Voretigene Neparvovec for the Treatment of RPE65-associated Retinal Dystrophy: Consensus and Recommendations from the Korea RPE65-IRD Consensus Paper Committee

Jinu Han(Jinu Han),Kwangsic Joo(Kwangsic Joo),Ungsoo Samuel Kim(Ungsoo Samuel Kim),Se Joon Woo(Se Joon Woo),Eun Kyoung Lee(Eun Kyoung Lee),Joo Yong Lee(Joo Yong Lee),Tae Kwann Park(Tae Kwann Park),San 대한안과학회 2023 Korean Journal of Ophthalmology Vol.37 No.2

Mutations in the RPE65 gene, associated with Leber congenital amaurosis, early-onset severe retinal dystrophy, and retinitispigmentosa, gained growing attention since gene therapy for patients with RPE65-associated retinal dystrophy is available inclinical practice. RPE65 gene accounts for a very small proportion of patients with inherited retinal degeneration, especiallyAsian patients. Because RPE65-associated retinal dystrophy shares common clinical characteristics, such as early-onset severenyctalopia, nystagmus, low vision, and progressive visual field constriction, with retinitis pigmentosa by other geneticmutations, appropriate genetic testing is essential to make a correct diagnosis. Also, fundus abnormalities can be minimal inearly childhood, and the phenotype is highly variable depending on the type of mutations in RPE65-associated retinal dystrophy,which makes a diagnostic difficulty. The aim of this paper is to review the epidemiology of RPE65-associated retinaldystrophy, mutation spectrum, genetic diagnosis, clinical characteristics, and voretigene neparvovec, a gene therapy productfor the treatment of RPE65-related retinal dystrophy.

Ophthalmological manifestations in patients with Leigh syndrome

Han, Jinu,Lee, Young-Mock,Kim, Sang Myung,Han, So Young,Lee, Jong Bok,Han, Sueng-Han British Medical Association 2015 British journal of ophthalmology Vol.99 No.4

<P><B>Background</B></P><P>To describe the ophthalmological manifestations in patients with childhood onset Leigh syndrome (LS) and investigate the correlation between genotypes and phenotypes in patients with LS.</P><P><B>Methods</B></P><P>Childhood onset LS was clinically and enzymatically confirmed in a total of 63 patients. Among them, 44 patients who underwent ophthalmologic consultation were included in this study. Patients with LS underwent genotyping for the whole genome of mitochondrial DNA and SURF1 mutations. The clinical demographic and ophthalmologic phenotypes were compared between the good prognosis group and the poor prognosis group.</P><P><B>Results</B></P><P>Strabismus (40.9%) was the most frequently observed ophthalmologic manifestation, followed by pigmentary retinopathy (22.5%), optic atrophy (22.5%), ptosis (15.9%), and nystagmus (13.6%). Thirteen patients were exotropes and five patients were esotropes. The mean exodeviation was 29.6±12.5 prism dioptres (PD) and the mean esodeviation was 24.0±8.9 PD. All patients with esotropia reported disease onset at <1 year old. Among 26 patients older than 4 years, eight (30.8%) patients had better than 0.4 in the best eye was noted. Eyelid ptosis was a main presenting sign in four patients (9.1%). Among these patients, two patients had m.13513G>A mutation in the <I>MT-ND5</I> gene. Age at onset was 2.47±2.06 years in the good prognosis group and 0.92±0.98 years in the poor prognosis group (p=0.002). Serum lactate peak concentration was 3.23±1.36 mmol/L in the good prognosis group and 4.54±2.31 mmol/L in the poor prognosis group (p=0.051).</P><P><B>Conclusions</B></P><P>LS is a group of mitochondrial disorders with variable ophthalmologic manifestations, the most frequent being strabismus in this study. Ptosis could be an initial sign in patients with LS and these patients can be easily misdiagnosed as having juvenile myasthenia gravis.</P>

Retinal Nerve Fiber Layer Thickness is Decreased in Patients With Hematologic Malignancy

Han, Jinu,Kim, Ji Hyun,Yoo, Hanna,Han, Sueng-Han,Hong, Samin,Seong, Gong Je,Kim, Chan Yun Wolters Kluwer Health, Inc. All rights reserved. 2016 Journal of glaucoma Vol.25 No.3

<P>Purpose: To investigate whether retinal nerve fiber layer (RNFL) thickness is decreased in patients with hematologic malignancy using optical coherence tomography (OCT). Patients and Methods: This prospective, observational cross-sectional study included 65 eyes from 34 patients with hematologic malignancy and 72 healthy control eyes. OCT-measured RNFL thickness parameters (average, 4 quadrants, and 12 clock-hour thickness) and RNFL defect in red-free photo were compared between patients with hematologic malignancy and controls. Results: Among average, quadrant, and clock-hour map, the only 11-o'clock RNFL in patients with hematologic malignancy was statistically thinner than in controls (P=0.021). The RNFL defect was detected in 21/65 (32.3%) patients with hematologic malignancy and in 5/72 (6.9%) controls (P<0.001). In patients with hematologic malignancy, the mean RNFL thickness was significantly lower in the severe and moderate anemia groups compared with the mild anemia group (P=0.011). In the generalized estimating equations model, the mean hemoglobin level was associated with RNFL thickness while correcting for inter-eye correlation, age, and refraction error (coefficient=3.685, P=0.006). Conclusions: The RNFL defect was frequently observed, and the RNFL was thinner in severe anemic patients with hematologic malignancy. These results suggest that chronic anemia may be a factor of RNFL loss.</P>

Recurrent Bilateral Retinal Vasculitis as a Manifestation of Post-streptococcal Uveitis Syndrome

( Jinu Han ),( Sung Chul Lee ),( Won Kyung Song ) 대한안과학회 2012 Korean Journal of Ophthalmology Vol.26 No.4

We report a case of post-streptococcal uveitis mainly presenting with bilateral recurrent retinal vasculitis in Korea. A 14-year-old Asian female presented with decreased visual acuity of 20 / 30 in the right eye and 20 / 25 in the left eye. The patient had a history of glomerulonephritis nine months before onset of uveitis. The manifestation of uveitis was predominantly retinal vasculitis. We presumed post-streptococcal uveitis because probable streptococcal infection was confirmed by anti-streptolysin O titer elevation. With topical and oral steroid treatments, the patient experienced complete vision recovery. Post-streptococcal uveitis occurs rarely and mostly involves young patients in the form of non-granulomatous anterior uveitis. However, as this case shows, it may primarily involve the posterior uvea without anterior inflammation and may recur.

안과 영역에서의 차세대 염기서열 분석

한진우(Jinu Han) 대한검안학회 2018 Annals of optometry and contact lens Vol.17 No.4

Next-generation sequencing is widely used in inherited diseases and cancer genetics fields. Next-generation sequencing technology provides accurate diagnosis in genetically heterogeneous disorders such as retinitis pigmentosa, Leber congenital amaurosis, or cone-rod dystrophy. However, the precise interpretation of variants produced by massively parallel sequencing is somewhat difficult to most of ophthalmologists, and misinterpretation of these variants lead to unwanted devastating consequences to the patients and their family. The molecular genetic findings need to be carefully evaluated in the context of the clinical findings to avoid misdiagnosis. Gene therapy trials are already in the market for specific forms of Leber congenital amaurosis. We are in the middle of exiting era of effective treatment for patients with inherited eye diseases, which was considered as incurable in the past. To success such a treatment, molecular diagnosis will become essential.

편측 상사근마비에서 상사시 각도에 따른 단일 하사근절제술의 치료 효과 및 유용성

이수경(Sukyung Lee),한진우(Jinu Han)한승한(Seung-han Han),신우범(Woo Beom Shin) 대한안과학회 2021 대한안과학회지 Vol.62 No.11

목적: 편측 상사근마비 환자에서 수술 전 상사시각에 따른 단일 하사근절제술의 유용성을 살펴본다. 대상과 방법: 편측 상사근마비 진단 하 일차적으로 단일 하사근절제술을 시행 받은 환자 99명을 수술 전 상사시각에 따라 15 prism diopters (PD) 이하(그룹 1), 16 PD 이상 20 PD 이하(그룹 2), 20 PD 초과(그룹 3)로 분류하여 수술 전후 상사시각 및 머리기울임 호전 여부를 분석하였다. 수술 성공은 잔여 상사시각이 5 PD 이하이고 과교정되지 않았을 때로 정의하였으며, 수술 전 상사시각이 5 PD 이하였을 경우 수술 후 잔여 상사시각과 머리기울임 호전이 있으며 과교정되지 않았을 때로 정의하였다. 결과: 전체 99명 중 그룹 1, 2, 3은 각각 65명, 22명, 12명이었으며, 모든 그룹에서 수술 후 상사시각의 유의한 호전을 보였다. 그룹 1에서 그룹 3으로 갈수록 상사시 교정 효과가 의미 있게 증가하였다. 머리기울임은 각 그룹의 80.3%, 95.0%, 90.9%에서 호전되었다. 각 그룹의 수술 성공률은 각각 87.7%, 77.3%, 50.0%였고, 그룹 1과 2 간에는 유의한 차이가 없었고 그룹 1과 3 사이에만 유의한 차이가 있었다. 결론: 수술 성공률과 머리기울임 호전, 과교정 등을 고려하였을 때, 수술 전 상사시각이 20 PD 이하인 편측 상사근마비 환자에서 단일 하사근절제술이 1차 수술로서 유용하다. 반면 수술 전 상사시각이 20 PD보다 큰 환자에서는 50%의 성공률을 보였으므로, 두 외안근의 동시 수술 혹은 단일 하사근절제술 시행 후 2차 수술의 필요성을 고려해야 한다. Purpose: To evaluate surgical outcome and effectiveness of inferior oblique (IO) myectomy on unilateral superior oblique palsy (SOP) as a primary treatment. Methods: This study is a retrospective review of the medical records of 99 patients who had undergone IO myectomy due to SOP as a first-line treatment. Sixty-five patients with hyperdeviation of 15 prism diopters (PD) or less were categorized into group 1, 22 patients with hyperdeviation between 16 PD to 20 PD into group 2, and 12 patients with hyperdeviation higher than 20 PD into group 3. Preoperative hyperdeviation, postoperative hyperdeviation, and improvement of head tilting were then compared between the 3 groups. Surgery was determined to be successful when the post-op residual hyperdeviation is less than 5 PD, or when the improvement of hyperdeviation and head tilting was noted, for the patients who had preoperative deviation less than 5 PD, and without hypercorrection. Results: All groups showed significant improvement of hyperdeviation, and the amount of correction was larger in group with larger preoperative hyperdeviation. 80.3%, 95.0%, and 90.9% of patients showed improvement of head tiling and success rate was 87.7%, 77.3%, and 50.0% in group 1, 2, and 3 respectively. Group 1 and 2, group 2 and 3 had no significant difference in success rate but only group 1 and 3 had significant difference. Conclusions: Considering success rate with improvement of head position, self-titrating and possibility of overcorrection, IO myectomy could be an effective option as a first-line surgical treatment for unilateral SOP with hyperdeviation of 20 PD or less. However, due to a 50% success rate in patients with hyperdeviation larger than 20 PD, a secondary operation must be considered following IO myectomy, or a two-muscle procedure must be considered as a primary treatment.

긴장 및 조절 눈모음과다 내사시 환자들에서의 사시 수술 후 결과

이민우(Minwoo Lee),한승한(Sueng-Han Han),한진우(Jinu Han) 대한안과학회 2018 대한안과학회지 Vol.59 No.5

목적: 높은 조절눈모음비(accommodative convergence per accommodation, AC/A) 눈모음과다 내사시 환자들과 낮은 조절눈모음 비를 가진 긴장 눈모음과다 내사시 환자들에서 양안 내직근 후전술(bilateral medial rectus recession)의 수술 결과를 비교하였다. 대상과 방법: 근거리 사시각이 원거리 사시각보다 10 prism diopter (PD) 이상 큰 환자들 중에서 양안 내직근 후전술을 시행한 환자들의 의무기록을 후향적으로 분석하였다. 눈모음과다 내사시 환자들 중 사시 수술을 경험한 모든 환자들의 의무 기록을 확인하였고, 긴장 눈모음과다 내사시 환자 6명과 높은 조절눈모음비(AC/A) 눈모음과다 내사시 환자 10명을 대상으로 하였다. 마지막 추적 관찰 기록에서 원거리와 근거리 주시 시 각도 편차가 10 PD 이하이며, 원거리와 근거리의 사시각이 8 PD 이하인 경우를 성공적인 수술 결과로 정의하였다. 결과: 수술 당시의 평균 연령은 긴장 눈모음과다 내사시군에서 5.9 ± 1.6세였고, 높은 조절눈모음비 눈모음과다 내사시군에서는 7.3 ± 2.9세로 관찰되었다(p=0.301). 수술 후 추적관찰기간은 긴장 눈모음과다 내사시군에서 2.7 ± 2.9년, 높은 조절눈모음비 눈모음과다 내사시군에서 4.0 ± 3.3년으로 유의미한 차이가 없었다(p=0.426). 근거리와 원거리 사시각의 차이는 모든 긴장 눈모음과다 내사시 환자(100%)에서 10 PD 이내로 줄어들었으나, 높은 조절눈모음비 눈모음과다 내사시군의 경우 10명 중 오직 6명(60%)만이 10 PD 이내로 줄어들었다. 수술의 성공률은 긴장 눈모음과다 내사시군에서 5명(83.3%), 높은 조절눈모음비 눈모음과다 내사시 환자군에서 5명(50%)으로 긴장 눈모음과다 내사시군에서 수술의 성공률이 더 높은 것을 확인하였으나, 숫자가 작아 통계적으로 유의미한 차이가 확인되지는 않았다(p=0.307, Fisher’s exact test). 긴장 눈모음과다 내사시 환자 5명에서는 증량 양안 내직근 후전술을 시행하였고 5명(100%) 모두에서 성공적인 수술 결과를 확인하였다. 결론: 긴장 눈모음과다 내사시 환자에서 양안 내직근 후전술을 시행하였을 때 6명 중 5명(83%)에서 성공적인 수술 결과를 확인하였으 며, 이는 높은 조절눈모음비 눈모음과다 내사시군에서 확인한 수술 성공률(50%)에 비해 높았다. 또한 높은 조절눈모음비 눈모음과다 내사시 환자군에서 증량 내직근 후전술을 시행할 때에 비하여 긴장 눈모음과다 내사시 환자군에서 증량 내직근 후전술을 시행할 때더욱 높은 성공률을 기대할 수 있을 것이다. <대한안과학회지 2018;59(5):465-470> Purpose: To investigate the surgical outcomes of augmented bilateral medial rectus (BMR) recession in patients with low accommodative convergence/accommodation (AC/A) ratio tonic convergence excess esotropia (ET) compared to high AC/A ratio convergence excess ET. Methods: This study included patients with esodeviation ≥10 prism diopter at near than at distance fixation who underwent BMR recession. The medical records of all esotropic patients with convergence excess who underwent strabismus surgery were reviewed. Six patients with tonic convergence excess and 10 patients with a high AC/A ratio met the study inclusion criteria. A successful outcome was defined as a near or distance angle of deviation ≤8 prism diopter and a ≤10 prism diopter difference between the two at the final recorded visit. Results: The mean age at surgery was 5.9 ± 1.6 years in the tonic convergence excess ET group and 7.3 ± 2.9 years in the high AC/A ET group (p = 0.301). The average length of the postoperative follow-up was 2.7 years (range, 0.6–8.4 years) in the tonic convergence excess ET group and 4.0 years (range, 0.6–8.4 years) in the high AC/A ET group (p = 0.426). Near-distance disparities were reduced in all patients with tonic convergence excess ET within 10 prism diopter postoperatively, but in only 6 of 10 patients in the high AC/A ET group. Five of 6 patients (83.3%) had successful outcomes in tonic convergence excess ET group; 5 of 10 patients (50%) had successful outcomes in the high AC/A ET group. Conclusions: In our series, five patients (83%) obtained successful results in the tonic convergence excess ET group compared with 50% in the high AC/A ET group. Augmented BMR recession can be safely performed in esotropic patients with tonic convergence excess. J Korean Ophthalmol Soc 2018;59(5):465-470

Optical Coherence Tomography Findings Facilitate the Diagnosis of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

Hyuna Cho,Chul Hyoung Lyoo,Sung Eun Park,Yuri Seo,Sueng-Han Han,Jinu Han 대한안과학회 2021 Korean Journal of Ophthalmology Vol.35 No.4

밀러-피셔증후군과 비커스태프 뇌줄기염의 임상적 특징

김민하(Min Ha Kim),서유리(Yuri Seo),한승한(Sueng-Han Han),한진우(Jinu Han) 대한검안학회 2020 Annals of optometry and contact lens Vol.19 No.4

Purpose: To investigate the clinical characteristics of patients clinically diagnosed with anti-GQ1b antibody syndrome. Methods: From November 2005 to July 2019, we retrospectively reviewed the medical records of 52 patients diagnosed with Miller-Fisher syndrome, Bickerstaff brainstem encephalitis or anti-GQ1b antibody syndrome. Symptom including acute ophthalmoplegia, ataxia, hyporeflexia and other neurologic features were reviewed. Laboratory results including cerebrospinal fluid (CSF) analysis and anti-ganglioside antibodies were also analyzed. Results: Among 52 patients, 40 were diagnosed with classic Miller-Fisher syndrome, 3 patients were Guillain-Barré syndrome with ophthalmoparesis, 1 patient was acute ophthalmoparesis without ataxia, 2 patients were acute ataxic neuropathy, and 6 patients were diagnosis with Bickerstaff brainstem encephalitis. Thirty five patients were male (67.3%), the mean age of onset was 39.3 ± 16.7 years, and average follow-up duration was 9.6 ± 15.9 months. Forty-four patients (84.6%) showed preceding infection, and upper respiratory infection was more common than gastrointestinal infection. Forty-nine patients (94.2%) showed ophthalmoplegia, 48 patients (92.3%) showed ataxia and hyporeflexia was presented in 43/51 patients (84.3%). Other than classic symptoms, dysarthria (21/52, 40.4%), dizziness (27/52, 51.9%), and paresthesia (23/52, 44.2%) was observed. Among 48 patients who underwent CSF analysis, 11 patients (22.9%) showed albumino-cytologic dissociation. Only 12 patients (23.1%) had positive anti-ganglioside antibodies. Conclusions: Anti-GQ1b antibody syndrome is not easy to differentiate from other diseases, careful physical examination and history taking is necessary to make correct diagnosis. The recognition of accompanying symptoms and signs could facilitate early and exact diagnosis of anti-GQ1b antibody syndrome.

용선계약상 면책조항과 불가항력조항의 차이점에 관한 연구 : Limbungan 사건을 사건을 중심으로

박진우(Jinu Park),한낙현(Nak-Hyun, Han) 한국국제상학회 2020 國際商學 Vol.35 No.3

Limbungan 사건은 정기대량화물 운송계약의 기간 도중 댐의 붕괴가 발생하여 화물제공의무에 위반한 용선자가 장기운송계약상의 면책규정에 의거하려고 한 것에 발단이 되고 있다. 이 사건 항소법원은 계약위반 후 손해배상액을 산정할 때 발생하는 사건을 고려한 두 사건인 Golden Victory호 사건에서의 귀족원판결과 Bunge v. Nidera 사건에서의 대법원판결을 구별했다. 항소법원은 이 두 사건이 이행기전 위반과 관련이 있고 이 사건이 실제 위반과 관련이 있다는 이유로 이를 정당화했다. 용선자는 대법원에 상고 허가를 신청하고 있는 중인데, 이것이 인정될 가능성이 높다. 본 연구에서는 Limbungan 사건의 면책규정에 대해 면책조항과 불가항력조항의 성질과 그 적용요건의 차이를 고려하여 분석하고, 또한 이행 의사의 여부에 불구하고 결과적으로 계약을 이행할 수 없었을 경우의 손해배상액의 산정방법에 대해 이행기 전 계약위반과 사실상의 계약위반에 대해서도 비교분석을 한다. Purpose : The purpose of this study aims to analyse the differences between exception clause and force majeure clause under charterparty with the Limbungan case. Research design, data, methodology : This paper focuses on the Limbungan case, and is carried out through the literature method using academic papers and internet data for the analysis of this case. Results : This result is as follows. First, although the doctrine of frustration, force majeure clauses, and exceptions clauses share many similarities, where a provision is clearly intended as an exceptions clause, it must be interpreted on its own terms in accordance with the usual rules of contractual construction. Second, although in cases of anticipatory breach, it may be appropriate to take into account a party’s willingness to perform and whether, even if willing, it would nevertheless have been excused from performance by later events. Conclusions : An exceptions clause does require the party seeking to rely on it to show that it would not have been in breach had the exception relied upon not occurred. It is unclear if the ‘but for’ test is to be applied to both force majeure and exceptions clauses. The contract may need to have additional provisions added on how the clause is to be interpreted.