The current study showed that the FT decreased significantly 2 h after IVR injection in patients with DME. Welch et al.  previously reported that the FT decreased significantly 1 to 2 h after intravitreal injection of bevacizumab (IVB) (Avastin, Genentech Inc., South San Francisco, CA) in seven patients with DME and two patients with exudative age-related macular degeneration (AMD). Those investigators reported a significant decrease in OCT thickness within 2 h after injection. Although they used a different anti-VEGF drug (bevacizumab) in patients with DME and AMD, the results agree with the current findings.
We observed a significant positive correlation between the ΔFT-2 h and ΔFT-1 m (Fig. 3). The current results suggested that we can predict the FT 1 month after an IVR injection by measuring the FT as early as 2 h after the IVR injection. Unfortunately, the long-term effect of IVR remains unknown due to the current short follow-up period. Therefore, we could not conclude definitively if the short-term effects of an IVR injection is correlated with the long-term effects more than 1 month after an IVR injection administered to treat DME. Further study with a longer follow-up period is warranted to examine whether the long-term effects of an IVR injection can be predictable based on the short-term effects.
Moreover, there was a significant correlation between the ΔVA-1d and ΔVA-1 m (Fig. 4), suggesting that it is possible to predict the BCVA 1 month after treatment by measuring the BCVA 1 day after IVR injection. Ma et al. reported that the FT 1 h after IVB injection significantly decreased compared with baseline and that a reduction in the FT 1 h after IVB was correlated significantly with the reduction in the central macular thickness 1 month after IVB injection in patients with both DME and macular oedema after branch retinal vein occlusion (BRVO) (total of 30 eyes). The authors speculated that the FT 1 month after treatment might be predictable by measuring it a few hours after IVB injection .
We found a significant correlation between the baseline FT and the FT at 1 month. It was reported that the baseline FT might predict the structural outcomes in response to IVR therapy . There also was a significant correlation between the baseline BCVA and the BCVA at 1 month. As previously reported, the baseline BCVA might predict the functional outcome after IVR therapy [9, 11]. Taken together, we speculated that measuring the efficacy as early as 1 day after an IVR injection in patients with DME might be predictive of the structural and functional effects of the IVR injection in addition to the prediction from the baseline FT and BCVA. In contrast, there was no significant (p = 0.06) correlation between the baseline BCVA and the ΔVA-1 m. However, eyes with a low baseline VA tended to have a large increase in the ΔVA-1 m in the current study as previously reported .
Previous major clinical trials have reported that the VA improvements from baseline tended to be associated with reductions in the FT from baseline [2, 3, 9, 10, 17]. Indeed, there was a significant (r = 0.48, p < 0.05) correlation between the ΔFT-1w and ΔVA-1w in the current study. Another clinical study with a large number of patients is needed to confirm the correlation between the improvements in BCVA and improvements in FT.
Pro re nata (PRN) regimens guided by VA have been reported to be effective for treating DME [3, 10, 18, 19]. However, patients might be undertreated based on OCT findings in treat-and-extend protocols . In order to choose adequate injection regimens, the ability to gauge the required treatment intensity might be helpful. The results of the current study indicated that the short-time change could help with this and predict the long-term response.
We recently determined the efficacy of IVR injections in patients with macular edema due to BRVO . In BRVO, the FT decreased significantly at 2 h, 1 day, 1 week, and 1 month after IVR injections, the same as in the current report. Although the baseline FT differed (522 ± 131 μm vs 452 ± 77 μm, BRVO vs DME, p = 0.049), the ΔFTs were significantly higher in BRVO compared with DME at 1 day, 1 week, and 1 month after IVR injections if the ΔFT was divided by the baseline FT (p < 0.001, by the two-way ANOVA and Sidak multiple comparisons test) (data not shown). We speculated that those differences in the efficacy of IVR injection between DME and BRVO might have resulted from the differences in the mechanisms of the macular edema. Campochiaro et al. reported that several cytokine levels in the aqueous humor differed between DME and the macular edema after BRVO . Further clinical studies including additional measurement of the intraocular cytokine levels in eyes treated with IVR injections are needed to clarify the differences between DME and macular edema after BRVO. We also believe that measuring the short-term effects of IVR injection is useful not only to predict the efficacy but also to consider the difference in the mechanisms of macular edema between DME and BRVO.
The current study had some limitations. First, the number of patients in this case series was too small to perform a subgroup analysis. Another larger clinical study is needed. Second, the current follow-up period was short and another clinical study with a long follow-up period is necessary to determine whether or not the short-term effects of an IVR injection on the BCVA and FT are correlated with the long-term effects of the IVR injection on the BCVA. Third, the current study had no control group. We could not exclude the influences of the natural disease course or the effects of previous treatments more than 10 weeks before IVR injection on the current results. It was reported that retinal thickness measurements vary over the course of a day . In the current study, we could not evaluate the effect of circadian fluctuation and the reproducibility and variations in the retinal thickness measurements in both healthy subjects and patients. Another clinical study that includes a control group and repeated measurements is needed.