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.

Static accommodative responses following adaptation to differential levels of blur.

PURPOSE: To investigate the effects of two levels of blur adaptation on visual resolution and steady-state accommodation responses in emmetropes and myopes. METHODS: Eleven emmetropes (mean refractive error +0.01 +/- 0.31 DS) and 11 early-onset myopes (EOM, mean refractive error -4.44 +/- 1.64 DS) fixated monocularly at 4 m in three trials of 45 min duration with either: optimal refractive correction, +1 DS defocus, or +3 DS defocus. Monocular logMAR visual acuity (VA) was measured at 10 min intervals during each trial, and immediately following completion of the trial. Accommodative stimulus-response function (ASRF), refractive error and pupil size were measured before and after each trial. RESULTS: Blur adaptation was found to have no effect on pupil size or baseline refraction, irrespective of the power of the blurring lens. Adaptation to +1 DS of defocus yielded an improvement in VA of -0.16 +/- 0.07 logMAR and -0.17 +/- 0.11 logMAR in the emmetropes and myopes respectively. An improvement in VA of -0.20 +/- 0.18 logMAR in the emmetropes and -0.26 +/- 0.17 logMAR in the myopes was observed following adaptation to +3 DS of defocus. The changes in acuity became significant following 30 min of exposure to defocus. Blur adaptation was found to have no effect on the ASRF gradient or individual steady-state accommodative responses. CONCLUSIONS: Following blur adaptation, visual resolution was found to increase in both emmetropes and myopes. The magnitude of the blur level did not produce significantly different increases in resolution. Blur adaptation failed to affect either the steady-state responses to an accommodative stimulus or ASRF gradient.

Open- and closed-loop regressions compared in myopic and emmetropic subjects.

Post-near task accommodation regressions have been measured in a number of studies to investigate the association between myopia and nearwork. The slow nature of the regression found when measuring both open- and closed-loop regressions in some subjects has been hypothesised to be associated with myopia development and progression. However, it is not known whether the speed and characteristics of the regression for an individual is the same under open- and closed-loop conditions. In this study we measured post-near task accommodation regression functions under open- and closed-loop conditions for myopic and emmetropic subjects. We compared the responses of each subject under the two conditions and found that some subjects responded differently depending on the condition (i.e. a fast regression under one condition and a slow regression under the other condition). When compared as a group, the myopic subjects showed significantly more prolonged open-loop regressions than closed-loop regressions. In terms of the effect on the post-task accommodation, the myopes appear to be more affected by the measurement conditions than the emmetropes in this study. The results highlight the importance of the type of accommodation stimulus when investigating the accommodation response.

Wavefront aberration and its relationship to the accommodative stimulus-response function in myopic subjects.

BACKGROUND: Autorefractors are increasingly used in myopia research because they are convenient tools to investigate aspects of the accommodation response. The degree to which the autorefractor measures are affected by ocular aberrations has been highlighted by studies that have shown changes in aberration levels through different parts of the pupil and with accommodation. We have compared accommodative accuracy as measured with a Shin-Nippon SRW 5000 autorefractor with wavefront error as measured with a Hartmann-Shack wavefront sensor to investigate how factors such as accommodation demand, ocular aberrations, and pupil size can influence autorefractor measures. METHODS: Accommodation stimulus-response curves were determined (using negative lenses) for 30 young healthy subjects (20 myopic [-0.75 to -6.00 D] and 10 emmetropic). Accommodation levels ranged from 0 to 4 D in 1 D steps. Wavefront aberrations were also determined for the same accommodation levels using a Hartmann-Shack wavefront sensor for both the subjects' natural pupil sizes and for a 2.9-mm pupil. RESULTS: For all subjects, there was a consistent increase in negative spherical aberration with increases in accommodative stimulus. However, there was no consistent change in paraxial spherocylindrical refractive correction with accommodation stimulus. For the emmetropic subjects, accommodation error as measured with the autorefractor was statistically similar to the total spherocylindrical correction for the eye as estimated by the Hartmann-Shack wavefront sensor, but only for a 2.9-mm pupil (the pupil size utilized by the autorefractor). For the myopic subjects, accommodation error as measured with the autorefractor was statistically similar to the higher-order aberrations, but only when measured for a natural pupil size. CONCLUSIONS: The relationship between the accommodation accuracy as measured with the autorefractor and the total wavefront aberration as measured with a Hartmann-Shack wavefront sensor is largely influenced by the higher-order (fourth and above) aberration levels. For the emmetropic subjects, the errors measured by the two methods agree when adjusted to measure at similar pupil sizes. For the myopic subjects with similar pupil sizes, however, the Hartmann-Shack wavefront sensor underestimates the accommodation error at higher accommodation levels (2 to 4 D) compared with the autorefractor.

The dependency of logMAR visual acuity measurements on chart design and scoring rule.

BACKGROUND: Visual acuity, increasingly measured using a logarithm of the minimum angle of resolution (logMAR) chart, is the "gold standard" by which the outcomes of the vast majority of clinical trials or interventions are judged. To allow comparison of results across studies, it is important that different charts provide equivalent results. METHODS: In a first experiment, we compared corrected visual acuity measurements from four different logMAR charts (Bailey-Lovie, ETDRS, Regan, and Waterloo). In a second experiment we compared unaided visual acuity scored using a psychometric function with the more clinical by-letter scoring. RESULTS: Experiment 1 showed significantly better visual acuity using the Regan chart compared with the other three charts, and further investigation suggested that this could be due to the font type used. Repeatability data from experiment 2 indicated that no extra repeatability was gained when using psychometric methods compared with the far simpler and quicker by-letter scoring. CONCLUSIONS: When comparing findings between studies, the type of chart and the scoring method used may have a significant effect on the results obtained and should therefore be taken into consideration. Also, the additional time and effort demanded for determining a psychometric function for single readings of the Regan visual acuity chart is not rewarded with improved repeatability.