Projection of Long-Term Visual Acuity Outcomes Based on Initial Treatment Response in Neovascular Age-Related Macular Degeneration

ObjectiveAge-related macular degeneration (ARMD) is a leading cause of visual impairment. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard treatment for wet ARMD. There is however, variability in patient responses, suggesting patient-specific factors influencing drug efficacy. We tested whether single nucleotide polymorphisms (SNPs) in genes encoding VEGF pathway members contribute to therapy response.Methods and analysisA retrospective cohort of 281 European wet ARMD patients treated with anti-VEGF was genotyped for 138 tagging SNPs in the VEGF pathway. Per patient, we collected best corrected visual acuity at baseline, after three loading injections and at 12 months. We also registered the injection number and changes in retinal morphology after three loading injections (central foveal thickness (CFT), intraretinal cysts and serous neuroepithelium detachment). Changes in CFT after 3 months were our primary outcome measure. Association of SNPs to response was assessed by binomial logistic regression. Replication was attempted by associating visual acuity changes to genotypes in an independent Japanese cohort.ResultsAssociation with treatment response was detected for seven SNPs, including in FLT4 (rs55667289: OR=0.746, 95% CI 0.63 to 0.88, p=0.0005) and KDR (rs7691507: OR=1.056, 95% CI 1.02 to 1.10, p=0.005; and rs2305945: OR=0.963, 95% CI 0.93 to 1.00, p=0.0472). Only association with rs55667289 in FLT4 survived multiple testing correction. This SNP was unavailable for testing in the replication cohort. Of six SNPs tested for replication, one was significant although not after multiple testing correction.ConclusionIdentifying genetic variants that define treatment response can help to develop individualised therapeutic approaches for wet ARMD patients and may point towards new targets in non-responders.

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

European Journal of Ophthalmology ◽

10.1177/1120672119839299 ◽

2019 ◽

Vol 30 (3) ◽

pp. 543-549 ◽

Cited By ~ 2

Author(s):

Corinne Fulcher ◽

Charlotte A Hazel ◽

Ian Pacey ◽

Hasan Ali ◽

Faruque D Ghanchi

Keyword(s):

Visual Acuity ◽

Macular Degeneration ◽

Predictive Factor ◽

Retinal Thickness ◽

Age Related Macular Degeneration ◽

Central Retinal Thickness ◽

Response To Treatment ◽

Long Term Outcome ◽

Age Related

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.

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Limited Treatment Response during Follow-up after Switching to Aflibercept in Neovascular Age-related Macular Degeneration

Journal of the Korean Ophthalmological Society ◽

10.3341/jkos.2021.62.9.1218 ◽

2021 ◽

Vol 62 (9) ◽

pp. 1218-1226

Author(s):

Gon Soo Choe ◽

Jong Woo Kim ◽

Chul Gu Kim ◽

Jae Hui Kim

Keyword(s):

Visual Acuity ◽

Retrospective Study ◽

Macular Degeneration ◽

Treatment Response ◽

Visual Outcome ◽

Age Related Macular Degeneration ◽

Neovascular Amd ◽

Age Related ◽

The Mean

Purpose: To investigate the limited response to aflibercept after switching to aflibercept in neovascular age-related macular degeneration (AMD). Methods: This retrospective study included 70 eyes with neovascular AMD that were initially treated with ranibizumab and then switched to aflibercept. The incidence and timing of the limited response to aflibercept were identified and visual outcome was compared between eyes with and without limited response. In addition, factors predictive of limited response were analyzed. Results: A limited response to aflibercept was noted in approximately 1/5 of the patients who underwent switching to aflibercept in neovascular AMD. Switching to aflibercept was performed at a mean of 16.2 ± 12.7 months after diagnosis. During the mean 34.7 months of follow-up after switching, limited response was noted in 15 eyes (21.4%) at a mean of 22.0 ± 13.9 months after switching. The degree of reduction in visual acuity was mean logMAR 0.34 ± 0.41 in eyes with limited response and mean 0.06 ± 0.20 in eyes without (p = 0.002). In addition, the duration between the diagnosis and the switching was shorter (p = 0.012), and the number of ranibizumab injections before switching was lower (p = 0.016) in eyes with limited response than in eyes without. Conclusions: Patients who showed limited response to aflibercept after switching to aflibercept showed a worse visual outcome. The probability of having a limited response is higher when the switching is performed earlier.

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Long‐term visual acuity in patients with age‐related macular degeneration treated with ranibizumab and persistence of subretinal fluid

Acta Ophthalmologica ◽

10.1111/j.1755-3768.2011.3214.x ◽

2011 ◽

Vol 89 (s248) ◽

pp. 0-0

Author(s):

S FERNANDEZ‐PEREZ ◽

C TORRON ◽

O RUIZ‐MORENO ◽

J LECINENA ◽

A PEREZ‐INIGO ◽

...

Keyword(s):

Visual Acuity ◽

Macular Degeneration ◽

Subretinal Fluid ◽

Age Related Macular Degeneration ◽

Age Related

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IMPLANTABLE TELESCOPE FOR END-STAGE AGE-RELATED MACULAR DEGENERATION: LONG-TERM VISUAL ACUITY AND SAFETY OUTCOMES

Evidence-Based Ophthalmology ◽

10.1097/ieb.0b013e31819de23e ◽

2009 ◽

Vol 10 (3) ◽

pp. 135-137

Author(s):

Emily C. Waisbren ◽

Melissa M. Brown

Keyword(s):

Visual Acuity ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Age Related ◽

Safety Outcomes ◽

End Stage

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Long-term Outcomes of Treat and Extend Regimen of Anti-vascular Endothelial Growth Factor in Neovascular Age-related Macular Degeneration

Journal of Ophthalmic and Vision Research ◽

10.18502/jovr.v15i3.7452 ◽

2020 ◽

Author(s):

Andy Lee ◽

Pooja G Garg ◽

Alice T Lyon ◽

Rukhsana Mirza ◽

Manjot K Gill

Keyword(s):

Visual Acuity ◽

Growth Factor ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Final Visit ◽

Treat And Extend ◽

Age Related ◽

Endothelial Growth Factor

Purpose: This study describes the long-term visual and anatomic outcomes of antivascular endothelial growth factor (VEGF) treatment using a treat and extend dosing regimen. Methods: This cross-sectional cohort study consisted of 224 treatment-naïve eyes with neovascular age-related macular degeneration (NV-AMD) from 202 patients that were treated with anti-VEGF agents bevacizumab, ranibizumab, and aflibercept using a treat and extend (TAE) regimen by four physician investigators in a large urban referral center from 2008 to 2015. Subjects were evaluated for visual acuity, injection frequency, and optical coherence tomography (OCT). Results: Over a seven-year follow-up period (mean 3.4 years), an average 20.2 ± 14.7 injections were administered with 8.4 injections in the first year and 5.5 injections by the seventh year of remaining eyes undergoing treatment. Visual acuity was 0.70 logMAR (20/100 Snellen) at the first visit and 0.67 logMAR (20/93 Snellen) at the final visit, with 74% of eyes maintaining or gaining more than 2 lines of vision. Long-term, 45.1% of eyes achieved 20/50 or better, while 27.1% were 20/200 or worse. Of the treated patients, 61.2% received monotherapy with no difference in visual acuity outcomes or number of injections between the agents used. OCT analysis showed decreased fluid from initial to final follow-up visit: 70.1–15.6% with sub-retinal fluid (SRF) and 47.3–18.8% with intraretinal fluid (IRF) with no difference between the agents were used. Conclusion: This study demonstrates that most patients (74%) improve or maintain visual acuity long-term using a TAE model with a significant portion (45.1%) achieving 20/50 or better visual acuity with sustained treatment.

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