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

Abstract

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.

Zusammenfassung

Hintergrund Der Vascular endothelial Growth Factor A (VEGF-A) ist der am häufigsten vorkommende Subtyp der VEGF-Gruppe und spielt u. a. eine wichtige Rolle in der Homöostase der Augenoberfläche und Regeneration der Hornhautnerven. Aktuelle Studien zeigen, dass eine wiederholte intravitreale Anti-VEGF-Injektionstherapie eine Reduktion der Nervendensität in der Hornhaut verursachen kann; dies kann zur Störung der kornealen Homöostase und dadurch zum trockenen Auge führen. Als Therapiemöglichkeiten des trockenen Auges, die das VEGF-A beinhalten, steht das Eigenblutserum (EBS) und Plasma rich in Growth Factors (PRGF) zur Verfügung. Das Ziel dieser Studie ist die Konzentration des VEGF-A in EBS und PRGF zu messen und zu vergleichen.

Material und Methoden Es wurde 2-mal eine Blutentnahme jeweils im Abstand weniger Tagen bei 10 gesunden Probanden durchgeführt, sodass insgesamt 20 Blutproben für die Herstellung von EBS und PRGF gewonnen wurden. Die Konzentration des VEGF-A wurde in Triplikaten mittels einer automatisierten Immun Assay Simple Plex gemessen.

Resultate Die Konzentration des VEGF-A zeigte eine interindividuelle Variabilität; in allen 20 Proben wurde eine signifikant höhere Konzentration des VEGF-A im EBS gemessen, im Vergleich zum PRGF (Mean 238,7 ± 146,6 pg/mL vs. 67,4 ± 46,3 pg/mL). Die Varianzanalyse ANOVA zeigte einen Unterschied des Means der VEGF-A-Konzentration zwischen EBS und PRGF von 168,1 pg/mL (95%-Konfidenzintervall: 142,4 – 193,9; p < 0,001).

Schlussfolgerungen Unsere Studie hat gezeigt, dass die Konzentration von VEGF-A im EBS höher ist als im PRGF. Dieses Ergebnis könnte einen wichtigen Hinweis geben in Bezug auf die Wahl der potenziellen Therapie des trockenen Auges, vor allem bei der neuropathischen Keratopathie, die nach wiederholten intravitrealen Anti-VEGF-Injektionen oder im Rahmen eines Sjögren-Syndroms auftreten kann. Hier kann es zu einer reduzierten VEGF-A-Konzentration im Tränenfilm und dadurch Störung der kornealen Homöostase kommen. Ob das Supplementieren des VEGF-A in Form von Augentropfen die korneale Homöostase wiederherstellen kann, sollte in weiterführenden, randomisiert kontrollierten Studien untersucht werden. Aufgrund der höheren VEGF-A-Konzentration wäre das EBS für solche Untersuchungen und Studien zu bevorzugen.

Key words

cornea - conjunctiva - lids

Schlüsselwörter

Kornea - Bindehaut - Tränenwege

Publication History

Received: 26 September 2021

Accepted: 06 February 2022

Article published online:
26 April 2022

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