Two-Week Central Macular Thickness Reduction Rate >37% Predicts the Long-Term Efficacy of Anti-vascular Endothelial Growth Factor Treatment for Macular Edema Secondary to Retinal Vein Occlusion

Abstract

Objective: To determine if the early response assessments can predict the long-term efficacy of anti-vascular endothelial growth factor (VEGF) treatment for macular edema secondary to retinal vein occlusion (RVO-ME).

Methods: A retrospective study of patients with diagnosis of RVO-ME and intravitreal anti-VEGF treatment was conducted. Clinical characteristics including age, gender, disease subtype and disease duration were recorded at baseline. The best corrected visual acuity (BCVA and logMAR), intraocular pressure (IOP), and central macular thickness (CMT) were recorded at baseline, 2 weeks, and every month (months 1-6) after injection. Further, we compared the early response assessments between the cured group (6-month CMT ≤ 250 μm) and the uncured group (6-month CMT > 250 μm).

Results: A total of 164 eyes in 164 patients (77 male and 87 female) were included. At each post-injection time point, both BCVA and CMT are significantly decreased from baseline (all P < 0.001). Spearman's test showed that 2-week CMT reduction rate after the first injection was negatively correlated with BCVA at 6 months (r = -0.359, P < 0.001). Compared with the uncured group (47 cases), the cured group (117 cases) was younger (59.53 ± 11.68 vs. 65.19 ± 13.10 years old, P < 0.01), had more BRVO patients (76.1% vs. 44.7%, P < 0.01), a shorter disease duration (1.92 ± 2.43 vs. 5.05 ± 4.32 months, P < 0.01), lower baseline CMT (527.09 ± 154.95 vs. 768.96 ± 287.75 μm, P < 0.01), and lower baseline BCVA (0.86 ± 0.44 vs. 1.31 ± 0.51, P < 0.01). At each post-injection time point, the cured group had lower CMT and BCVA values when compared to the uncured group (all P < 0.01), and the 2-week CMT reduction rate was identified as the earliest response time to predict the long-term treatment efficacy. Moreover, ROC curve analysis indicated that a 2-week CMT reduction rate >37% yielded the best cut-off point for predicting the long-term cure of anti-VEGF treatment at 6 months (P < 0.001). Multivariable logistic regression confirmed that the 2-week CMT reduction rate >37% was independently associated with the 6-month cured rate (OR = 9.639, 95% Cl = 1.030-90.227, P = 0.047).

Conclusion: Age, disease duration, baseline CMT, and baseline BCVA are associated with visual outcomes at 6-month of anti-VEGF treatment for RVO-ME. The "2-week CMT reduction rate >37%" after the first injection is an independent factor to predict better long-term outcomes.

Keywords: anti-vascular endothelial growth factor (anti-VEGF); central macular thickness (CMT); early response assessments; macular edema (ME); retinal vein occlusion (RVO).

FIGURE 1

The flow chart of enrolled patients.

FIGURE 2

(A) Comparison of CMT between the monoclonal antibody-treated group and the Fc-fusion protein-treated group. (B) Comparison of BCVA between the monoclonal antibody-treated group and the Fc-fusion protein-treated group. CMT and BCVA (logMAR) are significantly decreased from the baseline in both groups at half-month and 6 months after treatment. **Significant difference compared to the baseline (P < 0.01). However, there is no significant difference in mean CMT and BCVA (logMAR) between the two groups at half-month and 6 months post-treatment (P > 0.05). BCVA, best corrected visual acuity (logMAR). CMT, central macular thickness (μm).

FIGURE 3

Changes in mean BCVA and CMT before and after treatment in all affected eyes. (A,B) The mean BCVA (logMAR) and CMT are decreased significantly after treatment when compared to baseline. **Significant different compared to baseline (P < 0.01). (C) The drop magnitude of mean BCVA (logMAR) is compared to baseline at each observation time point after treatment, and it shows a notable decrease at 2 weeks after the first treatment with a change of 0.34 ± 0.36. (D) The drop rate of CMT at each observation time after treatment. It shows a notable reduction of CMT at 2 weeks after the first treatment, with a drop rate 34 ± 13 %. BCVA, best corrected visual acuity (logMAR). CMT, central macular thickness (μm).

FIGURE 4

Scatter plots of baseline and 6-month BCVA. (A–H) Scatter plots of 6-month BCVA (logMAR) and baseline indexes (age, disease duration, BCVA (logMAR), CMT, gender, disease subtype, and anti-VEGF drug subgroup). Six-month BCVA (logMAR) is strongly correlated with baseline BCVA (logMAR) (C), moderately correlated with baseline CMT (D), and weekly correlated with age (A) and duration of disease (B). Six-month BCVA (logMAR) is not correlated with gender (E), disease subtype (F), anti-VEGF drug subgroup (G), and the number of injections (H). BCVA: Best corrected visual acuity (logMAR). CMT, central macular thickness (μm); VEGF, vascular endothelial growth factor.

FIGURE 5

Scatter plots of the early follow-up indexes and 6-month BCVA. (A–C) Scatter plots of 6-month BCVA (logMAR) and early follow-up indexes (2-week BCVA (logMAR), 2-week CMT, and 2-week CMT reduction rate). Six-month BCVA (logMAR) is strongly correlated with 2-week BCVA (logMAR) after the first treatment (A). Six-month BCVA (logMAR) is moderately correlated with 2-week CMT after the first treatment (B). Six-month BCVA (logMAR) is weekly correlated with 2-week CMT reduction rate after the first treatment (C). BCVA: Best corrected visual acuity (logMAR). CMT, central macular thickness (μm).

FIGURE 6

Comparison of baseline characteristics between the cured group and the uncured group at the 6-month follow-up. There is no significant difference in Gender (F), anti-VEGF drug subgroup (E), and IOP (B) between the two groups. Comparison of the baseline age reveals the age in the cured group is significantly younger than that of the uncured group (t = –2.709, P = 0.007) (A). The cured group has 76.1% of BRVO, while the uncured group has 44.7% of BRVO, and the difference is statistically significant (χ² = 14.957, P < 0.001) (D). The duration of disease in the cured group is notably shorter than that of the uncured group (t = 4.678, P < 0.001) (C). **The difference is statistically significant (P < 0.01). mAb, the monoclonal antibody-based anti-VEGF drugs; Fc, Fc-fusion protein-based anti-VEGF drugs; BCVA, best corrected visual acuity (logMAR); BRVO, branch retinal vein occlusion; CMT, central macular thickness (μm); IOP, intraocular pressure; VEGF, vascular endothelial growth factor.

FIGURE 7

The changes of BCVA and CMT between the cured and uncured eyes before and after treatment. After treatment, the mean BCVA (logMAR) and CMT of the two groups are significantly lower than the baseline (p < 0.01). (A,B) Both mean BCVA (logMAR) and CMT of the cured group and uncured group are significantly lower than those of baseline (P < 0.01). (C,D) The cured group has significantly lower BCVA (logMAR) and CMT values compared with the uncured group at any time point after treatment (P < 0.01). (E) There is no significant difference in the number of injections between the cured group and the uncured group (P > 0.05). (F) The CMT reduction rate in the cured group is significantly higher than that of the uncured group 2 weeks after the first injection (P < 0.01). **The difference is statistically significant (P < 0.01). BCVA: Best corrected visual acuity (logMAR). CMT: Central macular thickness (μm).

FIGURE 8

Comparison of OCT images between one cured patient and one uncured patient before and after treatment. (A–D) panel shows the OCT images of a cured patient before treatment, 2 weeks, 1 month, and 6 months after treatment. (E–H) panel shows the OCT images of an uncured patient before treatment, 2 weeks, 1 month, and 6 months after treatment. It is noted that the CMT reduction in the cured patient is greater than that in the uncured patient 2 weeks after treatment. The CMT in the cured patient is 216 μm (arrow) at 6 months after treatment, versus 541 μm (star) in the uncured patient. CMT, central macular thickness; OCT, optical coherence tomography.

FIGURE 9

ROC curve plot of the 2-week CMT reduction rate after the first treatment and the cure of RVO patients after 6 months follow up (AUC = 0.816, sensitivity = 95.74%, specificity = 48.72%, Youden index = 0.4446, P < 0.001).