Bullous Keratopathy Clinical Trial
Official title:
Comparative Analysis of Human Amniotic Membrane Graft Versus Contact Lenses in Syntomathic Bullous Keratopathy
The amniotic membrane (AM) is an avascular structure derived from fetus, which is a good
choice for regenerative medicine and effective treatment in eye surface pathologies such as
bullous keratopathy (BK). This disease generates a chronic corneal edema evolving to the
production of vesicles and bullae, chronic eye pain and visual acuity decrease.
Definitive treatment for those patients is corneal transplant; however, donation is not
always available and thus requires long waiting times. The currently available palliative
treatment consists in the use of contact lenses to prevent the corneal epithelium from
falling. However, this may be associated with corneal neovascularization, lens displacement
or loss, infections, and discomfort for the patient.
The objective of this work was to compare the use of amniotic membrane grafts versus contact
lenses in patients suffering from BK awaiting a corneal transplant.
A randomized clinical trial assay was performed with patients with a clinical diagnosis of
BK. Twenty patients were randomized into 2 groups: amniotic membrane and therapeutic contact
lenses. Eye pain intensity (Analog visual scale), visual acuity (Snellen questioner), bullae
and corneal epithelial defects presence, as well as corneal neovascularization and
complications (biomicroscopy) were compared during 6 months.
INTRODUCTION Handling of patients with severe eye surface injuries has always been
challenging in the field of ophthalmology. One of the most significant pathologies causing
severe injuries is Bullous Keratopathy (BK). This disorder is caused by a failure in corneal
endothelial pump (Na+/K+/ATPase) characterized by chronic stromal edema, and it tends to
evolve to the production of corneal vesicles and bullae due to the drainage of fluid to the
anterior corneal layers as a consequence of intraocular pressure(1). Most common causes of
BK are intraocular surgical procedures including those related to cataract surgery(2). This
entity conforms the first cause for corneal transplant in the USA (from 26 to 50%) and the
second in Europe(3,4,5).
Clinically, BK is characterized by chronic ocular pain, which is secondary to recurrent
epithelial defects, ocular surface inflammation and visual sharpness decrease(1). Definitive
treatment for patients with BK with remaining visual potential is corneal transplant.
However, donor grafts are not always available and they often require long waiting times.
For those reasons, medical and surgical palliative measures should be temporarily used to
relief ocular pain. Among others, the use of therapeutic contact lenses stands out as one of
the best alternatives due to its contribution to the prevention of epithelial falling and
ulceration, acting as a mechanical bandage(6,7,8). These contact lenses do not improve
visual sharpness neither contribute to the resolution of the problem that originated corneal
edema. Besides, prolonged use of contact lenses may be associated to potential complications
such as ocular disturbance, superficial neovascularization, inflammation and corneal
infections, together with the economical expenses that patients have to deal with(6).
In 1940, De Roth described for the first time the use of human amniotic membrane (AM) in
ophthalmology, and since that date, multiple studies guaranteed its application as an
efficient treatment for ocular surface diseases(9,10, 11), including
BK(12,13,14,15,16,17,18). AM is a thin membrane covering the foetal side of the placenta,
and it consists of the external chorion (maternal origin) and the internal amnion (foetal
origin). Histologically, it is composed of three layers: epithelium, basal membrane and
stroma(19).
The therapeutic effect of the AM involves three basic synergistic actions on the ocular
surface: 1) induction of growth and proliferation of new epithelia on the tissues (cornea
and/or conjunctiva), 2) control of the inflammation of the tissues under the implant and 3)
inhibition of fibrosis and neovascularization of the corneal stroma(19). For all these
reasons AM might be an effective treatment to ameliorate disturbances generated by BK. In
addition, human amniotic epithelial cells do not express HLA surface antigens, which
justifies the absence of graft rejection in this type of transplants(20,21) and makes it a
highly safe procedure.
In the present work, we describe the results of a randomized clinical trial in which the AM
grafting technique was compared with the use of therapeutic contact lenses for the
management of symptomatic bullous keratopathy in patients waiting for a corneal transplant
at Carlos Van Buren Hospital from Valparaiso, Chile.
PATIENTS AND METHODS Study design Randomized clinical trial. Patients The universe of this
clinical trial are all patients with clinical diagnosis of symptomatic bullous keratopathy
(corneal bullae, recurrent eye pain, foreign body sensation and photophobia), diagnosed at
the Department of Ophthalmology Hospital Carlos Van Buren, Valparaiso, Chile, who were on
the waiting list for corneal transplant from January 2008 to October 2011. Excluded patients
were those with medical contraindication to undergo surgery with topical anesthesia,
patients with severe systemic conditions and patients with corneal infections.
Twenty patients, corresponding to universe of patients during this period, accepted to
participate in this study and were included in this clinical trial. All patients provided
written consent to participate in this study, and the trial was approved by the Ethics
Committee of the Faculty of Medicine, Universidad de Valparaiso (Nº 10/2011). Patients were
randomized on a simple random basis from a prefabricated list and divided into two groups:
study group (N=10), with the implant of the AM, and control group (N=10), in which contact
lenses were used.
Clinical data and variables considered for the study were: demography, etiology of BK,
ocular pain (evaluated by using a visual analogue scale ranging from 0 to 10) and visual
acuity (Snellen scale). By using a bio-microscope we evaluated the presence of bullae and
epithelial defects per quadrant (with fluorescein test) and neovascularization. After
treatment, the same equipment was used to check for presence of traces of AM and
complications (infection, wound dehiscence, etc) through serial controls performed over a
period of 6 months.
Interventions Human AM was prepared and preserved in the Biomedical Research Centre using a
method previously described by Lee and Tseng (1995). In the study group, amniotic membrane
(AM) grafts were implanted in the affected eyes using topical anesthesia. Each graft was
sutured to the bulbar conjunctive tissue using 10-0 nylon sutures and a reinforcement stitch
was applied at the cornea (Figure 1).
Therapeutic contact lenses were applied in all patients included in the control group and
the lenses were replaced every two months according to the pre-established gold standard for
this procedure.
Clinical follow-up examination was performed on days 1, 7, 30, and then monthly until 6
months for both groups. Both groups were managed with topical gentamicin each 4 hours during
the first week after surgery.
Statistical analysis. Data were analysed with Stata SE 12.0 software. Results corresponding
to continuous variables were described by medians and interquartile range (IQR) and
categorical medians were described by percentages and frequencies. Mann-Whitney statistical
test was used to detect statistical differences between two continuous variables, and Fisher
exact test was used for categorical variables. Association between quantitative variables
was established by Kendal's tau correlation test. For all analysis, a value of p<0.05 was
considered statistically significant and all analyses were carried out double tailed.
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Investigator, Outcomes Assessor), Primary Purpose: Treatment
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