Delay to Treatment and Visual Outcomes in Patients Treated With Anti-Vascular Endothelial Growth Factor for Age-Related Macular Degeneration

doi:10.1016/j.ajo.2011.09.013

American Journal of Ophthalmology

Volume 153, Issue 4, April 2012, Pages 678-686.e2

https://doi.org/10.1016/j.ajo.2011.09.013 Get rights and content

Purpose

To investigate the potential influences that affect visual acuity (VA) outcome in a clinic-based cohort of age-related macular degeneration (AMD) patients undergoing anti–vascular endothelial growth factor (anti-VEGF) treatment for choroidal neovascularization.

Design

Prospective interventional case series.

Methods

Patients with subfoveal choroidal neovascularization (CNV) secondary to AMD were prospectively recruited. A detailed questionnaire was given to patients at time of enrollment, to collect information relating to demographics, history of visual symptoms, visual acuity (VA), and treatment scheduling. Delay from symptoms to treatment (“Treatment delay”) was measured in terms of weeks and analyzed in tertiles. Information pertaining to treatment outcomes was collected over a 6-month period.

Results

One hundred eighty-five eyes of 185 patients were recruited into the study. Longer delay from first symptoms suggestive of CNV to first injection was a significant predictor (P = .015) of poorer treatment outcome, when controlling for age, sex, and baseline VA. Patients with a delay in treatment of 21 weeks or more compared to a delay of 7 weeks or less had an odds ratio of 2.62 (1.20, 5.68) for worsening vision after treatment.

Conclusions

Patients experiencing a longer delay between their first symptoms of CNV and their first anti-VEGF treatment have a significantly lower chance of improving vision at 6 months following anti-VEGF therapy. It is critical that this information reach those at potential vision loss from AMD, in order that prompt treatment may be instituted, to maximize the benefits of anti-VEGF treatment.

Section snippets

Study Design and Eligibility

Study patients were recruited consecutively between August 1, 2007 and December 31, 2008 from the Medical Retina Clinic at the Royal Victorian Eye and Ear Hospital and the private rooms of the Vision Retinal Institute Eastern, in Melbourne. All patients were over the age of 50 years and were diagnosed with subfoveal CNV (subfoveal lesions included those juxtafoveal lesions that could not be safely treated with either thermal laser or photodynamic therapy, without involvement of the center of

Population Characteristics

A total of 198 eyes from 192 patients were recruited into the study. Seven eyes of 7 patients failed to complete the follow-up period and were excluded. Of the 6 patients that had bilateral treatment, only the worse-seeing eye at 6 months was analyzed as we were particularly interested in determinants of poor outcomes. A total study population of 185 eyes of 185 patients was therefore analyzed for this study. Of these treated eyes, 75 had either bevacizumab or ranibizumab during the course of

Discussion

This study analyzed the influences upon clinic-based treatment outcomes of patients receiving either bevacizumab or ranibizumab for neovascular AMD. Our analyses found that better baseline vision was more likely to be associated with adverse visual outcomes. This has been documented previously9, 10 and is likely explained by the “ceiling” effect, where it is hard to improve vision where the vision is already good at baseline. We also demonstrated that longer treatment delay from first symptoms

Jonathan Lim, MBBS/BMedSci, is currently a Hospital Medical Officer at The Alfred Hospital, Melbourne, Australia. He received his medical degree from the University of Melbourne, during which he conducted ophthalmological research at the Centre for Eye Research Australia and undertook his medical elective at Moorfields Eye Hospital, London. He has presented research findings at the Royal Australian and New Zealand College of Ophthalmologists Annual Scientific Congress and at the Association for

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Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration
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OCT Prognostic Biomarkers for Progression to Late Age-related Macular Degeneration: A Systematic Review and Meta-analysis
2024, Ophthalmology Retina
To evaluate which OCT prognostic biomarkers best predict the risk of progression from early/intermediate to late age-related macular degeneration (AMD).
Among > 100 OCT prognostic biomarkers for AMD, it is unclear which are the most relevant for clinicians and researchers to focus on. This review evaluated which OCT biomarkers confer the greatest magnitude of prediction for progression to late AMD.
Study protocol was registered on PROSPERO (CRD42023400166). PubMed and Embase were searched from inception to March 2, 2023, and eligible studies assessed following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The primary outcome was any quantified risk of progression from treatment-naive early/intermediate AMD to late AMD, including hazard ratios (HRs), odds ratios (ORs), and standardized mean differences (at baseline, between eyes with versus without progression), subgrouped by each OCT biomarker. Further meta-analyses were subgrouped by progression to geographic atrophy or neovascularization.
A total of 114 quantified OCT prognostic biomarkers were identified. With high GRADE certainty of evidence, the greatest magnitudes of prediction to late AMD belonged to: external limiting membrane abnormality (OR, 15.42 [7.63, 31.17]), ellipsoid zone abnormality (OR, 10.8 [4.58, 25.46]), interdigitation zone abnormality (OR, 7.68 [2.57, 23]), concurrent large drusen and reticular pseudodrusen (HR, 6.73 [1.35, 33.65], hyporeflective drusen cores (HR, 2.48 [1.8, 3.4]; OR 1.85 [1.29, 2.66]), intraretinal hyperreflective foci (IHRF; HR, 2.16 [0.92, 5.07]; OR 5.08 [3.26, 7.92]), and large drusen (HR, 2.01 [1.35, 2.99]); OR, 1.98 [1.27, 3.08]). There was greater risk of geographic atrophy for IHRF and hyporeflective drusen cores (P < 0.05), and neovascularization for ellipsoid zone abnormality (P < 0.05). Other OCT biomarkers such as drusenoid pigment epithelium detachment, shallow irregular retinal pigment epithelium elevations, and nascent geographic atrophy exhibited large magnitudes of risk but required further studies for validation.
This review synthesizes the 6 most relevant OCT prognostic biomarkers for AMD with greater predictive ability than large drusen alone, for clinicians and researchers to focus on. Further study is required to validate other biomarkers with less than high certainty of evidence, and assess how the copresence of biomarkers may affect risks.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Pseudophakia as a surprising protective factor in neovascular age-related macular degeneration
2023, Journal Francais d'Ophtalmologie
To assess the impact of lens status on macular function among patients treated for neovascular age-related macular degeneration (nvAMD) in whom scheduled intravitreal injections were delayed.
We reviewed demographic and clinical data as well as macular optical coherence tomographic images of 34 patients (48 eyes) who did not follow their injection schedule during the first wave of COVID-19 in Israel. Functional worsening was defined as a loss of at least 0.1 in decimal best-corrected visual acuity (BCVA). Morphological worsening was defined as new or increased subretinal/intraretinal fluid or a new hemorrhage. OCT indices of quality were used as a measure for cataract density and progression.
Pseudophakia was associated with a better functional outcome than phakic status: there was a loss of 0.06 ± 0.12 vs. 0.15 ± 0.10 decimal BCVA in the pseudophakic and phakic eyes, respectively (P = .001). A similar trend was observed for morphological changes over the same period: there was an increase in macular thickness of 9 ± 26% vs.12 ± 40%, respectively (P = 0.79). During the first wave of COVID-19, the index of OCT quality remained stable for phakic eyes (26 ± 3.6 before the first wave of COVID-19, 26 ± 2.9 afterward; P = 1) and pseudophakic eyes (30 ± 2.4 before the first wave of COVID-19, 30 ± 2.6 afterward; P = 1).
Pseudophakic eyes with nvAMD that missed their scheduled intravitreal injections experienced fewer morphological and functional complications than phakic eyes with nvAMD.
Mesurer l’effet du statut cristallinien sur la fonction maculaire parmi des patients, traités pour dégénérescence maculaire liée à l’âge néovasculaire (DMLAnv), ayant subi un retard dans leur programme d’injections intravitréennes.
Les données démographiques et cliniques ainsi que les images en tomographie en cohérence optique (OCT) ont été analysées chez 34 patients (48 yeux) qui ont dévié de leur programme d’injections au cours de la première vague de COVID-19 en Israël. Nous avons défini une aggravation fonctionnelle comme une perte d’au moins 0,1 en valeur décimale d’acuité visuelle corrigée (AV) et une aggravation anatomique comme la survenue de liquides sous- ou intra-rétiniens ou leur augmentation quantitative. Les indices de qualité des images OCT, analysés diachroniquement, ont été utilisés comme mesure indirecte d’opacification du cristallin.
Dans notre cohorte, les yeux pseudophaques obtiennent un meilleur résultat fonctionnel que ceux phaques, les premiers accusant une perte de 0,06 ± 0,12 en VA décimale, les seconds de 0,15 ± 0,10 (p = 0,001). Une tendance similaire se dessine en ce qui concerne la morphologie maculaire: on constate une augmentation de 9 ± 26 % de l’épaisseur maculaire centrale parmi les yeux pseudophaques et de 12 ± 40 % parmi les yeux phaques (p = 0,79). Durant la première vague de COVID-19, les indices de qualités OCT restent stables pour les yeux phaques (26 ± 3,6 avant, 26 ± 2,9 après; p = 1) comme pour les pseudophaques (30 ± 2,4 avant, 30 ± 2,6 après; p = 1).
Dans la DMLAnv, les yeux pseudophaques qui n’ont pas reçu leurs injections intravitréennes à temps ont subi moins de dommages anatomiques et fonctionnels, à court terme, que les phaques.
Age-related macular degeneration
2023, The Lancet
Age-related macular degeneration is an increasingly important public health issue due to ageing populations and increased longevity. Age-related macular degeneration affects individuals older than 55 years and threatens high-acuity central vision required for important tasks such as reading, driving, and recognising faces. Advances in retinal imaging have identified biomarkers of progression to late age-related macular degeneration. New treatments for neovascular age-related macular degeneration offer potentially longer-lasting effects, and progress is being made towards a treatment for atrophic late age-related macular degeneration. An effective intervention to slow progression in the earlier stages of disease, or to prevent late age-related macular degeneration development remains elusive, and our understanding of underlying mechanistic pathways continues to evolve.
Treatment of neovascular age-related macular degeneration within 48 h from diagnosis improves long-term functional outcome
2023, Biomedicine and Pharmacotherapy
To evaluate long-term visual and anatomical outcomes in neovascular age-related macular degeneration (nAMD) patients treated with anti-vascular endothelial growth factor (VEGF) agents depending on the time delay from confirmed diagnosis to treatment initiation.
Seventy-three nAMD patients (73 eyes) treated with anti-VEGF agents for 12 months using the pro re nata regimen were included in this retrospective longitudinal study. Patients were split into 3 groups according to the time from diagnosis to first anti-VEGF injection: < 48 h (group 1); 48 h-7 days (group 2); > 7 days (group 3). Decimal best-corrected visual acuity (VA) and macular thickness (MT) were recorded at baseline and 1–2-, 3–4-, 6- and 12-month later. Furthermore, age, gender as well as the applied treatment and number of injections after 12 months of treatment were also registered and compared.
Long-term effect of the treatment demonstrated enhanced VA in group 1 patients compared with the rest of groups after 1–2-, 6-, and 12-month follow-up (P < 0.05). Positive effects of early treatment were additionally corroborated by the augmented percentage of patients with normal VA in the group 1 respect to the rest of groups over studied time points (P < 0.05). Moreover, the VA gain in nAMD at group 1 was obtained with a mean of 3.7 intravitreal injections over 1-year follow-up period. Regarding MT, non-significant difference was observed among groups.
An early initial treatment with VEGF inhibitors is critical to achieve the best functional benefits of this therapy in new-onset nAMD patients.
The Short-Term Compliance and Concordance to in Clinic Testing for Tablet-Based Home Monitoring in Age-Related Macular Degeneration
2022, American Journal of Ophthalmology
The aim of this study was to determine the short-term compliance with regular home monitoring of macular retinal sensitivity (RS) in intermediate age-related macular degeneration (iAMD). Home-based outcomes were compared with in-clinic outcomes determined using (1) the same tablet device under supervision, and (2) the Macular Integrity Assessment (MaIA) microperimeter.
Single-center longitudinal compliance and reliability study.
A total of 73 participants with iAMD were trained to perform macular field testing with the Melbourne Rapid Fields−macular (MRF-m) iPad application. Volunteers were asked to return 6 weekly tests from home, guided by audio instructions. We determined compliance with weekly testing and surveyed for factors that limited compliance. Test reliability (false positive, false negative) and RS were compared to in-clinic assays (MaIA). Data are given as mean ± SD or as median [quartile 1-3 range]. Group comparisons were achieved with bootstrap to define the 95% confidence limits.
A total of 59 participants submitted 6 home examinations with a median intertest interval of 8.0 [7.0-17] days. Compliance with weekly testing (7 days ±24 hours) was 55%. The main barrier to compliance was information technology (IT) logistic reasons. Of 694 home examinations submitted, 96% were reliable (false-positive results <25%). The mean RS returned by the tablet was significantly higher (+3.2 dB, P < .05) compared to the MaIA.
Home monitoring produces reliable results that differ from in-clinic tests because of test design. This should not affect self-monitoring once an at-home baseline is established, but these differences will affect comparisons with in-clinic outcomes. Reasonable compliance with weekly testing was achieved. Improved IT support might lead to better compliance.
Detecting retinal cell stress and apoptosis with DARC: Progression from lab to clinic
2022, Progress in Retinal and Eye Research
Citation Excerpt :
The cost of these invasive therapies is significant with each injection costing up to £1000 in the UK and some patients requiring monthly injections (Raftery et al., 2007). With the healthcare costs of managing patients with neovascular AMD increasing significantly, early diagnosis AMD is crucial in addition to developing robust methods to identify its progression early (Keenan et al., 2020; J. H. Lim et al., 2012). Neovascular AMD is characterised by the presence of intraretinal fluid, subretinal fluid and choroidal neovascularisation.
DARC (Detection of Apoptosing Retinal Cells) is a retinal imaging technology that has been developed within the last 2 decades from basic laboratory science to Phase 2 clinical trials. It uses ANX776 (fluorescently labelled Annexin A5) to identify stressed and apoptotic cells in the living eye. During its development, DARC has undergone biochemistry optimisation, scale-up and GMP manufacture and extensive preclinical evaluation. Initially tested in preclinical glaucoma and optic neuropathy models, it has also been investigated in AMD, Alzheimer's, Parkinson's and Diabetic models, and used to assess efficacy of therapies. Progression to clinical trials has not been speedy. Intravenous ANX776 has to date been found to be safe and well-tolerated in 129 patients, including 16 from Phase 1 and 113 from Phase 2. Results on glaucoma and AMD patients have been recently published, and suggest DARC with an AI-aided algorithm can be used to predict disease activity. New analyses of DARC in GA (Geographic Atrophy) prediction are reported here. Although further studies are needed to validate these findings, it appears there is potential for the technology to be used as a biomarker. Much larger clinical studies will be needed before it can be considered as a diagnostic, although the relatively non-invasive nature of the nasal as opposed to intravenous administration would widen its acceptability in the future as a screening tool.
This review describes DARC development and its progression into Phase 2 clinical trials from lab-based research. It discusses hypotheses, potential challenges, and regulatory hurdles in translating technology.

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Sanj Wickremasinghe is a consultant in the Medical Retina Unit at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia. He holds a research fellowship at the Macular Research Unit, within the Centre for Eye Research Australia. He completed specialist ophthalmic training at Moorfield's Eye Hospital, London and has fellowship experience both at Moorfields Eye Hospital and the Royal Victorian Eye and Ear Hospital. He is currently involved in research into the predictors of outcome in patients with neovascular AMD following intravitreal anti-VEGF treatment.

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Original articleDelay to Treatment and Visual Outcomes in Patients Treated With Anti-Vascular Endothelial Growth Factor for Age-Related Macular Degeneration

Purpose

Design

Methods

Results

Conclusions

Section snippets

Study Design and Eligibility

Population Characteristics

Discussion

Ophthalmology

Ranibizumab for neovascular age-related macular degeneration

N Engl J Med

Ranibizumab versus verteporfin for neovascular age-related macular degeneration

N Engl J Med

Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study

Ophthalmology

Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration

Ophthalmology

Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration

Retina

Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration

Retina

Original article
Delay to Treatment and Visual Outcomes in Patients Treated With Anti-Vascular Endothelial Growth Factor for Age-Related Macular Degeneration