Optimal Management of Polypoidal Choroidal Vasculopathy
Polypoidal choroidal vasculopathy (PCV) is a exudative neovascular maculopathy that is more frequently seen in Asian and Pacific individuals. There is some controversy if this is considered as a variant of neovascular age related macula degeneration (nAMD).
Early recognition of PCV from standard nAMD is important as there are some important differences in the management of these two conditions.
Identifying PCV from fundal examination and OCT imaging
The gold standard diagnosis of PCV is by indocyanine green angiography (ICGA). However, this is an invasive test and is not always easily available in general clinics. Interpretation of ICGA requires specialist expertise as well. Although ICGA is available in Retina Specialists, it is not feasible to perform ICG angiography in every single patient with nAMD to exclude PCV.
There are now two papers from the Asia-Pacific Ocular Imaging Society PCV Workgroup looking at non-ICGA features of PCV as diagnostic criteria. The first paper looks at patients with treatment naïve PCV. In these cases, sub-retinal pigment epithelium (RPE) ring-like lesion, en face OCT complex RPE elevation, and sharp-peaked pigment epithelium detachment (PED) individually have the highest predictive values and the highest inter-grader agreement in all the features studied. By combining these 3 features, it achieves an area under the receiver operating characteristic curve (AUC) of 0.9, corresponding to sensitivity of 0.75, specificity of 0.91, positive predictive value (PPV) of 0.93 and negative predictive value (NPV) of 0.68.
However, many patients with possible PCV have already been treated with anti-VEGF injections, and the above criteria may not apply. This group has published a second paper looking at the patients with treated PCV. The diagnostic criteria is slightly different in treated PCV patients, with the top performing features (in order of performance) being sharp peaked PED, sub-RPE ring-like lesion, and orange lesion on colour fundoscopy. This accounts for the fact that 30-40% of polyps (which appears as sub-RPE ring-like lesion) and complex PED can decrease in size following anti-VEGF therapy. Combination of these 3 features achieved an AUC of 0.85 with sensitivity 0.65, specificity 0.82, PPV 0.68 and NPV 0.88.
This second report also looks at the utility of using OCT features to guide photodynamic therapy (PDT) in PCV. There is good agreement between the treatment areas derived from OCT and ICGA. 100% of the polyp area and 91% of the branching vascular network area are found to be covered by the OCT derived treatment area.
EVEREST vs PLANET – the role of PDT in the treatment of PCV in the era of anti-VEGF
There are two seminal studies looking at the role of PDT, in combination with anti-VEGF injections, in the treatment of PCV. There are significant difference in the design of these two studies so one must be mindful of the nuances when comparing their results.
| 12 Month Results | Visual Acuity | Number of Injections | Polyp Closure Rate |
|---|---|---|---|
| EVEREST II | |||
| Ranibizumab only | +5.1 | 7.0 | 34.7% |
| Combination | +8.3 | 4.0 | 69.7% |
| PLANET | |||
| Aflibercept only | 10.7 | 8.1 | 31% |
| Combination | 10.8 | 8.1 | 38% |
EVEREST and EVEREST II (first year report here, second year report here) compare ranibizumab (lucentis) alone against ranibizumab (lucentis) with PDT at baseline for the management of PCV (note there was a PCV only group in EVEREST, but this was dropped in EVEREST II as this group did poorly). Ranibizumab was given once every 4 weeks for first three injections, then as required. PDT was performed in baseline for the PDT + ranibizumab group, then every 3 months as required.
The result showed non-inferiority of the PDT + ranibizumab group in terms of visual acuity as compared to ranibizumab only group (8.3 vs 5.1 letters gain in one year). The PDT + ranibizumab group also has a higher rate of polyp closure (69.3% vs 34.7%) and less number of injections (4.0 vs 7.0) in the first year. The same result persists to the year 2 of the study.
In contrast, the PLANET study (first year report here, second year report here) compares aflibercept (eylea) alone and aflibercept + rescue PDT in the treatment of PCV. Patients all received 3 loading dose of aflibercept every 4 weeks at the start of the study. For those whom did not respond adequately received either sham or actual PDT in accordance to their group, and also continued with aflibercept every 4 weeks until response is adequate. Otherwise, if the initial response was adequate, patients were given aflibercept every 8 weeks for the entirety of the study.
The visual acuity result of this study is excellent with no difference between the two groups (10.7 and 10.8 letter gain for aflibercept and aflibercept + rescue PDT group respectively). However, this study has underestimated the effect of PDT as only 12-14% of patients would have qualified from rescue PDT under the study protocol. This study reported the proportion of patients with complete absence of polyp as 38.9% for aflibercept group and 44.8% for aflibercept + rescue PDT group. Given only 89% of patients in this study had polyps at baseline, the polyp closure rate is 31% for the aflibercept group and 38% in the aflibercept + rescue PDT group. The mean number of injections for the first year was 8.1 for both groups. Similar results were reported in year 2 of this study.
Implication for practice
An awareness of non-ICGA criteria of PCV is crucial to recognize PCV in patients with suspected nAMD poorly responsive to treatment.
It is clear from these two studies that the polyp closure rate is higher with PDT, and this translates to a lower injection demand. This association is clear in the EVEREST and EVEREST II studies, and there is a trend to lower number of injections with PDT therapy in PLANET. The difference in visual acuity outcome between PLANET and EVEREST II is likely due to prn dosing strategy, which appears to be inferior to regular treatment or treat and extend strategy.
The role of PDT as an adjunct for polyp closure is echoed in the APOIS report, as the branching vascular network component of PCV can be controlled by anti-VEGF therapy.