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Бикбов Мухаррам Мухтарамович,
Бикбов Мухаррам Мухтарамович
Доктор медицинских наук, профессор, директор Уфимский научно-исследовательский институт глазных болезней Академии наук Республики Башкортостан, Уфа
Халимов Азат Рашидович,
Халимов Азат Рашидович
Кандидат биологических наук, заведующий научно-производственным отделом Уфимский научно-исследовательский институт глазных болезней Академии наук Республики Башкортостан, …
Усубов Эмин Логман оглы
Усубов Эмин Логман оглы
Кандидат медицинских наук, заведующий отделением хирургии роговицы и хрусталика Уфимский научно-исследовательский институт глазных болезней Академии …
В обзоре представлены основные сведения об ультрафиолетовом кросслинкинге (сшивании) роговицы, который нашел широкое применение в офтальмологии в лечении различных видов кератэктазий. Кросслинкинг основан на ультрафиолетовом (УФ) облучении роговицы длиной волны 370 нм в присутствии рибофлавина, приводящем к интракорнеальным фотохимическим взаимодействиям. В результате процедуры сшивания коллагена наблюдается увеличение прочностно-механических свойств роговицы, приостанавливается прогрессирование заболевания. В статье отображены этапы разработки метода и способы его выполнения, сферы клинического применения, описаны особенности происходящих биомеханических, биохимических, морфологических и ультраструктурных изменений в роговице, вызванных рибофлавин-УФА-индуцированным сшиванием.
Ophthalmology in Russia,
Journal Year:
2024,
Volume and Issue:
21(4), P. 802 - 808
Published: Dec. 24, 2024
Corneal
cross-linking
(CXL)
has
become
the
most
common
way
of
managing
keratectasia.
To
date,
Dresden
protocol
(G.
Wollensak
et
al.,
2003)
acquired
many
modifications,
in
which
composition
applied
agents
or
modes
CXL
procedure
have
been
changed.
This
article
presents
results
studying
morphological
changes
rabbit
cornea
vivo
after
using
riboflavin
solutions
different
composition.
Purpose
:
compare
effect
on
corneal
structure
experimental
animals
by
confocal
microscopy
with
saline,
dextran
and
hydroxypropylmethylcellulose.
Material
methods
.
The
study
was
performed
20
eyes
15
rabbits,
underwent
standard
(Epi-Off)
0.1
%
3
groups:
first
group
saline
used
as
a
base,
second
—
dextran,
third
1.0
hydroxypropyl
methylcellulose
(HPMC).
irradiation
mode:
mW/cm2,
30
minutes,
wavelength
370
nm.
condition
evaluated
at
3,
7,
14,
90
days
CXL.
Biomicroscopy
were
all
Heidelberg
Retinal
Tomographer
HRT-III
(Heidelberg
Engineering,
Germany).
Keratocyte
density
counted
depth
120–160
μm
central
zone
area
1
mm2.
Statistical
processing
Statistica
6.1
Excel
2010
programmes.
Results
In
biomicroscopy
corneas
showed
postoperative
epithelium
stroma
groups,
7
CXL,
there
decrease
keratocyte
density,
due
to
apoptosis,
observed
predominantly
anterior
layers
stroma.
number
keratocytes
192.5
±
29.8
cells/mm2,
2
227.4
38.2
204.4
32.6
cells/mm2
against
intact
control
352.8
35.2
cells/mm2.
There
not
statistically
significant
difference
between
groups.
Conclusion
lifetime
demonstrated
similar
early
period,
accompanied
loss
subepithelial
nerve
fibres,
development
lacunar
edema,
apoptosis
their
mainly
middle
beginning
repopulation
fibre
regeneration
30th
day
No
signs
endothelium
damage
detected.
A
comparative
assessment
greatest
effectiveness
techniques
0.1%
HPMC
can
be
given
basis
larger-scale
clinical
studies.
Russian Annals of Ophthalmology,
Journal Year:
2016,
Volume and Issue:
132(6), P. 29 - 29
Published: Jan. 1, 2016
To
evaluate
the
dynamics
of
riboflavin
changes
in
aqueous
humour
anterior
chamber
(AHAC)
rabbits'
eyes
during
standard
ultraviolet
(UV)
cross-linking
with
account
to
area
corneal
debridement.Forty
two
rabbits
were
studied
sequentially.
The
following
solutions
used
for
cornea
saturation:
IR
-
0.1%
isosmotic
riboflavin,
D
Dextralink
(0.1%
20%
dextran),
R
1.0%
hydroxypropylmethylcellulose
(HPMC).
Each
solution
was
evaluated
3
groups
that
differed
diameter
debridement:
group
1
Epi-Off
mm
(IR-3,
D-3,
P-3),
2
6
(IR-6,
D-6,
R-6),
and
9
(IR-9,
D-9,
R-9).
Aqueous
sampling
(252
samples
total)
performed
10-minute
intervals
within
a
60
minute
period.
Riboflavin
levels
measured
by
enzyme-linked
immunoassay
(ID-Vit
microbiological
test
system;
Immundiagnostik,
Germany).Stable
growth
rates
level
AHAC
(with
maximum
values
reached
at
30-40
min)
observed
R,
regardless
variant
debridement.
Moreover,
throughout
whole
follow-up
period
debridement,
provided
relatively
lower
concentration
as
compared
other
solutions.
At
30
minutes,
when
considered
ready
UV
irradiation,
ranged
from
385±26.1
μg/l
(D-9)
665±28
(R-9).
In
IR-9,
IR-6,
P-6,
IR-3,
P-3
found
be
same
range
starting
20
minutes.
However,
even
sufficient
or
cannot
guarantee
safe
effective
cross-linking,
since
removed
epithelium
limits
stroma
can
saturated
while
exposure
is
8-10
mm.Safe
efficient
may
only
under
saturation
which
turn
depends
greatly
on
debridement
(should
least
8-9
mm).
A
HPMC
enables
quick
pronounced
and,
thus,
procedure,
including
cases
insufficient
thickness.Цель
оценка
уровня
рибофлавина
во
влаге
передней
камеры
(ВПК)
глаза
экспериментальных
животных
в
динамике
при
стандартном
насыщении
стромы
роговицы
растворами
для
ультрафиолетового
(УФ)
кросслинкинга
зависимости
от
площади
ее
деэпителизации.
Материал
и
методы.
Исследования
проведены
последовательно
на
42
кроликах.
Для
насыщения
использовались
растворы
0,1%
изоосмотический
(ИР),
Декстралинк
(0,1%
рибофлавин
с
декстраном)
(Д),
1%
гидроксипропилметилцеллюлозой
(ГПМЦ)
(Р)
диаметра
деэпителизации
роговицы:
1-я
группа
мм
(ИР-3,
Д-3,
Р-3),
2-я
(ИР-6,
Д-6,
Р-6),
3-я
(ИР-9,
Д-9,
Р-9).
После
у
всех
течение
ч
интервалом
10
мин
выполняли
забор
ВПК
образца).
Уровень
определяли
методом
иммуноферментного
анализа
использованием
тест-системы
ID-Vit
('Immundiagnostik',
Германия).
Результаты.
Установлена
стабильная
динамика
роста
вариантах
эксперимента
использовании
растворов
Д
Р
максимумом
30-40-й
минуте.
Средство
все
сроки
наблюдения
независимо
удаленного
эпителия
обеспечивало
меньшую
концентрацию
по
сравнению
ИР
Р.
На
30-й
минуте
исследования,
когда
роговица
после
считается
готовой
к
УФ-облучению,
содержание
составляло
385±26,1
(Д-9)
до
(Р-9)
мкг/л.
В
этих
же
пределах
20-й
минуты
регистрировался
уровень
фотосенсибилизатора
группах
ИР-9,
ИР-6,
Р-6,
а
также
ИР-3,
Р-3.
Достаточная
концентрация
или
роговице
не
может
гарантировать
выполнение
качественного
безопасного
УФ-сшивания,
поскольку
площадь
образует
строме
ограниченную
зону,
пропитанную
рибофлавином,
так
как
выполнении
УФ-воздействию
подвергается
роговицы.
Заключение.
Безопасный
эффективный
стандартный
УФ-кросслинкинг
быть
выполнен
оптимальном
рибофлавином
преимущественно
за
счет
достаточной
(не
менее
мм).
Раствор
ГПМЦ
обеспечивает
быстрое
значимое
насыщение
фотосенсибилизатором,
что
позволяет
применять
его
процедуре
том
числе
пациентов
тонкой
роговицей.Цель
—
(«Immundiagnostik»,
30—40-й
8—10
роговицей.
Ophthalmology in Russia,
Journal Year:
2019,
Volume and Issue:
16(1S), P. 74 - 78
Published: April 22, 2019
The
article
presents
the
study
results
of
local
antioxidant
status
in
patients
with
progressive
keratoconus
and
its
dynamics
after
ultraviolet
corneal
crosslinking.
Purpose
:
to
oxidative
activity
tear
cornea
Patients
methods
.
To
assess
level
keratoconic
according
levels
total
(TAS)
superoxide
dismutase
(SOD)
fluid,
as
well
their
UV
crosslinking
were
investigated.
included
38
(38
eyes)
stage
I–II
(classification
Amsler),
men
—
24
(63.1
%),
women
14
(36.9
%).
standard
group
(S-CXL)
was
20
eyes,
pulsed
accelerated
protocol
(I-CXL)
18
eyes.
average
age
32.4
±
6.8
years.
As
a
control
group,
12
practically
healthy
individuals
selected.
time
observation
is
before
operation,
on
3rd,
7th,
14th
30th
days
procedure.
Results
On
basis
conducted
studies,
it
revealed
that
showed
statistically
significant
decrease
initial
indicator
TAS
by
40
%
amounted
1.68
0.21
mmol/l,
compared
people
2.82
0.15
mmol/l.
SOD
tears
also
lower
19
96.7
11.3
ng/ml,
119.1
16.5
ng/ml.
use
S-CXL
caused
during
first
3
subsequent
restoration
level.
pulse
A-CXL
this
indicator,
but
end
1st
month
higher
than
preoperative
better
when
using
protocol.
A
treatment
noted
days,
however,
more
collapse
Conclusion
data
had
shown
antioxidative
keratoconus.
Ultraviolet
causes
maximum
3rd
day
procedure,
from
gradual
recovery
observed.
contributed
pronounced
development
cross-linking
damage
It
manifests
itself
reduction
method.
Russian Ophthalmological Journal,
Journal Year:
2019,
Volume and Issue:
12(4), P. 83 - 91
Published: Dec. 12, 2019
The
first
part
of
the
review
[ROJ
2019;
12
(2):
83–95]
presented
a
detailed
description
and
clinical
interpretation
traditional
methods
drug
delivery
in
ophthalmology,
offered
an
analysis
their
advantages
disadvantages.
This
paper
is
second
review,
which
focuses
on
rarely
used
largely
forgotten
methods,
as
well
targeted
means
to
different
structures
eye.
Russian Annals of Ophthalmology,
Journal Year:
2020,
Volume and Issue:
136(5), P. 289 - 289
Published: Jan. 1, 2020
The
article
reviews
data
on
the
so
called
non-surgical
methods
of
keratoconus
(KC)
correction.
combined
approach
to
KC
treatment
entails
three
main
tasks:
prevention
progression,
optical
correction
induced
refractive
disorders,
and
structural
repair.
Measures
taken
accomplish
first
two
tasks
should
be
regarded
as
symptomatic
treatment,
while
addressing
last
task
requires
pathogenetically
oriented
solutions.
Corneal
cross-linking
disorders
with
rigid
gas
permeable
(RGP)
scleral
contact
lenses
choice
for
keratoconus.В
обзоре
представлены
данные
о
так
называемых
нехирургических
методах
коррекции
кератоконуса
(КК).
Комплексный
подход
к
корригирующему
воздействию
на
это
заболевание
роговицы
предполагает
решение
трех
основных
задач:
профилактику
прогрессирования,
оптическую
коррекцию
индуцированных
рефракционных
нарушений
и
восстановление
структурных
изменений.
Решение
первых
двух
следует
расценивать
как
симптоматическое,
а
последней
—
патогенетически
ориентированное.
Кросслинкинг
коллагена
с
помощью
жестких
газопроницаемых
склеральных
контактных
линз
рассматривать
в
качестве
«нехирургических»
методов
первого
выбора
симптоматической
кератоконуса.
Ophthalmology in Russia,
Journal Year:
2018,
Volume and Issue:
15(1), P. 32 - 37
Published: March 24, 2018
Purpose:
To
assess
the
topographic
location
of
demarcation
line
in
different
areas
cornea
after
standard
corneal
crosslinking.
Patients
and
methods.
12
patients
(15
eyes)
with
keratoconus
stages
1–2
Amsler-Kruimerich
classification
were
observed.
UV
cross-linking
was
performed
all
according
to
Dresden
protocol
0.1%
aqueous
solution
riboflavin.
The
underwent
optical
coherence
tomography
anterior
segment
eye
on
“DRI
OCT
Triton”
(“Topcon”,
Japan)
line.
Results.
Demarcation
revealed
1
month
most
cases
(87%).
Biomicroscopy
showed
that
DL
limited
middle
laers
stroma
from
posterior
one.
stromal
depth
averaged
305.73
±
41.08
μm
(range
282–345
μm)
at
center,
nasally
—
215.16
35.5
160–289
temporally
205,23
32.81
190–276
μm).
A
significant
difference
localization
central
zone
a
6
mm
(p
<
0.001)
noted.
Conclusion.
(обычно)
is
one
indicators
photochemical
process
cross-linking.
Optimal
timing
detection
following
collagen
crosslinking
2
weeks
3
months.
studied
different;
it
deeper
than
peripheral
ones.
Ophthalmology in Russia,
Journal Year:
2019,
Volume and Issue:
16(1S), P. 102 - 107
Published: April 22, 2019
The
purpose
:
to
establish
a
combined
approach
the
treatment
of
patients
with
epithelial
and
endothelial
cornea
dystrophy
(EED)
based
on
comparative
study
results
one-step
two-step
methods.
Patients
included
75
(81
eyes)
corneal
EED,
who
underwent
surgical
at
Ufa
Eye
Research
Institute
from
2011
2016.
were
divided
into
two
groups
—
main
group
consisted
43
(46
eyes,
57
%)
patients,
first
stage
CC
before
second
after
1–12
months
automated
posterior
lamellar
keratoplasty
(APLK).
In
control
group,
isolated
APLK
was
performed
in
32
(35
patients.
Results
.
After
(1–10
days)
an
increase
thickness
due
edema
enhancement
stroma
observed
I–III
EED.
3
months,
decrease
recorded
I-II
stages
disease
(p
<
0.05),
6
all
EED
compared
0.05).
According
optical
coherence
tomography
(OCT),
total
both
зфешутеы
noted
within
12
APLK:
667
±
65
μm
initially
594
31
μm,
where
there
pronounced
787
56
612
67
μm.
Conclusion
Corneal
cross-linking
provides
improvement
cornea,
manifested
reducing
its
thickness.
It
allows
delay
implementation
without
deterioration
I
up
6–12
II–III
3–6
months.
Ophthalmology Reports,
Journal Year:
2020,
Volume and Issue:
12(4), P. 29 - 34
Published: March 5, 2020
Corneal
collagen
crosslinking
is
one
of
the
most
effective
methods
prophylactics
and
treatment
progressive
corneal
ectasias.
In
literature,
there
are
occasional
data
related
to
remote
results
concerning
only
common
form
ectasias
keratoconus.
published
studies,
no
met
efficacy
in
other
forms
ectasias,
which
now
on
rise,
including
secondary
that
became
more
frequent
with
refractive
surgery.
The
number
diagnosed
cases
pellucid
marginal
degeneration
increased
as
well.
literature
shows
comparative
analysis
this
method
various
ectasias.
aim
investigation
was
evaluate
based
long-term
for
Materials
methods.
patients
ectasia
6
years
after
surgery
were
analyzed.
nosological
structure
study
included
keratoconus,
degeneration,
ectasia.
group
keratoconus
30
(30
eyes),
eyes).
performed
by
same
specialist,
during
first
or
second
year
follow-up.
Then
changes
state
cornea
visual
functions
monitored
years.
To
assess
efficacy,
preoperative
examination
interim
used.
Results.
all
groups,
an
increase
best
corrected
acuity,
a
decrease
index
asymmetry
surface
its
power
center
However,
obtained
groups
Russian Annals of Ophthalmology,
Journal Year:
2022,
Volume and Issue:
138(3), P. 118 - 118
Published: Jan. 1, 2022
The
article
reviews
the
current
available
data
on
signs
and
symptoms
of
dry
eye
syndrome
(DES)
in
patients
with
keratoconus
(KC),
describes
clinical
features
DES
KC
morphological
this
type
keratectasia
that
lead
to
manifestations
«dry
eye»,
highlights
risk
factors,
consequences
therapeutic
measures,
concomitant
ophthalmological
general
somatic
diseases
contribute
development
KC.В
настоящем
обзоре
представлены
имеющиеся
в
современной
литературе
сведения
о
клинических
симптомах
и
функциональных
признаках
синдрома
сухого
глаза
(ССГ)
при
кератоконусе
(КК).
Перечислены
клинические
особенности
ССГ
КК
морфологические
данного
вида
кератэктазии,
приводящие
к
клиническим
проявлениям
глаза.
Освещены
факторы
риска,
последствия
лечебных
мероприятий,
сопутствующие
офтальмологические
общесоматические
заболевания,
способствующие
развитию
КК.
Russian Ophthalmological Journal,
Journal Year:
2021,
Volume and Issue:
14(2), P. 36 - 41
Published: June 20, 2021
Purpose:to
assess
the
effect
of
ultraviolet
(UVA)
crosslinking
Bioplast
plastic
material
(silicon-dried
human
cornea)
on
its
biomechanical
stability
and
effectiveness
for
keratoplasty
in
corneal
ulcers.
Material
methods.
To
determine
maximum
rehydration
time,
12
samples
were
incubated
physiological
solution
(NaCl
0.9
%)
hours
monitored
thickness
using
optical
coherence
tomography
(OCT
Spectralis,
Heidelberg
Engineering).
After
epithelium
was
scarified
rehydrated
corneas
treated
withof
0.1%
riboflavin
30
minutes,
after
it
8
(experimental
group)
with
UVA
30minutes
(wavelength
370
nm,
power
3
mW/cm
2
)
a
UV-X
device
system
(IROC
AG,
Switzerland).
In
control
group
(4
samples),
no
performed.
The
elastic-strength
indicators
experimental
assessed
by
applying
uniaxial
tension
deformation
machine
(Autograph
AGS-H,
Japan).
examine
patients
(presented
clinical
examples)before
subjected
to
crosslinking,
set
standard
ophthalmic
tests
used.
Results.Rehydration
most
intensive
first
three
incubation,
during
which
time
tissue
increased
uniformly
50–55
μm/hour
700–710
μm,
while
further
incubation
showed
significant
additional
fluid
content
cornea.
strength
indices
elastic
modulus
significantly
comparison
group.
Clinical
examples
demonstrate
modified
organ-preserving
penetrating
case
perforatedcorneal
ulcer.
Conclusion.
increases
stability.
data
laboratory
studies
that
may
be
an
effective
replacement
native
donor
cornea
urgent
perforated