Revista Cubana de Oftalmología 2014;27(4):598-609

RESEARCH

Clinical and epidemiological

characterization of keratoconus

Clinical and epidemiological characterization of keratoconus

II Dr. Elizabeth T. Escalona

Dr. Zaadia Pérez Parra, Dr. Solaimi Ulloa Oliva,
Leyva, Dr. Alexeide C. Castillo Pérez, Dr. Susana Márquez Villalón
I I

I Cuban Institute of Ophthalmology "Ramón Pando Ferrer". La Habana, Cuba.

II San José General Hospital, Mayabeque. Cuba.

SUMMARY

Objective: to describe the clinical and epidemiological characteristics of

keratoconus in the Cuban Institute of Ophthalmology "Ramón Pando Ferrer".
Methods: a descriptive study was conducted in 72 patients (128 eyes) with
keratoconus, attended between January and December 2012, to identify general
and ocular diseases, time of use of contact lenses, clinical manifestations, type of
astigmatism, keratometric power, thickness of the central cornea, topography and
confocal microscopy.
Results: 50% of the patients showed a slow and progressive decrease in vision,
with a significant absence of general diseases. The prolonged use of contact lenses
(67%), the improvement of visual acuity with correction, and miopic composite
astigmatism (85.2%) were significant (p< 0.05). Decreased thickness of the
central cornea (493.2 µm) predominated. The keratometric power intervals of the
central cornea were equally represented (p= 0.211). By topography, irregular
astigmatism predominated
(99,2 %) and the central cone (87,5 %). Confocal microscopy reflected alterations
in almost all layers of the cornea.
Conclusions: Allergic keratoconjunctivitis is the eye disease most frequently
associated with keratoconus. It has a topographic pattern of irregular astigmatism
with central cone and visual acuity with correction, with contact lenses of 0.6.
Confocal microscopy is a valuable tool in the diagnosis of keratoconus.

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Keywords: keratoconus, clinical characterization, confocal microscopy.

ABSTRACT

Objective: to describe the clinical and epidemiological characteristics of

keratoconus treated at "Ramón Pando Ferrer" Cuban Institute of
Ophthalmology. Methods: a descriptive study was conducted in 72 patients
(128 eyes) with keratoconus, from January to December 2012, to identify
general and ocular diseases, length of time wearing the contact lenses, clinical
features, type of astigmatism, keratometric power and central corneal
thickness, topography and confocal microscopy.
Results: in the group, 50 % had slow gradual decrease of vision, with no
significant medical illnesses. Wearing contact lenses for a long time (67%), the
improvement of visual acuity with correction and myopic compound astigmatism
(85.2%) were significant (p< 0.05). Thinning of the central cornea (493.2
microns) predominated. Keratometric power intervals of the central cornea were
represented equally (p= 0.211). The irregular astigmatism (99.2%) and the
central cone (87.5%) prevailed in terms of topography. Confocal microscopy
changes in almost all the corneal layers.
Conclusions: Allergic keratoconjunctivitis is the most associated eye disease. It
has topographic pattern of irregular astigmatism with central cone and corrected
visual acuity, with 0,6 contact lenses. Confocal microscopy is a valuable tool in
the diagnosis of keratoconus.

Key words: keratoconus, clinical characterization, confocal microscopy.

INTRODUCTION

Keratoconus is a bilateral, progressive, noninflammatory corneal ectasia with

probably multifactorial etiology, which causes irregular mycopic astigmatism
and decreased visual acuity.

The first description in the literature of keratoconus appears in 1748, in a

doctoral dissertation, in which the German ophthalmologist Burchard Mauchart
called it Staphyloma diaphanum. However, it was not until 1854 that the British
physician John Nottingham clearly described this phenomenon and
distinguished it from other corneal ectasias.1
It is considered a rare disease, with a low incidence in the world population, which
is estimated at 2 cases/100,000 inhabitants/year and a prevalence of 54/100,000
inhabitants.2 As a result of the development and expansion of corneal surveyors
and artificial intelligence methods coupled to them that allow diagnosis in
subclinical stages, Most ophthalmologists consider the incidence to be much
higher and variable.

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Moderate and severe stages of the disease pose no diagnostic difficulty, which is
due to the presence of typical signs. However, the diagnosis of subclinical or mild
forms of keratoconus represents a challenge due to the absence of clinical signs or
the minimal presence of these.

Studies carried out in relation to the biomechanics of the cornea raise the
existence of structural changes (tissue destruction and scarring) of a tissue with
its altered capacity in response to oxidative damage that generates an
architectural weakness from which the structure yields to factors such as
intraocular pressure.3,4

Many hypotheses have been made regarding histopathological mechanisms. The

most proven is the increase in collagenous activity and the absence of protease
inhibitors. In recent years genetic theory has gained ground, especially in relation
to the discovery of the VSX 1 gene mutation on chromosome 22, found in 4% of
families. Consequently, a combination of genetic and mechanical hypotheses in
the etiology of keratoconus is considered more likely.5,6

In keratoconus treatment options we have correction with contact lenses of

special design, intrastromal rings and crosslinking of corneal collagen that
have allowed to delay or avoid corneal transplant surgery.

The documented studies on keratoconus are scarce in Cuba, so we proposed to

describe the clinical and epidemiological characteristics of keratoconus in the cornea
consultation of the Cuban Institute of Ophthalmology "Ramón Pando Ferrer".

METHODS

A descriptive, observational and prospective study was carried out, whose

universe was constituted by 72 patients (128 eyes) with diagnosis of keratoconus,
attended at the corneal consultation in 2012 at the Cuban Institute of
Ophthalmology "Ramón Pando Ferrer".

Each patient was previously advised to stop wearing contact lenses one month
before the consultation. Biomicroscopy was performed with slit lamp, schiascopy,
refraction, pachymetry, keratometry, corneal topography (Atlas, Zeiss) and
confocal microscopy (Confoscam4, NIDEK). The following variables were studied:
age, sex, associated systemic diseases, associated ophthalmological diseases,
time of use of contact lenses, symptoms, signs, type of astigmatism, central
corneal keratometric power, pachymetry, crystal-free visual acuity (CVA), crystal-
visual acuity (CVA), topographic pattern and histological alterations.

The data were obtained directly from the patient and collected in the model
created for this purpose. A database was created in SPSS version 11.5.1,
where information was processed and analyzed using descriptive and
inferential techniques.

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RESULTS

59.7% of the patients were female; The mean age was 35 years, while by age
group the 30 to 39 years interval was the most represented percentage, with age
averages by more or less similar sex (Table 1). Finally, it is shown that ages differ
significantly (p= 0.0000).

The association of general diseases was analyzed and it was found that 26.4%
had some disease, in correspondence mainly with bronchial asthma and
allergies (13.9% and 12.5% respectively). The absence of systemic diseases
associated with keratoconus was statistically significant in our study. The
absence of an association of diseases and keratoconus occurred in 71.9%.
Allergic keratoconjunctivitis (21.9%) was the most common ophthalmological
condition (Table 2).

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Half of the patients reported a slow and progressive decrease in vision, while 25
patients (34.7%) frequently changed their optical correction (Table 3). Symptoms
such as itching and contact lens intolerance were described by 18.1% of patients.
The presence of any ophthalmic sign was observed in 85.9% of the eyes, and the
most frequent were the conical cornea (38.3%), Munson’s sign (33.6%),
prominent corneal nerves (25.8%) and the scissor sign from schiascopia (65.6%).

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When analyzing the visual acuity, it was observed that the mean of the CVA was
0.1 while in the CVA it was 0.6 0.3 lines (Table 4), where a significant increase
of the CVA was observed (p= 0.000).

Compound myoal astigmatism was significant (p= 0.000) in 85.2% of the eyes, while
the remaining forms of astigmatism were uncommon, below 10% (Table 5).
Regarding the keratometric power of the central cornea, we found that the three
keratometric groups follow the same distribution (p= 0.211). The mean thickness of
the central cornea was 493.2 µm dispersed in 43.4, contained between 485.6 and
500.8 µm with 95% certainty. When comparing the average in microns of the
thickness of the central zone of the cornea with the standardized value (538.09 µm)
it is observed that it is significantly less (p= 0,000) both the estimated value on time
and per confidence interval.

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When evaluating the correction used, we found that 67% of the patients wore
contact lenses for a time greater than or equal to 12 years. The prolonged use
of contact lenses was significant in relation to the diagnosis of keratoconus (p=
0.000).

According to the topographic pattern, irregular astigmatism was significantly

higher (p= 0.000) often around 99.2%. The central location of the cone was
statistically significant (p= 0.000) at 87.5%, which is justified because 73,000,5%
of the eyes were classified as mild and moderate keratoconus (Table 6).

In confocal microscopy we find in the epithelium fine nerves that penetrate the
basal epithelium (96.1%) and abnormal reflectivity (62.5%). In the Bowman
membrane the most frequent alterations were hyperreflectivity (93.8%) and
invasion of keratocytes (92.2%).

In all the eyes studied, there was a decrease in the density of keratocytes and in the
transparency of the background, deep stromal hyperreflectivity and a decrease in the
cross-linking of collagen fibers. In addition, the

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presence of hyporeflective microsystems and striae with predominance of the

vertical orientation (93,8 %).

In the subepithelial nerve plexus (Fig.), the most frequent findings were the
decrease in nerve density (93.7%), nerve fibers that adopt oblique and
horizontal orientation (96.1%) and curvilinear form (86.7%).

ARGUING

The origin of keratoconus is not clearly defined, but there are several theories
that try to explain its presentation. Its incidence varies in several countries,
however, in Cuba there are no epidemiological studies that allow us to know the
true dimension of this condition. In this research keratoconus was more frequent
in the female sex and in the ages between 30-39 years.

Revised research found that the diagnosis of keratoconus was obtained around 24
age of 30, while in men it was a little more early
years of age each and mostly before the
diagnosis and faster evolution.7
Race is not reported as a determinant.

In relation to sex, literature is controversial; Some authors consider that it has the
same distribution in both sexes.7
However, in recent years it has been found that in some
series it would be more frequent in men in a percentage of around 60%.8,9

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La ausencia de asociación de enfermedades sistémicas al queratocono fue

estadísticamente significativa en este estudio y entre las enfermedades
oftalmológicas asociadas se encontró la queratoconjuntivitis alérgica como la más
frecuentemente reportada. Albertazzi plantea que el queratocono no asociado a
otras patologías es el probablemente más frecuente de todos; sin embargo, la
asociación a enfermedades sistémicas ha sido ampliamente documentada por
7,10,11
otros autores, entre las que se consideran el asma bronquial, la
queratoconjuntivitis alérgica y el antecedente de compresión, el frote y el
restregado ocular como las más frecuentes.

Estudios retrospectivos han encontrado una historia de uso de lentes de contacto

antes del diagnóstico de queratocono en 17,5 y 26,5 % de casos, lo que es
excepcional en portadores de lentes de contacto blandas. Esta asociación
circunstancial no demuestra una causa-efecto, se reporta una antigüedad media
11-13
en el porte de más de 12 años. En nuestro estudio fue significativo el tiempo
prolongado de uso de lentes de contacto en los pacientes evaluados.

A medida que el queratocono progresa, la agudeza visual se ve comprometida

por la distorsión que genera el cono. Como consecuencia, la aparición de una
fuerte miopía axial combinada con un alto astigmatismo irregular dificulta la
corrección óptica, y llega a inhabilitar a la persona afectada para el desarrollo de
una vida normal, quien requiere cambio frecuente de graduación. Los síntomas
más frecuentemente reportados en nuestra investigación fueron la disminución
lenta y progresiva de la visión y el cambio frecuente de lentes de contacto.

En correspondencia con los reportes de la literatura, los signos predominantes

fueron la córnea cónica, el signo de Munson y los nervios corneales
prominentes. Alió y otros encontraron que los nervios corneales son más
visibles y el anillo de Fleischer y las estrías de Vogt fueron visibles en un 50 %
cada uno. Al realizar la esquiascopia se producen sombras en tijera cuando el
11
queratocono es más avanzado.

Aunque no se logra el rango de visión superior a 0,7 (AVCC de 0,6 ± 0,3

líneas) pudimos observar que la AVCC obtenida en nuestro estudio fue
superior a las reportadas en la bibliografía consultada. Estudios realizados en
el Instituto Oftalmológico de Alicante encontraron un promedio de AVSC de 0,1
12
± 0,06 y el promedio de AVCC de 0,3 ± 0,08.

En este estudio predominó el astigmatismo miópico compuesto. El rango de 48-54

dioptrías queratométricas agrupó al mayor número de pacientes y la paquimetría
corneal media central fue de 493,2 µm. Estos resultados nos permiten agrupar a
nuestros pacientes en las etapas I-II del Sistema de Krumeich. Nuestros
resultados fueron paralelos a estudios publicados, donde la paquimetría de la
córnea central disminuye a medida que progresa el queratocono. Más
11
recientemente se ha podido demostrar que la paquimetría es un valor útil en el
diagnóstico del queratocono subclínico, que lo diferencia del adelgazamiento que
se puede encontrar por el uso del lente de contacto.

Al evaluar el patrón topográfico, encontramos de manera significativa la

presencia de astigmatismo irregular y localización central del cono. Autores
11
citados por Alió encontraron que el cono se localizó en el sector inferotemporal
en más de la mitad de los casos.

La microscopia confocal se presenta como una nueva herramienta que permite

observar en vivo la histología y complementar las observaciones de biomicroscopia
convencional, lo que constituye un reto para el mejor entendimiento de la

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histopatología corneal. En pacientes con queratocono encontramos diversas

alteraciones en casi todas las capas de la córnea, exceptuando el endotelio
corneal. Los hallazgos más frecuentes en nuestro estudio fueron presencia de
nervios finos que penetran en el epitelio basal, invasión de queratocitos e
hiperreflectividad de la membrana de Bowman, disminución del número de
queratocitos e hiperreflectividad estromal profunda, microestrías y estrías
hiporreflectivas con predominio de la orientación vertical.

Estudios consultados establecen que en el queratocono se encuentra alterado y

disminuido el entrecruzamiento de las fibras de colágeno, lo que junto a rupturas
en la membrana de Bowman favorecen la "debilidad estructural". En el plexo
nervioso sub-basal se encuentran configuraciones anómalas en el vértice del cono,
donde se observan haces de fibras nerviosas tortuosas, que adoptan orientación
oblícua y horizontal y disminución de la densidad de fibras nerviosas. La
membrana de Bowman presenta rupturas en sitios donde es atravesada por
terminales nerviosas, invadida por queratocitos provenientes del estroma corneal
anterior y por células epiteliales. Estos queratocitos se activan por interleuquinas
derivadas del epitelio y entran en un proceso llamado apoptosis, que si bien se
caracteriza por desarrollarse con una mínima liberación de enzimas
colagenolíticas, la cronicidad en el tiempo origina su pérdida más acentuada en el
6,14,15
estroma anterior, y deriva en un adelgazamiento localizado y progresivo.

Se concluye que los pacientes con diagnóstico de queratocono poseen una edad
media de 35 años de edad, con predominio del sexo femenino, antecedentes de
queratoconjuntivitis alérgica y agudeza visual corregida con lentes de contacto de
0,6, que clínicamente se clasifican en la etapa I y II del Sistema de Krumeich. La
queratoconjuntivitis alérgica es la enfermedad ocular más frecuentemente
asociada al queratocono. Posee un patrón topográfico de astigmatismo irregular
con cono central y agudeza visual con corrección, con lentes de contacto de 0,6.
La microscopia confocal constituye una herramienta valiosa en el diagnóstico del
queratocono.

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Recibido: 20 de junio de 2014.

Aprobado: 7 de agosto de 2014.

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Dra. Zaadia Pérez Parra. Instituto Cubano de Oftalmología "Ramón Pando

Ferrer". Ave. 76 No. 3104 entre 31 y 41 Marianao, La Habana, Cuba. Correo
electrónico: [email protected]

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