There is no information/literature regarding recycling rates of eyedrop containers until now. However, the recycling rate of plastic waste in 2021 was described by the Nature Conservation Union Germany (NABU, Conversio Study, Society for Packaging Market Research, Federal Environment Agency, 2022) with only 60%, i.e., 3.2 million tons of plastic. The recycling rate for paper (packagings) in Germany is specified by the Federal Environment Agency in 2020 with 74,3%, i.e., 13.97 million tons of packaging waste.

In this analysis, we were able to show that the prescription-based therapy of DED (including lubricants) causes a high total waste weight, which also increased substantially between 2016 and 2021. Especially plastic waste volume rose by 189% in these 5 years. Preparations with the ingredients hyaluronic acid, ciclosporin A, and hydrocortisone contributed the largest amounts of total plastic waste. This effect predominantly resulted from rising prescription figures for products containing hydrocortisone, hyaluronic acid, and ciclosporin A. The additional material of the inner packaging of Ikervis®, Vismed®, and Softacort® may have also contributed to this effect.

It is likely that the decrease in prescription rates and waste volume of euphrasia, dexpanthenol, and hypromellose in 2019 and 2020 were the results of the market launch of a new low-dose hydrocortisone product on 27th October 2017. Euphrasia was marketed as an anti-inflammatory eye drop, which soothes the eye when there is irritation as well as redness and allows inflammation to subside (package insert). Hydrocortisone is a potent and effective agent and may be prescribed in low doses as an alternative to euphrasia, dexpanthenol, and hypromellose [21,22,23].

Another interesting finding is the significant and constant increase (p < 0.0001) of the total prescriptions and thus the waste volume of ciclosporin A. Albeit ciclosporin A has long been known to be a safe and effective anti-inflammatory treatment for DED [24, 25], it first gained official market access as a commercially available product for the topic use in DED in Germany on 19th March 2015. The number of prescriptions documents the increasing use of this product. Although ciclosporin A only reached approximately half of the absolute prescription numbers for hydrocortisone, the waste volume for paper and plastic of those two products was not significantly different in the years 2019, 2020, and 2021 (Figure 1B). This is caused by the larger package size of ciclosporin A prescriptions, as the detailed annual PharMaAnalyst data shows (e.g., in 2021 hydrocortisone 128,100 packages with 30 SDU ≙ N1, ciclosporin A 19,200 packages with 30 SDU ≙ N1, and 34,500 packages with 90 SDU ≙ N2; the final amount of SDUs prescribed equals around 3.8 and 3.7 million for hydrocortisone and ciclosporin A, respectively).

As shown in Figure 1D, the paper weight per package does not rise to the same extent as the plastic weight per package for a bigger prescription size. This effect and the annually differing prescription sizes (e.g., increasingly for ciclosporin A N3) explain the different developments in the increase of paper waste compared to plastic waste over the years.

A limitation of our analysis might be, that—in order to calculate an average waste production during 30 days of therapy—we assume that 30 SDU and one MDU are used for 1 month. Possibly, some patients extend the use of SDU/MDU or even use several SDU per day or MDU per month, respectively. Therefore, in a follow-up project in our Dry Eye outpatient clinic, we will evaluate the real period of use and waste volume per 30-day therapy.

Our data show a rising number of prescriptions and waste weight volume. It could be argued that the COVID-19 pandemic might have contributed to the rising prescription numbers. Since currently in PharMaAnalyst there is no post-pandemic data available (currently last year in the database: 2021), we are not able to evaluate whether the COVID-19 pandemic influenced the prescription data. Furthermore, as our data shows steadily increasing prescription rates over 3 years prior to the pandemic, we consider this effect to be negligible.

Another important limitation of our analysis is that only products that are prescribed to patients with statutory health insurance are listed in the PharMaAnalyst database. Over-the-counter products (OTC) that do not require a prescription are not considered. As very few dry eye patients receive drops on prescription we assume, that the real total waste generated by OTC dry eye therapy is probably several times higher. Furthermore, also the analysis of products with a mandatory prescription (hydrocortisone, ciclosporin A) only covers 83 % of the German population. For this reason, we estimate that the total waste generated by products with a mandatory prescription is around 20% higher. Unfortunately, there is no data available about patients in the other insurance groups (private insurance, social welfare recipients, uninsured). In order to gain more information about possible differences in those groups and to collect real-world data about the use, cost, and insurance coverage of DED associated therapy, as well as the waste generated by those products, we already began a prospective cross-sectional study in our subspeciality dry eye clinic.

One further limitation is that the analysis of the number of prescribed packages or daily doses could lead to an overestimate of waste volume due to unfilled prescriptions. Unfortunately, there is no data about the number of unfilled prescriptions via PharMaAnalyst, and to our knowledge, there is currently no way to track the filling of prescriptions in Germany.

As our data clearly shows choosing an MDU can be a simple first step towards limiting the use of resources and the production of waste with DED treatment. Products in MDUs with filter systems have a significantly higher weight than those in MDUs without filter system. Interestingly in the cohort of products analyzed by us, this was observed not only for the plastic weight, but also the paper waste weight. Here, companies have a choice and may easily be able to minimize the use of paper.

QR-coded links to product information would further reduce the use of paper and lead to a more sustainable and environmentally conscious packaging option. Furthermore, to decrease the waste of paper in clinical practice, prescriptions and product information could be transmitted to the electronic medical record and be available to the patients on every PC, smartphone, or connected device. But a more thorough analysis of required resources (e.g. server and electricity) is required first. A balanced approach to dropper bottle choice is also warranted. Products in filterless MDUs require the addition of preservatives, which have other potential detrimental effects on the environment [26]. Using a MDU with an integrated filter may thus be the best compromise in terms of an ecologically sustainable packaging. This analysis of the current state of waste production for the first time provides specific figures on this so far ignored aspect of DED therapy. An ecologically sustainable, climate-neutral ophthalmology is the goal for the coming decades [27]. While the attempt at waste reduction may seem justified, the safety and efficacy of the treatment must remain the primary goal of patient care. To our knowledge, so far, no medical concern of using MDUs with filters compared to SDUs has been reported. A study which compared a single-dose and multi-dose system stated that the convenience of opening and applying eye drops and the number of drops retrieved were substantially better for multi-dose systems [28]. There is evidence that the use of MDUs with filters reduces contamination rates related to insufficient preservatives in MDUs without filters and optimized nozzle geometry. This suggests that MDUs with a filtration system may be superior to MDUs with preservatives but no filter [29, 30].

We hope that our findings can contribute a first step to a sustained reduction in CO2 emissions and reduce negative ecological effects potentially associated with the field of dry eye therapy. Further evidence and research are needed to generate additional knowledge not only on other forms of DED treatment, such as OTC products or single-use devices [31], but also on the impact of high-end diagnostic tools such as tear film interferometers and placido-based devices [32, 33].