Extremely varied phenotypes in granular corneal dystrophy type 2 heterozygotes.

PURPOSE: To investigate the phenotypic variability of patients bearing the heterozygous R124H mutation in the TGFBI (transforming growth factor-beta-induced) gene that causes granular corneal dystrophy type 2 (GCD2). METHODS: We describe the phenotypic range of GCD2 heterozygotes for the common R124H mutation in TGFBI; seven with an extremely mild phenotype and six with an extremely severe phenotype. Detailed slit-lamp photographs of these patients were generated. All patients had no history of ocular surgery and were diagnosed as being heterozygous for GCD2 by DNA analysis from peripheral blood. Expression levels of transforming growth factor-beta-induced protein (TGFBIp) were compared among cultured corneal fibroblasts from ten normal donors. RESULTS: We report profound differences in the severity of the phenotype across our case series. Two patients with a mild phenotype were diagnosed as unaffected at presentation; however follow-up examinations revealed granular deposits. Importantly, we also observed familial clustering of phenotypic variance; five patients from two families with a mild phenotype showed a similarly mild phenotype within family members. Similarly, six patients from two families with severe phenotypes showed corneal deposits with similar patterns and severity within each distinct family, but distinct patterns between families. TGFBIp expressions from different donor derived cultured corneal fibroblasts were different between one another. CONCLUSIONS: GCD2 heterozygotes have extremely varied phenotypes between individual patients. However phenotypes were broadly consistent within families, suggesting that the observed variable expressivity might be regulated by other genetic factors that could influence the abundance of TGFBIp or the function of the pathway. From a clinical perspective, our data also highlighted that genetic analysis and meticulous slit-lamp examination in both eyes at multiple time intervals is necessary.ope

Epithelial Wound Healing after Cataract Surgery Comparing Two Different Topical Fluoroquinolones

PURPOSE: To compare the epithelial wound healing response of two preservative-free fluoroquinolones, moxifloxacin and levofloxacin, in patients who underwent cataract surgery. MATERIALS AND METHODS: In this prospective, evaluator-masked, randomized clinical trial, 59 eyes of 50 patients who underwent cataract surgery were enrolled. Patients were randomized to receive moxifloxacin 0.5% (n=32 eyes) or levofloxacin 0.5% (n=27 eyes). All patients instilled moxifloxacin or levofloxain four times daily for 1 week prior to surgery and 2 weeks after surgery. The epithelial wound healing status in the corneal incision site was scanned with a raster scan mode of fourier-domain optical coherence tomography (FD-OCT). The number of eyes showing epithelial defect images and average number of corneal epithelial defect cuts per eye were compared between groups. All patients were evaluated on postoperative days 1, 2, 3, and 10. RESULTS: On postoperative days 1, 2, and 3, the number of eyes showing epithelial defects in FD-OCT was not statistically different (all p>0.05). The average number of corneal epithelial defect cuts was also not statistically different between the two groups (all p>0.05). No eyes showed epithelial defects on postoperative day 10 in either group. CONCLUSION: There were no differences on epithelial wound healing comparing these two different fluoroquinolones at the incision site of cataract surgery.ope

In Vivo Effects of 4th-generation Fluoroquinolone Antibiotics on Rabbit Corneal Keratocytes

4세대 퀴놀론계 항생제는 기존의 퀴놀론계 항생제보다 그람 양성균 및 비전형 세균에 효과가 있는 광범위 항생제로 최근 백내장 수술을 비롯하여 굴절 교정 수술과 관련된 감염의 예방과 치료를 위해 많이 사용되고 있는 약제이다. 이에 본 연구에서는 상용화 되어 있는 4세대 퀴놀론계 점안 항생제인 gatifloxacin 0.3%와 moxifloxacin 0.5%가 가토 각막 실질에 미치는 영향에 대해 알아보고자 하였다. 뉴질랜드산 흰 가토를 각각 우안은 12 mm 직경으로 각막 상피를 제거하고, 좌안은 각막 상피를 제거하지 않고 gatifloxacin, moxifloxacin, levofloxacin, 인공 눈물군으로 나누어 각 군당 14마리씩 총 56마리의 가토의 눈에 안약을 점안하였다. 안약 점안은 첫 48시간은 1시간 간격, 그 다음 48시간은 2시간 간격으로 양안에 1방울씩 점안하였으며, 안약 점안 96시간 후 가토를 희생하여 각막을 절제한 후 염증성 사이토카인인 TGF-β₁과 IL-1α의 발현 정도와 콜라겐 분해 효소인 Matrix metalloprotease (MMP-1, 2, 8, 9)의 발현 정도를 정량적으로 분석하여, 각막 상피 제거 여부 및 안약의 종류에 따라 차이가 있는지 알아보았으며, 투과전자현미경으로 각막 실질 세포의 미세 구조를 관찰하였다. 염증성 사이토카인인 TGF-β₁은 각막 상피 제거의 여부 및 안약 종류에 따라 차이가 나지 않았으며 IL-1α는 gatifloxacin, moxifloxacin, 인공 눈물군에서 각막 상피를 제거한 경우가 제거하지 않은 경우보다 통계적으로 유의하게 높게 측정되었다. 콜라겐 분해 효소인 MMP의 경우 안약의 종류와 관계없이 각막 상피를 제거한 군에서 MMP-2의 발현이 통계적으로 유의하게 증가되었다. MMP-1과 MMP-2의 발현은 각막 상피를 제거한 군과 제거하지 않은 군 모두에서 gatifloxacin을 사용한 경우가 moxifloxain, levofloxacin, 인공 눈물을 사용한 경우보다 통계적으로 유의하게 증가되어 있었다. MMP-8과 MMP-9의 발현은 각막 상피 제거 및 안약에 따른 차이가 없었다. 투과전자현미경으로 관찰한 각막 실질 세포의 변화는 moxifloxacin을 사용한 군에서 세포 소기관의 부종 및 세포질 내 공포 형성 등의 독성 변화를 보인 경우가 많았다. 결론적으로 4세대 퀴놀론계 점안 항생제 중 gatifloxacin은 각막 상피 결손이 있거나 정상인 경우 모두에서 기존의 퀴놀론계 점안 항생제보다 MMP-1과 MMP-2의 발현을 유의하게 증가시켰으며, moxifloxacin은 각막 실질 세포의 미세 구조에 변화를 일으켰다.;The purpose of this study was to examine the in vivo effect of fourth- generation fluoroquinolones (moxifloxacin and gatifloxacin) on rabbit corneal keratocytes by evaluating the expression of transforming growth factor (TGF)-β₁, interleukin (IL)-1α and matrix metalloproteinases (MMPs). Fifty six NewZealand white rabbits were randomly divided into 4 test groups of 14 rabbits per group: gatifloxacin 0.3%, moxifloxacin 0.5%, levofloxacin 0.5% or preservative-free artificial tear. In all rabbits, a 12-mm-diameter epithelial wound was mechanically made to the center of the right cornea. The left eye of each rabbit served as an intact control. All rabbits received one drop of the test eye drops every hour for 48 hours followed by every 2 hours for an additional 48 hours. The rabbits were sacrificed after 96 hours of instillation of the test eye drops.The expressions of TGF-β₁ and IL-1α were examined using rear-time polymerase chain reaction. The expression of MMP-1, MMP-2, MMP-8 and MMP-9 were evaluated by Western blot assay. The changes of structure of the cells were evaluated with transmission electron microscopy. The expression of TGF-β₁ was similar in both debrided and intact cornea in all test groups. IL-1α was highly detected in the debrided cornea than in the intact cornea which was treated with gatifloxacin, moxifloxacin and artificial tear group. In the gatifloxacin group, MMP-1 and MMP-2 were expressed greater than in the moxifloxacin group and all tested MMPs were expressed greater than in the levofloxacin group. In the levofloxacin group, expressions of the all MMPs were lowest in the test groups. Cytotoxic changes of keratocytes were detected more in the moxifloxacin group than in any other test groups. The fourth-generation fluoroquinolones induced more expressions of IL-1α and MMP-1 and MMP-2 and structural changes than third generation fluoroquinolone or artificial tear in the rabbit cornea. This study suggests that topical fourth-generation fluoroquinolones displayed the potentials to be cytotoxic to human corneal keratocytes.I. 서론 = 1 II. 연구대상 및 방법 = 3 A. 각막 상피 제거술 및 안약 점안 = 3 B. RT-PCR analysis를 이용한 mRNA 발현 분석 = 5 C. Western blot assay를 이용한 단백질 발현 분석 = 7 D. 투과전자현미경을 이용한 미세 구조 분석 = 8 E. 통계 분석 = 9 III. 연구 결과 = 10 A. RT-PCR analysis = 10 B. Western blot analysis = 14 C. 투과전자현미경 소견 = 22 IV. 고찰 = 25 V. 결론 = 31 참고문헌 = 32 ABSTRACT = 3

Changes in Corneal Keratometry Readings after Corneal Collagen Cross-Linking Using Alcohol in Keratoconus Patients.

PURPOSE: To evaluate the changes in corneal keratometry (K) readings after corneal collagen cross- linking (CXL) using 20% alcohol in primary keratoconus and keratectasia after refractive surgery. METHODS: Twelve eyes of 10 patients with primary keratoconus and 3 eyes of 3 patients with keratectasia after refractive surgery were included in the present study. Best-corrected visual acuity (BCVA) and mean K, corneal astigmatism by corneal topography, and mean K, corneal astigmatism, and spherical equivalent (SE) by auto refractometer were evaluated at baseline, and 6 months postoperatively. Eight eyes of 7 patients were also evaluated 1 year postoperatively. RESULTS: Mean BCVA improved from log MAR 0.66 +/- 0.50 to log MAR 0.55 +/- 0.58 (p = 0.100) at 6 month after CXL. In corneal topography, mean K significantly decreased from 50.04 +/- 5.88 D to 49.18 +/- 6.15 D (p = 0.019), and corneal astigmatism slightly decreased from 5.33 +/- 4.47 D to 5.29 +/- 4.88 D (p = 0.755) at 6 months after CXL. According to the auto refractometer, mean K significantly decreased from 48.53 +/- 5.94 D to 47.95 +/- 5.79 D (p = 0.038), corneal astigmatism significantly decreased from 3.95 +/- 2.54 D to 3.52 +/- 2.40 D (p = 0.010), and SE significantly decreased from -6.25 +/- 3.45 D to -5.40 +/- 2.91 D (p = 0.037) at 6 months after CXL. Significant mean K and corneal astigmatism decreases in topography were also observed at 1 year after CXL. Complications related to CXL were not observed. CONCLUSIONS: CXL using 20% alcohol appears to be a safe and promising treatment modality with less corneal stromal damage in progressive primary keratoconus and keratectasia after refractive surgery.ope

Analysis of medical litigations associated with keratorefractive surgery in Korea

Purpose: To analyze the results of court rulings regarding medical litigations involving keratorefractive surgery in Korea. Methods: We collected anonymized judgements involving keratorefractive surgery between 1990 and 2017 and analyzed the causes of medical litigations, the court rulings, reasons for compensation, and the total and average amounts finally awarded. Results: Nineteen of 31 litigations were related to laser in-situ keratomileusis, six to photorefractive keratectomy, and six to laser epithelial keratomileusis surgery. The reasons for litigation were as follows: glaucoma (8), corneal ectasia (7), infectious keratitis (5), retinal disease (2), dissatisfaction in visual outcome (2), photophobia (2), and other (5). Among the 31 cases, 17 (54.8%) litigations were decided in favor of the plaintiff; 14 (45.2%) litigations were decided against. The number of informed consent violations was 15 cases, with 13 cases for the plaintiff and two cases for the defendant, showing a statistically significant difference (p = 0.001). The cause of the lawsuit and injury type did not affect the outcome of the lawsuit. The total amount requested by the plaintiff was KRW 4,846,196,087, and the average amount was KRW 156,328,906. The total amount of damages awarded was KRW 885,804,168, and the average awarded was KRW 52,106,128. Additionally, glaucoma showed the highest total (KRW 393,121,061) and average (KRW 196,560,530) amounts of awarded damages. Conclusions: Nearly half of the lawsuits were handed down in favor of the plaintiff, with more than half involving damages in violation of informed consent. The results of this study are expected to help surgeons understand the reasons for and results of medical lawsuits regarding keratorefractive surgeries, to reduce these types of lawsuits in the future. © 2020 The Korean Ophthalmological Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited

Removal of Lymphangiectasis Using High-Frequency Radio Wave Electrosurgery

PURPOSE: To describe a novel technique using high-frequency radio wave electrosurgery (Ellman Surgitron Dual Frequency RF; Ellman International, Inc) for the management of lymphangiectasis. METHODS: Ablations were performed at the lowest power setting of 1 (of 100) in the cutting mode, producing the least amount of lateral heat. To prevent conjunctival hemorrhage, ablation was initiated immediately before introducing the tip of a needle electrode into the subconjunctival tissue under the target area. After the tip of the electrode reached the target area, ablation was maintained for 1 to 2 seconds on the surrounding area and for a longer time on the dilated lymphatic vessels, until the target conjunctiva blanched. These ablations were performed cautiously with the fine electrode to avoid thermal injury to the adjacent scleral tissue. RESULTS: Persistent lymphangiectasis accompanied by accumulated fluid was successively treated with high-frequency radio wave electrosurgery. Surgical time was less than 5 minutes. There were no intraoperative complications. Fourier domain optical coherence tomography revealed resolution of the accumulated fluid and a decrease of dilated lymphatic vessels. Postoperatively, no notable complications, such as charring, scarring of Tenon capsule, or symblepharon resulting from excessive cauterization, were observed. CONCLUSION: High-frequency radio wave electrosurgery may be a safe, quick, and effective modality for the treatment of symptomatic lymphangiectasis patients.ope

A modified-simple technique of removing the lens cortex during cataract surgery

We describe here a surgical technique of removing the remaining cortex after phacoemulsification without performing the conventional irrigation/aspiration (I/A) procedure. In this technique, the remaining cortex attached to the posterior capsule was separated and dissected into several pieces by continuous irrigation with balanced salt solution, which was supplied through a syringe attached to a bent, blunt-tip needle. Approximately, 10 s of manual irrigation separated most of the remaining cortex from the posterior capsule. Then, the capsular bag was inflated with an ophthalmic viscoelastic device (OVD), and this pushed the separated cortex toward the capsular fornix mechanically. An intraocular lens was inserted into the capsular bag, following which the remaining cortex and OVD were removed concomitantly using an automated I/A handpiece. This technique is a simple and easy maneuver to remove the cortex from all areas, including the subincisional area, and reduce the possibility of a posterior capsule tear

Pathogenesis and treatments of TGFBI corneal dystrophies

Transforming growth factor beta-induced (TGFBI) corneal dystrophies are a group of inherited progressive corneal diseases. Accumulation of transforming growth factor beta-induced protein (TGFBIp) is involved in the pathogenesis of TGFBI corneal dystrophies; however, the exact molecular mechanisms are not fully elucidated. In this review article, we summarize the current knowledge of TGFBI corneal dystrophies including clinical manifestations, epidemiology, most common and recently reported associated mutations for each disease, and treatment modalities. We review our current understanding of the molecular mechanisms of granular corneal dystrophy type 2 (GCD2) and studies of other TGFBI corneal dystrophies. In GCD2 corneal fibroblasts, alterations of morphological characteristics of corneal fibroblasts, increased susceptibility to intracellular oxidative stress, dysfunctional and fragmented mitochondria, defective autophagy, and alterations of cell cycle were observed. Other studies of mutated TGFBIp show changes in conformational structure, stability and proteolytic properties in lattice and granular corneal dystrophies. Future research should be directed toward elucidation of the biochemical mechanism of deposit formation, the relationship between the mutated TGFBIp and the other materials in the extracellular matrix, and the development of gene therapy and pharmaceutical agents. (C) 2015 Elsevier Ltd. All rights reserved

Investigation of Tear Lipid Layer Patterns According to Blinking among Dry Eye Patients

Purpose: To investigate tear lipid layer patterns according to blinking using an interferometer for dry eye patients. Methods: We retrospectively reviewed the medical records of 132 patients who underwent dry eye disease-related evaluation, including LipiView®, between August 2018 and January 2020. Data including past history, slit-lamp examination, tear film break-up time, Schirmer, Oxford score grading, lipid layer thickness (LLT), number of blinks, and tear lipid layer patterns according to blinking were collected. We subdivided dry eye as meibomian gland dysfunction (MGD), aqueous deficiency dry eye (ADDE), and combined ADDE/MGD (Combine); we also classified the tear lipid layer patterns as uphill, flat, downhill, and mix. Results: The numbers of patients in each tear lipid film pattern were as follows; uphill 45, flat 16, downhill 53, and mix 18. The statistically significant clinical characteristics among the four patterns were Oxford score (p = 0.001), LLT (p = 0.019), number of blinks (p = 0.001), number of partial blinks (p = 0.013), and the partial/total blinks ratio (p = 0.001). The most common pattern for MGD was downhill 44.7%; for Combine, downhill 40.7% and uphill 35.8%; and for ADDE, uphill 38.5%. Conclusions: The tear lipid layer graph patterns according to blinking using LipiView® were associated with the number of blinks, the partial/total blink ratio, and LLT. © 2021 The Korean Ophthalmological Societ

Safety of Using Matrix Metalloproteinase Inhibitor in Experimental Glaucoma Filtration Surgery

We evaluated the safety of matrix metalloproteinase (MMP) inhibitor in experimental glaucoma filtration surgery in an animal model. Fifteen New Zealand white rabbits underwent an experimental trabeculectomy and were randomly allocated into 3 groups according to the adjuvant agent: no treatment group (n = 5), 0.02% mitomycin C (MMC) soaking group (n = 5), and MMP inhibitor (ilomastat) subconjunctival injection group (n = 5). Slit lamp examination with Seidel testing, pachymetry, and specular microscopy was performed preoperatively and postoperatively. The conjunctiva and ciliary body toxicity were evaluated with scores according to the pathologic grading systems. Electron microscopy was used to examine the structural changes in cornea, conjunctiva, and ciliary body. In the ilomastat-treated group, there was no statistically significant change in central corneal thickness preoperatively and at 28 days postoperatively (P = 0.655). There were also no significant changes in specular microscopy findings over the duration of the study in the ilomastat-treated group. The conjunctival toxicity score was 1 in the control group, 1.5 in the ilomastat-treated group, and 2 in the MMC-treated group. When assessing ciliary body toxicity scores, the ilomastat-treated group score was 0.5 and the MMC-treated group score was 1.5. Transmission electron microscopy did not show structural changes in the cornea and ciliary body whereas the structural changes were noticed in MMC group. A single subconjunctival injection of MMP inhibitor during the experimental trabeculectomy showed a less toxic affect in the rabbit cornea, conjunctiva, and ciliary body compared to MMC