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Journal of Eye and Ophthalmology

ISSN 2055-2408 | Volume 4 | Article 2

Penelitian asli Akses terbuka

Evaluasi kelangsungan hidup sel-sel dalam retina-setelah perawatan laser


durasi rendah diukur dengan electroretinogram pada pasien dengan
retinopati diabetes

Arief S. Kartasasmita 1,2 *, Ohisa Harley 1,3, Irawati Irfani 1,2 dan Erwin Iskandar 1,2

Correspondence: a.kartasasmita@unpad.ac.id
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1 Department Ophthalmology, Universitas Padjadjaran, Bandung, Indonesia.


2 Cicendo National Eye Hospital, Bandung Indonesia.
3 Netra Eye Hospital, Bandung Indonesia.

Abstrak
Latar Belakang dan Tujuan: Untuk mengevaluasi kelangsungan hidup sel batin-retina setelah durasi rendah perawatan laser (50ms durasi) diukur dengan
electroretinogram pada pasien dengan retinopati diabetes

metode: Twenty-two eyes with severe nonproliferative diabetic retinopathy or proliferative diabetic retinopathy that underwent three
panretinal photocoagulation treatments were prospectively followed. The patients were divided into two groups involving the standard
laser or low-duration laser treatment. Survival of the inner retina was assessed using a full-field electroretinography involving changes in
amplitude and implicit times of the b-wave rod response.

Results: There was no significant change in amplitude in eyes treated with the low-duration laser (-14.29±30.479 µV; p=0.172), but
there was a significant change in eyes treated with the standard laser (-45.65±28.189 µV; p=0.001). There was no significant
change in implicit times in each group (p=0.177 and p=0.685, respectively). The change in amplitude in eyes treated with the low-
duration laser was significantly lower than in eyes treated with the standard laser (-71.43±25.408 versus 8.18±86.432, respectively;
p=0.018).

Conclusions: Treatment with the low-duration laser is effective in maintaining the survival of inner retinal cells.

Keywords: Low duration Laser, Inner Retina Survival, Diabetic Retinopathy

Introduction photoreceptors to reduce the oxygen demand in the outer lay- ers of the
Diabetic retinopathy (DR) is the leading cause of blindness due to the ischemic retina. The retinal pigment epithelium (RPE) absorbs the laser radiation and
condition of the disease. Numerous stud- ies have reported that growth transforms it into heat to destroy the surrounding cells, especially the
factors are the most important factors for the progression of DR leading to photoreceptors located above the RPE. By destroying some of the
neovasculariza- tion. Vascular endothelial growth factor (VEGF) is considered photoreceptors, oxygen from the choriocapillaris passes through the outer
the most important initiating factor responsible for severe complications due retina and goes directly to the inner retina to restabilize the oxygen sup- ply
to proliferative diabetic retinopathy (PDR) of the inner retinal layers. The and demand. It is therefore reasonable to assume that the objective of PRP is
incidence of blindness due to DR varies from 6.8–44.4%, and is increasing both to increase the oxygen supply to the inner retina to decrease the ischemic
in developed and developing countries [ 1 - 3 ]. condition by destroying some of the photoreceptors [ 5 ].

Panretinal photocoagulation (PRP) is still the main standard of treatment Unfortunately, heat from photocoagulation frequently not only destroys
for PDR [ 4 ]. This treatment destroys some of the photoreceptors but also affects other surround-

© 2017 Kartasasmita et al; licensee Herbert Publications Ltd. This is an Open Access article distributed under the terms of Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0 ). This
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Kartasasmita et al., Journal of Eye and Ophthalmology 2017,
http://www.hoajonline.com/journals/pdf/2055-2408-4-2.pdf doi: 10.7243/2055-2408-4-2

ing cells, including the inner retinal cells [ 6 ]. Many patients therefore still versi 16.0 (SPSS, Chicago, IL, USA).
experience reduced visual acuity and peripheral visual field defects. It is
known that >95% of the photorecep- tors are rod cells. After hasil
phototransduction, they collect the signals and transmit them to the inner Sebanyak 22 mata pasien dengan NPDR parah atau PDR dimasukkan.
retinal cells before they are transmitted to nerve fibers. Approximately 20– Usia pasien berkisar 43-68 tahun (rata-rata, 49,40 ± 7,412 tahun) di
100 rods converge to a single bipolar cell, and approximately 100 rod bipolar kelompok A (laser standar) dan 51- 68 tahun (rata-rata, 55,50 ± 5,442)
cells converge to a ganglion cell [ 7 ]. By preserving the inner retinal layers, pada kelompok B (durasi rendah laser). demografi pasien dan karakteristik
signals from unaffected photoreceptors can still be transmitted to bipolar awal dirangkum dalam Tabel 1 .
and other inner retinal cells to reduce the side effects of laser treatment. In
the present study, we therefore evaluated the efficacy of low-duration laser Mata dalam kelompok standar laser menerima rata-rata
treatment (50 ms) in preserving the survival of inner retinal cells in patients 1,680.10 tembakan dengan kekuatan rata-rata 170,33 mW, dan mata pada kelompok laser
with DR. durasi rendah menerima 2,157.40 tembakan dengan kekuatan rata-rata 259,67 mW seperti
yang ditunjukkan pada Meja 2 .

Perubahan kali amplitudo dan implisit ditunjukkan pada tabel 3 - 5 .


where significant comparisons are designated with appropriate p-values.
Patients and method s
This study was conducted from 2014 to 2015, adhered to the tenets of the
Declaration of Helsinki, and was approved by the Institutional Review Board Table 1. Demographic and Clinical Characteristics of The Patients.
at the University of Padjajaran. Inclusion criteria included patients ≥18 years
of age with proliferative diabetic retinopathy (PDR) or severe nonprolif-
Characteristic Group A Group B P value
erative diabetic retinopathy (severe NPDR) planned PRP, with the ability to
n =10 n=10
comply with testing and follow-ups. Exclusion criteria included patients with
Age (years)
significant media opacities and with a history of intraocular laser treatment or
Mean ± SD 49.40±7.412 55.50±5.442 0.0503
surgery. Writ- ten informed consent that adhered to good clinical practice
Range 43-68 51-68 --
regulations was obtained from each patient.
Diagnose (%)
Severe NPDR 2 (20%) 4 (40%) 0.628

PDR 8 (80%) 6 (60%) --


Ophthalmic examinations at baseline and 1 week after treatment
included ETDRS best-corrected visual acuity (BCVA); measurement of
intraocular pressure (IOP); slit-lamp biomicroscopy, indirect
Table 2. The Average PRP Setting in Group A and Group B.
ophthalmoscopy; and a full-field electroretinography (ERG) examination.
Setting Group A Group B P value
Fulfield erg was done using Roland ERG (Roland Electrophysiological
Instrument, Essen Germany) based on ISCEV standard with rod respons (n=10) (n=10)
using stimulative strength weaker than 2.5 logunit. All the patient had 20 Pulse Duration (ms) 100 50

minutes dark adaptation prior of rod response stimulation. Scotopic ff ERG Power (mW) 170.33±21.855 259.67±56.578 0.001*

was interpreted by implicit time and amplitude of b wave in rod response Number of Shots 1680.10±232.132 2157.40±465.796 0.010*
with normal criterion of implicit time 60-80 ms and amplitude 175-471
micronvolt.
Table 3. Comparison of The Amplitude in Rod Response between Pre- and Post
laser.
PRP dilakukan dalam tiga sesi pada interval 1 minggu menggunakan laser argon dengan Amplitude Group A (n=10) Group B (n=10)
celah-lampu biomicroscopy (Carl Zeiss Meditec, Jena, Jerman) dengan Omra-PRP 165 (US
Prelaser 61.59±29.873 61.59±29.873
Ophthal- mic, Doral, FL, USA) okular lensa kontak . Teknik PRP tampil sebagai menggambarkan
Postlaser 15.97±17.587 12.86±12.388
tempat lain [ 8 ]. Pasien diacak oleh blok permutated dan dibagi menjadi dua kelompok yang
Difference - 45.65±28.189 - 14.29±30.479
diobati dengan laser standar atau laser-durasi rendah. Perawatan laser standar sesuai dengan
P value 0.001* 0.172
ETDRS dilakukan dengan menggunakan durasi pulsa 100-ms dan 300-500-pM tempat dengan

daya laser disesuaikan untuk menghasilkan kelas 2-3 laser yang membakar. The durasi rendah

Laser terlibat pulsa 50-ms dan 300-500-pM tempat dengan daya laser yang disesuaikan untuk Table 4. Comparison of The Implicit Time in Rod Response between Pre-
menghasilkan kelas 2 laser yang membakar. and Post laser.

ImplicitTime Grup A (n = 10) Kelompok B ( n = 10)

Prelaser 87,60 ± 14,431 62.00 ± 37,974

Postlaser 69.95 ± 32,842 57,30 ± 32,442


A dipasangkan t test digunakan untuk menghasilkan p-nilai, dan nilai
<0,05 dianggap signifikan. Analisis statistik dilakukan dengan menggunakan Perbedaan - 17,66 ± 38,080 - 4.70 ± 35,425

software statistik SPSS untuk Windows, nilai P 0,177 0,685

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Kartasasmita et al., Jurnal Eye dan Ophthalmology 2017,
doi: 10,7243 / 2055-2408-4-2
http://www.hoajonline.com/journals/pdf/2055-2408-4-2.pdf

Ada perbedaan yang signifikan dalam amplitudo antara pra dan pasca laser mata ischemic process in this area was assumed to affect the rod responses using
pada kelompok A ( - 45,65 ± 28,189 μV; p = 0,001). Tidak ada perbedaan yang ERG, because this examination calculates the summation of electrical
signifikan pada kelompok B ( -14,29 ± 30,479 responses in all of the peripheral retina. Fundus photo angiography is known
μV ; p = 0,172). to be an appropriate method to evaluate ischemic areas.However, the
Setelah terapi, tidak ada perbedaan yang signifikan dalam waktu yang tersirat decreased amplitude of the rod response after standard laser treatment was
dalam setiap kelompok (p = 0,177 dan p = 0,685, secara berurut; tabel 4 ). significantly higher after the low-duration laser treatment.

tabel 5 menunjukkan perbedaan yang signifikan dalam perubahan amplitudo antara As previously mentioned, the objective of PRP is to restabi- lize the
kedua kelompok ( -71,43 ± 25,408 vs 8.18 ± 86,432; oxygen supply and consumption [ 13 ]. Laser treatment destroys some of the
p = 0,018), tetapi tidak ada perbedaan yang signifikan dalam perubahan photoreceptors and other surrounding cells, and cells damaged by ischemia
amplitudo di kali implisit antara kedua kelompok ( -15,21 ± 51,208 vs 17,04 ± can no longer consume oxygen [ 14 ]. However, oxygen consumption can be
82,808; p = 0,309). performed by other healthy retinal cells. The restabilized oxygenation in the
retina provides a good environment for repair of retinal tissue, so it is
Table 5. Comparison of Change in Amplitude and Implicit Time between Two possible that tissue repairing can compensate for the damage resulting from
Groups. laser treatment.
Group A Group B P value
(n=10) (n=10) In addition to evaluating the effects of laser treatment, we also determined
Change in Amplitude (%) -71.43±25.408 8.18±86.432 0.018* Change in the delay of the implicit time, which is the time required to reach the peak of
Implicit time (%) - 15.21±51.208 17.04±82.808 0.309 the wave, measured from the beginning of the stimulus to the peak of the
wave [ 15 ]. In contrast to a decreased amplitude, our analyses showed no
significant difference in the change of implicit times between the two groups
Diskusi (p=0.309). A possible explanation involves successful oxygenation in the retina
The results in the present study provide a better understand- ing of the laser after laser treatment, especially in the inner retinal layers. Repair of the tissue
effects on inner retinal cells. Because of their potential importance, we oc- curred in 3 days after laser treatment [ 16 ]. The ERG examina- tion that was
focused on the rod response and followed its changes during treatment. The performed a week after the last (third) session of PRP might therefore show
inner retina can only be quantitatively assessed using an ERG examination. improvement of electrical signals.
The b-waves reflect signal transmission from the photoreceptors to the inner
retinal cells. The amplitude of the b-wave may decrease if there are
conditions that affect this transmission. Previous studies analyzing the The post-laser implicit times improved in several eyes. The destruction
effects of standard (ETDRS) laser treatment of retinal cells have reported to damaged photoreceptors succeeded in restoring tissue oxygenation,
varying results. Gjotterberg et al. reported more damage to photoreceptors providing an opportunity for the undestroyed photoreceptors to optimize
than to inner retinal cells. Perlman et al. reported the same relative damage their functions. However, in other eyes, we also found a delayed implicit
to all layers, but Liang et al. reported more damage to inner retinal cells [ 9 - 11time compared with pre-laser levels, which could be caused by continued
]. ischemia and by the damaged retinal tissue.

Our results suggest that in clinical practice, use of the low- duration laser
Our study showed a significant difference in decreased amplitude might result in decreased inner retinal damage. A low-duration laser
(p=0.046) between the eyes treated with the standard laser versus eyes provides for retinal tissue repair. In the present study, two patients were
treated with the low-duration laser. The amplitude of b-waves decreased by excluded because they did not complete the procedures according to the
45.65% in the standard laser group, and 14.29% in the low-duration laser protocol. However, the post-laser ERG examination 2 months after the last
group. Lafond et al. also reported that standard (ETDRS) laser treatment session of PRP was still performed. In contrast to the other results, there was
resulted in a 71% decrease in the amplitude of b-waves [ 12 ]. It is possible that a surprising increase of amplitude. A possible explanation was the
the laser caused significant damage to the photoreceptors and to other cells restoration of retinal structure and its function, which has been postulated to
in the in- ner retinal layers, thus resulting in lower transmitted signals and occur 8 weeks after laser treatment. Sher et al. suggested that retinal
decreased amplitude. Taken together, the present study showed that a restoration could occur by retention of old synapses, the origination of new
standard laser caused more damaged to inner retinal cells than a low- synapses, or both [ 6 ].
duration laser.

The limitation of this study was the short follow-up time: only 1 week after the
There were two eyes in the low-duration group with a greater decrease last PRP treatment. However, we postulate that damage to the photoreceptors is
in amplitude than the other eyes. Although the exact reason was still most prevalent during this period, and the rod response in the ERG examination
unclear, it is possible that ischemia in the peripheral retina was still should provide the expected results. The small number of patients might also be
progressing. Unlike vitrectomy, the laser could not reach the anterior of the a limitation of this study, so additional studies
oraserrata. An

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Kartasasmita et al., Journal of Eye and Ophthalmology 2017,
http://www.hoajonline.com/journals/pdf/2055-2408-4-2.pdf doi: 10.7243/2055-2408-4-2

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Ucapan Terima Kasih


Para penulis ini mengakui dukungan dari Universitas
Padjadjaran Penelitian internal Grant.
sejarah Publikasi Kutipan:
Editor: Reas Khan Sulaimankutty, University of Pennsylvania, USA. Diterima: Kartasasmita AS, Harley O, Irfani I dan Iskandar E.
23-Jun-2017 Akhir Revisi: 24-Agustus-2017 yang diterima: 05-Sep-2017 Diterbitkan:
Evaluasi kelangsungan hidup sel-sel dalam retina-setelah durasi rendah
09-Sep-2017
perawatan laser diukur dengan electroretinogram pada pasien dengan
retinopati diabetes. J Ophthalmol Eye.
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