Research status of ciliary dysfunction and visual development related diseases / 中华眼底病杂志

Cilia are hair-like protuberance on cells of the human body that play a vital role in organs generation and maintenance. Abnormalities of ciliary structure and function affect almost every system of the body, such as the brain, eyes, liver, kidney, bone, reproductive system and so on. Retinal photoreceptor cells are one of sensory neurons which convert light stimuli into neurological responses. This process, called phototransduction, takes place in the outer segments (OS) of rod and cone photoreceptors. OS are specialized sensory cilia, and disruptions in cilia genes, which are causative in a growing number of non-syndromic retinal dystrophies, such as retinitis pigmentosa, Leber’s congenital amaurosis. These syndromes are genetically heterogeneous, involving mutations in a large number of genes. They show considerable clinical and genetic overlap. At present, there are few researches on retinal ciliopathies and clinical treatment strategy. This review shows a comprehensive overview of ciliary dysfunction and visual development related diseases, which contributes to understand the characteristics of these diseases and take early intervention in clinic.

Clinical evaluation for atropine penalization in treatment of moderate and severe anisometropic amblyopia / 中华实验眼科杂志

Objective@#To evaluate the effect of atropine penalization for treatment of moderate and severe anisometropic amblyopia.@*Methods@#Retrospective cohort study was performed.Eighty moderate and severe anisometropic amblyopia pediatric patients aged 4-7 years old were enrolled from December 2011 to November 2017 in Tianjin Eye Hospital and Beijing Children's Hospital.The subjects were divided into atropine penalization group and patching group according to the treatment, with 25 cases of moderate amblyopia and 15 cases of severe amblyopia in each group.The best corrected visual acuity (BCVA) of amblyopia in atropine penalization group and patching group before treatment, 2 months, 4 months, 6 months and 8 months after treatment were compared.The binocular visual function of each group was compared before and after treatment.The compliance and complications were also recorded.This study adhered to the Declaration of Helsinki, and was approved by the Ethics Committee of Tianjin Eye Hospital (2016-42) and Beijing Children's Hospital (2019-k-33).@*Results@#There were significant differences in BVCA between the two groups before and after treatment in cases with moderate amblyopia (Fgroup=3.104, P=0.032; Ftime=4.342, P=0.013); The BCVA of atropine penalization group was better than that of patching group at 2, 4, 6 and 8 months after treatment, the differences were statistically significant (all at P<0.05). There were significant differences in BCVA between the two groups before and after treatment in cases with severe amblyopia (Fgroup=3.149, P=0.016; Ftime=5.094, P=0.024); The BCVA of atropine penalization group was better than that of patching group at 2, 4, 6 and 8 months after treatment, the differences were statistically significant (all at P<0.05). The effective rates of stereopsis reconstruction in atropine penalization group were significantly higher than those in patching group in both moderate and severe amblyopia cases, and the differences were statistically significant (both at P<0.05). The compliance rate of moderate amblyopia in atropine penalization group was 96% (24/25), which was significantly higher than 76% (19/25) in patching group, the difference was statistically significant (χ2=4.153, P=0.042). The compliance rate of severe amblyopia in atropine penalization group was 100% (15/15), which was also significantly higher than 67% (10/15) in patching group, the difference was statistically significant (χ2=6.000, P=0.014). During the follow-up period, there were 4 cases with photophobia in the atropine penalization group.No adverse reaction was observed in the patching group.@*Conclusions@#Compared with patching, atropine penalization is an effective method in treatment of moderate and severe amblyopia, with the advantage in rapid improvement of visual acuity, stereopsis recovery and compliance of treatment.Atropine penalization is worthy for clinical application.

Disease genes detection of two anterior segment dysgenesis pedigree by whole exome sequence / 眼科新进展

Objective To identify the disease-causing gene mutation in families with anterior segment dysgenesis (ASD).Methods Two ASD families coming from Henan and Hebei provinces were enrolled in this study.Ocular examinations were performed,and periphery blood specimens were collected from each family member under the informed consent.The blood samples of 2 patients and 1 normal person in family 1 and 1 patient and 1 normal person in family 2 were analyzed by the whole exome sequences.The candidate genes were verified by Sanger sequence and predicted damages by PolyPhen-2 and SIFT Human Splicing Finder software.Results Family 1 including 9 patients were examined in serial 3 passages,which conformed to autosomal dominant inheritance pattern.Clinical examination revealed binocular anterior segment dysgenesis in the 9 patients.There were 13 SNV and 55 InDel candidate mutations.And missense mutation c.T2A(p.M1K)on PAX6 gene was found.Family 2 included 8 members,and 2 patients were examined.The splicing mutation c.357 + 1g ＞ c on the same gene was found.Conclusion T2A(p.M1 K) and c.357 + 1 g ＞ c mutations in PAX6 gene are responsible for ASD.Whole exome sequence provides a new approach to detect diseasecausing mutation of ASD with diversity clinical phenotypes.

Screening of TYR gene mutations and clinical classification in oculocutaneous albinism patients / 中华实验眼科杂志

Background Oculocutaneous albinism (OCA) is a hereditary disease of pigment absence in eyes,skin and hair due to the lack of congenital melanocyte.OCA is classified into 7 types based on different genetic mutations,and the mutation of tyrosinase (TYR) gene causes OCA type 1 (OCA1).OCA has obvious genetic heterogeneity and phenotypic heterogeneity.The molecular diagnosis of the mutant gene is helpful for the classification and molecular pathogenesis study of OCA.Objective This study was to screen the TYR mutation in OCA patients,and to analyze the association between the gene mutation type and clinical phenotype.Methods Ten patients with OCA were enrolled in Tianjin Ophthalmological Hospital from January 2011 to December 2014.The clinical and ocular manifestations of the patients were examined.Peripheral venous blood 3 ml was collected in the patients and their lineal relatives for the extraction of genomic DNA.Extracted DNA was amplified by PCR and the TYR gene sequence was analyzed,including all 5 exon coding sequence and exon 5 ' and 3' end and the non-coding region sequence of intron splicing in TYR gene.This study complied with Helsinki Declaration and the protocol was approved by Ethic Committee of Tianjin Eye Hospital.Informed consent was obtained from each subject.Results All the patients showed white or reddish hair and snow-white skin,and different degrees of pigment lack was seen in iris.The best corrected visual acuity of the patients was 0.05-0.2,and 3 patients complicated with nystagmus.Fundus findings showed a sunset-like change and dysplasia of macula.The TYR gene sequencing revealed that patient 1 was OCA1A subtype,with the compound heterozygous mutant of c.832C＞T (p.R278X) and c.1217C＞T (p.P406L),and his/her parents occurred the heterozygous mutation of exons P406L and R278X.The phenotype of the patient 1 was white hair and white iris.The patient 3 was OCA1B subtype,with the compound heterozygous mutations of c.1265G＞A (p.R422Q) and c.1217C＞T (p.P406L),showing an appearance of reddish brown hair and sallow iris.TYR gene mutant was not detected in other 8 patients.Conclusions The mutation of TYR gene is the main cause of OCA1 type.The phenotype of OCA1A subtype is no pigment in eyes and hair,and one of OCA1B subtype was obviously lessening of pigment.The difference of mutant genes of OCA is the cause of genetic and phenotypic heterogeneity.

Mutation analysis of Pax6 in Chinese patients with congenital aniridia / 中华实验眼科杂志

Background Congenital aniridia is a rare congenital autosomal dominant disease,which is shown as aniridia of double eyes,and the paired box gene 6 (Pax6) gene mutation is now known to be associated with congenital aniridia.Objective This study was to screen the Pax6 gene mutation in patients with congenital aniridia.Methods Eleven patients with congenital aniridia were enrolled in Tianjin Eye Hospital from August 2012 to October 2015,including 6 patients from 3 congenital aniridia family and 5 sporadic patients.All patients received routine ophthalmic examination.Peripheral venous blood of 3 ml was collected from the patients for DNA extraction according to the standard process of DNA isolation instructions,and all the exons of Pax6 gene,Elp4 gene,exon 5 ' and 3',intron splice sequence and SIMO sequence were amplified by PCR.Pax6 genes of the patients were sequenced using Sanger direct sequencing and multiplex ligation dependent probe amplification (MLPA) and compared with those of 500 ocular trauma patients.This study complied with Helsinki declaration,and written informed consent was obtained from each patient prior to any medical examination.Results Iris absence was found in all the patients,and the visions acuity was hand motion to 0.2.Lens dislocation was seen in 1 patient.Direct sequencing results found that three patients in AN-O1 family were c.688g＞t (p.E230X) mutation of Pax6 gene,and 3 of 5 sporadic patients carried c.468g＞a (p.W156X),c.613c＞t (p.Q205X) and c.141 +2t＞c mutant of Pax6 gene,and the c.688g＞t (pE230X) mutation was a novel-discovered mutation.No any mutation in Pax6,Elp4 gene and SIMO fragment was detected in 1 patient from AN-02 family,2 patients from AN-03 family and 2 sporadic patients by both direct sequencing and MLPA validation.No above-mentioned mutation was found in 500 normal individuals.Conclusions The mutation of Pax6 gene is a pathogenic mutation in congenital aniridia patients,and c.688g＞t (p.E230X) is a novel Pax6 mutant,which expanded the mutation spectrum of Pax6 gene.

Therapeutic evaluation of lateral rectus super-recession surgery for large angle divergence excess exotropia / 中华实验眼科杂志

Background In clinic practice,three or four rectus muscles often are needed to perform operation for the correction of large angle (＞50Δ) exotropia to avoid eye limited abduction due to lateral rectus superrecession.However,recent study reported that lateral rectus super-recession surgery can effectively correct large angle exotropia without remarkable abduction limitation.This outcome still need to be verified in clinical practice.Objective This study was to observe the outcome of bilateral rectus super-recession or medial rectus resection of the combined non-dominant eye for large angle exotropia.Methods A series case study was carried out.Fifty-one patients with intermittent or constant exotropia were enrolled in Tianjin Eye Hospital from May 2013 to October 2014.There were 29 intermittent exotropia and 22 constant exotropia among the 51 patients.Combined with adjustable sutures,bilateral lateral rectus super-recession or medial rectus resection of combined non-dominant eye was performed in all the eyes,and the examination of the anterior segment,fundus,ocular movement and binocular vision were performed before and after surgery.The deviation angle was measured by prism and alternate cover test.The individualized surgery procedure was designed according to medical history,ocular movement,sensory status and deviation angle.The patients were followed-up for at least 6 months.The eye position,ocular movement and binocular sensory function were compared between peoperation and postoperation.This study was approved by the Ethics Committee of Tianjin Eye Hospital.Written informed consents before the operation were obtained from all patient or their parents.Results Thirty-three patients underwent bilateral lateral super-recession and 18 patients underwent bilateral lateral super-recession of the medial rectus resection of the combined non-dominant eye.The mean angle of exotropia for seeing distance of 5 meters was (-70.57 ± 16.46) Δ (from-52 Δ to-120 Δ) and was (-75.65 ±16.14) Δ for seeing near (33 cm) (from-55Δ to-130Δ).The mean amount of left eye recession was 8-15 mm ([11.17±1.67] mm) and the right eye recession was 9-15 mm ([11.28±1.62] mm).The medial rectus of the dominant eye was resected by 3-6 mm.At the end of following-up,the mean angle of exotropia for seeing distance was (-3.45±4.20) Δ (from +4Δ to-14Δ) and was (-5.49±3.96) Δ for seeing near (from +4Δ to-14Δ).Surgical outcome was effective in 41 patients (80.4％),and 10 patients were undercorrected.The stereopsis of 32 patients improved after surgery,and 18 of 27 patients without preoperative stereopsis function obtained stereopsis after surgery.No ocular motility disorder was found in this group of patients after surgery.Conclusions Bilateral lateral rectus super-recesssion or medial rectus resection of combined non-dominant eye can effectively correct large angle exotropia and reduce the number and amount of surgical muscles without ocular motility disorder.