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Central Macular Thickness Changes after Pars Plana Vitrectomy and

Internal Limiting Membrane Peeling in patients with Non Proliferative
Diabetic Retinopathy with Refractory Diabetic Macular Edema

Putri Anggarani Idham1, Elvioza1, Anggun Rama Yudantha1, Joedo Prihartono2

1. Ophthalmology Department, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo

Hospital, Jakarta
2. Public Health Department, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital,
Jakarta

Aim: To assess the end result of vitrectomy and ILM peeling procedure in patient with NPDR
with refractory DME. Method: Single arm clinical trial (pre-test and post-test study) of
vitrectomy and ILM peeling procedure in patients with NPDR with refractory DME after
previous history of anti-VEGF intravitreal injection/s and/or intravitreal steroid injection/s
and/or macular photocoagulation laser. The patients range of best corrected visual acuity
(BVCA) between 20/80 – 20/400 with central macular thickness (CMT) >300 µm. We assessed
the CMT, the visual acuity before and after the treatment and the complications after treatment
in each visit. Result: Fifteen eyes from 15 subjects with age range 62,5 (39-72) years old was
observed for 3 months. Duration history of diabetes was 10 (3-8) years, HbA1C level was 6,4
(5,5-10,8) %. There was a significant different of CMT before treatment, 1 month, 2 months
and 3 months after treatment (p=<0,001). The BCVA was assessed using LogMar, there was
no significant difference before and after treatment (p=0,635). Two complications found during
this study was retinal detachment and macular hole. Conclusion : In this study, vitrectomy and
ILM peeling in patient with NPDR with refractory DME showed a significant CMT changes.
There was no significant different in BCVA yet majority of the subjects showed stable visual
acuity within the study period.

Keywords: Diabetic macular edema, Refractory, Vitrectomy, Internal Limiting Membrane

Peeling

Introduction
Diabetes mellitus is a non-stop growing and threatening global health issue.(1) Diabetic
Retinopathy is a microvascular complication that is often found in patient with diabetes
mellitus.(2) The prevalence of diabetic retinopathy in diabetic patient increased parallelly with
the duration of diabetic history and the patient’s age.(3, 4) Yau et al(5) reported the prevalence of
diabetic retinopathy in diabetic patient was 34,6%. Sya’baniah et al(6) conducted a study in
Cipto Mangunkusumo Hospital (RSCM) that showed incidence of diabetic retinopathy was
24,5% among the new screened diabetic patients in November 2010 until October 2011.
Diabetic retinopathy is the main caused of decreased vision in productive age and it is highly

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related with diabetic macular edema (DME). (7, 8) Epidemiology study reported the prevalence
of DME was 26% in total amount of patients with diabetic retinopathy. (9) Diabetic macular
edema is a thickening macular condition related to the abnormality of vascular permeability in
patients with diabetic retinopathy. (3) Increase level of blood glucose in a chronic duration will
cause a serious damage in the inner and outer retinal blood barrier that will resulted in hypoxic
state of the tissues, accumulation of free radical and inflammation mediators. These end results
will trigger vascular endothelial growth factor (VEGF) expression that play the important role
DME formation. The amount of VEGF that circulates at the anterior chamber and vitreous is
correlated with the severity of DME. This pathophysiology is the reason why the VEGF is the
main target of DME treatment. (10, 11) In 2005, ETDRS reported that photocoagulation laser was
the main therapy of DME. Meanwhile on the long term evaluation, 15% of total patients in the
study experienced decreased vision at least 3 rows in ETDRS chart in 3 years after treatment.
(12)
The standard therapy of DME was still developing until recently a pharmacology therapy
of intravitreal injection of anti-Vascular Endothelial Growth Factor (anti-VEGF) became the
most applicated therapy. (11, 13, 14) The effectivity of anti-VEGF intravitreal injection required a
repetitive procedure due to the agent will only last between 4-5 weeks in the vitreous. This
regiment considered costly and required a strict schedule for the injection sequels. Anti-VEGF
intravitreal injection is an invasive procedure that come with risk of complications. A
retrospective study in 1173 patients reported few complications found in 12 months of
observation in patients who received intravitreal injection of Bevacizumab, 7 cases of acute
blood pressure increment, 6 cases of cerebrovascular disease, 5 cases of myocardial infarct, 7
cases of endophthalmitis, 7 cases of tractional retinal detachment and 4 cases of uveitis. (1, 2, 11,
14-16)
The most challenging situation was that 50% of patients that received intravitreal injection
of anti-VEGF experienced persistent CMT with after repetition of injection in 1 year.

Along with the development of knowledge in pathogenesis of DME, few studies developed
certain therapies that focused on decreasing the vascular permeability. Vitrectomy and ILM
peeling were one of the considered alternative therapy, due to the cost, the strict visit and the
risk of complications in anti-VEGF intravitreal injection. There are few studies that performed
vitrectomy in refractory DME cases with previous history of multiple injections and
photocoagulation laser with no significant result. (2, 15, 17) Prospective study by Recchia et al(12)
reported the significant changes of CMT and improvement of visual acuity in 73% patient with
DME that underwent vitrectomy surgery. Few theories agreed with the role of vitrectomy as a
treatment of DME, the extraction of the vitreous gel during the vitrectomy could decrease the

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concentration of VEGF and vasoactive agents that accumulated inside the vitreous cavity,
vitrectomy could also increase the oxygenation of the inner retinal layer up to 10 times.(9, 18-21)
The improved oxygenation of the vitreous cavity and macula would cause the vascular
permeability to decrease hence the DME. Other study stated that after ILM peeling was done,
the compromised flow of the transretinal fluid that caused the DME will decrease and
improved, the improvement was caused by the better role of the diffusion barrier of the ILM,
the base membrane of the Muller cell. Histopathology study reported that the ILM in patients
with DME was significantly thicker, this condition could cause deprivation of oxygen diffusion
from the vitreous to the retina. Other theory stated that the repair mechanism of Muller cell
could be activated immediately after delamination of the ILM.(22-28) Internal limiting membrane
peeling could decrease the tangential traction, reduce the incident of epiretinal membrane, and
make sure that the posterior hyaloids is properly wiped out. (29) The objective of this study is
to assess the result of vitrectomy and ILM peeling procedure in NPDR patients with refractory
DME.

Method
This is a single arm clinical trial study (pre-test and post-test study), the study was conducted
in Ophthalmology Department – Faculty of Medicine in Kirana - Cipto Mangunkusumo
Hospital. This study was done in July 2018 until April 2019 with observation period of 3
months after the procedure was done.

The NPDR and refractory DME patients who had history of intravitreal injection was still
included in this study as long as the last injection/procedure was done ≥ 6 weeks before the
study started for intravitreal anti-VEGF injection and/or ≥ 3 months before the study started
for intravitreal triamcinolone acetonide injection and/or ≥ 3 months before the study started for
patients with history of macular photocoagulation laser. The other inclusion criteria are age
above 18 years old, with BCVA using the ETDRS chart in range of 20/80 – 200/400, CMT
>300 µm with no vitreomacular traction, clear refractive media, fully dilated pupil and
cooperative patients to undergo fundus photography. Patients who failed these criteria
underwent the rescue therapy according to the latest gold standard protocol of DME treatment.
The drop out criteria including patients who passed away during the study duration, patient
who failed to attend the scheduled visit during the observation duration and patient who
decided to drop off from the study. The subjects were fully assessed before entering the study,
the standard examination including the anamnesis, ophthalmology examination (BCVA using

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the ETDRS chart, intraocular pressure, slit lamp biomicroscopy examination), and the ancillary
test including the CMT measurement using the CIRRUS HD-OCT 5000 (Carl Zeiss Meditec,
Dublin, CA) using the macular thickness analysis mode in fully dilated pupil. The macular
OCT result was assessed by one consultant from the vitreoretina division, Kirana - Cipto
Mangunkusumo Hospital. The consultant assessed the patient based on the inclusion and
exclusion criteria, the possible subjects were offered to join this study. Once the patient agreed,
an informed consent must be signed by the subject.

The subjects underwent vitrectomy surgery in general anesthesia, a routine procedure done by
the subspecialist from the vitreoretinal subdivision. The procedure of the surgery was : (1)
Standard three-port pars plana sclerostomy (three-port vitrectomy) 3-4 mm posterior from the
limbus, (2) Viewing system using the endoillumination and wide-angle-viewing-system
(WAVS), (3) Extraction of vitreous gel and peeling off of the posterior hyaloid, (4) ILM
coloring using the ILM blue (brilliant blue G) in 2 minutes duration continued with ILM
peeling using the end-gripping forceps. The method of tamponade was using the air, (5) other
additional procedure was considered by the vitreoretinal surgeon during the surgery. The
patient was assessed and observed at the first, second and third month after the procedure. The
data collected was including the visual acuity, macular OCT, and possible complications after
the procedure. This study was approved by The Ethics Committee – Facaulty of Medicine -
University of Indonesia, this study complied with the tenets of the Declaration of Helsinki.

Result
There were 18 subjects participating in this study, the subjects included were instructed to
finish all the planned examinations and scheduled visit. Eighteen subjects were observed for 1
month, we found 2 subjects with complication at the 2 months observation sequences and 1
drop out patient who passed away due to systemic disease at the 2nd month, the cause of death
had no correlation with this study. These 3 subjects were still included at the initial assessment
and 1 month after procedure. The basic subject characteristics data are shown in table 4.1

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Table 4.1 Basic Subject Characteristics Data (n=18)
Characteristics n (%) Average ± SD or
Median (min-max)
Gender
Male 5 (27,8%)
Female 13 (72,2%)
Age (years) 62,5 (39 – 72)
DM duration (years) 10,0 (3,0 – 18,0)
DM duration; N(%)
< 10 years 6 (33,3%)
≥ 10 years 12 (66,7%)
Blood Pressure (mmHg)
Systolic 150,1 ± 21,9
Diastolic 72,5 ± 11,3
Total Cholesterol (mg/dl) 199,4 ± 42,1
Triglyceride 126,2 ± 46,9
Low Density Lipoprotein (LDL) 122,7 ± 40,8
High Density Lipoprotein (HDL) 49,8 ± 9,1
HbA1C (%) 6,4 (5,5 – 10,8)
Hypertension; N(%)
Yes 17 (94,44%)
No 1 (5,56%)
History of received injections
3x 11 (61,1%)
4x 6 (33,3%)
6x 1 (5,6%)

Table 4.2 showed the characteristics of initial assessment, there were 8 eyes (44,44%) with
CMT 300 – 400 µm, 5 eyes (27,78%) with CMT in range between 401 – 600 µm and 5 eyes
(27,75%) with CMT >600 µm. In this study, the initial BCVA in 11 subjects (61,11%) was
between the range of 6/24 – 6/60 and 7 subjects (38,89%) was between 3/60 - <6/60. The initial
intraocular pressure was varied between 6,7 – 18 mmHg. Eleven subjects had visual acuity
assessed using the ETDRS chart with median result of 43 (33-55) letters.

Table 4.2 Initial Characteristic of the Eye Assessments

Variables Score
Initial CMT (µm) 492,2 ± 165,4

Initial BCVA (LogMAR) 1,02 (1,30 – 0,60)

Initial BCVA (ETDRS letters) 43 (33 – 55)

Intraocular Pressure (mmHg) 13,1 ± 3,1

There was a significant changes of the CMT before and 1 month after procedure with
improvement  of 184,50 µm. The CMT before and after 1 month showed 16 out of 18 eyes

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(88,89%) had significantly decrement progression. Out of 16 eyes that showed improvement
in CMT, 13 eyes had CMT decrement > 80 µm, meanwhile 3 eyes showed decrement < 80 µm.

According to the visual acuity output in 1 month after procedure, there was no statistically
significant change compare to the initial visit. The BCVA data in 1 month after procedure
showed that 5 subjects experienced worsened visual acuity, 7 subjects had the same visual
acuity and 6 subjects reported improved visual acuity. One out of 6 patients with improved
visual acuity was able to read 5 extra letters which equal to 1 line in ETDRS chart compare to
the baseline visit. There was no increment of CMT found in group with decreased vision. There
was 1 subject with higher grade of cataract found in 1 month after procedure compare to the
initial visit, the subject underwent cataract extraction surgery using the phacoemulsification
technique and intra ocular lens implantation.

Table 4.3 Comparison of Variables Before therapy, One month, Two months and Three months
After Therapy
Variables Before 1 Month 2 Months 3 Months P Value
CMT (µm) 492,0 (303-895) 277,5 (97-809) 264 (147-608) 264,0 (142-660) 0,001a*

BCVA (LogMAR) 1,02 (0,6 – 1,30) 1,04 (0,60 – 1,70) 1,06 (0,52 – 2,00) 1,04 (0,52 – 2,00) 0,635a

IOP (mmHg) 13,1 ± 3,1 14,269 ± 3,71 14,08 ± 3,61 13,676 ± 2,37 0,692b

During the 3 months after procedure observation, there was a statistically significant change of
the CMT with  decrement of 221 µm compare to the data on the initial visit. During the
evaluation of the BCVA on the 3rd month there were 4 subjects with improved visual acuity, 9
subjects with stable visual acuity and 2 patients with decreased visual acuity. Photoreceptors
disruption was found in the 2 patients with worsened visual acuity.

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 Central Macular Thickness(µm )
600

500 492,0
400
277,5
300 264,0 264,0
CMT
200

100

0
0 1st month 2nd month 3rd month

Graphic 1. Graphic of The Median CMT Changes on Each Visit

The improvement of the median CMT in each scheduled visit are shown in graphic 1. There
was an outstanding decrement of CMT at the 1st month of observation and it continued in
stable line until the 3rd month of observation.

The unexpected event after the procedure is elaborated in table 4.6. There was one patient
that experienced retinal detachment, 1 patient had macular hole and 1 patient that passed
away due to systemic disorder, the casualty was not related to the procedure in this study.

Table 4.6 Unexpected Events after Vitrectomy

Side Effect n (%)
Ocular
Subconjunctival bleeding 0 (0)
Endophthalmitis 0 (0)
Rising TIO 0 (0)
Vitreous hemorrhage 0 (0)
Retinal tear / detachment 1 (5,56)
Others 1 (5,56)
Systemic
Stroke 0 (0)
Acute myocardial infraction 0 (0)
Others 0 (0)

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Discussion
Hypertension is one of the contributing risk factor in diabetic retinopathy, most of the patient
in this study had hypertension as their risk factor. The Wisconsin Epidemiologic Study of
Diabetic Retinopathy Study (WESDR) stated for every 10 mmHg increment of systolic and
diastolic pressure, the relative risk is of DME is increasing to 1,15 and 1,16 times. (30) Diabetes
caused blood vessels damage, hypertension could worsened this condition by increasing the
perfusion pressure of the vessels that create the high blood outflow.

Most of the patients in this study also had hypercholesterolemia. The blood lipid level is highly
related and could be one of the risk factors of diabetic retinopathy and DME. The changes in
the retinal microvascular permeability will cause the stagnant accumulation of lipoproteins that
could extravasate the vessels, this condition will create an irreversible damage of the
surrounding retinal cells. (32) A study stated that there was a correlation between high level of
triglyceride and LDL with DME. (33) Low density lipoprotein could increase the rate of pericyte
apoptosis in diabetic retinopathy. (34)

The compliance of blood sugar level is highly related with the development and progression of
diabetic retinopathy. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye
Study showed that the progression of diabetic retinopathy was slowing down in patients with
(34)
well-controlled cholesterol and blood sugar. The periodic measurement of HbA1C could
show the long-term compliance of hyperglycemia control. In this study, most of the patient had
experienced diabetes for ≥10 years yet only few of the subjects showed high level of HbA1C
≥ 7, this data showed that most of the patients had their HbA1C controlled when they took part
in this study, yet the severity of their diabetic retinopathy did not back up their HbA1C result.
The long duration of ≥10 years of diabetes could be one of the risk factors of the diabetic
retinopathy severity. This condition was backed up by WESDR study that stated the severity
of diabetic retinopathy was highly related with such conditions for example the history of long
duration of diabetes disease, high level of HbA1c, positive laboratory result of proteinuria, high
diastolic blood pressure, and certain gender in patients with diabetes for ≥10 years. (4)
Other
study by Chou et al(35) showed that the duration of diabetes exposure for ≥ 10 years had no
direct relation with DME, yet HbA1C level ≥ 8 could increase the risk of macular edema. Study
by Verma et al(36) reported that for every increment of 1% in HbA1C level, the relative risk of
DME increased 1,47 times. The previous study with much bigger sample size by the
DRCR.net(37) reported that vitrectomy and ILM peeling in patients with DME was significantly

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effective to decrease the CMT compare to their initial CMT data before the procedure, this
result is similar with this study. Randomized clinical trial by Raizada et al (38) also showed a
significant improvement of CMT with increment of 161,36 μm in 3 months follow up after
vitrectomy and ILM peeling. Parallel without study, previous mentioned study stated that
vitrectomy and ILM peeling was effective in reducing CMT in patients with DME.There are
few things that need to be highlighted before applying the result of this study, the study
subject’s characteristic of big sample size was conducted in the clinical setting in the US, that
study did not specifically mention the condition of the DME of their subjects whether it was a
naïve DME or refractory DME. Study by Raizada et al(38) included subjects from Asia (India)
where there base characteristic of the CMT is smaller than this study whish was 410 ±127 μm.

We found a significantly reduced CMT in our study at the 1 month and 3 months follow up.
The average CMT increment was 184,5 μm at the 1 month follow up and 221 μm at the 3
months follow up. At the 1 month follow up, we found 1 patient with worsened CMT compare
to the initial visit data, this increased CMT was also found in the fellow eye. This condition
was assumed to be related to the uncontrolled HbA1c level. The same patient then experienced
better CMT regression in follow up at the second and third month after the procedure. At the 2
months follow up, we found 1 patient with the increased CMT which was also found in the
fellow eye, this patient also experienced reduced CMT at the 3 months follow up.

The parameter in this study were the anatomical measurement of CMT and the periodically
assessed BCVA. The BCVA in this study did not change significantly between the initial visit
and the follow up in each month. This finding was different from study by Stolba et al(39) who
reported a statically significant improved visual acuity measured using the ETDRS chart in 1
month, 3 months and 6 months after the therapy. In their study the initial BCVA (LogMar) was
vary between 0,02-0,72 with average score of 0,28. The result of their study was aligned with
Raizada’s et al(38) who reported a significant changes of BCVA in their 3 months observation
after the therapy. This different result between our study and theirs probably happened due to
the initial visual acuity in their studies are better than this study.

In most of the subjects in this study, improvement of BCVA did not follow the reduced CMT.
Study by Radwan SH et al(40) reported that improvement of DME was not always followed by
improvement of the visual acuity. Study by Shah et al(41) reported that there was no significant
correlation between reduced CMT with the visual acuity. Clinical parameter of the visual acuity

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could be interfered by certain conditions such as the subjectivity of the patients, the grade of
the cataract, fovea avascular zone, disorganized retinal layers and or photoreceptors disruption,
mechanical trauma of the optic nerve during the surgery. (42-44)

During the 1 month follow up after the surgery, there were 5 patients with decreased visual
acuity, two of these patients experienced the improvement of their visual acuity at the 3 months
after therapy follow up and their visual acuity was maintained stable as it was on their initial
visit. One patient had decreased vision due to the higher grade of cataract, no cataract extraction
performed due to the clear visual axis. The other 2 patients were assumed to experienced
intraoperative mechanic trauma that caused their visual acuity did not improve at the 3rd months
after surgery.

In 1 month after therapy follow up, there was 1 patient with increased grade of cataract that
compromised the visual axis. At the initial visit, the patient was diagnosed with senile immature
cataract and the grading was increased after the procedure. We used the LOCS III system to
grade the cataract severity in this study. He underwent the cataract extraction surgery with
implantation of IOL so that the CMT and the BCVA can be assessed after. Incident of cataract
after vitrectomy can be caused by the changes in lens metabolism due to the fluctuating oxygen
pressure inside the eye. The vitreous protected the posterior past of the lens from the oxygen
exposure from the retinal vessels. During the vitrectomy, the exposure of the oxygen to the
lens increased and induced the formation of nuclear cataract.(45) Study by Holekamp et al(46)
reported that vitrectomy significantly increased the intraocular oxygen pressure during and
sometimes after the procedure. This high oxygen exposure caused certain changes in the lens
metabolism and it could form the nuclear cataract. In this patient the condition of the diabetic
retinopathy remained stable. Few studies reported that the progression of diabetic retinopathy
increased in 10-30% patients who underwent cataract surgery, yet other experts stated that the
progression of the diabetic retinopathy after the cataract surgery was depend on the severity of
the retinopathy during the surgery.(47) Modern techniques of cataract surgery most likely do not
affect the progression of the retinopathy.(48) There was no increment of the CMT at 2 months
follow up after the cataract extraction using the phacoemulsification technique with IOL
implantation.

The duration of the DME is affecting the central fovea, study by Sakata K et al(49) showed that
Blood flow Velocity (BFV) of the perifovea capillaries in patients with Clinically Significant

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Macular Edema (CSME) was significantly slower compare to BFV in patients with diabetes
without CSME and patients with no history of diabetes. The reduced BFV is related to the
thickening retina at the central fovea and the progression of the DME. The progressive
disappearance of the capillaries around the perifovea area mimicking an enlarged fovea
avascular zone (FAZ) and periofveal intercapillary area (PIA), this condition related to the
decreased vision in patients with diabetes. Diabetic Macular ischemia (DMI) is characterized
as enlarged and disruption of FAZ and diminished surrounding capillaries. Various study
conducted to find the correlation between DMI and decreased vision. A study showed that
patients with DME at the initial visit assessment will have certain limitation of visual acuity
improvement after therapy. This statement magnified the importance of assessing the severity
of the ischemic condition in patients with diabetes. Fluorescein angiography (FA) is the
standard imaging modality to assess the quality of DMI, yet it is hard to assess the quality of
FAZ using the FA in clinical settings. The Optical Coherence Tomography Angiography
(OCTA) is an alternative imaging used to asses FAZ in DMI. In this study, we did not perform
the OCTA at the beginning through the end since it was still not available during that period.
(50-52)

Another prognostic factor in visual acuity improvement in patient with DME is occurrence of
Disorganization of the retinal inner layers (DRIL). This condition described as abnormal
founding in OCT imaging such as disruption in one from 2 borders between ganglion cells and
the inner plexiform layer, inner nuclear layer and outer plexiform layer. A study showed that
patients with DME whom in followed up 4th month showed sign of DRIL were highly related
with the decrement of visual acuity at the 8th month assessment. (40, 43)
This report is similar
with research by Joltikov et al(53) who reported diabetic patients with no DME with DRIL
experienced decreased retinal function compare to diabetic patients without DRIL. The defect
at the retinal lamina could be an early sign of cellular damage. Retinal tissue is packed with
organized structures, any disruption in any layer especially the macula will decrease the visual
acuity. Study by Nicholson et al(54) reported that occurrence of DRIL was related with macular
capillary nonperfusion state. This report is aligned with study by Balaratnasingam et al(55) that
showed the severity of DRIL was related to the size of the fovea avascular zone in patients
with any degree of diabetic retinopathy without DME.

The disruption of the photoreceptors in patients with DME was also related to the output of the
visual acuity. The layers of photoreceptors are made of rod and cone cells at the internal and

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outer segments (IS/OS), this layer also is also connected to the other two layers of Ellipsoid
Zone and external limiting membrane layer. The integrity of these layers is vital for the visual
(56)
acuity outcome. The damage of the photoreceptors is the main contributor for the poor
outcome of visual acuity, there are few possibilities that caused the photoreceptors damage
such as the chronic duration of the edema, ischemia or foveal damage from photocoagulation
procedure.(57) A significant reduced CMT with no improvement of visual acuity could be
caused by certain reasons such long duration of macular edema before the therapy and the
severity of the macular ischemic condition.(41) In patients whose visual acuity did not improve,
there was a disruption of photoreceptors found during the macular OCT imaging.

Internal Limiting Membrane (ILM) peeling is a surgery technique at the transparent retinal
membrane, it requires certain coloring agent to facilitate the visualization and the peeling of
the ILM by the surgeon. Trypan blue or brilian blue G (BBG) is the coloring agent that
commonly use to facilitate the ILM peeling.(58) In this study, we used the BBG coloring agent
during the ILM peeling in every subjects. The BBG is selectively bonded and colored the ILM,
this coloring is similar with Indocyanine Green (ICG) coloring to optimize the ILM peeling.
The use of BBG is effectively good, it is proven form the outstanding clinical result without
any prove of toxicity that is confirmed by the focal ERG test. This coloring agent is a good
alternative for ICG and it is widely used yet there are controversial decission related to the
safety issue.(59)

The predominance of this study is the prospective design using the macular OCT assessment
and the standardize ETDRS chart to assess the visual acuity. This study is an early clinical trial
study to assess the changes of CMT and BCVA after vitrectomy in patients with NPDR and
refractory DME. This study showed that the response of therapy was satisfying at the 1-month
assessment and remained stable until the follow up at 3 months after therapy in patients with
refractory DME who had history of receiving intravitreal injection of anti-VEGF before.

The limitation of this study is the sample size due to the limitation of patients with refractory
DME in vitreoretinal division in Kirana - Cipto Mangunkusumo Hospital, some patients did
not fit the inclusion criteria and had to be excluded. The other weakness in this study was the
lack of information of the DME duration that the patients suffered. As stated earlier, the longer
the duration of the DME the more severe the macular damages. These limitations are similar
with other studies since it was very hard to determine the exact time when the DME was

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developed. Systemic risk factors compliances played a big role in this study, the uncontrolled
risk factors such as the blood pressure, HbA1C level, cholesterol level did not fully reflect the
systemic risk factors before the patient were included in this study. This study also did not
divide and grouped the patients according to the CMT and the initial visual acuity.

Conclusion
This study showed a significant CMT improvement in NPDR patients with refractory DME
who underwent vitrectomy and ILM peeling therapy. The outcome of the visual acuity showed
that there was no statistically significant difference yet most of the subjects had a stable visual
acuity after the therapy. There were 2 complications during the observation period which was
1 case of retinal detachment and 1 case of macular hole.

Disclosure
The author(s) have no financial disclosure related at any aspect of the issue

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