Autologous Serum (AS) Versus Platelet-rich plasma (PRP)

Platelet-rich plasma (PRP)

Platelet-rich plasma (PRP) contains a higher concentrated of growth factors which stimulate epithelial cells faster than Autologous Serum or whole blood and lead to faster healing. PRP is obtained via centrifugation from whole blood mixed with anticoagulant. Platelets are critically important in the wound-healing process. They translocate rapidly to the wound site and adhere to the damaged tissue, initiating a healing reaction which includes the release of a variety of cytokines and growth factors. Hartwig et al. reported a superior effect on cell growth in platelet releasates in PRP than in Autologous Serum owing to its high content of growth factors 

Platlets contain α-granules which liberate a very high concentration of:

-platelet-derived growth factors, 

-platelet factor IV, 

-transforming growth factor (TGF)-β 

-circulating stem cells 

Thus, PRP is known to harbor higher concentrations of growth factors and can promote effective wound healing and may be better than Autologous Serum in certain patients. 

PRP eye drops can be used to treat ocular surface diseases, such as:

-pain after LASIK (laser-assisted in situ keratomileusis)

-ocular surface diseases

-corneal ulcers

-severe dry eye

-ocular graft-versus-host disease, 

-persistent epithelial defects, 

-neurotropic keratopathy, 

- recurrent epithelial erosions: it reduces the risk of recurrent erosions 

-infectious keratitis

-persistent epithelial defects

Kim, et al. reported improved outcomes with PRP eye drops than Autologous Serum eye drops in patients with persistent epithelial defect after infectious keratitis, for instance (Reference 1).

Autologous Serum (AS)

Autologous Serum (AS) acts as a lubricant on the ocular surface and also supplies several essential substances for the recovery of damaged epithelium. 

It contains:

- vitamin A

- epidermal growth factor (EGF)

-fibronectin and a variety of cytokines  

-circulating stem cells 

These factors help with the proliferation, migration, and differentiation of the ocular surface epithelium cells which helps restore the eye surface to prevent pain or heal a patient from pain.

Autologous Serum eye drops have been used for years for the treatment of:

-ocular surface diseases, 

-corneal ulcers

-severe dry eye, 

-ocular graft-versus-host disease, 

-persistent epithelial defects, 

-neurotropic keratopathy, 

- recurrent epithelial erosions: it reduces the risk of recurrent erosions (Reference 2)

References:

1. Kim KM, Shin YT, Kim HK. Effect of autologous platelet-rich plasma on persistent corneal epithelial defect after infectious keratitis. Jpn J Ophthalmol. 2012;56:544–550.

2. Del Castillo JM, de la Casa JM, Sardina RC, et al. Treatment of recurrent corneal erosions using autologous serum. Cornea. 2002;21:781–783

3. Alio JL, Pastor S, Ruiz-Colecha J, et al. Treatment of ocular surface syndrome after LASIK with autologous platelet-rich plasma. J Refract Surg. 2007

4. Hartwig D, Harloff S, Liu L, et al. Epitheliotrophic capacity of a growth factor preparation produced from platelet concentrates on corneal epithelial cells: a potential agent for the treatment of ocular surface defects? Transfusion. 2004;44:1724–1731

5. Korean J Ophthalmol. 2016 Apr; 30(2): 101–107.

Autologous Platelet-rich Plasma Eye Drops in the Treatment of Recurrent Corneal Erosions

Jun Hun Lee,1 Myung Jun Kim,1 Sang Won Ha,2 and Hong Kyun Kim1

Autologous Serum and Platelet-Rich Plasma for Corneal Ulcers, Recurrent Erosions, and Dry Eyes

We are beginning to offer Platelet-Rich Plasma for our patients with Corneal Ulcers and dry eyes. 

Platelet-Rich Plasma (PRP) has been used for years in many different specialties. PRP is now being used to help heal patients with Corneal Ulcers, Recurrent Erosions, and Dry Eye as a way to stop the process of scar tissue formation and improve wound healing of damaged cells.  Though PRP has not been shown to restore meibomian glands yet, it has not been studied. I wonder if injecting PRP into the meibomian glands may help restore the glands. It may. Stem Cells though is likely better for injection into the Meibomian Glands. 

Platelet-Rich Plasma (PRP) is full of platelets which are good reservoirs of growth factors that improve wound healing and restore damaged ocular surfaces. 

We create PRP in a similar way we create autologous serum for a patient's own blood. We have been using Autologous Serum in hundreds of adults and children at Visionary Ophthalmology for about 25 years with very good results. I used Autologous Serum for adults at Harvard Medical School's Massachusetts Eye and Ear Infirmary rarely for many years when I was there on staff. 

For PRP, the blood is spun in a centrifuged to remove white and red blood cells to leave the platelets and growth factors. The plasma is placed into sterile eye droppers for topical administration. It is kept in the freezer until one plans to use it and then put in the refrigerator. They can be used for 1 week after defrosted. 

The biggest risk of using a blood product on a patient is a corneal infection. This is very rare but has been reported in patients who failed to keep the drops frozen or cold. I have not seen one yet from AS or PRP made in our office (nor at Harvard). Still any type of worsening while someone is using AS or PRP requires immediate attention and evaluation by an EyeMD. 

In future studies, a group of patients would have injection of Stem Cells in one eyelid and the other eyelid would be used as a control. Another set of patients would have PRP injected into the lower eyelid and the their other non-treated eye would serve as a control. 

Studies have shown Platelet rich plasma improved light sensitivity/photophobia, pain and inflammation. It helped reepithelialization of corneal epithelium, promoted corneal wound healing. It improved clinical conditions and resulted in improved vision in the majority of the patients

Sandra Lora Cremers, MD, FACS

Ophthalmology. 2007 Jul;114(7):1286-1293.e1. Epub 2007 Feb 26.

Use of autologous platelet-rich plasma in the treatment of dormant corneal ulcers.

Alio JL1, Abad M, Artola A, Rodriguez-Prats JL, Pastor S, Ruiz-Colecha J.

Author information

Abstract

PURPOSE:

To investigate the potential role of autologous platelet-rich plasma in promoting healing in dormant corneal ulcers.

DESIGN:

Prospective, consecutive, interventional, noncomparative, nonrandomized, observational study.

PARTICIPANTS:

Forty eyes of 38 patients with dormant corneal ulcers.

METHODS:

Autologous platelet-rich plasma was used in a total of 40 eyes with dormant corneal ulcers divided into 2 groups: group I, 26 eyes treated with topical eyedrops of autologous platelet-rich plasma (12 neurotrophic, 9 herpetic, and 5 immunological ulcers), and group II, 14 eyes treated surgically with a solid clot of autologous platelet-rich plasma combined with amniotic membrane transplantation in perforated corneas or with impending perforation. The treatment was used in patients with chronic nonhealing ulcers (mean, 2 years of evolution) that had been unresponsive to conventional topical therapy. Autologous blood from each patient was obtained by venipuncture, and platelet-rich plasma was prepared from each blood sample without additives.

MAIN OUTCOME MEASURES:

Ulcer size, inflammation, healing, visual acuity, and patient's subjective symptoms.

RESULTS:

Autologous platelet-rich plasma promoted healing of ulcers. In group I, 13 eyes healed, 11 eyes improved significantly, and 2 eyes showed no change. In group II, 10 eyes healed and 4 eyes improved significantly. Inflammation and subjective symptoms, particularly pain, improved in all patients. Vision remained stable or improved in all cases.

CONCLUSION:

Autologous platelet-rich plasma promoted healing of dormant corneal ulcers even in eyes threatened by corneal perforation and was accompanied by a reduction in pain and inflammation.

• Alio JL, Abad M, Artola A, et al. Use of autologous platelet-rich plasma in the treatment of dormant corneal ulcers. Ophthalmology. 2007.114:1286-1293.
• Kojima T, Ishida R, Dogru M, et al. The effect of autologous serum eye drops in the treatment of severe eye disease: a prospective randomized case-controlled study. Am J Ophthalmol. 2005;139:242-246.
• Tsifetaki N, Kitsos G, Paschides CA, et al. Oral pilocarpine for the treatment of ocular symptoms in patients with Sjögren’s syndrome: A randomised 12-week controlled study. Ann Rheum Dis. 2003;62:1204-1207.

Plast Reconstr Surg. 2012 Jan;129(1):46e-54e. doi: 10.1097/PRS.0b013e3182362010.

Nonactivated versus thrombin-activated platelets on wound healing and fibroblast-to-myofibroblast differentiation in vivo and in vitro.

Scherer SS1, Tobalem M, Vigato E, Heit Y, Modarressi A, Hinz B, Pittet B, Pietramaggiori G.

Author information

Abstract

BACKGROUND:

Platelet preparations for tissue healing are usually preactivated before application to deliver concentrated growth factors. In this study, the authors investigated the differences between nonactivated and thrombin-activated platelets in wound healing.

METHODS:

The healing effects (i.e., wound closure, myofibroblast formation, and angiogenesis) of nonactivated and thrombin-activated platelets were compared in experimental wounds in diabetic (db/db) animals. In vitro, fibroblast phenotype and function were tested in response to platelets and activated platelets. No treatment served as a negative control.

RESULTS:

Wounds treated with platelets reached 90 percent closure after 15 days, faster than activated platelets (26 days), and with higher levels of myofibroblasts and angiogenesis. In vitro, platelets enhanced cell migration and induced two-fold higher myofibroblast differentiation and contraction compared with activated platelets.

CONCLUSIONS:

Platelets stimulate wound healing more efficiently compared with activated platelets by enhancing fibroblast differentiation and contractile function. Similar levels of growth factors may induce different biological effects when delivered "on demand" rather than in an initial bolus.

PRP can be frozen but fresh is better.

BioMed Research International
Volume 2014 (2014), Article ID 692913, 10 pages
http://dx.doi.org/10.1155/2014/692913

Research Article

Does Platelet-Rich Plasma Freeze-Thawing Influence Growth Factor Release and Their Effects on Chondrocytes and Synoviocytes?

Alice Roffi,1 Giuseppe Filardo,2 Elisa Assirelli,3 Carola Cavallo,4 Annarita Cenacchi,5 Andrea Facchini,6,7 Brunella Grigolo,3 Elizaveta Kon,2 Erminia Mariani,6,7 Loredana Pratelli,8 Lia Pulsatelli,3 and Maurilio Marcacci2

1Nano-Biotechnology Laboratory, Rizzoli Orthopaedic Institute, Via di Barbiano 1, 40136 Bologna, Italy
2II Clinic-Biomechanics Laboratory and Nano-Biotechnology Laboratory, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy
3Laboratory of Immunorheumatology and Tissue Regeneration/RAMSES, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy
4Laboratory RAMSES, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy
5Immunohematology and Transfusion Medicine and Cell and Musculoskeletal Tissue Bank, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy
6Laboratory of Immunorheumatology and Tissue Regeneration Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy
7Department of Medical and Surgical Science, University of Bologna, Via Giuseppe Massarenti 9, 40138 Bologna, Italy
8Clinical Pathology Unit, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy

Received 27 February 2014; Accepted 23 June 2014; Published 17 July 2014

Current research aims to optimize PRP production and administration protocols. This study underlines two interesting aspects. The first one is that freeze/thawing affects PRP cell composition and its release of bioactive molecules. The second is that this different release kinetics does not significantly influence the effects on cell cultures. It is important to recognize that biological studies give important indications for the development of treatments, but their results do not always directly translate into clinical findings, as previously shown by the same clinical outcome reported using two biologically completely different procedures [35]. However, until clinical studies explore and clarify the effects of PRP storage on patient symptoms and functional improvement, this study suggests that freeze/thawing does not significantly affect PRP and can be considered as a storage option and thus simplify the management of patients undergoing multiple injection cycles of PRP.

Proof Meibomian Gland Probing Works

Many patients have been feeling significant relief of eye pain and discomfort with Meibomian Gland Probing with Meibomian Gland Expression.
Here are more studies showing the benefit of Meibomian Gland Probing.

In my opinion, just doing Meibomian Gland expression may not be enough to keep Meibomian Glands working for many patients. Performing a probing will break orifice scar tissue that is preventing the gland from expressing as much oil as it can. 

So far 95% of my patients have had relief with one MGP procedure. I do have about 5 patients with Sjögren's syndrome that return for probing about once every 1-3 months for probing given the relief it provides. I suspect their underlying inflammation re-scars the orifice of the gland. They feel relief for a few weeks, but then the pain returns. They are praying the Stem Cell Injection into the Meibomian Gland protocol we are launching will revive Meibomian Glands and prevent the need for repeated probings.

Sandra Lora Cremers, MD, FACS

This paper below is by a fellow colleague from Harvard who has no financial interest that I know of in probing. 

Ophthal Plast Reconstr Surg. 2017 Feb 17. doi: 10.1097/IOP.0000000000000876. [Epub ahead of print]

Dynamic Intraductal Meibomian Probing: A Modified Approach to the Treatment of Obstructive Meibomian Gland Dysfunction.

Syed ZA1, Sutula FC.

Author information

1

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, U.S.A.

Abstract

PURPOSE:

Obstructive meibomian gland dysfunction is a leading cause of ocular morbidity and its treatment remains a challenge. Meibomian gland probing was initially described in 2010. Here, the authors describe a modified technique, dynamic intraductal meibomian probing, which offers several advantages over the traditional approach including increased magnification, greater eyelid stabilization, enhanced anesthesia, and easier identification of gland orifices through the expression of meibum.

METHODS:

The authors conducted a retrospective chart review of 70 eyelids with treatment-resistant obstructive meibomian gland dysfunction undergoing dynamic intraductal meibomian probing between January 2013 and April 2015.

RESULTS:

Immediately after the procedure, 91.4% of cases experienced symptomatic improvement, and no complications were noted.

CONCLUSIONS:

Dynamic intraductal meibomian probing is an effective and safe treatment for obstructive meibomian gland dysfunction that is resistant to traditional therapies.

Cornea. 2016 Jun;35(6):721-4. doi: 10.1097/ICO.0000000000000820.

Effectiveness of Intraductal Meibomian Gland Probing for Obstructive Meibomian Gland Dysfunction.

Sik Sarman Z1, Cucen B, Yuksel N, Cengiz A, Caglar Y.

Author information

Abstract

PURPOSE:

To evaluate the short-term effectiveness of intraductal meibomian gland probing using modified Maskin cannulas in patients with obstructive meibomian gland dysfunction.

METHODS:

The study prospectively included 58 eyes of 30 patients with a diagnosis of meibomian gland dysfunction who were refractory to medical treatment for at least 6 months. The patients were divided into 4 groups according to the number of probing procedures applied. During probing, sterile modified Maskin probes 2, 2.5, 4, and 6 mm in length were used. A tarsal massage was recommended after medical treatment. Preoperatively, then postoperatively at 1 week, 1 month, and 3 months, the Schirmer 1 test was performed, tear break-up time was measured, and images of the anterior segment were recorded. In addition, the Ocular Surface Disease Index questionnaire was completed at baseline and at 3 months.

RESULTS:

In all groups, there were no statistically significant differences between Schirmer 1 test results at preoperative and postoperative 3 months, but tear break-up time values measured at baseline and at 3 months differed significantly (5 seconds, 13 seconds, P < 0.001). In the analyses of anterior segment photographs of all patients, statistically significant postprocedural decreases in conjunctival hyperemia (P < 0.0001) and eyelid margin vascularization (P = 0.004) were detected, and the later Ocular Surface Disease Index scores showed a significant improvement between preop and 3 months.

CONCLUSIONS:

A procedure using modified Maskin probes was effective and reliable in the short term for patients with meibomian gland dysfunction.

Cornea. 2016 Jun;35(6):725-30. doi: 10.1097/ICO.0000000000000777.

Efficacy of Intraductal Meibomian Gland Probing on Tear Function in Patients With Obstructive Meibomian Gland Dysfunction.

Ma X1, Lu Y.

Author information

1

Department of Ophthalmology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

Abstract

PURPOSE:

To assess the efficacy and safety of intraductal meibomian gland probing in patients with obstructive meibomian gland dysfunction who experienced little improvement with eyelid warming, massage, or artificial tears.

METHODS:

Forty-nine patients with obstructive meibomian gland dysfunction were randomly divided into 2 groups: intraductal meibomian gland probing with 0.1% fluorometholone (group I), and 0.1% fluorometholone alone (group II). Subjective symptom scores and objective signs, including lid margin abnormalities, meibum quality and expressibility, meibomian gland dropout, fluorescein staining, tear break-up time (TBUT), and Schirmer I test results, were recorded before treatment and after 1 day, 1 week, and 1 month posttreatment.

RESULTS:

Clinical subjective symptoms and objective signs including meibum grade, TBUT, lid margin abnormalities, and fluorescein staining demonstrated significant improvements in both groups after treatment over time (all P < 0.05), and group I was better than group II 1 month after treatment in meibum grade (6.1 ± 3.3 vs. 10.4 ± 4.9, respectively; P < 0.001), lid margin abnormalities (0.8 ± 0.1 vs. 1.3 ± 0.3, respectively; P < 0.001), and TBUT (8.2 ± 2.1 vs. 7.0 ± 3.0, respectively; P = 0.0293). Before applying any medications, 76% of patients obtained immediate symptom relief 1 day after probing. However, the Schirmer I test results and meibomian gland dropout were insignificant pre- and posttreatment in either group (P > 0.1, respectively).

CONCLUSIONS:

Intraductal meibomian gland probing demonstrated significant efficacy in symptom relief and tear film stabilization. Probing helped release accumulated meibum and could help increase the accessibility of diseased meibomian glands to topical corticosteroids.

Cornea. 2015 Oct;34(10):1206-8. doi: 10.1097/ICO.0000000000000558.

Analysis of Meibum Before and After Intraductal Meibomian Gland Probing in Eyes With Obstructive Meibomian Gland Dysfunction.

Nakayama N1, Kawashima M, Kaido M, Arita R, Tsubota K.

Author information

Abstract

PURPOSE:

To evaluate whether the amount of meibum and its viscosity change after intraductal meibomian gland probing in patients with refractory obstructive meibomian gland dysfunction (o-MGD).

METHODS:

Six lid margins of 3 patients with refractory o-MGD underwent intraductal meibomian gland probing. Meibum and the clinical outcome were evaluated before the procedure and at a 1-month postoperative visit. Meibum was quantified with a Meibometer, and its viscosity (Shimazaki grade) was assessed simultaneously. The tear film condition was evaluated by lipid layer interferometry (DR1, Kowa, Nagoya, Japan), and meibomian gland loss was analyzed by noncontact infrared meibography. Lid margin findings, tear break-up time, fluorescein score, and ocular symptoms were also assessed.

RESULTS:

At the postoperative visits, all cases showed improvements in meibum lipid levels (446-1376, 757-802, and 396-571 meibometer units) and meibum viscosity (grade 3-0, 3-1, and 3-2). Two cases showed an improvement in tear break-up time (2-5 and 0-6 seconds). No morphological changes in the meibomian gland were observed in any cases.

CONCLUSIONS:

Intraductal meibomian gland probing seems to improve meibomian gland lipid levels, and it may be a good treatment option for cases of o-MGD that are resistant to conventional treatment.