**Plasma in Clinical Practice**

**Chapter 2**

**Provisional chapter**

**The Use of Platelet-Rich Plasma in Dry Eye Disease**

**The Use of Platelet-Rich Plasma in Dry Eye Disease**

DOI: 10.5772/intechopen.76090

Dry eye affects 35% of population, and it is a cause of chronic pain and discomfort. The conventional treatment with lubricants is often not sufficient in moderate to severe cases, which can lead to complications such as keratopathies, corneal opacities, ocular perforations, and visual loss. Platelet-rich plasma (PRP) eyedrops have already been used in ocular surface diseases due to their role in epithelialization and the presence of growth factors and vitamins that are similar to human tears. We intend to make a literature review of the use of platelet-rich plasma in dry eye disease, and present the results of a 13 case series, of diabetic severe dry eye patients that used this alternative treatment.

In this chapter we will cover a brief literature review on the use of platelet concentrate in dry eye, especially in moderate and severe cases that are generally refractory to conventional treatment, and we will cite some results of its use in other areas of medicine by several authors.

The tear has several important functions to the ocular surface, such as lubrification, transport of oxygen, carbon dioxide and other metabolites, immunological actions, and maintenance a stable corneal surface, among others. It is rich in immunoglobulins, growth factors, and vitamin A. It

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

Marina Viegas Moura Rezende Ribeiro, Eurica Adélia Nogueira Ribeiro and

Marina Viegas Moura Rezende Ribeiro, Eurica Adélia Nogueira Ribeiro and

http://dx.doi.org/10.5772/intechopen.76090

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

**Keywords:** dry eye, platelet-rich plasma, wound healing

**2. Dry eye: definition and classification**

Luiz Feliciano Ribeiro

Luiz Feliciano Ribeiro

**Abstract**

**1. Introduction**

#### **The Use of Platelet-Rich Plasma in Dry Eye Disease The Use of Platelet-Rich Plasma in Dry Eye Disease**

DOI: 10.5772/intechopen.76090

Marina Viegas Moura Rezende Ribeiro, Eurica Adélia Nogueira Ribeiro and Luiz Feliciano Ribeiro Marina Viegas Moura Rezende Ribeiro, Eurica Adélia Nogueira Ribeiro and Luiz Feliciano Ribeiro

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.76090

#### **Abstract**

Dry eye affects 35% of population, and it is a cause of chronic pain and discomfort. The conventional treatment with lubricants is often not sufficient in moderate to severe cases, which can lead to complications such as keratopathies, corneal opacities, ocular perforations, and visual loss. Platelet-rich plasma (PRP) eyedrops have already been used in ocular surface diseases due to their role in epithelialization and the presence of growth factors and vitamins that are similar to human tears. We intend to make a literature review of the use of platelet-rich plasma in dry eye disease, and present the results of a 13 case series, of diabetic severe dry eye patients that used this alternative treatment.

**Keywords:** dry eye, platelet-rich plasma, wound healing

#### **1. Introduction**

In this chapter we will cover a brief literature review on the use of platelet concentrate in dry eye, especially in moderate and severe cases that are generally refractory to conventional treatment, and we will cite some results of its use in other areas of medicine by several authors.

### **2. Dry eye: definition and classification**

The tear has several important functions to the ocular surface, such as lubrification, transport of oxygen, carbon dioxide and other metabolites, immunological actions, and maintenance a stable corneal surface, among others. It is rich in immunoglobulins, growth factors, and vitamin A. It

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

is separated in three layers: the lipid layer, which protects the tear against evaporation and is secreted by Moll, Meibomian, and Zeiss glands [1]; the mucin layer produced by Manz glands, Henle crypts, and corneal and conjunctival cells—this one stays between the hydrophobic ocular surface and the hydrophilic tear film [2]; and the last and the most prevalent layer, the aqueous layer, produced by Wolfring and Krause glands [3].

in its classification [13]. It is more frequently in women [14], probably because of the hormone

The Use of Platelet-Rich Plasma in Dry Eye Disease http://dx.doi.org/10.5772/intechopen.76090 23

It is more common in Asia and Europe, with only one study showing the prevalence in South of Equator [4], and it seems to be also more frequent in older people, possibly because of the

Diagnosis is controversial, and literature shows the lack of correlation between some objective tests and symptoms; this is probably due to the difficulty in understanding dry eye patho-

There are some guidelines in this theme, and one of them is the American Academy of Ophthalmology that relates that dry eye diagnosis is obtained after a clinical approach that include asking the patient about exposition to dry eye risk factors and the most common symptoms and signs like redness, itching, photophobia, dryness, foreign body sensation, or pain. It is also important to ask the patient about the exposition to some kind of pollutant, if he is a smoker, if he has any systemic disease (like dermatological, allergic, or rheumatic diseases), checking the hygiene of eyelashes and eyelids, use of medications, eyedrop use, previous ocular surgeries [17], and use of a screening questionnaire as the OSDI (Ocular Surface Disease Index) [18]. The clinical history is followed by a complete ophthalmological exam, including evaluating the eyelids, skin, nerves, visual acuity, and biomicroscopy, and some specific tests like tear breakup time, tear film osmolarity determination, and ocular surface staining with fluorescein lissamine green [4]. The assessment of the tear meniscus (less than 0.35 mm is abnormal) can be performed, verifying if the blink rate is decreased and evaluate

the quality of the tear (if there are mucus and debris) and corneal topography [3].

protects the cell's stress; but none of them has the natural tear properties [20, 21].

Management of dry eye disease will depend on the cause of this condition and its severity. There is currently no cure for dry eye, and any causal factors that are amenable to treatment should be treated. It includes modifications of the environment; suspension of topical or systemic medications, associated with worsening when possible; artificial tear lubrification; and

Generally, the conventional treatment is the lubricants, but it does not resolve all the cases. There are a wide variety of artificial tears, like 1% sodium hyaluronate, hypotonic solutions, those that contains lipids or substances with bioadhesive properties and formulas that have substances that

Other therapies are topical cyclosporine and corticosteroids [22], but these have some disadvantages such as eye irritation and ocular pressure elevation and cataract, respectively [23, 24]. In moderate cases we can also use systemic supplements with omega-3 and linoleic acids and the increased consumption of water, lacrimal occlusion, and glasses use. In severe dry eye, in addition to all these treatments, we can take another measure like systemic cholinergic agonists, systemic anti-inflammatory agents, mucolytic agents, contact lenses, correction of

aging alterations in the lids, glands, ocular surface, and adnexal tissue [15].

effects in the ocular surface and eye glands [4].

**4. Diagnosis and treatment**

physiology [16].

eyelid hygiene [19].

The most recent definition of dry eye is that it is a multifactorial disease of the tears and ocular surface, which is accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles [4]. The inflammation of the ocular surface can be both the cause and the consequence of dry eye: dysfunction of the lacrimal glands alters the tear composition, leading to hyperosmolarity that stimulates more inflammation [5], and another factor recognized in dry eye pathogenesis is oxidative stress [6].

There are several risk factors for dry eye, all of them are controversial. These are female sex, menopause therapy, omega-3 deficiency, refractive surgeries; use of some medications as antihistaminic drugs, antihypertensive drugs, diuretics, antidepressants, and others; hepatitis C; radiation therapy; Asian race; HIV and HTLV infection; chemotherapy; isotretinoic acid use; large facetectomy incisions; low humidity environments; ovarian dysfunction; and sarcoidosis [7].

This disease is actually classified into two primary categories: these are tear-deficient and evaporative categories. The tear-deficient dry eye group generally can be due to Sjogren's syndrome or non-Sjogren's syndrome. Sjogren's syndrome is an exocrinopathy in which lacrimal secretion deficiency occurs due to an autoimmune process that affects the lacrimal glands, salivary glands, and other organs of the body [8]. Non-Sjogren's syndrome is caused by lacrimal diseases or lacrimal obstruction and by reflex alterations, without autoimmune factor role. Some causes are age-related dry eye, congenital alacrima, familial dysautonomia, sarcoidosis, lymphoma, AIDS (acquired immunodeficiency disease syndrome), gland denervation, lacrimal obstruction as in pemphigus, trigeminal injury, diabetes, neurotrophic keratopathy, use of contact lenses, and motor reflex block due to VII pair injury [9, 10]. The evaporative causes of dry eye disease are due to oil deficit, lid changes, use of contact lenses, or ocular surface diseases, as allergic conjunctivitis, and some of the iatrogenic dry eye that occurs after the use of systemic or topical medications or after surgeries or nonsurgical procedures [8, 11].

Dry eye can be also classified according to severity. One of the schemes is proposed by Delphi Panel [8, 12]. This classification in grades 1–4 (mild to severe) is based on the frequency or intensity of the dry eye symptoms and discomfort, the blurred vision and visual symptoms, conjunctival injection or redness, conjunctival staining, corneal staining, changes in the cornea and tear as in ocular surface, alterations in the glands and lids, tear film break-up time (TFBUT), and Schirmer's test values.
