Intravitreal Anti-vascular Endothelial Growth Factor Injections to Treat Neovascular Age-related Macular Degeneration: Long-term Treatment Outcomes

Yu Jeong Park; Gi Sung Son; Yoon Jeon Kim; June-Gone Kim; Young Hee Yoon; Joo Yong Lee

doi:10.3341/jkos.2018.59.12.1142

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Park, Son, Kim, Kim, Yoon, and Lee: Intravitreal Anti-vascular Endothelial Growth Factor Injections to Treat Neovascular Age-related Macular Degeneration: Long-term Treatment Outcomes

Original Article

Journal of the Korean Ophthalmological Society 2018; 59(12): 1142-1151.

Published online: 17 December 2018

DOI: https://doi.org/10.3341/jkos.2018.59.12.1142

Intravitreal Anti-vascular Endothelial Growth Factor Injections to Treat Neovascular Age-related Macular Degeneration: Long-term Treatment Outcomes

Yu Jeong Park, MD, Gi Sung Son, MD, Yoon Jeon Kim, MD, PhD, June-Gone Kim, MD, PhD, Young Hee Yoon, MD, PhD, Joo Yong Lee, MD, PhD

Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Address reprint requests to Joo Yong Lee, MD, PhD. Department of Ophthalmology, Asan Medical Center, #88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. Tel: 82-2-3010-3976, Fax: 82-2-470-6440, ophthalmo@amc.seoul.kr

Received 14 August 2018 Revised 2 October 2018 Accepted 23 November 2018

The Korean Ophthalmological Society

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

We assessed the visual and anatomical outcomes, and the safety profile of long-term intravitreal anti-vascular endothelial growth factor (VEGF) injections (aflibercept, ranibizumab, and bevacizumab) given to treat neovascular age-related macular degeneration (NAMD).

Methods

We analyzed medical records collected over 7 years of treatment-naive NAMD patients who received outpatient clinic-based intravitreal anti-VEGF injections. All were treated employing either “treat-and-extend” or “as needed” protocols at the discretion of the retinal specialist. The number of injections, adverse events associated with injection, and measures of visual acuity (VA), central foveal thickness (CFT), and intraocular pressure (IOP) were recorded.

Results

Overall, we assessed 196 eyes of 196 patients (average age 68.6 ± 9.6 years; 77 females). Patients received an average of 17.3 ± 13.5 injections over 78.0 ± 16.5 months of clinical follow-up. The initial mean VA (logMAR) was 0.75 ± 0.58 and the CFT was 349.7 ± 152.6 µm. Both parameters exhibited maximal improvements at the 6-month visit (p < 0.05). However, the clinical outcomes worsened over the 7-year clinical course; the best-corrected visual acuity (BCVA) was 0.91 ± 0.78 and the CFT was 284.5 ± 105.8 µm at 7 years. The BCVA at 7 years was significantly correlated with the initial BCVA. IOP-related events increased 11-fold and anterior chamber reactions increased 3-fold over the years, but no significant complications such as endophthalmitis were recorded.

Conclusions

The use of intravitreal anti-VEGF agents was associated with initial visual improvements over 6 months but did not prevent the worsening of NAMD over 5 years. The BCVA at the initial visit was a strong predictor of the final BCVA. A more intensive injection schedule might improve long-term outcomes.

Keywords: Age-related macular degeneration, Anti-vascular endothelial growth factor, Choroidal neovascularization

Figures and Tables

Figure 1

Temporal changes in the best-corrected visual acuity (BCVA). (A) Temporal change of mean BCVA over 7 years (in ETDRS letters; Snellen visual acuity scores were converted to ETDRS letter scores). (B) Temporal change of mean BCVA over 7 years (in ETDRS letter; converted in same manner as above graph) after imputation of missing values by the last-observation-carried-forward method (n = 37). ETDRS = early treatment diabetic retinopathy study; n = number of patients at the time of BCVA measurements.

Figure 2

Temporal change in central foveal thickness. The central foveal thickness improved gradually during the first 6 months, and maintained over 5 years.

Figure 3

Visual outcome (A), anatomical outcome (B) for different CNV subtypes in the subgroup of 65 patients who completed the 7-year follow-up. Occult CNV (n = 45), classic CNV (n = 5), PCV (n = 15). There was no significant difference between groups during follow-up periods (repeated measured ANOVA). Mean visual acuity and central foveal thickness of each group decreased over time and stabilized. CNV = choroidal neovascularization; PCV = polypoidal choroidal vasculopathy; BCVA = best-corrected visual acuity; n = number of eyes with CNV subtype; ANOVA = analysis of variance.

Table 1

Baseline characteristics of patients with neovascular age-related macular degeneration who satisfied inclusion criteria

Values are presented as mean ± standard deviation or number (%) unless otherwise indicated.

CNV = choroidal neovascularization; RAP = retinal angiomatous proliferation; PCV = polypoidal choroidal vasculopathy; BCVA = best-corrected visual acuity; logMAR = logarithm of minimal angle of resolution; CFT = central foveal thickness; VEGF = vascular endothelial growth factor.

Table 2

Mean changes in BCVA (logMAR) from baseline after intravitreal anti-vascular endothelial growth factor injection

Values are presented as mean ± standard deviation unless otherwise indicated. (a) visual acuity of drop-outs is disregarded (b) visual acuity of drop-outs is carried forward and included in the calculations.

BCVA = best-corrected visual acuity; VA = visual acuity.

^*Wilcoxon signed ranks test. p-value comparing each group to baseline BCVA (logMAR). There was no statistically significant difference in mean BCVA between the cohort without drop-outs and that with drop-outs included (all p > 0.05).

Table 3

Mean changes in central foveal thickness from baseline after intravitreal anti-vascular endothelial growth factor injection

Values are presented as mean ± standard deviation unless otherwise indicated.

CFT = central foveal thickness.

^*Wilcoxon signed ranks test.

Table 4

Association between characteristics and BCVA at 7th year (n = 88)

BCVA = best-corrected visual acuity; logMAR = logarithm of minimal angle of resolution; r = Pearson correlation coefficient.

^*Analysis was performed using Pearson correlation analysis.

Notes

^{Conflicts of Interest} The authors have no conflicts to disclose.

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