Preliminary report on screening IGSF3 gene mutation in families with congenital absence of lacrimal puncta and canaliculi

AIM: To investigate the efficacy and safety of phacoemulsification combined with goniosynechialysis and/or endoscopic cyclophotocoagulation (PGE group and PG group) for the treatment of patients with coexisting primary angle-closure glaucoma (PACG) and cataracts. Methods: The clinical data of patients with PACG and cataract were retrospectively reviewed. There was a total of 88 eyes in the study and were divided into two groups, 42 eyes in PGE group and 46 eyes in PG group. Surgery success cumulative survival, preoperative and postoperative intraocular pressure (IOP), number of IOP-lowering medications, best corrected visual acuity (BCVA) in the two groups were observed for more than 12mo and compared within each group and between two groups. Results: The mean IOP in Phaco-GSL-ECP group declined from 24.9 mm Hg preoperatively to 14.1 mm Hg at the first month after operation (P＜0.001) and 16.2 mm Hg at the last visit (P＜0.001). The mean IOP in Phaco-GSL group declined from 24.1 mm Hg preoperatively to 13.0 mm Hg at the first month (P＜0.001) and 15.3 mm Hg at the last visit (P＜0.005). The mean medications reliance in Phaco-GSL-ECP group was reduced from 1.62 preoperatively to 0.13 at the last visit (P＜0.001), meanwhile in Phaco-GSL group the mean medications reliance was reduced from 0.87 to 0.10 (P＜0.001). There was significant difference at baseline, then disappeared at the last visit (P=0.01 vs P=0.867). At the last visit, BCVA increased from 0.21 to 0.60 in Phaco-GSL-ECP group (P＜0.001) and from 0.25 to 0.67 in Phaco-GSL group (P＜0.001). The success rate of Phaco-GSL-ECP group at 1mo visit was 95.2%, at the last visit was 70.7%. The success rate of Phaco-GSL at 1mo was 100%, was 73.4% at the last visit. Conclusion: Phaco-GSL-ECP shows promise for PACG patients with cataracts to reduce IOP, lighten the medication burden and improve visual acuity, and Phaco-GSL still has its value in specific patients.     

Lacrimal Drainage System Obstruction

The lacrimal drainage system consists of the lacrimal puncta, inferior and superior canaliculi, common canaliculus, lacrimal sac, and nasolacrimal duct. It is classically divided into upper and lower portions. Obstruction of the drainage system can be congenital or acquired, and may result in persistent epiphora and mucopurulent discharge. This paper discusses the etiology, clinical picture, diagnosis, and surgical treatment of lacrimal drainage system obstruction.     

Diagnosis of lacrimal canalicular diseases using ultrasound biomicroscopy:a preliminary study

AIM: To evaluate the application of ultrasound biomicroscopy (UBM) in the examination of lacrimal canalicular diseases, and to investigate UBM image characteristics of lacrimal canaliculi in disease states.METHODS:Sixty cases (63 eyes, 69 canaliculi) of lacrimal canalicular diseases were enrolled that included 32 patients (32 eyes, 32 canaliculi) with chronic lacrimal canaliculitis, 18 patients (18 eyes, 18 canaliculi) with previous lacrimal canalicular laceration, 9 patients (12 eyes, 18 canaliculi) with congenital absence of lacrimal puncta and canaliculi, and 1 case (1 eye, 1 canaliculus) of canalicular mass. The patients were examined using UBM, and disease-specific features of the UBM images were noted.RESULTS:UBM imaging of lacrimal canaliculi in chronic canaliculitis patients showed obvious ectasia of the lacrimal canalicular lumen. Dot-like moderate echoic signals were detected on some ectatic lumina of the lacrimal canaliculus. Some lumen-like structures of the lower lacrimal canaliculus were observed in 2 (2 eyes, 2 canaliculi) of the 9 patients (12 eyes, 18 canaliculi) with congenital absence of the lacrimal canaliculus. Of the 18 patients (18 eyes, 18 canaliculi) with previous lacrimal canalicular laceration, the lacerated end on the nasal side of the lacrimal canaliculus was detected only in 14 patients (14 eyes, 14 canaliculi).CONCLUSION:UBM can be used to evaluate lacrimal canalicular diseases and can provide an imaging basis for the diagnosis of lacrimal canalicular diseases.     

鼻泪管引流管及硅胶管联合置管治疗泪道系统多点阻塞

目的:探讨泪点或泪小管狭窄合并鼻泪管阻塞或合并慢性泪囊炎的泪道引流管治疗方法。方法:临床诊断为泪点或泪小管狭窄合并鼻泪管阻塞或合并慢性泪囊炎的患者23例28眼,经泪道探通后,采用泪道引流管[1]和硅胶管联合置入治疗。结果:术后4mo拔管,随诊1a,患者23例28眼中,23眼无溢泪,泪道冲洗通畅,为治愈,治愈率82%。2眼少许溢泪,泪道冲洗时另一泪点少许返流,探针可达骨壁,可以入咽,为好转,好转率为7%。2眼泪道冲洗原路返流,针头不能达骨壁为无效;1眼泪道冲洗时探针可达鼻骨,但再次出现脓性分泌物,为无效,无效率为11%。结论:鼻泪管引流管和硅胶管联合置入是治疗泪道系统多点阻塞有效的治疗方法。     

泪道探通加冲洗治疗婴幼儿泪囊炎的临床研究

目的:研究泪道探通加冲洗治疗婴幼儿泪囊炎的临床疗效。方法:采用7号腰穿针自制的泪道探通冲洗器,黏膜麻醉后,止动。充分扩张泪小点后,将泪道探通冲洗器按常规探通术,由泪小点,泪小管,泪总管,泪囊,穿破隔膜及泪鼻管后,拔出针芯,接冲2g/L盐酸左氧氟沙星冲洗液,边退边冲,患儿出现吞咽动作或呛咳出冲洗液为度。结果:采用此方法治疗婴幼儿泪囊炎33例33眼均为一次性通畅。再次行泪道冲洗者5例5眼(15%),均为一次性治愈。结论:采用泪道探通加冲洗治疗婴幼儿泪囊炎,方法简便、省时,损伤小,疗效快捷,方便,患儿家属易接受。是目前治疗该病症的好方法。     

Conjunctival cicatrizing disease presenting with lacrimal obstruction

Patients with conjunctival cicatrizing disease may develop lacrimal obstruction. Little is published on lacrimal obstruction as the presenting feature of otherwise asymptomatic cicatrizing conjunctival disease. The records of all patients presenting between 1994 and 2015 with lacrimal obstruction found to have cicatrizing conjunctival disease were reviewed. Demographic details, clinical findings, disease progression and treatment were analyzed. Thirty-five patients (25 female), aged 43–91 years (median 74, mean 71.3 years) had epiphora and a mild conjunctival cicatrizing process. Nine patients had onset of epiphora after cataract surgery. All except one patient had obstruction of the proximal lacrimal system (punctum and/or canaliculus). In 14 cases, the obstruction was unilateral (both puncta or canaliculi), with one progressing to bilateral obstruction after 11 years. In 19, all 4 puncta or canaliculi were obstructed. Two patients had unilateral nasolacrimal duct obstruction; one developed contralateral canalicular obstruction 2 years later. Conjunctival biopsies were obtained in 19 of 35 cases (54%), and OCP immunohistochemistry was positive in 7/19 (37%). All other biopsies showed chronic inflammation. Two patients had lichen planus. In follow-up (range 0.1–11 years, mean 3.2 years), 2 patients’ conjunctival disease progressed mildly, and 3 progressed moderately, with 2 of these 5 having positive OCP immunohistochemistry, and 1 having lichen planus. Patients with conjunctival cicatrization may present with lacrimal obstruction, usually punctal or canalicular. Conjunctival disease is usually mild and non-progressive, but patients should be monitored for disease progression.     

泪道激光联合置管术治疗泪道阻塞性疾病的疗效观察

目的: 观察激光联合泪道置管治疗泪道阻塞性疾病疗效。方法: 泪道阻塞性疾病患者79例96眼,27眼(22眼泪小管、泪总管阻塞,5眼泪小管合并鼻泪管阻塞)行激光联合泪道引流管植入术;69眼(27眼鼻泪管阻塞,42眼慢性泪囊炎)行激光联合鼻泪管支架植入术。术后给予激素、抗生素眼药水点眼1wk,泪道引流管术后3～6mo顺利拔管,鼻泪管支架,4wk拔管,所有患者随访12mo。结果: 泪道引流管,鼻泪管支架取出后随访12mo,泪溢消失者79眼,泪溢好转者10眼,无效者7眼,泪溢但无脓,总有效率为93%,显效率82%。结论: 根据泪道阻塞部位选择泪道激光联合不同硅胶管植入是治疗泪道阻塞性疾病简便有效的方法,值得在基层医院推广。     

Novel mutations in the carbohydrate sulfotransferase gene (CHST6) in American patients with macular corneal dystrophy

PURPOSE: To further characterize the mutations within the CHST6 gene responsible for causing macular corneal dystrophy in a cohort of affected patients from the United States. DESIGN: Experimental study. METHODS: Genomic DNA was extracted from buccal epithelium of 16 affected patients (14 families), 17 unaffected relatives, and 127 controls, followed by polymerase chain reaction amplification and direct sequencing of the CHST6 coding region. Subtyping of affected patients into type I and II macular corneal dystrophy was performed by measuring antigenic keratan sulfate (AgKS) serum levels. Haplotype analysis was performed in families that demonstrated common mutations. RESULTS: CHST6 coding region analysis in 10 patients identified as having type I macular corneal dystrophy revealed 10 sequence changes: eight missense mutations, four of which are novel (Met104Val, Tyr110Cys, Gln122Pro, and Leu276Pro) and four of which have been reported previously (Ser51Leu, Pro72Ser, Cys102Gly, and Leu200Arg); one novel homozygous nonsense mutation in two patients from a single family (c. 1683C>T, Gln331X); and one frameshift mutation in a heterozygous state in a single patient (c.1744_1751dupGTGCGCTG). Mutation analysis in the four patients identified as having type II macular corneal dystrophy (serum samples were not obtained from two affected patients) revealed three patients heterozygous for either the c.923G>C, c.969C>A, or c.1519T>C sequence changes. The fourth patient was compound heterozygous for c.969C>A and c.1291T>G. None of these changes was observed in 127 control individuals. Haplotype analysis using microsatellite markers flanking the CHST6 gene did not reveal a common founder for the Leu200Arg (1291T>G) missense mutation, present in five families, identifying this position as a mutation hot-spot. CONCLUSIONS: A variety of previously unreported mutations in the coding region of the CHST6 gene are associated with type I macular corneal dystrophy in a cohort of patients from the United States.     

Novel mutations in CRYBB1/CRYBB2 identified by targeted exome sequencing in Chinese families with congenital cataract

AIM: To summarize the phenotypes and identify the underlying genetic cause of the CRYBB1 and CRYBB2 gene responsible for congenital cataract in two Chinese families. METHODS: Detailed family histories and clinical data were collected from patients during an ophthalmologic examination. Of 523 inheritable genetic vision system-related genes were captured and sequenced by targeted next-generation sequencing, and the results were confirmed by Sanger sequencing. The possible functional impacts of an amino acid substitution were performed with PolyPhen-2 and SIFT predictions. RESULTS: The patients in the two families were affected with congenital cataract. Sixty-five (FAMILY-1) and sixty-two (FAMILY-2) single-nucleotide polymorphisms and indels were selected by recommended filtering criteria. Segregation was then analyzed by applying Sanger sequencing with the family members. A heterozygous CRYBB1 mutation in exon 4 (c.347T>C, p.L116P) was identified in sixteen patients in FAMILY-1. A heterozygous CRYBB2 mutation in exon 5 (c.355G>A, p.G119R) was identified in three patients in FAMILY-2. Each mutation co-segregated with the affected individuals and did not exist in unaffected family members and 200 unrelated normal controls. The mutation was predicted to be highly conservative and to be deleterious by both PolyPhen-2 and SIFT. CONCLUSION: The CRYBB1 mutation (c.347T>C) and CRYBB2 mutation (c.355G>A) are novel in patients with congenital cataract. We summarize the variable phenotypes among the patients, which expanded the phenotypic spectrum of congenital cataract in a different ethnic background.     

慢性泪囊炎合并泪总管阻塞的手术治疗

目的:探讨慢性泪囊炎合并泪总管阻塞的手术方法及临床效果。方法:慢性泪囊炎合并泪总管阻塞患者46例48眼,全部先有流泪、脓性分泌物病史,直至泪囊区出现硬结,红肿,甚至皮肤溃破,经泪道冲洗检查确诊,行改良泪囊鼻腔吻合联合硅胶管植入术,术后随访3a,定期冲洗泪道,观察手术效果。结果:无流泪、脓性分泌物46眼(96%),泪囊区红肿消失,冲洗泪道通畅。2眼仍有流泪,无脓性分泌物,泪囊区红肿消失,泪道冲洗通畅,有效率100%。结论:改良泪囊鼻腔吻合联合硅胶管植入术一次性解决了鼻泪管泪总管同时阻塞的问题,避免患者再次手术的痛苦,减轻经济负担,是治疗慢性泪囊炎合并泪总管阻塞的有效方法。     

两种泪道探通冲洗术治疗先天性鼻泪管阻塞的疗效比较

目的:比较改良的冲洗式泪道探通术与泪道探通冲洗一体式治疗先天性鼻泪管阻塞的治疗效果。方法:选取2008-07/2012-09在我院门诊就诊的252例273眼先天性鼻泪管阻塞的患儿,作为本次的观察对象;其中140例156眼行改良的冲洗式泪道探通,112例117眼行泪道探通冲洗一体式治疗,比较两种方法的治疗效果,并随访1wk～1mo。结果:改良冲洗式泪道探通术一次性探通成功152眼,术后随访有2眼再次阻塞;泪道探通冲洗一体式一次性探通成功107眼,术后随访有8眼再次阻塞;两组比较差异明显具有统计学意义(P<0.05)。结论:改良的冲洗式泪道探通术对先天性鼻泪管阻塞的治疗效果明显优于泪道探通冲洗一体式。     

泪小管断裂吻合术使用麻醉导管作支撑物的效果分析

目的 探讨外伤性泪小管断裂吻合手术使用麻醉导管作支撑物的效果和并发症。方法 23例泪小管断裂患者，以麻醉导管作支撑物，在显微镜下吻合断裂的泪小管。结果 随访1～4年，发现使用麻醉导管作支撑物的吻合术23眼中有5眼泪点外翻，占21．74％。结论 麻醉导管质地较硬，长期留置易造成泪点外翻。     

Determination of relative contribution of the superior and inferior canaliculi to the lacrimal drainage system in health using the drop test

PURPOSE: The aim of this study was to explore the use of the 'drop test' as a method of assessing maximal lacrimal outflow capacity, and to measure the relative contribution of the superior and inferior canaliculi to the drainage capacity in normal subjects. METHOD: The drop test involves instilling measured aliquots of normal saline over 3-min periods to raise the tear lake medially. Both eyes were assessed; however, for the right lacrimal drainage system only, sequential insertion and then removal of silicone punctal plugs was performed. After each stage the maximal lacrimal drainage capacity was measured. no punctal plugs were placed in the puncta on the left side. RESULTS: Complete data were collected from 20 subjects with a mean age of 35.6 years. The intraclass correlation coefficient for the five left eye readings was 0.98 (CI 0.96-0.99) and the limits of agreement of a single reading were -22.6 to +93.0 micro L/3 min. Without intervention, no statistically significant difference was found in the mean lacrimal outflow between the left and right eyes (P = 0.16). A statistically significant reduction in outflow resulted from punctal occlusion (P < 0.05). Presenting the proportion of lacrimal outflow as a percentage of the combined values of the superior and inferior canaliculi, 59.9% of outflow occurred through the inferior canaliculus. CONCLUSION: The drop test was found to provide a simple and repeatable method of assessing lacrimal drainage in a minimally invasive manner in the clinical setting. In healthy volunteers in the supine position 60% of maximal lacrimal outflow capacity occurs through the inferior canaliculus.     

婴幼儿先天性鼻泪管阻塞的治疗探讨

目的：探讨不同年龄阶段的先天性鼻泪管阻塞的婴幼儿,在不同时期采取不同的治疗方法。 方法：将87例102眼患儿分成三个不同的年龄段组：第一组：25天龄~3月龄21例26眼;第二组：〉3~7月龄31例36眼;第三组：〉7~24月龄35例40眼。对第一组实行泪囊鼻泪管按摩＋滴眼液治疗;对第二组进行泪道加压冲洗治疗;对第三组施行鼻泪管探通术治疗。 结果：第一组患儿经泪囊鼻泪管按摩＋滴妥布霉素眼液治疗通畅者12眼,治愈率为46.2%;第二组患儿经泪道加压冲洗治疗通畅者33眼,治愈率为91.7%;第三组患儿经鼻泪管探通术治疗通畅者36眼,治愈率为90.0%。第二组和第三组效果明显优于第一组（χ2=15.71,P〈0.01;χ2=15.27,P〈0.01）;第二组和第三组治疗效果无明显差异（χ2=0.02,P〉0.05）。 结论：婴幼儿先天性鼻泪管阻塞应该区分年龄阶段,采取不同的治疗方法,才能获得较好的治疗效果,而泪道加压冲洗是治疗婴幼儿先天性鼻泪管阻塞的首选方式。     

先天性鼻泪管阻塞首次探通失败再治疗的临床分析

目的：分析我院就诊的28例首次泪道探通失败的先天性鼻泪管阻塞病例资料,总结再治疗策略。

方法：回顾性研究,选取2013-02-01/2017-12-31在我院就诊的591例患儿中的28例,均为首次泪道探通失败的先天性鼻泪管阻塞患儿(不包括外伤性和先天性泪道畸形),收集病史、鼻腔情况、首次探通年龄,治疗前后情况等病例资料。

结果：患儿28例中,15例经再次泪道探通联合置管术,取管后已治愈; 10例患儿经下鼻甲处理后,再次泪道探通联合置管术,取管后已治愈; 2例患儿经常发作急性泪囊炎,在全身麻醉下行鼻内窥镜下鼻腔泪囊吻合术; 1例骨性鼻泪管狭窄和阻塞患儿,有溢泪不伴溢脓,建议定期随访,13岁后鼻窦发育完全后行鼻内窥镜下鼻腔泪囊吻合术。

结论：先天性鼻泪管阻塞首次泪道探通失败再治疗需采取个性化的阶梯治疗方案,合理治疗该疾病。     

非典型Stickler综合征I型三个家系的遗传分析及产前诊断

目的：分析非典型Stickler综合征I型患者的临床表现和遗传学病因,为患者基因诊断、遗传咨询、产前诊断提供理论依据。方法：实验研究。收集3 个典型Stickler综合征I型家系患者的临床表型资料,采集患者及家系其他成员的外周血提取基因组DNA。应用全外显子组测序筛查可疑基因变异,对候选变异进行Sanger测序验证并检测家系全部受检者变异携带情况。通过人类基因变异数据库和PubMed数据库检索候选变异的致病性报道情况,依据美国医学遗传学和基因组学学院与分子病理学协会（ACMG）指南判断致病性及等级。依据先证者相关变异结果对孕妇行产前诊断。结果：纳入研究的3 个家系均检测到Stickler综合征I型致病基因变异。家系1 患者携带COL2A1基c.1693C>T（p.R565C）杂合变异,家系2 患者携带COL2A1基因c.2862C>T（p.G954=）杂合变异,家系3 患者携带COL2A1基因c.2355+1G>A（splicing）杂合变异。这3 个基因变异经保守性分析、功能预测并依据ACMG指南逐一打分判断为致病性变异。结论：全外显子组测序等分子遗传检测技术对非典型Stickler综合征I型的病因学诊断具有重要意义,本研究中3 个家系患者均找到遗传学病因,在基因水平确诊非典型Stickler综合征I型。     

No VSX1 gene mutations associated with keratoconus

PURPOSE: To determine whether mutations of the VSX1 gene play a pathogenetic role in the development of keratoconus (KTCN). METHODS: DNA extraction, PCR amplification, and direct sequencing of the VSX1 gene were performed in 100 unrelated patients with diagnoses of clinical and topographic features of KTCN. RESULTS: Of the four previously identified presumed pathogenic mutations in the VSX1 gene (Leu17Pro, Asp144Glu, Leu159Met, and Arg166Trp), only Asp144Glu was identified in a single affected patient. Two novel single nucleotide polymorphisms (SNPs), both resulting in synonymous substitutions, were identified: c.53G>T (Ser6Ser) in four affected patients and c.209G>T (Pro58Pro) in two affected patients. Two previously reported SNPs were also identified: c.426C>A (Arg131Ser) in one affected patient and c.581A>G (Ala182Ala) in 51 of the 100 affected patients. CONCLUSIONS: Only one of the presumed pathogenic mutations in the VSX1 gene, Asp144Glu, was identified in a single member of the cohort of affected patients. However, as previously demonstrated, Asp144Glu is a non-disease-causing polymorphism. The absence of pathogenic mutations in the VSX1 gene in a large number of unrelated KTCN patients indicates that other genetic factors are involved in the development of this disorder.     

Epiphora as a side effect of topical mitomycin C

AIM: To report symptoms and findings of lacrimal duct malfunction after topical mitomycin C (MMC) for conjunctival neoplasia. METHODS: 14 consecutive patients treated with 1-6 cycles of topical 0.04% MMC four times daily for periods of 2 weeks were interviewed about symptoms of lacrimal duct malfunction. Patients who complained of tearing had examination of the puncta and canaliculi including probing and lacrimal duct irrigation. RESULTS: Nine patients complained of epiphora after topical MMC. Three of these patients had normal puncta and canaliculi, patent to irrigation. In these patients epiphora ceased spontaneously after probing and irrigation. The additional six patients had stenosis of the punctum (n = 3), the common canaliculus (n = 1), both puncta and both canaliculi (n = 1) and complete occlusion of the lower canaliculus (n = 1). CONCLUSION: Obstruction of the puncta or canaliculi is not an infrequent event after topical 0.04% MMC.     

下泪小管断裂吻合术55例临床观察

目的：探讨下泪小管断裂伤术中泪小管鼻侧断端的简单有效的寻找方法及下泪小管断裂吻合术后的疗效评价。

方法：下泪小管断裂伤患者55例55眼采用在手术显微镜直视下或自上泪小点注入生理盐水必要时注射玻璃酸钠的方法寻找断裂的下泪小管的鼻侧断端。以0.8mm外径空心硅胶软管作为支撑物吻合泪小管周围组织2～3针,硅胶软管留置2～3mo。术后随访6～24mo。

结果：下泪小管断裂患者55例55眼均吻合成功。其中治愈49例(89.1%),好转5例(9.1%),无效1例(1.8%)。

结论：该方法是一种行之有效操作简单疗效确切的泪小管断裂吻合方法,适合在有显微手术条件的医院采用。     

激光泪道成形术治疗阻塞性泪道疾病1384例的疗效分析

目的 观察掺钕钇铝石榴石(neodymium-yttrium aluminum garnet, Nd:YAG)激光泪道成形术治疗阻塞性泪道疾病的疗效,并对泪道不同阻塞部位的疗效进行分析.方法 采用Nd:YAG激光泪道成形术治疗1 384 例(1 707眼) 阻塞性泪道疾病患者,按泪道阻塞的部位分为泪小点阻塞(35眼)、泪小管阻塞(625眼)、泪总管阻塞(598 眼)和鼻泪管阻塞(449 眼).术后定期冲洗泪道,随访6个月至3年,将各组疗效进行对比分析.结果 泪小点阻塞、泪小管阻塞、泪总管阻塞及鼻泪管阻塞组的治愈率分别为74.3%、40.0%、36.1 %和31.8 %,有效率分别为94.3 %、57.9%、51.2 %和43.8 %.结论 单纯Nd:YAG激光泪道成形术治疗泪小点阻塞效果最好,而治疗泪小管阻塞、泪总管阻塞及鼻泪管阻塞组的效果欠佳.(中国眼耳鼻喉科杂志,2009,9:101-102)