Abstract:AIM: To evaluate the effect of exogenous recombinant human bone morphogenic protein-7 (rhBMP-7) on transforming growth factor-β (TGF-β)-induced epithelial mesenchymal cell transition (EMT) and assessed its antifibrotic effect via topical application. METHODS: The cytotoxic effect of rhBMP-7 was evaluated and the EMT of human corneal epithelial cells (HECEs) was induced by TGF-β. HECEs were then cultured in the presence of rhBMP-7 and/or hyaluronic acid (HA). EMT markers, fibronectin, E-cadherin, α-smooth muscle actin (α-SMA), and matrix metaloproteinase-9 (MMP-9), were evaluated. The level of corneal fibrosis and the reepithelization rate were evaluated using a rabbit keratectomy model. Expression of α-SMA in keratocytes were quantified following treatment with different concentrations of rhBMP-7. RESULTS: Treatment with rhBMP-7 attenuated TGF-β-induced EMT in HECEs. It significantly attenuated fibronectin secretion (31.6%; P<0.05), the α-SMA protein level (72.2%; P<0.01), and MMP-9 expression (23.6%, P<0.05) in HECEs compared with cells grown in the presence of TGF-β alone. E-cadherin expression was significantly enhanced (289.7%; P<0.01) in the presence of rhBMP-7. Topical application of rhBMP-7 combined with 0.1% HA significantly reduced the amount of α-SMA+ cells by 43.18% (P<0.05) at a concentration of 2.5 µg/mL and by 47.73% (P<0.05) at 25 µg/mL, compared with the control group, without disturbing corneal reepithelization. CONCLUSION: rhBMP-7 attenuates TGF-β-induced EMT in vitro, and topical application of rhBMP-7 reduces keratocyte myodifferentiation during the early wound healing stages in vivo without hindering reepithelization. Topical rhBMP-7 application as biological eye drops seems to be feasible in diseases involving TGF-β-related corneal fibrosis with corneal reepithelization disorders.

Abstract:AIM: To select the optimal edge detection methods to identify the corneal surface, and compare three fitting curve equations with Matlab software. METHODS: Fifteen subjects were recruited. The corneal images from optical coherence tomography (OCT) were imported into Matlab software. Five edge detection methods (Canny, Log, Prewitt, Roberts, Sobel) were used to identify the corneal surface. Then two manual identifying methods (ginput and getpts) were applied to identify the edge coordinates respectively. The differences among these methods were compared. Binomial curve (y=Ax2+Bx+C), Polynomial curve [p(x)=p1xn+p2xn-1 +....+pnx+pn+1] and Conic section (Ax2+Bxy+Cy2+Dx+Ey+F=0) were used for curve fitting the corneal surface respectively. The relative merits among three fitting curves were analyzed. Finally, the eccentricity (e) obtained by corneal topography and conic section were compared with paired t-test. RESULTS: Five edge detection algorithms all had continuous coordinates which indicated the edge of the corneal surface. The ordinates of manual identifying were close to the inside of the actual edges. Binomial curve was greatly affected by tilt angle. Polynomial curve was lack of geometrical properties and unstable. Conic section could calculate the tilted symmetry axis, eccentricity, circle center, etc. There were no significant differences between ‘e’ values by corneal topography and conic section (t=0.9143, P=0.3760 >0.05). CONCLUSION: It is feasible to simulate the corneal surface with mathematical curve with Matlab software. Edge detection has better repeatability and higher efficiency. The manual identifying approach is an indispensable complement for detection. Polynomial and conic section are both the alternative methods for corneal curve fitting. Conic curve was the optimal choice based on the specific geometrical properties.

Abstract:AIM: To report a phenotypic variant pedigree of lattice corneal dystrophy (LCD) associated with two mutations, R124C and A546D, in the transforming growth factor beta-induced gene (TGFBI). METHODS: A detailed ocular examination was taken for all participants of a LCD family. Peripheral blood leukocytes from each participant were extracted to obtain the DNA. Polymerase chain reaction (PCR) of all seventeen exons of TGFBI gene was performed. The products were sequenced and analyzed. Histological examination was carried out after a penetrating keratoplasty from the right eye of proband. RESULTS: Genetic analysis showed that the proband and all 6 affected individuals harbored both a heterozygous CGC to TGC mutation at codon 124 and a heterozygous GCC to GAC mutation at codon 546 of TGFBI. None of the 100 control subjects and unaffected family members was positive for these two mutations. Ocular examination displayed multiple refractile lattice-like opacities in anterior stroma of the central cornea and small granular deposits in the peripheral cornea. The deposits were stained positively with Congo red indicating be amyloid in nature and situated mainly in the anterior and middle stroma. CONCLUSION: We observed a novel LCD family which carried two pathogenic mutations (R124C and A546D) in the TGFBI gene. The phenotypic features were apparently different from those associated with corresponding single mutations. The result reveals that although the definite mutation is the most important genetic cause of the disease, some different modifier alleles may influence the phenotype.

Abstract:AIM: To represent mathematically the intersection between the ectatic corneal geometry and the plane of intracorneal ring implants (ICRS) in order to determine the corneal response to ICRS surgery in keratoconus (KC). Thereafter, to present the concept and early results of a newly derived topography-guided nomogram for ICRS surgery for the treatment of keratectasia. METHODS: The corneal rings plane intersection was modelled to a conic section. Ring effect was the result of: the ring size, position (steep vs flat), location (distance from the geometric centre of the cornea), and the discrepancy between the ring’s curvature and the tunnel’s curvature. Femtosecond laser was used to create the tunnels and the incision sites were chosen according to the nomogram in order to place the thickest ring in the steepest portion of the cornea regardless of the astigmatism axis of refraction. RESULTS: The conic section had a more prolate shape in the steep area of the cornea than in the flat area, depending on the corneal sagittal curvature. Equal ring size had more flattening effect in the steep area than in the flat area. Thick segment should be implanted under the steep portion of the cornea regardless of the cylinder axis of refraction. Single segment in the steep area was sufficient in early and moderate cases of KC. The new nomogram provided more topographic regularity with significant reduction of astigmatism and better improvement in uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA) than the conventional nomogram. CONCLUSION: The newly derived nomogram can produce better results than the conventional nomogram. Moreover, based on this concept, a new nomogram can be integrated into the femtosecond laser software to create topography-guided, customized, elliptical tunnels with modified focal asphericity that allows for customized focal flattening of the irregularly steepened ectatic cornea.

Abstract: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 (-smooth muscle actin ((-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 (-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.

Abstract:AIM: To identify the expression of lens-related microRNAs (miRNAs) in the central epithelium of transparent infant lenses and congenital cataract. METHODS: Lens-related miRNAs were retrieved from PubMed database. The expression levels of these miRNAs in transparent infant lenses and congenital cataract were determined by stem-loop reverse transcription-polymerase chain reaction (RT-PCR). miRanda algorithm was used to predict the target genes of these differentially expressed miRNAs. The target mRNA was validated. RESULTS: Six lens-related miRNAs were retrieved from screening PubMed database. The most abundant miRNA in transparent infant lenses according to stem-loop RT-PCR was miR-184. miR-182 was up-regulated in congenital cataract. Contrarily, miR-204 and miR-124 was down-regulated. miR-204 exhibited a more significant decrease in expression than miR-124. In addition, Meis2 was predicted to be the target of miR-204 using miRanda algorithm. miR-204 mimic/antagomir transfection experiments suggested the negative correlation between the expression of miR-204 and Meis2. CONCLUSION: The expression levels of miR-182, miR-204 and miR-124 differ between the central epithelium of transparent infant lens and congenital cataract, suggesting their involvement in the pathogenesis of congenital cataract. miR-204 may act via silencing Meis2 to regulate lens development and congenital cataract formation.

Abstract:AIM: To investigate the effect of anti-vascular epithelial growth factor (VEGF) agents on the expression of fibrosis-related inflammatory mediators under normoxic and hypoxic conditions, and to further clarify the mechanism underlying fibrosis after anti-VEGF therapy. METHODS: Human retinal pigment epithelial (RPE) cells were incubated under normoxic and hypoxic conditions. For hypoxia treatment, CoCl2 at 200 μmol/L was added to the media. ARPE-19 cells were treated as following: 1) control group: no treatment; 2) bevacizumab group: bevacizumab at 0.25 mg/mL was added to the media; 3) hypoxia group: CoCl2 at 200 μmol/L was added to the media; 4) hypoxia+bevacizumab group: CoCl2 at 200 μmol/L and bevacizumab at 0.25 mg/mL were added to the media. The expression of interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α were evaluated using real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) at 6, 12, 24 and 48h. RESULTS: Both mRNA and protein levels of IL-1β, IL-6 and IL-8 were statistically significantly higher in the bevacizumab group than in the control group at each time point, and TNF-α gene and protein expression was only significantly higher only at 24 and 48h (P<0.05). Under hypoxic conditions, bevacizumab significantly increased the expression of IL-1β, IL-6, IL-8 and TNF-α at 6, 12, 24 and 48h (P<0.05). IL-1β, IL-8 and TNF-α peaked at 24h and IL-6 peaked at 12h after the bevacizumab treatment under both normoxic and hypoxic conditions. CONCLUSION: Treatment of ARPE-19 cells with bevacizumab can significantly increase the expression of fibrosis-related inflammatory mediators under both normoxic and hypoxic conditions. Inflammatory factors might be involved in the process of fibrosis after anti-VEGF therapy, and the up-regulation of inflammatory factors induced by anti-VEGF drugs might promote the fibrosis process.

Abstract:AIM: To analyze the relationship between the score obtained in the Risk Score System (RSS) proposed by Hicks et al with penetrating keratoplasty (PKP) graft failure at 1y postoperatively and among each factor in the RSS with the risk of PKP graft failure using univariate and multivariate analysis. METHODS: The retrospective cohort study had 152 PKPs from 152 patients. Eighteen cases were excluded from our study due to primary failure (10 cases), incomplete medical notes (5 cases) and follow-up less than 1y (3 cases). We included 134 PKPs from 134 patients stratified by preoperative risk score. Spearman coefficient was calculated for the relationship between the score obtained and risk of failure at 1y. Univariate and multivariate analysis were calculated for the impact of every single risk factor included in the RSS over graft failure at 1y. RESULTS: Spearman coefficient showed statistically significant correlation between the score in the RSS and graft failure (P<0.05). Multivariate logistic regression analysis showed no statistically significant relationship (P>0.05) between diagnosis and lens status with graft failure. The relationship between the other risk factors studied and graft failure was significant (P<0.05), although the results for previous grafts and graft failure was unreliable. None of our patients had previous blood transfusion, thus, it had no impact. CONCLUSION: After the application of multivariate analysis techniques, some risk factors do not show the expected impact over graft failure at 1y.

Abstract:AIM: To determine typical corneal changes of congenital aniridic keratopathy (CAK) using corneal topography and confocal systems, and to identify characteristics that might assist in early diagnosis. METHODS: Patients with CAK and healthy control subjects underwent detailed ophthalmic examinations including axial length, corneal thickness, tear film condition, corneal topography, and laser-scanning in vivo confocal microscopy (IVCM). RESULTS: In early stage aniridic keratopathy, Schirmer I test (SIT), break-up time (BUT), mean keratometry (mean K) and simulated keratometry (sim K) were reduced relative to controls (P<0.05), while simulation of corneal astigmatism (sim A) and corneal thickness were increased (P<0.05). In addition, significantly more eyes exhibited flat cornea compared with the control group. Inflammatory dendritic cells were present in the aniridic epithelium, with significantly increased density relative to controls (P<0.05). Palisade ridge-like features and abnormal cell morphology were observed in six out of sixteen CAK cases. In central cornea area, the aniridic corneas had the increased subbasal nerve density. CONCLUSION: These changes in corneal morphology in borderline situations can be useful to confirm the diagnosis of CAK.

Abstract:AIM: To compare visual, surgical and topographic outcomes of deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK) for keratoconus (KC). METHODS: In this multicenter, prospective, randomized clinical trial 76 eyes of 71 KC patients operated between January 2011 and July 2014 in 2 tertiary referral hospitals were included. Consecutive patients were alternately selected to receive one of the two surgical methods. Thirty eight eyes underwent DALK with the big-bubble technique and 38 eyes underwent PK. RESULTS: Mean best spectacle corrected visual acuity (BSCVA) at the first postoperative week (P=0.012) and the first postoperative month (P＜0.001) was statistically significantly higher in DALK group. The mean BSCVA at 12mo was not significantly different for DALK (0.30±1.99 logMAR) versus PK (0.40±0.33 logMAR) (P=0.104). The 76.3% of the eyes had a BSCVA over 0.5 in DALK and 47.4% in PK group (P=0.009). The 7.9% of the eyes had a BSCVA of 1.0 in DALK and 5.3% in PK group (P=0.644). Mean spherical equivalent was -2.94 D in DALK and -3.09 D in PK group. Mean topographic astigmatism was 4.62 D and 4.18 D respectively. Regular topographic patterns were observed in 31 (81.6%) of DALK and 29 (76.3%) of PK (P=0.574). The most frequent topographic pattern was oblate asymmetric bow tie, seen in 39.5% in DALK and 23.7% in PK. CONCLUSION: Big bubble DALK provides an earlier visual improvement compare to PK. However, visual and topographic outcomes are similar to those in PK at 1y. Postoperative complications including rejection and intraocular pressure elevation are more frequent in PK. DALK is a safer alternative to PK for KC. However, intraoperative perforation of the Descemet’s membrane is a significant complication.

Abstract:AIM: To evaluate the surgical treatment and visual outcomes of eyes with cataract and persistent hyperplastic primary vitreous (PHPV). METHODS: This retrospective study included patients with cataract and PHPV treated with various strategies. Anterior PHPV was treated using phacoemulsification with underwater electric coagulation on posterior capsule neovascularization, posterior capsulotomy, anterior vitrectomy, and intraocular lens (IOL) implantation. Posterior PHPV was treated with lensectomy, posterior vitrectomy, retinal photocoagulation, and IOL implantation or silicone oil tamponade. Visual acuity (VA), pattern visual evoked potential (P-VEP), anatomic recovery, postoperative complications, and amblyopia outcome were examined. Subjects were followed-up for 3-48mo after surgery. RESULTS: Of the 30 patients (33 eyes) with congenital cataract and PHPV included (average age, 39.30±35.47mo), 9 eyes had anterior PHPV and 24 had posterior PHPV. Thirty-two eyes were surgically treated. Eyes with anterior PHPV received an IOL during one-stage (6 eyes) and two-stage (3 eyes) implantation. Postoperative complications included retinal detachment (1 eye) and recurrent anterior chamber hemorrhage (1 eye). In eyes with posterior PHPV, 6 and 11 eyes received IOLs in one- and two-stage procedures, respectively. Silicone oil was retained in 2 eyes, and IOLs were not implanted in 4 eyes. VA significantly improved in 25 eyes following operations and 3-48mo of amblyopia treatment. P-VEP P100 was improved following surgery in both PHPV types. CONCLUSION: Our surgical strategies are appropriate and effective for anterior and posterior PHPV. Early surgical intervention and amblyopia therapy result in positive treatment outcomes.

Abstract:AIM: To evaluate the efficacy and safety of intravitreal ranibizumab (IVR) with panretinal photocoagulation (PRP) followed by trabeculectomy compared with Ahmed glaucoma valve (AGV) implantation in neovascular glaucoma (NVG). METHODS: This was a retrospective comparative study. We reviewed the cases of a total of 45 eyes from 45 NVG patients among which 23 eyes underwent AGV implantation and the other 22 underwent trabeculectomy. The causes of neovascular glaucoma included: diabetic retinopathy (25 eyes), and retinal vein occlusion (20 eyes). All patients received preoperative IVR combined with postoperative PRP. The mean best-corrected visual acuities (BCVA) were converted to the logarithms of the minimum angle of resolution (logMAR) for the statisitical analyses. Intraocular pressure (IOP), the logMAR BCVA and surgical complications were evaluated before and after surgery. The follow-up period was 12mo. RESULTS: A total of 39 cases showed complete regression of iris neovascularization at 7d after injection, and 6 cases showed a small amount of residual iris neovascularization. The success rates were 81.8% and 82.6% at 12mo after trabeculectomy and AGV implantation, respectively. In the trabeculectomy group, the logMAR BCVA improved at the last follow-up in 14 eyes, remained stable in 6 eyes and decreased in 2 eyes. In 4 cases, slight hyphemas developed after trabeculectomy. A shallow anterior chamber developed in 2 cases and 2 vitreous hemorrhages. In the AGV group, the logMAR BCVA improved in 14 eyes, remained stable in 5 eyes and decreased in 4 eyes. Slight hyphemas developed in 3 cases, and a shallow anterior chamber in 3 cases. The mean postoperative IOP was significantly lower in both groups after surgery (F=545.468, P<0.05), and the mean postoperative logMAR BCVA was also significantly improved (F=10.964, P<0.05) with no significant difference between two groups. CONCLUSION: It is safe and effective to treat NVG with this combined procedure, and we found similar results after IVR+AGV implantation+PRP and IVR+trabeculectomy+PRP in eyes with NVG.

Abstract:AIM: To evaluate the morphological changes in anterior segment in Chinese patients with uveal effusion (UE) after the attack of acute primary angle-closure (APAC) using ultrasound biomicroscopy (UBM), and to assess the clinical course and prognosis of the disease. METHODS: In a retrospective case series, 26 eyes in 26 consecutive patients diagnosed with UE after the treatment of intraocular pressure (IOP)-lowering medication for the attack of APAC were enrolled. The unaffected fellow eyes served as controls. The morphological changes were observed by ultrasonography, slit lamp microscopy and gonioscopy. UBM was used to assess the degree and extent of effusion based on the analysis of parameters associated with UE. RESULTS: The mean IOP was 9.2 (SD 2.1) mm Hg at the diagnosis of UE after IOP-lowering medication, while 14.1 (SD, 2.6) mm Hg in the fellow eyes (P=0.000). The anterior chamber depth (ACD) (P=0.000), angle opening distance at 500 μm (AOD500) (P<0.01) and anterior chamber angle (ACA) (P<0.05) were decreased significantly, while ciliary body thickness (CBT) (P<0.05) increased significantly in UE eyes. UE grade analysis showed 7 eyes in grade 1, 9 eyes in grade 2, and 10 eyes in grade 3. Quadrant scores were performed of 4 eyes in 1 quadrant, 3 eyes in 3 quadrants, and 19 eyes in 4 quadrants. There was the positive correlation between grade and quadrant score (r=0.644, P=0.000). The effusion on all eyes were recovered after medication, which mean IOP was 13.9 (SD, 2.8) mm Hg. CONCLUSION: UE is a frequent complication in Chinese patients after the attack of APAC, partially associated with hypotony. The severity of UE is correlation with height of effusion, extent of detachment, and shallower ACD.

Abstract:AIM: To report a cohort of patients with polypoidal choroidal vasculopathy (PCV) treated with photodynamic therapy (PDT) followed by intravitreal ranibizumab injection 24-48h later, and to compare the results between eyes with PCV treated by PDT followed by intravitreal anti-vascular endothelial growth factor (VEGF) injection and intravitreal anti-VEGF injection followed by PDT by Meta-analysis. METHODS: Retrospective study and systematic literature review. Medical records of patients with PCV who were initially treated using PDT followed by intravitreal ranibizumab injection 24-48h after PDT and had completed at least 2y follow-up were reviewed and analyzed. Clinical data, including age, sex, best-corrected visual acuity (BCVA), fundus photograph, fluorescein angiography, indocyanine green angiography and optical coherence tomography were investigated. A systematic literature review was also conducted, and a visual outcome of studies over 1y was compared using Meta-analysis. RESULTS: A total of 52 patients were included in the study. Mean BCVA at baseline and follow-up at 1 or 2y were 0.71±0.61, 0.51±0.36 and 0.68±0.51 logMAR, respectively. The cumulative hazard rate for recurrence at 1 and 2y follow-up was 15.4% and 30.3% respectively. The percentage of eyes with polyps regression at 3, 12 and 24mo follow-up was 88.5%, 84.6% and 67.3% respectively. A Meta-analysis based on 22 independent studies showed the overall vision improvements at 1, 2 and 3y follow-up were 0.13±0.04 (P<0.001), 0.12±0.03 (P<0.001), 0.16±0.06 (P<0.001), respectively. The proportion of polyps regression at 1y follow-up was 64.6% (95%CI: 51.5%, 77.7%, P<0.001) in 434 eyes treated by intravitreal anti-VEGF agents before PDT and 76.0% (95%CI: 64.8%, 87.3%, P=0.001) in 199 eyes treated by intravitreal anti-VEGF agents after PDT. CONCLUSION: Intravitreal ranibizumab injection 24-48h following PDT effectively stabilizes visual acuity in the eye with PCV. PDT followed by intravitreal anti-VEGF agents may contribute to a relatively higher proportion of polyps’ regression as compared to that of intravitreal anti-VEGF before PDT.

Abstract:AIM: To report the change in visual acuity and central macular thickness (CMT) following treatment with intravitreal aflibercept injections in patients with neovascular age-related macular degeneration (nAMD) with suboptimum response to ranibizumab. METHODS: This was a retrospective study. The inclusion criteria were patients with nAMD who responded poorly to ranibizumab. Patients then received either 3 consecutive aflibercept injections followed by PRN treatment or PRN alone. Primary endpoints were mean change in best-corrected visual acuity (BCVA) and CMT at 12mo. Secondary endpoints were number of injections and adverse events. RESULTS: Forty-nine eyes from 49 patients met the inclusion criteria and completed 12-month follow up on aflibercept. Thirty-eight eyes received 3 consecutive aflibercept injections followed by PRN treatment and 11 eyes received pro re nata (PRN) injections alone. At 12mo, mean BCVA improved by one letters (logMAR 0.56±0.31 to 0.54±0.34) and mean CMT decreased from 303.9±82.1 to 259.2±108.3 µm. Four percent of eyes gained 15 letters or more, 6% lost more than 15 letters and the remaining 90% had stable BCVA. The mean number of aflibercept injections was 6. There was one case of infectious endophthalmitis. CONCLUSION: Intravitreal aflibercept in patients with nAMD with a previous suboptimal response to ranibizumab resulted in an anatomical improvement in macular appearance at 12mo without a corresponding improvement in visual acuity.

Abstract:AIM: To assess the ganglion cell complex (GCC) thickness in diabetic eyes without retinopathy. METHODS: Two groups included 45 diabetic eyes without retinopathy and 21 non diabetic eyes. All subjects underwent full medical and ophthalmological history, full ophthalmological examination, measuring GCC thickness and central foveal thickness (CFT) using the RTVue® spectral domain-optical coherence tomography (SD-OCT), and HbA1C level. RESULTS: GCC focal loss volume (FLV%) was significantly more in diabetic eyes (22.2% below normal) than normal eyes (P=0.024). No statistically significant difference was found between the diabetic group and the control group regarding GCC global loss volume (GLV%) (P=0.160). CFT was positively correlated to the average, superior and inferior GCC (P=0.001, 0.000 and 0.001 respectively) and negatively correlated to GLV% and FLV% (P=0.002 and 0.031 respectively) in diabetic eyes. C/D ratio in diabetic eyes was negatively correlated to average, superior and inferior GCC (P=0.015, 0.007 and 0.017 respectively). The FLV% was negatively correlated to the refraction and level of HbA1c (P=0.019 and 0.013 respectively) and positively correlated to the best corrected visual acuity (BCVA) in logMAR in diabetic group (P=0.004). CONCLUSION: Significant GCC thinning in diabetes predates retinal vasculopathy, which is mainly focal rather than diffuse. It has no preference to either the superior or inferior halves of the macula. Increase of myopic error is significantly accompanied with increased focal GCC loss. GCC loss is accompanied with increased C/D ratio in diabetic eyes.

Abstract:AIM: To apply the multifractal analysis method as a quantitative approach to a comprehensive description of the microvascular network architecture of the normal human retina. METHODS: Fifty volunteers were enrolled in this study in the Ophthalmological Clinic of Cluj-Napoca, Romania, between January 2012 and January 2014. A set of 100 segmented and skeletonised human retinal images, corresponding to normal states of the retina were studied. An automatic unsupervised method for retinal vessel segmentation was applied before multifractal analysis. The multifractal analysis of digital retinal images was made with computer algorithms, applying the standard box-counting method. Statistical analyses were performed using the GraphPad InStat software. RESULTS: The architecture of normal human retinal microvascular network was able to be described using the multifractal geometry. The average of generalized dimensions (Dq) for q=0, 1, 2, the width of the multifractal spectrum (Δα=αmax - αmin) and the spectrum arms’ heights difference (│Δf│) of the normal images were expressed as mean±standard deviation (SD): for segmented versions, D0=1.7014±0.0057; D1=1.6507±0.0058; D2=1.5772±0.0059; Δα=0.92441±0.0085; │Δf│= 0.1453±0.0051; for skeletonised versions, D0=1.6303±0.0051; D1=1.6012±0.0059; D2=1.5531±0.0058; Δα=0.65032±0.0162; │Δf│= 0.0238±0.0161. The average of generalized dimensions (Dq) for q=0, 1, 2, the width of the multifractal spectrum (Δα) and the spectrum arms’ heights difference (│Δf│) of the segmented versions was slightly greater than the skeletonised versions. CONCLUSION: The multifractal analysis of fundus photographs may be used as a quantitative parameter for the evaluation of the complex three-dimensional structure of the retinal microvasculature as a potential marker for early detection of topological changes associated with retinal diseases.

Abstract:AIM: To evaluate the retinal vessel diameters in patients with migraine by optical coherence tomography (OCT). METHODS: In this cross-sectional study, 124 eyes of 62 patients with a diagnosis of unilateral migraine during attack-free period and 42 age- and sex-matched control subjects were included. Migraine patients were divided into the ≤2 migraine attacks per month group and the ≥5 migraine attacks per month group. All subjects underwent complete ophthalmological and neurological examinations before measurements. Retinal vessel diameters and choroidal thickness were examined with the Spectralis OCT. RESULTS: The mean diameters of the arteries in the eyes on the headache side of control group, ≥5 migraine attacks per month and ≤2 migraine attacks per month group at 480 µm from the optic disk (Raster 3) were 119.54±46.69, 136.68±25.93 and 119.34±31.75 µm respectively with a steady decline to 105.57±32.15, 118.18±31.87 and 108.05±38.77 µm at 1440 µm (Raster 7), the last measurement point, respectively. The retinal artery diameter measurements were significantly increased in ≥5 migraine attacks per month patients at four out of five measured points compared to control group (P<0.05). There were no statistical differences at any of the points of vein measurements. The choroidal thickness measurements were significantly decreased in ≥5 migraine attacks per month patients at all measured points compared to control group (P<0.05). CONCLUSION: The retinal artery diameter is found to increase significantly and the choroidal thickness is found to decrease in the eyes on the headache side in ≥5 migraine attacks per month patients compared to control group.

Abstract:AIM: To investigate quantitative and qualitative optical outcomes of single-step transepithelial photorefractive keratectomy (TransPRK) in high myopia. METHODS: In a prospective interventional case-series, 30 eyes with high myopia (-6.00 to -8.75 D) with (up to -3.00 D) or without astigmatism were enrolled from Bina Eye Hospital, Tehran, Iran. One-step TransPRK was performed with aberration-free aspherical optimized profile and SCHWIND AMARIS 500 laser. One-year follow-up results for refraction, visual acuities, vector analysis, ocular wave-front (OWF) and corneal wave-front (CWF) higher order aberrations (HOA), contrast sensitivity (CS), and post-operative haze were assessed. RESULTS: After the surgery, both photopic and mesopic CSs significantly improved (both P<0.001). We detected significant induction of OWF coma and trefoil (P<0.001 for both) HOAs; CWF coma (P=0.002), spherical (P<0.001), and tetrafoil (P=0.003) HOAs in 6 mm analysis diameter; and CWF trefoil (P=0.04) HOA in 4 mm analysis diameter. The range of mean induction observed for various HOAs was 0.005-0.11 µm. The 86.7% of eyes reached an uncorrected distance visual acuity of 20/20 or better; 96.7% of eyes were within ±0.5 D of targeted spherical refraction. In vector analysis, mean correction index value was 1.03 and mean index of success was 0.22. By 12mo after the operation, no eye lost any number of corrected distance visual acuity lines. We detected no corneal haze greater than 1+ throughout the follow-up. CONCLUSION: Our findings show promising effects of single-step TransPRK on quality of vision in high myopic eyes. It also improves refraction and visual acuity.

Abstract:AIM: To compare the repeatability/reproducibility of measurement by high-resolution Placido disk-based topography with that of a high-resolution rotating Scheimpflug camera and assess the agreement between the two instruments in measuring corneal power in eyes with keratoconus and post-laser in situ keratomileusis (LASIK). METHODS: One eye each of 36 keratoconic patients and 20 subjects who had undergone LASIK was included in this prospective observational study. Two independent examiners worked in a random order to take three measurements of each eye with both instruments. Four parameters were measured on the anterior cornea: steep keratometry (Ks), flat keratometry (Kf), mean keratometry (Km), and astigmatism (Ks-Kf). Intra-examiner repeatability and inter-examiner reproducibility were evaluated by calculating the within-subject standard deviation (Sw) the coefficient of repeatability (R), the coefficient of variation (CoV), and the intraclass correlation coefficient (ICC). Agreement between instruments was tested with the Bland-Altman method by calculating the 95% limits of agreement (95% LoA). RESULTS: In keratoconic eyes, the intra-examiner and inter-examiner ICC were >0.95. As compared with measurement by high-resolution Placido disk-based topography, the intra-examiner R of the high-resolution rotating Scheimpflug camera was lower for Kf (0.32 vs 0.88), Ks (0.61 vs 0.88), and Km (0.32 vs 0.84) but higher for Ks-Kf (0.70 vs 0.57). Inter-examiner R values were lower for all parameters measured using the high-resolution rotating Scheimpflug camera. The 95% LoA were -1.28 to +0.55 for Kf, -1.36 to +0.99 for Ks, -1.08 to +0.50 for Km, and -1.11 to +1.48 for Ks-Kf. In the post-LASIK eyes, the intra-examiner and inter-examiner ICC were >0.87 for all parameters. The intra-examiner and inter-examiner R were lower for all parameters measured using the high-resolution rotating Scheimpflug camera. The intra-examiner R was 0.17 vs 0.88 for Kf, 0.21 vs 0.88 for Ks, 0.17 vs 0.86 for Km, and 0.28 vs 0.33 for Ks-Kf. The inter-examiner R was 0.09 vs 0.64 for Kf, 0.15 vs 0.56 for Ks, 0.09 vs 0.59 for Km, and 0.18 vs 0.23 for Ks-Kf. The 95% LoA were -0.54 to +0.58 for Kf, -0.51 to +0.53 for Ks and Km, and -0.28 to +0.27 for Ks-Kf. CONCLUSION: As compared with Placido disk-based topography, the high-resolution rotating Scheimpflug camera provides more repeatable and reproducible measurements of Ks, Kf and Ks in keratoconic and post-LASIK eyes. Agreement between instruments is fair in keratoconus and very good in post-LASIK eyes.

Abstract:AIM: To report the epidemiology and incidence of vitreous hemorrhage and to evaluate risk factors for patients with vitreous hemorrhage (VH) in Taiwan. METHODS: A retrospective population-based study. Analyzing a sample of one million subjects from all enrollees of the Taiwan Health Insurance programme. All data were obtained from the Taiwan Health Insurance Research Database, which contained patient sex, date of birth, all records of clinical visits and hospitalizations, and diagnosis codes as included in the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). The main outcome measures were the incidence and risk factors of VH. CONCLUSION: The incidence of VH is estimated being 4.8 cases per 10 000 person-years in Taiwan. Age, male gender and having been prescribed anti-coagulation drugs are associated with the incidence of VH.

Abstract:AIM: To evaluate the distribution of refractive error in young subjects in a rural area of Paraguay in the context of an international cooperation campaign for the prevention of blindness. METHODS: A sample of 1466 young subjects (ranging from 3 to 22 years old), with a mean age of 11.21±3.63 years old, were examined to assess their distance visual acuity (VA) and refractive error. The first screening examination performed by trained volunteers, included visual acuity testing, autokeratometry and non-cycloplegic autorefraction. Inclusion criteria for a second complete cycloplegic eye examination by an optometrist were VA <20/25 (0.10 logMAR or 0.8 decimal) and/or corneal astigmatism ≥1.50 D. RESULTS: An uncorrected distance VA of 0 logMAR (1.0 decimal) was found in 89.2% of children. VA <20/25 and/or corneal astigmatism ≥1.50 D was found in 3.9% of children (n=57), with a prevalence of hyperopia of 5.2% (0.2% of the total) in this specific group. Furthermore, myopia (spherical equivalent ≤-0.5 D) was found in 37.7% of the refracted children (0.5% of the total). The prevalence of refractive astigmatism (cylinder ≤-1.50 D) was 15.8% (0.6% of the total). Visual impairment (VI) (0.05≤VA≤0.3) was found in 12/114 (0.4%) of the refracted eyes. Main causes for VI were refractive error (58%), retinal problems (17%, 2/12), albinism (17%, 2/12) and unknown (8%, 1/12). CONCLUSION: A low prevalence of refractive error has been found in this rural area of Paraguay, with higher prevalence of myopia than of hyperopia.

Abstract:AIM: To report on the utilization of eye care services and its associated factors among those with unilateral visual impairment (VI) in a rural South Indian population. METHODS: A population based cross-sectional study was conducted in three districts (Adilabad, Mahbubnagar and West Godavari) in the state of Andhra Pradesh, India. A detailed interview and a comprehensive eye examination were conducted. Those with unilateral VI were asked questions about noticing any change in vision and on utilization of eye care services. The most important reason reported by the participant for not utilizing the services was used for the analysis. Multiple logistic regression models were used to examine the association between noticing a change in vision and socio-demographic variables such as age, gender, education and area of residence, severity and causes of VI. RESULTS: Among the 4456 participants aged ≥16y who were administered the questionnaire, 53.2% were women, and 54.7% had no education. Of the 489 (11%; 95% CI: 10.1-11.9) people with unilateral VI, 399 (81.6%) participants reported noticing a change in their vision over the last five years but only 136 (34.1%) participants had sought eye care consultation. Those who had any education (OR: 1.9; 95% CI: 1.1-3.2), had blindness (OR: 2.7; 95% CI: 1.4-5.2), and cataract (OR: 2.1; 95% CI: 1.0-4.3) as a cause of unilateral VI were more like to seek eye care consultations. The most commonly reported reasons for not seeking eye care services were “do not have money for eye checkup” in 30.7% of the participants followed by “do not have a serious problem” (30.0%). CONCLUSION: A large proportion of rural population though noticed a change in their vision did not seek eye care due to financial and person-related reasons. Eye care service providers need to address these barriers to enhance the uptake of eye care services among those with unilateral VI.

Abstract:Leber’s congenital amaurosis (LCA) and recent gene therapy advancement for treating inherited retinopathies were extensive literature reviewed using MEDLINE, PubMed and EMBASE. Adeno-associated viral vectors were the most utilised vectors for ocular gene therapy. Cone photoreceptor cells might use an alternate pathway which was not reliant of the retinal pigment epithelium (RPE) derived retinoid isomerohydrolase (RPE65) to access the 11-cis retinal dehydechromophore. Research efforts dedicated on the progression of a gene-based therapy for the treatment of LCA2. Such gene therapy approaches were extremely successful in canine, porcine and rodent LCA2 models. The recombinant AAV2.hRPE65v2 adeno-associated vector contained the RPE65 cDNA and was replication deficient. Its in vitro injection in target cells induced RPE65 protein production. The gene therapy trials that were so far conducted for inherited retinopathies have generated promising results. Phase I clinical trials to cure LCA and choroideremia demonstrated that adeno-associated viral vectors containing RPE genes and photoreceptors respectively, could be successfully administered to inherited retinopathy patients. A phase III trial is presently ongoing and if successful, it will lead the way to additional gene therapy attempts to cure monogenic, inherited retinopathies.

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