Journal Reading Safety and Efficacy Intracameral Moxifloxacin Randomized Controlled Trial

Safety and Efficacy of Intracameral
Moxifloxacin for Prevention of Post-cataract

Endophthalmitis:
Randomized Controlled
Oleh :
Clinical Trial
Prima Rizky Nur Rasyid
Pembimbing :
dr. Hj. Alteriana Mydriati Sita Pritasari, Sp.M (K)
Departemen Ilmu Kesehatan Mata
Journal Reading Prodi Pendidikan Profesi Dokter

Fakultas Kedokteran Unissula
JUDUL
JURNAL
PENULIS
TAHUN TERBIT & PENERBIT
Identitas Jurnal
ABSTRAK
(Abstract)
Abstrak
PENDAHULUAN
(Introduction)
Introduction
At a glance Endophthalmitis  rare but poor visual prognosis
Pain in the eye
Visual loss
Clinical signs of ocular infections

iridocyclitis, fibrin, and hypopyon
Vitritis
Acute postoperative endophthalmitis after
phacoemulsification caused by
Pseudomonas aeruginosa.
Source : researchgate.net
Introduction
Safety and Efficacy of Intracameral Moxifloxacin for Prevention of Post-cataract Endophthalmitis:
Randomized Controlled Clinical Trial
European Society of Cataract and

2007 Refractive Surgeons (ESCRS)
Published result of a multicenter clinical
trial Intracameral (IC) Cefuroxime in the
prevention of postoperative
endophthalmitis
Result :
IC cefuroxime significantly reduced
the risk for acute postoperative
endophthalmitis after cataract surgery
A systematic review and two meta-analyses

have confirmed the relevance of that study, the results of which
have contributed to the adoption of IC cefuroxime by
numerous surgeons, in particular, in Europe.
Introduction
Source : Arshinoff, Steve. Intracameral Prophylaxis

In Cataract Surgery
However,
the commercial brand of IC cefuroxime (Aprokam)
is unavailable in most countries, including Brazil.
Procedures to prepare the drug in the operating

room create the risk for dilution errors and
contamination, factors that could lead to
intraocular toxicity and infection.
Overdoses of IC Cefuroxime
1 MACULAR EDEMA
2 RETINAL VASCULAR LEAKAGE
3 UVEITIS
4 ENDOTHELIAL TOXICITY
5 TOXIC ANTERIOR SEGMENT SYNDROME

Introduction
In one study,
7 consecutive patients
developed Endophthalmitis caused by Fusarium species
after the use of an ad hoc formulation of IC cefuroxime
Ç akırM, _Imamoglu S,Ç ekiç O, Bozkurt E, Alag€oz N, Oks€uz L, Yilmaz OF. An outbreak of early-onset
endophthalmitis caused by Fusarium species following cataract surgery. Curr Eye Res 2009; 34:988–995
Introduction
Classification
Quinolone 4th Gen
Advantage Antibiotic
broad spectrum
Againts Gram positive, Gram
Moxifloxacin negative, Atypical
Microorganisms & Anaerob
bacterias
Clinical Use has been used worldwide

in the off-label prevention of
post-cataract endophthalmitis
Researchs No controlled and randomized clinical trials to evaluate

the efficacy of the routine use of IC moxifloxacin were
found in the literature.
Introduction
This study aimed to
determine the safety and efficacy of a single

intraoperative ic application of 0.5% moxifloxacin
for the prevention of acute endophthalmitis
after cataract surgery
PASIEN & METODE
PENELITIAN
(Patients and Methods)
Patients & Methods
This study was a single-site prospective

parallel-group randomized partially masked
phase 3 clinical trial
The trial was registered in

May 2016 and began in June 2016
(clinicatrials.gov identifier: NCT02770729).
Inclusion Criterias
1 THE INDICATION OF CATARACT SURGERY
2 AT LEAST 40 YEARS OLD OF AGE

Exclusion Criterias
1 MOXIFLOXACIN ALLERGY
2 TRAUMATIC CATARACT with

OCULAR PERFORATION
3 CATARACT SURGERY associated with

OTHER PROCEDURES
4 SIGNS OF OCULAR OR PERIOCULAR INFECTION
5 ADVANCED GLAUCOMA
6 SEVERE OCULAR SURFACE DISEASE

Patients & Methods
Data were collected from patients undergoing cataract surgery in the three
hospitals managed by the University of Campinas (UNICAMP) :
The UNICAMP The State Hospital The Divinolandia

Clinical Hospital of Sumare Regional Hospital
Collected data from each patient
1 MEDICAL RECORDS
2 FOLLOW-UP DATA AT
1, 7, 30 & 45 DAYS
POST-OPERATIVE
3 4
ROUTINE PRE- DATA FROM
OPERATIVE CLINICAL INTRAOPERATIVE
EXAMINATION DATA EVALUATIONS
Patients & Methods
Patients were randomly divided into two groups that were

approximately equal in size and stratified by sex.
?
Group A Group B
(Moxifloxacin Group) (Control Group)
Treatment Treatment
Received a single IC injection of 0.03 Received no IC moxifloxacin injection at
mL of undiluted 0.5% moxifloxacin the end of cataract surgery
from a sealed bottle to guarantee that
the solution was free from any
contamination (150 mg in 0.03 mL
Vigamox solution) at the end of the
cataract surgery
BOTH GROUPS  immediate postoperative treatment consisted of the application of 0.5% moxifloxacin and
0.1% dexamethasone eyedrops, followed by bandages. The postoperative regimen also consisted of
0.5% moxifloxacin and 0.1% dexamethasone eyedrops for 7 days.
Patients & Methods
Corrected distance visual acuity

Surgical protocols, instrumentation, and (CDVA), corneal endothelial cell
techniques are standardized in all 3 hospitals, density (ECD), intraocular pressure
as are the intraoperative drugs, irrigating (IOP), and central corneal
solutions, ophthalmic viscosurgical devices, thickness (CCT) from baseline to
blades, and intraocular lenses (IOLs). the 6-week follow-up visit. Sample
Size
Standardization Secondary Outcome
Surgery Primary Outcome

Sample size was calculated based on a
Performed by ophthalmology residents, incidence of presumed or previous assessment that found a 0.3%
under senior surgeon supervision in culture-proven acute post- frequency of endophthalmitis secondary to
accordance with the protocols used in operative endophthalmitis cataract surgeries without prophylactic
the Department of Ophthalmology of the occurring any time between antibiotic treatment at the Clinical Hospital
UNICAMP. surgery and the 6-week of UNICAMP in 2015.
follow-up visit.
Patients & Methods
The parameters adopted were a one-tailed confidence

level of 95%, 80% power, a 1:1 ratio of exposed
to nonexposed patients, and a null frequency
of endophthalmitis at the moxifloxacin group,
which resulted in approximately 2600
participants per group.
The trial would be suspended if a difference

between the two groups lower than a type I error
(a) of 4% was found in the pre-analysis of 25%, 50%,
62.5%, 75%, and 87.5% of the total number of patients
included.
Patients & Methods
Although the initial plan was to enroll 5200 patients in the trial, the study was
suspended by ethical reasons after an interim analysis of 3640 patients
demonstrated a significant decrease in the risk for postoperative
endophthalmitis associated with IC moxifloxacin injection versus no IC
moxifloxacin injection.
ANALISA STATISTI
K
(Statistical Analysis)
Statistical Analysis
(1) 02 (2)
Data are expressed as the means Between-group differences of
±SD and 95% confidence interval continuous variables were
(CI) compared using the Mann-Whitney
P value U test
01
< 0,05 :
statistically
(4) significant
03 (3)
One-sided test for incidence of Categorical variables were
endophthalmitis was considered compared using the chi-square test
appropriate because the occurrence or the Fisher exact test, when
of endophthalmitis is unlikely related appropriate
to the administration of moxifloxacin
04
from a sealed bottle.
HASIL
(Result)
This study enrolled 3640 patients between
June 29, 2016, and May 7, 2018
The patients were randomized into Group

A (IC moxifloxacin) or Group B (no IC
injection [control group]).
In total, 1818 patients in the IC moxifloxacin

group and 1822 patients in the control group
completed the 6 weeks of follow-up care; 23
patients and 20 patients were lost to follow-
up in the moxifloxacin group and the control
group, respectively
Result
A statistically significant difference
was observed at baseline between
the groups only in the case of the
ECD parameter
Result
Incidence of Endophthalmitis within
6 Weeks of Follow-up
The incidence of endophthalmitis within 6 weeks of

follow-up was 1 (0.05%) of 1818 eyes in the moxifloxacin
group (Group A) and 7 (0.38%) of 1822 eyes in the control
group (Group B) (P = .035).
There were no significant differences
No ocular or systemic study-related
in CDVA (P = .202), ECD (P = .482),
adverse events occurred.
IOP (P = .105), or CCT (P = .558).
Result
Incidence of Intraoperative Events
similar in both groups
The incidence of posterior
1 2
capsule rupture with vitreous loss The incidence of aphakia
was 14 (0.77%) of 1818 eyes in the
was 150 (8.25%) of 1818 eyes in the
moxifloxacin group and 20 (1.09%) of
moxifloxacin group (Group A) and
1822 eyes in the control group
137 (7.51%) of 1822 eyes in the
(P = .304)
control group (Group B) (P = .413).
The incidence of nucleus drop
3
into the vitreous cavity
was 9 (0.49%) of 1818 eyes and 9
(0.49%) of 1822 eyes in the
moxifloxacin group and control
group, respectively (P = .99).
Of the 8 cases, 3 (37.5%) were culture positive for Streptococcus
The median time to onset after surgery
pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA),
was 6.5 days (range 2 to 15 days).
and Pseudomonas aeruginosa.
According to the antibiogram, both S. pneumoniae and P. aeruginosa were sensitive

to fluoroquinolones, whereas MRSA was sensitive only to vancomycin. Result
Pembahasan
(Discussion)
Discussion
The incidence of endophthalmitis was

significantly higher in patients who did not
receive IC moxifloxacin.
There were no significant differences in

CDVA, ECD, IOP, or CCT between the two
groups.
These findings are consistent with several

retrospective studies that have evaluated
the safety and efficacy of IC moxifloxacin.
Nevertheless, even in the moxifloxacin group, the risk for endophthalmitis resulting from
highly resistant bacteria such as MRSA was not eliminated completely.
Discussion
The incidence of endophthalmitis without IC antibiotics varies between studies about 1,23% - 0,03%
Discussion
Herrinton et al. demonstrated that, even with rates as low as 0.07%, there is
room for incremental improvement with IC antibiotics.
It is important to emphasize that the current study included surgeries

performed by surgeons in training at a teaching hospital and therefore, there was a
possible increased risk for surgical complications, including
endophthalmitis.
Discussion
it is possible that with greater enrollment,
the difference might have failed to reach
clinical significance.
The limited sample size

and the low number of
cases of endophthalmitis
Low Rate of Culture-

proven Endophthalmitis
PCR tests were not available.
Furthermore, the culture-proven
rate of infection was 37.5%, similar
to that of other studies.
Limitations of this study

Discussion
rare case Cataract surgeries performed

but devastating prognosis worldwide continues to
increase from time
to time
Endophthalmitis
Different drugs, doses, routes, and strategies of administration have

prophylaxis strategies have been evaluated. Despite the variety of approaches
that have been tested and suggested,
become a relevant issue there is currently no single standard protocol.
Discussion
Preferred Practice Pattern guidelines from

The use of IC antibiotics
the American Academy of Ophthalmology
Even so, many surgeons choose to use topical antibiotics

for prophylaxis because of the unavailability of an IC drug.
The effect of antibiotic eyedrops used days or hours

before the surgical procedure is still controversial
Discussion
the preoperative and postoperative use of topical antibiotics

The Swedish study produced no benefit when compared with the prophylactic
use of 0.05% chlorhexidine and IC cefuroxime.
no significant reduction in conjunctival flora after the use of

He et al. fourth-generation quinolones either 1 day or 3 days
preoperatively.
no statistically significant differences in their comparison
Moss et al. of fourth-generation quinolone 3 days before the procedure
to preoperative povidone–iodine
the use of preoperative and postoperative antibiotic eyedrops

These findings support the conclusion of the
offers no benefit relative to the intraoperative injection of IC
ESCRS clinical trial2 and the two subsequent
cefuroxime, and, counterproductively, can induce bacterial
meta-analyses
resistance.
Discussion
The ESCRS’s RCT Retrospective studies

approximately 5-fold reduction in Tested other antibiotics such as
endophthalmitis rates associated vancomycin and moxifloxacin.
with IC cefuroxime
Pictures source : Arshinoff, Steve. Intracameral

Prophylaxis In Cataract Surgery
Discussion
have been evaluated through multiple retrospective

Retrospective studies cohort studies and the first RCT is this study
Cavalcanti Lira et al.

Tested other antibiotics such as tested its safety by comparing first 150 surgery
vancomycin and moxifloxacin. without vs next 150 surgery with IC moxifloxacin
no significant differences of CDVA, ECD, IOP, or CCT
from baseline to 2 years after surgery
became contraindicated and is no
longer used Masuura et al.
• Retinal toxicity reported (postoperative found 150 mg/mL to be safe and provided a
hemorrhagic occlusive retinal vasculitis) concentration above MIC90 for 2 hours against
• Lower spectrum of action against gram- most resistant pathogens.
negative bacteria
Researchs of the drug’s safety

Discussion
Retrospective studies
Masuura et al. Haripriya et al.

18.000 surgeries with doses ranging from Retrospective analysis of 600 000 surgeries
50 to 500 mg/mL IC moxifloxacin substantially reduced
• 3-fold in the case of manual small incision
found that moxifloxacin provided a 3-fold
cataract surgery and
decrease in the risk for endophthalmitis
• nearly 6-fold in the case of phacoemulsification.
Researchs of the drug’s efficacy

Discussion
No randomized controlled trials have been performed or have demonstrated

that IC moxifloxacin is more effective than cefuroxime in eradicating the
microorganisms that most frequently cause endophthalmitis.
Research from Swedish (retrospective)

 cefuroxime less effective against gram-negative bacteria, and some of those
surgeons reported switching to moxifloxacin because of its broader spectrum of
activity.
Recently Metaanalysis
 concluded that IC cefuroxime and moxifloxacin reduced rates of
endophthalmitis when compared with controls, with minimal to no toxicity
events at standard doses.
Researchs of the drug’s efficacy

KESIMPULAN
(Conclusion)
Conclusion
This is the first randomized controlled trial to demonstrate the prophylactic efficacy of IC
moxifloxacin, which was found to significantly reduce the overall rate of endophthalmitis
when all patients received the same standardized postoperative topical antibiotic regimen.
This study demonstrates that the IC injection of moxifloxacin is a safe and effective
method for reducing the risk for postcataract endophthalmitis. This study contributes
significantly to the prevention of postoperative endophthalmitis,
in particular in regions of the world with limited access to drugs produced for IC use.
CRITICAL
APPRAISAL
Judul
No Kriteria Ya (+), Tidak (-)

1 Jumlah kata dalam judul, ≤ 12 kata + (12 kata)
2 Deskripsi Judul Menggambarkan isi utama

penelitian dan tanpa singkatan
3 Daftar penulis sesuai aturan jurnal +
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5 Tempat & waktu penelitian dalam judul +
Abstrak
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2 Mencakup IMRC +
3 Secara keseluruhan informatif +
4 Tanpa singkatan selain yang baku +
5 Kurang dari 250 kata -(279 kata)

Pendahuluan

1 Terdiri dari 2 bagian atau 2 paragraf -
2 Paragraf pertama mengemukakan alasan dilakukan +
penelitian
3 Paragraf ke 2 menyatakan hipotesis atau tujuan +
penelitian
4 Didukung oleh pustaka yang relevan +
5 Kurang dari 1 halaman -
Bahan & Metode
No Kriteria Ya(+), Tidak (-)

1 Jenis dan rancangan penelitian +
2 Waktu dan tempat penelitian +
3 Populasi Sumber +
4 Teknik sampling +
5 Kriteria inklusi +
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7 Perkiraan dan perhitungan besar sempel +
8 Perincian cara penelitian +
9 Blind +
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Hasil
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2 Tabel karakteristik +
3 Tabel hasil penelitian +
4 Komentar dan pendapat penulis tentang hasil +
5 Tabel analisis data dengan uji +
Diskusi, Kesimpulan & Daftar Pustaka
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2 Pembahasan dan kesimpulan dipaparkan dengan jelas +
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Validitas Interna Hubungan Nonkausal
No Kriteria Hasil
1 Apakah hasil dipengaruhi oleh bias? Tidak
2 Apakah hasil dipengaruhi oleh faktor peluang? Ya
3 Apakah observasi dipengaruhi oleh faktor perancu? Tidak

Validitas Interna Hubungan Kausal
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1. Apakah hubungan waktu benar? Ya
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4. Apakah hasil konsisten dalam penelitian ini? Ya
Apakah ada koherensi hasil studi dengan
5. Ya
fakta di masyarakat?
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2. Apakah hasil dapat diterapkan pada populasi terjangkau? Ya
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Importancy
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4. Apakah analisis dilakukan secara multivariabel Ya

Applicability
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penelitian dengan mempertimbangkan transportability, kondisi
pasien, dokter, pelayanan kesehatan, ekonomi, social, budaya,
agama)
 YA
NO KRITERIA +/-
1 VALIDITY
Validitas Interna Hubungan Kausal +
Validitas Interna Hubungan Non Kausal +
Validitas Eksterna +
2. IMPORTANCY +
3. APPLICABILITY +
Thank You

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Safety and Efficacy of Intracameral

Moxifloxacin for Prevention of Post-cataract

Departemen Ilmu Kesehatan Mata

Journal Reading Prodi Pendidikan Profesi Dokter

TAHUN TERBIT & PENERBIT

Pain in the eye

Clinical signs of ocular infections

European Society of Cataract and

A systematic review and two meta-analyses

Source : Arshinoff, Steve. Intracameral Prophylaxis

Procedures to prepare the drug in the operating

2 RETINAL VASCULAR LEAKAGE

5 TOXIC ANTERIOR SEGMENT SYNDROME

Clinical Use has been used worldwide

Researchs No controlled and randomized clinical trials to evaluate

This study aimed to

determine the safety and efficacy of a single

This study was a single-site prospective

The trial was registered in

1 THE INDICATION OF CATARACT SURGERY

2 AT LEAST 40 YEARS OLD OF AGE

2 TRAUMATIC CATARACT with

3 CATARACT SURGERY associated with

4 SIGNS OF OCULAR OR PERIOCULAR INFECTION

6 SEVERE OCULAR SURFACE DISEASE

The UNICAMP The State Hospital The Divinolandia

Patients were randomly divided into two groups that were

Corrected distance visual acuity

Surgery Primary Outcome

The parameters adopted were a one-tailed confidence

The trial would be suspended if a difference

The patients were randomized into Group

In total, 1818 patients in the IC moxifloxacin

The incidence of endophthalmitis within 6 weeks of

The incidence of posterior

The incidence of nucleus drop

According to the antibiogram, both S. pneumoniae and P. aeruginosa were sensitive

The incidence of endophthalmitis was

There were no significant differences in

These findings are consistent with several

It is important to emphasize that the current study included surgeries

The limited sample size

Low Rate of Culture-

Limitations of this study

rare case Cataract surgeries performed

Different drugs, doses, routes, and strategies of administration have

Preferred Practice Pattern guidelines from

Even so, many surgeons choose to use topical antibiotics

The effect of antibiotic eyedrops used days or hours

the preoperative and postoperative use of topical antibiotics

no significant reduction in conjunctival flora after the use of

the use of preoperative and postoperative antibiotic eyedrops

The ESCRS’s RCT Retrospective studies

Pictures source : Arshinoff, Steve. Intracameral

have been evaluated through multiple retrospective

Cavalcanti Lira et al.

Researchs of the drug’s safety

Masuura et al. Haripriya et al.

Researchs of the drug’s efficacy

No randomized controlled trials have been performed or have demonstrated

Research from Swedish (retrospective)

Researchs of the drug’s efficacy

No Kriteria Ya (+), Tidak (-)