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Abstrak :
Macular edema is a kind of human sight disease as a result of advanced stage of diabetic retinopathy. It affects the central vision of patients and in severe cases lead to blindness. However, it is still difficult to diagnose the grade of macular edema quickly and accurately even by the medical doctor's skill. This paper proposes a new method to classify fundus images of diabetics by combining Self-Organizing Maps (SOM) and Generalized Vector Quantization (GLVQ) that will produce optimal weight in grading macular edema disease class. The proposed method consists of two learning phases. In the first phase, SOM is used to obtain the optimal weight based on dataset and random weight input. The second phase, GLVQ is used as main method to train data based on optimal weight gained from SOM. Final weights from GLVQ are used in fundus image classification. Experimental result shows that the proposed method is good for classification, with accuracy, sensitivity, and specificity at 80%, 100%, and 60%, respectively.

Abstrak :
ABSTRAK
Latar Belakang: terapi injeksi intravitreal bevacizumab monoterapi pasien edema makula diabetik dengan ketebalan makula sentral lebih dari 400 µm dinilai kurang efektif. Kortikosteroid dinilai dapat membantu mencegah progresifitas edema makula diabetik terkait proses inflamasi.

Tujuan: Mengetahui hasil terapi injeksi intravitreal kombinasi bevacizumab dan deksametason dibandingkan dengan injeksi intravitreal bevacizumab monoterapi pada pasien dengan edema makula diabetik derajat sedang hingga berat

Metodologi: penelitian eksperimental randomisasi acak terkontrol dua kelompok yaitu: kelompok dengan terapi intravitreal bevacizumab 1,25mg (kelompok A) dan terapi injeksi intravitreal bevacizumab 1,25mg dan deksametason 0,5mg (kelompok B). Luaran sensitifitas retina, ketebalan makula sentral serta tajam penglihatan dievaluasi pada minggu pertama dan keempat.

Hasil: sebanyak masing-masing 22 orang diteliti di kelompok A dan kelompok B. Median usia pada kelompok A adalah 53,1 + 8,4 dan kelompok B adalah 55,1 + 8. Terdapat perbaikan sensitifitas retina sebanyak 2,1 dB di kelompok A dan 2,03 dB di kelompok B (p=0,673). Perbaikan ketebalan makula sentral didapatkan sebanyak 217µ m pada kelompok A dan 249 µm pada kelompok B (p=0,992). Perbaikan tajam penglihatan dengan koreksi pada kelompok A sebanyak 8,5 huruf dan 7,5 huruf pada kelompok B (p=0,61). Analisis intragroup menunjukkan perbaikan yang signifikan di masing-masing luaran penelitian pada kedua kelompok.

Kesimpulan: Terapi kombinasi bevacizumab dan deksametason menjunjukkan perbaikan secara klinis pada luaran sensitivitas retina, ketebalan makula sentral serta tajam penglihatan dengan koreksi. Perbandingan antara kedua grup tidak signifikan secara statistik. Tren positif tampak kategori adanya kista pada Spectrum Domain Optical Coherence Tomography (SD-OCT) dan pasien dengan Non-Proliferative Diabetic Retinopathy (NPDR).

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ABSTRACT
Background: Bevacizumab intravitreal injection therapy in patients with diabetic macular edema (DME) especially with a central macular thickness more than 400 μm is considered ineffective. Corticosteroid addition to the standard therapy can help prevent the inflammation that happens in the progression of diabetic macular edema

Objective: to compare the result of combination of bevacizumab and dexamethasone intravitreal injection with bevacizumab monotherapy in patient with moderate to severe diabetic macular edema.

Methods: randomized controlled trial in two parallel group. Group A received bevacizumab intravitreal 1.25mg in 0.05cc, group B received bevacizumab 1.25mg and dexamethasone 0.5mg. Retinal sensitivity, central macular thickness (CMT) and visual acuity (VA) are evaluated in first and fourth week after injection.

Result: 22 patients from each group were evaluated. Median of age was 53,1+ 8,4 in group A and 55,1 + 8 in group B. Improvement of retinal sensitivity was 2.1dB and 2.03dB in group A and B respectively (p=0,673). There was reduction in CMT about 217µm in group A and 249 µm in group B (p=0,992). Visual acuity (VA) outcomes showed little difference between groups; +8.5 letter and +7.5 letter in group A and group B respectively. Intragroup analysis shows significant differentiation in each outcome in both groups.

Conclusion: combination of intravitreal bevacizumab and dexamethasone clinically improved retinal sensitivity, CMT and VA in patient with DME. There was no statistical difference between in retinal sensitivity, CMT and VA after therapy in both groups. Positive trend was showed especially in patient with cyst appearance in Spectrum Domain Optical Coherence Tomography (OCT) and Non-proliferative Diabetic Retinopathy (NPDR) patient.

Abstrak :
Edema makula diabetik atau Diabetic Macular Edema (DME) merupakan penyebab utama kehilangan penglihatan pada pasien diabetes. Patofisiologi DME bersifat multifaktorial dan kompleks. Rusaknya sawar darah retina mengakibatkan penumpukan carian abnormal dan penebalan makula retina yang diinduksi oleh berbagai faktor seperti iskemia, peningkatan Vascular Endothelial Growth Factor (VEGF), radikal bebas, disfungsi perisit dan endotel, serta inflamasi. Penelitian ini menilai efektivitas injeksi loading dose bevacizumab dengan kombinasi inisial deksametason dibandingkan loading dose bevacizumab. Pada studi ini dilakukan uji klinis acak terkontrol dengan randomisasi pada dua kelompok yaitu: kelompok dengan terapi loading dose bevacizumab 1,25mg dengan kombinasi inisial deksametason 0,5mg (studi) dan injeksi loading dose bevacizumab 1,25mg (kontrol). Luaran sensitifitas retina, tajam penglihatan serta CMT dievaluasi pada minggu pertama, keempat, kedelapan dan keduabelas. Sebanyak 22 orang diteliti di kelompok studi dan 21 orang kelompok kontrol. Median usia kelompok studi 53,3 + 10,9 dan kontrol 54,1 + 7,3. Dilakukan analisa terhadap sensitifitas retina, tajam penglihatan serta CMT pada kelompok studi (10 orang) dan kontrol (13 orang). Terdapat perbaikan ketebalan makula sentral 205,5μm (studi) dan 87 μm (kontrol) dengan p=0,010. Perbaikan tajam penglihatan dengan koreksi pada studi 13,5 huruf dan 3 huruf pada kelompok kontrol (p=0,23). Terdapat perbaikan sensitifitas retina 1.02 dB di kelompok studi dan 0,68 dB pada kontrol (p=0,832). Analisis intragroup menunjukkan perbaikan signifikan pada pemeriksaan CMT kedua kelompok dan pada pemeriksaan tajam penglihatan pada kelompok studi. Berdasarkan analisa pendahuluan ini dapat memberikan bukti adanya potensi untuk dilakukan penyelesaian seluruh jumlah sampel hingga akhir dimana terdapat kecendrungan perbaikan secara klinis pada setiap luaran. ......Diabetic Macular Edema is a major cause of vision loss in diabetic patients. The pathophysiology is multifactorial and complex. The damage of the retinal blood barrier results in a buildup of fluid and thickening of the macula that induced by ischemia, Vascular Endothelial Growth Factor, free radicals, pericyte, endothelial dysfunction, and inflammation. This study assessed the effectiveness of bevacizumab loading dose with initial combination versus a bevacizumab monotherapy. In this study, a randomized controlled trial was carried out in two groups, a 1.25 mg bevacizumab loading dose with a combination of the initial 0.5 mg dexamethasone (study) and a 1.25 mg bevacizumab loading dose (control). Retinal sensitivity, visual acuity and CMT were evaluated at the first, fourth, eighth and twelfth weeks. A total of 22 people (study) and 21 people (control). The median age of was 53.3 + 10.9 (study) and 54.1 + 7.3 (control). Retinal sensitivity, visual acuity and CMT were analyzed in study group (10 people) and (13 people) control group. There was an improvement in CMT 205.5μm (study) and 87μm (control) with p = 0.010. Visual acuity improvement 13.5 letters (study) and 3 letters (control) with p = 0.23 and retinal sensitivity 1.02 dB (study) 0.68 dB (control) with p = 0.832. Intragroup analysis showed significant improvements of the CMT examination in both groups and in the visual acuity examination in study group. Based on this preliminary analysis, it can provide the potential for completion of the entire sample size until the end where there is a tendency for clinical improvement in each outcome.

Abstrak :
Perkembangan terapi edema makula diabetik hingga saat ini terus dieksplorasi, dengan terapi anti-VEGF sebagai lini pertama. Yellow Subthreshold Micropulse Laser (SMPL) merupakan inovasi laser fotokoagulasi konvensional yang menargetkan epitel pigmen retina (RPE) telah dianggap aman terhadap populasi kaukasian. Laser tersebut diajukan sebagai alternatif terapi edema makula ringan dengan ketebalan retina di bawah 400 μm. Data prospektif perubahan struktural dan elektrofisiologis SMPL sebagai monoterapi pada non proliferative diabetic retinopathy (NPDR) dengan DME ringan masih terbatas, khususnya di Asia yang memiliki perbedaan ketebalan densitas RPE. Studi eksperimental pre-post tanpa pembanding ini bertujuan untuk mengetahui perubahan Average Macular Thickness (AMT), amplitudo dan waktu implisit gelombang P1 dan N1 mfERG, dan DR score pada DME ringan pasca SMPL. Subyek yang masuk kriteria inklusi dilakukan laser SMPL dengan follow-up untuk menilai AMT dengan Optical Coherence Tomography (OCT) pada 4 dan 8 minggu, serta mfERG, dan DR score menggunakan RETeval Handheld ERG pada 8 minggu pasca laser. Terdapat 15 subyek (17 mata) yang diikutkan pada studi ini. Hasil menunjukkan perbaikan AMT signifikan pada minggu ke-8 pasca laser (p=0.001). Amplitudo dan waktu implisit gelombang P1 dan N1 tidak menunjukkan adanya perubahan bermakna pada setiap ring (p>0.05). Pemeriksaan DR score seluruh pasien DME menunjukkan hasil abnormal sesuai cut-off studi sebelumnya, serta tidak menunjukkan perubahan bermakna antara sebelum dan setelah terapi (p>0.05). Penelitian ini menunjukkan adanya perbaikan anatomis makula dan stabilisasi kondisi sel fotoreseptor dan Muler dilihat dari nilai elektrofisiologis dalam followup 8 minggu. Terapi SMPL dapat dipertimbangkan sebagai alternatif terapi yang aman dan bermanfaat untuk kasus NPDR dengan DME ringan. ......The management of DME is still under investigating and research, with currently intra vitreal anti-VEGF as the mainstay therapy. Yellow Subthreshold Micropulse Laser (SMPL) is a conventional photocoagulation laser innovation that targets retinal pigment epithelium (RPE) and has been reported its safety on Caucasian population. This laser method is considered as an alternative treatment for mild DME with retinal thickness below 400 μm. Prospective data on structural and electrophysiological changes of SMPL as monotherapy in non-proliferative diabetic retinopathy (NPDR) with mild DME are still limited, especially in Asia that has RPE density thickness differences. This pre-post study without comparison aims to determine changes in average macular thickness, amplitude and implicit time of P1 and N1 mfERG, and DR score in mild DME post SMPL. Subjects who met the inclusion criteria underwent SMPL laser was examined using Optical Coherence Tomography for average macular thickness parameter at 4- and 8-week post-laser, as well as mfERG and DR score using RETeval handheld ERG at 8-week post-laser. Fifteen subjects (17 eyes) were included in the study. Remarkable AMT improvement at 8-week post-laser was noted in this study (p=0.001). The amplitudes and implicit times of P1 and N1 waves showed no significant changes in each ring (p>0.05). All DME eyes showed abnormal DR score results at baseline according to the cut-off value of previous studies. There was no significant changes of DR score after therapy (p>0.05). This study showed an anatomical improvement of the macula and stabilization of photoreceptor and Muller cells as seen from electrophysiological values at 8-week follow-up. SMPL can be considered as a safe and beneficial alternative therapy in NPDR cases with mild DME.

Abstrak :
Latar Belakang: Tata laksana edema makula terus dievaluasi, dengan terapi anti-VEGF sebagai lini pertama. Subthreshold micropulse laser (SML) diajukan sebagai alternatif adjuvan. Studi retrospektif terdahulu menunjukkan efektivitas SML 577-nm sebagai monoterapi pada edema makula dengan ketebalan di bawah 400 μm. Akan tetapi, data prospektif efektivitas SML sebagai adjuvan masih minim. Tujuan: Menilai pengaruh pemberian kombinasi bevacizumab dan laser SML 577-nm dibanding bevacizumab monoterapi terhadap ketebalan makula sentral dan tajam penglihatan pasien edema makula diabetik ringan-sedang. Metode: Penelitian ini merupakan studi eksperimental lengan ganda. Dilakukan randomisasi acak terhadap pasien edema makula diabetik dengan rentang ketebalan makula 300-600 μm, kelompok kontrol mendapatkan protokol standar. Kelompok studi mendapatkan adjuvan laser SML kuning satu minggu pascainjeksi. Pasien menjalani follow-up penilaian tajam penglihatan dan ketebalan makula sentral pada 28 dan 35 hari pascainjeksi. Hasil: Terdapat 26 subjek yang terbagi rata pada kelompok studi dan kontrol. Ditemukan signifikansi nilai CMT pada kontrol 28 hari dan 35 hari pascainjeksi baik pada kelompok studi (p=0,011 dan 0,014) maupun kontrol (p=0,006 dan p=0,001). Akan tetapi, tidak ditemukan perbedaan signifikansi selisih nilai CMT antara kedua kelompok pada kontrol 28 hari (p=0,317) dan 35 hari (p=0,84). Tidak ditemukan perbedaan selisih TPDK ETDRS antara kelompok studi dan kontrol pada kelompok 28 hari (p=0,568) dan 35 hari (p=0,128) pascainjeksi. Kesimpulan: Kombinasi SML dengan bevacizumab intravitreal dapat mengurangi ketebalan makula sentral dan memperbaiki tajam penglihatan namun tidak ditemui perbedaan yang signifikan dengan monoterapi standar. ......Background: The management of macular edema is constantly evaluated, with anti-VEGF therapy being the first line. Subthreshold micropulse laser (SML) has been proposed as an alternative adjuvant. A previous retrospective study demonstrated the effectiveness of 577-nm SML as monotherapy in macular edema with CMT below 400 μm. However, prospective data on the effectiveness of SML as an adjuvant are lacking. Objective: To assess the effect of the combination of bevacizumab and 577-nm SML laser compared to bevacizumab monotherapy on central macular thickness and visual acuity in mild-moderate diabetic macular edema patients. Methods: This research is a double arm experimental study. A randomized trial was performed on diabetic macular edema patients with macular thickness range of 300-600 μm. The control group received a standard protocol and the study group received a yellow SML laser adjuvant one week after injection. Patients underwent follow-up assessment of visual acuity and central macular thickness at 28 and 35 days postinjection. Results: There were 26 subjects which were equally divided into study and control groups. Significant decrease in CMT were found in study group (p=0.011 and 0.014) and the control group (p=0.006 and p=0.001). However, there was no significant difference in delta CMT values between the two groups in the 28-day (p=0.317) and 35-day controls (p=0.84). There was no difference in ∆TPDK ETDRS between the study and control groups at 28 days (p=0.568) and 35 days (p=0.128) after injection. Conclusion: The combination of SML and intravitreal bevacizumab can reduce central macular thickness and improve visual acuity but there was no significant difference with standard monotherapy.