The Lucerne Protocol for the Production of Autologous Serum Eyedrops

Sanak, Frantisek; Baenninger, Philipp B.; Kaufmann, C.; Iselin, Katja; Bachmann, Lucas M.; Buhl, Daniela; Thiel, Michael

doi:10.1055/a-1354-6565

Cited by 5 publications

(8 citation statements)

References 9 publications

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“…The most common method used for VEGF quantification was an enzyme-linked immunosorbent assay (ELISA) from R&D (R&D Systems Inc), which was used in 30 studies [ 41 , 43 , 44 , 46 , 49 , 50 , 53 – 55 , 57 – 59 , 61 – 67 , 69 – 78 , 82 ] ( Table 2 ). Eight studies used a kit for VEGF quantification based on Luminex or Bioplex platforms [ 42 , 45 , 47 , 52 , 56 , 60 , 73 , 80 ], and 12 studies used other commercial or home-brew assays [ 46 , 48 , 51 , 57 , 62 , 68 , 74 , 79 – 83 ].…”

Section: Resultsmentioning

confidence: 99%

“…The impact of centrifugation parameters on VEGF levels was investigated in eight of the included publications [ 42 , 46 , 49 , 53 , 54 , 68 , 71 , 73 ] ( Fig 3C ). Four studies compared VEGF levels depending on the centrifugation time [ 42 , 49 , 54 , 68 ] and six depending on the centrifugal force [ 42 , 49 , 53 , 54 , 68 , 71 ]. Seven studies evaluated plasma samples [ 42 , 46 , 49 , 53 , 54 , 71 , 73 ], and two studies investigated serum samples [ 53 , 68 ].…”

Section: Resultsmentioning

confidence: 99%

“…Four studies compared VEGF levels depending on the centrifugation time [ 42 , 49 , 54 , 68 ] and six depending on the centrifugal force [ 42 , 49 , 53 , 54 , 68 , 71 ]. Seven studies evaluated plasma samples [ 42 , 46 , 49 , 53 , 54 , 71 , 73 ], and two studies investigated serum samples [ 53 , 68 ]. EDTA-plasma was used in five studies [ 42 , 46 , 53 , 71 , 73 ], and citrate-plasma [ 49 , 54 ] was used in two studies.…”

Section: Resultsmentioning

confidence: 99%

“…Three studies [ 42 , 49 , 54 ] reported a change in plasma VEGF levels depending on the centrifugation time while one found no differences for serum samples [ 68 ]. Two [ 42 , 49 ] studies reported higher levels for shorter programs; these studies concurrently changed centrifugation temperature and centrifugal force when assessing the impact of time.…”

Section: Resultsmentioning

confidence: 99%

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A systematic review and meta-analysis of preanalytical factors and methodological differences influencing the measurement of circulating vascular endothelial growth factor

et al. 2022

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Background Intraocular treatment with antibodies targeting vascular endothelial growth factor (anti-VEGF) inhibits pathological vessel growth in adults and preterm infants. Recently, concerns regarding the impact of anti-VEGF treatment on systemic VEGF levels in preterm infants have been raised. Earlier studies suggest that preanalytical and methodological parameters impact analytical VEGF concentrations, but we have not found a comprehensive systematic review covering preanalytical procedures and methods for VEGF measurements. Objective This review aimed to evaluate the most critical factors during sample collection, sample handling, and the analytical methods that influence VEGF levels and therefore should be considered when planning a prospective collection of samples to get reproducible, comparable results. Material and methods PubMed and Scopus databases were searched 2021/Nov/11. In addition, identification of records via other methods included reference, citation, and Google Scholar searches. Rayyan QCRI was used to handle duplicates and the selection process. Publications reporting preanalytical handling and/or methodological comparisons using human blood samples were included. Exclusion criteria were biological, environmental, genetic, or physiological factors affecting VEGF. The data extraction sheets included bias assessment using the QUADAS-2 tool, evaluating patient selection, index-test, reference standard, and flow and timing. Concentrations of VEGF and results from statistical comparisons of analytical methods and/or preanalytical sample handling and/or different sample systems were extracted. The publications covering preanalytical procedures were further categorized based on the stage of the preanalytical procedure. Meta-analysis was used to visualize VEGF concentrations among healthy individuals. The quality of evidence was rated according to GRADE. Results We identified 1596 publications, and, after the screening process, 43 were considered eligible for this systematic review. The risk of bias estimation was difficult for 2/4 domains due to non-reported information. Four critical steps in the preanalytical process that impacted VEGF quantification were identified: blood drawing and the handling before, during, and after centrifugation. Sub-categorization of those elements resulted in nine findings, rated from moderate to very low evidence grade. The choice of sample system was the most reported factor. VEGF levels (mean [95% CI]) in serum (n = 906, 20 publications), (252.5 [213.1–291.9] pg/mL), were approximated to ninefold higher than in plasma (n = 1122, 23 publications), (27.8 [23.6–32.1] pg/mL), based on summarized VEGF levels with meta-analysis. Notably, most reported plasma levels were below the calibration range of the used method. Conclusion When measuring circulating VEGF levels, choice of sample system and sample handling are important factors to consider for ensuring high reproducibility and allowing study comparisons. Protocol: CRD42020192433

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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A systematic review and meta-analysis of preanalytical factors and methodological differences influencing the measurement of circulating vascular endothelial growth factor

et al. 2022

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“…After providing informed consent, 10 healthy volunteers (age 29 – 57years; average 42 years) donated blood on two separate occasions, 2 to 8 days apart. Thus, we processed a total of 20 blood samples according to the following protocols in order to obtain both SED and PRGF 17 , 18 . Levels of VEGF-A were quantified by a Simple Plex platform (ProteinSimple, San Jose, California, USA), which is a fully automated immunoassay system in a highly controlled microenvironment.…”

Section: Methodsmentioning

confidence: 99%

VEGF-A in Serum and Plasma Rich in Growth Factors (PRGF) Eye Drops

Sanak

Baenninger

Iselin

et al. 2022

Klin Monbl Augenheilkd

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Background Vascular endothelial growth factor (VEGF)-A, the most abundant subtype of the VEGF family in the eye, plays an important role in corneal homeostasis due to its ability to mediate corneal nerve repair. Repeated intravitreal anti-VEGF injections were shown to significantly reduce corneal nerve density, which might negatively affect corneal homeostasis and lead to a neuropathic dry eye disease. Currently, there are two effective modalities to treat dry eye while supplying VEGF to the ocular surface: serum eye drops (SED) and eye drops manufactured from plasma rich in growth factors (PRGF). The purpose of this study was to measure the VEGF-A concentration in SED and PRGF eye drops. Material and Methods Ten healthy volunteers donated blood on two separate occasions, 2 – 8 days apart. Thus, a total of 20 blood samples were processed to obtain both SED and PRGF. Concentrations of VEGF-A were quantified by a Simple Plex platform run in triplicate. Results The VEGF-A concentration in SED and PRGF was very similar between the two blood samples drawn from one individual donor but showed substantial interindividual variability. However, in all 20 samples, VEGF concentrations were substantially higher in SED samples (mean 238.7 ± 146.6 pg/mL) compared to PRGF samples (mean 67.4 ± 46.3 pg/mL). Based upon the analysis of variance (ANOVA) model for the measured concentrations with fixed effects for specimen (SED vs. PRGF) and subject, the mean difference between the SED and PRGF concentration was 168.1 pg/mL (95% confidence interval: [142.4, 193.9], p < 0.001). Conclusion Our study showed that the VEGF concentration was higher in SED than in PRGF. This is an important finding, particularly for potential treatment of dry eye disease in patients with neuropathic eye disease, especially in patients that received repeated anti-VEGF intravitreal injections, or in patients with Sjögrenʼs disease, where the level of VEGF in tears might be pathologically decreased. Hypothetically, VEGF might be needed to restore ocular surface homeostasis. Although growing evidence has shown that VEGF-A plays an important role in corneal homeostasis, only a randomized prospective clinical trial will show whether supplying VEGF-A to the ocular surface might successfully restore the corneal homeostasis and overcome the problem of corneal neuropathy in these patients. For such a trial, based on our results, an undiluted SED should be preferred over a PRGF due to the higher content of VEGF-A.

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Five-Year Risk and Safety Profile of Autologous Serum Eye Drop Therapy

Sanak,

Iselin,

Job

et al. 2024

Klin Monbl Augenheilkd

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Purpose To evaluate the risk and safety profile of autologous serum eye drop therapy in clinical routine over a period of 5 years. Methods This retrospective study involved all patients treated with autologous serum between July 2014 and December 2019 at a tertiary ophthalmic referral center. The electronic patient record system was searched for all patients with autologous serum eye drop therapy at any time point. These records were subsequently searched for keywords such as infectious keratitis, corneal ulcer, conjunctivitis, or endophthalmitis at any recorded contact. The probability of an association between the therapy with autologous serum eye drops and infectious complications was investigated independently by three corneal specialists and rated as likely, potential, or unlikely. Results In total, 752 patients were treated with autologous serum eye drops between July 2014 and December 2019. There were 5 384 batches with a total of 107 680 bottles of serum eye drops that had been produced and dispensed for these patients during this period. The records of 291 patient showed a combination of autologous serum therapy and at least one keyword for infectious diseases. In 288 patients, individual case analyses revealed an unlikely association between the therapy and infection, as their infectious episodes occurred either before the start of the therapy, more than 1 month after the therapy ceased, or in the contralateral untreated eye in the case of unilateral therapy. Three cases of infectious keratitis were classified as potentially associated with autologous serum therapy. However, all three patients suffered from chronic anterior eye diseases with a high risk of spontaneous infectious complications independent of therapy with autologous eye drops. None of the infectious events was rated as being likely due to the serum eye drops. Conclusions Serum eye drops are often used in patients with severe or chronic anterior eye diseases with an intrinsic risk of infectious diseases. Despite these preexisting risk factors, autologous serum eye drops can be considered safe, even in patients with a compromised ocular surface.

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The Lucerne Protocol for the Production of Autologous Serum Eyedrops

Cited by 5 publications

References 9 publications

A systematic review and meta-analysis of preanalytical factors and methodological differences influencing the measurement of circulating vascular endothelial growth factor

A systematic review and meta-analysis of preanalytical factors and methodological differences influencing the measurement of circulating vascular endothelial growth factor

VEGF-A in Serum and Plasma Rich in Growth Factors (PRGF) Eye Drops

Five-Year Risk and Safety Profile of Autologous Serum Eye Drop Therapy

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