Four-Year Treatment Results of Neovascular Age-Related Macular Degeneration With Ranibizumab and Causes for Discontinuation of Treatment

doi:10.1016/j.ajo.2012.06.031

American Journal of Ophthalmology

Volume 155, Issue 1, January 2013, Pages 89-95.e3

https://doi.org/10.1016/j.ajo.2012.06.031 Get rights and content

Purpose

To evaluate 4-year treatment results of neovascular age-related macular degeneration with ranibizumab using a variable dosing regimen.

Design

Retrospective, single-center chart review.

Methods

This was a retrospective single-center study that included 855 patients with neovascular age-related macular degeneration receiving treatment with ranibizumab during a 4-year period. Included in the study were patients with a minimum follow-up of 15 months and all patients who terminated treatment regardless of follow-up.

Results

A total of 1321 patients were treated over the 4-year period, and 855 patients were eligible for inclusion. Of those, 456 patients were still receiving active treatment, whereas 399 patients had discontinued treatment. Overall treatment results showed a significant decrease in vision from 53.2 Early Treatment Diabetic Retinopathy Study letters (range, 1 to 85 letters) to 50.5 letters (range, 1 to 87 letters; P < .001). Mean follow-up was 23.3 months (range, 4 to 48 months). The reason for discontinuing treatment in 181 patients was no signs of activity, whereas 113 patients were judged to be nontreatable. Thirty-six patients declined further treatment for various reasons.

Conclusions

This report shows that when follow-up extends beyond 2 to 3 years, visual acuity does seem to decrease. Our data show that different responder groups can be identified: bad or nonresponders (approximately 15% of all patients) and good responders (approximately 21% of all patients). These 2 groups in general can be identified within the first 2 years of treatment, whereas the third group of regular responders (approximately 64% of all patients) require continuous monitoring and treatment for years.

Section snippets

Methods

This was a single-center study of 1321 patients with neovascular AMD who received treatment with ranibizumab in the 4-year period from April 2007 to April 2011. Included in the review of treatment results are patients with a minimum of 12 months of follow-up from the assessment visit after the third injection (minimum of 15 months of follow-up from initiation of treatment). All patients who terminated treatment in the 4-year period were included in the study, regardless of length of follow-up.

Patients

The 855 eyes included in the review were divided into 2 groups, one with 456 patients currently in active treatment and another with 399 patients who have discontinued treatment (Table 1). Overall treatment results show a significant decrease in vision from 53.2 letters (range, 1 to 85 letters) to 50.5 letters (range, 1 to 87 letters; P < .001, paired-sample t test). The mean number of injections was 8.7 (range, 1 to 35). Mean duration of follow-up was 23.3 months (range, 4 to 48 months).

Patients Currently in Active Treatment

The

Discussion

In this study, we analyzed 4-year single-center data on ranibizumab treatment for neovascular AMD, including a more detailed study of the patients who discontinued the treatment.

Mads Falk, MD, is currently a PhD fellow at the Department of Ophthalmology, Copenhagen University Hospital Roskilde in Denmark. He graduated from the University of Copenhagen in 2007. He is interested in the immunological changes in age-related macular degeneration.

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Assessment of the perception of healthcare barriers and the impact of intravitreal injections on neovascular age-related macular degeneration
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La DMAEn y su tratamiento suponen una importante carga asistencial para los pacientes, existiendo un gran miedo a la ceguera y a perder su independencia, siendo la principal barrera el largo tiempo de espera en consulta.
To evaluate the perception of barriers in healthcare and the impact of intravitreal injections in patients with neovascular age-related macular degeneration (nAMD).
Cross-sectional study including 108 patients with nAMD in treatment with intravitreal injections. The patients answered a questionnaire with 26 questions (score from 1 to 5) divided in three sections: 1) the disease and its treatment with injections; 2) healthcare barriers, and 3) new technologies.
The mean age was 80.4 ± 7.0 years and visual acuity (VA) was 75.2 ± 12.4 letters. The main barriers in healthcare were long waiting times (72%), followed by other comorbidities (10%). Some 63% of patients have to wait between 3 and 5 hours to attend their clinical visit. Significant anxiety due to the injections (2.8 ± 1.3) was observed, being present in 71% of the cases the day before. A great fear of blindness and losing independence was observed (4.4 ± 0.9 and 4.3 ± 1.1), with no differences in relation to VA, age or sex (P ≥ .135). Moreover, 28% of the patients reported that it was quite or very difficult for them to attend the clinical visit, with 69% of the total showing great interest in having a diagnostic device at home.
The nAMD and its treatment represent a significant burden on patients, among whom there is a great fear of blindness and of losing their independence, the main barrier being the long waiting time for the clinical visit.
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2020, Ophthalmology Retina
Citation Excerpt :
Registration trials for ranibizumab (monthly) and aflibercept (every 2 months after 3 monthly loading doses) and the monthly ranibizumab and bevacizumab arms of CATT show an average 1-year improvement of 8.5 letters across these studies (Table 1),1–4 whereas the current real-world study showed a mean gain of only 1 letter after a mean of 7.3 anti-VEGF injections. Numerous real-world studies of anti-VEGF therapy in nAMD have reported similar poor visual outcomes.5–19 In one particularly relevant real-world study using a database of American Academy of Ophthalmology members (Intelligent Research in Sight [IRIS] registry), 13 859 nAMD patients received an average of 6.1 anti-VEGF injections and experienced a mean improvement of 0.05 logarithm of the minimum angle of resolution (2.5 letters).19
This study assessed anti–vascular endothelial growth factor (VEGF) therapy intensity and its relationship with visual acuity (VA) change in real-world neovascular age-related macular degeneration (nAMD) patients.
This retrospective analysis was performed on a large database of aggregated, longitudinal, de-identified electronic medical records from a geographically and demographically diverse sample of patients of United States retina specialists (Vestrum Health Retina Database).
Treatment-naïve nAMD patients who underwent anti-VEGF injections between January 1, 2012, and October 31, 2016, were eligible if follow-up data were available before October 31, 2017.
Age, gender, anti-VEGF treatment type, number of treatments, and VA were extracted from the database.
Mean VA change assessed at 1 year and stratified based on number of anti-VEGF injections received over 1 year.
In this analysis, 49 485 eyes were included. The mean age was 80.9 years, and 64% were female. Mean baseline VA was 53.8 letters (Snellen equivalent, 20/80). At 1 year, after a mean of 7.3 anti-VEGF injections, there was a mean gain of 1 letter (0.95 letter; 95% confidence interval [CI] for change in VA, +0.77 to +1.13 letter; P < 0.001). When stratified by anti-VEGF agent, the mean VA changes were nearly identical at 1 year. There was a linear relationship between mean letters gained and mean number of injections, between 4 and 10 injections over 1 year, with 4 or fewer or 10 or more injections associated with loss of vision or a plateau, respectively. Greater mean 1-year change in VA also trended with worse baseline VA; those patients with better VA at presentation tended to be particularly vulnerable to vision loss. Those who received the fewest injections tended to be older and have worse baseline VA.
Real-world nAMD patients receive fewer anti-VEGF injections and experience worse visual outcomes compared with patients receiving fixed, frequent therapy in randomized controlled trials. Mean change in VA correlates with treatment intensity at 1 year, but with ceiling effects related to treatment intensity and baseline VA. Older patients and those with poor baseline VA may be particularly prone to undertreatment.

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Torben Lykke Sørensen is a Clinical Associate Research Professor at the University of Copenhagen, Denmark. He completed his MD from the University of Copenhagen and received his Doctor of Medical Sciences Degree (DMSc) from the University of Copenhagen in 2004. He is a board-certified ophthalmologist, chief physician and Director of Research at the Department of Ophthalmology, Copenhagen University Hospital Roskilde. He holds a Hirsch-index of 16 and is currently supervising 2 PhD students.

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Original articleFour-Year Treatment Results of Neovascular Age-Related Macular Degeneration With Ranibizumab and Causes for Discontinuation of Treatment

Purpose

Design

Methods

Results

Conclusions

Section snippets

Methods

Patients

Patients Currently in Active Treatment

Discussion

Ophthalmology

Am J Ophthalmol

Ranibizumab 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

An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration

Am J Ophthalmol

Effectiveness of ranibizumab for neovascular age-related macular degeneration using clinician-determined retreatment strategy

Br J Ophthalmol

Ranibizumab and bevacizumab for neovascular age-related macular degeneration

N Engl J Med

Original article
Four-Year Treatment Results of Neovascular Age-Related Macular Degeneration With Ranibizumab and Causes for Discontinuation of Treatment