Strabismus and amblyopia are the commonly eye diseases.Great progress has been achieved in the treating strabismus and amblyopia in recent years.But some essential problems should be considered to gain better therapeutic results for strabismus and amblyopia patients.For example,what is the goal of strabismus surgery? What is the timing(when to treat strabismus and when to treat amblyopia) for strabismic amblyopia? What are the guidelines of amblyopia treatment? Here are summaries and comments round above problems which are expected to be useful for strabismus and amblyopia treatment.

Congenital cataract is responsible for approximately one tenth of childhood blindness worldwide.Generally,cataract includes three inheriting types:autosomal dominant,autosomal recessive or X-linked.The identified genes so far for hereditary cataracts in both human and animal model mainly include encoding structural lens protein,gap junction protein,membrane protein and regulatory protein involved in lens development.Crystallins are the major structural protein of the lens.Mutation in the crystallin genes can result in lens opacity.Understanding of the mechanism of hereditary cataract may also be helpful for us to understand the involvement of environmental and nutritional factors in the process of lens opacification.The function of the crystallins proteins,the mutations in crystallin genes and associated phenotypes are summarized.

Background The visual development is completed during the critical period in human and mammals.However,the critical period is not the initial of receiving visual experience.It is known that before the onset of critical period in mammals,such as mouse,there is an earlier stage for visual development,the pre-critical period.The research of response characteristics of the visual cortical neurons and the synaptic plasticity in the pre-critical period is still in the exploratory stage.Objective The study aimed to preliminarily investigate the response properties of neurons and synaptic plasticity in mouse visual cortex during the pre-critical period.Methods Fortyeight postnatal day 13-17 C57BL/6J mice were used for in vivo whole-cell recordings and in vitro brain slice wholecell recordings.In vivo whole-cell recordings were done in anesthetized mice.Moving bars in different directions were produced and controlled by a Matlab program.Cell recordings were obtained at the depth of layer Ⅳ of visual cortex.Step current stimuli under current clamp were given to measure the membrane response properties of neurons.Optimal visual stimuli were given to measure the in vivo largest responses of membrane potentials.In vitro experiments were performed after in vivo experiments.All cells were given current step stimuli to measure the membrane response properties of neurons.Different intensities of white-matter-to-layer-Ⅳpathway stimulation were given to measure the evoked response properties.All cells from 48 mice were randomized into 4 groups according to different stimulus training modes,including low frequency stimulation (LFS),high frequency theta-burst stimulation (TBS),pre-post synaptic timing stimulation (pre-post TS) and post-pre synaptic timing stimulation (post-pre TS).Under the voltage clamp of-70 mV,excitatory postsynaptic currents (EPSCs) before and after training were recorded to measure the plastic changes of excitatory synaptic connections.pClamp 10 was used for the pre-analysis of data and Matlab 2008a was used for statistical analysis.The use and care of the animals followed the Statement for the Use of Animals in Ophthalmic and Vision Research.Results Thirty-nine cells and 48 cells were successfully recorded in the in vivo and in vitro experiments,respectively.The steady-state average number of action potentials (APs) were (1.01 ± 0.03)/sweep and (1.01 ±0.05)/sweep,the AP thresholds were (-40.2 ± 3.2) mV and (-39.6 ±2.0) mV,and the threshold step current levels were (126.7 ± 17.4) pA and (129.6 ± 17.5) pA in the in vivo and in vitro recordings,respectively,with no significant differences between them (APs:t =0.512,P =0.610;AP thresholds:t =-1.074,P =0.286;current levels:t =-0.776,P =0.440).Under the optimal visual or pathway stimulation,the average peak response of membrane potentials was (7.3 ±4.3)mV and (6.4±2.8)mV with rarely evoked APs in the in vivo and in vitro experiments,respectively,with no significant difference between them (t =1.234,P =0.221).Under the in vitro recording,the EPSCs before LFS were [(138.1 ±51.9)pA],which was significantly higher than that after LFS [(76.1 ± 34.8)pA] (t=4.437,P=0.001),but no significant differences were seen in EPSCs before and after TBS (t=-0.756,P=0.466).The EPSCs before and after pre-post TS were (122.4±62.2)pA and (78.5±46.7)pA,and those before and after post-pre TS were (131.9 ±48.0) pA and (74.3 ± 30.7) pA,showing significant differences between them (pre-post TS:t =3.558,P =0.004;post-pre TS:t =4.283,P =0.001).Conclusions The construction of fundamental neural circuits in layer Ⅳ of mouse visual cortex is completed during pre-critical period.However,the membrane responsive capability of neurons and the synaptic connections are in an immature state,and the evoked responses to visual pathway inputs are basically subthreshold.The strength of synaptic connections is depressed with low frequency stimulation or pre-post/post-pre synaptic timing stimulation,and kept unchanged with high frequency stimulation.The development of visual neural system of PSP in mouse presents different characteristics from CP.

RNA interference (RNAi) is a process triggered by the introduction of small double strand RNA (dsRNA),which leads to a specific degradation of messenger RNA and therefore regulate the expression of target gene.Being one of post transcriptional gene silencing (PTGS),RNAi is found to extensively exist in the body.Some researches of ophthalmology showed that RNAi can be used to prevent and treat multiple eye diseases,including ocular neovascularization,anti-fibrosis,intraocular tumors,autoimmune uveoretinitis,etc.RNAi plays role in switching on and off the target gene.Because RNAi can inhibit gene expression specifically and efficiently,it has gained increasing attention in recent years.The basic concept,acting mechanics and character of RNAi and its application in ophthalmology were summarized.

Background EyeLink 2000 high speed video eye tracker has been used in ophthalmology to evaluate the ocular movement ability.Its systemic precision depends on the performance of the eye tracker, and it is also an essential parameter for the evaluation of the data quality.Therefore, the impact of infrared intensity should be illustrated.Objective This study was to assess the systemic precision of the video eye tracker and evaluate the impact of infrared intensity on the result.Methods The EyeLink 2000 high speed video eye tracker and a pair of artificial eyes were used in this study.Firstly the artificial eyes were fixed to the corresponding position as the real human eyes.Each session of recording was undertaken under the different infrared intensities (100％ , 75％ and 50％).The sampling frequency of binocular recording was set as 1 000 Hz.Each session was sequentially recorded for 60 seconds.The systemic precision was calculated as the root mean square (RMS) of angular distances between successive data points.The RMS values under the different infrared intensities were compared.Results The highest RMS values were (0.005 01 ± 0.000 20) ° under the 100％ infrared intensity.As the decline of infrared intensities ,RMS values were gradually raised, showing a significant difference among different infrared intensity groups (F =3 791.447, P＜0.01).The differences were also significant between different groups (all at P＜0.05).Conclusions EyeLink 2 000 video eye tracker has good system precision.The infrared intensity influence the system precision of the video eye tracker.

Background The extraocular muscles (EOMs) Pulley in primate is related to the function of EOMs,but there are arguments about that.The location of rabbit's eyes is different from the primate.Study on the structure of the extraocular muscle connective tissue in rabbit may play a role to analyze the function of the EOMs Pulley.Objective The structure of the connective tissue around EOMs in rabbit was studied,the difference between this structure in rabbit and homan' s EOMs Pulley in past reports was analyzed,and then,the role of EOMs Pulley to ocular movement was investigated.Methods Five adult rabbits were involved.The gross anatomy of an orbit in each rabbit was observed.The other orbit was processed with paraffin imbedding and coronal serial sections.A murine monocolonal antibody to α-smooth muscle actin(α-SMA) was used to show the smooth muscle,while Weigert stain was used to show muscle and collagen,and Masson trichrome stain to show the elastin.Results An encircling ring of collagen circled every EOM.The collagen ring was thin and connected to the orbital layer muscle fiber loosely.Collagen tissues coupled to adjacent EOMs.Less elastin fibers and scanty the smooth muscle cells were embedded in the collagen.Conclusions The connective tissue around rectus in rabbit is different from that in human with developed binocular ocular movements.It shows that connective tissue around EOMs may be related to the function of ocular movements.

Background Age-related macular degeneration (AMD) is a group of vision-threatening eye disorders.Previous researches showed that the activation of Akt/mammalian target of rapamycin (Akt/mTOR) pathway closely related to the mechanism of AMD.A new specific method to inhibit Akt/mTOR pathway will become a breakthrough for the treatment of AMD.Objective This study was to establish a mouse fibroblast cell line (NIH/3T3) which can stably inhibit the expression of mTOR gene and provide a cell model for the study on the function of Akt/mTOR pathway in AMD and observe the influence of mTOR gene knockdown on related proteins.Methods Three short hairpin RNAs (shRNAs) targeting mTOR gene were designed and synthesized based on murine mTOR mRNA sequence.Double-strand shRNA hairpins were separately cloned into PIGZ-green fluorescent protein (GFP) +Puro vectors to produce recombination plasmids.The packaged lentiviral plasmids and RNAi plasmids were co-transfected into NIH/3T3 cells,a mouse fibroblast line.After puromycin selection and culture expansion,0.5 mg/L puromycin was added the culture medium to establish stable cell clones.The expressions of mTOR mRNA and protein in NIH/3T3 cells were detected by real-time PCR and Western blot respectively,and the inhibitory efficiency of interference was analyzed.Results Transfected GFP-labeled NIH/3T3 cells by lentiviral presented the green fluoresccence with the efficiency of infection of 90％ in the third day.Real-time PCR showed a distinct band of mTOR mRNA in 184 bp.The knockdown rate for sh1,sh2 and sh3 were respectively 31.3％,31.8％ and 45.3％ in the lower multipolicity of infection (MOI) group ;while in the higher MOI group,the knockdown rate for sh1,sh2 and sh3 were 47.1％,56.5％ and 71.6％ respectively.Western blot assay exhibited weakened expression band of mTOR protein in NIH/3T3 cell line for sh1,sh2 and sh3 in both lower and higher MOI groups with the weakest expression for sh3.Conclusions A stable mouse fibroblast cell line is established by the inhibition of mTOR with RNA interference technique,which can provide a cell model for studying the function of Akt/mTOR pathway in AMD.

Background The characteristics of eye movement waveforms in congenital nystagmus eyes is so complicated that the time-series waveform can hardly demonstrate the oscillational kinetic property of the eye movement of nystagmus,which is not convenient for the clinical diagnosis and evaluation.The eye movement system is a nonlinear feedback control system,and phase portrait analysis is a useful method in describing the characteristics of movement in a nonlinear system.Objective This study was to establish the phase portrait analysis method of the eye movement waveforms in congenital nystagmus eyes and provide a new technique for the clinical diagnosis and evaluation of congenital nystagmus.Methods A prospective series-case observational study was performed.This study complied with the Declaration of Helsinki and was approved by Ethic Commission of Tianjin Eye Hospital.Written informed consent was obtained from each patient before examination.Twenty-five patients with congenital nystagmus were enrolled and received examination of video-oculography (VOG) in Tianjin Eye Hospital from April 2012 to February 2013,including 12 patients with congenital motor nystagmus (CMN) and 13 patients with latent nystagmus (LN).The VOG data were format-converted and processed by a Matlab routine.VOG-based phase portraits of eye movement cycles were drawn and related parameters were measured from the phase portraits for further analysis and comparison.Main measurement indexes were cycle position shift (CPS),slow phase peak velocity (SPV),standardized slow-phase peak (SSPV),fast phase peak velocity (FPV) and standardized fast-phase peak velocity (SFPV).Two principal types of waveforms,increasing-velocity type and decreasing-velocity type were compared.Results The phase portraits of the waveforms of congenital nystagmus were cycles of reciprocating trajectories.The slow phases were in dense ribbon region,and the fast phases were in sparse annular region,and all the trajectories travelled in clockwise.The CPS,SPV and FPV of increasing-velocity type were (4.646 ± 1.565),(223.821 ± 114.049),(767.481 ±263.560) ° per second,respectively.The CPS,SPV and FPV of decreasing-velocity type were (9.373 ±4.189),(357.531 ± 154.300) and (1 148.706 ±541.362) ° per second,respectively.The SPVs and FPVs of both increasing-velocity type and decreasing-velocity type showed strong correlation with CPS,respectively (the increasing-velocity type:rSPV-CPS =0.685,P=0.000;rFPV-CPS =0.680,P=0.000;the decreasing-velocity type rSPV-CPS =0.783,P =0.000;rFPV-CPS =0.803,P =0.000).FPVs were significantly larger than SPVs in both types of waveforms (t =6.558,P =0.000;t =5.068,P =0.000).The SSPV of increasing-velocity type was (48.062 ± 15.365) ° per second,which was slightly larger than (41.099± 17.027) ° per second of decreasing-velocity type,with no significant difference between them (t=1.070,P=0.296).The SFPV of increasing-velocity type was (171.186±47.825)° per second,which was larger than (125.317-±38.266)° per second of decreasing-velocity type,showing a significant difference between them (t =2.658,P =0.014).Conclusions Phase portraits can visualize the cyclically dynamic features of congenital nystagmus in a direct way.It facilitates the measurement of eye movement amplitude,speed and other parameters.The phase portrait analysis method provides a novel useful tool in the clinical diagnosis and treatment efficacy evaluation of congenital nystagmus.

Objective Although the ocular motility examination has been traditionally used in the diagnosis of complex strabismus resulting from cranial nerve (CN) and extraocular muscles (EOM) abnormalities, magnetic resonance imaging (MRI) now permits the direct imaging of lesions in CNs and EOMs. Methods Twenty-six patients with complex strabismus underwent MRI examination on 1.5 T MR unit (Twinspeed, GE). Nerves to EOMs were imaged with T1 weighted in orbits in all patients using phase array surface colls. Results Patients with Duane syndrome ( 15 cases, 19 eyes) all exhibited absence or hypoplasia of abducens nerve (CN6), always with mild hypoplasia and apparent misdirection of oculomotor nerve ( CN3 ) to the lateral rectus muscle in the orbit, and there were no hypoplasia of EOMs. Patients with congenital fibrosis of EOMs (9 cases, 16 eyes) exhibited severe hypoplasia of CN3 and CN6, and EOMs appeared hypoplasia to a different degree, particularly severe for the superior rectus and levated palpted muscles. Multiple nerves displayed aplasia in patients with Mobius syndrome (1 case, 2 eyes) and there was abnormal branch from CN3 to lateral rectus. The tendons of bilateral superior oblique muscles were thin in the patients with Brown syndrome ( 1 case, 2 eyes). Conclusion MRI can directly demonstrate absence or hypoplasia of CNs and corresponding EOM abnormalities in congenital complex strabismus, which suggests that the mechanism of congenital complex strabismus is perhaps abnormal innervation or displasia of the ocular motor nerves.

Objective To explore the relevant factors of functionally healing the basic type of intermittent exotropia.Methods A prospective observation study was designed.One hundred and thirty-two cases with basic type of intermittent exotropia in Tianjin Eye Hospital from August 2015 to March 2016.Pre-and post-operation examinations to each patient,including the tests of ocular alignment,Worth four-dot test at 2 m and 33 cm,Titmus,functional visual analyzer (FVA),Frisby Davis distance (FD2) were used to explore the influencing factors of postoperative eye position and stereoscopic reconstruction,and to find the cutoff point of surgery.This study followed the Declaration of Helsinki.This study protocol was approved by Ethic Committee of Tianjin Eye Hospital (No.YKLL-2015-8-21).Written informed consent was obtained from each patient or guardian prior to entering study cohort.Results At 6 months postoperatively,there were 84 cases of orthopedic position,4 cases of overcorrection and 44 cases of undercorrection.The success rate was 63.6％.The deviation at day 1 and peripheral fusion function were statistically significant to postoperative eye position (b =-0.093,P =0.037;b =0.725,P =0.017).The area under the receiver operating characteristic (ROC) curve was 0.645,which showed that the result of Worth four-dot test at 33 cm had lower diagnostic value.Seventy-two cases with eye position between 0 and +10 PD at 1 day postoperatively were all successful in eye position at 6 months postoperatively.The postoperative eye position was the influencing factor for postoperative distance stereo with FVA (x2 =4.036,P =0.045).The age of onset and the preoperative distance stereoacuity with FD2 were the influencing factors of postoperative distance stereo reconstruction (b =-0.213,P =0.023;b =0.021,P =0.036).The area under the ROC curve of the age of onset and the preoperative distance stereoacuity with FD2 was 0.257 and 0.752,respectively.The former had no diagnostic value,and the latter had a medium diagnostic value.The best cutoff point was 22.5" with FD2 at 6 m.Conclusions Success rate of postoperative eye position is affected by the postoperative deviation at day 1.The optimal deviation at post-operation day 1 is 0-10 PD.Postoperative distance stereopsis is improved well and the surgery should be done before the distance stereoacuity is decreased to 22.5" with FD2 at 6 m.