In this study, we used OCTA to study the evolution of neovascularization in PDR after PRP therapy throughout 6-month follow-up period. It was demonstrated that the NVE regression started as early as 1 week following the first PRP session and lasted at least for 3 months.
PRP has been recommended in the latest Diabetic Retinopathy Clinical Guidelines released by American Academy of Ophthalmology in 2017[8] as the primary treatment of PDR. However, this destructive treatment may be associated with side effects such as pain, transient blurring, macular edema and loss of peripheral or night vision. Although it has been recommended by ETDRS to repeat PRP sessions from 3 months on in PDR patients[4], treatment regimens including interval between sessions and timing of additional laser varied across different studies. In this context, precise quantification of retinal NV area may be crucial for evaluating the efficacy of treatment regimens. Several authors have used FFA to investigate NV changes at 1 ~ 12 months after PRP, but the invasive nature and dye leakage related with FFA hindered frequent and accurate measurement of NV area[9–11]. With the recent availability of OCTA, retinal NV could be regularly followed up at short intervals. Russell JF et al imaged the NV in PDR patients from 1 week to 3 months after PRP with both FFA and OCTA, supporting the use of OCTA for longitudinal evaluation of NV[12]. In the current study, NVE size was serially measured at 7 timepoints, and to our knowledge, this is the first study that has used OCTA to describe in detail the evolution of retinal NV during and after PRP sessions.
Our findings suggest an early and relatively durable response of retinal NV to PRP therapy in treatment-naïve PDR patients, that is, a significant regression of NVE can be detected as early as 1 week after the first PRP session and lasted until 3 months, and significant changes of NVE occurred from baseline to post-1st PRP. Therefore, if one wants to decide whether a retinal NV is responsive to PRP therapy, one could make this determination as early as 1 week after the first session. In addition, if one wants to re-treat retinal NV with additional laser when the therapeutic response is starting to wear off, one may need to wait for at least 3 months, which is consistent with the recommendations by ETDRS. If local intensive laser treatment for NVE was added to these patients as ETDRS prescribed, more significant NVE regression could be anticipated. Unlike the significant regression of NVE, BCVA in our patients showed no evident improvement except at 3 months, which may be due to the inevitable side effects related with laser. However, BCVA in these patients was not significantly worsening during PRP sessions, and BCVA at 6 months was still comparable with baseline, suggesting that laser regimen in this study was reasonable and effective in regressing NV and avoiding side effects as well.
Previous studies of FFA evaluating the response of retinal NV to PRP observed that anti-NV effect of PRP could last no more than 6 months[9–11], which is in line with the current study and suggests a relatively durable response of retinal NV to PRP treatment. As OCTA is a new imaging modality, it has been used by few authors to observe NV changes after PRP treatment. Russell JF et al imaged the NV in 20 eyes from 1 week to 3 months after PRP using both FFA and OCTA and reported similar progression or regression of NV with both methods[12]. Fawzi AA et al found that PRP has increased macular blood flow which could be measured by several OCTA parameters[13]. Our study firstly evaluated the NV changes during PRP sessions and demonstrated a very quick response of NV to PRP in treatment-naïve patients, supporting the use of PRP as primary treatment in such patients. Moreover, the comparison between two adjacent timepoints further demonstrated the short-term and long-term effect of PRP. Laser was administered on the nasal side during the 1st PRP session, which might cover more NV around the optic disc and should be the reason why more significant NVE regression was observed after this session. On the contrary, the increase of NVE area between 3 months and 6 months suggested that additional laser should be considered during this period.
OCTA was used in this study to establish the changes of NVE over time following PRP treatment. We found that NVE area could be rapidly quantified on OCTA, and it was feasible to follow up patients at short intervals without concern for potential FFA-related adverse events. Therefore, OCTA could be a useful imaging modality in monitoring the efficacy of treatment regimens in PDR patients, which reinforces the results obtained by Russel JF et al[12]. Since it was reported that 60% of patients with PDR responded to PRP treatment with NV regression within 3 months[11], OCTA could be potentially used in the irresponsive cases to monitor the changes of NV for the reference of treatment regimens such as timing of additional laser and combination of other treatment.
This pilot study has several limitations. First, the small sample size and relatively short follow-up period did not allow a comprehensive evaluation of NVE changes following PRP treatment. Further studies to analyze larger datasets are needed to reinforce our results. A second limitation is that the observation of NVE was restricted within a narrow field of view and peripheral NVE could not be visualized. The development of OCTA imaging such as wide-angle display should address this concern. Third, OCTA images may be also affected by several types of artifacts. Although images with severe artifacts affecting the measurement have been excluded, the potential effect of some artifacts should be carefully evaluated. Some authors have adjusted the image size according to individual axial length[7]. Axial length correction was not performed in this study because all included cases had a refractive errer less than ± 3.0D, but this might have an impact on the area calculation of new vessel area. NVE area in this study was automatically calculated using the Angiovue software through multiplying the number of pixels for which the decorrelation value was above that of the background. This was dependent on the image quality and might influence the repeatability of measurements in some cases. The leakage of new vessel could not be identified with OCTA as with FFA, thus the activity of NV could be not being directly evaluated, and the presence of residual vessels on OCTA may or may not correlate with activity or risk of vision loss. Therefore, in cases with persistent NV on OCTA, FFA is warranted to assess its activity, and the prognosis of such blood vessels needs further investigation. In one of our cases, shrinking NVE was present on OCTA image of one year after PRP, but no fluorescein leakage was observed on FFA at the same time (Fig. 3), suggesting that endothelial cells of these residual blood vessels may have improved even normal function. However, the prognosis of such blood vessels is still unclear and needs further observation.