Diabetes more than retinopathy,it’s effect on the anterior segment of eye

Diabetes mellitus(DM)is one of the chronic metabolic noncommunicable diseases that has attained worldwide epidemics.It threatens healthy life around the globe,with mild-to-severe secondary complications and leads to significant illness including nephropathy,neuropathy,retinopathy,and macrovascular abnormalities including peripheral vasculopathy,and ischaemic heart disease.Research into diabetic retinopathy(DR),which affects one-third of persons with diabetes,has made considerable strides in recent years.In addition,it can lead to several anterior segment complications such as glaucoma,cataract,cornea,conjunctiva,lacrimal glands and other ocular surface diseases.Uncontrolled DM also caused gradual damage to corneal nerves and epithelial cells,which raises the likelihood of anterior segment diseases including corneal ulcers,dry eye disease,and chronic epithelial abnormalities.Although DR and other associated ocular complications are well-known,the complexity of its aetiology and diagnosis makes therapeutic intervention challenging.Strict glycaemic control,early detection and regular screening,and meticulous management is the key to halting the progression of the disease.In this review manuscript,we aim to provide an in-depth understanding of the broad spectrum of diabetic complications in the anterior segment of the ocular tissues and illustrate the progression of diabetes and its pathophysiology,epidemiology,and prospective therapeutic targets.This first such review article will highlight the role of diagnosing and treating patients with a plethora of anterior segment diseases associated with diabetes,which are often neglected.

Reactive uveitis, retinal vasculitis and scleritis as ocular end-stage of Acanthamoeba keratitis: a histological study

We analysed histologically two Acanthamoeba keratitis(AK) eyes with anterior and posterior segment inflammation and blindness. Two enucleated eyes of 2 patients(age 45 and 51y) with AK(PCR of epithelial abrasion positive) were analysed. Histological analysis was performed using hematoxylin-eosin, periodic acid-Schiff and G?m?rimethenamine silver staining. We could not observe Acanthamoeba trophozoites or cysts neither in the cornea nor in other ocular tissues. Meanwhile, we found uveitis, retinal vasculitis and scleritis in these eyes, due to the long-standing, recalcitrant AK. So in this stage of AK, systemic immune suppression may be necessary for a longer time period.

Infl iximab relieves blood retinal barrier breakdown through the p38 MAPK pathway in a diabetic rat model

AIM： To clarify the mechanism of infliximab treatment in diabetic macular edema （DME） and to provide a new alternative therapy for DME. METHODS： Rats were randomly divided into the control group, the model group and the infliximab treatment group. A diabetic rat model was created. The concentration of TNF-α in the vitreous body was detected by ELISA. The expressions of B-Raf, p38, claudin-1 and occludin in the retina were detected by Western blot. The integrity of the blood retinal barrier （BRB） was measured using Evan＇s blue as a tracer. RESULTS： After three months and six months of the diabetes model, the vitreous TNF-α level in the model group was higher than that of the control group. It was also higher in treated group than that of the control group but was lower than that of the model group. The differences among the three groups were statistically significant （at 3mo, F=857.098, P〈0.001; 6mo, F=1261.897, P〈0.001）. The retina B-Raf and p38 levels in the model group were higher than that of the control group. They were also higher in treated group than that of the control group but were lower than that of the model group. The differences among the three groups were statistically significant （B-Raf at 3mo, F=106.596, P〈0.001 and at 6mo, F=200.681, P〈0.001; p38 at 3mo, F=41.662, P〈0.001 and at 6mo, F=67.979, P〈0.001）. The retina claudin-1 and occludin levels in the model group were lower than that of the control group. They were also lower in treated group than that of the control group but were higher than that of the model group. The differences among three groups were statistically significant （claudin-1 at3mo, F=-139.088, P〈0.001 and at 6mo, F=128.415, P〈0.001; occludin at 3mo, F=-92.733, P〈0.001 and at 6mo, F--104.478, P〈0.001）. The retinal Evans blue leakage in the model group was higher than that of the control group. It was also higher in treated group than that of the control group but was lower than that of the model group. The differences among the three groups were statistically significant （at 3mo, F=-447.946, P〈0.001; at 6mo, F＇=-1610.732, P〈0.001）. CONCLUSION： In-α diabetic rat model, infliximab may relieve TNF-α induced BRB breakdown via the B-Raf and p38 signaling pathway.

年轻患者视网膜前膜的自发分离:个案观察及文献回顾

Background: Idiopathic epiretinal membranes (ERM) grow on the surface of the i nternal limiting membrane (ILM) and are a very uncommon condition in young subje cts. Methods: We report six young subjects withERM and describe the spontaneous separation of the membranes. The functional and anatomical recovery was assessed by Snellen visual acuity, Amsler grid and funduscopy. Selected cases were addit ionally assessed by optical coherence tomography (OCT). Results: All subjects in itially claimed a sudden, unilateral, reduction in visual acuity (VA) with sever e distortion at the age of 15-30 years. No ocular trauma or disease was ascerta ined in any case. Initial fundus examination demonstrated a gray-whitish ERM wi th translucent stress lines over the macula. Visual recovery occurred in all cas es after resolution of the ERM. Sequential OCT demonstrated the successive peeli ng of an ERM accompanied by normalization of foveal thickness. Conclusions: Youn g subjects should b e counseled about the favorable prognosis for maintaining go od vision and possible spontaneous membrane separation. Conservative observation is advocated if the visual disturbance is located temporally, as functional rec overy and spontaneous membrane separation may occur. When the contracting forces of the immature ERM are stronger than its adhesions to the retina, the membrane may separate spontaneously.

360°视网膜切开联合黄斑转位治疗新生血管性老年黄斑变性后的视功能改变

Objective To measure the change in vision and visual outcomes at 12 months aft er macular translocation with 360°retinectomy (MT360) and silicone oil tamponad e in patients with bilateral vision loss resulting from subfoveal choroidal neov ascular membranes in age-related macular degeneration (AMD). Design A prospecti ve, interventional, consecutive, noncomparative case series. Participants Sixty -four patients with bilateral vision loss resulting from neovascular AMD. Metho ds Eligible patients had AMD with subfoveal choroidal neovascularization in the operative eye and a maximum of 6 months of central vision loss. Preoperative and 12-month postoperative evaluations included standardized testing of near and d istance acuity and reading speed. Patients underwent MT360 with silicone oil tam ponade, followed 2 months later by extraocular muscle surgery and silicone oil r emoval. Main outcome measures Change in distance acuity, near acuity, and readin g speed at 12 months after MT360 compared with those values before surgery. Resu lts Sixty-one patients were followed up for 12 months. All eyes were translocat ed successfully. Median distance acuity letter score improved from 62 letters (S nellen equivalent of approximately 20/125) before surgery to 69 letters (approxi mately 20/80) by 12 months after surgery (P=0.03). Median near acuity improved f rom 0.70 logarithm of the minimum angle of resolution (logMAR) units (approximat ely 20/100) before surgery to 0.44 logMAR units (approximately 20/55) at 12 mont hs (P < 0.001). Median reading speed improved from 71 words per minute (wpm) bef ore surgery to 105 wpm at 12 months after surgery (P < 0.001). At 12 months, dis tance acuity improved by 1 or more lines in 32 patients (52%). In patients with either preoperative distance or near acuity of 20/80 or better, 74%and 95%of patients, respectively, remained in this range of acuity. In patients with eithe r preoperative distance or near acuity of worse than 20/80, 40%and 48%of patie nts, respectively, improved to 20/80 or better. Postoperative retinal detachment developed in 5 patients (8%), with the macula involved in 2 patients, and all retinas were reattached successfully. Conclusions Macular translocation with 360 °retinectomy with silicone oil tamponade is effective in significantly improvin g visual function in patients with neovascular AMD, as demonstrated by the impro vement in distance and near acuity and reading speed at 12 months after surgery in these patients. Although this is a complex surgical intervention, patients wi th preoperative visual acuity of 20/80 or better at near or distance are highly likely to retain the 20/80 or better acuity at 12 months after surgery. Macular translocation with 360°retinectomy is an effective treatment option for patient s with vision loss in their second eye resulting from neovascular AMD.

谷胱甘肽S转移酶M1阳性基因型能否防止原发性开角型青光眼

Purpose: To find out whether the polymorphism at GSTM1, GSTT1 and GSTP1 loci is associated with increased susceptibility to glaucoma. Methods: We genotyped 15 3 primary open angle patients and 159 healthy controls. Genomic DNA from periphe ral blood was examined using polymerase chain reaction and defined for the genet ic polymorphisms of glutathione S-transferase. Results: The frequency of theGST M1 null genotype individuals among the glaucoma patients was significanlty highe r than in controls (54.9 vs 40.9%) with odds ratio of 1.64 (95%CI: 1.10-2.59) . The frequency of the GSTT1 and GSTP1 in both groups were not statistically dif ferent. Conclusion: The present study suggests that the GSTM1 null genotype may be a genetic risk factor for development of primary open angle glaucoma. Further associations studies in other polymorphic genes for xenobiotic-metabolizing en zymes are needed to elucidate the environmental-genetic interaction in the unde rlying cause of primary open angle glaucoma.

自然视觉状态下的调节迟滞:近视眼和正视眼儿童的对照研究

Purpose: To determine whether or not myopic children have a larger lag of acco mmodation than emmetropic children under natural seeing conditions. Methods: In 61 myopic children (age, 9.5±1.3 years; spherical equivalent refractive error, -6.50 to-1.00D), accommodative response was objectively measured while they we re binocularly viewing a target at 50.5, 32.5, 20.9, or 16.0 cm (1.98-6.25 D) t hrough fully correcting glasses. In the 33 children who habitually wore spectacl es, the accommodative responses were also measured while they wore their own spe ctacles. As controls, 18 emmetropic children were recruited. Accommodative respo nse gradients and lags were compared between the groups after calibration for re sidual refractive errors and the vertex distance of the glasses. Results: With f ully correcting glasses, the myopic children showed a larger mean lag of accommo dation than the emmetropic children, as well as wide intersubject variation. How ever, when the children wore their habitual, usually undercorrecting, spectacles , accommodative lags markedly decreased, and a significant correlation was found between residual refractive errors after correcting for the spectacles and acco mmodative lags. Myopic children with near-point exophoria tended to show smalle r lags of accommodation. Conclusion: Under binocular viewing conditions, myopic children when viewing the target through fully correcting glasses tend to show l arger lags of accommodation than emmetropic children, but the lags of accommodat ion are usually reduced by their spectacle undercorrection.

50岁以下患者的非动脉炎性缺血性视神经病变

Purpose: The goal of our study was to compare the case histories and clinical findings in three young patients (aged < 50 years) who had undergone their first attack of non-arteritic ischaemic optic neuropathy (NAION).We intended to cons ider whether NAION at a relatively young age might comprise a separate pathologi cal and diagnostic entity. Results: All three cases revealed some common charact eristics. All of them experienced recurrent attacks with bilateral manifestation s that led to severe loss of vision and visual field defects. The patients had a lso suffered from diabetes mellitus for a long time, but none of them had diabet ic retinopathy. Conclusion: The case histories of these relatively young patient s showed some differences, including recurrences and more severe loss of vision, to those of elderly patients. However, all the signs we found had been reported previously, although much less frequently, in NAION cases among elderly patient s. The clinical and laboratory findings definitely exclude the possibility of an alternative diagnosis. Hence, our results do not support the notion of a differ ent pathomechanism of NAION at a young age and its existence as a separate disea se entity.

Pressure balance and imbalance in the optic nerve chamber： The Beijing Intracranial and Intraocular Pressure (iCOP) Study

To determine the interdependence of intracranial pressure(ICP) and intraocular pressure(IOP) and how it affects optic nerve pressures, eight normal dogs were examined using pressure-sensing probes implanted into the left ventricle, lumbar cistern, optic nerve subarachnoid space in the left eye, and anterior chamber in the left eye. This allowed ICP, lumbar cistern pressure(LCP), optic nerve subarachnoid space pressure(ONSP) and IOP to be simultaneously recorded. After establishing baseline pressure levels, pressure changes that resulted from lowering ICP(via shunting cerebrospinal fluid(CSF) from the ventricle) were recorded. At baseline, all examined pressures were different(ICP>LCP>ONSP), but correlated(P<0.001). As ICP was lowered during CSF shunting, IOP also dropped in a parallel time course so that the trans-lamina cribrosa gradient(TLPG) remained stable(ICP-IOP dependent zone). However, once ICP fell below a critical breakpoint, ICP and IOP became uncoupled and TLPG changed as ICP declined(ICP-IOP independent zone). The optic nerve pressure gradient(ONPG) and trans-optic nerve pressure gradient(TOPG) increased linearly as ICP decreased through both the ICP-IOP dependent and independent zones. We conclude that ICP and IOP are coupled in a specific pressure range, but when ICP drops below a critical point, IOP and ICP become uncoupled and TLPG increases. When ICP drops, a rise in the ONPG and TOPG creates more pressure and reduces CSF flow around the optic nerve. This change may play a role in the development and progression of various ophthalmic and neurological diseases, including glaucoma.

Genome-wide analysis identified 17 new loci influencing intraocular pressure in Chinese population

Intraocular pressure(IOP) is a major risk factor for glaucoma. Genetic determinants of intraocular pressure can provide critical insights into the genetic architecture of glaucoma and, as a result, open new avenues for therapeutic intervention. We performed a genome-wide association study and replication analysis of 8,552 Chinese participants. In the genome-wide association study, we identified 51 loci that surpassed the significance of P<9×10^(-7), and we formally replicated these loci. A combined discovery and replication meta-analysis identified 21 genome-wide loci that surpassed the genome-wide significance of P<5×10^(-8), including 4 previously reported loci: rs145063132(7 p21.2, ETV1/DGKB), rs548030386(7 q31.2, ST7 near CAV1/CAV2), rs7047871(9 p24.2, GLIS3), and rs2472494(9 q31.1, ABCA1/SLC44 A1). Of the 17 newly identified loci, five were reported to have ocular related phenotypes: PTCH2(rs7525308 in 1 p34.1), LRIF1/DRAM2(rs1282146 in 1 p13.3), COLEC11(rs201143466 in 2 p25.3),SPTBN1(rs4514918 in 2 p16.2), and CRK(rs11078446 in 17 p13.3). The genetic loci identified in this study not only increase our understanding of the genes involved in intraocular pressure but also provide important genetic markers to improve future genetic screening and drug discovery for intraocular pressure disorders.

Polarization sensitive optical coherence tomography with single input for imaging depth-resolved collagen organizations

Collagen organization plays an important role in maintaining structural integrity and determining tissue function.Polarization-sensitive optical coherence tomography(PSOCT)is a promising noninvasive three-dimensional imaging tool for mapping collagen organization in vivo.While PSOCT systems with multiple polarization inputs have demonstrated the ability to visualize depth-resolved collagen organization,systems,which use a single input polarization state have not yet demonstrated sufficient reconstruction quality.Herein we describe a PSOCT based polarization state transmission model that reveals the depth-dependent polarization state evolution of light backscattered within a birefringent sample.Based on this model,we propose a polarization state tracing method that relies on a discrete differential geometric analysis of the evolution of the polarization state in depth along the Poincare sphere for depth-resolved birefringent imaging using only one single input polarization state.We demonstrate the ability of this method to visualize depth-resolved myocardial architecture in both healthy and infarcted rodent hearts(ex vivo)and collagen structures responsible for skin tension lines at various anatomical locations on the face of a healthy human volunteer(in vivo).