Tesis

Perbandingan Efek Pemberian Diklofenak Sediaan Oral Dan Tetes Mata 0,1% Terhadap Fibrosis Pasca Operasi Strabismus: Evaluasi Histopatologi Dan Α-Smooth Muscle Actin Pada Kelinci Model = Effect of Oral and 0.1% Topical Diclofenac Sodium on Fibrosis Following Strabismus Surgery: Histopathologic and α-Smooth Muscle Actin Evaluation in Rabbit Model.

Latar Belakang: Fibrosis dalam bentuk adhesi jaringan maupun jaringan parut teregang menjadi salah satu faktor yang mempengaruhi luaran hasil operasi strabismus. Obat golongan anti-inflamasi non-steroid, salah satunya natrium diklofenak, merupakan obat yang mampu menekan proses inflamasi sehingga dipikirkan dapat memodulasi penyembuhan luka, termasuk fibrosis pada otot ekstraokular pasca operasi strabismus. Tujuan: Membandingkan efek pemberian diklofenak sediaan oral atau tetes mata 0,1% terhadap pembentukan fibrosis pasca operasi strabismus pada hewan coba kelinci model. Metode: Penelitian eksperimental ini dilakukan pada kelinci model yang dilakukan operasi reses otot rekrus superior. Dilakukan randomisasi acak terkontrol tiga kelompok dengan membagi kelinci menjadi: kelompok dengan terapi diklofenak oral 2 x 5 mg/kg selama 3 hari (kelompok A), tetes mata natrium diklofenak 0,1% 3x sehari selama 3 hari (kelompok B), dan kontrol (kelompok C). Setelah hari ke-14 pasca operasi, dilakukan enukleasi lalu dinilai skor adhesi makroskopik, histopatologi inflamasi (haematoxylin & eosin), skor adhesi mikroskopik dan persentase area fibrosis (Masson’s trichrome), serta ekspresi α-smooth muscle actin (α-SMA, imunohistokimia) oleh ahli patologi anatomik menggunakan penilaian semi-kuantitatif dan kuantitatif (ImageJ) dengan nilai reciprocal staining intensity (RSI). Hasil: Enam kelinci (12 mata) terbagi dalam tiga kelompok perlakuan. Tidak terdapat perbedaan skor adhesi makroskopik (p=0,13), adhesi mikroskopik (p=0,28), dan histopatologi inflamasi (p=0,26). Persentase area fibrosis kelompok diklofenak tetes mata (12,44 % (8,63 – 18,29)) lebih sedikit dibandingkan kelompok diklofenak oral (26,76 % (21,38-37,56)) maupun kontrol (27,80 % (16,42 – 36,28); uji Kruskal-Wallis p = 0,04, post-hoc kelompok oral vs tetes mata p = 0,03 dan kelompok tetes mata vs kontrol p=0,04). Penilaian ekspresi α-SMA semi-kuantitatif tidak dijumpai perbedaan antar ketiga kelompok. Analisis RSI mendapatkan bahwa kelompok diklofenak tetes mata memiliki ekspresi α-SMA yang lebih rendah (diklofenak tetes mata = 174,08 ± 21,78 vs diklofenak oral = 206,50 ± 18,93 vs kontrol = 212,58 ± 12,06; one-way ANOVA p = 0.03; post-hoc bonferroni diklofenak tetes mata vs kontrol p= 0,04). Kesimpulan: Tidak terdapat perbedaan skor adhesi makroskopik, mikroskopik, serta histopatologi inflamasi antara kelompok perlakuan diklofenak oral, diklofenak tetes mata, maupun kontrol. Pemberian diklofenak tetes mata 0,1% menunjukkan penurunan area fibrosis dibandingkan kelompok diklofenak oral maupun kontrol. Melalui penilaian RSI, terdapat penurunan ekspresi α-SMA dengan pemberian diklofenak tetes mata 0,1%.
Kata Kunci: α-smooth muscle actin, diklofenak, fibrosis, otot ekstraokular, penyembuhan luka


Background: Fibrosis in the form of tissue adhesions and stretched scar is one factor that affects the outcome of strabismus surgery. Non-steroidal anti-inflammatory drugs, including diclofenac sodium, is a drug that suppresses the inflammatory process and potentially modulates wound healing, including fibrosis in extraocular muscle after strabismus surgery. Objective: To compare the effect of oral and 0.1% topical diclofenac sodium on fibrosis formation following strabismus surgery in the rabbit model. Methods: This experimental study was conducted on rabbit model that underwent superior rectus recession. A randomized controlled trial was performed in three groups: a group treated with oral diclofenac 2 x 5 mg/kg for 3 days (group A), 0.1% diclofenac sodium eye drops 3 times/day for 3 days (group B), and controls (group C). On the 14 th postoperative day, enucleation was performed. Macroscopic adhesion score, inflammation histopathology score (haematoxylin & eosin), microscopic adhesion score and percentage of fibrosis area (Masson's trichrome), and expression of α-smooth muscle actin (α-SMA, immunohistochemistry) were assessed by an anatomic pathologist using a semi-quantitative and quantitative assessment (ImageJ) showing reciprocal staining intensity (RSI) values. Result: Six rabbits (12 eyes) were divided into three treatment groups. There was no difference in macroscopic adhesion (p=0.13), microscopic adhesion (p=0.28), and inflammation histopathology score (p=0.26). The percentage of fibrosis area in topical diclofenac group (12.44% (8.63 – 18.29)) was less than the oral diclofenac group (26.76% (21.38-37.56)) and controls (27.80% (16.42 – 36.28); Kruskal-Wallis test p = 0.04, posthoc oral vs. eye drops p = 0.03 and eye drops vs controls p = 0.04). The semi-quantitative α-SMA expression assessment found no difference between all groups. RSI analysis found that topical diclofenac group had a lower α-SMA expression (diclofenac eye drops = 174.08 ± 21.78 vs. oral diclofenac = 206.50 ± 18.93 vs. control = 212.58 ± 12.06; oneway ANOVA p = 0.03; post-hoc bonferroni diclofenac eye drops vs controls p = 0.04). Conclusion: There was no difference on macroscopic adhesion, microscopic adhesion, and inflammatory histopathology scores in all groups. The administration of 0.1% diclofenac eye drops showed a decrease in the area of fibrosis compared to oral diclofenac and control groups. Through the RSI assessment, there was a significant decrease in the expression of α-SMA with the administration of 0.1% diclofenac eye drops.
Keywords: α-smooth muscle actin, diclofenac, extraocular muscle, fibrosis, wound healing