The effect of intravenous high-dose glucocorticoids and orbital decompression surgery on sight-threatening thyroid-associated ophthalmopathy

AIM: To report the effects of intravenous high-dose glucocorticoids(iv GC) and orbital decompression(OD) surgery for treatment of sight-threatening thyroid-associated ophthalmopathy(TAO).METHODS: A retrospective review of medical records from patients with sight-threatening TAO [definite or highly suspected dysthyroid optic neuropathy(DON)] treated with iv GC(60 cases) and OD(25 cases) was conducted at the Zhongshan Ophthalmic Center between January 2001 and January 2009. Patients were initially treated with iv GC(iv GC group). If no significant improvement in visual function was obtained, they then received OD surgery(OD group). The pre-versus post-treatment efficacies of either iv GC or OD in these patients were assessed using several indices, including visual acuity, intraocular pressure, ocular alignment, ocular motility, and exophthalmos. RESULTS: Nighty-one eyes had definite DON while 79 were considered to have highly suspected DON. In the iv GC group, 51 individuals(85.0%) eventually demonstrated normal vision, while 10 patients(16.7%) demonstrated a reduction in deviation(P<0.01), and 35 cases(58.3%) showed slight improvements in ocular motility(P<0.01). In OD group, visual acuity improved in 24 cases(96.0%, P<0.01) and all patients showed varying reductions of exophthalmos(mean: 4.35±1.13 mm, P<0.01). Eight cases(32.0%) experienced an 8-15 PD reduction of deviation and ocular motility improved in 12 cases(48.0%), while 3 patients(12.0%) developed new-onset strabismus with diplopia post-surgically(P<0.01). Patients were followed up at an average of 1.55±1.07 y. CONCLUSION: Both iv GC and OD show good therapeutic efficacy in the treatment of sight-threatening TAO. Thepresence of extremely poor eyesight(≥0.5 log MAR) was corrected in some patients with iv GC alone, thus sparing these patients from subsequent OD surgery. In patients who were refractory to steroids, subsequent OD surgery often provided satisfactory outcomes, however, new-onset strabismus with diplopia was observed in 12.0% of these cases.

5-aza-2'-deoxycytidine in the regulation of antioxidant enzymes in retinal endothelial cells and rat diabetic retina

AIM: To investigate the roles of a DNA methyltransferase(DNMT) inhibitor 5-aza-2'-deoxycytidine(5-aza-dC) in the regulation of antioxidant enzymes in diabetic retinopathy(DR) models. METHODS: DNMTs expressions and activity, and changes of two key antioxidant enzymes in DR, MnSOD(encoded by SOD2 gene) and glutathione S-transferase theta 1(GSTT1), were quantified in the isolated human retinal endothelial cells(HRECs) exposed to high glucose(HG) with or without 5-aza-dC treatment. The downstream exacerbating factors including vascular endothelial growth factor(VEGF), intercellular adhesion molecule 1(ICAM-1) and matrix metalloproteinase 2(MMP2), which are implicated in the pathogenesis of DR and closely related to oxidative stress were also analyzed. The key parameters were confirmed in the retina from streptozotocin(STZ) diabetic rats. RESULTS: DNMTs expression and DNMT activity was induced in HRECs exposed to HG. Hyperglycemia decreased MnSOD and GSTT1 expression. 5-aza-dC administration effectively suppressed DNMTs expression and activity and reversed the MnSOD and GSTT1 expression under HG condition. VEGF, ICAM-1 and MMP2 induced by HG were also suppressed by 5-aza-dC treatment. Similar results were observed in the retina from STZ diabetic rats. CONCLUSION: Our findings suggest that DNA methylation may serves as one of the mechanisms of antioxidant defense system disruption in DR progression. Modulation of DNA methylation using pharmaceutic means such as DNMT inhibitors could help maintain redox homeostasis and prevent further progression of DR.

Application of visual electrophysiology for the diagnosis and treatment of cataracts

Visual electrophysiology is widely used in clinical ophthalmology. It is also of significant value in the objective assessment of visual function in adult and pediatric cataract patients and for the diagnosis of and research on retinal and visual pathway diseases. This article systematically reviews visual electrophysiology techniques, their applications in the diagnosis and treatment of adult and pediatric cataracts, and factors influencing the application of visual electrophysiology during surgical treatment for cataracts.

Imaging characteristics and surgical management of orbital neurilemmomas

AIM: To review imaging characteristics and surgical outcomes of orbital neurilemmoma. METHODS: Retrospective review of 21 patients with orbital neurilemmoma managed at the Zhongshan Ophthalmic Center of Sun Yat-sen University from June 2005 to December 2016. All patients underwent surgical excision following preoperative imaging including ultrasonography, computed tomography(CT) and magnetic resonance imaging(MRI).RESULTS: Among these patients, 11 were male and 10 were female, with age ranging from 12 to 75y(average, 40.3 y). Ultrasound of the orbit showed a roundish well-demarcated orbital mass with low or middle internal reflectivity in each case. Dark inner liquid fields were detected in 28.6% of these cases. Doppler ultrasound demonstrated blood flow signals in these masses. CT showed that the tumors were either homogeneous or heterogeneous. MRI of T1 WI revealed isointense or hypointense tumors, while the T2 WI indicated heterogeneous hyperintense lesions. Gd contrast MRI demonstrated heterogenous or homogeneous enhancement initiating from the wide area of the lesion. Six patients underwent lateral orbitotomy and 15 anterior orbitotomy. All tumors were completely removed. After a mean followup of 1.8 y, 3 patients experienced reduced vision while the remaining 10 patients showed improved vision after surgery. One patient experienced a mild limitation of upward motility. No recurrence occurred. CONCLUSION: Orbital neurilemmoma is a relatively rare, benign orbital tumor. Effective diagnosis requires a combination of ultrasonography, CT and/or MRI. These imaging techniques are also vital to differentiate neurilemmomas from other orbital masses like that of cavernous hemangiomas and meningiomas.Successful treatment requires complete resection of the neurilemmomas as performed either by lateral or anterior orbitotomy. Recurrence is rare after complete removal.

Biomechanics of sclera crosslinked using genipin in rabbit

AIM:To strengthen the biomechanics of collagen by crosslinking rabbit scleral collagen with genipin to develop a new therapy for preventing myopic progression. METHODS:Ten New Zealand rabbits were treated with 0.5 mmol/L genipin injected into the sub-Tenon's capsule in the right eyes. Untreated contralateral eyes served as the control. The treated area was cut into scleral strips measuring 4.0 mm×10.0 mm for stress-strain measurements(n=5). The remaining five treated eyes were prepared for histological examination.RESULTS:Compared to the untreated scleral strips,the genipin-crosslinked scleral strips showed that the ultimate stress and Young's modulus at 10% strain were increased by the amplitude of 130% and 303% respectively,ultimate strain was decreased by 24%. There had no α-smooth muscle actin(α-SMA)positive cells in control and treated sclera. Histologically,there was no sign of apoptosis in the sclera,choroid,and retina; and no side effects were found in the peripheral cornea and optic nerve adjacent to the treatment area.CONCLUSION:Genipin induced crosslinking of collagen can increase its biomechanical behavior by direct strengthening of the extracellular matrix in rabbit sclera,with no α-SMA expression seen in the myofibroblasts. As there is no evidence of cytotoxicity in the scleral,choroidal,and retinal cells,genipin is likely a promising agent to strengthen the weakened sclera to prevent myopic progression.

Diagnosis and surgical management of isolated inferior oblique palsy

●AIM:To describe the etiology,clinical characteristics,surgical options and surgical outcomes of isolated inferior oblique palsy(IOP).●METHODS:A retrospective review was performed on patients with isolated IOP who were seen between January 2010 and June 2017.The following clinical data were obtained from the patients’charts:visual acuity,ocular alignment,ocular motility,cyclotorsion,stereoacuity,Parks three-step test,surgical methods,surgical outcomes and complications.Surgical success was defined as horizontal deviation≤10 prism diopters(PD)and a vertical deviation≤5 PD in primary gaze at both near and distant vision as assessed at last follow-up.●RESULTS:The records from a total of 18 patients(8 males and 10 females)with an average age of 27.56 y were included in this study.The right eye was affected in 11 patients,the left in 6 patients and both eyes in 1 patient.Twelve cases(66.7%)were congenital and 6(33.3%)were acquired IOP.The 6 acquired cases involved 2 resulting from orbital trauma/surgery,2 from midbrain microvascular ischemia,1 from myasthenia gravis and 1 of unknown etiology.Strabismus surgery was performed in 13 cases.Surgical techniques included weakening of superior oblique and vertical rectus recession and resection.After a mean follow-up of 15.11 mo,the corrected vertical deviation in primary position was 19.92±8.52 PD(P=0.000)and the corrected horizontal deviation was 14.31±12.68 PD(P=0.002).The surgical success rate was 61.5%and no surgical complications were present.●CONCLUSION:Isolated IOP represents a rare condition,with most cases(66.7%)involving a congenital basis.The acquired cases included vascular,orbital trauma/surgery and myasthenia gravis.Weakening of the ipsilateral superior oblique muscle and/or contralateral superior rectus recession often resulted in favorable surgical outcomes with a surgical success rate of 61.5%.

Construction of databases:advances and significance in clinical research

Widely used in clinical research, the database is a new type of data management automation technology and the most efficient tool for data management. In this article, we first explain some basic concepts, such as the definition, classification, and establishment of databases. Afterward, the workflow for establishing databases, inputting data, verifying data, and managing databases is presented. Meanwhile, by discussing the application of databases in clinical research, we illuminate the important role of databases in clinical research practice. Lastly, we introduce the reanalysis of randomized controlled trials(RCTs) and cloud computing techniques, showing the most recent advancements of databases in clinical research.

Congenital ocular counter-roll:a review of cases treated exclusively by ophthalmologists

AIM:To review the demographics,clinical manifestations,and surgical experiences of patients with congenital ocular counter-roll,whose treatments were performed exclusively by ophthalmologists.METHODS:A retrospective review was conducted consisting of patients who received strabismus surgery between 2017 to 2019.Patients with obvious ocular counter-roll were included.RESULTS:A total of 7008 patients who received strabismus surgery,28(12 males,16 females)were diagnosed as congenital ocular counter-roll,accounting for 0.40%.All patients were initially misdiagnosed:21 patients were misdiagnosed as superior oblique palsy(SOP),3 as inferior oblique overaction,2 as dissociated vertical deviation(DVD),1 as superior oblique overaction with A-pattern exotropia,and 1 as medial rectus palsy.The mean±SD age was 12.4±9.4 y(range 2.5-36 y).The most common clinical findings included ocular counter-roll,vertical deviation or vertical deviation combined with outward deviation and head tilt.At follow-up,an excellent surgical result was achieved in 20 patients.Preoperative horizontal deviation of 26±24 prism diopter(PD)and vertical deviation of 18±12 PD were reduced to 0±12 PD(P=0.0001)and 3±4 PD(P=0.001),respectively.CONCLUSION:Congenital ocular counter-roll is a rare supranuclear vertical strabismus caused by congenital abnormalities involving vestibule-ocular reflex pathways.In addition to ocular counter-roll,the most salient clinical features included,but are not limited to,hyperdeviation,outward deviation,overelevation in adduction and head tilt.

Response letter for “Mesenchymal stem cell secretome to control inflammation in allergic conjunctivitis”

Dr.Spampinato gave an insightful comment on'Mesenchymal stem cell secretome to control inflammation in allergic conjunctivitis'(1).Dr.Spampinato proposed that it is key to get the complete knowledge of mesenchymal stem cell(MSC)secretome composition in order to better understand MSC secretome and to achieve the best therapeutic effect of MSC secretome for clinic setting.

X-ray diffraction enhanced imaging study of intraocular tumors in human beings

Diffraction enhanced imaging(DEI) with edge enhancement is suitable for the observation of weakly absorbing objects.The potential ability of the DEI was explored for displaying the microanatomy and pathology of human eyeball in this work.The images of surgical specimens from malignant intraocular tumor of hospitalized patients were taken using the hard X-rays from the topography station of Beamline 4W1A at Beijing Synchrotron Radiation Facility(BSRF).The obtained radiographic images were analyzed in correlation with those of pathology.The results show that the anatomic and pathologic details of intraocular tumors in human beings can be observed clearly by DEI for the first time,with good visualization of the microscopic details of eyeball ring such as sclera,choroids and other details of intraocular organelles.And the best resolution of DEI images reaches up to the magnitude of several tens of μm.The results suggest that it is capable of exhibiting clearly the details of intraocular tumor using DEI method.

Targeting the adenosine A2A receptor for neuroprotection and cognitive improvement in traumatic brain injury and Parkinson's disease

Adenosine exerts its dual functions of homeostasis and neuromodulation in the brain by acting at mainly 2 G-protein coupled receptors,called A1 and A2A receptors.The adenosine A2A receptor(A2AR)antagonists have been clinically pursued for the last 2 decades,leading to final approval of the istradefylline,an A2AR antagonist,for the treatment of OFF-Parkinson's disease(PD)patients.The approval paves the way to develop novel therapeutic methods for A2AR antagonists to address 2 major unmet medical needs in PD and traumatic brain injury(TBI),namely neuroprotection or improving cognition.In this review,we first consider the evidence for aberrantly increased adenosine signaling in PD and TBI and the sufficiency of the increased A2AR signaling to trigger neurotoxicity and cognitive impairment.We further discuss the increasing preclinical data on the reversal of cognitive deficits in PD and TBI by A2AR antagonists through control of degenerative proteins and synaptotoxicity,and on protection against TBI and PD pathologies by A2AR antagonists through control of neuroinflammation.Moreover,we provide the supporting evidence from multiple human prospective epidemiological studies which revealed an inverse relation between the consumption of caffeine and the risk of developing PD and cognitive decline in aging population and Alzheimer's disease patients.Collectively,the convergence of clinical,epidemiological and experimental evidence supports the validity of A2AR as a new therapeutic target and facilitates the design of A2AR antagonists in clinical trials for disease-modifying and cognitive benefit in PD and TBI patients.

MYRF:A Mysterious Membrane-bound Transcription Factor Involved in Myelin Development and Human Diseases

The myelin regulatory factor gene(MYRF)encodes a protein evolutionarily conserved from invertebrates to vertebrates,representing a novel type of membrane-bound transcriptional factor(MBTF).In vertebrates,MYRF protein is required for myelin development and maintenance[1,2].