Which one is better Platelet Rich Plasma (PRP) or Autologous Serum (AS)?

We have had many patients who have used AS drops in one eye and PRP in the other eye. Approximately 90% prefer their platelet-rich plasma. But this is not a prospective, double-blind study nor published. This is based on one surgeon’s experience over 7 years using PRP drops.

There is very little money to be made in patients using their own cells. Thus, there is a lack of studies comparing these a patient’s own preservative-free cells to FDA-approved drugs for dry eye and allergy.

PRP and AS are very safe. I have yet to see an infection from either. There are a couple of case reports of patients getting a corneal ulcer from autologous serum, but this is very rare. I could not find a case report to date reporting a corneal infection from PRP. Instead, there are papers noting how PRP helps with stubborn corneal infections as PRP is a potent anti-inflammatory and antibiotic. I suspect those patients who did have a corneal infection with autologous serum had little to no meibomian glands: they were so dry as to set them up for an infection. But the reports were published before meibography was available.

There are some studies beginning to come out comparing AS to PRP. The below is an example, but we rarely use 100% of either. There have been some studies that 20% is the best concentration and 100% may be too many growth factors or too overwhelming. Still, there are not many studies to indicate what percentage is the best. Most of our patients benefit from 20% AS or 20% PRP. Less than 1% need a higher percentage of either. A couple of patients noted improvement when using both.

For Corneal Neuropathy, the majority of my patients feel improvement in pain scores with PRP.

There is a good deal of data I will start posting below on such studies to back up our finding as well.**

PRP decreases dry eye symptoms in the majority of patients. Less than 1% of our patients have had no improvement in symptoms with their PRP: some of these are corneal neuralgia patients. But the only way to know if it will help is to try PRP 20% non preserved in one eye and use the other eye as a control. I could not find any publications noting that PRP makes corneal neuralgia worse.

The question of using PRP in patients with neuropathic pain is addressed in the below paper by Neurobiologist Kuffler (Mol Neurobiol.2013 Oct;48(2):315-3doi: 10.1007/s12035-013-8494-7. Epub 2013 Jul 7. Platelet-rich plasma and the elimination of neuropathic pain. Damien P Kuffler 1

“Platelet-rich plasma contains multipotent MSCs, which is also referred to as mesenchymal stromal cells, may be responsible for some of the influences exerted by applied platelet-rich plasma [220–222]. In one series of experiments, isolated MSCs applied to the end of transected peripheral nerves did promote enhanced axon regeneration [69]. The promotion of axon regeneration may result from MSCs secretion of NGF, BDNF, and their promotion of angiogenesis [70, 223]. A recent study suggested that the MSC may result from their differentiation into a Schwann cell phenotype which promotes axonal regeneration equivalent to that of Schwann cells in vitro and in vivo [223, 224]. Therefore, by promoting axon regeneration and the restoration of normal axon biophysical properties, MSCs within PRP may be an important part of the mechanism by which PRP leads to the reduction in neuropathic pain [70, 225].”

Another important observation from this study was that in all the patients, their neuropathic pain began to subside within 3 weeks of the application of the PRP, weeks before any target tissues had become reinnervated. Importantly, the neuropathic pain of each patient remained reduced/eliminated for a minimum of 6 years post-surgery. Finally, there was no apparent correlation between the degree of neurological recovery of function (number of axons that reinnervated their targets) and the extent of reduction/elimination of neuropathic pain. Therefore, these data indicate that a single application of PRP can result in the long-term reduction/elimination of neuropathic pain. However, it is not known whether the long-term influence on neuropathic pain resulted from the application of the PRP, the reestablishment of axon contact with Schwann cells, or their reinnervating targets. Further clinical studies are required to confirm these results, to determine its reliability, the nerve conditions under which it is effective, and whether the application of PRP to refreshed stumps of nerves which have no targets, such as those of amputees.

Conclusions Extensive data indicate that the application of PRP to sites of neuropathic pain, such as muscle injuries and sprained joints, triggers a reduction and/or elimination of that pain. Other data indicate that the application of PRP to the central nerve stump of an injured nerve both induces axon regeneration that would not otherwise have occurred and leads to the elimination and reduction of neuropathic pain. However, other data indicate that PRP neither reduces neuropathic pain nor induce enhanced axon regeneration. On the contrary, it is important to consider a number of important issues as to why the positive claims may be correct before accepting the negative claims. First, were the compositions of the PRP used in the different studies the same or even similar? Depending on the whole blood separation device used to obtain PRP, its composition can vary greatly in terms of the number of platelets, the ratio of unactivated vs. activated platelets, the number of MSCs, and the number of erythrocytes and white blood cells. Even if similar studies were performed on the same animal model, the outcomes could still be significantly different because different compositions of PRP that were used. Second, if similar studies were performed on different animal models or clinically, the same separation device produces PRP with greatly different compositions. Therefore, even when using the identical device to prepare the PRP, one cannot reliably compare the results from clinical and animal model data, or between different animal models. Third, the conclusion that platelet-released factors which do not directly reduce neuropathic pain is based on the emphasis looking for a direct action of the factors. This question is appropriately asked as whether the application of PRP leads to inducing the cellular events which further leads to the elimination of neuropathic pain. This review concludes first, that factors released by platelets and stem cells within platelet-rich plasma lead directly to the elimination of neuropathic pain by triggering enhanced inflammation and its resolution, followed by the full cascade of the wound healing process, including the regenerative process resulting in axon regeneration and target reinnervation. These in turn allow axons to take up target-released factors that eliminate of nociceptive neuron hyperexcitability and thereby eliminate neuropathic pain. It is also concluded that similar or other platelet- or stem cell-released factors act directly on neurons to promote axon regeneration, which Mol Neurobiol leads to the re-establishment of normal axon biophysical properties, the elimination of hyperexcitability, and the elimination of neuropathic pain.”

That was 2013! Still, no one has a double-blinded, randomized, prospective study with PRP or comparing PRP and AS. These are expensive studies. We need funding for independent (ie, non-sponsored by drug companies) doctors and surgeons to do this study.

SLC

1.BMJ Open

. 2021 Jun 30;11(6):e048479. doi: 10.1136/bmjopen-2020-048479.

Comparison of treatment efficacy between 100% platelet-rich plasma and 100% serum eye drops in moderate-to-severe dry eye disease: a randomised controlled trial protocol

Passara Jongkhajornpong 1 2, Pawin Numthavaj 3, Thunyarat Anothaisintawee 3 4, Kaevalin Lekhanont 1, Gareth McKay 5, John Attia 6, Ammarin Thakkinstian 2Affiliations expand

PMID: 34193498
PMCID: PMC8246355
DOI: 10.1136/bmjopen-2020-048479

Free PMC article

Abstract

Introduction: Dry eye disease (DED) is a common eye problem. Although the disease is not fatal, it substantially reduces quality of life and creates a high economic burden, especially in patients with moderate-to-severe DED. Several biological tear substitutes (eg, autologous serum (AS), autologous platelet-rich plasma (APRP) and autologous platelet lysate) could effectively improve dry eyes. However, evidence on their comparative efficacy is controversial. This study aims to compare the efficacy of 100% APRP with 100% AS eye drops in patients with moderate-to-severe DED.

Methods and analysis: The study is a single-centre, double-blinded randomised, parallel, non-inferiority trial. One hundred and thirty patients with moderate-to-severe DED, aged 18-70 years will be recruited from outpatient clinic, Department of Ophthalmology, Ramathibodi Hospital, Bangkok from February 2021 to January 2023. Patients will be randomised to receive either 100% APRP or 100% AS eye drops (1:1 ratio) for 4 weeks. The primary outcomes are ocular surface disease index (OSDI) and ocular surface staining (OSS) evaluated using the Oxford scale. Secondary outcomes are fluorescein break-up time, Schirmer’s I test, meibomian gland parameters and adverse events. Other measured outcomes include best-corrected visual acuity, intraocular pressure and compliance.

Ethics and dissemination: The study protocol and any supplements used in conducting this trial have been approved by the Ethics Committee of Faculty of Medicine, Ramathibodi Hospital, Mahidol University (MURA2020/1930). Informed consent will be obtained from all patients before study entry. Results will be presented in peer-reviewed journals and international conferences.

Trial registration number: NCT04683796.

This article uses “autologous conditioned serum (ACS)” which sounds the same as Autologous Serum but the full paper is not available on Pubmed at John’s Hopkins. Acta Orthop Traumatol Turc

. 2020 Jul;54(4):438-444. doi: 10.5152/j.aott.2020.18498.

Comparison on effects of platelet-rich plasma versus autologous conditioned serum on Achilles tendon healing in a rat model

Erdinç Genç 1, Serdar Yüksel 1, Aysel Çağlar 2, Ozan Beytemur 1, M Akif Güleç 1Affiliations expand

PMID: 32812877
PMCID: PMC7444885
DOI: 10.5152/j.aott.2020.18498

Free PMC article

Abstract

Objective: The aim of this study was to compare the effects of local administrations of platelet-rich plasma (PRP) with autologous conditioned serum (ACS) on Achilles tendon healing in a rat model.

Methods: In this study, 40 male Sprague-Dawley rats, aged 12 months and weighing 350 to 400 g were used. The rats were divided into three groups (n=10 in each group): a control group and two treatment groups (PRP vs ACS). A standardized procedure was applied for the complete rupture and repair of the Achilles tendon in each group. The PRP group received one dose of PRP on the operative area, and ACS group received ACS at 24, 48, and 72 hours after the surgery. The control group received no injection. Animals were sacrificed 30 days after the operation, and tendon healing in each group was assessed histopathologically based on Bonar’s semi-quantitative score and Movin’s semi-quantitative grading scale. For the biomechanical analyses, unoperated Achilles tendons of all rats in the control and ACS groups were also harvested, and pulling tests were applied to the specimen to measure the longitudinal axis strength. The highest force value among the data obtained was defined as the maximum strength value (Fmax).

Results: The mean Bonar’s score was significantly lower in the PRP group (3.8±0.8) than in the ACS (4.8±0.45) and control groups (5.2±0.837) (p=0.0028). The mean Movin’s score was significantly lower in the PRP group (7.80±1.49) than in the ACS (9.8±1) and control groups (11.2±2.4) (p=0.029). The ratio of type I collagen was significantly higher in the PRP group (60±6) than in the ACS (52±4.5) and control groups (42±9) (p=0.005). Biomechanical results obtained from operated sites were comparable in terms of Fmax among groups (PRP, 33.93±2.61; ACS, 35.24±3.26; control, 35.69±3.62) (p=0.674). Similarly, the results obtained from unoperated sites were comparable among groups (PRP, 47.71±1.21; ACS, 48.14±2; control, 49.14.69±1.88) (p=0.395).

Conclusion: In terms of histopathological results, PRP seems to be more effective than ACS for Achilles tendon healing in rats.

2. Acta Ophthalmol

. 2017 Dec;95(8):e693-e705. doi: 10.1111/aos.13371. Epub 2017 Mar 7.

Serum from plasma rich in growth factors regenerates rabbit corneas by promoting cell proliferation, migration, differentiation, adhesion and limbal stemness

Jaime Etxebarria 1 2, Sara Sanz-Lázaro 1, Raquel Hernáez-Moya 1, Vanesa Freire 1 3, Juan A Durán 3 4, María-Celia Morales 1, Noelia Andollo 1Affiliations collapse

Affiliations

1Department of Cell Biology and Histology, School of Medicine and Nursing, BioCruces Health Research Institute, University of the Basque Country, Begiker, Leioa, Spain.
2Department of Ophthalmology, BioCruces Health Research Institute, University Hospital of Cruces, Begiker, Barakaldo, Spain.
3R & D Department, Instituto Clínico-Quirúrgico de Oftalmología, Bilbao, Spain.
4Department of Ophthalmology, School of Medicine and Nursing, BioCruces Health Research Institute, University of the Basque Country, Begiker, Leioa, Spain.

PMID: 28266180
DOI: 10.1111/aos.13371

Free article

Abstract

Purpose: To evaluate the regenerating potential and the mechanisms through which the autologous serum derived from plasma rich in growth factors (s-PRGF) favours corneal wound healing in vitro and in vivo.

Methods: We compared the effect of various concentrations of s-PRGF versus fetal bovine serum (FBS) and control treatment in rabbit primary corneal epithelial and stromal cells and wounded rabbit corneas. Cell proliferation was measured using an enzymatic colorimetric assay. In vitro and in vivo wound-healing progression was assessed by image-analysis software. Migration and invasion were evaluated using transfilter assays. Histological structure was analysed in stained sections. Protein expression was evaluated by immunohistochemistry.

Results: s-PRGF promoted the robust proliferation of epithelial cultures at any concentration, similar to FBS. Likewise, s-PRGF and FBS produced similar re-epithelialization rates in in vitro wound-healing assays. In vivo, s-PRGF treatment accelerated corneal wound healing in comparison with control treatment. This difference was significant only for 100% s-PRGF treatment in our healthy rabbit model. Histological analysis confirmed normal epithelialization in all cases. Immunohistochemistry showed a higher expression of cytokeratins 3/76 and 15, zonula occludens-1 and alpha-smooth muscle actin proteins as a function of s-PRGF concentration. Notably, keratocyte density in the anterior third of the stroma increased with increase in s-PRGF concentration, suggesting an in vivo chemotactic effect of s-PRGF on keratocytes that was further confirmed in vitro.

Conclusion: s-PRGF promotes proliferation and migration and influences limbal stemness, adhesion and fibrosis during corneal healing.

Corneal Neuralgia and PRP: **Mol Neurobiol

. 2013 Oct;48(2):315-32. doi: 10.1007/s12035-013-8494-7. Epub 2013 Jul 7.

Platelet-rich plasma and the elimination of neuropathic pain

Damien P Kuffler 1Affiliations expand

PMID: 23832571
DOI: 10.1007/s12035-013-8494-7

Abstract

Peripheral neuropathic pain typically results from trauma-induced nociceptive neuron hyperexcitability and their spontaneous ectopic activity. This pain persists until the trauma-induced cascade of events runs its full course, which results in complete tissue repair, including the nociceptive neurons recovering their normal biophysical properties, ceasing to be hyperexcitable, and stopping having spontaneous electrical activity. However, if a wound undergoes no, insufficient, or too much inflammation, or if a wound becomes stuck in an inflammatory state, chronic neuropathic pain persists. Although various drugs and techniques provide temporary relief from chronic neuropathic pain, many have serious side effects, are not effective, none promotes the completion of the wound healing process, and none provides permanent pain relief. This paper examines the hypothesis that chronic neuropathic pain can be permanently eliminated by applying platelet-rich plasma to the site at which the pain originates, thereby triggering the complete cascade of events involved in normal wound repair. Many published papers claim that the clinical application of platelet-rich plasma to painful sites, such as muscle injuries and joints, or to the ends of nerves evoking chronic neuropathic pain, a process often referred to as prolotherapy, eliminates pain initiated at such sites. However, there is no published explanation of a possible mechanism/s by which platelet-rich plasma may accomplish this effect. This paper discusses the normal physiological cascade of trauma-induced events that lead to chronic neuropathic pain and its eventual elimination, techniques being studied to reduce or eliminate neuropathic pain, and how the application of platelet-rich plasma may lead to the permanent elimination of neuropathic pain. It concludes that platelet-rich plasma eliminates neuropathic pain primarily by platelet- and stem cell-released factors initiating the complex cascade of wound healing events, starting with the induction of enhanced inflammation and its complete resolution, followed by all the subsequent steps of tissue remodeling, wound repair and axon regeneration that result in the elimination of neuropathic pain, and also by some of these same factors acting directly on neurons to promote axon regeneration thereby eliminating neuropathic pain.