Real-world treatment outcomes of combined therapy with photodynamic therapy and anti-VEGF injections in patients with polypoidal choroidal vasculopathy: Eperience in a tertiary centre
Author: Siyin Liu (United Kingdom)
Co-authors: Romi Chhabra
Polypoidal choroidal vasculopathy (PCV) is an exudative maculopathy, currently recognised as a phenotype of neovascular age-related macular degeneration (n-AMD) with higher prevalence in Asian and African descent than in Caucasians. The treatment of choice for PCV is controversial. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) has been the predominant treatment for all subtypes of n-AMD including PCV. Photodynamic therapy with verteporfin (PDT) is shown to cause regression of polypoidal lesions. Previous trials demonstrated superior outcomes of combination therapy with anti-VEGF injection and PDT in treatment-naive patients. In practice, the fundoscopic features of n-AMD and PCV may be indistinguishable, OCT and OCT-Angiography can also be of limited value in discerning the two pathologies, indocyanine-green angiography (ICG-A) remains the gold standard imaging modality to confirm definite diagnosis of PCV. But due to the relatively lower incidence of PCV in the Western world, ICG-A is only performed in eyes refractory to anti-VEGF injections and PDT considered as a treatment option. While most previous studies demonstrated efficacy of combination therapy in treatment-naive eyes, this retrospective analysis aims to evaluate the real-world outcomes of PDT for PCV pre-treated with anti-VEGF injections, taking the diagnostic challenge of PCV into consideration.
Single centre retrospective case-series. Patients attending the Macular Treatment Centre, Manchester Royal Eye Hospital, which is a tertiary referral centre for the north west of UK.
We reviewed all consecutive cases of PCV treated with PDT from 1st Jan 2016 to 31st Dec 2019 to enable a minimum 12 months of follow-up after PDT. Data was extracted from the Medisoft electronic patient record system and paper-based records. Eyes with pre-existing non-macular visually-impairing pathology such as glaucoma or cataracts were excluded. Each eye was analysed individually, irrespective of the status and treatment received in the other eye. OCT and OCT-A, but not ICG-A, were routinely performed in all patients at initial consultation. ICG-A was only performed when clinical suspicion of PCV aroused due to sub-optimal response to Anti- VEGF therapy. Baseline data including demographic information, age of onset, initial diagnosis, time to correct identification of polypoidal lesions (diagnostic delay), location of polyps, baseline best corrected visual acuity (BCVA, in EDTRS letter score) at presentation and on the day of PDT and number of anti-VEGF injections per year before PDT were collected. Anti-VEGF injections received by patients included 2.0mg of aflibercept and/or 0.5mg of ranibizumab. Patients were followed-up for at least 12 months after PDT. Outcome measures include BCVA and the numbers of anti-VEGF injections required per year after PDT, disease activity (as assessed by visual acuity and OCT parameters) and anti-VEGF injection regimen. All statistical analyses were performed using SPSS.
61 cases were identified, 5 cases were excluded due to pre-existing visually impairing pathology. Initial diagnosis at presentation included n-AMD (n=39, 69.6%) and CSCR (n=2, 3.6%). The mean (SD) diagnostic delay in these 41 patients (Delayed group) from initial presentation to correct identification of polypoidal lesions was 24.6 months (±21.5). 26.8% (n=15) were however diagnosed as PCV at presentation (Treatment-Naïve group). The mean post-PDT follow-up was 33.9 months (Range: 12 - 81 months). Overall, mean (SD) BCVA letter-score significantly improved from 59.4 (±19.2) letters before PDT to 64.6 (±18.0) at final follow-up visit (p=0.035). In the Delayed group, mean BCVA significantly dropped from 62.2 (±13.4) letters at first presentation to 56.6 (±18.2) letters on the day of PDT, despite anti-VEGF injections (p=0.015), but improved to 62.5 (±17.5) at final follow-up post-PDT (p=0.037); in Treatment-naive group, mean BCVA before PDT was 74.4 (±18.3) and 75.2 (±17.7) at final visit (p=0.803). There was no significant difference in final BCVA between Delayed and Treatment-naive groups (p=0.074). The mean change of BCVA 12-months after PDT was a gain of 6.2 (±12.2) letters. In the Delayed group, the mean (SD) number of anti-VEGF injection administered per year prior to PDT was 10.4 (±6.7), compared to 6.6 (3.9) injections per year after PDT (p=0.002); In Treatment-naive group, the mean number of anti-VEGF injections received per year after PDT was 2.39 (2.45), which was significantly less than those in patients with diagnostic delay (p<0.001). At their final visit, PDT was able to extend anti-VEGF injection regimen to 8-weekly in 27.7% of patients in Delayed group, 10-weekly in 4.3%, 12-weekly in 8.5%, PRN in 8.5%, and no injection required in 23.4%; whilst 27.7% of cases still requiring injection interval less than 8-weekly. In the Treatment-naïve group, after PDT 33.3% of patients only required PRN anti-VEGF injection at their final visit, 55.6% did not require injection, whilst 11.1% of cases still requiring injection interval less than 8-weekly.
There is limited evidence on the efficacy of PDT in treating patients with PCV already receiving regular anti-VEGF injections, as most existing studies focus on assessing the efficacy of PDT in treatment-naïve patients. Our study demonstrates that in eyes with PCV receiving anti-VEGF injections, PDT was able to improve BCVA and reduce the injection burden, even after a period of diagnostic delay. It also highlights that in case of strong clinical suspicion, if ICGA performed at the outset and PDT performed, the number of anti-VEGF injections required can be significantly reduced. Our experience provides real-world evidence that supports the use of combination treatment with ICGA guided PDT in association with anti-VEGF in PCV.
Secretariat Address European Society of Retina Specialists Ground Floor, The Apex Building Blackthorn Road
Sandyford Business Park
Co Dublin, D18 H6K2