Does the Probability of Survival Calculated by the Trauma and Injury Severity Score Method Accurately Reflect the Severity of Neurotrauma Patients Admitted to Regional Trauma Centers in Korea?

BACKGROUND: Assessing and improving the quality of trauma care is crucial in modern trauma systems and centers. In Korea, evaluations of regional trauma centers are conducted annually to assess and improve trauma management quality. This includes using the Trauma and Injury Severity Score (TRISS) method to calculate the W-score and mortality Observed-to-Expected ratio (O:E ratio), which are used to evaluate the quality of care. We analyzed the potential for overestimation of the probability of survival using TRISS method for patients with neurotrauma, as well as the potential for errors when evaluating and comparing regional trauma centers. METHODS: We included patients who visited the regional trauma center between 2019 and 2021 and compared their probability of survival of the TRISS method, W-score, mortality O:E ratio, and misclassification rates. The patient groups were further subdivided into smaller subgroups based on age, Glasgow Coma Scale (GCS), and Injury Severity Score, and comparisons were made between the neurotrauma and non-neurotrauma groups within each subgroup. RESULTS: A total of 4,045 patients were enrolled in the study, with 1,639 of them having neurotrauma. The neurotrauma patient group had a W-score of -0.68 and a mortality O:E ratio of 1.044. The misclassification rate was found to be 13.3%, and patients with a GCS of 8 or less had a higher misclassification rate of 37.4%. CONCLUSION: The limitations of using the TRISS method for predicting outcomes in patients with severe neurotrauma are exposed in this study. The TRISS methodology demonstrated a high misclassification rate of approximately 40% in subgroups of patients with GCS less than 9, indicating that it may be less reliable in predicting outcomes for severely injured patients with low GCS. Clinicians and researchers should be cautious when using the TRISS method and consider alternative methods to evaluate patient outcomes and compare the quality of care provided by different trauma centers.

Comparison of ocular biometric measurements in patients with cataract using three swept-source optical coherence tomography devices.

BACKGROUND: Precise measurement of ocular biometry is critical for determining intraocular lens power. Newly developed swept-source optical coherence tomography (SS-OCT) - based ocular biometric devices, ANTERION and CASIA2 provide ocular biometric measurements as IOLMaster 700. This study aimed to assess agreement between three devices. METHODS: This retrospective comparative study includes patients with cataract who underwent ocular biometric measurements with three devices, ANTERION, CASIA2, and IOLMaster 700, at Seoul National University Hospital, in April 2020. Anterior keratometry, total keratometry, central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), and axial length (AL) were the main parameters for the comparison. To assess the agreement between the devices, intraclass coefficient (ICC) and Bland-Altman analysis with 95% limits of agreement (LoA) were used. RESULTS: A total of 47 eyes of 29 patients were measured with three devices. Average anterior keratometry showed excellent agreement (ICC ≥ 0.989), and the mean difference was less than 0.1 D. However, the ICC of the total average keratometry ranged from 0.808 to 0.952, and the difference was more than 0.43 D. The AL measured by ANTERION and IOLMaster 700 showed excellent agreement (ICC = 0.999), and the mean difference was 0.005 mm. The ANTERION and IOLMaster 700 did not obtain AL in six (12.8%) and three (6.4%) cases, respectively (P = 0.001 by Fisher's exact test). The CCT, ACD, and LT also showed excellent agreement (ICC > 0.9). CONCLUSIONS: The new SS-OCT-based devices, ANTERION, and CASIA2 showed a good agreement with IOLMaster 700 in measuring ocular biometry except for the total keratometry. The AL of ANTERION and IOLMaster 700 showed excellent agreement.

Long-term survival of full-thickness corneal xenografts from α1,3-galactosyltransferase gene-knockout miniature pigs in non-human primates.

BACKGROUND: We aimed to investigate (a) the long-term survival of corneal grafts from α1,3-galactosyltransferase gene-knockout miniature (GTKOm) pigs in non-human primates as a primary outcome and (b) the effect of anti-CD20 antibody on the survival of corneal grafts from GTKOm pigs as a secondary outcome. METHODS: Nine rhesus macaques undergoing full-thickness corneal xenotransplantation using GTKOm pigs were systemically administered steroid, basiliximab, intravenous immunoglobulin, and tacrolimus with (CD20 group) or without (control group) anti-CD20 antibody. RESULTS: Graft survival was significantly longer (P = .008) in the CD20 group (>375, >187, >187, >83 days) than control group (165, 91, 72, 55, 37 days). When we compared the graft survival time between older (>7- month-old) and younger (≤7-month-old) aged donor recipients, there was no significant difference. Activated B cells were lower in the CD20 group than control group (P = .026). Aqueous humor complement C3a was increased in the control group at last examination (P = .043) and was higher than that in the CD20 group (P = .014). Anti-αGal IgG/M levels were unchanged in both groups. At last examination, anti-non-Gal IgG was increased in the control group alone (P = .013). CONCLUSIONS: The GTKOm pig corneal graft achieved long-term survival when combined with anti-CD20 antibody treatment. Inhibition of activated B cells and complement is imperative even when using GTKO pig corneas.

Protocol for the first clinical trial to investigate safety and efficacy of corneal xenotransplantation in patients with corneal opacity, corneal perforation, or impending corneal perforation.

BACKGROUND: Xenotransplantation using fresh porcine corneas has been suggested as a feasible alternative to overcome the shortage of human donor corneas. Successful long-term survival of grafts without evidence of xenozoonosis in clinically applicable pig-to-non-human primate corneal transplantation model has brought researchers close to human clinical trials. Accordingly, we aimed to prepare a clinical trial protocol to conduct the first corneal xenotransplantation. METHODS: We developed the clinical trial protocol based on international consensus statement on conditions for undertaking clinical trials of corneal xenotransplantation developed by the International Xenotransplantation Society. Detailed contents of the protocol have been modified with reference to comments provided by ophthalmologists and multidisciplinary experts, including an infectionist, an organ transplantation specialist, a clinical pharmacologist, a neuropsychiatrist, a laboratory medicine doctor, and a microbiologist. RESULTS: Two patients with bilateral legal corneal blindness (best-corrected visual acuity ≤20/200 in the better eye and ≤20/1000 in the candidate eye) or with (impending) corneal perforation will be enrolled. During the screening period, participants and their family members will have two separate deep consideration periods before signing informed consent forms. Each patient will undergo corneal xenotransplantation using fresh corneas from Seoul National University miniature pigs. Commercially available immunosuppressants will be administered and systemic infection prophylaxis will be performed according to the program schedule. After transplantation, each patient will be monitored at a specialized clinic to investigate safety up to 2 years and efficacy up to 1 year. CONCLUSIONS: A detailed clinical trial protocol for the first corneal xenotransplantation reflecting the global guidelines is provided.

Long-term safety outcome of systemic immunosuppression in pig-to-nonhuman primate corneal xenotransplantation.

BACKGROUND: Safety concerns exist for corneal recipients under immunosuppression. We report long-term safety results of porcine corneal xenotransplantation under immunosuppression in nonhuman primates. METHODS: Systemic monitoring data from 49 Chinese rhesus macaques that received pig corneal transplant between 2009 and 2018 were retrospectively reviewed. The recipients were divided into 4 groups depending on the systemic immunosuppressants used: (a) conventional steroid group; costimulation blockade groups ([b] anti-CD154 antibody, [c] anti-CD40 antibody); and (d) commercially available immunosuppressants (anti-CD20 antibody, tacrolimus, basiliximab) group. We compared results of general condition monitoring; hematologic, biochemical, and electrolyte tests; and Rhesus Cytomegalovirus infection monitoring. RESULTS: All recipients recovered from early weight loss. White blood cell counts significantly decreased at 6 months in the steroid and anti-CD154 groups. Abnormal liver and kidney function and electrolyte imbalance were not observed in all groups. The mean value of Rhesus Cytomegalovirus DNA copies was consistently lower than 200 copies/mL, and antibody titers did not change over time in all groups. Tacrolimus-associated thrombotic microangiopathy was developed in one case, which resolved after discontinuation of tacrolimus. In 2017, a simian varicella virus outbreak led to clinical signs in 5 that received immunosuppressive therapies, of which 3 died. CONCLUSION: Costimulatory blockade-based and anti-CD20 antibody/tacrolimus-based immunosuppressive therapies seem to be comparably safe with steroid therapy in nonhuman primates receiving corneal xenotransplantation, as they did not reactivate Rhesus Cytomegalovirus and maintained manageable systemic status. Although reactivation is rare, antiviral prophylaxis for simian varicella virus should be considered in immunocompromised hosts.

Long-term safety from transmission of porcine endogenous retrovirus after pig-to-non-human primate corneal transplantation.

BACKGROUND: The risk of xenozoonosis mainly by porcine endogenous retrovirus (PERV) has been considered as one of the main hurdles in xenotransplantation and therefore should be elucidated prior to the clinical use of porcine corneal grafts. Accordingly, an investigation was performed to analyze the infectivity of PERVs from porcine keratocytes to human cells, and the long-term risk of transmission of PERVs was determined using pig-to-non-human primate (NHP) corneal transplantation models. METHODS: The infectivity of PERVs from the SNU miniature pig keratocytes was investigated by coculture with a human embryonic kidney cell line. Twenty-two rhesus macaques underwent xenocorneal transplantation as follows: (i) group 1 (n=4): anterior lamellar keratoplasty (LKP) with freshly preserved porcine corneas, (ii) group 2 (n=5): anterior LKP with decellularized porcine corneas followed by penetrating keratoplasty (PKP) with allografts, (iii) group 3 (n=3): PKP under steroid-based immunosuppression, (iv) group 4 (n=4): PKP under anti-CD154 antibody-based immunosuppression, (v) group 5 (n=4): deep anterior LKP with freshly preserved porcine corneas under anti-CD40 antibody-based immunosuppression, and (vi) group 6 (n=2): PKP under anti-CD40 antibody-based immunosuppression. Postoperative blood samples were serially collected, and tissue samples were obtained from thirteen different organs at the end of each experiment. The existence of PERV DNA and RNA was investigated using PCR and RT-PCR. RESULTS: Using two independent in vitro infectivity tests, neither PERV pol nor pig mitochondrial cytochrome oxidase II was detected after 41 and 92 days of coculture, respectively. After xenocorneal transplantation, a total of 257 serial peripheral blood mononuclear cell samples, 34 serial plasma samples, and 282 tissue samples were obtained from the NHP recipients up to 1176 days post-transplantation. No PERV transmission was evident in any samples. CONCLUSIONS: Within the limits of this study, there is no evidence to support any risk of PERV transmission from porcine corneal tissues to NHP recipients, despite the existence of PERV-expressing cells in porcine corneas.

Anti-CD40 antibody-mediated costimulation blockade promotes long-term survival of deep-lamellar porcine corneal grafts in non-human primates.

BACKGROUND: Corneal xenotransplantation is an effective solution for the shortage of human donor corneas, and the porcine cornea may be a suitable candidate for the donor cornea because of its optical similarity with humans. However, it is necessary to administer additional immunosuppressants to overcome antigenic differences. We aimed to investigate the feasibility of porcine corneas with anti-CD40 antibody-mediated costimulation blockade in a clinically applicable pig-to-non-human primate corneal xenotransplantation model. METHODS: Five Chinese rhesus macaques underwent deep-lamellar corneal transplantation using clinically acceptable sized (7.5 mm diameter) porcine corneal grafts. The anti-CD40 antibody was intravenously administered on a programmed schedule. Graft survival, central corneal thickness, and intraocular pressure were evaluated. Changes in effector and memory T and B cell subsets and anti-αGal and donor-specific antibodies were investigated in the blood, and the changes in complement levels in the aqueous humor and blood were evaluated. Memory cell profiles in the anti-CD40 antibody-treated group were compared with those from the anti-CD154 antibody-treated group or rejected controls presented in our previous report. The changes in anti-αGal, non-αGal, and donor-specific antibodies after 6 months were compared with baseline values. RESULTS: Anti-CD40 antibody-mediated costimulation blockade resulted in the successful survival of xenocorneal grafts (>389, >382, >236, >201, and >61 days), with 80% reaching 6 months of survival. Injection of anti-CD40 antibody considerably reduced the infiltration of inflammatory cells into the grafts and significantly blocked the complement response in the aqueous humor (P=.0159, Mann-Whitney U test). Systemic expansion of central or effector memory T cells was abrogated in the anti-CD40 antibody-treated primates compared with those in the rejected controls (P<.05, Mann-Whitney U test) or those in the anti-CD154 antibody-treated primates (P>.05, Mann-Whitney U test). The levels of anti-αGal, non-αGal, and donor-specific antibodies at 6 months were not significantly increased compared with baseline levels (P>.05, Wilcoxon signed rank test). CONCLUSIONS: An anti-CD40 antibody-mediated blockade appears to be effective immunosuppressive approach for porcine corneal deep-lamellar xenotransplantation in primates.

Prophylactic removal and microbiological evaluation of calcified plaques after pterygium surgery.

PURPOSE: The aim of this study was to investigate microbiological characteristics of prophylactically removed calcified plaques developed after pterygium excision, and to evaluate risk factors for the growth of microorganisms. METHODS: Only exposed calcified plaques developed at the same site of previous pterygium excision were prospectively removed in 15 eyes of 14 patients. Plaques were completely removed, divided into small pieces and evaluated for microbiological identification. Underlying scleral defects were reconstructed using a conjunctival autograft, amniotic membranes and scleral patch grafts according to the size and depth of the defects. Based on the results of microbiologic cultures, eyes were divided into two groups and risk factors for microbial growth were analyzed. RESULTS: At surgery, the mean age of the patients was 71.2 ± 5.8 years and 71.4 % were females. The mean time interval between pterygium excision and calcified plaque removal was 19.3 ± 13.8 years. Six of 15 (40 %) removed plaques showed bacterial growth, and Stenotrophomonas maltophilia was the most frequently isolated microorganism. The size of calcified plaques was the only risk factor for culture-positive results (p = 0.045). Underlying scleral defects were successfully repaired without any serious complication. CONCLUSIONS: Microorganisms can be isolated from calcified plaques developed at the site of previous pterygium excision, and the size of plaques is the only risk factor for culture-positive results. To remove potential source of infection, prophylactic removal of calcified plaques and scleral surface reconstruction should be considered, especially when the plaques are exposed and large.

Corneal keloid: four case reports of clinicopathological features and surgical outcome.

BACKGROUND: Surgical outcome of corneal keloid is largely variable depending on reports, although surgical management is inevitable in visually significant cases. We here report clinical features, histopathological findings, and surgical outcome of four cases of corneal keloid. CASE PRESENTATION: Four Korean male patients without a history of corneal trauma or disease were clinically and histologically evaluated for a slowly-growing, white opacity in the cornea. On slit lamp examination, corneal lesions appeared as a solitary, pearly white, well-circumscribed nodule with a smooth and glistening surface. Because the lesions involved the visual axis deteriorating the visual acuity, the nodules were surgically removed by superficial keratectomy in all patients. Amniotic membrane transplantation was combined in three patients, and an intraoperative mitomycin C application in two patients. Hematoxylin-eosin staining of the excised nodules revealed epithelial hyperplasia, Bowman's layer disruption, thick and irregularly-arranged collagen fibers in the stroma, and accumulation of prominent fibroblasts, which are consistent with the diagnosis of corneal keloid. The corneal keloids recurred in all patients within 10 months of surgical excision and outgrew the boundary of the excised area. CONCLUSION: A diagnosis of corneal keloid should be suspected in patients presenting with an enlarging, white, glistening corneal nodule, even in the absence of a history of corneal trauma or disease. The recurrence is common after surgical excision, and the lesion can be exacerbated by surgery.

Estimation of axial curvature of anterior sclera: correlation between axial length and anterior scleral curvature as affected by angle kappa.

BACKGROUND: Though the development and fitting of scleral contact lenses are expanding steadily, there is no simple method to provide scleral metrics for scleral contact lens fitting yet. The aim of this study was to establish formulae for estimation of the axial radius of curvature (ARC) of the anterior sclera using ocular biometric parameters that can be easily obtained with conventional devices. METHODS: A semi-automated stitching method and a computational analysis tool for calculating ARC were developed by using the ImageJ and MATLAB software. The ARC of all the ocular surface points were analyzed from the composite horizontal cross-sectional images of the right eyes of 24 volunteers; these measurements were obtained using anterior segment optical coherence tomography for a previous study (AS-OCT; Visante). Ocular biometric parameters were obtained from the same volunteers with slit-scanning topography and partial coherence interferometry. Correlation analysis was performed between the ARC at 8 mm to the axis line (ARC[8]) and other ocular parameters (including age). With ARC obtained on several nasal and temporal points (7.0, 7.5, 8.0, 8.5, and 9.0 mm from the axis line), univariate and multivariate linear regression analyses were performed to develop a model for estimating ARC with the help of ocular biometric parameters. RESULTS: Axial length, spherical equivalent, and angle kappa showed correlations with temporal ARC[8] (tARC[8]; Pearson's r = 0.653, -0.579, and -0.341; P = 0.001, 0.015, and 0.015, respectively). White-to-white corneal diameter (WTW) and anterior chamber depth (ACD) showed correlation with nasal ARC[8] (nARC[8]; Pearson's r = -0.492 and -0.461; P = 0.015 and 0.023, respectively). The formulae for estimating scleral curvatures (tARC, nARC, and average ARC) were developed as a function of axial length, ACD, WTW, and distance from the axis line, with good determinant power (72 - 80 %; SPSS ver. 22.0). Angle kappa showed strong correlation with axial length (Pearson's r = -0.813, P <0.001), and the different correlation patterns of nasal and temporal ARC with axial length can be explained by the ocular surface deviation represented by angle kappa. CONCLUSIONS: Axial length, ACD, and WTW are useful parameters for estimating the ARC of the anterior sclera, which is important for the haptic design of scleral contact lenses. Angle kappa affects the discrepancies between the nasal and temporal scleral curvature.

The attitude toward xenocorneal transplantation in wait-listed subjects for corneal transplantation in Korea.

Shortage of donor cornea is a significant problem in Asia, and xenocorneal transplantation is being actively studied to alleviate this problem. However, the attitudes of subjects who await corneal transplants toward xenocorneal transplantation are not known at all. Thus, this study aimed to investigate the attitudes of subjects on the waiting lists for corneal transplants, toward corneal xenotransplantation. A telephone questionnaire survey comprising six items was conducted in 132 subjects among the wait-listed individuals (n = 590) who were awaiting corneal transplantation or had undergone corneal transplantation at Seoul National University Hospital from July, 2003 to August, 2012. Among six inquiries, four questions were used to analyze attitudes toward corneal xenotransplantation. Each question pertained to (1) the acceptance of xenocorneal transplantation, (2) willingness to participate in clinical trials, (3) worries in xenocorneal transplantation, and (4) the concern of self-identity or social life after xenocorneal transplantation. To analyze demographic factors influencing the question, the subjects were arbitrarily divided into two groups: the young (age < 60 yr, n = 58) and the elderly (age ≥ 60 yr, n = 74) or the less-educated (n = 53) and the well-educated with high school diploma, college graduation, or higher education (n = 79). Collected demographic data were analyzed as influencing factors on each question using a chi-square and logistic regression tests. In this study, 42.4% of the subjects (n = 56) expressed favorable views on xenocorneal transplantation using porcine corneas to cure visual loss from corneal blindness. Among those subjects expressing favorable views (n = 56), the willingness to participate in clinical trials, knowing they and their spouses must undergo long-term surveillance, was 62.5% (n = 35). There were 76.5% of subjects (n = 101) expressing worries regarding xenocorneal transplantation, while 28.8% of subjects (n = 38) expressed their concerns about self-identity or social life after xenotransplantation. Younger subjects expressed more worry about xenotransplantation than elderly subjects. The well-educated expressed less concern over self-identity and social life than the less-educated. This survey among subjects who are wait-listed for corneal transplant or who have received a corneal transplant demonstrates that there is an interest in xenocorneal transplantation as an alternate procedure, although there are worries about the procedure that should be further explored in educational campaigns and future studies of the general population.

Cross-reactivity between decellularized porcine corneal lamellae for corneal xenobridging and subsequent corneal allotransplants.

The purpose of this study is to investigate cross-reactivity between hypertonic saline-treated decellularized porcine corneal lamellae for corneal xenobridging and subsequent corneal allotransplants. Five Chinese rhesus macaques, which had undergone anterior partial thickness corneal transplantation using hypertonic saline-treated decellularized porcine corneal lamellae in preceding experiments, were used as recipients for subsequent full-thickness corneal allografts. To determine whether sensitization of recipients to xenoantigens leads to cross-reactivity against alloantigens, we compared; (i) allogeneic one-way mixed lymphocyte reaction (MLR) of peripheral blood mononuclear cells (PBMCs) from xeno-sensitized recipients with that of PBMCs from naïve rhesus macaques, and (ii) amounts of IgG antibodies that bound to the PBMCs of a rhesus panel (five monkeys) before and after xeno-sensitization. Graft survival and immunologic profiles including memory T-cell subsets and donor rhesus-specific antibodies were also evaluated. No hyperacute or acute rejection was observed within a month of subsequent allotransplantation in any recipient. Alloreactivity by MLR was not different between xeno-sensitized rhesus recipients and naïve rhesus monkeys. Panel-reactive IgG antibodies were unchanged after xeno-sensitization, and no change in donor rhesus-specific antibodies was observed in any recipient. No significant changes in memory T-cell subsets were observed during the early post-operative period in any recipient. Decellularized porcine corneal lamellae may not increase cross-reactivity to alloantigens, and thus, porcine corneal lamellae may be used as a bridge to subsequent corneal allografting.

The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of xenocorneal transplantation.

To develop an international consensus regarding the appropriate conditions for undertaking clinical trials in xenocorneal transplantation, here we review specific ethical, logistical, scientific, and regulatory issues regarding xenocorneal transplantation, and propose guidelines for conduct of clinical xenocorneal transplantation trials. These proposed guidelines are modeled on the published consensus statement of the International Xenotransplantation Association regarding recommended guidelines for conduct of clinical islet xenotransplantation. It is expected that this initial consensus statement will be revised over time in response to scientific advances in the field, and changes in the regulatory framework based on accumulating clinical experience.

Tosufloxacin deposits in compromised corneas.

PURPOSE: To report the adverse effects of topical tosufloxacin in two patients with corneal deposits in compromised cornea. CASE REPORT: Tosufloxacin was administered topically to a 13-month-old girl after penetrating keratoplasty in the left eye. Three days posttransplantation, corneal precipitations appeared and thereafter continuously increased. An 80-year-old woman, who maintained postoperative multiple topical medications including tosufloxacin, presented dense white deposits in the left eye a month postoperation. In both cases, the deposits showed a granular pattern and were limited to areas of large epithelial defects. After discontinuation of tosufloxacin, the deposits slowly decreased and completely disappeared in a few weeks. In the former case, corneal re-epithelialization was significantly disturbed and resulted in anterior stromal opacity, whereas visual acuity and visualization of the retina were severely interfered in the latter case. CONCLUSIONS: Tosufloxacin can precipitate especially on compromised corneal surfaces. Therefore, topical tosufloxacin should be avoided in patients who are at risk of losing corneal surface integrity.

Measurement of anterior scleral curvature using anterior segment OCT.

PURPOSE: To investigate and validate methods for measuring the radius of anterior scleral curvature using anterior segment optical coherence tomography images. METHODS: Twenty-four volunteers were enrolled in this study. Anterior segment optical coherence tomography images, centered on horizontal/vertical limbus, including adjacent anterior sclera, were obtained in addition to conventional images centered on the optical axis. Central horizontal, nasal, and temporal optical coherence tomography images were consolidated to a new image for subsequent analyses. The reference points of limbal surface and three scleral points were marked nasally and temporally. The radius of a best-fit circle to the six scleral points was derived (the BFC [best-fit circle] method) and the radii of two circles, the centers of which are on the optical axis and pass through the points of the scleral surface at 2 mm from the limbus nasally and temporally, were calculated (the axial method). To assess the reliability and accuracy of each method, intraobserver and interobserver agreements were analyzed and the radii of contact lenses with known curvatures were measured. RESULTS: The mean (±SD) radius of a BFC was 13.12 (±0.80) mm. The mean (±SD) radius of nasal anterior scleral curvature (13.33 ± 1.12 mm) was significantly greater than that of temporal anterior scleral curvature (12.32 ± 0.77 mm) (paired samples t test, p < 0.001). The BFC and axial methods showed excellent intraobserver and interobserver agreements for measurements (intraclass correlation coefficient > 0.75, p < 0.001), whereas both methods showed a tendency to slightly underestimate the actual curvature of a rigid contact lens of known dimensions (-0.07 ± 0.13 mm [the BFC method] and -0.19 ± 0.07 mm [the axial method], Wilcoxon signed rank test, p = 0.173 and p = 0.028, respectively). CONCLUSIONS: Anterior segment optical coherence tomography is a valuable tool for measuring the radii of anterior scleral curvatures by image processing and mathematical calculation and can provide useful information in specific clinical situations such as designing scleral lenses.

Feasibility of oral doxycycline as first-line therapy for conjunctival mucosa-associated lymphoid tissue lymphoma.

OBJECTIVES: To investigate the long-term outcomes of oral doxycycline as first-line treatment in patients with conjunctival extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). METHODS: In this case series, the medical records of 67 patients with conjunctival MALT lymphoma who received doxycycline as their primary treatment and were followed up for at least 5 years were retrospectively reviewed. Progression-free survival (PFS) was analysed at 3, 5, and 10 years after the initial doxycycline treatment. A Cox proportional hazards model was used to assess the independent risk factors for progression. RESULTS: After the initial treatment, 25 patients (37.3%) achieved a complete response, 8 patients (11.9%) achieved a partial response, 30 patients (44.8%) showed stable disease, and 4 patients (6.0%) showed disease progression. The median PFS in all patients was 168 months, and the 3-, 5- and 10-year PFS rates for all patients were 70%, 65%, and 62%, respectively. No further progression was observed 6 years after the initial doxycycline treatment. Younger age and TNM stage T1c were significant risk factors for the time to progression in the multivariate Cox regression analysis (p < 0.05). Additional doxycycline (>2 cycles) showed no benefit. There were no serious adverse events associated with doxycycline therapy, and most patients were successfully salvaged by second-line treatments, including radiotherapy and chemotherapy. CONCLUSION: In this case series, oral doxycycline treatment yielded acceptable long-term PFS with minimal complications. Especially in patients with stage T1a or T1b conjunctival MALT lymphoma, first-line doxycycline treatment could be considered under close monitoring for at least 6 years.

Ethical and regulatory guidelines in clinical trials of xenocorneal transplantation in Korea; the Korean xenocorneal transplantation consensus statement.

BACKGROUND: To establish the consensus about the conditions for undertaking clinical trials in xenocorneal transplantation in Korea, specific issues regarding the xenocorneal transplantation on ethical and regulatory aspects are addressed, and the guidelines to conduct clinical trial of the xenocorneal transplantation are proposed. METHOD AND RESULTS: Chapter 1 reviews the key ethical requirements and progress of a Korean regulatory framework for clinical trials of xenocorneal transplantation. Chapters 2-7 provide recommendations on source pigs, quality control of porcine corneal procurement, preclinical efficacy required to justify a clinical trial, strategies to prevent transmission of porcine endogenous retrovirus (PERV), patient selection for clinical trials, and informed consent in xenocorneal transplantation using either cellularized or decellularized porcine graft, which are essentially based on the International Xenotransplantation Association (IXA) islet xenotransplantation consensus statement. The consensus statement of the inclusion criteria for the patients' selection has been made by the executive board members in Korean External Eye Disease Society. CONCLUSIONS: This consensus statement will be a good initiative for Korean Food and Drug Administration to discuss final regulatory guidelines in conducting clinical trials of xenocorneal transplantation in Korea and for International Xenotransplantation Association to develop International Consensus Standards of Xenocorneal Transplantation.

Structure-function relationship in glaucoma: Optical coherence tomography en face imaging vs. red-free fundus photography.

BACKGROUND/OBJECTIVES: To analyse retinal nerve fibre layer (RNFL) defect measurements obtained from red-free fundus photography and optical coherence tomography (OCT) en face imaging, respectively, and to compare them for the strength of the structure-function association. SUBJECTS/METHODS: Two hundred and fifty-six glaucomatous eyes of 256 patients with localized RNFL defect on red-free fundus photography were enrolled. A subgroup analysis included 81 highly myopic eyes (≤ -6.0 dioptres). Angular width of RNFL defect was compared between red-free fundus photography (i.e., red-free RNFL defect) and OCT en face imaging (i.e., en face RNFL defect). The correlation between angular width of each RNFL defect and functional outcomes, reported as mean deviation (MD) and pattern standard deviation (PSD), were assessed and compared. RESULTS: The angular width of en face RNFL defect was measured smaller than that of red-free RNFL defect in 91.0% eyes (mean difference, 19.98°). The association of en face RNFL defect with MD and PSD was stronger (R2 = 0.311 and R2 = 0.372, respectively) than that of red-free RNFL defect with MD and PSD (R2 = 0.162 and R2 = 0.137, respectively) (P < 0.05 for all). Especially in highly myopic eyes, the association of en face RNFL defect with MD and PSD was much stronger (R2 = 0.503 and R2 = 0.555, respectively) than that of red-free RNFL defect with MD and PSD (R2 = 0.216 and R2 = 0.166, respectively) (P < 0.05 for all). CONCLUSIONS: En face RNFL defect showed a higher correlation with severity of visual field loss than did red-free RNFL defect. The same dynamic was observed for highly myopic eyes.

Screening fundus photography predicts and reveals risk factors for glaucoma conversion in eyes with large optic disc cupping.

This study aimed to investigate the risk factors for glaucoma conversion and progression in eyes with large optic disc cupping without retinal nerve fiber layer defect (RNFLD). Five hundred forty-two eyes of 271 subjects who had a vertical cup-to-disc ratio (CDR) ≥ 0.6 without RNFLD were enrolled. Characteristics for optic disc configuration (including CDR, vertical cupping, ISNT rule, disc ovality, peripapillary atrophy [PPA]-to-disc area [DA] ratio, and lamina cribrosa pore visibility) and blood vessels (including central retinal vessel trunk [CRVT] nasalization, bayoneting of vessels, baring of circumlinear vessels, history of disc hemorrhage [DH] and vessel narrowing/sclerotic change) were evaluated. From a median follow-up of 11.3 years, 26.6% of eyes (n = 144) developed RNFLD within a median of 5.1 years. Baseline factors, including vertical CDR ≥ 0.7 (hazard ratio [HR] = 2.12), vertical cupping (HR = 1.93), ISNT rule violation (HR = 2.84), disc ovality ≥ 1.2 (HR = 1.61), PPA-to-DA ratio ≥ 0.4 (HR = 1.77), CRVT nasalization ≥ 60% (HR = 1.77), vessel narrowing/sclerotic change (HR = 2.13), DH history (HR = 5.60), and baseline intraocular pressure ≥ 14 mmHg (HR = 1.70) were significantly associated with glaucoma conversion (all Ps < 0.05). An HR-matched scoring system based on initial fundus photography predicted glaucoma conversion with specificity of 90.4%. Careful examination of the optic nerve head and vascular structures can help to predict the risk of glaucoma conversion in eyes with large optic disc cupping.