Perspectives and Update on the Global Shortage of Verteporfin (Visudyne®).

An ongoing global shortage of verteporfin (Visudyne®) limits the treatment possibilities for several chorioretinal diseases, including central serous chorioretinopathy, choroidal hemangioma, and polypoidal choroidal vasculopathy. Verteporfin is required to perform photodynamic therapy in these ocular diseases. Therefore, the current situation has a substantial impact on eye care worldwide. The worldwide supply of verteporfin appears to be manufactured by a single factory, which is situated in the United States. The distribution of verteporfin is done by different companies for different regions of the world. Official communication on the shortage by the responsible companies has been scarce and over the past years several promises with regards to resolution of the shortage have not been fulfilled. The delivery of new batches of verteporfin is at irregular intervals, unpredictable, and may not be fairly balanced between different regions or countries in the world. To ensure a fair distribution of available verteporfin within a country, several measures can be taken. In the Netherlands, a national committee, consisting of ophthalmologists, is in place to arrange this. On the European level, the European Union and European Medicine Agency have plans to monitor medicine shortages more closely and to intervene if necessary. With a more intensified monitoring and regulation of medicine supplies, future impending shortages may be prevented. Remarkably, the amount of medicine shortages is increasing, having a significant and sometimes irreversible impact on patient care. Thus, efforts should be undertaken to minimize the consequences and, whenever possible, to prevent future medicine shortages.

NOn-Pachychoroid PEripapillary Schisis (NOPPES) of the Retina: A New Phenotype and its Differential Diagnosis.

PURPOSE: The presence of peripapillary intraretinal fluid (IRF) has a broad differential diagnosis, including several types of neovascular and pachychoroid-related diseases. However, the clinician may encounter cases without signs of neovascular or pachychoroid disease, or any other previously described diagnosis. For these patients, we propose the term NOn-Pachychoroid PEripapillary Schisis (NOPPES) of the retina, and we discuss the differential diagnosis. DESIGN: A retrospective chart study set in a tertiary referral center for retinal diseases in Amsterdam, the Netherlands. METHODS: Using multimodal imaging, cases suspected of peripapillary pachychoroid syndrome were reviewed. Cases without signs of neovascular or pachychoroid disease were included in this study. These cases were discussed in a group of senior retinal specialists to establish a diagnosis, and if there was no evidence for any previously described diagnostic entity, these cases were categorized as NOPPES. RESULTS: Four cases of NOPPES were identified, 3 female patients and 1 male patient, aged between 58 and 75 years. Two patients were myopic, and 1 patient had a mild hyperopia. Three out of 4 cases showed unilateral peripapillary IRF, and 1 case had bilateral IRF. No improvement was seen after intravitreal bevacizumab or aflibercept, nepafenac eye drops, oral acetazolamide, vitrectomy with internal limiting membrane peeling, or surgery for carotid stenosis. One case showed a reduction in IRF after starting prednisolone eye drops. CONCLUSIONS: We describe NOPPES, a new form of peripapillary schisis-like IRF. NOPPES seems relatively therapy-resistant. More research is needed to delineate the clinical spectrum of NOPPES and its pathogenesis and treatment.

European Prevalence of Polypoidal Choroidal Vasculopathy: A Systematic Review, Meta-Analysis, and Forecasting Study.

The purpose of this study was to provide an estimate of the number of current and future patients with polypoidal choroidal vasculopathy (PCV) in Europe. We systematically searched 11 literature databases on 18 May 2022 for studies on the prevalence of PCV among a consecutive and representative group of patients with suspected neovascular age-related macular degeneration (AMD). Prevalence of PCV in patients with suspected neovascular AMD was summarized and included in a prevalence meta-analysis. We then used current population data and population forecasts by Eurostat and the Office for National Statistics to determine current and future number of patients with neovascular AMD in Europe. Then, we calculated the number of patients with PCV with our calculated estimate of the prevalence of PCV among Europeans suspected with neovascular AMD. A total of five eligible studies were identified which included a total of 1359 patients. All these studies used the gold standard of indocyanine green angiography as a routine part of their diagnostic approach. Among patients undergoing detailed retinal examination for suspected neovascular AMD, our meta-analysis calculated the prevalence of PCV to be 8.3% (95% confidence interval: 6.8-9.8%). Our population estimates find that a total of 217,404 patients with PCV exist in Europe in the year 2022, which constitutes 0.04% of the entire population of Europe. This number is estimated to increase to 287,517 patients in the year 2040. Our estimates are important for different healthcare stakeholders, especially when planning and allocating expensive resources.

Clinical impact of the worldwide shortage of verteporfin (Visudyne®) on ophthalmic care.

INTRODUCTION: Since July 2021, a worldwide shortage of verteporfin (Visudyne®) occurred: an essential medicine required for photodynamic therapy (PDT). PDT with verteporfin has a broad range of indications in ophthalmology, including chronic central serous chorioretinopathy, polypoidal choroidal vasculopathy and choroidal haemangioma. For these disorders, PDT is either the first-choice treatment or regarded as a major treatment option. MATERIALS AND METHODS: A questionnaire was sent to key opinion leaders in the field of medical retina throughout the world, to assess the role of PDT in their country and the effects of the shortage of verteporfin. In addition, information on the application of alternative treatments during shortage of verteporfin was obtained, to further assess the impact of the shortage. RESULTS: Our questionnaire indicated that the shortage of verteporfin had a major impact on ophthalmic care worldwide and was regarded to be a serious problem by most of our respondents. However, even though there is ample evidence to support the use of PDT in several chorioretinal diseases, we found notable differences in its use in normal patient care throughout the world. Various alternative management strategies were noted during the verteporfin shortage, including lowering the dose of verteporfin per patient, the use of alternative treatment strategies and the use of a centralized system for allocating the remaining ampoules of verteporfin in some countries. CONCLUSION: The shortage of verteporfin has had a large effect on the care of ophthalmic patients across the world and may have resulted in significant and irreversible vision loss. Mitigation strategies should be developed in consultation with all stakeholders to avoid future medication shortages of verteporfin and other unique ophthalmic medications. These strategies may include mandatory stock keeping, compulsory licensing to an alternative manufacturer or incentivizing the development of competition, for example through novel public-private partnerships.

Community-acquired meningitis in adults caused by Escherichia coli in Denmark and The Netherlands.

OBJECTIVES: We aimed to examine risk factors, presenting characteristics and complications of Escherichia coli community-acquired bacterial meningitis in adults. METHODS: Observational cohort study of adults > 16 years of age with cerebrospinal fluid culture-positive E. coli meningitis in Denmark and the Netherlands. Exclusion criteria were primary brain abscess, previous neurosurgery and nosocomial infections. We analysed baseline characteristics, concomitant infections and neurological complications. Outcome was assessed using the Glasgow Outcome Scale score (GOS) at discharge with GOS 1-4 categorised as unfavourable outcome. RESULTS: We identified 36 patients with a median age of 69 years (interquartile range 61-83) of whom 15 (42%) were females. Immuno-compromise was present in 11 (31%) patients. Nineteen (53%) patients had concomitant infections consisting of urinary tract infections in 13 (36%), pneumonia in three (9%) and septic arthritis in two (6%). Bacteraemia with E. coli was found in 26 of 34 (76%) patients. Thirteen patients died (36%) and unfavourable outcome at discharge occurred in 23 (64%). Deaths were attributed to systemic complications in 12 (92%) patients. CONCLUSION: Community-acquired E. coli meningitis in adults is a severe disease that primarily occurs in elderly patients with concomitant infections and an immunocompromised state. Outcome is often poor and mainly caused by systemic complications.