ABSTRACT
BACKGROUND: Under the influence of the COVID 19 pandemic and the lockdown in Germany, there were significantly fewer consultations in almost all medical disciplines. Especially given the need for consistent treatment and follow-up of nAMD patients, this can have far-reaching consequences for visual function, especially in elderly patients. METHODS: In a retrospective analysis of nAMD patients, the number of visits (IVI or follow-up), OCTs or IVIs performed and the mean worst visual acuity for the period before and after the first COVID 19-associated lockdown were compared in a portal-based collaboration of 50 eye care practices. Patients were treated according to the pro re nata (PRN) regimen that included intravitreal injection of VEGF inhibitors based on activity criteria in the OCT follow-up. RESULTS: A total of 34,660 visits from 55 months were included in the analysis. Before lockdown (16 March 2020), an average of 81.8% ± 2.1% of patients were regularly checked or treated (every 4 to 5 weeks). With the onset of lockdown, the proportion of patients receiving optimum treatment dropped to 64.0%. Initially, the proportion of OCT follow-ups decreased from 48.4% to 30.9% and, with a delay, the proportion of injections decreased from 57.5% to 45.8%. This was also reflected in the number of OCT follow-ups: 15.5 before, 11.4 during and 17.2 after lockdown (p < 0.001). In 29% of cases, an individual worsening of visual acuity by more than 0.1 logMAR after the end of the lockdown compared to before the lockdown could be observed. On average, mean visual acuity decreased significantly by 0.054 logMAR (p < 10-11). This significant impairment was not reversed again during the remaining observation period, although the number of visits, OCT examinations and IVIs in the following 12 months were at the pre-lockdown level. CONCLUSIONS: The pandemic-related lockdown resulted in unintended treatment breaks in nAMD patients receiving IVI therapy. The decrease in visits as well as in IVIs caused a loss of visual function in the observed cohort. The consistent treatment regimen of nAMD patients was resumed shortly after the lockdown with an immediate normalization of the number of OCT examinations and IVIs. However, a permanent loss of visual function was observed, and this did not improve within a year after the lockdown. This finding highlights the importance of better case management, leading to improved patient adherence in the event of further waves of COVID or other pandemics.
ABSTRACT
Generalized arterial calcification of infancy (GACI) is a rare disorder caused by ENPP1 or ABCC6 variants. GACI is characterized by low pyrophosphate, arterial calcification, and high mortality during the first year of life, but the natural course and possible differences between the causative genes remain unknown. In all, 247 individual records for patients with GACI (from birth to 58.3 years of age) across 19 countries were reviewed. Overall mortality was 54.7% (13.4% in utero or stillborn), with a 50.4% probability of death before the age of 6 months (critical period). Contrary to previous publications, we found that bisphosphonate treatment had no survival benefit based on a start-time matched analysis and inconclusive results when initiated within 2 weeks of birth. Despite a similar prevalence of GACI phenotypes between ENPP1 and ABCC6 deficiencies, including arterial calcification (77.2% and 89.5%, respectively), organ calcification (65.8% and 84.2%, respectively), and cardiovascular complications (58.4% and 78.9%, respectively), mortality was higher for ENPP1 versus ABCC6 variants (40.5% versus 10.5%, respectively; p = 0.0157). Higher prevalence of rickets was reported in 70.8% of surviving affected individuals with ENPP1 compared with that of ABCC6 (11.8%; p = 0.0001). Eleven affected individuals presenting with rickets and without a GACI diagnosis, termed autosomal recessive hypophosphatemic rickets type 2 (ARHR2), all had confirmed ENPP1 variants. Approximately 70% of these patients demonstrated evidence of ectopic calcification or complications similar to those seen in individuals with GACI, which shows that ARHR2 is not a distinct condition from GACI but represents part of the spectrum of ENPP1 deficiency. Overall, this study identified an early mortality risk in GACI patients despite attempts to treat with bisphosphonates, high prevalence of rickets almost exclusive to ENPP1 deficiency, and a spectrum of heterogenous calcification and multiple organ complications with both ENPP1 and ABCC6 variants, which suggests an overlapping pathology. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.
