Intravitreal Injection Rates for Neovascular Age-Related Macular Degeneration in Australia During the 2020 COVID-19 Lockdowns

ABSTRACT Purpose We investigate the impact of COVID-19 and lockdowns on anti-vascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (AMD) in Victoria (Australian state with highest burden of COVID-19 in 2020) and Australia, by examining anti-VEGF prescriptions supplied for AMD treatment between 2018 and 2020. Methods We performed a retrospective, population-based analysis of aflibercept and ranibizumab prescriptions supplied for the treatment of AMD in Victoria and Australia between 1 January 2018 and 31 December 2020, as recorded by the Pharmaceutical Benefits Scheme (PBS) and Repatriation PBS, the Australian Government program subsidising medication costs for Australian residents and veterans. Poisson models and univariate regression were used to descriptively examine trends in monthly anti-VEGF prescription rates with time and changes in monthly prescription rates (prescription rate ratios [RR]). Results In 2020, anti-VEGF AMD prescription rates in Victoria decreased by 18% during the nationwide lockdown between March and May (RR 0.82, 95% CI: 0.80–0.85, p < .001), and by 24% during the Victorian-specific lockdown between July and October (RR 0.76, 95% CI: 0.73–0.78, p < .001). In Australia, prescription rates tended to decrease between January and October 2020, reducing by 25% (RR 0.75, 95% CI: 0.74–0.77, p < .001) between these months, including between March and April (RR 0.94, 95% CI: 0.92–0.95, p < .001) but not April and May (RR 1.10, 95% CI: 1.09–1.12, p < .001). Conclusion In 2020, anti-VEGF prescriptions for AMD treatment decreased modestly in Victoria during both lockdowns and in Australia during the year. Decreases may represent reduced treatment because of COVID-19, including public health orders, patients’ self-limiting care, and ophthalmologists treating-and-extending to maximum intervals.

Coronavirus disease 2019 (COVID-19) and community lockdowns have caused a decrease in healthcare utilisation. 1 This may impact patients with neovascular age-related macular degeneration (AMD), as timely administration of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment prevents AMD progression and vision loss.In 2020, increasing COVID-19 incidence in Australia led to lockdowns between March and May (all states and territories), and July and October (in Melbourne, Victoria).The state of Victoria experienced the greatest burden of COVID-19 in 2020, with 89% of Australia's 909 deaths. 2 The impact of COVID-19 on anti-VEGF treatment for AMD in Australia remains unknown.This study aimed to explore and compare anti-VEGF treatment prescribed for AMD in Victoria and Australia between 2018 and 2020.
The 2020 Pharmaceutical Benefits Scheme (PBS) and Repatriation PBS (RPBS) Schedule lists aflibercept and ranibizumab for AMD treatment, 3 enabling Australian citizens, permanent residents, and veteranssubsidised access to these treatments.We performed a retrospective population-based study examining aflibercept (PBS/RPBS item numbers 2168D and 12152N) and ranibizumab (item numbers 1382R and 10138N) prescriptions supplied for AMD treatment in Australian states and territories between 1 January 2018 and 31 December 2020, as recorded by the PBS and RPBS.The data accessed and analysed in this study is made available by Services Australia, an Australian Commonwealth Agency. 4The study was conducted in accordance with the tenets of the Declaration of Helsinki and was approved by The Royal Victorian Eye and Ear Hospital Human Research Ethics Committee (reference, 22/1546HL).The requirement for individual consent was waived as the data interrogated are routinely collected and are non-identifiable.Monthly anti-VEGF prescription rates were calculated by dividing aflibercept and ranibizumab total prescriptions supplied each month by Australian Bureau of Statistics' estimated resident population on 30 June 2018-2020.We used univariable Poisson regression to descriptively examine trends and changes in monthly prescription rates (rate ratios) over time, and difference-in-differences (DID) models to compare anti-VEGF prescriptions supplied in lockdown and non-lockdown months in 2020 with their equivalent months in 2018 and 2019.Analyses were performed using Stata/MP 17.0 (StataCorp).
In Australia, anti-VEGF prescription rates for AMD tended to decrease between January and October 2020 (Figure 2), reducing by 25% (RR 0.75, 95% CI: 0.74-0.77,p < .001).Prescription rates increased 55% between October and December 2020 (RR 1.55, 95% CI: 1.53-1.57,p < .001).During the nationwide lockdown, prescription rates decreased between March and April (RR 0.94, 95% CI: 0.92-0.95,p < .001)and increased between April and May (RR 1.10, 95% CI: 1.09-1.12,p < .001).Anti-VEGF monthly supply in Australia ranged from 115-142, 112-185, and 112-174 prescriptions per 100,000 people in 2018, 2019, and 2020, respectively.The total number of anti-VEGF prescriptions supplied for AMD treatment in Australia in 2018, 2019, and 2020 were 372,264, 413,312, and 415,059, respectively, with annual prescription rates (prescriptions per 100,000 people) of 1490, 1629, and 1615, respectively.In 2019, prescription rates increased by 58% between April and May (RR 1.58, 95% CI: 1.56-1.60,p < .001).Using DID models comparing anti-VEGF prescriptions in lockdown months (March-May) and non-  In 2020, anti-VEGF prescriptions for AMD treatment decreased modestly in Victoria during both lockdowns and in Australia during the year.Fewer anti-VEGF prescriptions were supplied in Victoria and Australia during lockdown months than non-lockdown months in 2020 when compared with equivalent months in 2019.Interestingly, a greater number of anti-VEGF prescriptions were supplied during lockdown months than nonlockdown months in Victoria in 2020 than these same months in 2018, which is likely explained in part by the unusually low number of anti-VEGF prescriptions in July 2018 (prescription rate, 44.9 per 100,000 people), the lowest number of prescriptions during the study period.The reasons for the marked decrease in prescriptions supplied in this month, and similarly for the marked increase in prescriptions supplied in May 2019, are ultimately unknown.One possible explanation is a shortage of ranibizumab and/or aflibercept therapies leading to decreases and subsequent rebounds in prescriptions supplied.However, to our knowledge, the Australian Therapeutic Goods Administration only reported a shortage for aflibercept on one occasion during the study period, in November 2020 (non-lockdown month), and this shortage had an impact rating of low (not medium, high, or critical). 5Variation in prescribing behaviours is also possible.
7][8][9] Decreased anti-VEGF prescription rates in Victoria and Australia may reflect reduced AMD treatment as a result of COVID-19, potentially due to public health orders, patients' self-limiting ophthalmic care, and ophthalmologists' decision to treat-and-extend to maximum intervals (as per Royal Australian and New Zealand College of Ophthalmologist COVID-19 Guidelines). 10Increased prescription rates in Australia between October and December 2020 may represent a rebound effect.Additional Australian population-based studies examining AMD treatment rates and visual outcomes during COVID-19 would be useful to both confirm a decrease in AMD treatment and its likely impact on rates of vision loss.

Disclosure statement
None of the authors have any proprietary interests or conflicts of interest related to this submission.

Figure 1 .
Figure 1.Anti-vascular endothelial growth factor intravitreal prescription rates (per 100,000 people) for the treatment of neovascular age-related macular degeneration in Victoria, 2018-2020.
lockdown months in 2020, with equivalent months in 2019 and 2018, there were 15511 and 29729 fewer prescriptions in 2020 than 2019 and 2018, respectively.

Figure 2 .
Figure 2. Anti-vascular endothelial growth factor intravitreal prescription rates (per 100,000 people) for the treatment of neovascular age-related macular degeneration in Australia, 2018-2020.