May 2, 2009

Scope of super-resolution in central vision

Background:The term super-resolution refers to computational enhancement of detail in sets of similar images, particularly undersampled images. Undersampling is a key feature of visual disorders associated with neuroretinal matrix damage....

Macular Volume Determined by Optical Coherence Tomography as a Measure of Neuronal Loss in Multiple Sclerosis

Inner (area adjacent to the fovea) and outer regions of the macula differ with respect to relative thicknesses of the ganglion cell layer (neurons) vs retinal nerve fiber layer (RNFL; axons). To determine how inner vs outer macular volumes relate to peripapillary RNFL thickness and visual function in multiple sclerosis (MS) and to examine how these patterns differ among eyes with vs without a history of acute optic neuritis (ON). Study using cross-sectional optical coherence tomography. Three academic tertiary care MS centers. Patients with MS, diagnosed by standard criteria, and disease-free control participants. Optical coherence tomography was used to measure macular volumes and RNFL thickness. Visual function was assessed using low-contrast letter acuity and high-contrast visual acuity (Early Treatment Diabetic Retinopathy Study charts). Among eyes of patients with MS (n = 1058 eyes of 530 patients), reduced macular volumes were associated with peripapillary RNFL thinning; 10-microm differences in RNFL thickness (9.6% of thickness in control participants without disease) corresponded to 0.20-mm(3) reductions in total macular volume (2.9% of volume in control participants without disease, P < .001). This relation was similar for eyes of MS patients with and without a history of ON. Although peripapillary RNFL thinning was more strongly associated with decrements in outer compared with inner macular volumes, correlations with inner macular volume were significant (r = 0.58, P < .001) and of slightly greater magnitude for eyes of MS patients with a history of ON vs eyes of MS patients without a history of ON (r = 0.61 vs r = 0.50). Lower (worse) visual function scores were associated with reduced total, inner, and outer macular volumes. However, accounting for peripapillary RNFL thickness, the relation between vision and inner macular volume remained significant and unchanged in magnitude, suggesting that this region contains retinal structures separate from RNFL axons that are important to vision. Analogous to studies of gray matter in MS, these data provide evidence that reductions of volume in the macula (approximately 34% neuronal cells by average thickness) accompany RNFL axonal loss. Peripapillary RNFL thinning and inner macular volume loss are less strongly linked in eyes of MS patients without a history of ON than in eyes of MS patients with a history of ON, suggesting alternative mechanisms for neuronal cell loss. Longitudinal studies with segmentation of retinal layers will further explore the relation and timing of ganglion cell degeneration and RNFL thinning in MS.

Effects of combination therapy with verteporfin photodynamic therapy and ranibizumab in patients with age-related macular degeneration

This open-label, prospective, small-scale study investigated the benefits of same-day verteporfin and intravitreal ranibizumab in patients with predominantly classic, minimally classic or occult subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration. Patients received verteporfin at baseline and at month 3, if leakage persisted. Ranibizumab (0.5 mg) was given at baseline and months 1, 2 and 3, and thereafter at monthly intervals if required. Same-day ranibizumab was given ≥ 1 hr after verteporfin. Fifteen patients [11 male, four female; mean age 75.5 years (range 54-94 years)] were treated. At day 360, mean visual acuity (VA) had improved by 10.9 letters. An increase of ≥ 15 and ≥ 30 letters (i.e. ≥ 3 and ≥ 6 lines) was observed in seven (47%) patients and one patient (7%), respectively. Mean central retinal thickness (CRT) decreased by 85 μm. At days 7, 14 and 30, CNV perfusion was absent in 14/15 patients. Mean lesion area had reduced from baseline by 23.1% at day 120, 25.5% at day 180 and 23.6% at day 360. There were no visual safety concerns and intraocular pressures remained normal. Only two serious adverse events were recorded over the 12-month period, and neither was considered to be related to treatment. Same-day verteporfin plus ranibizumab improved VA, reduced CRT, prevented CNV perfusion and reduced lesion area safely over 12 months. Further investigation is warranted to confirm whether this combination improves long-term vision and reduces the need for retreatment.

Stability of visual outcome from 7 years in children treated surgically for bilateral dense congenital cataracts before 37 weeks of age

To study the long-term visual outcome and the age at which final visual acuity can be predicted in a population sample of children treated surgically for bilateral dense congenital cataract before 37 weeks of age. In addition, we assessed the influence of associated risk factors and compared the visual development of these aphakic children with presumably blocked visual input before early surgery to that of normal children in Sweden. The 18 patients included were followed for at least 10 years postoperatively. The median age at last visit was 15.5 years (range 10-18). The best-corrected visual acuity (BCVA) was tested monocularly with a logarithmically scaled letter acuity test from 4 years of age to late teens. Other registered postoperative data were presence of manifest nystagmus, strabismus and complications. The BCVA of the better-seeing eye reached a plateau at 7 years of age. Age at surgery of 80 days or less characterized the majority of cases with a logMAR ≤ 0.3 with a threshold effect between 80 and 130 days of age. Compared to normal children in Sweden, the long-term visual outcome showed a deficit of 0.5-0.6 logMAR. In spite of optimized care and surgery before 9 months, the BCVA was subnormal in our population compared to healthy children. The long-term visual outcome can be predicted at 7 years of age. Screening with early detection followed by surgery before the end of the third month is important to decrease the risk of marked acuity loss.

Continuous anti-VEGF treatment with ranibizumab for polypoidal choroidal vasculopathy: 6-month results

AimTo evaluate the short-term efficacy and safety of monthly intravitreal injections of ranibizumab in patients with polypoidal choroidal vasculopathy (PCV) and active exudation or haemorrhage.MethodsA prospective, open-label trial of monthly...

Visual Acuity Outcomes after Cataract Surgery in Patients with Age-Related Macular Degeneration: Age-Related Eye Disease Study Report No. 27

To evaluate visual acuity outcomes after cataract surgery in patients with varying degrees of age-related macular degeneration (AMD). Cohort study. A total of 4757 participants enrolled in the Age-Related Eye Disease Study (AREDS), a prospective, multicenter, epidemiological study of the clinical course of cataract and AMD and a randomized controlled trial of antioxidants and minerals. Standardized lens and fundus photographs, performed at baseline and annual visits, were graded by a centralized reading center using standardized protocols for severity of AMD and lens opacities. History of cataract surgery was obtained every 6 months. Analyses were conducted using multivariate logistic regression. The change in best-corrected visual acuity (BCVA) after cataract surgery compared with preoperative BCVA. Visual acuity results were analyzed for 1939 eyes that had cataract surgery during AREDS. The mean time from cataract surgery to measurement of postoperative BCVA was 6.9 months. After adjustment for age at surgery, gender, type, and severity of cataract, the mean change in visual acuity at the next study visit after the cataract surgery was as follows: Eyes without AMD gained 8.4 letters of acuity (P<0.0001), eyes with mild AMD gained 6.1 letters of visual acuity (P<0.0001), eyes with moderate AMD gained 3.9 letters (P<0.0001), and eyes with advanced AMD gained 1.9 letters (P = 0.04). The statistically significant gain in visual acuity after cataract surgery was maintained an average of 1.4 years after cataract surgery. On average, participants with varying severity of AMD benefited from cataract surgery with an increase in visual acuity postoperatively. This average gain in visual acuity persisted for at least 18 months.

Damage to the Optic Radiation in Multiple Sclerosis Is Associated With Retinal Injury and Visual Disability

To determine whether damage to the optic radiation (OR) in multiple sclerosis (MS) is associated with optic nerve injury and visual dysfunction. Case-control study. Referral center. Ninety referred patients with MS and 29 healthy volunteers. Magnetic resonance imaging indices along the OR were reconstructed with diffusion tensor tractography. Retinal nerve fiber layer thickness and visual acuity at high and low contrast were measured in a subset of the MS group (n = 36). All tested magnetic resonance imaging indices (fractional anisotropy [FA]; mean, parallel, and perpendicular [lambda( perpendicular)] diffusivity; T2 relaxation time; and magnetization transfer ratio) were significantly abnormal in patients with MS. Mean retinal nerve fiber layer thickness was significantly correlated with FA (r = 0.55; P < .001) and lambda( perpendicular) (r = -0.37; P = .001). The retinal nerve fiber layer thickness in the nasal retinal quadrant was also specifically correlated with FA and lambda( perpendicular) in the synaptically connected contralateral OR. In individuals with less severely damaged optic nerves (mean retinal nerve fiber layer thickness >80 mum), letter acuity scores at 2.5% contrast were correlated with OR-specific FA (r = 0.55; P = .004), lambda( perpendicular) (r = -0.40; P = .04), and magnetization transfer ratio (r = 0.54; P = .01), as well as the fraction of OR volume made up of lesions (r = -0.69; P < .001). Fractional anisotropy and lambda( perpendicular) are potentially useful quantitative magnetic resonance imaging biomarkers of OR-specific damage in MS. Such damage is associated with retinal injury and visual disability.

A Phase IIIb Study to Evaluate the Safety of Ranibizumab in Subjects with Neovascular Age-related Macular Degeneration

To evaluate the safety and efficacy of intravitreal ranibizumab in a large population of subjects with neovascular age-related macular degeneration (AMD). Twelve-month randomized (cohort 1) or open-label (cohort 2) multicenter clinical trial. A total of 4300 subjects with angiographically determined subfoveal choroidal neovascularization (CNV) secondary to AMD. Cohort 1 subjects were randomized 1:1 to receive 0.3 mg (n = 1169) or 0.5 mg (n = 1209) intravitreal ranibizumab for 3 monthly loading doses. Dose groups were stratified by AMD treatment history (treatment-naïve vs. previously treated). Cohort 1 subjects were retreated on the basis of optical coherence tomography (OCT) or visual acuity (VA) criteria. Cohort 2 subjects (n = 1922) received an initial intravitreal dose of 0.5 mg ranibizumab and were retreated at physician discretion. Safety was evaluated at all visits. Safety outcomes included the incidence of ocular and nonocular adverse events (AEs) and serious adverse events (SAEs). Efficacy outcomes included changes in best-corrected VA over time. Some 81.7% of cohort 1 subjects and 49.9% of cohort 2 subjects completed the 12-month study. The average total number of ranibizumab injections was 4.9 for cohort 1 and 3.6 for cohort 2. The incidence of vascular and nonvascular deaths during the 12-month study was 0.9% and 0.7% in the cohort 1 0.3 mg group, 0.8% and 1.5% in the cohort 1 0.5 mg group, and 0.7% and 0.9% in cohort 2, respectively. The incidence of death due to unknown cause was 0.1% in both cohort 1 dose groups and cohort 2. The number of vascular deaths and deaths due to unknown cause did not differ across cohorts or dose groups. Stroke rates were 0.7%, 1.2%, and 0.6% in the 0.3 mg and 0.5 mg groups and cohort 2, respectively. At month 12, cohort 1 treatment-naïve subjects had gained an average of 0.5 (0.3 mg) and 2.3 (0.5 mg) VA letters and previously treated subjects had gained 1.7 (0.3 mg) and 2.3 (0.5 mg) VA letters. Intravitreal ranibizumab was safe and well tolerated in a large population of subjects with neovascular AMD. Ranibizumab had a beneficial effect on VA. Future investigations will seek to establish optimal dosing regimens for persons with neovascular AMD. Proprietary or commercial disclosure may be found after the references.

Verteporfin PDT for subfoveal occult CNV in AMD: two-year results of a randomized trial

ABSTRACTObjective: To determine whether verteporfin photodynamic therapy (PDT) can safely reduce the risk of vision loss in patients with subfoveal occult with no classic choroidal neovascularization (CNV) due to age-related macular degeneration.Research design and methods: Eligible patients were ≥50 years of age with lesion size ≤6 disc areas and best-corrected vision 20/40–20/200. A total of 364 patients with occult with no classic CNV were randomly assigned 2 : 1 to verteporfin PDT (n = 244) or placebo (n = 120). The primary outcome measures were loss of ≥15 and ≥30 letters of visual acuity (VA) from baseline at 12 and 24 months.Results: A total of 37% and 47% of verteporfin-treated patients versus 45% and 53% of placebo recipients lost ≥15 letters of VA at month 12 and month 24, respectively; 16% and 23% of verteporfin-treated patients versus 17% and 25% of placebo recipients lost ≥30 letters at month 12 and month 24, respectively. These differences were not statistically significant. Four (1.6%) verteporfin-treated patients and one placebo patient (who received verteporfin in error) experienced an acute severe VA decrease; all five patients recovered some degree of vision. No unexpected ocular or systemic adverse events were identified.Conclusions: Verteporfin PDT in the treatment of occult with no classic CNV was safe and well-tolerated. The differences between the two groups in the primary efficacy variables were not significant. Baseline characteristics and patient selection methods may have contributed to the small treatment effect.Trial registration: ClinicalTrials.gov identifier: NCT00121407.

Two years' clinical experience with the preferential looking technique for visual acuity determination in infants and young children.

Two years' experience with a preferential looking technique for visual acuity determination was evaluated. Ninety-three patients were tested during this period, but selected groups (34 patients) were reported on earlier. In 59 patients aged 2 months to 13.75 years 131 testing procedures were performed. Diagnostic groups included uncomplicated strabismus (n = 26), strabismus combined with neurological disturbances (n = 16), neurological disturbances alone (n = 11) and other ocular diseases (n = 6). In addition, several of the children were mentally retarded. In 52 of the 59 patients in this study valuable results were obtained, while no useful information could be gathered from the remaining 7 patients. The findings influenced therapy strategies in 24 patients, and subsequent testing reflected therapeutic effectiveness. The test was successful in 7 of 8 patients referred from other clinics for estimation of visual function. Although established acuity thresholds should be regarded as conservative estimates, and not directly comparable to Snellen letter acuity notations, the preferential looking technique proved to be quite valuable in a paediatric ophthalmology unit. Main indications were amblyopia detection, control of therapeutic measures in strabismics, including pre-operative evaluation, and estimation of visual capacity in children with psychomotor retardation.

Retinal nerve fiber thickness in inflammatory demyelinating diseases of childhood onset

Purpose To evaluate retinal nerve fiber layer thickness (RNFLT) using optical coherence tomography (OCT) in children with acquired demyelinating diseases. Methods This is a cross-sectional study of patients seen between 2006–2008 at the Pediatric MS Center of the Jacobs Neurological Institute. Consensus definitions for pediatric demyelinating disease were followed. All children received OCT testing and assessment of visual acuity (VA) using Snellen and low contrast letter acuity (LCLA) charts. Results Thirty-eight children diagnosed with acquired demyelinating disease, 15 healthy controls, and five children with other neurological disorders (OND) were included. Average RNFLT in healthy controls was 107 ± 12 μm(n = 30) versus 108 ± 5 μm (n = 10) in OND controls. In children with multiple sclerosis, average RNFLT ± SD was 99 ± 14 μm in unaffected (n = 24) versus 83 ± 12 μmin eyes affected by optic neuritis (“affected eyes”) (n = 10). Average RNFLT in children with acute disseminated encephalomyelitis and transverse myelitis was 102 ± 15 μm in unaffected (n = 18) versus 67 ± 17 μm in affected eyes (n = 6). In children with optic neuritis (ON), average RNFLT ± SD was 97 ± 13 μm in unaffected (n = 5) versus 89 ± 12 μm in affected eyes (n = 9). Differences between children with demyelinating disease and controls and between ON and nonON eyes were statistically significant (P < 0.001). Bivariate correlations of RNFLT with LCLA (P = 0.002) and VA (P < 0.001) were significant. Conclusions OCT may be a valuable tool for the assessment and monitoring of anterior optic pathway dysfunction in children with demyelinating diseases.

Relationship of optic nerve and brain conventional and non-conventional MRI measures and retinal nerve fiber layer thickness, as assessed by OCT and GDx: A pilot study

Background Measurement of retinal nerve fiber layer (RNFL) thickness in multiple sclerosis (MS) is gaining increasing attention. Objectives To explore the relationship between RNFL thickness as measured by optical coherence tomography (OCT) and scanning laser polarimetry with variable corneal compensation (GDx), and conventional and non-conventional optic nerve and brain MRI measures. Methods Twelve relapsing–remitting (RR) MS patients (12 affected and 12 unaffected eyes) and 4 age- and sex-matched normal controls (NC) (8 unaffected eyes) were enrolled. Four MS patients had a history of bilateral optic neuritis (ON), four had a history of unilateral ON, and 4 had no history of ON. Optic nerve MRI measurements included the length of T2 lesions, measurement of optic nerve atrophy, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) measures. Optic nerve atrophy was measured by a novel method with high reproducibility. Brain MRI measurements included T1 and T2 lesion volumes (LVs) and their relative MTRs, and tissue class specific atrophy, MTR and DTI measures. Measures of RNFL were evaluated with OCT and GDx. We also evaluated both high and low contrast letter acuities (LCLA) in order to determine the relationship between vision, MRI metrics, and retinal structural architecture. Results LCLA, RNFL-OCT and optic nerve radius measures showed more robust differences between NC and MS patients, and between MS patients with affected and unaffected eyes. T2-LV and T1-LV, as well as gray matter atrophy, DTI and MTR measures were related to LCLA and RNFL thickness. Unique additive variance regression models showed that both brain and optic nerve MRI measures independently accounted for about 50% of the variance in LCLA and RNFL thickness. In reverse models, about 20% of the additional independent variance was explained by optic nerve or brain MRI metrics. Conclusions Measurement of RNFL thickness and radius of the optic nerve should be preferred to the other optic nerve MRI measures in clinical studies. Whole brain lesion and GM measures are predictive of impaired visual function with corresponding structural concomitants.

Verteporfin Photodynamic Therapy Combined With Intravitreal Bevacizumab for Neovascular Age-Related Macular Degeneration

To assess outcomes for patients with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) treated with verteporfin photodynamic therapy (PDT) and bevacizumab. Retrospective, case series database study (registry). We included 1196 patients with CNV due to AMD who received > or =1 combination treatment of 1.25 mg intravitreal bevacizumab within 14 days of verteporfin PDT. Retrospective analysis of baseline data with ongoing follow-up. Physicians from 45 clinical centers entered patient data at baseline and follow-up examinations, including subsequent treatments, into a secure, Web-accessed database. Snellen visual acuity (VA) was converted to logarithm of the minimum angle of resolution (logMAR) for statistical analyses. Change from baseline in VA and retreatment rates of any therapy after the initial combination treatment. Of 1196 patients, 1073 patients had > or =6 months of follow-up. For these 1073 patients, mean baseline VA was 0.967 logMAR (approximate Snellen 20/185) and 56.3% of patients (604/1073) were treatment naïve. After their baseline combination treatment, patients received a mean of 0.6 additional verteporfin PDT retreatments and 2.0 bevacizumab retreatments over a mean follow-up period of 15.0 months. By 12 months, 82% of patients (578/701) had stable or improved vision (loss of <3 lines or a gain in VA), 36% (255/701) improved by > or =3 lines, and 17% (121/701) improved by > or =6 lines. By 12 months, patients gained approximately 1.2 lines (6 letters) of VA from baseline. Patients who were treatment naïve gained significantly more VA by month 12 (+8.4 letters) compared with those who had been previously treated (+2.4 letters; P<0.01). Most serious adverse events (26/30) were judged by investigators as not related to any study treatment, although 3 ocular events were judged related to bevacizumab alone, and 1 ocular event was judged related to both bevacizumab and PDT. Combination therapy with PDT and bevacizumab led to vision benefit for most patients, particularly those who were treatment naïve at baseline. The number of retreatments was lower than published reports with either treatment delivered as monotherapy. Randomized clinical trials are underway to confirm these findings.

Vision related quality of life in multiple sclerosis: correlation with new measures of low and high contrast letter acuity

Objective:To examine the relation between low contrast letter acuity, a new visual function test for multiple sclerosis (MS) trials, and vision targeted health related quality of life (HRQOL).Methods:Patients in this...

Factors Affecting Development of Motor Skills in Extremely Low Birth Weight Children

Purpose: The aim of this study is to analyze the impact of ophthalmic and neonatal factors on motor development in extremely low birth weight (ELBW) children. Methods: Sixty-four ELBW children at least 3 years of age were recruited. Visual acuity (VA) was assessed using the Teller acuity cards (TACs) and a letter test, if possible. A validated questionnaire assessing 25 fine (part A) and 20 gross motor (part B) skills was administered to the parents. Data were collected on retinopathy of prematurity (ROP) zone, intraventricular haemorrhage (IVH), length of stay in hospital, and number of days on oxygen. Results: Abnormal TAC acuity was associated with significantly lower scores on both parts A and B (part A: 21.5 versus 11.8, p < 0.001; part B: 17.5 versus 13.2, p < 0.001). Linear regression demonstrates a significant direct relationship between letter acuity and score A only (p = 0.03, r2 = 0.179). Neither length of hospital stay, number of days ventilated, nor a history of IVH were associated with score A or B. However, the presence of ROP zone 1 was associated with a lower score A (p = 0.03). Conclusion: In this ELBW cohort VA and ophthalmic factors were the only factors associated with scores of development, particularly fine motor development.

Retinal architecture predicts pupillary reflex metrics in MS

Objective To study the relation of retinal nerve fiber layer thinning to clinical and physiologic measures of visual function in patients with MS or neuromyelitis optica and unilateral optic neuropathy. Methods We studied a cohort of control subjects (n = 64) and patients (n = 24) with evidence of unilateral thinning of their average retinal nerve fiber layer as measured by optical coherence tomography in order to characterize the relationship between ganglion cell axonal degeneration and its impact upon vision and pupillary light reflex metrics using infrared pupillometry. Results When compared to the normal fellow eye, and with respect to normal subjects’ eyes, we confirmed significant abnormalities in retinal nerve fiber layer thickness, total macular volume, low-contrast letter acuity, and pupillary reflex metrics in the eye with the thinner retinal nerve fiber layer. For each −5% change in pupil diameter, there was a corresponding 7.1 µm reduction in the average retinal nerve fiber layer thickness. There was a significant difference between the pupillary metric of percent change in diameter and a decrease in low-contrast letter acuity (P < 0.001). Each −5% change in pupil diameter was associated with a substantial 3.4 line loss of low-contrast letter acuity (P < 0.001). Each −5% change in pupil diameter was associated with a 0.2 mm2 decrease in total macular volume (P < 0.001). Conclusion These findings further corroborate the hypothesis that the retina can be utilized as a model to advance our understanding of the mechanisms of axonal and neurodegeneration, and the corresponding impact of these processes upon the pathophysiology of MS and related disorders.

Thresholds for Sampled Sloan Letters Are Smaller Than Sample Spacing

Although the effect of spatial sampling on the visibility of grating stimuli is well described and well understood, little research has been conducted into the effects of spatial sampling on the visibility of letter optotypes. The purpose of this study was to investigate whether thresholds for spatially sampled Sloan letters were equal to or significantly smaller than the spacing between spatial samples. For four visually normal subjects, we measured Sloan letter acuity thresholds, presented on a computer monitor, after the letters had been sampled by sampling arrays with 6.285 elements per square degree, (23.9 min of arc between samples for a square packed array). We used four different sampling arrays: square packed; hexagonally packed; a cone-like array with positive contrast; and a cone-like array with negative contrast. Thresholds were assessed using letter-counting rules and also Probit analysis. Although results depended on array type, and the definition of sample spacing, letter acuity thresholds were substantially less than estimates of sample spacing by between 0.290 log units (49% less) (hexagonally sampled Probit thresholds compared with spacing between hexagonal samples) to 0.136 log units (27% less) (positive contrast cone-like sampled letter-counting thresholds compared with spacing between rows of hexagonal samples). Sample spacing is not an absolute limit for Sloan letter thresholds. By comparison with previous measurements of human foveal cone sampling of space, our findings suggest that cone sampling limits for Sloan letters could be as small as 20/4.

Retinal Imaging by Laser Polarimetry and Optical Coherence Tomography Evidence of Axonal Degeneration in Multiple Sclerosis

Optical coherence tomography (OCT) and scanning laser polarimetry with variable corneal compensation (GDx) are similar yet provide information on different aspects of retinal nerve fiber layer (RNFL) structure (thickness values similar to histology for OCT vs birefringence of microtubules for GDx). To compare the ability of OCT and GDx to distinguish eyes of patients with multiple sclerosis (MS) from eyes of disease-free controls and thus identify RNFL abnormalities. We also sought to examine the capacity of these techniques to distinguish MS eyes from those without a history of optic neuritis and to correlate with visual function. Cross-sectional study. Academic tertiary care MS center. Eighty patients with MS (155 eyes) and 43 disease-free controls (85 eyes) underwent both OCT and GDx imaging using protocols that measure RNFL thickness. Areas under the curve (AUC), adjusted for within-patient, intereye correlations, were used to compare the abilities of OCT and GDx temporal-superior-nasal-inferior-temporal average RNFL thicknesses to discriminate between MS and control eyes and to distinguish MS eyes with a history of optic neuritis. Visual function was evaluated using low-contrast letter acuity and high-contrast visual acuity. Average peripapillary RNFL thickness (360 degrees around the optic disc) was reduced in patients with MS compared with controls for both methods. Age-adjusted AUC did not differ between OCT (0.80; 95% confidence interval [CI], 0.72-0.88) and GDx (0.78; 95% CI, 0.68-0.86; P = .38). Optical coherence tomography-measured RNFL thickness was somewhat better at distinguishing MS eyes with a history of optic neuritis from those without (OCT: AUC, 0.73; 95% CI, 0.64-0.82; GDx: AUC, 0.66; 95% CI, 0.57-0.66; P = .17). Linear correlations of RNFL thickness for OCT vs GDx were significant yet moderate (r = 0.67, P < .001); RNFL thickness measures correlated moderately and significantly with low-contrast acuity (OCT: r = 0.54, P < .001; GDx: r = 0.55, P < .001) and correlated less with high-contrast visual acuity (OCT: r = 0.44, P < .001; GDx: r = 0.32, P < .001). Scanning laser polarimetry with variable corneal compensation measurements of RNFL thickness corroborates OCT evidence of visual pathway axonal loss in MS and provides new insight into structural aspects of axonal loss that relate to RNFL birefringence (microtubule integrity). These results support validity for RNFL thickness as a marker for axonal degeneration and support use of these techniques in clinical trials that examine neuroprotective and other disease-modifying therapies.