Correlation of ischemic ophthalmopathy with lacunar infarction

AIM: To investigate the effects of nintedanib thermo-sensitive hydrogel (NTH) on neovascularization and related markers in corneal alkali burns of Wistar rats. METHODS: NTH was prepared by grinding, and its phase-transition temperature was determined. Thirty specific-pathogen-free Wistar rats served as a model of corneal alkali burn in the right eye were randomly divided into 3 groups (n=10, each): model group treated with 0.9% saline once a day, NTH group with 0.2% nintedanib b.i.d, and dexamethasone (DEX) group with DEX ointment once a day. The left eye of rats served as the controls. The corneal transparency was observed under a slit-lamp microscope, and the area of neovascularization was calculated. On day 7, the rats were sacrificed, and the cornea was removed and embedded with paraffin, then stained with hematoxylin-eosin, and the expression of VEGFR-2 and CD31 in the corneal tissues of each group was detected by immunofluorescence. RESULTS: The phase-transition temperature of nintedanib obtained by grinding was 37°C after adding artificial tears. The results of the alkali burn model indicated that the growth rate of neovascularization in the NTH group was slower than that in the model group, and the neovascularization area was significantly smaller than that in the model group (P<0.05). Moreover. CD31 and VEGFR-2 expression levels in the NTH group were significantly lower than those in the model group. CONCLUSION: NTH becomes colloidal at body temperature, which is beneficial for releasing the drug slowly and can significantly inhibit the neovascularization of corneal induced by alkali burn in rats.     

Amniotic Membrane Transplant for Bullous Keratopathy: Confocal Microscopy & Anterior Segment Optical Coherence Tomography

Purpose: To assess amniotic membrane retention after amniotic membrane transplant in bullous keratopathy patients and whether there were any corneal structural changes that may hinder further penetrating keratoplasty

Methods: A retrospective study including 22 patients who have undergone amniotic membrane transplant from 1 Jan 1998 till 30 Jun 2016. Confocal microscopy and anterior segment optical coherence tomography (ASOCT) were performed to assess the retention of amniotic membrane and to detect any corneal structural changes. The comparison was made with 5 controls who had bullous keratopathy awaiting endothelial keratoplasty.

Results: Patients had a mean follow-up of 61 ± 33.7 months. Pain reduction was significant (p < .001) although it did not significantly correlate with the regularity of the superficial, intermediate or basal epithelial layers, nor with the retention of the amniotic membrane. No long-term structural changes that may hinder future penetrating keratoplasty were detected.

Conclusion: This procedure is a safe and effective long-term treatment for symptomatic bullous keratopathy patients.     

Hippo/YAP信号通路在眼部作用的研究进展

Hippo-YAP通路在机体发育和疾病发生中均具有重要作用。Hippo-YAP通路的调节紊乱可能导致病理组织过度生长和肿瘤的进展；近年来研究发现，Hippo-YAP信号通路的异常调节可能与眼部疾病相关，如圆锥角膜、Sveinsson 脉络膜视网膜萎缩和视网膜变性等，本文就Hippo/YAP 在眼部作用的研究进展进行系统综述，为眼部疾病的治疗提供理论基础。     

The effect of time on grading corneal fluorescein and conjunctival lissamine green staining

PurposeTo explore the effect of time on grading corneal fluorescein and conjunctival lissamine green staining in dry eye disease (DED).MethodsPhotographs of 68 subjects with non-Sjogren's DED (nSS DED) and 32 with Sjogren's DED (SS DED) were taken of corneal fluorescein staining, then conjunctival lissamine green staining every 30 s for at least 5 min. Photographs of one randomly selected eye were then randomly ordered and graded on a scale from 0 to 5 (severe staining) by two clinicians, masked to both site and subject. The average time required to reach the maximum grade of staining (Gmax) was calculated.ResultsThe median time (upper and lower quartiles) to corneal fluorescein Gmax was 2.6 (1.3–5.3) minutes for nSS DED and 3.8 (2.6–5.4) minutes for SS DED, a statistically significant difference (Mann Whitney U test, p = 0.018). In contrast, the median time to the Gmax for lissamine green staining of the nasal and temporal conjunctiva was 0.5 (0.5–1.1 nasal, 0.5–0.8 temporal) minutes for nSS DED and 0.5 (0.5–0.8 nasal, 0.5–0.5 temporal) minutes for SS DED subjects, which was not statistically significant (p ≥ 0.383).ConclusionsThe time required to reach the maximum grade of corneal fluorescein staining, but not conjunctival lissamine green staining, varied widely and was significantly longer in subjects with Sjögren's Syndrome. Early observation of corneal fluorescein staining can lead to under-grading, which may impact the diagnosis and assessment of treatment in DED. Further study of the best time to assess corneal fluorescein staining in various DED populations is warranted.     

Ocular anatomy and physiology relevant to anaesthesia

An understanding of the anatomy of the orbit is essential for performing regional anaesthesia for ophthalmic surgery. This article will discuss ocular anatomy in terms of the orbit and its contents, its associated muscles, nerves and blood supply, as well as basic ocular physiological principles.     

VEGF-B selectively regenerates injured peripheral neurons and restores sensory and trophic functions

VEGF-B primarily provides neuroprotection and improves survival in CNS-derived neurons. However, its actions on the peripheral nervous system have been less characterized. We examined whether VEGF-B mediates peripheral nerve repair. We found that VEGF-B induced extensive neurite growth and branching in trigeminal ganglia neurons in a manner that required selective activation of transmembrane receptors and was distinct from VEGF-A–induced neuronal growth. VEGF-B–induced neurite elongation required PI3K and Notch signaling. In vivo, VEGF-B is required for normal nerve regeneration: mice lacking VEGF-B showed impaired nerve repair with concomitant impaired trophic function. VEGF-B treatment increased nerve regeneration, sensation recovery, and trophic functions of injured corneal peripheral nerves in VEGF-B–deficient and wild-type animals, without affecting uninjured nerves. These selective effects of VEGF-B on injured nerves and its lack of angiogenic activity makes VEGF-B a suitable therapeutic target to treat nerve injury.Nerves can be damaged either through trauma or disease. Nerves from the peripheral nervous system (PNS) have significantly greater capacity to regenerate and reinnervate their original targets after injury, compared with nerves from the CNS. The successful regeneration of PNS neurons requires a number of intrinsic and extrinsic factors, as well as a permissive microenvironment for axonal regrowth (1). Among the numerous growth factors able to induce nerve regeneration, the family of VEGFs has been implicated as a potent mediator of developmental neurogenesis and adult nerve regeneration (2–4). VEGF-A is a well-characterized and potent angiogenic factor but is also a strong inducer of nerve growth. Several studies have demonstrated that both VEGF-A and -B are expressed during peripheral nerve injury (2, 5). In the setting of injury, VEGF-B plays a role in cell survival, nerve protection, and growth (5, 6). The survival effect of VEGF-B on brain cortical neurons, retinal neurons, and motor neurons in the spinal cord is indicative of its pleiotropic role (5). VEGF-B treatment reduced stroke volume in a middle cerebral artery ligation model and increased survival of retinal ganglion cells in an optic nerve crush injury model (7), and VEGF-B knockout mice suffered severe strokes and exacerbated retinal ganglion cell death in both injury models (7–9). VEGF-B has also been used with promising results in Parkinson’s disease (10) and amyotrophic lateral sclerosis models (11).Given the ability of VEGF-B to regulate both vascular endothelial cells (angiogenesis) as well as axonal growth and survival after injury, it is unclear whether VEGF-B exerts its effects on nerve regeneration through the increase in blood supply or through direct effects on nerve tissue. Indeed, specific studies on its role on peripheral neurons independent of its vascular role are lacking. We have previously reported that VEGF-A can stimulate trigeminal neuronal cell growth and enhance cornea nerve regeneration, resulting in anatomical and functional recovery of peripheral injured nerves independently of its angiogenic effects (12). Here we studied the neuro-regenerative potential of VEGF-B in an avascular model of peripheral nerve injury in mice and the signaling elements involved in the induction of nerve growth. Our results demonstrated tha (i) peripheral nerve regeneration is impaired in mice lacking VEGF-B, (ii) VEGF-B can restore the anatomic and function innervation of target tissues by induction of nerve growth and nerve regeneration, (iii) the effects of VEGF-B are specific for injured nerves and are independent of any vascular effect, and (iv) the effects of VEGF-B on nerve regeneration are distinct from those observed for VEGF-A.     

基于快、慢速加载单轴拉伸数据识别的角膜生物力学特性比较

目的 比较基于快、慢速加载单轴拉伸数据确定的角膜生物力学特性参数。方法 选取15只健康成年兔的角膜进行平均加载速率为0.16、0.02 mm/s单轴拉伸实验,分别获得应力-应变以及应力松弛数据;分别利用黏超弹性模型、1阶Ogden模型和2阶Prony级数模型对加卸载迟滞环曲线、应力-应变曲线、应力松弛曲线进行分析。基于黏超弹性模型拟合快速加卸载迟滞环曲线确定的参数集记为Gvh。拟合慢速加载的应力-应变、应力松弛数据的材料参数集记为GOP。利用相关性分析比较Gvh与GOP之间参数的相关性。结果对快速加卸载迟滞环数据、慢速加载的应力 应变数据与应力松弛数据的拟合优度R2都大于0.95。Gvh与GOP中6个参数中5个（μ,A1,A2,τ1,τ2）差异明显（P<005）,并且两参数组中Ogden模型参数呈正相关。结论 基于快、慢速加载的单轴拉伸数据识别的角膜生物力学参数具有差异性。研究结果为进一步探索利用临床数据识别角膜生物力学特性提供前期的研究基础。     

Defective ceramide synthases in mice cause reduced amplitudes in electroretinograms and altered sphingolipid composition in retina and cornea

Complex sphingolipids are strongly expressed in neuronal tissue and contain ceramides in their backbone. Ceramides are synthesized by six ceramide synthases (CerS1–6). Although it is known that each tissue has a unique profile of ceramide synthase expression and ceramide synthases are implicated in several neurodegenerative disorders, the expression of ceramide synthase isoforms has not been investigated in the retina. Here we demonstrate CerS1, CerS2 and CerS4 expression in mouse retina and cornea, with CerS4 ubiquitously expressed in all retinal neurons and Müller cells. To test whether ceramide synthase deficiency affects retinal function, we compared electroretinograms and retina morphology between wild‐type and CerS1‐, CerS2‐ and CerS4‐deficient mice. Electroretinograms were strongly reduced in amplitude in ceramide synthase‐deficient mice, suggesting that signalling in the outer retina is affected. However, the number of photoreceptors and cone outer segment length were unaltered and no changes in retinal layer thickness or synaptic structures were found. Mass spectrometric analyses of ceramides, hexosyl‐ceramides and sphingomyelins showed that C20 to C24 acyl‐containing species were decreased whereas C16‐containing species were increased in the retina of ceramide synthase‐deficient mice. Similar but smaller changes were also found in the cornea. Thus, we hypothesize that the replacement of very long‐chain fatty acyl residues by shorter C16 residues may affect the electrical properties of retina and cornea, and alter receptor‐mediated signal transduction, vesicle‐mediated synaptic transmission or corneal light transmission. Future studies need to identify the molecular targets of ceramides or derived sphingolipids in light signal transduction and transmission in the eye.     

长期配戴软性接触镜后角膜组织的病理改变

目的：探讨配戴不同时间软性接触镜( SCL)后对患者角膜组织的病理变化。
　　方法：应用共焦显微镜分别检查中低度近视SCL组(150例)和对照组(150例)戴镜1,3,5,8,10a以上的中央角膜和周边角膜的变化。
　　结果：戴镜5 a后SCL组中央角膜基底细胞密度低于对照组(P<0.05),上皮层可见微小囊泡及类似角膜营养不良的角膜小滴,上皮下Langerhans细胞密度及神经纤维曲折度大于对照组( P<0.05)。 SCL组中央角膜浅基质层细胞密度低于对照组(P<0.05),各组基质层中白色点状物密度均高于对照组( P<0.05)。 SCL组内皮细胞形态变化明显,但两组内皮细胞密度无差异( P>0.05)。 SCL组中央角膜上皮层厚度小于对照组(P<0.05)。
　　结论：SCL引起角膜组织的改变随戴镜时间的延长逐渐明显,且这种改变不容忽视。     

不同分级原发性高血压对角膜内皮细胞的影响

目的：通过角膜内皮细胞计探讨不同分级原发性高血压对角膜内皮细胞的影响。

方法：采用病例对照研究,病例组为确诊原发性高血压的患者71例142眼,其中高血压1级组22例44眼、高血压2级组23例46眼、高血压3级组26例52眼; 对照组为健康查体者69例138眼,两组的年龄、性别差异均无统计学意义(P>0.05),且均排除全身、眼部疾病史。检测角膜内皮细胞的平均细胞面积、平均密度、变异系数及六角形细胞比例,两组进行统计学比较。

结果：病例组与对照组角膜内皮细胞的平均细胞面积、细胞密度的差异无统计学意义(P>0.05),但病例组较对照组的变异系数增大(t=3.34,P<0.05),六角形细胞比例下降(t=-2.07,P<0.05); 病例组中高血压1级组、2级组、3级组的平均细胞面积、细胞密度的差异无统计学意义(P>0.05),而变异系数、六角形细胞比例的差异有统计学意义(P<0.05)。

结论：原发性高血压患者的角膜内皮细胞与对照组相比,变异系数增大、六角形细胞比例下降,高血压分级不同其变异系数、六角形细胞比例不同。