JOURNAL READING

Effect of hypothermic perfusion on

phacoemulsification in eyes with hard
nuclear cataract: randomized trial
Wan W, Jiang L, Ji Y, Xun Y, Xiong L, Xiang Y, Li R, Li Z, Wang X, Stewart JM, Hu K

Adviser

dr. A. Kentar Arimadyo Sulakso, M.Si.Med, Sp.M (K)

By
Salmah Alaydrus
 INTRODUCTION
Pachoemulsification
• Phacoemulsification is the most effective method to remove cataract
• Advantage: Safe and predictable
• Disadvantage:
• Postoperative incision burns
• Corneal edema
• Anterior chamber (AC) inflammation
• Decompensation of the corneal endothelium
• Complications are usually seen in patients with complex cataract (hard nuclear cataract, complicated cataract, or cataract combined
with glaucoma)

Hypothermia
• A protective factor that improves the body’s tolerance to ischemia and hypoxia
• Hypothermia  reducing tissue metabolism  treat heart damage and brain damage
• Ocular field  hypothermia can protect the retina from acute ischemic damage
• Hypothesis: hypothermia has a protective effect on corneal endothelial cells during phacoemulsification
OBJECTIVE

To evaluate the effectiveness and safety of hypothermic

perfusion in the phacoemulsification of hard nuclear cataract

To reduce the thermal injury caused by US energy in phacoemulsification

To improve the prognosis of cataract patients

MATERIALS AND METHODS

Prospective randomized controlled study (Animal experiments,

Patient Clinical Trials)

Ethics approval was obtained from the Ethics Committee of the

First Affiliated Hospital of Chongqing Medical University
MATERIALS AND METHODS (Animal Experiments)

• the Experimental Animal

White rabbits • randomly assigned
Surgeries
Center, Chongqing • Group A: 15 rabbits,
Medical University • (2.5 kg ± 2.5 [SD] Group B: 15 rabbits, • under anesthesia
• 12 to 15 weeks old, Group C: 10 rabbits • performed by same
• 20 males and 20 females surgeon
• no abnormal appearance • Ssme procedur in human
of the eyes patients

Obtained 3 groups
MATERIALS AND METHODS (Animal Experiments)

Intravenous injection of
3% sodium pentobarbital
(3 mL/kg)
Pupils of right eyes were
dilated with tropicamide
eyedrops
Eyelids were opened with 4oC in Group A Energy of 40%
a lid speculum 10oC in Group B Time of 20 seconds in
Eyes were then disinfected total (phacoemulsification
24oC in Group C
with topical povidone– for 5 seconds; pause for 5
iodine seconds, repeated 4 times)

Temperature of perfusion

Phacoemulsification
Anesthesia

procedure
Disinfected
Thermometer:
thermocouple probes
(BAT-12, Physitemp
Instruments, LLC)
Monitoring realt-time
temperatur: thermometer
inserted into the AC and
corneal incision
MATERIALS AND METHODS (Animal Experiments)

Figure 1. A thermometer was

inserted into the AC through
the auxiliary incision on the
cornea
limbus (A) and into the main
incision (B). The real-time
temperatures in the AC and
main incision were
consistently recorded during
phacoemulsification in the eyes
of
the rabbits (AC = anterior
chamber)
MATERIALS AND METHODS (Animal Experiments)

Optical coherence (Topcon SP-3000P, Into grades Corneal tissue was

tomography (OCT) Topcon Corp.)  To evaluate the collected
(Spectralis OCT, corneal endothelial cell postoperative At 1 day and 7 days
Heidelberg count inflammation reaction postoperative
Engineering GmbH)  Slitlamp evaluation Euthanasia with

Cell count

Categories of AC flare and

cells

Immunohistochemical
Thickness determination

central retinal
thickness
Anterior segment OCT
(AS-OCT) (Cirrus HD-
OCT 1000, Carl Zeiss
Meditec AG)  central
corneal and incisional
corneal thickness
observation
shortly before and 1
sodium pentobarbital
day and 7 days after
the surgical procedure
 AC inflammatory
cell count
MATERIALS AND METHODS (Patient Clinical Trials)

Approved by the Institutional Review Board of the First

Affiliated Hospital of Chongqing Medical University, China

Registered with the Chinese Clinical Trial Registry, number

ChiCTR1800016145

Possible risks, benefits of the intervention, written informed

consent was obtained from all the participants
MATERIALS AND METHODS (Patient Clinical Trials)

Patients with senile hard nuclear cataracts (grades 3 to 5 according to the

Lens Opacities Classification System III) from First Affiliated Hospital of
Chongqing Medical University (November 2017 – February 2018)

Exclusion criteria were previous ocular surgery, surgery combined with other
ocular surgeries, previous use of contact lenses, and patient age less than 20
years

Participants, the surgeon, and the examiners were masked to the grouping.
The clinical trials were based on the results of the animal experiments
MATERIALS AND METHODS (Patient Clinical Trials)

• the first eye was included

2 groups • hypothermia group  4oC Preoperative
in the study if both eyes • room temperature was set
required treatment with • randomly separated using to 24oC • visual acuity
cataract surgery a computer-generated • intraocular pressure (IOP)
random number table • AS-OCT
• two groups (Group A and
• OCT of the fundus
Group B)
• corneal ECC
• corneal thickness
Patients Temperature
MATERIALS AND METHODS (Patient Clinical Trials)

Topically Eyelids were 4oC in Group A Incision: a

anesthetized with opened with a lid 24oC in Group B standard 2.8 mm
benoxinate speculum (w1.5-1.75 mm)
Temperature clear corneal
Eyes were then probe: record of

Temperature of perfusion

Phacoemulsification
Anesthesia

procedure
Disinfected
disinfected with incision
AC temperature
topical povidone– and main incision Implantation of an
iodine intraocular lens by
the same surgeon
MATERIALS AND METHODS (Patient Clinical Trials)

Figure 2. A thermometer was

inserted into the AC (A) and
the main incision (B). The real-
time temperatures in the AC
and main incision were
consistently recorded during
phacoemulsification in the
patient clinical trials
(AC Z anterior chamber)
MATERIALS AND METHODS (Patient Clinical Trials)

Tobramycin– Corrected distance 1 day and 7 days Into grades

dexamethasone ointment visual acuity (CDVA) postoperative To evaluate the
was applied to the ocular Slitlamp evaluation of AS-OCT, OCT of the postoperative
surface the anterior and posterior fundus, Corneal ECC, inflammation reaction
Topical combination of segments CCT, ICT, AC

Categories of AC aqueous
Postoperative therapies

Postoperative examinations

flare and cells

Cell count
levofloxacin 5.0%, IOP inflammatory
diclofenac sodium 1.0%,
and prednisolone 1.0% 4 Fundus examination
times a day and after pupillary dilation
tobramycin 0.3%–
dexamethasone 0.1%
ointment every night for
2 weeks
MATERIALS AND METHODS (statistical analysis)

• Statitical analysis  SPSS Statistics software (version 16.0, SPSS, Inc.)

• Kruskal Wallis test  compare variables

• Wilcoxon test  compare paired variables
• Pearson chi-square and Fisher exact tests  categorical variables

• Pearson and Spearman tests  correlational analysis

• P < 0.05 were considered statistically significant

RESULTS (Temperature Measurements)

Figure 3. Ocular temperatures including

AC temperatures recorded before
phacoemulsification as well as AC and
incision temperatures during
phacoemulsification) under the perfusion
temperature of 24oC (room temperature),
10oC, and 4oC in the animal experiments
(AC = anterior chamber; phaco =
phacoemulsification; temp =
temperature)
RESULTS (Corneal Morphological Changes)

Figure 4. Histological findings of corneal

inflammation in each group (hematoxylin and
eosin stained, 100 original magnification) in
animal experiments. All the sections show a
preserved corneal structure.
RESULTS (Anterior Chamber Inflammation Reaction)

Figure 4. A small amount of inflammatory cell

infiltration is observed in the 4oC group. Corneal
stromal edema with inflammatory cell infiltration
is observed in the room temperature group.
Arrow heads show inflammatory cells and
corneal stromal edema (RT = room temperature)
RESULTS (Patient Clinical Trials)

• 80 patients with senile hard nuclear cataracts (grades 3 to 4)

• All the investigated patients were followed from 1 day to 30 days

• Group A (4oC) group comprised 48 patients

• Group B (24oC, room temperature) 32 patients

• There were no statistically significant differences in sex, age, mean phacoemulsification time, or mean US
energy between the two groups (P > .05)
RESULTS
RESULTS (Temperature Measurements)

Figure 5. Changes in AC and incision

temperatures during phacoemulsification
in each group in the patient clinical trials.
Both the AC and incision temperatures
were elevated as the phacoemulsification
was prolonged. The incision temperature
rose sharply when the ultrasound lasted
for 4 seconds (AC = anterior chamber;
phaco = phacoemulsification; temp =
temperature)
RESULTS (Corneal Thickness)

• AS-OCT  CCT and ICT measurement

• Performed on the first and seventh postoperative day

• The mean CCT was 600.7 ± 51.8 μm in the 4oC group (P = .001)
• The mean ICT was 859.2 ± 177.8 μm in the 4oC group (P = .001)

• There was no difference in corneal thickness between the two groups at 7 days postoperatively (P > .05)
RESULTS (Endothelial Cell Count and Density)
• Assessed microscopically and checked for hexagonal cells
• Performed on the first and seventh postoperative day

• The mean endhotelial cell density (1st day) 2369.1 ± 362.6 cells/mm2 (4oC group)
• The mean endhotelial cell density (1st day) 2173.6 ± 297.7 cells/mm2 (control room temperature group)
• P = .036

• Percentage of hexagonal cells (49.3 ± 9.0) (4oC group)

• Percentage of hexagonal cells (40.6 ± 9.5) (control room temperature group)
• P = .001

• No significant endothelial morphological difference between the two groups was found 7 days
postoperatively (P > .05)
RESULTS (Anterior Chamber Inflammation Reaction)

• Graded to evaluate the postoperative inflammation reaction

• The mean AC inflammation reaction grade of the 4 oC group 0.6 ± 0.6

• The mean AC inflammation reaction grade of the room temperature group 1.3 ± 1.0
• P = .004

• There were no significant differences between the two groups at 7 days postoperatively(P > .05)
RESULTS (Clinical Parameters)
DISCUSSION
• Transient temperature 68.3oC
• Mean temperature 56.7oC
• Continous lasted for 4
seconds
• Further study should procced
Pachoemulsification
Cooling perfusion
• Decrease the real-time
temperature of the incision and
the AC
• 4oC and 10oC irrigation fluid
was similar in rabbit models 
difference was not clear enough
and the rabbit cornea is thinner
than human cornea
• Might be favorable to protect the
corneal endothelium and alleviate
corneal edema in the early
postoperative
• CCT was thinner than in the room
temperature group
• cornea structure might be more
stable
Hyporthermia
DISCUSSION
Prior studies
• Incisional temperature (44.2oC, porcine eye)  corneal burning, high irregular astigmatism,
corneal melts, and scarring and thinning of the cornea
• AC cooling  effectively reduce thermal burns
• Corneal cooling ( photorefractive keratectomy)  effectively reduced postoperative pain,
corneal haze, and myopic regression (baseline myopia between-6.00 diopters (D) and -9.75
(D))
• Contact lenses with a cooling system  reduced the corneal damage ( laser power)
• Ice-cold eye mask increased patients’ comfort level and reduced inflammation after cataract
surgery
• Eye cold patch (transepithelial photorefractive keratectomy)  effectively relieved pain and
inflammation and reduced the use of painkillers without side effects
• Local hypothermia (prolonged vitrectomy)  decrease inflammation in the early
postoperative stage
DISCUSSION

• Transient hypothermia  effective preconditioning stimulus for inducing tolerance to ischemic or

hypoxic injury in several systems

• Exposure to a cold environment affects expression of some proteins or cytokines that could regulate
metabolism

• Hypothermic perfusion would only resolve the corneal injury and inflammatory reaction in the early
postoperative period
DISCUSSION

All the eyes

Should be
were
compared with
anesthetized
larger datasets
topically

Patient’s Should be
intraoperative validated by
comfort should Limitations different
be monitored tertiary centers

Biochemical Further study

studies are with a larger
required sample
CONCLUSION

The thermal rise was more significant than expected when the phaco power lasted longer in
phacoemulsification of hard nuclear cataracts

Hypothermia was a protective intervention to reduce cornea edema, endothelial lesions,

and ocular anterior segmental inflammation caused by thermal damage

Further study with a larger sample size should proceed to confirm the positive results
CRITICAL APPRAISAL

STUDY IDENTIFICATION
More than 12 words, can illustrate the journal content
Too long/ short? generally

Illustrate the observed variables? Yes

Non standard Abbreviation? No

Yes. Ke Hu, MD, PhD, Department of Ophthalmology, 1 You
Any corresponding author and email? Yi Rd, Yu Zhong District, Chongqing 400016, China. Email:
42222@qq.com
CRITICAL APPRAISAL
Yes. An issue focused in terms of hypothermic
perfusion effect on
Did the trial address a clearly focused issue? phacoemulsification in eyes with hard nuclear
cataract and compare between 4oC and room
temperature group
Yes. Patients with senile hard nuclear cataracts
(grades 3 to
5 according to the Lens Opacities Classification
System III)8
Was the assignment of patients to treatments randomised? who were scheduled to undergo
phacoemulsification were recruited at the First
Affiliated Hospital of Chongqing Medical
University from November 2017 to February 2018
Yes. The trial was not stopped early and the
Were all of the patients who entered the trial properly
patients analysed in the groups to which they were
accounted for at its conclusion? randomised
CRITICAL APPRAISAL
Were patients, health workers and study personnel ‘blind’
to treatment?
Were the groups similar at the start of the trial?
Aside from the experimental intervention, were the groups
treated equally?
How large was the treatment effect?
Yes. The participants, the surgeon, and the
examiners were masked to the grouping
No. There were no statistically significant
differences in sex, age, mean phacoemulsification
time, or
mean US energy between the two groups (P > .05)
Yes. 4oC and room temperature group were treated
equally on the preoperative, during operative and
postoperative intervention
The outcome measurement in temperature
measurements, corneal thickness, endothelial cell
count and density, anterior chamber inflammation
reaction and clinical parameters
CRITICAL APPRAISAL
How precise was the estimate of the treatment effect?
Temperature Measurements. No detail
of confidence interval (p)
Corneal Thickness. P = .001 for mean
CCT and p < .001 for mean ICT
Endothelial Cell Count and Density. P
= 0.36 for endothelial cell densities and p
= .001 for percentage of hexagonal cells
Anterior Chamber Inflammation
Reaction. P = .004 for mean AC
inflammation reaction grade
Clinical Parameters. P > .05 for visual
outcomes and p > .05 for complications
7 days postoperation p > .05
CRITICAL APPRAISAL
Can the results be applied to the local population, or in your Yes. We have the same race with China
context? people (ASEAN)
Yes. This study considered corneal
thickness, endothelial cell count and
Were all clinically important outcomes considered? density, anterior chamber inflammation
reaction and clinical parameters beside
temperature measurements
Yes. Many patients who undergo cataract
surgeries in China are from economically
underdeveloped regions and have hard
nuclear cataracts above grade 3 this study
Are the benefits worth the harms and costs? aimed to simulate such extremely hard
conditions and clarify whether
hypothermic perfusion would be a
protective factor for these patient