Predicting visual outcomes in patients treated with aflibercept for neovascular age-related macular degeneration: Data from a real-world clinical setting.

BACKGROUND/OBJECTIVES: There is a significant variation in the way neovascular age-related macular degeneration patients respond to anti-vascular endothelial growth factor treatment. Both the financial and time cost of treatment are significant. As such, being able to predict patient response to treatment is valuable. SUBJECTS/METHODS: 72 eyes treated with intravitreal aflibercept were retrospectively included in analysis. For each subject, visual acuity (letters) and central retinal thickness (µm) at baseline, second, third and fourth visits, as well as 12-month visits, were collated; a plot of visual acuity versus time was generated and a slope of the first three (slope3) and first four (slope4) visits was calculated. Differences in visual acuity at each visit compared to baseline were determined, as well as percentage differences in central retinal thickness at each visit compared to baseline. Lesion sub-type and the presence of fluid and haemorrhage were also recorded. RESULTS: The average change in visual acuity over 12 months was +3.2 ± 13.4 letters with 91.2% of patients losing <15 letters. Slope4 was the only significant predictive factor for 'visual acuity change over 12 months' (p < 0.001). Change in central retinal thickness, lesion sub-type, haemorrhage at baseline and the location of fluid at baseline were not useful predictive factors in long-term outcome. CONCLUSION: Aflibercept is an effective treatment option for neovascular age-related macular degeneration; however, the long-term response should not be predicted until at least three loading dose injections have been given. Visual acuity measures at each visit should be examined, as it is the trend in visual acuity across the first four visits (slope4) rather than the difference in visual acuity between two visits that is the predictive factor.

Prehension of a Flanked Target in Individuals With Amblyopia.

PURPOSE: Reduced binocularity is a prominent feature of amblyopia and binocular cues are thought to be important for prehension. We examine prehension in individuals with amblyopia when the target-object was flanked, thus mimicking everyday prehension. METHODS: Amblyopes (n = 20, 36.4 ± 11.7 years; 6 anisometropic, 3 strabismic, 11 mixed) and visually-healthy controls (n = 20, 27.5 ± 6.3 years) reached forward, grasped, and lifted a cylindrical target-object that was flanked with objects either (lateral) side of the target, or in front and behind it in depth. Only six amblyopes (30%) had measurable stereoacuity. Trials were completed in binocular and monocular viewing, using the better eye in amblyopic participants. RESULTS: Compared with visual normals, amblyopes displayed a longer overall movement time (P = 0.031), lower average reach velocity (P = 0.021), smaller maximum aperture (P = 0.007), and a longer duration between object contact and lift (P = 0.003). Differences between groups were more apparent when the flankers were in front and behind, compared with either side, as evidenced by significant group-by-flanker configuration interactions for reach duration (P < 0.001), size and timing of maximum aperture (P ≤ 0.009), end-of-reach to object-contact (P < 0.001), and object-contact to lift (P = 0.044), suggesting that amblyopic deficits are greatest when binocular cues are richest. Both groups demonstrated a significant binocular advantage, in that in both groups performance was worse for monocular compared with binocular viewing, but interestingly, amblyopic deficits in binocular viewing largely persisted during monocular viewing with the better eye. CONCLUSIONS: These results suggest that amblyopes either display considerable residual binocularity or that they have adapted to make good use of their abnormal binocularity.

Binocular summation and other forms of non-dominant eye contribution in individuals with strabismic amblyopia during habitual viewing.

BACKGROUND: Adults with amblyopia ('lazy eye'), long-standing strabismus (ocular misalignment) or both typically do not experience visual symptoms because the signal from weaker eye is given less weight than the signal from its fellow. Here we examine the contribution of the weaker eye of individuals with strabismus and amblyopia with both eyes open and with the deviating eye in its anomalous motor position. METHODOLOGY/RESULTS: The task consisted of a blue-on-yellow detection task along a horizontal line across the central 50 degrees of the visual field. We compare the results obtained in ten individuals with strabismic amblyopia with ten visual normals. At each field location in each participant, we examined how the sensitivity exhibited under binocular conditions compared with sensitivity from four predictions, (i) a model of binocular summation, (ii) the average of the monocular sensitivities, (iii) dominant-eye sensitivity or (iv) non-dominant-eye sensitivity. The proportion of field locations for which the binocular summation model provided the best description of binocular sensitivity was similar in normals (50.6%) and amblyopes (48.2%). Average monocular sensitivity matched binocular sensitivity in 14.1% of amblyopes' field locations compared to 8.8% of normals'. Dominant-eye sensitivity explained sensitivity at 27.1% of field locations in amblyopes but 21.2% in normals. Non-dominant-eye sensitivity explained sensitivity at 10.6% of field locations in amblyopes but 19.4% in normals. Binocular summation provided the best description of the sensitivity profile in 6/10 amblyopes compared to 7/10 of normals. In three amblyopes, dominant-eye sensitivity most closely reflected binocular sensitivity (compared to two normals) and in the remaining amblyope, binocular sensitivity approximated to an average of the monocular sensitivities. CONCLUSIONS: Our results suggest a strong positive contribution in habitual viewing from the non-dominant eye in strabismic amblyopes. This is consistent with evidence from other sources that binocular mechanisms are frequently intact in strabismic and amblyopic individuals.

Off-axis partial coherence interferometry in myopes and emmetropes.

PURPOSE: This study describes the axial and peripheral dimensions of myopic and emmetropic eyes in a wide range of retinal locations using a non-contact optical biometer (Zeiss IOLMaster) based upon the principle of partial coherence interferometry. Understanding the optical properties of the peripheral eye may provide insight into myopia development and the possible effects on off-axis visual performance. METHODS: Fifty-two myopes (spherical equivalent between -2.00 and -9.62 D) and 27 emmetropes (spherical equivalent between -0.50 and +0.50 D) with astigmatism less than 0.75 D, participated in this study. Axial length and peripheral cornea to retina lengths were measured using partial coherence interferometry at the fovea and up to ± 30° eccentricity along the horizontal and vertical meridian in 10° steps. Relative cornea to retina length was calculated by subtracting the axial length from that obtained at each peripheral location. RESULTS: Our results showed significant differences between refractive groups for both horizontal (p < 0.001) and vertical (p < 0.001) meridians, illustrating that the retinal shape profile is significantly different between myopes and emmetropes. Myopic eyes exhibited a greater rate of change in cornea to retina lengths with increasing eccentricity than emmetropic eyes, with the temporal portion of the retina exhibiting the steepest shift. In addition, significant nasal-temporal asymmetry was observed, which was more pronounced in myopic eyes. CONCLUSIONS: Axial and peripheral cornea to retina dimension measurements, using partial coherence interferometry, suggest that myopic eyes tend toward an ellipsoid shape compared to the spherical emmetropic eyes.

Bilateral changes in foveal structure in individuals with amblyopia.

PURPOSE: To examine foveal structure in amblyopia using spectral-domain optical coherence tomography (SD-OCT). DESIGN: Prospective, cross-sectional study. PARTICIPANTS AND CONTROLS: Two subject groups were recruited to the study: 85 amblyopes (34 adults, 51 children) and 110 visually normal controls (44 adults, 66 children). METHODS: A detailed eye examination, including an SD-OCT scan, was performed in all participants. A total of 390 eyes of 195 subjects were imaged using a 3-dimensional (3D) macula scan covering a nominal 6 × 6-mm area with a resolution of 256 × 256 (65,536 axial scans). Data from the B-scans bisecting the fovea both horizontally and vertically were fitted with a mathematical model of the fovea to determine a range of foveal parameters. MAIN OUTCOME MEASURES: Foveal thickness, foveal pit depth, and foveal pit slope. RESULTS: Bilateral differences between the eyes of amblyopes compared with visually normal controls were found. The difference between foveal structure in amblyopic participants relative to structure in subjects with normal vision persisted even when variables such as age, ethnicity, axial length, and sex were taken into account. Amblyopes showed increased foveal thickness (+8.31 µm; P = 0.006) and a reduction in pit depth in the horizontal meridian (-10.06 µm; P = 0.005) but not in the vertical meridian (P = 0.082) when compared with subjects with normal vision. Foveal pit slopes were found to be approximately 1 degree flatter in the nasal (P = 0.033) and temporal (P = 0.014) meridians in amblyopes, but differences between amblyopes and controls in the superior (P = 0.061) and inferior (P = 0.087) meridians did not reach statistical significance. No statistically significant interocular differences were found in the foveal structure between amblyopic and fellow eyes. CONCLUSIONS: Differences were found in the foveal structure in both eyes of amblyopes compared with subjects with normal vision. These differences consisted of increased foveal thickness, reduced pit depth when measured along the horizontal meridian, and flattening of the nasal and temporal sides of the foveal pit.

A limited role for suppression in the central field of individuals with strabismic amblyopia.

BACKGROUND: Although their eyes are pointing in different directions, people with long-standing strabismic amblyopia typically do not experience double-vision or indeed any visual symptoms arising from their condition. It is generally believed that the phenomenon of suppression plays a major role in dealing with the consequences of amblyopia and strabismus, by preventing images from the weaker/deviating eye from reaching conscious awareness. Suppression is thus a highly sophisticated coping mechanism. Although suppression has been studied for over 100 years the literature is equivocal in relation to the extent of the retina that is suppressed, though the method used to investigate suppression is crucial to the outcome. There is growing evidence that some measurement methods lead to artefactual claims that suppression exists when it does not. METHODOLOGY/RESULTS: Here we present the results of an experiment conducted with a new method to examine the prevalence, depth and extent of suppression in ten individuals with strabismic amblyopia. Seven subjects (70%) showed no evidence whatsoever for suppression and in the three individuals who did (30%), the depth and extent of suppression was small. CONCLUSIONS: Suppression may play a much smaller role in dealing with the negative consequences of strabismic amblyopia than previously thought. Whereas recent claims of this nature have been made only in those with micro-strabismus our results show extremely limited evidence for suppression across the central visual field in strabismic amblyopes more generally. Instead of suppressing the image from the weaker/deviating eye, we suggest the visual system of individuals with strabismic amblyopia may act to maximise the possibilities for binocular co-operation. This is consistent with recent evidence from strabismic and amblyopic individuals that their binocular mechanisms are intact, and that, just as in visual normals, performance with two eyes is better than with the better eye alone in these individuals.

Cross-sectional sample of peripheral refraction in four meridians in myopes and emmetropes.

PURPOSE: The study of peripheral refractive error is of growing interest as degradation of the retinal image quality in the periphery is known to affect central refractive error development and ocular shape in animal models. The purpose of this study was to measure peripheral refraction across the horizontal, vertical, and two oblique meridians in a group of myopic and emmetropic adults and to investigate retinal asymmetry in the human retina. METHODS: Thirty-one myopes (spherical equivalent between -2.00 and -9.62 D) and 20 emmetropes (spherical equivalent between -0.50 and +0.50 D) with astigmatism less than -0.75 D, participated in the project. Noncycloplegic peripheral refraction measurements were captured with an autorefractor (NVision K-5001; Shin-Nippon, Tokyo, Japan) at the fovea and up to 30° eccentricity in the horizontal, vertical, and two oblique meridians in 10° steps. RPR was calculated by subtracting the foveal spherical equivalent refraction from that obtained at each eccentric location. RESULTS: Along all measured meridians, myopic eyes showed a relative hyperopic shift in the periphery, with the superior-temporal portion of the retina exhibiting the smallest shift. Emmetropic eyes, however, exhibited a relatively consistent refractive profile across all meridians and eccentricities, confirming a spherical retinal shape for this group. In addition, off-axis astigmatism increased with eccentricity in all meridians. CONCLUSIONS: These results suggest that the myopic eye tends toward an ellipsoid shape, rather than the globular shape of an emmetropic eye.

The effect of instrument alignment on peripheral refraction measurements by automated optometer.

PURPOSE: Interest in peripheral refraction measurement has grown in recent years in response to the insight it may provide into myopia development. In light of the likely increase in the clinical use of open-field autorefractors for peripheral refraction measurements, the question of instrument alignment and its impact on the accuracy of refraction measurements is raised. The aim of this study was to investigate the accuracy and precision when an open-field device was moved away from alignment with the corneal reflex towards the pupil margins, and to determine the optimum alignment position for peripheral refraction measurements. METHODS: Autorefractions were performed on the right eyes of 10 healthy participants using the Shin-Nippon NVision-K 5001 autorefractor. At least five measurements were taken with the subject fixating a distance target in the primary position of gaze, and then four peripheral fixation targets located along the horizontal meridian (10° and 20° eccentricities in the nasal and temporal retina). Measurements were taken at seven alignment positions across the pupil for each fixation angle. Refraction was recorded as the spherical and cylindrical power. RESULTS: The central objective refraction achieved under cycloplegia based on the autorefraction result for the whole sample, ranged between -5.62 D and +1.85 D for the value of sphere, with a maximum astigmatism of -1.00 D. Acceptable alignment position range varied with fixation angle but was -1.0 to +1.0 mm in width across the pupil. Peripheral refraction measurements centred on the entrance pupil were as reliable as those centred on the corneal reflex. CONCLUSIONS: Our data suggest that for peripheral refraction measurements, there is a range of acceptable positions and operators can be confident of the validity of results obtained if aligned half way between the pupil centre and corneal reflex. The alignment becomes more critical at greater eccentricities.

Central and peripheral visual performance in myopes: contact lenses versus spectacles.

PURPOSE: Myopia is known to degrade visual performance with both optical and retinal changes implicated. Whether contact lenses or spectacles provide better visual performance for myopes is still under debate. The purpose of this study was to examine central and peripheral visual function in myopic subjects corrected with contact lenses versus spectacles. METHODS: Size thresholds were measured at 13 locations for 20 myopic subjects (mean spherical equivalent refractive error (SE): -6.43±1.22 D and cylinder power: -0.23±0.22 D) corrected with contact lenses (new etafilcon A contact lens, fitted 15 min prior to measurements) versus spectacles. Measurements were taken at both low (δl/l=14%) and high (δl/l=100%) contrast levels. The data were analysed using one way repeated-measures ANOVA. RESULTS: Size thresholds increased with eccentricity in a similar manner for both forms of optical correction. Repeated-measures ANOVA showed no statistically significant difference in central and peripheral visual performance between the two forms of correction for both low and high contrast tasks. The outcome remained the same following correction for spectacle magnification. CONCLUSION: Eye care practitioners can be confident that modern soft contact lenses do not impair visual performance compared to spectacle lenses for the majority of myopes.

Changes to control of adaptive gait in individuals with long-standing reduced stereoacuity.

PURPOSE: Gait during obstacle negotiation is adapted in visually normal subjects whose vision is temporarily and unilaterally blurred or occluded. This study was conducted to examine whether gait parameters in individuals with long-standing deficient stereopsis are similarly adapted. METHODS: Twelve visually normal subjects and 16 individuals with deficient stereopsis due to amblyopia and/or its associated conditions negotiated floor-based obstacles of different heights (7-22 cm). Trials were conducted during binocular viewing and monocular occlusion. Analyses focused on foot placement before the obstacle and toe clearance over it. RESULTS: Across all viewing conditions, there were significant group-by-obstacle height interactions for toe clearance (P < 0.001), walking velocity (P = 0.003), and penultimate step length (P = 0.022). Toe clearance decreased (approximately 0.7 cm) with increasing obstacle height in visually normal subjects, but it increased (approximately 1.5 cm) with increasing obstacle height in the stereo-deficient group. Walking velocity and penultimate step length decreased with increasing obstacle height in both groups, but the reduction was more pronounced in stereo-deficient individuals. Post hoc analyses indicated group differences in toe clearance and penultimate step length when negotiating the highest obstacle (P < 0.05). CONCLUSIONS: Occlusion of either eye caused significant and similar gait changes in both groups, suggesting that in stereo-deficient individuals, as in visually normal subjects, both eyes contribute usefully to the execution of adaptive gait. Under monocular and binocular viewing, obstacle-crossing performance in stereo-deficient individuals was more cautious when compared with that of visually normal subjects, but this difference became evident only when the subjects were negotiating higher obstacles; suggesting that such individuals may be at greater risk of tripping or falling during everyday locomotion.

Repeatability and reproducibility of macular thickness measurements using fourier domain optical coherence tomography.

AIM: To evaluate repeatability and reproducibility of macular thickness measurements in visually normal eyes using the Topcon 3D OCT-1000. METHODS: Phase 1 investigated scan repeatability, the effect of age and pupil dilation. Two groups (6 younger and 6 older participants) had one eye scanned 5 times pre and post- dilation by 1 operator. Phase 2 investigated between-operator, within and between-visit reproducibility. 10 participants had 1 un-dilated eye scanned 3 times on 2 separate visits by 2 operators. RESULTS: PHASE 1: No significant difference existed between repeat scans (p=0.75) and no significant difference was found pre- and post-dilation (p=0.54). In the younger group variation was low (95% limits +/- 3.62microm) and comparable across all retinal regions. The older group demonstrated greater variation (95% limits +/- 7.6microm). PHASE 2: For a given retinal location, 95% confidence limits for within-operator, within-visit reproducibility was 5.16microm. This value increased to 5.56microm for the same operator over two visits and to 6.18microm for two operators over two visits. CONCLUSION: A high level repeatability, close to 6microm, of macular thickness measurement is possible using the 3D OCT- 1000. Measured differences in macular thickness between successive visits that exceed 6microm in pre-presbyopic individuals are therefore likely to reflect actual structural change. OCT measures are more variable in older individuals and it is advisable to take a series of scans so that outliers can be more easily identified.

Evidence for a learning effect in short-wavelength automated perimetry.

PURPOSE: To document the magnitude of any learning effect for short-wavelength automated perimetry (SWAP) in patients with either ocular hypertension (OHT) or open-angle glaucoma (OAG) who are experienced in standard automated perimetry (SAP). DESIGN: Experimental study. PARTICIPANTS: Thirty-five patients (22 with OHT and 13 with OAG) who had previously undergone at least 3 threshold SAP visual field examinations with the Humphrey Field Analyzer (HFA; Carl Zeiss Meditech Inc., Dublin, CA), and 9 patients with OHT who had not previously undertaken any form of perimetry. METHODS: Each patient attended for SWAP on 5 occasions, each separated by 1 week. At each visit, both eyes were examined using Program 24-2 of the HFA; the right eye was always examined before the left eye. MAIN OUTCOME MEASURES: (1) Change over the 5 examinations, in each eye, of the visual field indices Mean Deviation (MD), Short-term Fluctuation (SF), Pattern Standard Deviation (PSD), and Corrected Pattern Standard Deviation. (2) Change in each eye between Visits 1 and 5 in proportionate Mean Sensitivity (pMS) for the central annulus of stimulus locations compared with that for the peripheral annulus thereby determining the influence of stimulus eccentricity on any alteration in sensitivity. (3) Change between Visits 1 and 5 in the number and magnitude of the Pattern Deviation (PD) probability levels associated with any alteration in sensitivity. RESULTS: The MD, SF, and PSD each improved over the 5 examinations (each at P<0.001). The improvement in pMS between Visits 1 and 5 was greater for the peripheral annulus than for the central annulus by approximately twofold for the patients with OAG. Considerable variation was present between patients, within and between groups, in the number of locations exhibiting an improving sensitivity between Visits 1 and 5 by 1 or more PD probability levels. CONCLUSIONS: Care should be taken to ensure that, during the initial examinations, apparent field loss with SWAP in patients exhibiting a normal field by SAP is not the result of inexperience in SWAP. Apparently deeper or wider field loss in the initial examinations with SWAP compared with that exhibited by SAP in OAG also may arise from inexperience in SWAP.

A comparison of the effects of ageing upon vernier and bisection acuity.

While most positional acuity tasks exhibit an age-related decline in performance, the effect of ageing upon vernier acuity continues to be the subject of some debate. In the present study we employed a stimulus design that enabled the simultaneous determination of bisection and vernier acuities in 36 subjects, aged between 22 and 84 years. This approach provided a means for directly testing the hypothesis that ageing affects bisection acuity but not vernier acuity by ensuring that differences in stimulus configuration and in the subject's task were kept to an absolute minimum. Optimum thresholds increased as a function of age for both bisection and vernier tasks. Inter-subject threshold variability also increased with age. Issues surrounding the comparison of absolute vernier thresholds across different studies are discussed and two important methodological factors are identified: the precise statistical method used to estimate thresholds, and the magnitude, in angular terms, of the smallest spatial offset of the elements of the vernier stimulus which can be displayed. Comparison with previously published data indicates that the discrepancy between this study and most previous investigations with respect to the effect of age upon vernier performance can be at least partly accounted for by differences in the minimum displayable vernier offset. Vernier thresholds do increase with age. The increased variability of vernier thresholds in older subjects would appear to limit the diagnostic value of the test as a means of enabling normal ageing to be distinguished from visual loss due to pathology of the eye or visual system.

Nonveridical visual perception in human amblyopia.

PURPOSE: Amblyopia is a developmental disorder of spatial vision. There is evidence to suggest that some amblyopes misperceive spatial structure when viewing with the affected eye. However, there are few examples of these perceptual errors in the literature. This study was an investigation of the prevalence and nature of misperceptions in human amblyopia. METHODS: Thirty amblyopes with strabismus and/or anisometropia participated in the study. Subjects viewed sinusoidal gratings of various spatial frequencies, orientations, and contrasts. After interocular comparison, subjects sketched the subjective appearance of those stimuli that had nonveridical appearances. RESULTS: Nonveridical visual perception was revealed in 20 amblyopes ( approximately 67%). In some subjects, misperceptions were present despite the absence of a deficit in contrast sensitivity. The presence of distortions was not simply linked to the depth of amblyopia, and anisometropes were affected as well as those with strabismus. In most cases, these spatial distortions arose at spatial frequencies far below the contrast detection acuity cutoff. Errors in perception became more severe at higher spatial frequencies, with low spatial frequencies being mostly perceived veridically. The prevalence and severity of misperceptions were frequently found to depend on the orientation of the grating used in the test, with horizontal orientations typically less affected than other orientations. Contrast had a much smaller effect on misperceptions, although there were cases in which severity was greater at higher contrasts. CONCLUSIONS: Many types of misperceptions documented in the present study have appeared in previous investigations. This suggests that the wide range of distortions previously reported reflect genuine intersubject differences. It is proposed that nonveridical perception in human amblyopia has its origins in errors in the neural coding of orientation in primary visual cortex.