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Borja de la Sen-Corcuera,1,2 Jesús Montero-Iruzubieta,3,4 Ronald M Sánchez-Ávila,1,5 Gorka Orive,1,2 Eduardo Anitua,1,2 Manuel Caro-Magdaleno,4 Jesús Merayo-Lloves5 1Biotechnology Institute (BTI), Vitoria, Spain; 2University Institute for Regenerative Medicine and Oral Implantology (UIRMI), Vitoria, Spain; 3Clínica Cartujavisión, Sevilla, Spain; 4Hospital Universitario Virgen de Macarena, Sevilla, Spain; 5Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Universidad de Oviedo, Oviedo, SpainCorrespondence: Ronald M Sánchez-ÁvilaInstituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Avda Dres Fernández-Vega Num 34, Oviedo E-33012 Principado de Asturias, SpainTel +34 985240141Fax +34 985233288Email ronald.sanchezavila@gmail.comPurpose: The objective was to evaluate the clinical results obtained from the use of immunosafe plasma rich in growth factors (isPRGF) in the treatment of patients with cicatrizing conjunctivitis (CC) who had not responded to the usual therapy.Patients and Methods: This is a retrospective study that included patients diagnosed with CC, in whom isPRGF was used in different phases (I: eye drops; II: eye drops and injectable; III: eye drops, injectable and surgical treatment) to achieve control of the inflammation. As a clinical follow-up of the patients, the better corrected visual acuity (BCVA), degree of inflammation (measured from 1 to 4), the severity of the CC, Schirmer I test, IOP and TBUT were analyzed. The adverse events were also evaluated.Results: Ten eyes (6 patients) were evaluated, 50% corresponded to Stevens–Johnson Syndrome and 50% to ocular mucous membrane pemphigoid. The mean age was 59.7 ± 16.5 (39– 80) years, and 50% were women. Fifty per cent of the cases were initially considered severe CC, and 10% of the cases (one eye of one patient) were considered severe CC at the end of the treatment (p = 0.046). The initial degree of inflammation was 2 in 4 eyes, 3 in two eyes, and 4 in 4 eyes, and final inflammation degree was 1 in all cases (p = 0.004). Twenty per cent of the cases achieved stability in Phase I of the treatment with immunosafe PRGF, 70% with both Phases I and II, and only one case underwent Phase III to achieve stability. The IOP improved significantly (p = 0.027) though the BCVA, TBUT and Schirmer I test showed no significant changes. The follow-up time was 23.1 ± 6.7 (13.6– 30.3) months. No adverse effects were reported.Conclusion: Treatment with PRGF technology in its injectable and topical immunosafe formulations may be a novel alternative for the treatment of patients with CC, given its complement activity modulating effect, as well as its anti-inflammatory, antifibrotic and regenerative properties.Keywords: immunosafe plasma rich in growth factors, isPRGF, Stevens–Johnson syndrome, ocular mucous membrane pemphigoid, blood derivatives

Background/aims: Corneal endothelial cell loss contributes to transplant failure. Autologous plasma products (APP) activate salvaging pathways that can prevent oxidative stress perioperatively. This study aimed to evaluate the safety of intraoperative incubation of full-thickness corneal grafts in platelet-rich plasma (aPRP) and plasma rich in growth factors (PRGF-Endoret) in mitigating postoperative corneal endothelial cell loss (ECL)., Methods: Pilot study including patients undergoing penetrating keratoplasty (PK) for various indications between June 2021 and December 2022. Patients were randomly assigned to receive either aPRP or PRGF-Endoret incubation, while those who declined intervention served as the control group. Demographic and clinical data were collected, including preoperative and postoperative endothelial cell count, intraocular pressure, pachymetry, and adverse reactions., Results: Thirty individuals who underwent PK completed follow-up: eight from the aPRP group, 10 from the PRGF-Endoret group, and 12 from the control group. No adverse events related to APP treatment were recorded. In the first and third postoperative months, the APP group had significantly lower ECL percentages (37% vs. 25%, p  = 0.02, and 44% vs. 33%, p  = 0.02, respectively); this trend was maintained in the sixth month. When stratified, the PRGF-Endoret group showed significant differences in ECL reduction compared to controls at both time points ( p  = 0.03 and p  = 0.05, respectively). The aPRP group showed a similar statistically significant outcome exclusively on the third postoperative month ( p  = 0.04). APP tended to reduce corneal edema faster than controls. Hexagonality was significantly better in the APP groups in the first and third months, particularly in the PRGF-Endoret group ( p  < 0.005)., Conclusion: Preoperative incubation with APP is safe and promotes better endothelial cell quality and quantity in the early postoperative period following PK. These findings suggest a potential clinical benefit in enhancing graft outcomes and warrant further investigation., Competing Interests: EO: J&J, Alcon, and Allergan. BS-C and EA: BTI-health. AS: Brill Pharma, Abbvie, and GlaxoSmithKline. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mercado, Hernández, Lopez-Rojas, De La Sen-Corcuera, Anitua, Barraquer, Gutiérrez, Otero and Sabater.)

Purpose: In the last few decades, several blood derived products such as platelet-rich plasma (PRP), plasma rich in growth factors (PRGF) and autologous serum (AS) have been used for the treatment of ocular surface disorders. Recently, insulin has been proposed to be used as an alternative for the treatment of ocular surface diseases. The aim of this study was to evaluate the biological potential of PRGF eye drops in comparison with AS and insulin on ocular surface cells., Methods: Blood from three healthy young donors was collected to obtain autologous serum (AS) eye drops and plasma rich in growth factors (PRGF) eye drops. Insulin (Actrapid ® ) was diluted at 1 and 0.2 IU/mL. The biological potential of PRGF, AS and insulin was assessed by proliferation in HCE, HK and HConF cells. Wound healing assay was performed in HCE cells after incubation with the different treatments. HConF and HK cells were differentiated to myofibroblast after treatment with 2.5 ng/mL of TGF-β1 and then incubated with all treatments., Results: PRGF eye drops induced significantly higher proliferation rate compared to AS or insulin in HConF and HK cells, but not in HCE cells. In addition, the percentage of wound healing area was significantly reduced after PRGF treatment in comparison with AS or insulin treatment. Furthermore, PRGF significantly reduced the number of myodifferentiated cells compared to AS and insulin at both concentrations analyzed., Conclusion: The results obtained in the present study show that PRGF increases the biological activity of the ocular surface cells and reduces the expression of fibrosis marker compared to insulin or AS., Translational Relevance: The present study suggests that plasma rich in growth factors eye drops are a more effective therapy than insulin and autologous serum eye drops for the treatment of ocular surface diseases.

The aim of this study was to evaluate the use of PRGF (plasma rich in growth factors) as an adjuvant to PPV (pars plana vitrectomy) in recurrent, persistent, or poor prognosis MH (macular hole). Patients with MH were treated with PPV plus adjuvant therapy (PRGF membrane (mPRGF) and injectable liquid PRGF (iPRGF)). The anatomical closure of MH and postoperative BCVA (best-corrected visual acuity) were evaluated. Eight eyes (eight patients) were evaluated: myopic MH (MMH, n = 4), idiopathic MH (IMH, n = 2), iatrogenic n = 1, traumatic n = 1. The mean age was 53.1 ± 19.3 years. Hence, 66.7% ( n = 4) of patients previously had internal limiting membrane peeling. Five patients (62.5%) received mPRGF and iPRGF, and three patients (37.5%) received iPRGF. Gas tamponade (C3F8) was placed in seven cases and one case of silicone oil. Anatomic closure of MH was achieved in seven eyes (87.5%) and BCVA improved in six cases. In the MMH group, visual acuity improved in two lines of vision. Follow-up time was 27.2 ± 9.0 months. No adverse events or MH recurrences were recorded during follow-up. The use of PRGF as an adjuvant therapy to PPV can be useful to improve anatomical closure and visual acuity in MH surgery.

Purpose: To review safety and efficacy of combined plasma rich in growth factors (PRGF) eye drops and scleral contact lens (SCL) therapy in patients with ocular surface disease., Methods: Patients with ocular surface disease of various etiologies were screened for at least 3 months of concurrent treatment with PRGF and SCL. Retrospective pre- and post-treatment measurements were collected, including patient satisfaction, severity and frequency of dry eye symptoms measured by a modified Symptom Assessment in Dry Eye (SANDE) questionnaire, visual acuity, and number of concurrent treatments., Results: 26 patients with ocular surface disease were included in the study with 20 patients answering the questionnaire (77% response rate). There were no adverse events reported. Most patients thought the combined therapy was better than previous treatments and would recommend to others (80%, 90% respectively). SANDE scores significantly decreased after use of concurrent therapy. There was a small but significant decrease in the number of other concurrent treatments. Visual acuity was unchanged., Conclusions: This retrospective cohort study found PRGF used in combination with SCL is safe and significantly decreases symptoms in patients with recalcitrant ocular surface disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This prospective and comparative study aimed to compare the use of a conjunctival autograft (CAG), plasma rich in growth factors fibrin membrane (mPRGF) or amniotic membrane transplantation (AMT) in primary pterygium surgery. Patients were assigned for surgery with CAG (group A), mPRGF (group B), or AMT (group C). Pterygium recurrence, Best Corrected Visual Acuity (BCVA), graft size (measured with anterior segment optical coherence tomography (AS-OCT)), and ocular surface symptoms (visual analogue scale (VAS) and ocular surface disease index (OSDI)) were evaluated. Thirteen eyes in group A, 26 in group B, and 10 in group C were evaluated. No changes in BCVA ( p > 0.05) were found. Recurrence cases for groups A, B, and C were none, two, and two, respectively, and three cases of pyogenic granulomas in group A. The horizontal/vertical graft size was lower in group B vs group A ( p < 0.05) from months 1 to 12. The improvement in VAS frequency for groups A, B, and C was: 35.5%, 86.2%, and 39.1%, respectively. The OSDI scale reduction for groups A, B, and C was: 12.7%, 39.0%, and 84.1%. The use of the three surgical techniques as a graft for primary pterygium surgery was safe and effective, showing similar results. The mPRGF graft represents an autologous novel approach for pterygium surgery.

This study aimed to investigate the use of Plasma Rich in Growth Factors (PRGF) associated with tissue ReGeneraTing Agent (RGTA) drops for the treatment of noninfectious corneal ulcers. RGTA treatment was applied (one drop every two days); however, if ulcer closure was not achieved, PRGF eye drops treatment was added (four times/day). The time taken to reach the ulcer closure, the Best Corrected Visual Acuity (BCVA), intraocular pressure (IOP), Visual Analog Scale (VAS, in terms of frequency and severity of symptoms), and Ocular Surface Disease Index (OSDI) were evaluated. Seventy-four patients (79 eyes) were included, and the mean age was 56.8 ± 17.3 years. The neurotrophic corneal ulcer was the most frequent disorder ( n = 27, 34.2%), mainly for herpes virus ( n = 15, 19.0%). The time of PRGF eye drops treatment associated with the RGTA matrix was 4.2 ± 2.2 (1.5-9.0) months, and the follow-up period was 44.9 ± 31.5 months. The ulcer closure was achieved in 76 eyes (96.2%). BCVA, VAS and OSDI improved from the baseline ( p < 0.001), and IOP remained unchanged ( p = 0.665). RGTA and PRGF in noninfectious ulcers were effective and could be a therapeutic alternative for this type of corneal disease.