Introduction: The use of blood derivatives and especially Plasma rich in growth factors (PRGF), for regenerative purposes has been a common trend along the last decades in the field of oral surgery, dermatology, orthopedics, and more recently in ophthalmology.
Areas covered: PRGF is a type of platelet-rich plasma that is being explored for the treatment of ocular injuries. The present review article highlights 50 ophthalmology-related publications about the application of PRGF in the treatment of acute and chronic pathologies in ophthalmology as well as most relevant challenges and future prospects.
Expert opinion: PRGF technology provides a wide range of formulations that can be used therapeutically in many different acute and chronic ocular pathologies. In addition to eye drops enriched with autologous growth factors, PRGF enables the preparation of both immunologically safe and fibrin-based formulations. Recent advances in the field have promoted PRGF storage for 12 months under freezing conditions, its daily use for 7 days at room temperature and the freeze-dried formulation. The thermally treated immune-safe formulation has shown promising clinical results for the treatment of several diseases such as Sjögren syndrome, graft versus host disease or cicatrizing conjunctivitis. In addition, several fibrin formulations have been pre-clinically evaluated and clinically incorporated as an adjuvant to ocular surface or glaucoma surgeries, dermal fat graft procedures, limbal stem cell expansion and retinal surgeries. The present review explores the latest scientific and clinical data, current challenges, and main prospects of this technology for the treatment of several ocular injuries.
*PRGF compared with Autologous Serum (Pre-Clinical Evidence):
Anitua E, de la Fuente M, Muruzabal F, Riestra A, Merayo-Lloves J, Orive G. Exp Eye Res. 2015 Jun;135:118-26. doi: 10.1016/j.exer.2015.02.016. Epub 2015 Feb 21. PMID: 25708868.
Conclusion/Findings: “…significant higher levels of all growth factors analyzed in PRGF eye drops compared to AS. Moreover, PRGF eye drops enhanced significantly the biological outcomes of both HK and HConF, and reduced TGF-b1-induced myofibroblast differentiation in contrast to autologous serum eye drops (AS). In summary, these results suggest that PRGF exerts enhanced biological outcomes than AS. PRGF may improve the treatment of ocular surface wound healing minimizing the scar formation compared to AS. Results obtained herein suggest that PRGF protects and reverses the myofibroblast phenotype while promotes cell proliferation and migration.”
*PRGF compared with Autologous Serum and PRP (Pre-Clinical Evidence):
Corneal wound healing promoted by 3 blood derivatives: an in vitro and in vivo comparative study.
Freire V, Andollo N, Etxebarria J, Hernáez-Moya R, Durán JA, Morales MC. Cornea. 2014 Jun;33(6):614-20. doi: 10.1097/ICO.0000000000000109. PMID: 24727633.
Conclusion/Findings: In vitro data show statistically significant differences in the healing process with all the derivatives compared with the control, but 2 of them (AS and s-PRGF) induced markedly faster wound healing. In contrast, although the mean time required to complete in vivo reepithelization was similar to that of AS and s-PRGF treatment, only wounds treated with s-PRGF were significantly smaller in size from 2.5 days onward with respect to the control treatment. …the corneal wound-healing progresses differently with each derivative, being faster in vitro under AS and s-PRGF treatment and producing in vivo the greatest decrease in wound size under s-PRGF treatment.”
*Endoret PRGF: Safety and Efficacy in Ocular Surface Disorders (Clinical Evidence)
Merayo-Lloves J, Sanchez-Avila RM, Riestra AC, Anitua E, Begoña L, Orive G, Fernandez-Vega L. Ophthalmic Res. 2016 Jul;56(2):68-73. doi: 10.1159/000444496. Epub 2016 May 28. PMID: 27229893.
Description: This retrospective study included patients with EDE treated between January 2011 and December 2013. Outcome measures including signs and symptoms of the disease were evaluated before and after treatment. The influence of some of the patient’s clinical variables on results was assessed. Safety assessment was also performed.
Findings & Conclusions: Eighty-three patients with a total of 156 eyes were evaluated. Statistically significant reductions in the Ocular Surface Disease Index (38.2%), best-corrected visual acuity (27.4%), Visual Analogue Scale scores for frequency (32%) and severity (34%), and a significant improvement in the Schirmer test scores (177.5%) were observed (p < 0.05). The results were stratified according to the identified potential effect modifiers. Only four adverse events were reported. All of them were mild and resolved within a few days.
Results suggest that PRGF eye drops could be a safe and effective treatment in reducing EDE signs and symptoms.
*Endoret PRGF: Safety and Efficacy in Ocular Surface Disorders (Clinical Evidence)
Sanchez-Avila RM, Merayo-Lloves J, Riestra AC, Fernandez-Vega Cueto L, Anitua E, Begoña L, Muruzabal F, Orive G. Int Ophthalmol. 2018 Jun;38(3):1193-1204. doi: 10.1007/s10792-017-0582-7. Epub 2017 Jun 15. PMID: 28620707.
Description: This retrospective study included patients with stages 2-3 of NK treated with PRGF eye-drops. Primary endpoint was the resolution time of corneal ulcer defect. Outcome measures including percentage of ulcer closure at 4 weeks, Ocular Surface Disease Index (OSDI), Best-Corrected Visual Acuity (BCVA) and Visual Analogue Scale (VAS) were also evaluated before and after treatment with PRGF. The influence of some patients’ clinical variables on results was assessed. Safety assessment was also performed reporting all adverse events.
Findings & Conclusions: Thirty-eight treated eyes in a total of thirty-one patients were evaluated, of which five cases had no prior response to autologous serum treatment. Most cases (97.4%) achieved the complete resolution of corneal defect/ulcer. Mean resolution time was 11.4 weeks (SD = 13.7). A statistical significant (p < 0.05) reduction in OSDI (60.9%), VAS frequency (59.9%), VAS severity (57.0%) and improvement in BCVA (52.8%) was observed. The results were stratified according to the pathology stage and to the identified potential effect modifiers variables. Only one adverse event was reported in one patient (2.6%).
PRGF eye-drops could be a safe and effective therapeutic option for patients with stages 2-3 of NK, showing high rates of corneal defect/ulcer resolution in short times, either in reducing signs and symptoms of NK, and therefore preventing the progression of NK to greater ocular complications.
