Workshop on Eye Drops of Human Origin (EDHO) Vienna, Austria, 2022 May
Following a very successful workshop in Zurich 2018 on human platelet lysates (1,2), the Cellular Therapies Working Party decided to continue with bi-annual, intensive scientific workshops focusing on the novel use of blood derivatives in the manufacture of therapeutic cellular therapy products. The main aims of these workshops are to develop consensus guidelines and expert opinions on regulations, methodology and clinical use. Ample time for interactive discussions is an essential component of this format, together with a manageable participant number to facilitate this.
A workshop on Eye Drops of Human Origin (EDHO) was planned originally in March 2020 in Vienna. The workshop was unfortunately cancelled due to the first COVID-19 wave. Thereafter, the working party made additional unsuccessful attempts to organize the meeting but were reined in by the continuing pandemic. Finally, a window of opportunity allowed for the workshop to be held at Billrothhaus, the headquarters for the imperial Medical Society of Vienna, with more than 40 speakers (a hybrid of in person and virtual via video conferencing) and about 40 in-person attendees.
The workshop began with a review of the last ISBT survey carried out by Denese Marks (3). In view of the plethora of production methodology for eye drops, the different regulatory approaches and the emergence of novel products including amniotic membrane, platelet lysate and cord blood derived eyedrops, it was felt that the time was right to conduct another survey, addressing some of these variabilities in more detail.
A beautifully delivered introduction by the anatomist Friedrich Paulsen highlighting the complexity of healthy human tears production set the stage for the rest of the workshop. The functional interplay of different glands in the anterior eye, the multiple layers of tears and the sufficiency of production are all critical to prevent diseases. Sonja Mertsch presented her work on the tissue engineering of lacrimal glands and the secretome of tears. Reinhard Henschler focused on the comparison of the content of healthy human tears to serum and showed that not many parameters in current products matched with healthy human tears. Platelet lysate is one alternative to serum eye drops, and Thierry Burnouf closed the session by elucidating the content of human platelets and platelet lysate.
The second session was an introduction to different eye diseases requiring EDHO demonstrating that despite differences in the pathogenesis of various eye diseases, there are common pathways of inflammation and immunoregulation of the anterior eye which would allow for the use of EDHOs. Diseases such as neurotrophic keratopathy (Phillipp Roberts), GvHD (Tina Dietrich-Ntoukas), dry eye disease and Sjögrens Syndrome (Jutta Horwath Winter) were highlighted and the place of EDHOs in the treatment of these diseases. Unfortunately, current ophthalmological recommendations for the use of EDHO may be too late in the course of the disease and the question arose whether efficacy would be better if used in more early phases of the disease. Such guidelines have been published in the United Kingdom and were elaborated by Saaeha Rauz.
It is well recognized that not all individuals are able to donate autologous eyedrops for use. In addition, there may be advantages to using allogeneic eyedrops, and this was discussed by Christian Gabriel and Birgit Gathof. The general outcome was that allogeneic donations are a promising alternative that needs to be explored, as autologous donors are not always healthy and single donations may not fulfil the minimum requirements for effector substances.
Production methodology for EDHO is certainly a “hot” topic with no international gold standard currently available. Denese Marks described a way to produce serum eye drops in a large blood centre, while Dirk de Korte presented the fully automated system used by Sanquin in the Netherlands. Gerda Leitner gave an insight into the particular problems that smaller production centres face, and how to avoid them. Finally, Mickey Koh (Chairman of the Cellular Therapies Working Party) described the labelling of EDHOs and how ISBT128 can help achieve consistency and harmonization.
Quality standards for EDHO were also discussed and this included issues with small source volume, differences in regulatory requirements for microbiological testing. The advantage of pooled products, which are mainly allogeneic, may have an advantage as reducing inconsistencies as well as the number of tests required, but dedicated pathogen reduction treatment may have to be considered. The comparison with platelet lysates was made by Katharina Schallmoser where consensus recommendations published after the last workshop are now widely accepted.
New developments were part of the next session in which Paolo Rebulla presented eye drops derived from cord blood, and Rita Piteira discussed their results with eye drops from amniotic extracts. Both are getting more attraction in the EDHO environment as they enable new ways of using materials that would otherwise be discarded and from immunologically naïve sources.
In terms of clinical efficacy, promising data is available, but there are very few prospective randomized controlled clinical studies. However, Neera Jagirdar presented encouraging preliminary data from a phase III trial of platelet lysates for patients with ocular GVHD, while Marina Buzzi spoke about cord blood derived allogeneic EDHOs. The session was closed by Piera Versura, who argued that EDHO should be used earlier in the disease course.
One of the most pressing issues with cell-based products is the complex regulatory environment that is present. EDHO may be variously regulated as a blood product, as a drug or even as magistral preparations, which are prepared in a pharmacy for an individual patient. Regulators from Austria, Germany and Italy showed their approaches to regulation of EDHO. All participants concluded that harmonization is required.
The workshop was a very intense meeting lasting 3 days and conducted in a joyful and productive mood. All participants enjoyed the Heurigen (traditional winery serving food and their own locally grown wine) and beautiful Vienna was showcased by the wonderful weather. The working party plans to follow up with publications and a webinar.
- Henschler R, Gabriel C, Schallmoser K, Burnouf T, Koh MBC. Human platelet lysate current standards and future developments. Transfusion. 2019 Apr;59(4):1407-1413
- Schallmoser K, Henschler R, Gabriel C, Koh MBC, Burnouf T. Production and quality Requirements of human platelet lysate: A Position Statement from the working party on cellular therapies of the International Society of Blood Transfusion. Trends in Biotechnology, 2020; 38(1): 13−23.
- Marks DC, van der Meer PF; Biomedical Excellence for Safer Transfusion (BEST) Collaborative. Serum eye drops: a survey of international production methods. Vox Sang. 2017 May;112(4):310-317