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"Latar belakang: Ulkus kornea dapat menyebabkan kebutaan karena sikatriks kornea. Transplantasi kornea sebagai tatalaksana sikatriks kornea berisiko tinggi mengalami kegagalan dengan adanya neovaskular pada kornea resipien. VEGF-A diduga sebagai faktor angiogenik utama dalam terbentuknya neovaskular kornea. Berdasarkan pengamatan klinis, neovaskular kornea pada pasien ulkus kornea bakteri lebih luas dibandingkan ulkus kornea jamur, namun belum pernah dibandingkan secara ilmiah. Tujuan: Studi ini membandingkan VEGF-A air mata dan neovaskularisasi kornea antara ulkus kornea bakteri dan jamur. Korelasi antara VEGF-A dengan luas neovaskular juga dihitung. Metode: Penelitian dilakukan terhadap pasien ulkus kornea bakteri dan jamur dengan sampel foto kornea dan air mata. Pengambilan sampel dilakukan pada hari pertama kedatangan dan diulang pada minggu keempat. Analisis foto kornea menggunakan peranti lunak ImageJ® untuk menilai luas neovaskular kornea dan luas defek kornea. Analisis VEGF-A air mata menggunakan enzyme-linked immunosorbent assay (ELISA). Perbedaan dianggap signifikan jika p<0,05. Hasil: Didapatkan 12 subjek ulkus kornea bakteri dan 10 subjek ulkus kornea jamur dengan rerata usia 37 tahun. Bakteri terbanyak Pseudomonas aeruginosa. dan jamur terbanyak Fusarium sp. Defek kornea setara pada awal (bakteri 25,6% (1,8-81,5) vs jamur 22,7% (3,0-45,0), p = 0,644) dan membaik pada minggu keempat (bakteri 0,04% (0-30,5) vs jamur 2,5% (0-15,1), p=0,368). Luas neovaskular kornea pada hari pertama setara (bakteri 10,3% (2,3-37,5) vs jamur 8,0% (3,7-22,8), p = 0,262) namun pada minggu keempat lebih luas pada kelompok bakteri (bakteri 21,6% (2,3-58,0) vs jamur 11,0% (5,4-22,5), p=0,033). VEGF-A air mata setara pada hari pertama (bakteri 215,6 pg/ml (58,0-1111,6) vs jamur 339,3 pg/ml (22,7-1313,0), p=0,391) dan minggu keempat (bakteri 399,7 pg/ml (181,9-1496,3) vs jamur 743,8 pg/ml (78,7-1416,5), p=0,792). Tidak didapatkan korelasi VEGF-A terhadap luas area neovaskular kornea (hari pertama r -0,28, p=0,212, minggu keempat r -0,04 p=0,855). Kesimpulan: Perbedaan luas neovaskular pada minggu keempat diduga karena faktor proangiogenik pada bakteri yang jarasnya melalui VEGF-A serta faktor antiangiogenik pada jamur yang mengalahkan pengaruh VEGF-A. Diperlukan penelitian mendasar yang mencari faktor antiangiogenik tersebut pada jamur.

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Background: Corneal ulcer can cause blindness due to corneal cicatrix. Corneal transplantation as the treatment of corneal cicatrix had higher risk for rejection or failure if the recipient’s cornea possessed neovascularization. VEGF-A was thought to be the major angiogenic factor in corneal neovascularization. Based on clinical observation, corneal neovascularization in bacterial corneal ulcers had more area than in fungal corneal ulcers, however it was never proved scientifically. Objective: This study aimed to compare tear fluid VEGF-A and corneal neovascularization between bacterial and fungal corneal ulcers. The correlation between VEGF-A and neovascular area was also measured. Methods: Corneal photograph and tear fluid samples of bacterial and fungal in corneal ulcer patients were studied. Sample was taken at the first visit and at the fourth week follow up. Corneal photograph was analyzed using ImageJ® software to measure neovascular area and defect area. Tear fluid VEGF-A was examined using enzyme-linked immunosorbent assay (ELISA). Difference was considered significant if p<0,05. Results: There were 12 bacterial corneal ulcer patients and 10 fungal corneal ulcer patients with mean age 37 years old. Most common bacteria was Pseudomonas aeruginosa and most common fungi was Fusarium sp. Corneal defect area between the groups was similar at the first visit (bacterial 25,6% (1,8-81,5) vs fungal 22,7% (3,0-45,0), p = 0,644) and improved at the fourth week (bacterial 0,04% (0-30,5) vs fungal 2,5% (0-15,1), p=0,368). Neovascular area was similar among the groups at the first visit (bacterial 10,3% (2,3-37,5) vs fungal 8,0% (3,7-22,8), p = 0,262), however bacterial group showed larger area at the fourth week (bacterial 21,6% (2,3-58,0) vs fungal 11,0% (5,4-22,5), p=0,033). Tear fluid VEGF-A was similar at the first visit (bacterial 215,6 pg/ml (58,0-1111,6) vs fungal 339,3 pg/ml (22,7-1313,0), p=0,391) and the fourth week (bacterial 399,7 pg/ml (181,9-1496,3) vs fungal 743,8 pg/ml (78,7-1416,5), p=0,792). No correlation obtained between VEGF-A and corneal neovascular area (first visit r -0,28, p=0,212, fourth week r -0,04 p=0,855). Conclusion: The difference of neovascular area at the fourth week could be due to proangiogenic factor of bacteria through its effect on VEGF-A and antiangiogenic factor in fungi that may overcome VEGF-A effect. Further study is needed to confirm the antiangiogenic factor that fungi possess."

"Latar belakang: Ulkus kornea adalah salah satu penyakit infeksi mata yang banyak ditemukan di negara berkembang termasuk Indonesia. Tatalaksana ulkus kornea bakteri konvensional umumnya dapat menimbulkan jaringan parut kornea permanen yang dapat menurunkan tajam penglihatan. Penggunaan transplantasi membran amnion (TMA) pada ulkus kornea dapat mempercepat proses penyembuhan dan mengurangi terbentuknya jaringan parut kornea. Membran amnion diduga menjadi kerangka baru dan mengekspresi beberapa komponen biologis yang berperan membantu proses epitelisasi dan pembentukan jaringan parut di kornea. Tujuan: Mengetahui dan membuktikan perbedaan perubahan klinis pada kelompok TMA dan terapi standar (non-MA) pada pasien dengan ulkus kornea bakteri, perbedaan perubahan kadar protein TNF-, MMP-9, TGF-β1 di air mata dan ekspresi mRNA TNF-, MMP-9, TGF-β1, dan TGF-β2 di air mata dan kornea. Metode: Penelitian tahap pertama, dilakukan penilaian klinis sebelum dan sesudah pada grup TMA dan terapi standar (non-TMA) dengan menilai tajam penglihatan, waktu epitelisasi total, waktu pembentukan sikatrik total dan derajat sikatrik serta uji kadar protein TNF-, MMP-9, TGF-β1 di air mata dengan pemeriksaan ELISA. Penelitian tahap kedua, dilakukan pemeriksaan ekspresi mRNA TNF-, MMP-9, TGF-β1, dan TGF-β2 di air mata dan kornea dengan pemeriksaan quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR). Hasil: Hasil penelitian pertama, pada grup TMA terjadi perbaikan yang signifikan bermakna pada tajam penglihatan (p=0.001), waktu epitelisasi total (p=0.002), waktu terbentuk sikatrik total (p=0.005), dan derajat sikatrik (p=0.001) dibandingkan grup non-TMA. Hasil kadar proteinTNF-, MMP-9, dan TGF-β1 di air mata tidak terjadi perubahan yang bermakna sebelum dan sesudah dan tidak terdapat perbedaan bermakna pada kedua grup (p>0.005). Pada hasil penelitian kedua, ekspresi mRNA TNF-α menurun paling tinggi pada grup TMA (0.824 ± 0), MMP-9 meningkat paling tinggi pada grup TMA (66.698 ± 24.948), TGF-β1 meningkat paling tinggi pada grup TMA (34.425 ± 14.025), sedangkan TGF-β2 mengalami peningkatan tertinggi pada grup non-TMA (114.049 ± 55.344). Kesimpulan: Terdapat perbaikan klinis yang signifikan pasca TMA, sejalan dengan ekspresi gen dari molekul yang terkait ditandai dengan penurunan inflamasi, re-epitelisasi yang lebih cepat, dan pengurangan pembentukan sikatrik. Kadar protein dan ekspresi gen molekul inflamasi di air mata tidak dapat dijadikan penanda untuk proses yang terjadi di kornea.

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Background: Corneal ulcer is one of ocular infection disease that is commonly found in developing country like Indonesia. The conventional treatment for bacterial corneal ulcer usually causes the forming of permanent corneal scar which results in decrease of visual acuity. The use of amniotic membrane transplantation (AMT) in corneal ulcer is believed can shorten the healing process and reduce corneal scar. Amniotic membrane is expected to become as a new scaffold and have several biological properties that play a role in epithelization process and fibrotic tissue formation.

Objective: To evaluate and establish the clinical differences on amniotic membrane transplantation and standard therapy of patients with bacterial corneal ulcer, and laboratory evaluation of protein level and mRNA expression changes of TNF-, MMP-9, TGF-β1 and TGF-β2 in tears and corneal tissue.

Method: This study was divided into two phases on two groups of AMT and standard therapy group (non-AMT). On the first phase, clinical evaluation was examined include visual acuity, total duration of epithelization, total duration of scar formation and the degree of corneal scar, along with laboratory of protein level of TNF-, MMP-9, TGF-β1 in tears with ELISA. On the second phase, mRNA expression of TNF-, MMP-9, TGF-β1, and TGF-β2 in tears and cornea were examined with quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR).

Result: The result of first phase on TMA group showed significant improvement on visual acuity (p=0.001), total duration of epithelization (p=0.002), total duration of scar formation (p=0.005), and cicatrix degree (p=0.001) compared to non-TMA group and a non-significant result on protein level of TNF-, MMP-9, TGF-β1 in tears on both groups (p>0.005).On the second phase, mRNA expression of TNF-showed the highest decrease on TMA group (0.824 ± 0), MMP-9 showed the highest increase on group TMA (66.698 ± 24.948),TGF-β1 expression increased the highest on TMA group (34.425 ± 14.025), whereas TGF-β2 showed the highest result on non-TMA group (114.049 ± 55.344).

Conclusion: There was significant clinical improvement observed in TMA group parallel with related molecular genetic expression, indicated decreasing of inflammation, faster re-epithelization, and less dense scar formation. Protein level and genetic molecular expression in tears are poor predictors of processes occurring in the cornea."