Abstract:AIM: To characterize changes in the cornea nerve and pain responses in fungal keratitis (FK). METHODS: A retrospective analysis of in vivo confocal microscopy images of 11 FK corneas was performed, and the results were compared with those for 11 normal corneas. Subbasal corneal nerves were analyzed for total nerve number, main nerve trunk number, branching patterns and tortuosity. C57BL/6 mice were infected with Aspergillus fumigatus. Disease severity was determined through clinical scoring and slit lamp photography. Corneas were harvested at 1, 3, 5, and 7d post infection (p.i.) and assessed for β III tubulin. Corneal mechanical sensitivity thresholds were detected by von Frey test. β-endorphin (β-EP) and μ receptor protein expression was detected through Western blotting. RESULTS: Total nerve number, main nerve trunk number, and nerve branching were significantly lower in FK patients than in controls, but tortuosity was not significantly different. In infected mice, subbasal nerve density decreased from 1d p.i., reaching a minimum at 5d p.i. Clinical scores rose at 1d p.i., peaked at 3d p.i., and decreased at 5d p.i. Mechanical sensitivity thresholds showed the same trends. β-EP and μ receptor protein expression increased after infection. CONCLUSION: Corneal nerve density is lower in FK patients and Aspergillus fumigatus-infected mice than in controls. Pain sensitivity decreases with postinfection corneal ulcer aggravation. β-EP and μ receptor proteins are both upregulated in infected mouse corneas.

Abstract:AIM: To investigate the expression of lacrimal androgen-binding proteins (ABPs) in mice Pseudomonas aeruginosa (P. aeruginosa) keratitis. METHODS: P. aeruginosa mice model from different gender was developed by intra-stromal injection. The expression of lacrimal ABPs in lacrimal gland specimens from P. aeruginosa keratitis mice was detected by the quantitative polymerase chain reaction (qRT-PCR). Corneal virulence was evaluated based on clinical scores. To study the mechanism of lacrimal ABPs’ expression, experimental subjects were pre-treated with 4E-BP1 inhibitor, and were used to evaluate the expression levels by qRT-PCR. RESULTS: Compared with control groups, the expression of ABPα, ABPη and ABPζ in lacrimal gland from P. aeruginosa keratitis mice had no meaningful changes, while ABPε and ABPδ were significantly higher at 1d after infection. The expression of ABPδ in lacrimal gland of male mice was higher than female mice, regardless of whether or not P. aeruginosa keratitis occurred. After 4E-BP1 inhibitor subconjunctival injection or lacrimal injection, the expression of ABPδ and ABPε has no significant change compared with the control group. CONCLUSION: ABPδ and ABPε secreted by mice lacrimal gland may involve in the progress of alleviating the severity of corneal damage in P. aeruginosa keratitis. The expression of ABPδ and ABPε upon P. aeruginosa infection is independent of cap-dependent mRNA translation activated by 4E-BP1.

Abstract:AIM: To evaluate the effects of epidermal growth factor (EGF) on transforming growth factor-beta1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in human corneal epithelial cells (HCECs). METHODS: HCECs were cultured and treated with TGF-β1 for establishing the model of EMT in vitro. Biological effect of EGF on TGF-β1-induced EMT was evaluated. Proteins and mRNAs expression changes of E-cadherin, N-cadherin and Fibronectin (EMT-relative markers) after TGF-β1 or TGF-β1 combined EGF treatment were detected by Western blot and RT-PCR, respectively. Viability and migration of HCECs were measured by CCK-8, transwell cell migration assay and cell scratch wound healing assay. Activation of Smad2, ERK, p38, JNK and Akt signaling pathways were evaluated by Western blot. Inhibitors of relevant signaling pathways were added to the HCECs to explore the key signal mechanism. RESULTS: With treatment of TGF-β1 only, three EMT-relative proteins and mRNA expression showed that EMT up-regulated in a concentration-dependent and time-dependent manner, with significantly decreasing cell viability (TGF-β1≥5 ng/mL, P<0.05) and increasing cell migration (TGF-β1≥5 ng/mL, P<0.01). The phosphorylation of Smad2 and p38 was a key process of TGF-β1-induced EMT. Meanwhile, EMT-relative proteins and mRNA expression showed that EGF inhibited TGF-β1-indued EMT, with significantly increasing cell viability (EGF≥10 ng/mL, P<0.01). It was noteworthy that EGF significantly enhanced cell migration although EMT was inhibited (EGF≥10 ng/mL, P<0.01), and the blockage of p38 (by SB202190, a p38 inhibitor) was a potential mechanism of this phenomenon. CONCLUSION: EGF inhibits TGF-β1-induced EMT via suppressive p38, and promotes cells proliferation and migration in a non-EMT process by inhibiting p38 pathway.

Abstract:AIM: To investigate the expression and possible role of the autophagy related protein p62 and LC3 in the retina based on a rat model of acute ocular hypertension. METHODS: Fifty rats were randomized into five groups: control group A, B, C, and D. Groups A to D all received normal saline perfusion into the anterior chamber with pressure of 80 mm Hg for one hour, and retina tissue was obtained at 6, 12, 24 and 48h after perfusion respectively, to investigate the activation of autophagy following ischemia-reperfusion. The distribution and semi-quantification of autophagy related protein p62 and LC3 in the retina were detected using immunohistochemistry technique. The expression level of these two proteins was evaluated using Western blot. RESULTS: The number of retinal ganglion cells (RGCs) decreased with increasing reperfusion time, and significant reduction in the retinal thickness was observed 48h after perfusion. In normal adult rats, LC3 protein was mainly expressed in the ganglion cell layer (GCL), and p62 protein was expressed in the nerve fiber layer (NFL), GCL, inner plexiform layer (IPL), inner nuclear layer (INL) and outer plexiform layer (OPL). In comparison to the control group, the expression level of LC3- II was higher in all the experimental groups (P<0.05), with the peak expression at 12h after reperfusion. Additionally, the expression level of p62 was higher in all the experimental groups than the control (P<0.05, except for group A), with the peak level occurred 24h after reperfusion. CONCLUSION: Both p62 and LC3 show low level and uneven expression in the retina of normal adult rats. Acute ocular hypertension can lead to upregulation of LC3- II and p62 expression in the retina. Autophagy flux is damaged 12h after reperfusion, potentially resulting in further loss of RGCs.

Abstract:AIM: To make an electrophysiological demonstration of a possible jaw muscle afferents-oculomotor neural pathway that was proposed by our previous works on rats, which substantiates an early “release hypothesis” on pathogenesis of human Marcus Gunn Syndrome (MGS). METHODS: Extracellular unit discharge recording was applied and both orthodromic and spontaneous unitary firing were recorded in the oculomotor nucleus (III), and the complex of pre-oculomotor interstitial nucleus of Cajal and Darkschewitsch nucleus (INC/DN), following electric stimulation of the ipsilateral masseter nerve (MN) in rats. RESULTS: Extracellular orthodromic unit discharges, with latencies of 3.7±1.3 and 4.7±2.9ms, were recorded unilaterally in the III, and the INC/DN neurons, respectively. Spontaneous unit discharges were also recorded mostly in the INC/DN and less frequently in the III. Train stimulation could prompt either facilitation or inhibition on those spontaneous unit discharges. The inhibition pattern of train stimulation on the spontaneous discharging was rather different in the III and INC/DN. A slow inhibitory pattern in which spontaneous firing rate decreased further and further following repeated train stimulation was observed in the III. While, some high spontaneous firing rate units, responding promptly to the train stimuli with a short-term inhibition and recovered quickly when stimuli are off, were recorded in the INC/DN. However, orthodromic unit discharge was not recorded in the III and INC/DN in a considerable number of experiment animals. CONCLUSION: A residual neuronal circuit might exist in mammals for the primitive jaw-eyelid reflex observed in amphibians, which might not be well-developed in all experimental mammals in current study. Nonetheless, this pathway can be still considered as a neuroanatomic substrate for development of MGS in some cases among all MGS with different kind of etiology.

Abstract:AIM: To describe using spectral-domain optical coherence tomography the regeneration of the foveal morphology after pars plana (re)vitrectomy surgery and gas tamponade combined with injection of autologous platelet concentrate to treat full-thickness macular holes, and to describe different anatomical outcome. METHODS: A retrospective case series of 8 eyes of 8 patients was described. RESULTS: In all cases investigated, the platelet-assisted closure of macular holes was associated with a rapid resolution of cystic cavities in the foveal walls. In two patients, there was a regular regeneration of the foveal morphology after hole closure; the regenerated central fovea had a regular structure with a foveola and photoreceptors. In three other patients, there was an irregular regeneration of the fovea; a foveola was not formed, photoreceptor cells were absent from the foveal center, and the center was composed of Müller and retinal pigment epithelial (RPE) cells. The foveal regeneration after hole closure may proceed with or without a temporary detachment of the foveal center from the RPE, and with or without a direct contact between the central outer nuclear layer (ONL) and the RPE. Contacts between the ONL and RPE were observed only in patients with an irregular foveal regeneration after hole closure. CONCLUSION: The data show that there are different modes of foveal regeneration after closure of macular holes with (re)vitrectomy and platelet concentrate. It is suggested that the regular regeneration of the foveal morphology proceeds by Müller cell-mediated tissue movements without cell proliferation, whereas the irregular foveal regeneration proceeds in part by proliferation of Müller and RPE cells.

Abstract:AIM: To compare the short-term visual outcomes, residual refractive cylinder, and rotation stability after Tecnis toric intraocular lens (IOL) implantation during femtosecond laser-assisted cataract surgery (Femto phaco) and conventional phacoemulsification surgery (Conventional phaco). METHODS: In a prospective cohort study, Conventional phaco and Femto phaco (anterior capsulotomy and lens fragmentation by a femtosecond laser) with Tecnis toric IOL implantation were performed in 40 eyes from 36 patients and 37 eyes from 33 patients, respectively. The uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and manifest refraction were assessed during 1d, 1wk, and 1mo follow-ups. The orientation of the Tecnis Toric IOL was evaluated during 1wk and 1mo follow-ups. RESULTS: There were no significant differences in UDCA or CDVA between two groups at 1mo postoperatively, though relatively more subjects had UDVA values of 20/25 or better in Femto phaco group than in the Conventional group (P>0.05). A lower but not significantly lower rate of having more than 5° of IOL rotation was observed in Femto phaco group at the 1-month follow-up, while a significant lower rate of residual astigmatism of ≤1 D was observed in Femto phaco group. CONCLUSION: The Femto phaco group has significantly more subjects with the residual astigmatism of ≤1 D, but there are no significant differences in rotation stability and visual outcomes as compared with the Conventional phaco group after the application of the Tecnis toric IOL in this cohort.

Abstract:AIM: To provide statistical evidence for the use of antibiotics in ophthalmology by assessing the distribution and antibiotic sensitivity of bacterial isolates from ocular specimens with suspected microbial infections. METHODS: This study applied a retrospective analysis of 3690 bacterial isolates from ocular specimens, which were obtained from the conjunctiva, cornea, aqueous humor, vitreous body, and other ocular sites of the patients at Shandong Eye Institute in northern China from January 2013 to December 2017. The parameters assessed mainly included the distribution of isolated bacteria and the results of susceptibility tests for antibiotics. In the analysis of antibiotic sensitivities, the bacteria were divided into four groups according to gram staining, and statistical methods were used to compare their antibiotic sensitivities. RESULTS: Among the 3690 isolated bacterial strains, Staphylococcus epidermidis (2007, 54.39%) accounted for the highest proportion. As for the total isolates, their sensitivity rate to gatifloxacin was up to 90.01%, with four types of gram-stained bacteria being all highly sensitive to it, but their sensitivity rate to levofloxacin was only 51.91%. The sensitivity rate of gram-negative bacilli (G-B) to levofloxacin was 83.66%, significantly higher than the other three types of gram-stained bacteria (P<0.05). Gram-positive cocci (G+C, 97.95%) and gram-positive bacilli (G+B, 97.54%) were more sensitive to vancomycin than gram-negative cocci (G-C, 70.59%) and G-B (68.57%; P<0.05). For fusidic acid, the sensitivity rates of G+C (89.83%) and G+B (73.37%) were significantly higher than that of G-B (29.83%; P<0.05). The gram-negative bacteria’s sensitivity rate to cefuroxime was as low as 59.25%, but only G-B was less sensitive to cefuroxime (57.28%), while G-C was still highly sensitive (89.29%). The sensitivity rate of gram-positive bacteria to moxifloxacin was as high as 80.28%, but only G+C was highly sensitive to moxifloxacin (81.21%), while G+B was still less sensitive (32.00%). CONCLUSION: Staphylococcus epidermidis is the predominant isolate in all ocular specimens with bacteria. Gatifloxacin is more suitable for topical prophylactic use than levofloxacin in ophthalmology when necessary. Vancomycin and fusidic acid both have better effects on gram-positive bacteria than gram-negative bacteria. More accurate antibiotic sensitivity analysis results can be obtained when a more detailed bacterial classification and more appropriate statistical methods are performed.

Abstract:AIM: To evaluate the accuracy of three commonly used biometric formulae across different axial lengths (ALs) at one United States Veterans Affairs teaching hospital. METHODS: A retrospective chart review was conducted from November 2013 to May 2018. One eye of each patient who underwent cataract surgery with a monofocal intraocular lens (IOL) was included. The range of postoperative follow-up period was from 3wk to 4mo. The Holladay 2, Barrett Universal II, and Hill-Radial Basis Function (Hill-RBF) formulae were used to predict the postoperative refraction for all cataract surgeries. For each formula, we calculated the prediction errors [including mean absolute prediction error (MAE)] and the percentage of eyes within ±0.25 diopter (D) and ±0.5 D of predicted refraction. We performed subgroup analyses for short (AL<22.0 mm), medium (AL 22.0-25.0 mm), and long eyes (AL>25.0 mm). RESULTS: A total of 1131 patients were screened, and 909 met the inclusion criteria. Resident ophthalmologists were the primary surgeons in 710 (78.1%) cases. We found no statistically significant difference in predictive accuracy among the three formulae over the entire AL range or in the short, medium, and long eye subgroups. Across the entire AL range, the Hill-RBF formula resulted in the lowest MAE (0.384 D) and the highest percentage of eyes with postoperative refraction within ±0.25 D (42.7%) and ±0.5 D (75.5%) of predicted. All three formulae had the highest MAEs (>0.5 D) and lowest percentage within ±0.5 D of predicted refraction (<55%) in short eyes. CONCLUSION: In cataract surgery patients at our teaching hospital, three commonly used biometric formulae demonstrate similar refractive accuracy across all ALs. Short eyes pose the greatest challenge to predicting postoperative refractive error.

Abstract:AIM: To evaluate functional outcome of sutureless scleral tunnel intraocular lens (SSTIOL) in children with crystalline lens subluxation of more than 7 clock hours. METHODS: A prospective interventional study was conducted consisting of 45 eyes of 44 children in age group 6-18y having >7 clock hours of lens subluxation who underwent lensectomy-vitrectomy followed by SSTIOL implantation. Primary outcome was improvement in best corrected visual acuity (BCVA) and secondary outcomes were assessment of intraocular lens (IOL) tilt using ultrasound biomicroscopy (UBM), mean change in astigmatism at last follow-up of 1y and associated complications. RESULTS: The mean preoperative and postoperative BCVA was 1.05±0.28 and 0.64±0.45 (logMAR) respectively (P=0.001) at last follow-up. The mean astigmatism preoperatively and postoperatively was -4.17±2.69 D and -1.86±1.25 D respectively (P=0.011). Significant IOL tilt (>5 degrees) was present in 5 cases. The mean percentage endothelial loss was 3.65%±1.92%. The most serious complication encountered was retinal detachment seen in 2 cases. CONCLUSION: SSTIOL implantation provides efficient visual rehabilitation in children provided there is stringent case selection. We recommend caution in children having white-to-white distance >12 mm and presence of peripheral retinal degenerations.

Abstract:AIM: To evaluate the patterns of macular ganglion cell-inner plexiform layer (GCIPL) loss in normal tension glaucoma (NTG) and primary open angle glaucoma (POAG) in a detailed, disease severity-matched way; and to assess the diagnostic capabilities of GCIPL thickness parameters in discriminating NTG or POAG from normal subjects. METHODS: A total of 157 eyes of 157 subjects, including 57 normal eyes, 51 eyes with POAG and 49 eyes with NTG were enrolled and strictly matched in age, refraction, and disease severity between POAG and NTG groups. The average, minimum, superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal GCIPL thickness, and the average, superior, temporal, inferior, and nasal retinal nerve fiber layer (RNFL) thickness were obtained by Cirrus optical coherence tomography (OCT). The diagnostic capabilities of OCT parameters were assessed by area under receiver operating characteristic (AUROC) curves. RESULTS: Among all the OCT thickness parameters, no statistical significant difference between NTG group and POAG group was found (all P>0.05). In discriminating NTG or POAG from normal subjects, the average and inferior RNFL thickness, and the minimum GCIPL thickness had better diagnostic capabilities. There was no significant difference in AUROC curve between the best GCIPL thickness parameter (minimum GCIPL) and the best RNFL thickness parameter in discriminating NTG (inferior RNFL; P=0.076) and indiscriminating POAG (average RNFL; P=0.913) from normal eyes. CONCLUSION: Localized GCIPL loss, especially in the inferior and inferotemporal sectors, is more common in NTG than in POAG. Among all the GCIPL thickness parameters, the minimum GCIPL thickness has the best diagnostic performance in differentiating NTG or POAG from normal subjects, which is comparable to that of the average and inferior RNFL thickness.

Abstract:AIM: To assess the effect of lens status on sustained intraocular pressure (IOP) elevation in patients treated intravitreally with anti-vascular endothelial growth factor (VEGF) agents. METHODS: Data were retrospectively collected for all patients treated with intravitreal injections of anti-VEGF medication at a tertiary medical center in July 2015. Findings were analyzed by lens status during 6 months’ follow-up. The main outcome measure was a sustained increase in IOP (≥21 mm Hg or change of ≥6 mm Hg from baseline on ≥2 consecutive visits, or addition of a new IOP-lowering medication during follow-up). RESULTS: A total of 119 eyes of 100 patients met the study criteria: 40 phakic, 40 pseudophakic, and 39 pseudophakic after Nd:YAG capsulotomy. The rate of sustained IOP elevation was significantly higher in the post-capsulotomy group (23.1%) than in the phakic/pseudophakic groups (8.1%; P=0.032), with no statistically significant differences among the 3 groups in mean number of injections, either total (P=0.82) or by type of anti-VEGF mediation (bevacizumab: P=0.19; ranibizumab: P=0.13), or mean follow-up time (P=0.70). CONCLUSION: Nd:YAG capsulotomy appears to be a risk factor for sustained IOP elevation in patients receiving intravitreal anti-VEGF injections. This finding has important implications given the growing use of anti-VEGF treatment and the irreversible effects of elevated IOP.

Abstract:AIM: To study antibiotic resistance patterns and susceptibility to eye antiseptic picloxydine of conjunctival flora in patients undergoing intravitreal injections (IVIs). METHODS: Conjunctival swabs were taken in 4 groups of patients, 20 patients in each group (n=80): without IVIs and ophthalmic operations in history (group N1; control group); with the first IVI and antibiotic eye drops Tobrex applied 3d before IVI and 5d after it (group N2); with 20 or more IVIs and repeated courses of antibiotic eye drops (group N3); with the first IVI and antiseptic eye drops Vitabact (picloxydine) applied 3d before IVI and 5d after it (group N4). In groups N2 and N4 swabs were taken at baseline and after the treatment. Efficacy of picloxydine in inhibition of growth of conjunctival isolates susceptible and resistant to antibiotic was studied in vitro. Minimal inhibition concentrations (MIC) were determined with microdilution test. RESULTS: Two of the three patients who had to undergo the IVI procedure showed conjunctiva bacterial contamination. Along with few Staphylococcus aureus and Gram-negative isolates susceptible to most antibiotics, the majority (71%-77%) of causative agents were coagulase-negative Staphylococci (CoNS), 40%-50% of which were multidrug resistant (MDR). Eye disinfection in the operating room and peri-injection courses of Tobrex or Vitabact resulted in total elimination of isolates found at baseline. However, in 10% and 20% of patients, respectively, recolonization of the conjunctiva with differing strains occurred. In patients with repeated IVI and Tobrex/Maxitrol treatment, the conjunctival flora showed high resistance rates: 90% of CoNS were MDR. In the in vitro study, picloxydine showed bactericidal effect against Staphylococci isolates both antibiotic resistant and susceptible with MIC≥13.56 μg/mL. Incubation of bacteria for 15min in Vitabact eye drops, commercially available form of picloxydine, 434 μg/mL, showed total loss of colony forming units of all tested isolates including Pseudomonas aeruginosa. CONCLUSION: The confirmed efficacy of eye antiseptic picloxydine against conjunctival bacterial isolates and the presence of its commercial form, 0.05% eye drops, convenient for use by patients before and after injection, make this eye antiseptic promising for prophylaxis of IVI-associated infectious complications.

Abstract:AIM: To compare the qualitative and quantitative features among untreated polypoidal choroidal vasculopathy (PCV), neovascular age-related macular degeneration (nv-AMD) and central serous chorioretinopathy (CSC) using optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: This retrospective study included 16 eyes with thin-choroid PCV, 18 eyes with thick-choroid PCV, 16 eyes with nv-AMD and 17 eyes with CSC, respectively. The indicators were obtained by OCT and OCTA. RESULTS: Sub-foveal choroidal thickness (SFCT) in CSC was thicker compared to other groups (all P<0.05). SFCT in nv-AMD was thicker compared to thin-choroid PCV, but thinner compared with thick-choroid PCV (both P<0.05). As the ratio of thickness of Haller’s layer to thickness of SFCT, which of thin-choroid PCV was significantly higher than CSC (P<0.001). Likewise, thick-choroid PCV had significantly higher ratio than nv-AMD (P=0.016) or CSC (P<0.001). There were differences among them in pigment epithelium detachment (PED). The whole-superficial retinal vessel density (RVD), deep RVD and choroidal capillary vessel density (CCVD) in CSC were significantly higher compared to other three groups, respectively (all P<0.05). The whole CCVD in nv-AMD was higher compared to thick-choroid PCV (P=0.032). Cross-sectional local angiographic form was 87.50%, 83.33%, 0 and 35.29% in thin-choroid PCV, thick-choroid PCV, nv-AMD and CSC, respectively. Cross-sectional diffuse angiographic form was 12.50%, 16.67%, 100% and 5.88% in thin-choroid PCV, thick-choroid PCV, nv-AMD and CSC, respectively. CONCLUSION: Combination of OCT and OCTA can effectively observe the significant alterations existed in PCV, CSC and nv-AMD, and there are distinctive differences among them. The pathogenesis is not exactly the same between PCV and nv-AMD, or PCV and CSC.

Abstract:AIM: To compare two different anti-vascular endothelial growth factor (anti-VEGF) treatment regimens’-a priori pro re nata (PRN) and PRN regimen following the loading phase-anatomical and functional results in neovascular age-related macular degeneration (nAMD) patients. METHODS: Totally 544 nAMD patients followed and treated with aflibercept (n=135) and ranibizumab (n=409) at 9 different centers between 2013 and 2015 were enrolled into this retrospective multicenter study. Patients with initial best corrected visual acuity (BCVA) interval of 1.3-0.3 (logMAR) and a minimum follow-up of 12mo were included. Patients under two different regimens-a priori pro re nata (1+PRN) or 3 consecutive intravitreal injections followed by a PRN regimen (3+PRN)-were compared in BCVA at 3th, 6th and 12th months, and in central macular thickness (CMT) at 6th and 12th months. The total study group, intravitreal ranibizumab (IVR) and intravitreal aflibercept (IVA) groups were evaluated separately. RESULTS: The mean CMT decreased in the 1+PRN (n=101) regimen from 407 to 358 and 340 μm and in the 3+PRN (n=443) group from 398 to 318 and finally to 310 μm at months 6 and 12, respectively. Anatomically, the CMT reduction at 6th month (48.5 vs 76.4; P<0.05) was statistically significant in favor of 3+PRN group. BCVA changed in 1+PRN group from 0.77 to 0.78, 0.75 and 0.75; in 3+PRN group from 0.81 to 0.69, 0.72, and 0.76 at months 3, 6, and 12, respectively. Visual gain was statistically better in 3+PRN group at 3th month (-0.01 vs 0.12; P<0.001). In IVR group, CMT reduction was in greater in 3+PRN at 6th (44 vs 72) and 12th month (61 vs 84), but statistically insignificant. The 3+PRN group revealed statistically better visual results at 3th month (-0.02 vs 0.11, P<0.05). In IVA group, although statistically insignificant, CMT reduction (61 vs 89, 6th month; 85 vs 97, 12th month) and visual gain (0.02 vs 0.16; 0.02 vs 0.14; 0.05 vs 0.11) was found in favor of 3+PRN group at all visits. CONCLUSION: The loading dose of anti-VEGF treatments in nAMD leads to significantly better anatomical and functional results, regardless of the agent, specially in early follow-up interval.

Abstract:AIM: To describe the clinical features and multimodal images of unilateral foveomacular retinitis in young Korean soldiers. METHODS: Ten patients having foveomacular retinitis were included. Fluorescein angiography, fundus autofluorescence (FAF), infrared reflectance (IR), and spectral-domain optical coherence tomography (SD-OCT) were analyzed. RESULTS: All patients were young males experienced insidious visual decline without exposure to bright light. Initial and final vision ranged from hand movement to 20/20 (median 20/200) and 20/2000 to 20/20 (median 20/500), respectively. Vision decreased in 6 patients while improved in two. Typical macular abnormality was yellow granular spots. SD-OCT showed ellipsoid zone (EZ) or interdigitation zone (IZ) disruption of fovea. The degree of EZ/IZ damage correlated with vision. Lesions were clearly visualized through IR and matched with SD-OCT findings. CONCLUSION: This is the first case series of foveomacular retinitis diagnosed with multimodal imaging. Foveomacular retinitis should be suspected in sudden unilateral visual decline especially in young soldiers. SD-OCT is the most important diagnostic modality.

Abstract:AIM: To elucidate the changes of different ganglion cell layer (GCL) thinning patterns between the optic neuritis (ON) and non-arteritic anterior ischemic optic neuropathy (NAION). METHODS: A prospective, observational study was conducted to evaluate the timing of GCL changes between acute ON and NAION using optical coherence tomography. RESULTS: Thinning on optical coherence tomography in the NAION group occurs as early as 11d after symptomatic onset of vision loss and follows an altitudinal pattern. The mean superior-inferior GCL thickness difference in the NAION cohort was clinically significant at 5.7 μm in the NAION cohort compared to controls of 0.8 μm (P=0.032), but not significant in the ON group compared to controls with both groups measuring 1.1 μm. Global thinning was significant for the ON group compared to controls at 7.2 μm (P=0.011) but not the NAION group compared to controls at 1.35 μm. CONCLUSION: These findings suggest that future treatments for NAION should be given early, and possibly before 11d in order to prevent GCL and irreversible vision loss.

Abstract:AIM: To investigate the efficacy and safety of the treatment of endoscopic trans-ethmosphenoid optic canal decompression (ETOCD) with combination of steroid in patients with newly onset indirect traumatic optic neuropathy (ITON) and compare the outcome between immediate ETOCD treatment and ETOCD with preoperative steroid treatment. METHODS: Patients presented as newly onset ITON (suffered trauma within 3d) at a tertiary medical center between Mar 1st, 2016 and Mar 1st, 2018 were enrolled in this study. All patients were equally and randomly divided into 2 groups. Cases in group A were performed ETOCD immediately after admition while cases in group B were prescribed by methylprednisolone (20 mg/kg · d) for 3d before ETOCD. Methylprednisolone (20 mg/kg · d) was used after surgery for 6d in group A and 3d in group B. Follow-up was up to 3mo in all cases. Visual acuity (VA) before and after treatment between the two groups were taken into comparison. RESULTS: Complete postoperative data were acquired from 34 patients in group A and from 32 patients in group B. Group A had significantly higher effective rate in VA than group B (χ2 =4.905, P=0.027). CONCLUSION: For patients with newly onset ITON, combination treatment of ETOCD with high-dose steroid is an effective and safe way. Immediate surgery will lead to better prognosis for these cases.

Abstract:AIM: To evaluate the safety and efficacy of transepithelial photorefractive keratectomy (t-PRK) with adjuvant mitomycin C (MMC) versus femtosecond laser assisted keratomileusis (Femto-LASIK) in correction of high myopia. METHODS: Prospective randomized comparative study including 156 eyes of 156 patients with high myopia and a spherical equivalent refraction (SER) <-6.00 D. They were divided randomly into two groups: Group A included 72 eyes treated with t-PRK with adjuvant MMC and Group B included 84 eyes treated with Femto-LASIK. Visual acuity, SER, corneal topography, pachymetry and keratometry were assessed for 12mo postoperatively. RESULTS: The preoperative mean SER was -8.86±1.81 and -9.25±1.70 D in t-PRK MMC group and Femto-LASIK respectively (P=0.99) which improved to -0.65±0.43 D and -0.69±0.50 D at 12mo follow up. Mean SER remained stable during the 12mo of follow-up, with no statistically significant difference between the two groups (P=0.64). In t-PRK MMC group, only six eyes needed retreatment after six months of follow up. And two eyes showed haze (one reversible haze grade 2, while the other had dense irreversible haze grade 4). CONCLUSION: t-PRK MMC provides safe and satisfactory visual outcomes and acceptable risk as Femto-LASIK in patients with high myopia.

Abstract:AIM: To measure the depths of different regions of the anterior chamber (AC) in healthy Chinese adults, and to explore possible correlations with age or gender. METHODS: The AC was imaged by swept-source optical coherence tomography in healthy Chinese adults. The horizontal scan of the right eye was used to measure the anterior chamber depth (ACD) at 199 points. RESULTS: A total of 309 images from 309 subjects were analyzed. The ACD values at nearly all locations were negatively correlated with age (all P<0.05), except for ACD1, 2, 198, and 199 (correspond to the iris roots). The mean annual decrease 0.013±0.005 mm/y for all ACDs combined, 0.008±0.004 mm/y for the peripheral region, 0.017±0.003 mm/y for the middle peripheral region, and 0.014±0.001 mm/y for the central region. The mean annual decrease was significantly different among these three regions (P<0.001). The ACD was greater in males than in females (P<0.05). The mean difference in ACD between males and females was 0.081±0.025 mm. CONCLUSION: This study showed that optical coherence tomography can be used to measure the ACD of different regions of the AC. We found reductions in ACD with age, although the reduction varied among different points, in healthy Chinese adults.

Abstract:AIM: To compare the anatomic and functional outcomes between vitrectomy with internal limiting membrane (ILM) peeling and internal ILM flap insertion technique for high myopia macular hole (MH). METHODS: PubMed, Cochrane Library, EMBASE, and CNKI were systematically searched, and all studies involved MH were included. The closure rate of MH and the postoperative best-corrected visual acuity (BCVA) at 6mo after the initial surgery were the primary measures. All statistical tests were performed in Review Manager 5.3. RESULTS: Five studies that included 151 eyes of 151 patients were finally included, all of which were retrospectively comparative studies. Between the pars plana vitrectomy (PPV) with ILM peeling surgery and the ILM insertion technique, the latter had significantly better efficacy with respect to the closure rate of MH (OR=21.32, 95%CI=7.25-62.67, P<0.001); However, regarding BCVA at 6mo after the initial surgery in MH, there was no statistical significance between the groups (OR=-0.04, 95%CI=-0.22-0.14, P=0.66). In addition, regarding the rate of retinal reattachment after the initial surgery, the two different methods were not significantly different (OR=2.22, 95%CI=0.34-14.32, P=0.4). CONCLUSION: Both ILM peeling and ILM insertion technique could significantly improve anatomic outcomes of MH in high myopia with or without retinal detachment (RD), and anatomic outcomes are more effective. However, there is no statistical significance in BCVA at 6mo after the initial surgery in MH, or in the rate of retinal reattachment after the first surgery, between the two methods.

Abstract:AIM: To compare the effectiveness of two well described machine learning modalities, ocular coherence tomography (OCT) and fundal photography, in terms of diagnostic accuracy in the screening and diagnosis of glaucoma. METHODS: A systematic search of Embase and PubMed databases was undertaken up to 1st of February 2019. Articles were identified alongside their reference lists and relevant studies were aggregated. A Meta-analysis of diagnostic accuracy in terms of area under the receiver operating curve (AUROC) was performed. For the studies which did not report an AUROC, reported sensitivity and specificity values were combined to create a summary ROC curve which was included in the Meta-analysis. RESULTS: A total of 23 studies were deemed suitable for inclusion in the Meta-analysis. This included 10 papers from the OCT cohort and 13 from the fundal photos cohort. Random effects Meta-analysis gave a pooled AUROC of 0.957 (95%CI=0.917 to 0.997) for fundal photos and 0.923 (95%CI=0.889 to 0.957) for the OCT cohort. The slightly higher accuracy of fundal photos methods is likely attributable to the much larger database of images used to train the models (59 788 vs 1743). CONCLUSION: No demonstrable difference is shown between the diagnostic accuracy of the two modalities. The ease of access and lower cost associated with fundal photo acquisition make that the more appealing option in terms of screening on a global scale, however further studies need to be undertaken, owing largely to the poor study quality associated with the fundal photography cohort.

Abstract:Scleritis and other autoimmune diseases are characterized by an imbalance in the levels of pro-inflammatory and anti-inflammatory molecules with the balance tilted more towards the former due to the failure of recognition of self. The triggering of inflammatory process could be ascribed to the presence of cytoplasmic DNA/chromatin that leads to activation of cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway and enhanced expression of NF-κB that results in an increase in the production of pro-inflammatory bioactive lipids. Bioactive lipids gamma-linolenic acid (GLA), dihomo-GLA (DGLA), prostaglandin E1 (PGE1), prostacyclin (PGI2) and lipoxin A4, resolvins, protectins and maresins have anti-inflammatory actions, bind to DNA to render it non-antigenic and are decreased in autoimmune diseases. These results suggest that efforts designed to enhance the production of anti-inflammatory bioactive lipids may form a new approach to autoimmune diseases. Local injection or infusion of lipoxins, resolvins, protectins and maresins or their precursors such as arachidonic acid may be exploited in the prevention and management of autoimmune diseases including scleritis, uveitis and lupus/rheumatoid arthritis.

Abstract:AIM: To unravel the primary open angle glaucoma (POAG) related proteomic changes in aqueous humour (AH). METHODS: Totally 35 patients listed for cataract surgery (controls: n=12, age: 67.4±13.6y) or trabeculectomy for POAG (n=23, age: 72.5±8.3y) were included. AH samples of those patients were obtained during cataract surgery or trabeculectomy. AH samples were subsequently pooled into the experimental groups under equal contribution in terms of protein amount of each individual patient. Protein samples were analyzed by a linear trap quadrupol Orbitrap Mass Spectrometry device with an upstream liquid chromatography system. The obtained raw data were analyzed using the Maxquant proteome software and compared. Proteins with a fold-change ratio higher than a cut-off of 2 were considered as noticeably altered. RESULTS: A total number of 175 proteins could be identified out of the AH from POAG and cataract by means of quantitative mass spectrometric analysis. Apolipoprotein D (fold change, 3.16 times), complement C3 (2.96), pigment epithelium-derived factor (2.86), dickkopf-related protein 3 (2.18) and wingless-related integration (Wnt) inhibitory factor 1 (2.35) were significantly upregulated within the AH of glaucoma compared to cataract serving as controls. CONCLUSION: AH provides a tool to analyze changes in glaucoma and shows striking changes in Wnt signaling inhibitory molecules and other proteins.

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