Retinal function beyond foveal vision is not routinely examined in the clinical screening and management of diabetic retinopathy although growing evidence suggests it may precede structural changes. ...In this study we compare optical coherence tomography (OCT) based macular structure with function measured objectively with the ObjectiveFIELD Analyzer (OFA), and with Matrix perimetry. We did that longitudinally in Type 2 diabetes (T2D) patients with mild Diabetic Macular Oedema (DMO) with good vision and a similar number of T2D patients without DMO, to evaluate changes in retinal function more peripherally over the natural course of retinopathy.
Both eyes of 16 T2D patients (65.0 ± 10.1, 10 females), 10 with baseline DMO, were followed for up longitudinally for 27 months providing 94 data sets. Vasculopathy was assessed by fundus photography. Retinopathy was graded using to Early Treatment of Diabetic Retinopathy Study (ETDRS) guidelines. Posterior-pole OCT quantified a 64-region/eye thickness grid. Retinal function was measured with 10-2 Matrix perimetry, and the FDA-cleared OFA. Two multifocal pupillographic objective perimetry (mfPOP) variants presented 44 stimuli/eye within either the central 30° or 60° of the visual field, providing sensitivities and delays for each test-region. OCT, Matrix and 30° OFA data were mapped to a common 44 region/eye grid allowing change over time to be compared at the same retinal regions.
In eyes that presented with DMO at baseline, mean retinal thickness reduced from 237 ± 25 μm to 234.2 ± 26.7 μm, while the initially non-DMO eyes significantly increased their mean thickness from 250.7 ± 24.4 μm to 255.7 ± 20.6 μm (both p<0.05). Eyes that reduced in retinal thickness over time recovered to more normal OFA sensitivities and delays (all p<0.021). Matrix perimetry quantified fewer regions that changed significantly over the 27 months, mostly presenting in the central 8 degrees.
Changes in retinal function measured by OFA possibly offer greater power to monitor DMO over time than Matrix perimetry data.
Previous studies and community information about everyday difficulties in age-related macular degeneration (AMD) have focussed on domains such as reading and driving. Here, we provide the first ...in-depth examination of how impaired face perception impacts social interactions and quality of life in AMD. We also develop a Faces and Social Life in AMD brochure and information sheet, plus accompanying conversation starter, aimed at AMD patients and those who interact with them (family, friends, nursing home staff).
Semi-structured face-to-face interviews were conducted with 21 AMD patients covering the full range from mild vision loss to legally blind. Thematic analysis was used to explore the range of patient experiences.
Patients reported faces appeared blurred and/or distorted. They described recurrent failures to recognise others' identity, facial expressions and emotional states, plus failures of alternative non-face strategies (e.g., hairstyle, voice). They reported failures to follow social nuances (e.g., to pick up that someone was joking), and feelings of missing out ('I can't join in'). Concern about offending others (e.g., by unintentionally ignoring them) was common, as were concerns of appearing fraudulent ('Other people don't understand'). Many reported social disengagement. Many reported specifically face-perception-related reductions in social life, confidence, and quality of life. All effects were observed even with only mild vision loss. Patients endorsed the value of our Faces and Social Life in AMD Information Sheet, developed from the interview results, and supported future technological assistance (digital image enhancement).
Poor face perception in AMD is an important domain contributing to impaired social interactions and quality of life. This domain should be directly assessed in quantitative quality of life measures, and in resources designed to improve community understanding. The identity-related social difficulties mirror those in prosopagnosia, of cortical rather than retinal origin, implying findings may generalise to all low-vision disorders.
To report and compare 10-year treatment outcomes of vascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration (nAMD) from Australia and New Zealand (ANZ) ...and Switzerland.
Retrospective, comparative, interventional case series.
We analyzed 712 treatment-naive eyes (ANZ, n = 474; Switzerland, n = 321) starting anti-VEGF for nAMD in routine clinical practice between January 1, 2006, and December 31, 2008, tracked in the prospectively designed observational database, the Fight Retinal Blindness! registry. The primary outcome was mean change in visual acuity (VA in logMAR letters) in eyes that completed 10 years of treatment.
The mean VA in 132 eyes (28%) from ANZ patients who completed 10 years of treatment dropped by 0.9 letters from baseline (95% confidence interval CI, −4.9 to 3.1; P = 0.7) with 42% achieving ≥20/40, whereas the 37 eyes (12%) from Swiss subjects lost 14.9 letters (95% CI, −24 to −5.7; P < 0.001) with 35% achieving ≥20/40. Eyes from ANZ patients received more injections than eyes from Swiss subjects over 10 years (a median of 53 vs 42, respectively) from fewer visits with better disease control (proportion of visits with active disease: 38% vs 69%, respectively), suggesting a treat-and-extend regimen versus a pro re nata regimen (treatment given only when the lesion is active). Macular atrophy and subretinal fibrosis were the main reasons for 10 letter loss in the subset of eyes analyzed retrospectively. The mean VA of eyes from both regions that discontinued treatment within 10 years had fallen below the baseline at their final visit.
Eyes with nAMD may achieve satisfactory long-term visual outcomes if they receive adequate treatment. Central macular atrophy does not develop universally in eyes receiving long-term treatment with VEGF inhibitors as previously feared. Visual outcomes were better in eyes from ANZ patients, likely because they received more injections.
•Visual outcomes at 10 years were reasonably good, with adequate treatment.•Disease control was better using the treat-and-extend regimen.•More patients with eyes with initially good vision completed 10 years of treatment.•Vascular endothelial growth factor inhibitors were well tolerated over 10 years.Abstract
To report 24-month outcomes of a treat and extend (T&E) regimen using aflibercept in eyes with neovascular age-related macular degeneration.
This was a database observational study that included ...treatment-naive eyes with neovascular age-related macular degeneration tracked by the Fight Retinal Blindness! outcome registry completing 24 months of sole monotherapy with aflibercept treatment under a T&E regimen between November 1, 2012 and January 31, 2014. Locally weighted scatterplot smoothing curves were used to display visual acuity outcomes. Main outcome measures were change in visual acuity at 24 months and number of injections and visits during the study period.
The study population, identified by reviewing the database, consisted of 136 eyes from 123 patients completing 24 months of follow-up on aflibercept. Mean (SD) age was 77.2 (7.0) years, 59% were female. Mean visual acuity increased from 61.4 (∼20/60; SD 17.4) letters at baseline to 67.4 (∼20/45; SD 17.7) letters at 24 months (+6.0 letters 95% confidence interval: 3.3-8.5; P < 0.001). From baseline to 24 months, the proportion of eyes with visual acuity ≥70 letters (20/40) increased (40%-58%, P < 0.001) and the proportion of eyes with visual acuity ≤35 letters (20/200) remained the same (10%; P = 0.547). Ninety-eight per cent of eyes starting with visual acuity ≥70 letters (20/40) were able to maintain this up to 24 months. From the first to the second year of treatment, the mean number of injections (7.8 2.1 vs. 5.7 2.6; P < 0.001) and visits (8.7 1.7 vs. 6.5 2.4; P < 0.001) decreased for eyes completing 24 months of treatment. When data from 60 eligible eyes that did not complete 2 years follow-up, along with 14 eyes that switched to ranibizumab, were included using last observation carried forward, the mean change in visual acuity from baseline was +5.6 letters (95% confidence interval: 3.3-7.7).
These data indicate that eyes treated with aflibercept, as a sole therapy, in routine clinical practice with a T&E regimen can achieve good visual outcomes while decreasing the burden of treatments and clinic visits.
To report 24-month outcomes of anti-vascular endothelial growth factor (VEGF) therapy for treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) using a treat and extend ...treatment regimen in routine clinical practice.
Database observational study.
We included treatment-naïve eyes receiving predominantly ranibizumab for nAMD in routine clinical practice treated using a treat and extend regimen that were tracked in the Fight Retinal Blindness observational registry.
A cohort of eyes treated by practitioners using exclusively a treat and extend regimen was extracted from the Fight Retinal Blindness observational registry.
Change in visual acuity (VA) over 2 years and number of injections and visits.
Data from 1198 eyes from 1011 patients receiving anti-VEGF therapy using a treat and extend regimen for treatment-naïve nAMD between January 2007 and December 2012 and with 24-month follow-up were included in the analysis. Mean VA increased by +5.3 logarithm of the minimum angle of resolution letters from 56.5 letters (20/80+1) at initial visit to 61.8 (20/60+2) letters at 24 months. Mean VA gains improved and number of injections increased with successive years from +2.7 letters for eyes commencing in 2007 after a mean of 9.7 injections in 2 years, to +7.8 letters for eyes commencing in 2012 after a mean of 14.2 injections over 2 years. The proportion of eyes with VA >20/40 increased from 27% when starting treatment to 45% after 24 months; the proportion with vision of <20/200 remained unchanged (13% initial, 11% at 24 months). Of the included eyes, 90.5% avoided a vision loss of ≥15 letters. There was an overall mean of 13.0 injections over the 24 months, 7.5 injections in the first year and 5.5 in the second year, with a mean of 14.8 clinic visits.
These data indicate that eyes managed in routine clinical practice with a treat and extend regimen can achieve good visual outcomes while decreasing the burden of treatments and clinic visits.
To present the treatment patterns, disease activity, and visual outcomes of eyes in the maintenance phase of a treat-and-extend regimen for neovascular age-related macular degeneration (nAMD). To ...compare the maintenance phase behavior of eyes with a shorter induction phase (≤3 injections) with those requiring a longer induction phase (>3 injections).
Database observational study.
Eyes with nAMD receiving anti-vascular endothelial growth factor (VEGF) treatment using a treat-and-extend protocol. Persistently active eyes were excluded, as were eyes with <12 months follow-up during the maintenance phase.
Clinical information from a large prospective international voluntary registry of nAMD was analyzed. The maintenance phase was defined as starting at the first clinician-reported grading of lesion inactivity.
For analyses by eye: treatment interval at first reactivation; time to first reactivation; and visual acuity change during the study period. For analyses by visit: choroidal neovascular membrane activity graded by the treating physician; time since previous injection; and visual acuity loss since previous injection (>0 letters and ≥15 letters).
The mean change in visual acuity during the maintenance phase was +1.0 letters at 12 months -0.6 letters at 24 months and -1.5 at 36 months. Median treatment interval increased from 35 days at study entry to 63 days at 12 months and was 60 days at 36 months. 38.5% of eyes remained inactive at all observed visits during the maintenance phase (minimum 1 year follow-up, mean 945 days). The most common treatment interval at first reactivation was 8 weeks. Treatment intervals beyond 12 weeks seemed to be associated with increased risk of disease reactivation, with risk of reactivation reaching 37.4% at treatment intervals of ≥20 weeks. Eyes with a longer induction phase had worse visual outcomes in the maintenance phase, and earlier and more-frequent disease reactivation, although they received injections less frequently.
The detailed behavior of eyes in the maintenance phase of treat-and-extend management for nAMD is presented. Visual acuity was well maintained during the study period. The most common interval at which reactivation first occurred was 8 weeks. Longer duration of induction phase was associated with worse visual acuity outcomes and earlier disease reactivation, perhaps because of undertreatment.
To assess the incidence, cumulative rate, and long-term outcomes of infectious and noninfectious endophthalmitis after intravitreal injections (IVTs) of anti-vascular endothelial growth factor (VEGF) ...agents.
Database study, prospectively designed.
Treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) tracked by the Fight Retinal Blindness! (FRB!) registry that commenced anti-VEGF therapy between January 1, 2006, and November 30, 2016.
Cumulative rate of endophthalmitis and survival curves were measured using Cox-proportional hazards models. Locally weighted scatterplot smoothing curves were used to display visual acuity (VA).
Incidence and cumulative rate of endophthalmitis, and change in VA 12 months after endophthalmitis.
Infectious endophthalmitis developed in 18 of 88 150 injections (1/4897 injections 0.020%; 95% confidence interval CI, 0.012-0.032) with no difference found between types of anti-VEGF medications (P = 0.896). The cumulative rate of infectious endophthalmitis per patient was 0.055%, 0.183%, 0.360%, 0.360%, 0.555%, and 0.843% after 10, 20, 30, 40, 50, and 60 IVTs, respectively. However, the "risk" of infectious endophthalmitis did not increase with each successive injection (P = 0.202). Noninfectious endophthalmitis developed in 11 of 88 150 injections (1/8013 injections 0.012%; 95% CI, 0.006-0.022). The cumulative rate of noninfectious endophthalmitis per patient was 0.087% and 0.228% after 10 and 20 IVTs, respectively, and then remained stable up to 60 IVTs. The incidence of noninfectious endophthalmitis was higher for bevacizumab (8/9931, 0.081%) compared with ranibizumab (3/54 776, 0.005%; P = 0.005) and aflibercept (0/23 425; P = 0.016), and no differences were observed between ranibizumab and aflibercept (P = 1.0). The 12-month VA in infectious and noninfectious endophthalmitis was within ±2 lines of before endophthalmitis in 53% and 75% of eyes, respectively; a loss >2 lines was observed in 31% and 25% of eyes, respectively.
The incidences of infectious and noninfectious endophthalmitis after IVT were low, and the risk did not increase with each successive injection. We found higher rates of noninfectious endophthalmitis with bevacizumab compared with ranibizumab or aflibercept. Three quarters of cases with infectious and two thirds of cases with noninfectious endophthalmitis retained vision within 10 letters of the pre-endophthalmitis level.
To analyze the long-term outcomes of eyes with neovascular age-related macular degeneration (AMD) starting treatment with vascular endothelial growth factor (VEGF) inhibitors at least 5 years ...earlier.
Database observational study.
Treatment-naïve eyes with neovascular AMD tracked by the Fight Retinal Blindness outcome registry that received at least 1 anti-VEGF injection.
Locally weighted scatterplot smoothing curves were used to display visual acuity (VA) results.
Change in mean VA and number of injections and visits from baseline up to 7 years after initiating treatment.
The mean follow-up time of all 1212 identified eyes was 53.5 months, and 549 (45%) continued attending after 60 months. Mean VA improved from 55.1 to 61.4 letters after 6 months and remained above the mean presenting VA for approximately 6 years. After 7 years, mean VA was 2.6 letters lower than baseline for the 131 eyes still being followed; 40% had VA ≥70 (20/40) letters, and 18% had VA ≤35 letters (20/200). Of those with 20/40 VA before treatment, 40% had lost it after 7 years. Geographic atrophy affecting the fovea was thought to be the cause of a ≥10-letter loss after 6.5 years in 37% of a subset of such eyes that were retrospectively analyzed. A median of 6 injections and 9 visits were recorded over the first 12 months, and then 5 treatments and 7 to 9 visits per annum thereafter through 7 years. Treatment was discontinued for 663 eyes (53%) within the first 5 years. Despite initial gains in vision, the mean VA of these eyes had deteriorated to baseline or worse around the time treatment was discontinued. The rate of serious adverse events was low.
Good long-term outcomes of VEGF inhibition for neovascular AMD were found in this study. These results may be better than other reports because more injections were given to our patients, possibly associated with a greater incentive for the physician to treat. Further studies to determine how to maximize the proportion of eyes that retain the initial VA gains of anti-VEGF are warranted.
Purpose
To evaluate the effect of preoperative optical coherence tomography (OCT) features on postoperative visual acuity and change in acuity after epiretinal membrane (ERM) surgery.
Methods
This ...was a retrospective consecutive case series of patients with symptomatic idiopathic ERMs who underwent vitrectomy and membrane peel between 2008 and 2013. The main outcomes were postoperative letter score and change in letter score. The association between visual acuity and OCT features was estimated using linear regression, correcting for important baseline covariates. OCT features included central foveal thickness, maximum retinal thickness, retinal cross-sectional area, central photoreceptor thickness, central epiretinal membrane, intraretinal cyst presence and location, retinal contraction, foveal ellipsoid zone and external limiting membrane integrity, and pseudoholes.
Results
A total of 79 patients were included in the study. Mean visual acuity was 65.0 letters preoperatively and 68.9 letters postoperatively, with average follow-up of 92 days. Better postoperative visual acuity was associated with the presence of preoperative retinal contraction (6.4 letters
P
= 0.027) and lower preoperative maximum retinal thickness values (0.34 letters per 10 μm reduction,
P
= 0.003). Change in visual acuity was associated with preoperative foveal ellipsoid zone attenuation (6.6 letters more improvement when present,
P
= 0.013). Preoperative pseudoholes were associated with a smaller change in visual acuity (7.4 letters less improvement,
P
= 0.034). No other OCT features were significant, including intraretinal cyst presence and location. Better preoperative visual acuity was associated with better postoperative acuity, but less change in visual acuity postoperatively.
Conclusion
Preoperative maximum retinal thickness and retinal contraction were predictive of better postoperative visual acuity, while patients with a preoperative attenuated foveal ellipsoid zone were most likely to improve. Patients with preoperative pseudoholes had slightly worse visual acuity postoperatively. Although better preoperative vision was associated with better postoperative vision, it was associated with less change in visual acuity, emphasizing the importance of careful consideration of the desired surgical goals before advising surgery for ERM.
Purpose
To compare diagnostic power for different severities of age-related macular degeneration (AMD) of two-dimensional macular pigment optical densities (2D-MPOD) and spatially matched objective ...perimetry, with standard perimetry and best-corrected visual acuity (BCVA).
Methods
The ObjectiveField Analyser (OFA) provided objective perimetry, and a Heidelberg Spectralis optical coherence tomography (OCT) measured 2D-MPOD in AMD patients, both completed twice over 0.99 ± 0.16 years. From each 2D-MPOD image, we extracted 20 regions/macula, matched to the 20 OFA stimuli/macula. For each region, we calculated 7 measures from the 2D-MPOD pixel values and correlated those with OFA sensitivities and delays. We quantified 2D-MPOD changes, the ability of 2D-MPOD and OFA to discriminate AMD stages, and the discriminatory power of Matrix perimetry and BCVA using percentage area under receiver operator characteristic plots (%AUROC).
Results
In 58 eyes of 29 subjects (71.6 ± 6.3 years, 22 females), we found significant correlations between 2D-MPOD and OFA sensitivities for Age-Related Eye Disease Studies (AREDS)-3 and AREDS-4 severities. Delays showed significant correlations with AREDS-2. For AREDS-4, correlations extended across all eccentricities. Regression associated with the Bland–Altman plots showed significant changes in 2D-MPOD over the study period,
especially variability measures
. MPOD per-region medians discriminated AREDS-1 from AREDS-3 eyes at a %AUROC of 80.0 ± 6.3%, outperforming OFA, Matrix perimetry, and BCVA.
Conclusions
MPOD changes correlated with central functional changes and significant correlations extended peripherally in later-stage AMD. Good diagnostic power for earlier-stage AMD and significant change over the study suggest that 2D-MPOD and OFA may provide effective biomarkers.
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