Abstract:AIM: To investigate the relationships between the changes of heat shock protein 27 antibody (anti-HSP27) in serum/cerebrospinal fluid (CSF), intraocular pressure (IOP), retinal ganglion cell (RGC) apoptosis in a rat glaucoma model and disclose the underlying pathogenesis of glaucoma. METHODS: A total of 115 Wistar rats were randomly divided into 4 groups. Group 1 was the ocular hypertension group by condensing 3 episcleral & limbal veins or episcleral area of right eye (HP group, n=25) and sham operation group with conjunctiva incision without coagulation (n=25). Group 2: HSP27 or dose-matched PBS was injected into the vitreous (V-HSP27 group, n=15; V-PBS group, n=15). Group 3: HSP27 and complete Freund’s adjuvant or dose-matched PBS was injected subcutaneously into the hind limb accompanied intraperitoneal injection of pertussis toxin [sensitized group (I-HSP27 group), n=15; I-PBS group, n=15)]. Group 4 was normal group without any treatment (n=5). IOPs of the rats were measured before, day 3, weeks 1, 2, 4, 6, and 8 after treatment. Paraffin-embedded sections were prepared for HE staining and RGCs apoptosis were detected by TUNEL. Anti-HSP27 level in serum and CSF were examined by ELISA. RESULTS: IOPs were elevated significantly in HP and V-HSP27, V-PBS groups (P<0.01) and positively related to anti-HSP27 levels in serum and CSFs. Anti-HSP27 levels in serum and CSF were elevated significantly in I-HSP27 group compared to other groups (P<0.05). However, the IOPs did not show any relationship with the high-level anti-HSP27 in serum and CSFs. RGC apoptosis were all elevated significantly in the HP, V-HSP27, V-PBS and I-HSP27 groups and also positively relative with anti-HSP27 level in serum and CSFs except that high-level of anti-HSP27 in the serum of I-HSP group. CONCLUSION: The increases of anti-HSP27 levels in serum and CSFs both promote IOP escalation and the increase of RGC apoptosis in retina when anti-HSP27 is at low level. The case of high-level anti-HSP27 is opposite and shows protective function in preventing IOP increase and RGC apoptosis.

Abstract:AIM: To explore the mRNA and pathways related to retinoblastoma (RB) genesis and development. METHODS: Microarray datasets GSE29683 (human) and GSE29685 (mouse) were downloaded from NCBI GEO database. Homologous genes between the two species were identified using WGCNA, followed by protein-protein interaction (PPI) network construction and gene enrichment analysis. Disease-related miRNAs and pathways were retrieved from miR2Disease database and Comparative Toxicogenomics Database (CTD), respectively. RESULTS: A total of 352 homologous genes were identified. Two pathways including “cell cycle” and “pathway in cancer” in CTD and enrichment analysis were identified and seven miRNAs (including hsa-miR-373, hsa-miR-34a, hsa-miR-129, hsa-miR-494, hsa-miR-503, hsa-let-7 and hsa-miR-518c) were associated with RB. miRNAs modulate “cell cycle” and “pathway in cancer” pathways via regulating 13 genes (including CCND1, CDC25C, E2F2, CDKN2D and TGFB2). CONCLUSION: These results suggest that these miRNAs play crucial roles in RB genesis through “cell cycle” and “pathway in cancer” pathways by regulating their targets including CCND1, CDC25C, E2F2 and CDKN2D.

Abstract:AIM: To investigate the role of moesin and its underlying signal transduction in retinal vascular damage induced by retinal ischemia-reperfusion (RIR) insult. METHODS: C57BL/6 mice were subjected to continued ischemia for 45min, followed by blood reperfusion. The expression and phosphorylation of moesin in retinal vessels were detected by immunohistochemistry and Western blotting. The inner blood-retinal barrier was evaluated using FITC-dextran leakage assay on whole-mount retina. Further studies were conducted to explore the effects of p38 mitogen-activated protein kinase (MAPK) pathway on the involvement of moesin in RIR-evoked retinal vascular hyperpermeability response. RESULTS: It revealed that RIR induced moesin phosphorylation in a time-dependent manner after reperfusion. The phosphorylation of moesin was alleviated by inhibitions of p38 MAPK, while this treatment also ameliorated the dysfunction of inner blood-retinal barrier. CONCLUSION: The results suggest that moesin is involved in RIR-evoked retinal vascular endothelial dysfunction and the phosphorylation of moesin is triggered via p38 MAPK activation.

Abstract:AIM: To test our hypothesis that activation of protein kinase A (PKA) signal pathway by β-adrenergic agonist plays an important role in the protecting of cultured retinal pigment epithelial (RPE) cells against the hydroxychloroquine (HCQ) toxicity. METHODS: Cultured human RPE cells were treated with 1) HCQ, 2) HCQ with salbutamol (a β2-adrenergic receptor agonist), and 3) HCQ with salbutamol and a PKA inhibitor, and compared these to 4) untreated cells (controls). After treated for 24h, cell vacuolation, cells viability, PKA and PKA kinase activity levels were determined by the measurement of the size of vacuoles using Image J software, the cell counting with a dye-exclusion testing, Western blot and PKA kinase detection, respectively. RESULTS: Cell vacuolation and cell death of cultured RPE cells were significantly increased by the treatment of HCQ. Salbutamol significantly elevated PKA and PKA activity levels and this was associated with the inhibition of the vacuolation and cell death. The PKA inhibitor significantly decreased the PKA levels and eliminated the protective effects of salbutamol on HCQ-treated RPE cells. CONCLUSION: The PKA pathway plays an important role in the protective effects of β2-adrenergic agonist on the RPE cells against HCQ toxicity. These findings reveal a novel potential strategy against HCQ retinopathy by treatment with PKA activating medications.

Abstract:AIM: To compare the Barrett True-K formula with other formulas integrated in Lenstar 900 to predict intraocular lens (IOL) power after small-incision lenticule extraction (SMILE). METHODS: A theoretical prospective study was performed to predict the ratio of equivalent IOL power before and after SMILE using the SRK/T (Sanders, Retzlaff, Kraff/theoretical), Holladay 1, Haigis, and Barrett True-K formulas and compare the stability of their predictions. The study included 54 eyes (54 cases) with a manifest refraction spherical equivalent (MRSE) of -4.99±1.45 D. They were divided into two groups: 27 eyes with axial length of 24-26 mm in Group A, and 27 eyes with axial length >26 mm in Group B. All subjects enrolled in this study were examined with the Lenstar 900 before and 6mo after SMILE including measurements of axial length, corneal curvature, and anterior chamber depth (ACD). RESULTS: The prediction of equivalent IOL power of the two groups was more stable for the Barrett True-K formula, especially in long axial length eyes (Group B). The respective percentages for the SRK/T, Holladay 1, Haigis, and Barrett True-K formulas were 7.4%, 7.4%, 85.19%, and 88.89% for a margin of error within 0.5 D; 25.92%, 51.84%, 100%, and 100% for a margin of error within 1.0 D in Group A; 33.33%, 40.74%, 44.44%, and 81.48% for a margin of error within 0.5 D; and 44.44%, 59.26%, 66.66%, and 92.59% for a margin of error within 1.0 D in Group B. The respective percentages for Barrett True-K formulas were 100% for a margin of error within 2.0 D in Group B. CONCLUSION: Theoretically, the Barrett True-K formula provides more stable predictions than other formulas for cataract eyes after SMILE.

Abstract:AIM: To compare long-term postoperative outcomes of manual and femtosecond assisted corneal trephination in deep anterior lamellar keratoplasty (FS-DALK) for keratoconus. METHODS: In the retrospective study, 17 consecutive eyes that underwent vertical side cut incision FS-DALK and 22 eyes that underwent trephine incision DALK were collected over a 2-year period. Main measurements included postoperative uncorrected-visual acuity (UCVA), corrected distance visual acuity (CDVA), refractive sphere and cylinder, manifest refraction spherical equivalent (MRSE), flat and steep corneal keratometry (K1 and K2), endothelial cell density (ECD), and time of epithelium healing and suture removal. RESULTS: Groups were comparable for diagnosis and preoperative visual acuity. Follow-up averaged 23mo (range, 12-36mo). At 12mo, the mean UCVA was better in the manual-DALK group (P=0.039), and the refractive sphere was lower in the FS-DALK group (P=0.040). MRSE between groups differed at 1, 6, and 12mo postoperatively (P=0.047, 0.025, 0.042, respectively). Mean CDVA, cylinder, K1, K2, corneal astigmatism, ECD, and time of epithelium healing were similar between groups. Stability of MRSE, ECD, and K1 returned sooner after FS-DALK. Initial loosened suture removal time was earlier in the manual-DALK group (P=0.042) while complete suture removal time was similar (P=0.122). CONCLUSION: Manual and femtosecond assisted corneal trephination in DALK are options for advanced keratoconus. FS-DALK do not result in improved visual acuity but it is more stable during the follow-up period. FS-DALK in the present form show limited benefit, so surgical design and parameters still need to be optimized and explored.

Abstract:AIM: To assess the effect of photoactivated chromophore for keratitis crosslinking (PACK-CXL) in case of severe keratitis with melting on the electrophysiological function of the retina and the optic nerve. METHODS: The study included 32 eyes of 32 patients with smear positive severe infectious keratitis with corneal melting. The patients were randomly divided into two groups. Group I (control group) included 16 eyes received systemic and topical antimicrobial drugs guarded by culture and sensitivity test. Group II underwent CXL and then continued their antimicrobial treatment. Full field electroretinogram (ERG) and flash visual evoked potential (VEP) were done for each patient in both groups basically and then 1wk, 1 and 3mo post-treatment to assess the changes in the electrophysiological function of the retina and optic nerve. RESULTS: Healing of 10 eyes in group I in comparison to 14 eyes in group II was recorded. The mean duration of healing was 36.56±5.21d in group I vs 20.2±4.4d in group II (P<0.005). In group II, ERG showed an insignificant reduction of all parameters of ERG and VEP after CXL. The amplitude of scotopic rod response, oscillatory potential amplitude, flicker amplitude and photopic cone response were insignificantly decreased (P=0.4, 0.8, 0.1, and 0.3 respectively). There were insignificant prolongation of latencies of scotopic rod, oscillatory potential, flicker and photopic cone response (P=0.2, 0.7, 0.5 and 0.1). There was slight delay in latency of VEP without a significant reduction in amplitude. CONCLUSION: CXL is an effective technique in treatment of severe infectious keratitis with melting as it halts the melting process with acceptable safety on the retinal and optic nerve function.

Abstract:AIM: To investigate the effects of intraocular lens (IOL) implantation on visual field (VF) in patients with glaucoma and comorbid cataracts (G&C) with different disease severities. METHODS: Totally 56 eyes of 50 patients with primary G&C were included. All patients were divided into three groups based on the severity of the VF defect: the mild, moderate, and severe stage. Phacoemulsification was performed for cataract removal combined with IOL implantation. Visual acuity (VA) and VF tests were performed for all enrolled patients, up to 3mo after surgery. Changes in VF threshold and global VF index in various groups were also recorded before and after surgery. The mean light sensitivity (MS) values and the changes following surgery (DMS) were compared between the three groups. Advanced Glaucoma Intervention Study (AGIS) scoring was analyzed on all VF results for analysis of changes in VF before and after surgery. RESULTS: Following surgery, the MS values of the three groups of G&C increased significantly, while the AGIS scores decreased statistically in all groups. The DMS values for the three zones in moderate and severe stage but not mild stage were statistically different between zones. The DMS value was significantly higher in zone I than those in zone II and III (zone I>zone II>zone III; P<0.05). The DMS was significantly higher in zone I than that in zone III in moderate stage patients (zone I>zone II>zone III; P<0.01), while the DMS values in the severe stage patients was significantly higher in zone I than those in zone II and III (zone I>zone II>zone III; P<0.01). CONCLUSION: The mean VF sensitivity of glaucoma patients increased significantly after cataract removal and IOL implantation. Variations in the severity and distribution of characteristics of VF defects result in differences in postoperative VF improvements after cataract surgery. The magnitude of increase in VF sensitivity is associated with VF defect characteristic in glaucoma.

Abstract:AIM: To investigate the effect of capsular tension ring (CTR) implantation on predicted refractive error after cataract surgery in patients with pseudoexfoliation (PEX) syndrome. METHODS: This double-blind randomized clinical trial was conducted on 60 patients with PEX syndrome referring to Imam Khomeini Hospital affiliated to Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran, for undergoing cataract surgery. The study population was divided into two groups, namely CTR group (n=30) and non-CTR group (control group; n=30). The refractive error and anterior chamber depth (ACD) were measured 1wk, 1mo, and 3mo after phacoemulsification (PE) surgery. RESULTS: The results indicated no statistically significant difference between the two groups in terms of predicted refractive error (obtained by subtracting preoperative predicted refractive error from actual postoperative refractive error) 1wk (P=0.47), 1mo (P=0.30), and 3mo (P=0.06) after the PE surgery. Regarding the CTR group, the changes of ACD was statistically significant 1 and 3mo after the PE surgery, compared to those obtained 1wk post-surgery (P=0.005). CONCLUSION: The CTR implantation in PEX cataractous patients without zonulysis has no statistically significant effect on the predicted refraction and ACD changes after PE. The predicted refraction error has a hyperopic shift in both groups. The results reveal the unnecessary of calculating modified IOL in CTR implantation.

Abstract:AIM: To assess the changes in the anterior chamber parameters using Pentacam following four different lines of treatment of primary angle-closure glaucoma (PACG). METHODS: A retrospective comparative study included 126 patients (126 eye) presented within 24-48h after acute angle-closure glaucoma (AACG). Patients were divided into 2 groups: group A (68 eyes) with controlled intraocular pressure (IOP) ≤21 mm Hg, which included subgroup A1 (34 eyes) with clear lens underwent Nd:YAG laser peripheral iridotomy (LPI) and subgroup A2 (34 eyes) with cataract underwent standard phacoemulsification; and group B (58 eyes) with uncontrolled IOP, which included subgroup B1 (30 eyes) with clear lens underwent trabeculectomy and subgroup B2 (28 eyes) with cataract underwent combined phacoemulsification and trabeculectomy. Patients were followed up for at least 3mo. Primary outcomes were Pentacam anterior segment measurements [anterior chamber angle (ACA) and depth (ACD)]. Secondary outcomes were changes in IOP, visual acuity (VA) and recorded complications. RESULTS: At the 3rd month, there was significant increase in the ACA values in all studied groups compared to preoperative values (P<0.001). The highest percent of increase in ACA was recorded in phacotrabeculectomy group B2 (128.40%). There was significant increase in ACD values at 3rd month compared with baseline values (P<0.001) for groups A1, A2, and B2; without change in B1 trabeculectomy group. The maximum deepening of ACD was noticed in group B2 with 94.27% increase. Significant decrease in postoperative IOP in groups A2, B1 and B2 (P<0.001, P=0.014, and P<0.001 respectively). In group A1 there was significant increase in 3rd month postoperative IOP from baseline values (P<0.001). The maximum decrease in IOP was noticed in group B2 with 59.54% decrease. VA improvement in 3rd month postoperative was recorded in all studied groups, maximum VA improvement was observed in group B2 up to 0.2 logMAR. CONCLUSION: Pentacam can be a helpful tool in studying and comparing the effect of the different lines of management of PACG on the anterior chamber measures. Phacotrabeculectomy was proved to be an effective line for managing PACG with resultant significant increase in the anterior chamber parameters, IOP reduction as well as maximum VA improvement. LPI has only temporary effect on IOP with significant changes in ACA and ACD. Phacoemuslification alone can be an option in treating PACG. Trabeculectomy resulted in temporary increase in the anterior chamber parameter which subsequently returned to baseline values.

Abstract:AIM: To measure the concentration of vascular endothelial growth factor-A (VEGF-A), and placental growth factor (PLGF) in aqueous humor of uveal melanoma patients before and after Iodine-125 plaque therapy (IPT), determine the postoperative fluctuation and evaluate associated factors in vivo. METHODS: Participants were 18 Chinese patients with uveal melanoma who were elected to IPT. Undiluted aqueous humor samples were collected at Iodine plaque implant and removal time, then stored immediately at -80℃ until assayed. The concentration of VEGF-A, PLGF and other 7 cytokines comprising interleukin-2 (IL-2), IL-8, IL-10, interferon (IFN)-γ, programmed death (PD)-1, transforming growth factor (TGF)-β1 and insulin-like growth factor (IGF)-1 in aqueous humor was measured using Raybiotech immunoassay kit, a high throughput strategy. The VEGF-A and PLGF levels were compared across preoperation and postoperation subgroups, as well as those of other 7 interleukins. Correlation and grouped analyses were conducted to determine the independent effects of clinical parameters and other cytokines on VEGF-A and PLGF concentration or fluctuation. This study set a self-control design. RESULTS: VEGF-A (P=0.038) and PLGF (P=0.026) were the only two increased cytokines after IPT. Preoperative and postoperative level of VEGF-A and PLGF (r=0.575, P=0.013; r=0.987, P<0.001) correlated with each other significantly. Level of VEGF-A (r=0.626, P=0.005; r=0.588, P=0.01) and PLGF (r=0.616, P=0.007; r=0.588, P=0.01) had positive correlation with tumor thickness consistently. Elevated VEGF-A or PLGF level were strong predictive factors of each other (P=0.007, OR=60.0). The elevated VEGF-A group showed a higher postoperative level of IFN-γ (P=0.005), IL-2 (P<0.001) and IL-10 (P=0.004) in aqueous humor. When the elevated PLGF group got similar results that a higher postoperative level of IFN-γ (P=0.007), IL-2 (P<0.001) and IL-10 (P=0.013) in aqueous humor. CONCLUSION: This study reveals that VEGF-A and PLGF in aqueous humor significantly increased with tumor thickness and radiation process in uveal melanoma patients. VEGF-A and PLGF may be crucial in uveal melanoma genesis and radiotherapy reactions. Immune mediators comprised IFN-γ, IL-2 and IL-10 could play roles in the link between inflammation and angiogenesis in uveal melanoma when exposed to radiotherapy.

Abstract:AIM: To evaluate the effects of intravitreal conbercept (IVC) as adjunctive treatments before panretinal photocoagulation (PRP) to decrease hyperreflective dots (HRDs) in Chinese proliferative diabetic retinopathy (PDR) patients. METHODS: Fifty-nine enrolled patients were categorized into 2 groups: single dose IVC (0.5 mg/0.05 mL) 1wk before PRP (Plus group) or PRP only (PRP group). Six months later, we measured the best corrected visual acuity (BCVA), central macula thickness (CMT) by optical coherence tomography and counted the number of HRDs in different retina layers. RESULTS: The average CMT significantly decreased in Plus group but increased in PRP group. The average BCVA in the Plus group was also significantly better than that in the PRP group. Total HRDs decreased in the Plus group but increased in PRP group significantly. IVC pre-treatment has beneficial effects on reducing HRDs forming in the inner retina layer while the PRP alone increased the HRDs in the outer retina layer. CONCLUSION: IVC is a promising adjunctive treatment to PRP in the treatment of PDR. Single dose IVC one week before PRP is suggested to improve retina blood-retina barrier, decrease lipid exudate and inhibit HRDs development in PDR.

Abstract:AIM: To assess the impact of macular surgery on the functional and anatomic outcomes in patients with grade 2 epiretinal membrane (ERM), and the effect of internal limiting membrane (ILM) peeling on visual acuity and to analyze the long-term effect of pars plana vitrectomy (PPV) on intraocular pressure (IOP). METHODS: Pseudophakic eyes (62 eyes) diagnosed as idiopathic grade 2 ERM with at least 6mo postoperative follow-up were included in this retrospective study. The fellow eye was nonvitrectomized. Patients were divided into two groups: group 1 (29 eyes) treated with ERM and ILM peeling and group 2 (33 eyes) with only ERM peeling. Preoperative and postoperative best corrected visual acuity (BCVA), slit-lamp, and a dilated fundus examination was performed. IOP was measured with Goldman applanation tonometer before, day 1 and first week and each visit after surgery. The incidence of significant IOP elevation was compared between vitrectomized eyes and nonvitrectomized fellow eyes. RESULTS: Visual improvement was statistically significant and similar in both groups (P=0.008 in group 1, P=0.002 in group 2, P=0.09 inter-group). The amount of decrease in central macular thickness was statistically significant and similar in both groups (P=0.005 group 1, P=0.008 group 2, P=0.37 intergroup). At the final follow-up (14.1±9.6mo) the incidence of significant IOP elevation was 4% in vitrectomized eyes (three eyes) and 3% (two eyes) in the nonvitrectomized fellow eyes (P=0.12). Four eyes (12.1%) had recurrent ERM after a mean follow-up of 8.6±1.1mo in group 2, there was no recurrence in group 1 (P=0.01). CONCLUSION: Recurrence of ERM may be decreased by ILM peeling during ERM surgery. However, it seems that ILM peeling do not affect the functional outcome and 23-gauge PPV alone do not have a significant effect on IOP.

Abstract:AIM: To quantitatively investigate the retinal vascular diameter changes, analyzing the early and long-term effects on the retinal circulation, with 6-month follow-up. METHODS: Patients underwent horizontal strabismus surgery were enrolled prospectively. Retinal vessel diameters on color fundus photographs were assessed before and 1, 7d, 6mo after surgery, using a computer-assisted quantitative assessment software. To evaluate the retinal vascular caliber changes, retinal vascular diameters were calculated by means of the Parr–Hubbard formula as the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). The arteriovenous ratio (AVR) was calculated as CRAE divided by CRVE. RESULTS: A total of 154 eyes of 104 consecutive patients were included. Compared with the data before surgery (121.55±24.67), the mean CRAE (131.18±28.29) significantly increased 1d after surgery (P=0.003), but went back to baseline level at 7d (118.89±30.35, P=0.15), and 6mo (123.22±15.32, P=0.60), so did the AVR (P<0.001, P=0.08, P=0.07). As for the mean CRVE, there was no significant difference between those four time points (172.43±33.25, 175.57±36.98, 174.03±40.18, 174.86±20.46, P=1.00). CONCLUSION: Strabismus surgery on both lateral and media rectus muscles, or single media rectus muscle may increase retinal blood flow during the early postoperative period, but would return to normal later. The number of transected anterior ciliary arteries rather might be the main cause of retinal hemodynamic changes early after strabismus surgery.

Abstract:AIM: To evaluate the intra-operator repeatability of time domain and swept-source Fourier domain anterior segment optical coherence tomography (AS-OCT), namely, Visante AS-OCT and Casia SS-1000 OCT, in measuring the preoperative parameters of implantable collamer lens (ICL) in myopic eyes, as well as the agreement between the two devices. METHODS: A total of 97 eyes from 49 myopes were investigated in this prospective case series study. The anterior chamber depth (ACD), angle-to-angle distance (ATA), pupil diameter (PD) and crystalline lens rise (CLR) in all subjects were measured for three times during one session by the same operator. The repeatability was evaluated using the within-subject standard deviation (Sw), repeatability limits and intraclass correlation coefficients (ICC). The agreement between the two systems was evaluated using the Bland-Altman plots and 95% limits of agreement (LoA). RESULTS: The repeatability limits of Visante AS-OCT in measuring ACD, ATA, PD and CLR were 0.099, 0.141, 0.304, and 0.079 mm, respectively. The repeatability limits of Casia SS-1000 OCT in measuring ACD, ATA, PD, and CLR were 0.105, 0.127, 0.357, and 0.082 mm, respectively. Excellent repeatability could be attained in both devices, with the ICC>0.8 for all the measured variables. The interdevice agreement was excellent (P>0.05) for ACD and ATA, but poor (P<0.05) for PD and CLR. CONCLUSION: Good repeatability can be attained by time domain and swept-source Fourier-domain OCT for all the measured variables. Moreover, interdevice agreement analysis suggests that interchangeable measurements between two devices can be achieved for ACD and ATA, but not for PD and CLR; but the differences in measurements were not clinically significant.

Abstract:AIM: To evaluate the moderate-term success and calculate the mean dose-effect ratio in large-angle esotropic patients who underwent three muscle surgery. METHODS: In a retrospective study, we reviewed the medical records of 37 patients with large-angle esotropia who underwent bilateral medial rectus recession and one lateral rectus resection. Sex, age at surgery time, amount of recessed or resected muscles in millimeter (mm), pre- and postoperative alignment in prism diopter (D), dose/response ratio, and presence of amblyopia and other associated vertical deviations were recorded. RESULTS: The mean age of subjects at surgery was 12.2±12.3y (range: 1-57). The mean preoperative deviation of 70.4±8.1 D (range: 60-85 D) decreased to a mean of 5.4±8.1 D (range: 0-30 D) postoperatively (P<0.005). Successful alignment was achieved in 30 of 37 patients (81%) at a mean follow-up of 15.7±20.1mo (range: 3-90). The mean amount of recession and resection was 17.59±1.29 mm, and a mean dose-response ratio of 3.79±81 (range: 2.83-4.66) was determined. CONCLUSION: Three-muscle surgery for large-angle esotropia results in good moderate-term outcomes without high rates of overcorrection or undercorrection.

Abstract:AIM: To investigate the therapeutic effects of simultaneous horizontal and vertical operations on dissociated vertical deviation (DVD) associated with other deviations. METHODS: Forty-five cases of DVD with horizontal and torsional strabismus underwent combined operation were collected retrospectively. All clinical records were analyzed. All patients were followed up for 6 to 24mo. Wilcoxon signed-ranks test was performed to evaluate the changes of vertical and horizontal deviation. χ2 test was used to evaluate the changes of binocular visual function. RESULTS: Forty-five cases included 36 patients with intermittent exotropia and binocular inferior oblique overaction (IOOA), 5 patients with concomitant esotropia and binocular IOOA, 4 patients with intermittent exotropia and monocular superior oblique palsy. The superior rectus recession (SRR) combined with horizontal rectus recession and the myectomy of inferior oblique or anterior transposition were operated simultaneously to correct all types of strabismus. There were 43 cases who achieved normal eye position in vertical direction, while 2 cases were with undercorrection of 5Δ to 6Δ. In patients with horizontal strabismus, 2 cases of exotropia were with overcorrection of 6Δ to 8Δ, 1 case of esotropia was with undercorrection of 6Δ, and 1 case of monocular superior oblique palsy with compensatory head posture was not significantly improved. The binocular visual function of most patients recovered after operation. The difference of the binocular visual function and eye position were significant compared with that before operation (P<0.05). CONCLUSION: The simultaneous operation on DVD with horizontal and torsional strabismus is successful.

Abstract:AIM: To summarize quantitatively the prospective association between physical activity and age-related cataract (ARC) risk. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were systematically searched for all relevant follow up studies until July 2019. Multivariable-adjusted relative risks (RRs) and corresponding 95% confidence intervals (CIs) from individual studies were used to calculate the overall summary estimates. The dose-response relationship was assessed using generalized least-squares trend estimation. RESULTS: Six prospective cohort studies, involving 19 173 cases in 6.2-12.1y follow up of 171 620 participants, were included in the analysis. Increased physical activity was significantly associated with reduced risk of ARC by 10% (RR: 0.90; 95%CI: 0.81, 0.99, P=0.04). Stratified analysis by assessment method for physical activity suggest that studies using metabolic equivalent (MET) per day tended to report a slightly stronger association with ARC (RR: 0.85; 95%CI: 0.81, 0.90, P<0.001) than studies which assessed activity by weekly activity (RR: 0.96; 95%CI: 0.89, 1.03, P=0.24). Dose-response analysis indicated that the risk of ARC decreased by 2% (RR: 0.98; 95%CI: 0.98, 0.99, P<0.001) for every 6 METs per day increase in activity. CONCLUSION: The findings from this Meta-analysis provide additional evidence that increased physical activity is inversely associated with ARC risk dose-responsively.

Abstract:AIM: To conduct a systematic review and Meta-analysis to examine the association between uveitis and psoriatic disease, and to evaluate whether one condition predisposes individuals to the other. METHODS: We performed a comprehensive search of PubMed and EMBASE to identify cohort studies examining the association between uveitis and psoriatic disease [psoriasis and/or psoriatic arthritis (PsA)]. We used a random-effects model to calculate the pooled relative risks (RRs) adjusted for confounders, along with the 95% confidence intervals (CIs). RESULTS: This Meta-analysis included a total of 6 studies and a maximum of 80 178 648 participants. Compared with non-psoriatic controls, uveitis risk was significantly elevated in patients with psoriasis (RR=1.49; 95%CI: 1.08-2.07), and PsA (RR=3.16; 95%CI: 2.16-4.63). Furthermore, pre-existing uveitis was associated with a significantly increased risk of psoriasis (RR=1.62; 95%CI: 1.44-1.83), and PsA (RR=4.44; 95%CI: 3.52-5.60). CONCLUSION: The results of this systematic review and Meta-analysis suggest an overall positive bidirectional association between uveitis and psoriatic disease (psoriasis and PsA), warranting increased awareness among clinicians involved in the management of these two conditions. Therefore, there remains a need for more detailed studies of the possible common pathogenesis of psoriatic disease and uveitis.

Abstract:Non-simulator-based examination methods of the fundal examination have shown to be cost-effective. We reviewed different non-simulator-based direct fundoscopy examination methods used in undergraduate curricula and their outcomes. PubMed (MEDLINE) and Cochrane Database of Systematic Reviews were searched using standard Medical Subject Heading (MeSH) terms ophthalmoscopy, medical education, undergraduate medical education, medical student, educational assessment and learning. The search included publications until 28th February 2019. We obtained 34 articles after screening abstracts; of them, 12 articles were included in the qualitative synthesis. The studies were comprised of diverse teaching methods which included fundal photograph matching with corresponding eye, continuous education using community-based eye clinics, formal instructions and demonstrations prior to skills training, ophthalmoscopy skills practice using eye pathologies, teaching versus conventional ophthalmoscopy and group-based teaching. We concluded that non-simulator-based techniques such as use of fundal photograph matching of an eye of a volunteer, introduction to eye pathologies, smaller student groups and formal instructions with video demonstrations prior to skills training were highly effective in teaching direct ophthalmoscopy for undergraduate medical students.

Abstract:AIM: To evaluate accuracy of axis alignment and refractive results of toric phakic intraocular lens (IOL) implantation using a digital imaging system. METHODS: This retrospective study investigated toric implantable collamer lens (ICL) implantation in 30 eyes of 21 patients with myopic astigmatism more than 2.0 D guided with digital imaging system. Data were collected during the first week after phakic IOL implantation. RESULTS: Thirty eyes of 21 patients were included in our study. Patients includes 9 males and 12 females. The mean age of the patients was 26.5±7.1 (range 21-44)y. The mean preoperative manifest astigmatism was 3.2±1.7 (range from 2.25 to 4.75) D. The mean postoperative uncorrected distance visual acuity (UCDVA) were 0.07±0.07 (range from 0.1 to 0.0) logMAR. The mean postoperative residual refractive cylinder was 0.25±0.29 (range 0-0.75) D. Eyes with postoperative residual refractive cylinder of 0.5 D or less represented 80% (24 eyes). The mean postoperative toric IOL misalignment measured by the OPD scan III was 1.9°±1.45° (range from 0 to 5°). CONCLUSION: Image guided system allows accurate alignment of toric ICL. This is associated with good postoperative visual acuity and low residual refractive astigmatism which correlates with the precision of toric phakic IOL alignment.

Abstract:AIM: To identify the disease-associated mutations in a Chinese Stargardt disease (STGD) family, extend the existing spectrum of disease-causing mutations and further define the genotype-phenotype correlations. METHODS: A Chinese STGD family and 200 normal controls were collected. Whole exome sequencing (WES) and bioinformatics analysis were performed to find the pathogenic gene mutation. Physico-chemical parameters of mutant and wildtype proteins were computed by ProtParam tool. Domains analysis was performed by SMART online software. HOPE online software was used to analyze the structural effects of mutation. Immunofluorescence, quantitative real-time polymerase chain reaction and Western blotting were used for expression analysis. RESULTS: Using WES, a novel homozygous mutation (NM_000350: c.G3190C, p.G1064R) in ABCA4 gene was identified. This mutation showed co-segregation with phenotype in this family. It was not found in the 200 unrelated health controls and absent from any databases. It was considered “Deleterious” as predicted by five function prediction softwares, and was highly conserved during evolution. ABCA4 was expressed highly in the human eye and mouse retina. The p.G1064R was located in AAA domain, may force the local backbone into an incorrect conformation, disturb the local structure, and reduce the activity of ATPase resulting in the disease pathology. CONCLUSION: We define a novel pathogenic mutation (c.G3190C of ABCA4) of STGD. This extends the existing spectrum of disease-causing mutations and further defines the genotype-phenotype correlations.

Abstract:AIM: To determine whether ophthalmic photographers (OPs) can conduct virtual clinics (VCs) in medical retina appropriately and whether this increases clinic capacity. METHODS: Three OPs underwent a training programme to learn how to assess and manage macular edema secondary to diabetes or retinal vein occlusion. The 300 consecutive patients over a 7-month observation period in 2018 were assessed in VCs by both OPs and medical retina consultants. The degree of agreement in treatment decisions between doctors and photographers, as well as adverse events, was recorded. The change in number of patients seen in VCs over two years was also measured. RESULTS: There was 100% agreement in management decisions between doctors and photographers during the 300-patient observation period. No adverse events were recorded. In 2017, 572 patients were seen in VCs by doctors. After OP clinics were introduced in 2018, this number increased by 24% to 709 patients seen by both photographers and doctors. There was a significant increase in mean number of patients seen per month between 2017 (47.7±11.7) and 2018 (59.1±14.4; P=0.045, 95%CI -22.5 to -0.296). CONCLUSION: OPs can manage certain medical retina patients in VCs appropriately and can increase clinic capacity significantly for particular conditions.

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