Chronic dry eye disease affects patients’ quality of life, their ability to work and participate in the community. In addition to the more common treatments available for dry eye disease, Plasma Rich in Growth Factors (PRGF) are a new generation of autologous eye drops for severe dry eye that are made from patients’ own platelets.
According to DEWS II report, Dry Eye Disease (DED) is a symptomatic disease, characterised by a vicious cycle of tear film instability and hyperosmolarity, which leads to increased ocular surface inflammation, damage and neurosensory abnormalities.
While the majority of your general dry eye patients (58 per cent) will have mild disease, 30 per cent will have moderate and 12 per cent will suffer from severe disease.1
Moderate to severe DED is associated with significant pain, limitations in performing daily activities, reduced vitality, poor general health, and often depression.2
Moderate to severe DED is associated with significant pain, limitations in performing daily activities, reduced vitality, poor general health, and often depression
There are many options to help address the symptoms of mild dry eye disease including dietary changes, supplements, over the counter drops, and the recently PBS listed Nova Tears. Chronic dry eye disease will require additional therapies that can include intense pulsed light, LipiFLow, topical anti-inflammatory medication and autologous eye drops.
LipiFlow, a thermal pulsation device, offers heat and physical massage to treat evaporative dry eye. Greiner conducted a long term study which demonstrated improvements in meibomian gland secretion score, OSDI and SPEED scores, and tear film break-up time (T FBUT) following treatment using the LipiFlow system they remained statistically significant for 12 months.3
Although the mechanism of action is unknown, early studies are showing that intense pulsed light (IPL) can be a beneficial treatment for meibomian gland dysfunction (MGD). Associate Professor Jennifer Craig and colleagues, in a monocular eye trial, found improvements in non-invasive tear break-up time (N ITBUT) were seen at day 45 in the treated eye with no improvements detected in the non-treated eye.4 Assuming the mechanism of action is similar to that of IPL use in dermatology to treat rosacea, the light energy is absorbed by oxyhemoglobin in the blood vessels causing coagulation and subsequent closing of the blood vessels, thus preventing infiltration of inflammatory mediators into the meibomian glands.3
TOPICAL ANTI-INFLAMMATORY MEDICATION
Cyclosporine A addresses multiple causes of dry eye. The use of cyclosporine results in down-regulation of inflammatory cytokines in the conjunctiva and lacrimal gland, which is believed to enhance tear production. It also decreases epithelial cell apoptosis and increases goblet cell density.5 In a randomised, investigatormasked trial, one group of patients was provided artificial tears while the other was provided cyclosporin 0.05 per cent dosed twice daily. At 12 months only 6 per cent of the cyclosporin group had experienced dry eye disease progression compared to 32 per cent in the artificial tear group.6
Corticosteroids can be used to treat inflammation and ocular allergy. Multiple studies have shown the effectiveness of steroids in the management of dry eye.5 If inflammation is secondary to conditions like blepharitis it is essential to treat these either prior to, or in conjunction with, management of the inflammation. Due to the known side effects of steroids like glaucoma, infectious keratitis and corneal thinning, patients being managed with steroids should be monitored regularly.
Autologous serum has the same pH, osmolarity, essential nutrients, bactericidal properties and growth factors as the natural tear film, components not found in commercially prepared artificial tears.5 In patients with severe dry eye disease including those with Sjogren’s syndrome, autologous serum drops have been shown to improve symptoms, corneal and conjunctival staining, tear osmolarity, TBUT, and goblet cell density.5
Autologous serum offers significant benefits to patients with ocular surface disease compared to standard lubricating drops. Autologous serum however, still contains pro-inflammatory cytokines expressed by leucocytes.7 Another downside with autologous serum is that the preparation, including dilution and storage protocols, are not standardised,7 impacting reproducibility with a potential flow on effect to efficacy. The growth factors stored in platelets are essential to promote healing. If there were a way to increase the concentration of the growth factors while removing any pro-inflammatory cells when preparing the serum eye drops, this would enhance the therapeutic properties of the solution with obvious benefits for patients.
AUTOLOGOUS PLASMA RICH IN GROWTH FACTORS (PRGF)
The Endoret system by Biotechology Institute is an innovative technology that, through a standardised preparation protocol including activation of the platelets with calcium chloride, is able to produce autologous plasma rich in growth factors (PRGF) eye drops. Calcium chloride is used to release the growth factors from the platelets because it enables a physiologic release without immunologic reaction and the appearance of coagulopathies.8 This process also allows for the release of growth factors in the absence of leukocytes, thus avoiding any pro-inflammatory effects.8 A single sample of blood will prepare three months’ supply of eyes drops. These are provided to patients in a custom storage container, which they store in the freezer. As each vial is used, the patient removes a new vial from the freezer to defrost. This is then placed into the drop administration device, which patients can carry with them and use as prescribed.
Multiple ocular surface disorders are characterised by an impaired tissue repair process including dry eye disease, recurrent corneal erosion syndrome, persistent epithelial defects, corneal dystrophies, and neurotrophic ulcers.7 The use of PRGF in the treatment of dry eye disease and persistent epithelial defects was first investigated by Vanesa Freire and colleagues, and published in 2012. They compared the in vitro effect on human corneal epithelial cells of three blood derivatives, autologous serum (AS), platelet rich plasma (PRP) and PRGF. PRP has a high centration of platelets, however these platelets are not activated nor removed. When PRP preparation is frozen for preservation the platelets break, making the preparation cloudy. This debris is thought to induce apoptotic cell death.8 In this study, PRGF stimulated a higher concentration of epithelial growth factor (EGF) and upregulation of expression of several genes involved in communication and cell differentiation compared to the other blood derivatives. PRGF-incubated epithelium presented a heterogenous morphology, exhibiting differentiated and non-differentiated cell phenotypes while AS and PRP-incubated epithelial cells were more homogenous. They concluded that these results supported the use of serum derived from PRGF for the treatment of ocular surface disorders.
In a study of 16 patients with moderate to severe dry eye unresponsive to other therapies, autologous PRGF drops resulted in improvement of symptoms as well as squamous metaplasia after three months.9 Symptom improvement was classified as mild in 25 per cent of patients, moderate in 31.25 per cent, and substantial in 43.75 per cent of patients.9
In another study, 20 eyes with persistent epithelial defects (PED) from various underlying etiopathologies including neurogenic, iatrogenic, associated with burning or secondary to severe dry eye were treated with autologous PRGF.10 The mean duration of PED prior to PRGF treatment was 26.7 weeks ranging from one to 104 weeks.10 The epithelial defect was restored in 85 per cent of cases with a mean epithelialisation time of 10.9 weeks ranging from two to 39 weeks.10 Autologous PRGF has also been shown to stimulate wound healing and reduce corneal haze following photorefractive keratotomy surgery.10
Accurate diagnosis is critical to an effective dry eye management plan. Ensuring the patient understands the multiple contributing factors to their condition and the need to manage each of these will improve compliance. For patients who are non-responsive to therapy or have persistent corneal staining, autologous PRGF may provide symptomatic relief and corneal re-epithelisation.
Colette Parkinson is a qualified optometrist and the global product director, diagnostics and visualisation with Alcon, based in Fort Worth, Dallas USA.
- www.clspectrum.com/issues/2012/july-2012/2012- annual-report-on-dry-eye-diseasesBron et al TFOS DEWS2 Pathophysiology Report The Ocular Surface 2017
- Greiner et al. What to Expect from Your Dry-Eye Device Review of Ophthalmology 2015
- Craig et al. Prospective Trial of Intense Pulsed Light for the Treatment of Meibomian Gland Dysfunction IVOF 2015
- Hessen and Akpek. Dry Eye: an Inflammatory Ocular Disease J Ophthalmic Vis Res 2014
- Rao SN Topical Cyclosporin 0.05% for the treatment of dry eye disease progression J Ocular Pharmacol Ther 2010
- Anitua et al. Autologous Serum and Plasma Rich in Growth Factors in Ophthalmology: Preclinical and Clinical Studies Acta Ophthalmologica 2015
- Freire et al. In Vitro Effects of Three Blood Derivatives on Human Corneal Epithelial Cells Invest Ophthalmol Vis Sci 2012
- Lopez-Plandolit et al. Efﬁcacy of Plasma Rich in Growth Factors for the Treatment of Dry Eye Cornea 2011
- Lopez-Plandolit et al. Plasma Rich in Growth Factors as a Therapeutic Agent for Persistent Corneal Epithelial Defects Cornea 2010
- Anitua et al. Plasma Rich in Growth Factors (PRGFEndoret) Stimulates Corneal Wound Healing and Reduces Haze Formation After PRK Surgery Experimental Eye Research 2013