This prospective study investigated the association between the change in FAZ and VD with final BCVA, metamorphopsia and aniseikonia in eyes after surgery for macula-off RRD. We also investigated the evolution of the FAZ and VD during 12 months of follow-up.
This study is the first to investigate the change in FAZ and VD caused by macula-off RRD. Owing to the interindividual variability of FAZ and VD, it is not possible to use one reference value for all patients. Considering the FAZ and parafoveal VD are symmetrical in both eyes in healthy subjects,
33 we used the healthy fellow eyes as a reference and calculated the difference of FAZ, VD, and visual function in the study eye compared with the fellow eye for each patient. We noted that the FAZ difference of the DCP was strongly correlated with BCVA difference. Previous studies which investigated the association between the FAZ in the superficial capillary plexus and DCP with BCVA produced inconsistent results: Bonfiglio et al.
19 and Yui et al.
16 reported strong correlations between FAZ and BCVA, whereas Sato et al.
18 did not find any correlation between the FAZ and BCVA. These inconsistent results may be due to the fact that the values of the study eyes were analyzed without considering the healthy eye as a control. Thus, for future studies it would be of additional value to interpret the OCTA parameter values of the study eye in reference to the healthy eye, to take the interindividual variability of OCTA parameters into account.
We observed a trend of smaller FAZ in the study eyes compared with the healthy control eyes in all three plexuses, but there was no evidence that there was a difference between both eyes for all plexuses. The current literature reports contradicting results regarding the FAZ after surgery for macula-off RRD. One study
19 reported no difference in FAZ between macula-off RRD eyes and control eyes, and two other studies
15,17 reported larger FAZ in macula-off RRD eyes compared with control eyes. These contradicting results can be explained by differences in control groups. Identical to our study, Bonfiglio et al.
19 measured the healthy fellow eye of the macula-off RRD patients as control. This method is appropriate because the FAZ has been shown to be similar in both eyes of healthy volunteers, but varies among individuals.
35 Agarwal et al.
15 compared macula-off RRD eyes to eyes of healthy control subjects and found a larger FAZ in macula-off RRD eyes. It is possible that the difference in FAZ between the study and control group is caused by the variability of FAZ in the groups. The study of Woo et al.
17 included patients with macula-on and macula-off RRD, and, although they measured the healthy fellow eyes as controls, macula-off eyes were compared with the control eyes of both macula-on and macula-off patients. Similar to the study of Agarwal et al.,
15 the observed difference could also be due to the interindividual variability of FAZ.
We hypothesized that the DCP may be upregulated after RRD to provide oxygen to the photoreceptors, resulting in a decreased FAZ and an increased VD. Variations in the two parameters could explain the variation in visual recovery observed in patients with macula-off RRD. The results of our current study partially support our hypothesis. The FAZ difference of particularly the DCP was strongly correlated with the BCVA difference at 12 months after surgery. This finding means that the BCVA is higher when the FAZ in the study eye is smaller compared with the healthy control eye. We also noted that a decrease in FAZ was already present at 6 weeks after surgery, because there was no evidence that the FAZ changed during follow-up. This decrease in the FAZ area may be caused by angiogenesis in the DCP to compensate for the damage caused by RRD. In patients after an ischemic stroke, angiogenesis has been associated with improved functional outcomes, which resulted in interventions to promote angiogenesis in these patients.
36 It is possible that similar pathways occur in macula-off RRD, in which case therapeutic stimulation of angiogenesis in the DCP could be beneficial to photoreceptor regeneration. Hence, stimulation of angiogenesis can be a new possibility of therapeutic intervention to improve visual function outcomes in patients with macula-off RRD.
Another possible explanation for the decrease in the FAZ area is a contraction of the retina, which may occur in RRD eyes.
37 However, retinal contraction would most likely result in macropsia,
38 and the majority of our patients perceived micropsia.
As for the parafoveal VD, there were no differences between the study and control eyes over time and no strong correlation was found between the parafoveal VD difference and BCVA difference. OCTA detects flow but does not provide information about the flow rate,
39 so although the parafoveal VD was unchanged, it is possible that the flow rate was increased in study eyes. Further research is necessary to confirm our hypothesis.
Considering the variation of BCVA in patients after macula-off RRD,
1,2 it would be of additional value to identify early postoperative predictors of final BCVA. We speculated that the FAZ difference of the DCP at 1.5 months postoperatively could serve as an early predictor of final BCVA, because there was no evidence that the FAZ difference of the DCP changed during follow-up, and the value at 12 months postoperatively was associated with final BCVA difference. Unfortunately, our speculation could not be confirmed because additional analyses showed no strong correlation between the FAZ difference of the DCP at 1.5 months and the final BCVA difference.
FAZ and parafoveal VD reached high levels of reproducibility in patients after surgery for macula-off RRD. We expected that the reproducibility would be higher in healthy control eyes, but we found a large variation of average mean absolute deviation for both FAZ and parafoveal VD. This was due to one or two outliers in each series, which had a large impact owing to the small sample size. The outliers were caused by floaters, which resulted in a difference in signal between two consecutive scans. However, there was no evidence that the reproducibility of control eyes was different from study eyes.
This study protocol was initially designed to investigate the correlation between the duration of macular detachment and visual function outcomes.
40 We did not find a correlation between duration of macular detachment and final BCVA in this study, which may seem counterintuitive; animal studies have shown that photoreceptor apoptosis peaks at 2 to 3 days after RD and decreases to a low level 7 days after RD.
21,22 Our inability to determine the exact onset of macular detachment in humans may explain why the results of animal studies do not clearly match those found in clinical studies.
Because the OCTA parameters were the secondary outcome parameters of the study protocol, an a priori sample size calculation was not performed. Therefore, the observed correlations in current study should therefore be interpreted with caution as these results can be an overestimation of the real effect size.
41 However, an estimate based on the results of current study (sample size = 47, r
s = 0.5, one‐sided significance level of α = 0.05) yields a post hoc power of 98% (G*Power, version 3.1.9.6). These results warrant a properly powered study of the association between the FAZ and BCVA in the near future.
The strengths of our study are that it is the largest OCTA study of patients with macula-off RRD in the current literature; the long follow-up; the analysis of the SVP, ICP, and DCP separately; and preoperative OCT to confirm macular status. Furthermore, all postoperative assessments were performed by one investigator.
As for limitations, not all study eyes were pseudophakic and, although the OCTA scan quality was not compromised, cataract may have influenced the VD measurement as well as visual acuity outcome. In contrast, FAZ measurement is more robust and not strongly affected by cataract.
42 Cataract could also interfere with final BCVA. However, all patients were monitored during 12 months of follow-up, which included BCVA measurement and cataract evaluation. Phacoemulsification was performed when cataract was considered to compromise vision. Hence, the interference of cataract on final BCVA was limited.
In addition, reliable visualization of the choroidal blood flow was not feasible with the OCTA used in this study. Including the choroidal blood flow would offer a more comprehensive evaluation of chorioretinal microvasculature.
In conclusion, although FAZ and VD remained stable during 12 months after surgery for macula-off RRD, a smaller FAZ in the DCP is associated with better final BCVA. Our findings suggest that angiogenesis has occurred and is associated with improved BCVA, which may offer new possibilities in therapeutic interventions for patients with RRD.