[Comparison of posterior vitreous detachment after femtosecond laser and microkeratome-assisted lase in situ keratomileusis].

OBJECTIVE: To compare the incidence of posterior vitreous detachment (PVD) early after femtosecond laser and microkeratome-assisted LASIK and their changes after follow-up observation. METHODS: It was a prospective study. According to the choices of the patients, 40 cases (80 eyes) underwent femtosecond laser (INTRALASE FS 60, Abbott Medical Optics, American) LASIK surgery in the femtosecond group and 40 cases (80 eyes) underwent microkeratome-assisted (AMADEUS II, Ziemer, Switzerland) LASIK surgery in the microkeratome group. The occurrence of PVD was observed by B ultrasound and OCT examination pre- and 1 week, 1, 3 and 6 months post-operatively. Data from one eye in each patient were randomly selected for statistical analysis. Independent sample χ(2) test was used to compare postoperative PVD between these two groups. Multiple logistic regression was used to investigate the association of PVD changes with age, gender, eye, axial length, refraction, IOP, corneal thickness and suction time. RESULTS: In femtosecond group, 18 eyes (45.0%) had partial PVD before surgery. In 11 eyes (27.5%), PVD developed in non-PVD eye or PVD increased in eyes already had PVD preoperatively. In microkeratome group, 21 eyes (52.5%) had partial PVD preoperatively. In 8 eyes (20.0%), PVD developed in non-PVD eyes or PVD increased in eyes already had PVD preoperatively. There was no statistically significant difference between these 2 groups (χ(2) = 2.257, P = 0.133). Logistic regression analysis indicated that the suction time was associated with the postoperative development of PVD in femtosecond group (OR = 1.089, P = 0.027) and long axial length was a significant risk factor for the development of PVD in microkeratome group (OR = 4.712, P = 0.007). No serious posterior segment complications such as retinal breaks or retinal detachment were observed postoperatively. CONCLUSIONS: INTRALASE FS 60 femtosecond laser does not increase the incidence of PVD compared to AMADEUS II microkeratome-assisted LASIK. PVD is more likely to occur in eyes with long axial length. No serious posterior segment complications were observed during the 6 month follow-up period.

Insulin-like growth factor-2 antisense oligonucleotides inhibits myopia by expression blocking of retinal insulin-like growth factor-2 in guinea pig.

OBJECTIVE: To clarify the role of IGF-2 on the development of myopia, the dynamic expression of IGF-2 was investigated in the FD eyes' retina, and the effects of intravitreous injection with IGF-2 ASON was studied on the diopter and axial eye length of FD eyes. METHODS: 64 guinea pigs were divided into 2 groups. In group A (n = 24), the right eyes were covered. On days 7, 14 and 21, the diopter, axial eye length and level of IGF-2 of both eyes were measured in every 8 guinea pigs. In group B (n = 40), the right eyes were covered. On day 1, the right eyes were received intravitreal injection with 40 µg IGF-2SON, 10 µg, 20 µg or 40 µg IGF-2 ASON. The diopter, axial eye length and level of IGF-2 were measured on day 14. RESULTS: FD eyes showed myopic shift, axial length enlongation, and up-regulation in retinal IGF-2 from day 7 to day 21. The level of retinal IGF-2 in FD eyes was higher than that in non-FD eyes. Compare with FD eyes without injection, the myopia diopter of FD eyes decreased in received intravitreous injection with IGF-2 ASON, axial length shortened, and down-regulated with retinal IGF-2. With the increase dose of IGF-2 ASON, the change of myopic diopter, axial length, and level of retinal IGF-2 were showed more and more significant. CONCLUSIONS: FD is effective to up-regulate the level of retinal IGF-2 expression in guinea pig. Intravitreous injection with IGF-2 ASON can inhibit the development of myopia.

[Research status of photodynamic therapy for corneal neovascularization].

Pathological corneal neovascularization is an important reason of visual impairment. Research outcomes showed that angiogenesis mechanism is similar in all the tissues of the body and photodynamic therapy demonstrate a useful effect in blocking tumor and choroidal neovascularization. This method is currently being tried for the treatment of corneal neovascularization. This paper will review the research status of photodynamic therapy in corneal neovascularization using various photosensitizers.

[Zebrafish-a new animal models of anterior segment embryonic development and diseases basic research].

In recent years, zebrafish has become ideal animal models of human disease with its unique characteristics, such as small body, fecundity, fast development and growth, embryo transparency, and so on. Furthermore, the structure and gene of zebrafish eye are highly conservative with human eye, which make ophthalmologists to pay close attention to zebrafish. This review focus on the studies and applications on zebrafish embryonic development of anterior segment, including the morphogenesis of cornea, lens and anterior chamber, and diseases of anterior segment (corneal diseases, cataract, glaucoma).

[Clinical research of the phakic foldable angle-supported intraocular lens for the correction of high myopia].

OBJECTIVE: To assess the safety, efficacy, predictability and stability of the phakic foldable angle-supported intraocular lens (IOL) (CACHET IOL, Alcon Inc., USA.) for correction of high-to-extremely high myopia in adults. METHODS: In this prospective study, 29 eyes of 15 patients were implanted with CACHET phakic angle-supported IOL and followed for 1 year postoperatively. Preoperative manifest refractive sphere was -12.08 ± 2.44 diopters (D). Visual acuity(uncorrected visual acuity, UCVA; best spectacle-corrected visual acuity, BSCVA), predictability and stability of manifest refraction spherical equivalent (MRSE), adverse events, and endothelial cell density were analyzed primarily during 1-year of follow-up. RESULTS: After 1 year of follow-up, a BSCVA of 0.6 or better was achieved by 100% of eyes; 9.7% (26/29) had a BSCVA of 1.0 or better; no eyes lost ≥ 1 line BSCVA, 62.1%(18/29) had no change in lines of BSCVA, 31.0% (9/29) gained 1 line of BSCVA, 3.4% (1/29) gained 2 line of BSCVA, and 3.4% (1/29) gained more than 2 line of BSCVA; the safety index was 1.13 (1.08/0.96); UCVA of 1.0 or better was achieved by 58.6% (17/29), 100% had an UCVA of 0.5 or better, 86.2% (25/29) of eyes achieved a UCVA of 0.8 or better, and 93.1% (27/29) of eyes achieved a UCVA of 0.6 or better; the efficacy index was 1.03(0.99/0.96). The overall mean percentage change in endothelial cell density 1 year after surgery was -0.23% ± 4.80%. Five eyes (17.2%) had increased intraocular pressure (IOP) on the day of surgery. No pupil ovalization, pupillary block, or retinal detachment events were observed. Glare (6.9%, 2/29) and halo (13.8%, 4/29) mainly appeared in the first month after surgery, and had no influence on driving in night. CONCLUSIONS: After 1 year of follow-up, the implantation of phakic foldable angle-supported IOL was proved to be safe, effective and predictable with minimal complications in patients with high myopia. Due to the limitation of visiting time, long-term of clinical investigation is necessary to verify the safety and efficacy of this IOL.

[Investigation of the role of mesenchymal stem cells on keratoplasty rejection].

OBJECTIVE: To investigate the effect of mesenchymal stem cells (MSC) on keratoplasty rejection in a rat mode. METHODS: MSC from bone marrow of Wistar rats was cultured. Corneas of Wistar rats (donors) were transplanted to Lewis rats (recipients). Transplanted rats were randomly divided into A, B, C three groups. Rats in group B were injected with MSC suspended in PBS via the tail vein continually for three days before the surgery, while rats in group C accepted similar MSC transplantation after the surgery. The rats in group A were given the same volume of PBS. Grafts were scored for corneal transparency, edema and extent of neovascularization by slit lamp observation. Expressions of CD(4), CD(8), CD(25) and CD(45) in corneas 10 days after transplantation were examined by immunohistochemistry. RESULTS: The survival time of the corneal grafts in group C [(9.9 ± 0.69) d] was significantly prolonged compared with that of the group A and group B [(11.83 ± 0.54), (16.89 ± 1.91) d] (F = 5.732, P = 0.001, 0.019). Expression level of CD(4), CD(8), CD(25) of the corneal grafts in group C was lower than that of group A and group B (t = 2.477, 2.359, 2.445, P = 0.024, 0.042, 0.030). CONCLUSION: Post-operative injection of MSCs could inhibit keratoplasty rejection and prolong the corneal allografts survival in a rat model.

A novel analysis of Scheimpflug total corneal refractive power following corneal cross-linking in mild to moderate keratoconus.

AIM: To detect an earlier improvement in mild to moderate keratoconus following corneal cross-linking (CXL) with total corneal refractive power (TCRP) using ray tracing method. METHODS: A total of 40 eyes of 30 consecutive patients who underwent CXL for progressive keratoconus were retrospectively enrolled. The following keratometric parameters provided by Pentacam HR, including maximum keratometry (Kmax), steepest keratometry (Ksteep), 3 mm zonal TCRP centered over corneal apex (TCRPapex,zone 3 mm), zonal mean keratometry and TCRP centered over corneal cone (Kmcone,zone and TCRPcone,zone 1, 2, 3 mm) were evaluated preoperatively and 1, 3, 6, and 12mo postoperatively. Groups 1 and 2 were defined based on Kmax at postoperative 1mo as improved (the initial improvement group) or worsen (the initial deterioration group) compared to the preoperative level. RESULTS: In the overall group, only keratometric parameters based on ray tracing method displayed significant improvement early at 3mo postoperatively, in which TCRPcone,zone 1 mm and 2 mm exhibited the largest flattening (0.57 D and 0.53 D, respectively). In Group 1, only Kmax, Kmcone,zone 2 mm and TCRPcone,zone 2 mm showed significant improvement initially at 1mo postoperatively, in which Kmax exhibited the largest improvement (1.05 D), followed by TCRPcone,zone 2 mm (0.82 D). In Group 2, only keratometric parameters based on ray tracing method and Kmcone,zone 3 mm showed slight but not significant improvement early at 3mo, in which TCRPcone,zone 3 mm displayed the most improvement (0.19 D), followed by TCRPcone,zone 2 mm (0.15 D). CONCLUSION: The findings indicate that a 2 mm zonal TCRP centered over Kmax could earlier detect keratometric improvement by CXL compared to other commonly used parameters in mild to moderate keratoconic eyes.

Comparative study of objective visual quality between FS-LASIK and SMART in myopia.

AIM: To compare the changes in the objective visual quality of patients with low and moderate myopia postoperatively after transepithelial photorefractive keratectomy using the smart pulse technology (SMART) and femtosecond laser in situ keratomileusis (FS-LASIK). METHODS: Corneal higher-order aberrations (HOAs), horizontal coma, vertical coma and spherical aberration were measured using Pentacam, and cutoff for modulation transfer function (MTF cutoff), objective scatter index (OSI) and Strehl ratio (SR) was measured using an optical quality analysis system (OQAS-II), before and after operation at 1, 3, and 6mo, and data were analyzed by repeated measurement two-way analysis of variance. RESULTS: The difference in uncorrected distance visual acuity between SMART and FS-LASIK was statistically significant only 1wk postoperatively. Approximately 86.36% and 80.69% of patients with spherical equivalent (SE) in ±0.50 D were observed in the SMART and FS-LASIK groups, respectively. No significant difference was observed in SE between the two groups (P=0.509). The HOAs increased postoperatively compared with those before surgery in both groups (P<0.05). No significant difference in HOA, corneal horizontal coma, spherical aberration, ΔHOA, Δhorizontal coma, and Δspherical aberration were observed between the two group (P>0.05). Corneal vertical coma and Δcorneal vertical coma in the FS-LASIK group were higher than those in the SMART group (P<0.05). The OSI of both groups at 1mo after surgery was higher than that before surgery (P<0.05). At 3 and 6mo postoperatively, the OSI in the FS-LASIK group was slightly higher than that in the SMART group (P=0.040 and 0.047, respectively). At 6mo after surgery, the MTF cutoff was statistically significant different between the two groups (P=0.026). No significant difference in SR between the FS-LASIK and SMART groups was observed at 1, 3, and 6mo postoperatively (P>0.05). CONCLUSION: The HOAs increase and visual quality is delayed in both groups postoperatively, and the long-term objective visual quality after SMART is slightly better than that after FS-LASIK.

Incidence and characteristics of unilateral keratoconus classified on corneal topography.

PURPOSE: To evaluate the characteristics of unilateral keratoconus defined on the basis of corneal topography and analyze videokeratography parameters between fellow eyes and normal controls. METHODS: A total of 111 patients with clinical keratoconus were prospectively enrolled. Both eyes were evaluated with Tomey (Tomey Corp) and Orbscan II (Bausch & Lomb) corneal topography systems. The patient was classified as having unilateral keratoconus if one eye had clinical keratoconus and the other eye did not have any topographic signs of keratoconus such as asymmetric videokeratographic pattern, positive result in Tomey keratoconus screening, maximum posterior elevation >40 µm, or corneal thinnest pachymetry <500 µm. Clinical characteristics and 13 Orbscan II quantitative indices between keratoconic and fellow eyes and normal control eyes were evaluated. RESULTS: Five (4.5%) of 111 patients with keratoconus had no topographic evidence of keratoconus in the fellow eye. All clinically normal fellow eyes had symmetric bowtie patterns. Statistically significant differences were noted in maximum posterior elevation, corneal irregularity, and corneal thinnest values between keratoconic eyes and fellow eyes, and between keratoconic eyes and control eyes. Only 3-mm irregularity was significantly higher in the fellow eyes compared with control eyes (P<.05). An increased trend for corneal 5-mm irregularity was found in fellow eyes compared to control eyes. CONCLUSIONS: The incidence of unilateral keratoconus was 4.5%. A trend of higher irregularity was found in fellow eyes compared with control eyes. This finding indicates that fellow eyes may show a certain low-expressivity morphologic feature of keratoconus.

[Prevalence survey of visual impairment in a multiethnic rural district in the high altitude area of Yunnan Province, China].

OBJECTIVE: To estimate the prevalence and causes of visual impairment by a population-based survey conducted in Gongshan County of Yunnan Province. METHODS: Cluster sampling method was used for sample selection. In person interview, pilot study, visual acuity (VA) check, intraocular pressure, slit lamp microscopy and fundus examination were performed. The diagnoses of blindness (VA<0.05) and visual impairment (VA<0.3 to ≥0.05) were based on best-corrected visual acuity in the better eye. The prevalence of visual impairment was calculated as to age, gender, education, ethnic group and altitude of living area. The dominant causes of blindness and visual impairment were then identified. The comparison of prevalence among different group examined by four-fold table Chi-square test, R×2 Chi-square test and trend Chi-square test. RESULTS: Among 3070 eligible residents, 2460 (80.1%) were finally enrolled in the present study. The total prevalence of visual impairment was 6.46%. The bilateral blindness and unilateral blindness was 19 and 46 respectively. The bilateral and unilateral low vision was 49 and 45 respectively. There was no statistical significant difference of prevalence of visual impairment among different ethnic groups (χ2=0.75, P=0.388). There was significantly statistical difference of prevalence of visual impairment among groups who lives in different altitude area (χ2=18.34, P=0.000). High prevalence were also observed in the elder (≥70 years), illiterate and outdoor-workers, which was 2.24%, 4.19%, 5.65% respectively. The leading causes of bilateral blindness was cataract (42.1%, 8/19), corneal opacity (26.3%, 5/19), and retinal abnormality (21.1%, 4/19). The leading cause of bilateral low vision was also cataract (42.9%, 21/49). CONCLUSIONS: Cataract was the dominant cause of visual impairment in Gongshan County of Yunnan Province. The study highlights an urgent need of visual impairment prevention program conducted by local public heath intervention, especially focusing on cataract treatment.

Immunologic mechanism of fungal keratitis.

Fungal keratitis (FK) is a refractory disease that poses a serious threat to vision, with common risk factors like eye trauma, contact lens wearing, topical corticosteroids and antibiotic abuse. Nowadays, topical and systemic anti-fungal drugs and ocular surgeries are still the main therapeutic modalities. However, the pathogenesis of FK, especially the immunologic mechanism within it, has not yet been deeply clarified. A better understanding of the pathogenesis of FK is imperative for more effective therapies and prognosis. Meanwhile, the immune protection strategies are also urgently required to manage FK. This review highlights recent advances in the immunologic mechanism in the pathogenesis of FK, in hope of providing valuable reference information for more effective anti-fungal treatment.

The correlation between the regulation of recombinant human IGF-2 on eye growth and form-deprivation in guinea pig.

OBJECTIVE: By investigating the effects of recombinant human IGF-2 (rhIGF-2) on the diopter, axial eye length and the expression of IGF-2 in non-form-deprivation (FD) and FD eyes of guinea pig, we tried to elucidate the relationship between the effects of rhIGF-2 on eye growth and FD in guinea pig. METHODS: Eighty 3-week-old guinea pigs were included in the study, which were divided into two groups randomly. Group A (n = 40) was the non-FD group, Thirty-two guinea pigs received intravitreal injections of either 1 ng, 10 ng, 100 ng rhIGF-2 or bovine serum albumin (BSA) to the right eye; eight guinea pigs who received no intravitreal injections served as control. Group B (n = 40) was the FD group; the right eyes were form-deprived, and received the same disposals as group A. The diopter and the axial eye length of all guinea pigs were measured at day 14. The expression of IGF-2 in the retina was measured by Western blot. RESULTS: After 14 days, FD eyes were high myopia. The axial length of FD eyes was significant for longer than that of non-FD eyes. The expression of IGF-2 in the retina of FD eyes was up-regulated. In non-FD group, there was no significant difference in the diopter and axial eye length among rhIGF-2 injection eyes, BSA injection eyes and control eyes, but the expression of IGF-2 in the retina of 10 ng and 100 ng rhIGF-2 injection eyes was obviously down-regulated. In the FDM (form-deprivation myopia) group, the myopic diopter and axial eye length increased in 10 ng and 100 ng rhIGF-2 injection eyes compared with those in BSA injection eyes and control eyes. The level of IGF-2 expression in the retina of 10 ng and 100 ng rhIGF-2 injection eyes was obviously down-regulated. The diopter and expression of IGF-2 in the retina of rhIGF-2 injection eyes was negatively correlated with the dose of each injection, which was positively correlated with the axial length. CONCLUSION: RhIGF-2 intravitreous injection does not affect the diopter and axial length in non-FD eyes of guinea pig, while it can induce a significant increase in myopic diopter and axial length of FD eyes. RhIGF-2 can promote the development of FDM on the condition of FD.

Pathophysiological Role and Drug Modulation of Calcium Transport in Ocular Surface Cells.

The ocular surface structure and extraocular accessory organs constitute the ocular surface system, which includes the cornea, conjunctiva, eyelids, lacrimal organs, and lacrimal passages. This system is composed of, and stabilized by, the corneal epithelium, conjunctival cells, conjunctival goblet cells, lacrimal acinar cells and Tenon's fibroblasts, all of which maintain the healthy eyeball surface system. Ocular surface diseases are commonly referred to corneal and conjunctival disease and external ocular disease, resulting from damage to the ocular surface structure. A growing body of evidence has indicated that abnormal activation of the KCa3.1 channel and Ca2+/ calmodulin-dependent kinase initiates ocular injury. Signaling pathways downstream of the irregular Ca2+ influx induce cell progression and migration, and impair tight junctions, epithelial transport and secretory function. In this overview, we summarize the current knowledge regarding ocular surface disease in terms of physical and pathological alteration of the ocular system. We dissect in-depth, the mechanisms underlying disease progression, and we describe the current calcium transport therapeutics and the obstacles that remain to be solved. Finally, we summarize how to integrate the research results into clinical practice in the future.

PPARγ: the dominant regulator among PPARs in dry eye lacrimal gland and diabetic lacrimal gland.

AIM: To investigate the regulatory roles of the members of the peroxisome proliferator-activated receptor (PPAR) family in lacrimal gland dysfunction under conditions of desiccating stress or diabetes. METHODS: Quantitative polymerase chain reaction (qPCR) was used to examine the expression of PPARs in the cornea, conjunctiva, meibomian gland, and lacrimal gland in adult rats. The rats were divided into 3 groups: a control group, dry eye group, and diabetic group. The phenol red threads test, tear film break-up time (BUT) test and fluorescein staining were carried out to evaluate the development of dry eye. Based on bioinformatics research, qPCR was used to examine the expression level of PPARγ, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), sirtuin 1 (Sirt1), myeloid differentiation factor 88 (MyD88) and transforming growth factor-ß (TGF-ß) in the lacrimal glands. RESULTS: PPARα and PPARß/δ were mainly expressed in the conjunctiva and the lacrimal gland, respectively. However, PPARγ was expressed in both the conjunctiva and lacrimal gland, at much higher levels than those measured for PPARα and PPARß/δ. Dry eye rats and diabetic rats both showed decreased tear secretion, shortened BUT, and increased corneal staining. Significant changes in gene expression were observed compared with the control group. In the lacrimal glands of dry eye rats and diabetic rats, expression of PPARγ decreased (P<0.05), expression of Sirt1 also decreased (P<0.01), whereas expression of TNF-α, IL-1ß, IL-6, MyD88, and TGF-ß increased (P<0.05). CONCLUSION: Among PPARs, PPARγ might play a dominant role in the regulation of metabolic- and inflammatory-signaling pathways on the ocular surfaces and in lacrimal glands. Down-regulation of PPARγ is highly relevant to lacrimal gland dysfunction under desiccating-stress and diabetic conditions. PPARγ, thus, is a potential therapeutic target in the treatment of environment- or diabetes-induced dry eye diseases.

Effects of congenital ptosis on the refractive development of eye and vision in children.

AIM: To investigate the influence of unilateral congenital ptosis on the development of the eye and vision in children. METHODS: In this prospective observational study, 41 patients with unilateral congenital ptosis were enrolled (age range 3-15y). The blepharoptosis was divided into 3 subgroups according to the margin reflex distance-1 (MRD-1), including mild group (MRD-1≥2 mm), moderate group (0≤MRD-1<2 mm), and severe group (MRD-1<0 mm). The fellow eyes served as controls. All subjects underwent ocular examinations, including axial length, keratometry, and refractive error. RESULTS: The incidence of astigmatism (ptotic eyes: 58.5% vs fellow eyes: 24.4%, P=0.002) and magnitude of cylindrical power (ptotic eyes: -0.86±0.79 D vs fellow eyes: -0.43±0.63 D, P=0.003) differed significantly between the ptotic eyes and the fellow eyes. The spherical equivalent refraction (P=0.006), spherical power (P=0.01), cylindrical power (P=0.011), axial length-corneal radius (AL/CR) ratio (P=0.009), frequency of hyperopia (P=0.002) and astigmatism (P=0.004) were significantly different among the ptotic eye subgroups and the fellow eye group. In addition, in patients with congenital ptosis, the incidence of amblyopia is 43.9% and the incidence of anisometropia is 24.4%. More importantly, the ratio of AL/CR showed significantly positive correlation with the severity of ptosis (P=0.002). CONCLUSION: Congenital ptosis may lead to a delayed eyeball development in the aspect of AL/CR. The risk of amblyopia is also increased due to visual deprivation and aggravated anisometropia, particularly in severe ptosis case.

Identification of tear fluid biomarkers in dry eye syndrome using iTRAQ quantitative proteomics.

The proteins found in tears have an important role in the maintenance of the ocular surface and changes in the quality and quantity of tear components reflect changes in the health of the ocular surface. In this study, we have used quantitative proteomics, iTRAQ technology coupled with 2D-nanoLC-nano-ESI-MS/MS and with a statistical model to uncover proteins that are significantly and reliably changed in the tears of dry eye patients in an effort to reveal potential biomarker candidates. Fifty-six patients with dry eye and 40 healthy subjects were recruited for this study. In total, 93 tear proteins were identified with a ProtScore >or=2 (>or=99% confidence). Associated with dry eye were 6 up-regulated proteins, alpha-enolase, alpha-1-acid glycoprotein 1, S100 A8 (calgranulin A), S100 A9 (calgranulin B), S100 A4 and S100 A11 (calgizzarin) and 4 down-regulated proteins, prolactin-inducible protein (PIP), lipocalin-1, lactoferrin and lysozyme. Receiver operating curves (ROC) were evaluated for individual biomarker candidates and a biomarker panel. With the use of a 4-protein biomarker panel, the diagnostic accuracy for dry eye was 96% (sensitivity, 91.0%; specificity, 90.0%). Two biomarker candidates (alpha-enolase and S100 A4) generated from iTRAQ experiments were successfully verified using an ELISA assay. The levels of these 10 tear proteins reflect aqueous secretion deficiency by lacrimal gland, inflammatory status of the ocular surface. The clinical classification of the severity of the dry eye condition was successfully correlated to the proteomics by using three proteins that are associated with inflammation, alpha1-acid glycoprotein 1, S100 A8 and S100 A9. The nine tear protein biomarker candidates (except alpha1-acid glycoprotein 1) were also verified using an independent age-matched patient sample set. This study demonstrated that iTRAQ technology combined with 2D-nanoLC-nanoESI-MS/MS quantitative proteomics is a powerful tool for biomarker discovery.

Gene-based Therapeutic Tools in the Treatment of Cornea Disease.

BACKGROUND: As one of the main blinding ocular diseases, corneal blindness resulted from neovascularization that disrupts the angiogenic privilege of corneal avascularity. Following neovascularization, inflammatory cells are infiltrating into cornea to strengthen corneal injury. How to maintain corneal angiogenic privilege to treat corneal disease has been investigated for decades. METHODOLOGY: Local administration of viral and non-viral-mediated anti-angiogenic factors reduces angiogenic protein expression in situ with limited or free of off-target effects upon gene delivery. Recently, Mesenchymal Stem Cells (MSCs) have been studied to treat corneal diseases. Once MSCs are manipulated to express certain genes of interest, they could achieve superior therapeutic efficacy after transplantation. DISCUSSION: In the text, we first introduce the pathological development of corneal disease in the aspects of neovascularization and inflammation. We summarize how MSCs become an ideal candidate in cell therapy for treating injured cornea, focusing on cell biology, property and features. We provide an updated review of gene-based therapies in animals and preclinical studies in the aspects of controlling target gene expression, safety and efficacy. Gene transfer vectors are potent to induce candidate protein expression. Delivered by vectors, MSCs are equipped with certain characters by expressing a protein of interest, which facilitates better for MSC-mediated therapeutic intervention for the treatment of corneal disease. CONCLUSION: As the core of this review, we discuss how MSCs could be engineered to be vector system to achieve enhanced therapeutic efficiency after injection.

Accuracy of corneal astigmatism correction with two Barrett Toric calculation methods.

AIM: To compare the prediction error between Barrett Toric calculator and the new online AcrySof Toric calculator which incorporated Barrett astigmatism algorithm in Chinese cataract eyes with normal axial length and anterior chamber depth (ACD). METHODS: Prospective case-control study. All the cases had axial length (21-26 mm) with ACD no less than 2.4 mm. Keratometric values were measured by LenSTAR 900. The Barrett Toric calculator was used in group 1. In group 2, SRK-T formula was used to determine the spherical power of the Toric lens, and subsequent calculation of the cylinder type was performed using the new online Alcon Toric calculator. At 1 and 3mo after surgery, a comprehensive subjective optometry was performed. The predicted residual astigmatism calculated by the two calculators was compared with that obtained by postoperative refraction, and the difference was defined as the astigmatism correction error [error of refractive astigmatism (ERA)]. The error magnitude (EM) refers to the algebraic deviation of ERA, and the error vector (EV) indicates the vector deviation of ERA. The influence of the two calculation methods on the correction accuracy of toric IOL was quantitatively analyzed. RESULTS: The |EM| obtained at 1mo after surgery were 0.21±0.12 D, 0.22±0.18 D in group 1 and group 2 respectively, and correspondingly turned to be 0.19±0.13 D, 0.20±0.19 D at 3mo after surgery, with no statistical difference (P=0.633, P=0.877). The vector analysis showed that |EV| values in two groups at 1mo after surgery were 0.29±0.14@105 (D@angle) and 0.35±0.20@113 (D@angle), respectively, whereas |EV| values 3mo after surgery were 0.27±0.16@86 (D@angle) and 0.32±0.23@102 (D@angle), respectively. The differences between the groups were not statistically significant (P=0.119, P=0.261). CONCLUSION: The clinical effect of Barrett Toric calculator has a much more accurate tendency than that of new online AcrySof Toric calculator, but is not evident in cases with normal axial length and normal anterior posterior ratio.

Puerarin regulates neovascular glaucoma through pigment epithelium­derived growth factor­induced NF­κB signaling pathway.

Neovascular glaucoma is an ophthalmic disease and a potentially blinding secondary glaucoma caused by the formation of abnormal new blood vessels on the iris, which can prevent the normal drainage of water from the anterior segment of the eye. Evidence from China has suggested that puerarin benefits many diseases including myocardial infarction, stable angina, cerebral ischemia and glaucoma in a clinical setting. In the present study, the aim was to investigate the efficacies of puerarin on neovascular glaucoma in a mouse model. The molecular mechanism of puerarin­mediated treatment for neovascular glaucoma was also investigated both in vitro and in vivo. Inflammatory responses in mice with neovascular glaucoma were analyzed by western blotting. Oxidative stress levels were investigated following treatment with puerarin in a mouse model of neovascular glaucoma. The results indicated that puerarin markedly improved growth of vascular endothelial cells. The present study reported that puerarin treatment markedly decreased interleukin (IL)­1ß, IL­17A and tumor necrosis factor­α expression levels in mice with neovascular glaucoma. It was found that puerarin significantly decreased oxidative stress levels by reducing reactive oxygen species, superoxide dismutase and malondialdehyde levels, as well as neuronal nitric oxide synthase (NOS) and inducible NOS expression levels. Results indicated that expression levels of pigment epithelium­derived growth factor were significantly inhibited following treatment with puerarin. Mechanism analysis demonstrated that treatment with puerarin effectively inhibited nuclear factor (NF)­κB activity and its target protein levels p65, inhibitor of NF­κB kinase subunit ß and inhibitor of NF­κB kinase subunit α in vascular endothelial cells. Increasing endothelial­derived growth factor (EDGF) expression levels could stimulate NF­κB activity and abolish the inhibitory effects of puerarin. An animal study reported that puerarin treatment presented therapeutic effects for mice with neovascular glaucoma. Numbers of new vessels in iris were recovered to normal following puerarin treatment. In conclusion, these results indicated that puerarin treatment can inhibit inflammatory responses and oxidative stress, platelet­derived growth factor (PDGF) expression and NF­κB activity, suggesting puerarin may be a potential agent for the treatment of neovascular glaucoma through PDGF­induced NF­κB signaling pathway.

Angiopoietin-like 3 Is a Potential Biomarker for Retinopathy in Type 2 Diabetic Patients.

PURPOSE: To investigate whether angiopoietin-like 3 (ANGPTL3) and angiopoietin-like 4 (ANGPTL4) are differentially associated with the severity of retinopathy in patients with type 2 diabetes mellitus (T2DM). DESIGN: Cross-sectional study. METHODS: Serum levels of ANGPTL3, ANGPTL4, high-sensitivity C-reactive protein (CRP), vascular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and vascular endothelial growth factor (VEGF) were quantified by ELISA. Retinal images were recorded to assess the grade of diabetic retinopathy (DR). Multivariable-adjusted logistic analysis was performed to estimate the association of each biomarker and DR stage. RESULTS: Among 1192 T2DM patients, 426 (35.7%) had nonproliferative diabetic retinopathy (NPDR) and 56 (4.5%) had proliferative diabetic retinopathy (PDR). After adjusting for covariables, the odds ratios expressing the risk of having DR vs no DR (n = 710 vs 482) were 1.23 (95% confidence interval [CI], 1.08-1.40, P = .002) for ANGPTL3; 0.90 (95% CI, 0.79-1.02; P = .095) for ANGPTL4; and 1.14 (95% CI, 1.00-1.29; P = .044) for VEGF. The risk of having no DR vs NPDR (n = 710 vs 426) was 1.16 (95% CI, 1.01-1.32; P = .036) for ANGPTL3; 0.90 (95% CI, 0.79-1.04; P = .15) for ANGPTL4; and 1.14 (95% CI, 1.00-1.31; P = .045) for VEGF. The odds ratios of having NPDR vs PDR (n = 426 vs 56) was 1.47 (95% CI, 1.03-2.10; P = .035) for serum ANGPTL3; 0.96 (95% CI, 0.69-1.35; P = .83) for ANGPTL4; and 1.05 (95% CI, 0.77-1.45; P = .74) for VEGF. CONCLUSIONS: ANGPTL3 is independently and strongly associated with DR progression in all stages. Blockade of ANGPTL3 signal in retina might postpone the onset and development of DR in T2DM patients.