September 2018

CORNEA

Presentation spotlight
Reversing dry eye and ocular surface disease


by Stefanie Petrou Binder, MD, EyeWorld Contributing Writer












Slit lamp exam showed intense punctate keratopathy in both eyes and filamentary keratitis in the left eye.
Source: Merce Morral, MD, PhD








The patient underwent treatment with PRGF eye drops for 2 months. A significant improvement in symptoms (especially photophobia) and signs was observed. Minimal fluorescein staining was seen and complete resolution of filamentary keratitis.
Source: Merce Morral, MD, PhD

 

Indispensable femto

Tal Raviv, MD, discusses
complex cases for which
femto is indispensable.

Case study report supports the implementation of plasma rich in growth factors (PRGF) for the management of severe dry eye, with benefits that extend beyond reducing dry eye symptoms

Steroids and lubricants may ameliorate dry eye symptoms, but they do not address the root of the problem. Healing the cornea, particularly in the presence of advanced ocular surface disease (OSD), requires a different approach and is far more beneficial for eye health and good vision. According to a case study presented at the 22nd ESCRS Winter Meeting, plasma rich in growth factors (PRGF) may represent an effective means to handle dry eye in these patients.

When steroids aren’t enough

The case was presented by Merce Morral, MD, PhD, Instituto de Microcirurgia Ocular, Barcelona, Spain, who described a 62-year-old female patient who had been suffering from severe dry eye for 20 years. The patient had primary biliary cirrhosis and secondary Sjögren’s syndrome. She came to Dr. Morral’s clinic with complaints of intense photophobia and a foreign body sensation in her eyes. Severe ocular surface disease was noted upon examination, with clinically significant cataract in both eyes. The patient had Fuchs’ endothelial dystrophy and a history of cyclosporine 0.05% intolerance.
The patient was a high hyperope (+7.00) with a corrected visual acuity (CDVA) of 0.2 (right eye) and 0.5 (left eye). Her IOP was 14 mm Hg and aqueous tear secretion was significantly reduced (Schirmer’s test: 4 mm right side, 0 mm left). The slit lamp exam revealed filaments with fluorescein staining, with the meibomian glands, however, within normal limits.
Dr. Morral was faced with the dilemma of deciding how to approach management. “What we had to do first was improve the ocular surface, knowing that it was likely to worsen after the surgery,” Dr. Morral explained. “Secondly, we needed to manage the ocular surface because ocular surface disease can affect IOL power calculations. Cataract surgery can only be performed when the ocular surface is taken care of. This patient had some serious symptoms associated with dry eye, including significant ocular surface inflammation, severe aqueous deficiency, and filamentary keratitis.”
The treatment began with topical steroids and diverse lubricants and a vitamin A ointment at bedtime. Although the patient had a significant symptomatic improvement 2 months later, Dr. Morral could note no change in ocular surface disease when she examined the patient by slit lamp. She added PRGF (Endoret), a technology developed by the BTI Biotechnology Institute of Spain, into the treatment mix at this point, prescribing drops four to five times per day, in addition to the previously prescribed regimen. Two months after the addition of plasma rich in growth factors, there was a significant improvement in both symptoms and ocular surface signs.
Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film and accompanied by ocular symptoms in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles. One study that investigated PRGF effects on wound healing and haze formation after PRK surgery in mice found that PRGF stimulated the proliferation and migration of epithelial cells, allowing regeneration, corneal wound healing, and a reduced haze formation.1 Another study by the same investigative team that reviewed the technology of PRGF in ocular surface disorders found its use in enhancing tissue regeneration to be safe and efficient.2 In yet another investigation, results suggested that PRGF could reduce scarring while stimulating wound healing of the ocular surface.3
Ocular surface wound healing is mediated by different growth factors. PRGF is an autologous platelet-enriched plasma obtained from the patient’s own blood, which is activated by calcium chloride to release different biologically active proteins that influence and promote processes such as cell recruitment, cell growth, and cell differentiation.

After OSD is stabilized

PRGF demonstrated corneal healing effects, allowing Dr. Morral to consider the next step in her patient’s treatment. The patient’s corrected distance visual acuity was 0.2 (right eye) and 0.4 (left eye), and the IOP was 15 mm Hg. With the cornea stabilized, she took the next step to carry out cataract surgery, with toric IOL implantation. She explained that toric IOLs were considered only because the topography and keratometry were consistent, measured on the same devices and stable over time from one visit to the next. She noted postoperative edema for 1 month after surgery, which slowly resolved. She also observed a temporary worsening of the ocular surface disease, which was expected and also resolved.
“We kept the patient on plasma rich in growth factor eye drops four to five times daily, along with a steroid, that we slowly tapered down, lubricants, an ocular hypertensor, and hyperosmotic ointment at bedtime to help the cornea recover after the surgery, as she also had Fuchs’ dystrophy,” Dr. Morral explained. “By 6 months postoperatively, she was asymptomatic with absolutely no photophobia, although she still had a few bad days here and there. We have kept her on low-dose steroids and plasma rich in growth factor, and there has been no IOP increase.”
She explained that endothelial cell loss and the corneal nerve density were related. One study that evaluated the changes in corneal endothelial cell density in dry eye patients showed that endothelial malfunction could affect the ocular surface. The study implicated the potential supportive role of nerve derived molecules for cornea endothelial cells in dry eye disease patients with a reduced corneal nerve density as causing an accelerated corneal endothelial cell loss over time.4
Dry eye is common in elderly patients and being multifactorial in nature, has proven to be tough to manage. The hallmarks of dry eye are discomfort, foreign body sensation, visual disturbance, and tear film instability that may in turn cause damage to the ocular surface, if left untreated. It can affect different parts of the ocular surface, including the meibomian glands, the main lacrimal gland, and the ocular surface nerves. Dry eye is triggered by stress to the ocular surface, antigens, and genetic factors. It is perpetuated through the body’s inflammatory response and is associated with the long-term use of certain medications, advanced age and female gender, allergies, prolonged screen time, laser surgery, diabetes, and autoimmune disorders like Sjögren’s syndrome and rheumatoid arthritis.
Dr. Morral said that in patients with OSD, cataract, and Fuchs’ dystrophy, it is essential to treat the inflammation with steroids, cyclosporine, and lifitegrast, when available. EW

References

1. Anitua E, et al. Plasma rich in growth factors (PRGF-Endoret) stimulates corneal wound healing and reduces haze formation after PRK surgery. Exp Eye Res. 2013;115:153–161.
2. Anitua E, et al. Plasma rich in growth factors for the treatment of ocular surface diseases. Curr Eye Res. 2016;41:875–82.
3. Anitua E, et al. Plasma rich in growth factors (PRGF-Endoret) stimulates proliferation and migration of primary keratocytes and conjunctival fibroblasts and inhibits and reverts TGF-beta1-induced myodifferentiation. Invest Ophthalmol Vis Sci. 2011;52:6066–73.
4. Kheirkhah A, et al. Patients with dry eye disease and low subbasal nerve density are at high risk for accelerated corneal endothelial cell loss. Cornea. 2017;36:196–201.

Editors’ note: Dr. Morral has financial interests with Shire (Lexington, Massachusetts), Alcon (Fort Worth, Texas), and AVX Pharma (Barcelona, Spain).

Contact information

Morral
: Merce.morral@gmail.com

Reversing dry eye and ocular surface disease Reversing dry eye and ocular surface disease
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